Rare Cancer News & Clinical Trials » Endocrine/Neuroendocrine

Endocrine/Neuroendocrine (571 unread)

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$Permalink for 'Intratumoral STING agonist reverses immune evasion in PD-(L)1-refractory Merkel cell carcinoma: mechanistic insights from detailed biomarker analyses'$

Intratumoral STING agonist reverses immune evasion in PD-(L)1-refractory Merkel cell carcinoma: mechanistic insights from detailed biomarker analyses

Fetched: October 16th, 2024, 2:01am UTC by Thomas Pulliam

J Immunother Cancer. 2024 Oct 14;12(10):e009803. doi: 10.1136/jitc-2024-009803.

ABSTRACT

BACKGROUND: Antibodies blocking programmed death (PD)-1 or its ligand (PD-L1) have revolutionized cancer care, but many patients do not experience durable benefits. Novel treatments to stimulate antitumor immunity are needed in the PD-(L)1 refractory setting. The stimulator of interferon genes (STING) protein, an innate sensor of cytoplasmic DNA, is a promising target with several agonists in development. However, response rates in most recent clinical trials have been low and mechanisms of response remain unclear. We report detailed biomarker analyses in a patient with anti-PD-L1 refractory, Merkel cell polyomavirus (MCPyV)-positive, metastatic Merkel cell carcinoma (MCC) who was treated with an intratumoral (IT) STING agonist (ADU-S100) plus intravenous anti-PD-1 antibody (spartalizumab) and experienced a durable objective response with regression of both injected and non-injected lesions.

METHODS: We analyzed pretreatment and post-treatment tumor and peripheral blood samples from our patient with single-cell RNA sequencing, 30-parameter flow cytometry, T cell receptor sequencing, and multiplexed immunohistochemistry. We analyzed cancer-specific CD8 T cells using human leukocyte antigen (HLA)-I tetramers loaded with MCPyV peptides. We also analyzed STING expression and signaling in the tumor microenvironment (TME) of 88 additional MCC tumor specimens and in MCC cell lines.

RESULTS: We observed high levels of MCPyV-specific T cells (12% of T cells) in our patient's tumor at baseline. These cancer-specific CD8 T cells exhibited characteristics of exhaustion including high TOX and low TCF1 proteins. Following treatment with STING-agonist plus anti-PD-1, IT CD8 T cells expanded threefold. We also observed evidence of likely improved antigen presentation in the MCC TME (greater than fourfold increase of HLA-I-positive cancer cells). STING expression was not detected in any cancer cells within our patient's tumor or in 88 other MCC tumors, however high STING expression was observed in immune and stromal cells within all 89 MCC tumors.

CONCLUSIONS: Our results suggest that STING agonists may be able to work indirectly in MCC via signaling through immune and stromal cells in the TME, and may not necessarily need STING expression in the cancer cells. This approach may be particularly effective in tumors that are already infiltrated by inflammatory cells in the TME but are evading immune detection via HLA-I downregulation.

PMID:39401968 | DOI:10.1136/jitc-2024-009803

$Permalink for 'Hypofractionated versus standard fractionation radiotherapy for merkel cell carcinoma'$

Hypofractionated versus standard fractionation radiotherapy for merkel cell carcinoma

Fetched: October 16th, 2024, 2:01am UTC by Lorein Gonzalez

Radiat Oncol. 2024 Oct 11;19(1):142. doi: 10.1186/s13014-024-02516-4.

ABSTRACT

PURPOSE/OBJECTIVE(S): Merkel cell carcinoma (MCC) radiation treatment has historically consisted of standard 1.8-2 Gy fractions treated daily over 4-6 weeks. Hypofractionated treatment regimens have demonstrated tumor control and toxicity equivalence to standard fractionation regimens for common cutaneous malignancies such as basal cell and squamous cell carcinomas. Herein we report the outcomes of hypofractionated versus standard fractionation radiotherapy for MCC at our institution.

MATERIALS/METHODS: The study involved a retrospective review of MCC patients treated with radiotherapy. Treatment characteristics and patient outcomes, including acute toxicities, disease recurrence and survival data were collected. The cumulative incidence of local and distant failures was estimated, with death as a competing risk.

RESULTS: A total of 29 treatment courses for 24 patients were included, of which 13 involved standard fractionation with curative intent, 10 involved hypofractionated radiotherapy with curative intent, and 6 involved single fraction (8 Gy) palliative radiation. Half the patients were treated to a head/neck site. A subset of patients treated adjuvantly with curative intent included 8 standard fractionation and 8 hypofractionated radiotherapy patients. No statistically significant differences in local and/or distant failure or overall survival was observed between the patient groups.

CONCLUSION: Hypofractionated radiotherapy for MCC was associated with similar treatment outcomes relative to standard fractionation. In our limited patient sample, hypofractionated radiation treatment achieved similar results with similar toxicity and fewer treatments. Further analysis of a larger patient population with longer follow up is needed to confirm treatment tolerability and efficacy.

PMID:39394124 | PMC:PMC11468079 | DOI:10.1186/s13014-024-02516-4

Paraneoplastic Neurologic Syndromes Associated With Merkel Cell Carcinoma

Fetched: October 16th, 2024, 2:01am UTC by NicolÃ¡s Lundahl Ciano-Petersen

Neurol Neuroimmunol Neuroinflamm. 2024 Nov;11(6):e200260. doi: 10.1212/NXI.0000000000200260. Epub 2024 Oct 7.

ABSTRACT

BACKGROUND AND OBJECTIVES: To define the clinical and immunologic profile of patients with paraneoplastic neurologic syndromes (PNSs) associated with Merkel cell carcinoma (MCC).

METHODS: Retrospective analysis was conducted on patients with suspected MCC-related PNS assessed at the French Reference Center, and cases were identified by a systematic review of the literature (MEDLINE, Embase) following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

RESULTS: A total of 17 patients were identified in our center and 30 in the systematic review, resulting in an overall cohort of 47 patients. The median age was 65 years (range 41-90), and 30 of 46 (65%) were men. Lambert-Eaton myasthenic syndrome (LEMS) (14/47, 29%), rapidly progressive cerebellar syndrome (11/47, 23%), and encephalomyelitis (EM) (8/47, 17%) were the most common associated clinical phenotypes. The most frequently associated neural antibodies (Abs) were voltage-gated calcium channel (VGCC)-Abs (14/45, 31%), followed by Hu-Abs (8/45, 17%) and neurofilament (NF)-Abs (8/45, 17%). Patients with NF-Abs only exhibited CNS disorders (8/8, 100%) and often had antibodies against >1 NF subunit (6/8, 75%). At onset, 26 of 43 patients (60%) had no identifiable primary skin tumor but had lymph node metastasis; these patients were more frequently men (21/26, 80%, vs 7/17, 41%; p = 0.007), had more frequently VGCC-Abs (12/26, 46%, vs 2/17, 11%, p = 0.02) predominantly among those with LEMS, and presented reduced mortality than patients with a known primary tumor (5/25, 20%, vs 8/15, 53%; p = 0.02).

DISCUSSION: MCC-related PNSs present as a heterogeneous clinical spectrum including central and/or peripheral nervous system disorders such as LEMS, RCPS, and EM, mainly associated with VGCC-Abs, NF-Abs, and Hu-Abs. NF-Abs were only seen among patients with CNS disorders. At onset, the absence of a primary skin tumor but presence of lymph node metastasis is frequently observed, and this particular clinical presentation is linked to reduced mortality, highlighting distinctive clinical and immunologic features of MCC-related PNS.

PMID:39388653 | DOI:10.1212/NXI.0000000000200260

Dermatologic surgery during pregnancy and lactation

Fetched: October 16th, 2024, 2:01am UTC by Daniel Czesla

Dermatologie (Heidelb). 2024 Oct 10. doi: 10.1007/s00105-024-05418-4. Online ahead of print.

ABSTRACT

It may be necessary for patients to undergo (dermato-)surgical procedures during pregnancy or lactation. Often, there are no drug approvals or guidelines in this context. The following article describes the most common dermatologic surgical conditions during pregnancy and lactation, as well as the special therapeutic considerations and risks to be aware of during treatment. Dermatosurgical procedures are subject to strict indications. Most of these procedures can be performed during pregnancy, but the risks to the mother and fetus must be carefully weighed against the disadvantages of nonsurgical therapy. Although surgery can be performed safely in any trimester, the second trimester and immediate postpartum period are optimal. Surgery should not be delayed for melanoma or high-risk skin cancer. Perioperative positioning and choice of analgesics, antiseptics, anesthetics and antibiotics must be considered carefully to avoid risks to the patient, fetus and infant.

PMID:39387862 | DOI:10.1007/s00105-024-05418-4

Survival outcomes in patients with de novo metastatic Merkel cell carcinoma according to site of metastases

Fetched: October 16th, 2024, 2:01am UTC by Karam Khaddour

Front Oncol. 2024 Sep 16;14:1444590. doi: 10.3389/fonc.2024.1444590. eCollection 2024.

ABSTRACT

INTRODUCTION: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine malignancy of the skin with a predilection for metastases. This study investigates the clinical outcomes in patients presenting with de novo Stage IV MCC according to the metastatic site(s) at presentation.

MATERIALS AND METHODS: Patients who presented with one or more sites of distant metastatic MCC at initial diagnosis between 2009 and 2023 were identified. The presence or absence of one or more metastases in each organ was categorized for each patient at the time of diagnosis. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Competing risk analysis was used to estimate the cumulative occurrence risk of MCC-specific death. Fisher's exact test was used for response rate analysis. Results were considered statically significant if p < 0.05.

RESULTS: Thirty-four patients presented with de novo distant metastatic MCC. There was no association between the number of metastatic sites at diagnosis and OS (p= 0.58), PFS (p=0.79), or response rates (p=0.53). However, the presence of bone metastases was associated with significantly shorter OS (8.2 versus 25.2 months, HR: 2.4, 95% CI 1.01-5.7, p= 0.04). MCC-specific death in patients with lymph node metastases was significantly lower than in patients without (HR: 0.28, 95% CI: 0.09-0.87, p= 0.013). The presence of bone metastases tended to associate with an increased risk of MCC-specific death, although not statistically significant. The location of metastases was not associated with the response rate to first-line treatment. There was no significant association between site of metastases and PFS.

CONCLUSION: In this cohort of patients with de novo metastatic MCC, the presence of bone metastases, but not the number of organs involved, was associated with significantly worse OS. The presence of lymph node metastases was associated with lower MCC-specific death. Further research is warranted in larger cohorts to investigate the impact of the location of metastases on clinical outcomes.

PMID:39351362 | PMC:PMC11439816 | DOI:10.3389/fonc.2024.1444590

Permalink for 'Merkel cell carcinoma-derived macrophage migration inhibitory factor (MIF) may promote persistence of Chronic Lymphocytic Leukemia'

Merkel cell carcinoma-derived macrophage migration inhibitory factor (MIF) may promote persistence of Chronic Lymphocytic Leukemia

Fetched: October 16th, 2024, 2:01am UTC by Gabriel F Alencar

bioRxiv [Preprint]. 2024 Sep 18:2024.09.09.611517. doi: 10.1101/2024.09.09.611517.

ABSTRACT

While concurrent diagnoses of Merkel cell carcinoma (MCC) and other cancers, like Chronic lymphocytic leukemia (CLL), are rare, patients with MCC have a 30-fold higher incidence of CLL. While these increases have been attributed to the ability of CLL to suppress immune responses allowing for the emergence of MCC, here we found evidence that MCC could support the persistence of CLL. Using single cell sequencing approaches and computational analyses of MCC and CLL from a patient where both cancers were present in the same lymph node, we found that production of macrophage migration inhibitory factor (MIF) by MCC could promote the persistence of CLL through stimulation of CD74 and CXCR4. These results may explain why blood cell counts rapidly normalized after treatment for MCC and were maintained at normal levels despite the absence of treatment for CLL.

PMID:39345457 | PMC:PMC11429610 | DOI:10.1101/2024.09.09.611517

Permalink for 'Exploring the effects of Merkel cell polyomavirus T antigens expression in REH and MCC13 cells by methylome and transcriptome profiling'

Exploring the effects of Merkel cell polyomavirus T antigens expression in REH and MCC13 cells by methylome and transcriptome profiling

Fetched: October 16th, 2024, 2:01am UTC by Amanda Macamo

J Med Virol. 2024 Oct;96(10):e29938. doi: 10.1002/jmv.29938.

ABSTRACT

Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer with a tripled incidence in the US and Europe over the past decade. Around 80% of MCC is linked to Merkel cell polyomavirus, but the cell of origin remains unknown. We stably introduced Merkel cell polyomavirus (MCPyV)-sT) and LT antigens to MCC13 and REH cell lines, analyzing DNA methylation and gene transcriptional regulation. Gene ontology analysis assessed MCPyV effects, and integrative analysis correlated gene expression and methylation. Expression patterns were compared with 15 previously sequenced primary MCCs. We found that MCPyV-LT induces DNA methylation changes in both cell lines, while MCPyV-sT only affected REH cells. Greater gene expression changes are observed in MCC13 cells, with upregulated genes associated with cellular components and downregulated genes related to biological processes. Integrative analysis of differentially expressed genes (DEG) and differentially methylated regions (DMR) of REH cell lines revealed that no genes were commonly methylated and differentially expressed. The study compared DEGs and DMG in MCC13 and REH cells to overlapping genes in MCPyV-positive cell lines (MKL1, MKL2, and WaGa), identifying hypomethylated genes in the gene body and hypermethylated genes at TSS1500. GO analysis of the two cell lines showed that MCPyV-TAs can downregulate genes in MHC-I pathways; this downregulation offers a target that can be used to create novel and efficient MCC immunotherapy approaches. Finally, it was confirmed that MCPyV-LT controls gene expression in MCC tissues using an integrative investigation of DNA methylation and gene expression.

PMID:39344364 | DOI:10.1002/jmv.29938

POU4F3 is a Sensitive and Specific Marker of Merkel Cell Carcinoma

Fetched: October 16th, 2024, 2:01am UTC by Pawel Karpinski

Mod Pathol. 2024 Sep 26:100627. doi: 10.1016/j.modpat.2024.100627. Online ahead of print.

ABSTRACT

Although of therapeutic importance, a single sensitive and specific immunostain to distinguish Merkel cell carcinoma (MCC) from mimics is not currently available. In addition, single tumor cells are difficult to detect in sentinel lymph node biopsy. Leveraging publicly available data sets of 9264 solid tumors and over 600,000 single-cell transcriptomes, we identified POU4F3 to be a specific marker of MCC. Analyses of Pan-Cancer RNA bulk sequencing data of 24 tumor types from Tumor Cancer Genomic Atlas (TCGA) datasets as well as non-TCGA SCLC and MCC datasets confirmed POU4F3 specificity for MCC. Single-cell RNA sequencing analyses also confirmed lack of POU4F3 expression in lung small cell carcinoma as well as a variety of normal tissues. Nuclear POU4F3 immunohistochemical expression was noted in 98.7% of 153 MCCs and in only 1.7% of mimics (3 of 180 cases, including 95 small cell carcinomas of which 55 from lung and the remainder from other sites). Three POU4F3-positive non-MCC cases were from lung (2 cases) and vagina (1 case). All 153 tested MCC cases were negative for ASCL1, a key transcriptional regulator highly expressed in SCLC. NeuroD1 was seen in a subset of MCC cases (20.9%, 32/153). POU4F3 immunostain was performed on 29 sentinel lymph nodes and strong POU4F3 nuclear expression facilitated ease of metastasis detection, even single tumor cells. Our study built on prior works shows that POU4F3 to be a sensitive and specific clinical marker of MCC.

PMID:39341281 | DOI:10.1016/j.modpat.2024.100627

The Role of the Large T Antigen in the Molecular Pathogenesis of Merkel Cell Carcinoma

Fetched: October 16th, 2024, 2:01am UTC by Julia Myrda

Genes (Basel). 2024 Aug 27;15(9):1127. doi: 10.3390/genes15091127.

ABSTRACT

The large T antigen (LT) of the Merkel cell polyomavirus (MCPyV) is crucial for Merkel cell carcinoma (MCC), a rare but very aggressive form of neuroendocrine skin cancer. The clonal integration of MCPyV DNA into the host genome is a signature event of this malignancy. The resulting expression of oncogenes, including the small T (sT) antigen and a truncated form of the LT (truncLT), directly contribute to carcinogenesis. The truncation of the C-terminus of LT prevents the virus from replicating due to the loss of the origin binding domain (OBD) and the helicase domain. This precludes cytopathic effects that would lead to DNA damage and ultimately cell death. At the same time, the LxCxE motif in the N-terminus is retained, allowing truncLT to bind the retinoblastoma protein (pRb), a cellular tumor suppressor. The continuously inactivated pRb promotes cell proliferation and tumor development. truncLT exerts several classical functions of an oncogene: altering the host cell cycle, suppressing innate immune responses to viral DNA, causing immune escape, and shifting metabolism in favor of cancer cells. Given its central role in MCC, the LT is a major target for therapeutic interventions with novel approaches, such as immune checkpoint inhibition, T cell-based immunotherapy, and cancer vaccines.

PMID:39336718 | PMC:PMC11431464 | DOI:10.3390/genes15091127

Aberrant positivity for BCOR immunohistochemistry in merkel cell carcinoma - a potential diagnostic pitfall

Fetched: October 16th, 2024, 2:01am UTC by Viola Katharina Vetter

Diagn Pathol. 2024 Sep 27;19(1):130. doi: 10.1186/s13000-024-01552-8.

ABSTRACT

BACKRGOUND: Merkel cell carcinoma (MCC) is a rare, aggressive primary cutaneous neuroendocrine carcinoma, frequently associated with clonal Merkel cell polyomavirus integration. MCC can pose significant diagnostic challenges due to its diverse clinical presentation and its broad histological differential diagnosis. Histologically, MCC presents as a small-round-blue cell neoplasm, where the differential diagnosis includes basal cell carcinoma, melanoma, hematologic malignancies, round cell sarcoma and metastatic small cell carcinoma of any site. We here report strong aberrant immunoreactivity for BCOR in MCC, a marker commonly used to identify round cell sarcomas and other neoplasms with BCOR alterations.

METHODS: Based on strong BCOR expression in three index cases of MCC, clinically mistaken as sarcoma, a retrospective analysis of three patient cohorts, comprising 31 MCC, 19 small cell lung carcinoma (SCLC) and 5 cases of neoplasms with molecularly confirmed BCOR alteration was conducted. Immunohistochemical staining intensity and localization for BCOR was semi-quantitatively analyzed.

RESULTS: Three cases, clinically and radiologically mimicking a sarcoma were analyzed in our soft tissue and bone pathology service. Histologically, the cases showed sheets of a small round blue cell neoplasm. A broad panel of immunohistochemistry was used for lineage classification. Positivity for synaptophysin, CK20 and Merkel cell polyoma virus large T-antigen lead to the diagnosis of a MCC. Interestingly, all cases showed strong positive nuclear staining for BCOR, which was included for the initial work-up with the clinical differential of a round cell sarcoma. We analyzed a larger retrospective MCC cohort and found aberrant weak to strong BCOR positivity (nuclear and/or cytoplasmic) in up to 90% of the cases. As a positive control, we compared the expression to a small group of BCOR-altered neoplasms. Furthermore, we investigated a cohort of SCLC as another neuroendocrine neoplasm and found in all cases a diffuse moderate to strong BCOR positivity.

CONCLUSIONS: This study demonstrates that neuroendocrine neoplasms, such as MCC and SCLC can express strong aberrant BCOR. This might represent a diagnostic challenge or pitfall, in particular when MCC is clinically mistaken as a soft tissue or a bone sarcoma.

PMID:39334415 | PMC:PMC11437883 | DOI:10.1186/s13000-024-01552-8

Are There More Human Cancer Viruses Left to Be Found?

Fetched: October 16th, 2024, 2:01am UTC by Patrick S Moore

Annu Rev Virol. 2024 Sep;11(1):239-259. doi: 10.1146/annurev-virology-111821-103721.

ABSTRACT

Of the thousands of viruses infecting humans, only seven cause cancer in the general population. Tumor sequencing is now a common cancer medicine procedure, and so it seems likely that more human cancer viruses already would have been found if they exist. Here, we review cancer characteristics that can inform a dedicated search for new cancer viruses, focusing on Kaposi sarcoma herpesvirus and Merkel cell polyomavirus as the most recent examples of successful genomic and transcriptomic searches. We emphasize the importance of epidemiology in determining which cancers to examine and describe approaches to virus discovery. Barriers to virus discovery, such as novel genomes and viral suppression of messenger RNA expression, may exist that prevent virus discovery using existing approaches. Optimally virus hunting should be performed in such a way that if no virus is found, the tumor can be reasonably excluded from having an infectious etiology and new information about the biology of the tumor can be found.

PMID:39326883 | DOI:10.1146/annurev-virology-111821-103721

13-year survival oligometastatic Merkel cell carcinoma: a case report

Fetched: October 16th, 2024, 2:01am UTC by I Trampetti

J Med Case Rep. 2024 Sep 18;18(1):455. doi: 10.1186/s13256-024-04750-6.

ABSTRACT

BACKGROUND: Merkel cell carcinomas are rare, aggressive skin tumors with high metastatic potential and poor prognosis. Their treatment is classically based on surgery with adjuvant external radiotherapy for localized tumors or on immunotherapy or chemotherapy, sometimes associated with radiotherapy, for metastatic stages. Those tumors are highly radiosensitive due to their neuroendocrine and undifferentiated nature, but they usually fail to rapidly respond to treatment.

CASE PRESENTATION: We report the case of a 65-year-old retired female patient of Caucasian (German) origin with locally advanced Merkel cell carcinoma of the buttock, with pancreatic metastases synchronous at diagnosis, treated with local radiotherapy of the right buttock without regional lymph node irradiation followed by a sequential chemotherapy; 1 year later, the patient developed an isolated pancreatic recurrence treated with exclusive radiotherapy. The patient was still alive at 13 years with complete remission.

CONCLUSION: External radiotherapy can be an effective alternative to surgery for locally advanced or even oligometastatic Merkel cell carcinomas.

PMID:39289742 | PMC:PMC11409691 | DOI:10.1186/s13256-024-04750-6

Merkel Cell Carcinoma Case Reports With Merkel Cell Polyomavirus Test and Review of the Literature

Fetched: October 16th, 2024, 2:01am UTC by Jingxiu Chai

Am J Dermatopathol. 2024 Sep 17. doi: 10.1097/DAD.0000000000002837. Online ahead of print.

ABSTRACT

Merkel cell carcinoma (MCC) is known as a rare and highly malignant neuroendocrine skin cancer and often occurs in the sun-exposed parts of the elderly individuals. In this article, we reported 2 cases of MCC and reviewed relative literature. Case 1 was a 91-year-old woman who presented with a half-year history of a brown nodule on the left temple. The histopathological and immunohistochemistry examination diagnosis was MCC with negative staining of Merkel cell polyomavirus large T antigen (CM2B4). Case 2 was a 76-year-old man with a nodule on his right buttock that gradually increased from approximately 3 mm to 1.5 cm in diameter in 1 month without pain. The biopsy diagnosis was MCC with positive staining of CM2B4. Previous studies have found that the genetic mutation and prognosis of polyomavirus-associated MCC (MCCP) and nonviral MCC (MCCN) are significantly different. Large T antigen plays a crucial role in Merkel cell polyomavirus (MCPyV) oncogenesis. Testing for the MCPyV at the onset of MCC is recommended, which is helpful in predicting the prognosis of patients.

PMID:39288754 | DOI:10.1097/DAD.0000000000002837

Monoclonal antibodies for inflammatory, autoimmune and oncological skin diseases

Fetched: October 16th, 2024, 2:01am UTC by Maria Kinberger

Dermatologie (Heidelb). 2024 Oct;75(10):762-774. doi: 10.1007/s00105-024-05413-9. Epub 2024 Sep 13.

ABSTRACT

In 1997 rituximab, a genetically engineered chimeric monoclonal antibody (mAb) targeting CD20 expressed on B cells was approved for treatment of non-Hodgkin's lymphoma. Since then, pharmacological improvements combined with increased knowledge on the immunopathogenesis of diseases led to the development of specific mAb targeting different antigens (e.g., interleukins or transmembrane receptors). This approach reshaped the therapeutic methodology in many fields, including dermatology. Nowadays, the treatment of frequent and possibly impairing inflammatory disorders such as psoriasis, atopic dermatitis or hidradenitis suppurativa have different mAbs approved for both adult and pediatric patients. This class of drugs often shows a more favorable outcome and a better safety profile than routine immunosuppressants, such as steroids and steroid-sparing substances. For many years mAbs also represented a pillar of oncological treatment for severe diseases such as malignant melanoma or Merkel cell carcinoma. This review summarizes the current knowledge on already approved and promising new mAbs for the treatment of inflammatory and oncological skin diseases.

PMID:39271491 | DOI:10.1007/s00105-024-05413-9

Permalink for 'Personalised PET imaging in oncology: an umbrella review of meta-analyses to guide the appropriate radiopharmaceutical choice and indication'

Personalised PET imaging in oncology: an umbrella review of meta-analyses to guide the appropriate radiopharmaceutical choice and indication

Fetched: October 16th, 2024, 2:01am UTC by Margarita Kirienko

Eur J Nucl Med Mol Imaging. 2024 Sep 11. doi: 10.1007/s00259-024-06882-9. Online ahead of print.

ABSTRACT

PURPOSE: For several years, oncological positron emission tomography (PET) has developed beyond 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG). This umbrella review of meta-analyses aims to provide up-to-date, comprehensive, high-level evidence to support appropriate referral for a specific radiopharmaceutical PET/computed tomography (CT) or PET/magnetic resonance (MR) in the diagnosis and staging of solid cancers other than brain malignancies.

METHODS: We performed a systematic literature search on the PubMed/MEDLINE and EMBASE databases for meta-analyses assessing the accuracy of PET/CT and/or PET/MRI with [¹⁸F]FDG, somatostatin- receptor-targeting ⁶⁸Ga-DOTA-peptides, ¹⁸F-labelled dihydroxyphenylalanine ([¹⁸F]DOPA), prostate-specific membrane antigen (PSMA)-targeted radioligands, and fibroblast activation protein inhibitors (FAPI) in the diagnosis/disease characterisation and staging of solid cancers other than brain tumours.

RESULTS: The literature search yielded 449 scientific articles. After screening titles and abstracts and applying inclusion and exclusion criteria, we selected 173 meta-analyses to assess the strength of evidence. One article was selected from references. Sixty-four meta-analyses were finally considered. The current evidence corroborates the role of [¹⁸F]FDG as the main player in molecular imaging; PSMA tracers are useful in staging and re-staging prostate cancer; somatostatin-targeting peptides (e.g. [⁶⁸Ga]Ga- DOTA-TOC and -TATE) or [¹⁸F]DOPA are valuable in neuroendocrine tumours (NETs). FAPI has emerged in gastric cancer assessment. According to search and selection criteria, no satisfactory meta-analysis was selected for the diagnosis/detection of oesophageal cancer, the diagnosis/detection and N staging of small cell lung cancer and hepatic cell carcinoma, the diagnosis/detection and M staging of melanoma and Merkel cell carcinoma, cervical, vulvar and penis cancers, the N and M staging of lung and gastroenteropancreatic NET, testicular cancer, and chondrosarcoma, and the M staging of differentiated thyroid, bladder and anal cancers.

CONCLUSION: The comprehensive high-level evidence synthesised in the present umbrella review serves as a guiding compass for clinicians and imagers, aiding them in navigating the increasingly intricate seascape of PET examinations.

PMID:39256216 | DOI:10.1007/s00259-024-06882-9

Updates in the Management of Advanced Nonmelanoma Skin Cancer

Fetched: October 16th, 2024, 2:01am UTC by Flora Yan

Surg Oncol Clin N Am. 2024 Oct;33(4):723-733. doi: 10.1016/j.soc.2024.04.006. Epub 2024 Jun 5.

ABSTRACT

Basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and Merkel cell carcinoma (MCC) comprise the majority of nonmelanoma skin cancers. Advances have been made in treatment. Sentinel node biopsy should be considered for locally advanced, clinically node-negative cSCCs and MCCs. BCC patients failing traditional surgery and/or radiation are candidates for systemic hedgehog inhibitor therapy. Immune checkpoint inhibitor treatment is available for patients who failed traditional treatment with surgery and/or radiation or who are not candidates for these modalities. Specifically, cemiplimab is approved for advanced BCC; cemiplimab and pembrolizumab for advanced cSCC; and avelumab, pembrolizumab, and retifanlimab-dlwr for recurrent/metastatic MCC.

PMID:39244290 | DOI:10.1016/j.soc.2024.04.006

Permalink for 'Durability of response to immune checkpoint blockade following treatment discontinuation and efficacy of rechallenge in advanced Merkel cell carcinoma'

Durability of response to immune checkpoint blockade following treatment discontinuation and efficacy of rechallenge in advanced Merkel cell carcinoma

Fetched: October 16th, 2024, 2:01am UTC by Tanya Ramadoss

J Immunother Cancer. 2024 Sep 5;12(9):e009816. doi: 10.1136/jitc-2024-009816.

ABSTRACT

BACKGROUND: Advanced Merkel cell carcinoma (MCC) has a high response rate to immune checkpoint blockade (ICB) therapy, but the durability of responses once treatment is discontinued remains unclear. We therefore reviewed the long-term outcomes of advanced patients with MCC who discontinued ICB treatment after achieving favorable initial response.

METHODS: We performed a retrospective review of advanced patients with MCC treated at a single high-volume referral center, including all patients who received at least one dose of anti-programmed death receptor 1 (ligand) monotherapy for unresectable or metastatic disease, achieved stable disease (SD) or better, and discontinued treatment for a reason other than disease progression.

RESULTS: Of 195 advanced patients with MCC treated with ICB, we identified 45 who met the study criteria. Of these, 21 (46.6%) had a complete response (CR) to initial ICB treatment, 23 (51.1%) a partial response and 1 (2.2%) SD. 25 (55.6%) patients discontinued ICB electively and 20 (44.4%) discontinued due to toxicity. In total, 21 of the 45 patients (46.6%) experienced disease progression at a median of 11.3 months (range 2.1-22.7 months) from ICB cessation. There was a lower rate of progression in patients who achieved CR versus non-CR (23.8% vs 66.7%, p=0.006) and a trend towards a lower rate in those who discontinued electively versus due to toxicity (36.0% vs 60.0%, p=0.14). There was a higher risk for progression in patients with viral positive MCC compared with viral negative MCC (75.0 vs 30.8%, p=0.02). 16 of the 21 patients who experienced progression were retreated subsequently with ICB therapy, including both single-agent rechallenge (12) and escalation to combination ICB (4). 11 of 15 evaluable ICB-retreated patients (73.3%) achieved an objective response.

CONCLUSIONS: Patients with advanced MCC have a substantial risk of disease progression following treatment discontinuation despite initial favorable ICB response, particularly in those that achieve less than a CR. Most of these patients maintain sensitivity to retreatment with the same drug class. Virus-positive MCC may be a risk factor for post-discontinuation relapse, which should be validated in future studies.

PMID:39242118 | PMC:PMC11381633 | DOI:10.1136/jitc-2024-009816

Merkel Cell Polyomavirus-Pathophysiology and Treatment in the Era of Gene-Targeted Therapies

Fetched: October 16th, 2024, 2:01am UTC by Trairong Chokwassanasakulkit

Rev Med Virol. 2024 Sep;34(5):e2580. doi: 10.1002/rmv.2580.

ABSTRACT

Merkel cell polyomavirus (MCPyV) is a significant contributor to the development of Merkel cell carcinoma (MCC), an aggressive skin cancer with high recurrence and a low survival rate. In fact, it is the deadliest skin cancer. The precise routes of transmission for MCPyV-positive MCC remain unclear, but several factors may trigger its development. Conventional treatments for MCC are not highly effective, especially in patients with metastasis, with a clear need for new treatment options. Gene-targeted therapies hold great promise for the treatment of MCC, including the use of siRNA and CRISPR/Cas (C/Cas) but critically none have yet been translated into clinical trials. Validating this approach is the fact that several siRNA products are already FDA licenced, while C/Cas has entered clinical trial, albeit for conditions other than MCC. There are many challenges that must be overcome to move from preclinical research to the clinic. In this review, we provide a comprehensive summary of the current understanding of MCC, with a particular focus on MCPyV-positive MCC, and the status of gene-targeted therapies. Additionally, we discuss the major obstacles that impede MCC research and explore future prospects.

PMID:39228116 | DOI:10.1002/rmv.2580

Permalink for 'A Novel Artificial Intelligence-Based Parameterization Approach of the Stromal Landscape in Merkel Cell Carcinoma: A Multi-Institutional Study'

A Novel Artificial Intelligence-Based Parameterization Approach of the Stromal Landscape in Merkel Cell Carcinoma: A Multi-Institutional Study

Fetched: October 16th, 2024, 2:01am UTC by Chau M Bui

Lab Invest. 2024 Sep;104(9):102123. doi: 10.1016/j.labinv.2024.102123. Epub 2024 Aug 13.

ABSTRACT

Tumor-stroma ratio (TSR) has been recognized as a valuable prognostic indicator in various solid tumors. This study aimed to examine the clinicopathologic relevance of TSR in Merkel cell carcinoma (MCC) using artificial intelligence (AI)-based parameterization of the stromal landscape and validate TSR scores generated by our AI model against those assessed by humans. One hundred twelve MCC cases with whole-slide images were collected from 4 different institutions. Whole-slide images were first partitioned into 128 Ã— 128-pixel "mini-patches," then classified using a novel framework, termed pre-tumor and stroma (Pre-TOAST) and TOAST, whose output equaled the probability of the minipatch representing tumor cells rather than stroma. Hierarchical random samplings of 50 minipatches per region were performed throughout 50 regions per slide. TSR and tumor-stroma landscape (TSL) parameters were estimated using the maximum-likelihood algorithm. Receiver operating characteristic curves showed that the area under the curve value of Pre-TOAST in discriminating classes of interest including tumor cells, collagenous stroma, and lymphocytes from nonclasses of interest including hemorrhage, space, and necrosis was 1.00. The area under the curve value of TOAST in differentiating tumor cells from related stroma was 0.93. MCC stroma was categorized into TSR high (TSR â‰¥ 50%) and TSR low (TSR < 50%) using both AI- and human pathology-based methods. The AI-based TSR-high subgroup exhibited notably shorter metastasis-free survival (MFS) with a statistical significance of P = .029. Interestingly, pathologist-determined TSR subgroups lacked statistical significance in recurrence-free survival, MFS, and overall survival (P > .05). Density-based spatial clustering of applications with noise analysis identified the following 2 distinct TSL clusters: TSL1 and TSL2. TSL2 showed significantly shorter recurrence-free survival (P = .045) and markedly reduced MFS (P < .001) compared with TSL1. TSL classification appears to offer better prognostic discrimination than traditional TSR evaluation in MCC. TSL can be reliably calculated using an AI-based classification framework and predict various prognostic features of MCC.

PMID:39147033 | DOI:10.1016/j.labinv.2024.102123

Retifanlimab in metastatic Merkel cell carcinoma in first line

Fetched: September 4th, 2024, 2:03am UTC by Clara Zucman-Rossi

Bull Cancer. 2024 Oct;111(10):906-908. doi: 10.1016/j.bulcan.2024.06.009. Epub 2024 Sep 2.

NO ABSTRACT

PMID:39227198 | DOI:10.1016/j.bulcan.2024.06.009

Human Viral Oncoproteins and Ubiquitin-Proteasome System

Fetched: September 4th, 2024, 2:03am UTC by Zahra Rafiei Atani

Glob Med Genet. 2024 Sep 2;11(4):285-296. doi: 10.1055/s-0044-1790210. eCollection 2024 Dec.

ABSTRACT

Some human cancers worldwide may be related to human tumor viruses. Knowing, controlling, and managing the viruses that cause cancers remain a problem. Also, tumor viruses use ubiquitin-proteasome system (UPS) that can alter host cellular processes through UPS. Human tumor viruses cause persistent infections, due to their ability to infect their host cells without killing them. Tumor viruses such as Epstein-Barr virus, hepatitis C virus, hepatitis B virus, human papillomaviruses, human T cell leukemia virus, Kaposi's sarcoma-associated herpesvirus, and Merkel cell polyomavirus are associated with human malignancies. They interfere with the regulation of cell cycle and control of apoptosis, which are important for cellular functions. These viral oncoproteins bind directly or indirectly to the components of UPS, modifying cellular pathways and suppressor proteins like p53 and pRb. They can also cause progression of malignancy. In this review, we focused on how viral oncoproteins bind to the components of the UPS and how these interactions induce the degradation of cellular proteins for their survival.

PMID:39224462 | PMC:PMC11368560 | DOI:10.1055/s-0044-1790210

Mixed Neuroendocrine-Squamous Cell Carcinoma of the Hand With Metastatic Dissemination: A Case Report

Fetched: September 4th, 2024, 2:03am UTC by Jubril Adepoju

Eplasty. 2024 Aug 15;24:e45. eCollection 2024.

ABSTRACT

Cutaneous manifestations of mixed neuroendocrine non-neuroendocrine neoplasms remain a diagnostic rarity. Predominantly identified within internal glandular organs, the digestive tract, and in the hepatobiliary system, this case report illustrates a unique occurrence of a mixed squamous cell and neuroendocrine tumor in the index finger of a justice-affected patient. We discuss the complexities of diagnosis and complications as well as emphasize the importance for hand surgeons to recognize presentations like this and the need for vigilant follow-up and improved care coordination.

PMID:39224411 | PMC:PMC11367163

68Ga-DOTATATE PET/CT Imaging of a Solitary Nasopharyngeal Metastasis of Merkel Cell Carcinoma

Fetched: September 4th, 2024, 2:03am UTC by Haoyuan Ding

Clin Nucl Med. 2024 Oct 1;49(10):973-974. doi: 10.1097/RLU.0000000000005283. Epub 2024 May 26.

ABSTRACT

Merkel cell carcinoma (MCC) is an uncommon highly aggressive cutaneous neuroendocrine neoplasm with high mortality. Rarer still is nasopharyngeal metastasis of MCC. Herein, we report the 68Ga-DOTATATE PET/CT findings of MCC with metastasis to the nasopharynx in a 53-year-old man who underwent surgery for MCC in his thigh 2 years ago.

PMID:39223731 | DOI:10.1097/RLU.0000000000005283

Blastic plasmacytoid dendritic cell neoplasm of skin, a rare dermatohematologic malignancy-A case report

Fetched: September 1st, 2024, 2:01am UTC by Ramtin Edjtemaei

Clin Case Rep. 2024 Aug 28;12(9):e9398. doi: 10.1002/ccr3.9398. eCollection 2024 Sep.

ABSTRACT

KEY CLINICAL MESSAGE: Blastic plasmacytoid dendritic cell neoplasm is a rare hematologic malignancy and appropriate diagnosis encounters difficulties in both clinical and pathologic aspects. This case report aims to present a clinical case to help familiar clinicians and pathologists with this rare entity.

ABSTRACT: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an uncommon hematologic malignancy. Because of the rarity of the disease and aggressive behavior, we present this case. A 71-year-old man presented with a forehead ulcerated skin lesion. On histopathologic examination, pan-dermal atypical mononuclear infiltrate, consisting of small-medium sized cells with fine chromatin pattern was seen without epidermotropism which were immunoreactive for CD123, CD56, TdT and CD4, while negative for CD3, CD20, and MPO that confirmed the diagnosis of BPDCN. BPDCN is a highly aggressive hematologic malignancy derived from plasmacytoid dendritic cells. Male-to-female ratio is 3.3:1. Skin involvement can present as either an isolated purplish nodule or disseminated purplish nodules or papules or macules. On microscopic examination, skin involvement is characterized by monomorphic infiltrates of immature neoplastic cells with blastoid morphology, involving the superficial and deep dermis, often with extension into the subcutis with epidermal spare. Immunophenotyping shows usually positive reactions for CD123, CD45, CD4, CD56, TCL1, CD2AP, CD43, BCL2, TdT, Granzyme B, and TCF4, whereas tumor cells are negative for CD3, CD19, CD20, MPO, CD13 and Lysozyme. Differential diagnoses of BPDCN include myeloid sarcoma, myelomonocytic leukemia, mature plasmacytoid dendritic cell proliferation (MPDCP) and Merkel cell carcinoma. Pathologists ought to be familiar with this WHO entity for early disease diagnosis, because of disease rarity and diagnosis difficulties.

PMID:39210931 | PMC:PMC11358202 | DOI:10.1002/ccr3.9398

Emerging Indications for Neoadjuvant Systemic Therapies in Cutaneous Malignancies

Fetched: August 28th, 2024, 2:01am UTC by Domingos SÃ¡vio do Rego Lins Junior

Med Sci (Basel). 2024 Jul 23;12(3):35. doi: 10.3390/medsci12030035.

ABSTRACT

Patients with cutaneous malignancies and locoregional involvement represent a high-risk population for disease recurrence, even if they receive optimal surgery and adjuvant treatment. Here, we discuss how neoadjuvant therapy has the potential to offer significant advantages over adjuvant treatment, further improving outcomes in some patients with skin cancers, including melanoma, Merkel cell carcinoma, and cutaneous squamous-cell carcinoma. Both preclinical studies and in vivo trials have demonstrated that exposure to immunotherapy prior to surgical resection can trigger a broader and more robust immune response, resulting in increased tumor cell antigen presentation and improved targeting by immune cells, potentially resulting in superior outcomes. In addition, neoadjuvant approaches hold the possibility of providing a platform for evaluating pathological responses in the resected lesion, optimizing the prognosis and enabling personalized adaptive management, in addition to expedited drug development. However, more data are still needed to determine the ideal patient selection and the best treatment framework and to identify reliable biomarkers of treatment responses. Although there are ongoing questions regarding neoadjuvant treatment, current data support a paradigm shift toward considering neoadjuvant therapy as the standard approach for selecting patients with high-risk skin tumors.

PMID:39189198 | PMC:PMC11348210 | DOI:10.3390/medsci12030035

A Rapidly Developing Nodule in a Patient With Hairy Cell Leukemia in Remission: Merkel Cell Carcinoma: A Case Report

Fetched: August 28th, 2024, 2:01am UTC by Sotirios Sachanas

In Vivo. 2024 Sep-Oct;38(5):2540-2544. doi: 10.21873/invivo.13727.

ABSTRACT

BACKGROUND/AIM: Hairy cell leukemia (HCL) is a well-known lymphoproliferative disease with very effective treatment approaches primarily relying on purine analogues. However, these treatments are associated with profound and prolonged immunosuppression. Merkel cell carcinoma (MCC) is a rare and extremely aggressive skin tumor with an increased incidence in immunocompromised patients.

CASE REPORT: We report a case of a patient with HCL who was diagnosed with MCC, while in remission following retreatment with pentostatin, which induced a profound decrease in CD4 (+) T-cells.

CONCLUSION: Our case provides further evidence supporting the hypothesis of a significant association between immunosuppression and MCC pathogenesis.

PMID:39187345 | PMC:PMC11363770 | DOI:10.21873/invivo.13727

Permalink for 'Human papillomavirus and Merkel cell polyomavirus in Korean patients with nonsmall cell lung cancer: Evaluation and genetic variability of the noncoding control region'

Human papillomavirus and Merkel cell polyomavirus in Korean patients with nonsmall cell lung cancer: Evaluation and genetic variability of the noncoding control region

Fetched: August 27th, 2024, 2:02am UTC by Hyoung-Tae Jin

J Med Virol. 2024 Aug;96(8):e29880. doi: 10.1002/jmv.29880.

ABSTRACT

Human papillomavirus (HPV) is an important causative factor of cervical cancer and is associated with nonsmall cell lung cancer (NSCLC). Merkel cell polyomavirus (MCPyV) is a rare and highly fatal cutaneous virus that can cause Merkel cell carcinoma (MCC). Although coinfection with oncogenic HPV and MCPyV may increase cancer risk, a definitive etiological link has not been established. Recently, genomic variation and genetic diversity in the MCPyV noncoding control region (NCCR) among ethnic groups has been reported. The current study aimed to provide accurate prevalence information on HPV and MCPyV infection/coinfection in NSCLC patients and to evaluate and confirm Korean MCPyV NCCR variant genotypes and sequences. DNA from 150 NSCLC tissues and 150 adjacent control tissues was assessed via polymerase chain reaction (PCR) targeting regions of the large T antigen (LT-ag), viral capsid protein 1 (VP1), and NCCR. MCPyV was detected in 22.7% (34 of 150) of NSCLC tissues and 8.0% (12 of 150) of adjacent tissues from Korean patients. The incidence rates of HPV with and without MCPyV were 26.5% (nine of 34) and 12.9% (15 of 116). The MCPyV NCCR genotype prevalence in Korean patients was 21.3% (32 of 150) for subtype I and 6% (nine of 150) for subtype IIc. Subtype I, a predominant East Asian strain containing 25 bp tandem repeats, was most common in the MCPyV NCCR data set. Our results confirm that coinfection with other tumor-associated viruses is not associated with NSCLC. Although the role of NCCR rearrangements in MCPyV infection remains unknown, future studies are warranted to determine the associations of MCPyV NCCR sequence rearrangements with specific diseases.

PMID:39185678 | DOI:10.1002/jmv.29880

Permalink for 'Development of a Multiplex Immunofluorescence Assay for Tumor Microenvironment Studies of Human and Murine Merkel Cell Carcinoma'

Development of a Multiplex Immunofluorescence Assay for Tumor Microenvironment Studies of Human and Murine Merkel Cell Carcinoma

Fetched: August 27th, 2024, 2:02am UTC by Lei Sun

Lab Invest. 2024 Aug 23;104(10):102128. doi: 10.1016/j.labinv.2024.102128. Online ahead of print.

ABSTRACT

Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma. Checkpoint inhibitor immunotherapy plays an essential role in management of advanced MCC; however, predictors of immunotherapy response remain poorly defined. Syngeneic mouse models suitable for testing novel immunotherapy and combination therapy approaches are likely to soon become available and will require assays for evaluating the tumor microenvironment (TME). Multiplex immunofluorescence (mIF) is a powerful approach to characterize the TME for understanding immunotherapy responses and immune surveillance. In this method article, we provide detailed instructions on assay development for mIF, using as examples 2 new mIF panels for TME investigations of human and murine MCC tumors. Specifically, we demonstrate panels that allow simultaneous visualization of the Merkel cell master transcription factor SOX2 for tumor cell identification, alongside T-cell markers (CD3, CD8, and FOXP3), macrophage markers (F4/80 for mouse and CD163 for human tumors), together with the checkpoint marker PD-L1 for human tumors, and the myeloid-derived suppressor cell marker Arg1 for mouse tumors. We provide detailed protocols for investigators to incorporate these mIF panels into their investigations of human and murine MCC. We also provide fundamental guidance for mIF assay development that will be broadly useful for investigators who consider modifying the panels presented in this study or developing their own mIF panels.

PMID:39182611 | DOI:10.1016/j.labinv.2024.102128

Association of polyomavirus infection with lung cancer: A systematic review and meta-analysis

Fetched: August 27th, 2024, 2:02am UTC by Mohamed J Saadh

Pathol Res Pract. 2024 Oct;262:155521. doi: 10.1016/j.prp.2024.155521. Epub 2024 Aug 10.

ABSTRACT

AIM: The objective of this study was to investigate the pooled prevalence and possible association between polyomavirus infection and lung cancer.

METHODS: A systematic publication search was conducted by identifying relevant cross-sectional and case-control studies from major online databases. Heterogeneity, OR, and corresponding 95 % CI were applied to all studies through meta-analysis and forest plot. Random effects models were used to calculate the overall pooled prevalence. Visual inspection of a funnel plot plotting the log-transformed OR and its associated standard error of the log (OR) was combined with the Begg and Egger test to examine the presence and influence of publication bias. Analyzes were performed using Stata software v.14.1.

RESULTS: 23 articles (33 datasets) were included in the meta-analysis, of which 14 datasets were case/control and the rest were cross-sectional studies. The pooled polyomavirus infection rate in lung cancer patients was 0.06 % (0.02-0.11 %). In subgroup analysis, the pooled prevalence of JCV, MCPyV, KI, SV40, BKV, WU, MU, and STL was 21 %, 7 %, 6 %, 2 %, 0 %, 0 %, 0 %, and 0 % respectively. An association has been found between polyomavirus infection and lung cancer [summary OR 6.33 (95 % CI (1.76-22.77); I2=67.45 %)]. The subgroup analysis, based on the virus type, showed a strong association between MCPyV and lung cancer [summary OR 13.61 (95 % CI 2.41-76.59; I2=40.0 %)]. despite the high prevalence of JCV DNA in lung cancer tissue, analysis of case-control studies showed that JCV is not associated with lung cancer and does not increase the risk of lung cancer.

CONCLUSION: This study showed a significant association between polyomaviruses infection with lung cancer. The results also revealed a pooled prevalence of 6 % for polyomaviruses in lung tumor patients. Altogether, the findings of the present work suggest that Merkel cell polyomavirus infection is a potential risk factor for lung cancer.

PMID:39182450 | DOI:10.1016/j.prp.2024.155521

Mohs Micrographic Surgery of Uncommon Tumors (Angiosarcoma, Eccrine, Paget, and Merkel Cell)

Fetched: August 22nd, 2024, 2:01am UTC by Tatiana V. Camayo

2024 Jul 13. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Janâ€“.

ABSTRACT

Mohs micrographic surgery (MMS) is a surgical technique commonly used to treat cutaneous malignancies such as squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). MMS is performed in several stages, progressively removing malignant tissue while preserving healthy tissue and achieving high cure rates. The main advantage of MMS is the ability to assess all margins through the removal of tumor layers, which are processed in frozen sections. This histological assessment of the entire margin is crucial to determine tumor clearance before defect reconstruction, usually occurring in a single surgical session.

MMS is currently the mainstay treatment for non-melanoma skin cancer, including SCC and BCC. MMS has shown benefits in treating these cancers, significantly reducing recurrence rates in both tumors. Uncommon cutaneous malignancies (UCMs) are skin tumors that, although infrequent, are usually associated with poor outcomes and worse prognosis compared to their more common counterparts. MMS has proven useful in treating UCMs, such as dermatofibrosarcoma protuberans. Recently, several studies have highlighted different UCMs treated with MMS, including angiosarcoma, eccrine malignant tumors, Paget disease, and Merkel cell carcinoma (MCC).

Due to their high metastatic potential, MMS's role in treating UCMs has been questioned, especially in angiosarcoma and MCC. Usually, UCMs benefit from treatment with wide local excisions (WLEs). However, MMS has been used alternative option for UCMs over the past decade, supported by several case reports and series demonstrating its beneficial effects on UCM management. In recent years, study groups worldwide have assessed the efficacy, impact on prognosis, and relevance of MMS beyond its common indications. Nonetheless, the value of MMS for some UCMs remains to be fully defined. The following discussion reviews the available evidence on the role of MMS in treating specific UCMs.

PMID:39163450 | Bookshelf:NBK606085

Applications of cell therapy in the treatment of virus-associated cancers

Fetched: August 20th, 2024, 2:01am UTC by Keri Toner

Nat Rev Clin Oncol. 2024 Oct;21(10):709-724. doi: 10.1038/s41571-024-00930-x. Epub 2024 Aug 19.

ABSTRACT

A diverse range of viruses have well-established roles as the primary driver of oncogenesis in various haematological malignancies and solid tumours. Indeed, estimates suggest that approximately 1.5 million patients annually are diagnosed with virus-related cancers. The predominant human oncoviruses include Epstein-Barr virus (EBV), Kaposi sarcoma-associated herpesvirus (KSHV), hepatitis B and C viruses (HBV and HCV), human papillomavirus (HPV), human T-lymphotropic virus type 1 (HTLV1), and Merkel cell polyomavirus (MCPyV). In addition, although not inherently oncogenic, human immunodeficiency virus (HIV) is associated with immunosuppression that contributes to the development of AIDS-defining cancers (specifically, Kaposi sarcoma, aggressive B cell non-Hodgkin lymphoma and cervical cancer). Given that an adaptive T cell-mediated immune response is crucial for the control of viral infections, increasing research is being focused on evaluating virus-specific T cell therapies for the treatment of virus-associated cancers. In this Review, we briefly outline the roles of viruses in the pathogenesis of these malignancies before describing progress to date in the field of virus-specific T cell therapy and evaluating the potential utility of these therapies to treat or possibly even prevent virus-related malignancies.

PMID:39160243 | DOI:10.1038/s41571-024-00930-x

Recurrent Merkel Cell Carcinoma Following COVID-19 Treatment

Fetched: August 20th, 2024, 2:01am UTC by Hirofumi Kawamoto

Cureus. 2024 Jul 18;16(7):e64863. doi: 10.7759/cureus.64863. eCollection 2024 Jul.

ABSTRACT

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer influenced by the immune system. Recent studies suggest that viral infections, notably COVID-19, may exacerbate such malignancies. This case report explores potential mechanisms by which SARS-CoV-2, the virus responsible for COVID-19, could influence the behavior and proliferation of malignant tumor cells. Emerging evidence indicates that COVID-19 may disrupt immune surveillance and modulation, which are critical in controlling the spread and severity of cancers, including MCC. Additionally, the cytokine storm induced by COVID-19 is proposed to facilitate tumorigenic activity, potentially enhancing MCC aggressiveness. By integrating clinical findings with contemporary immunological and virological theories, this report aims to contribute to the understanding of COVID-19's impact on cancer progression, specifically MCC, emphasizing the need for comprehensive management strategies in cancer patients during the pandemic.

PMID:39156288 | PMC:PMC11330325 | DOI:10.7759/cureus.64863

Late subsequent Merkel cell carcinoma after 21 years of the first primary diagnosis: When to de-escalate surveillance?

Fetched: August 20th, 2024, 2:01am UTC by Luis J Borda

Clin Case Rep. 2024 Aug 15;12(8):e9340. doi: 10.1002/ccr3.9340. eCollection 2024 Aug.

ABSTRACT

KEY CLINICAL MESSAGE: Merkel cell carcinoma (MCC) presents challenges in surveillance due to varied recurrence rates and uncertain follow-up protocols, especially in late recurrent cases. These cases need personalized monitoring strategies beyond traditional timelines, such as clinical and molecular factors, in order to optimize patient outcomes.

ABSTRACT: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer with neuroendocrine differentiation with a propensity for recurrence following initial treatment. Surveillance strategies for MCC patients lack specificity, and the duration of surveillance remains uncertain, posing challenges in identifying appropriate follow-up intervals. Therefore, we present a 94-year-old woman, with history of stage IA MCC in her left nasal wall 21 years prior, that presented with a dome-shaped eroded nodule on her left fifth finger. Biopsy showed characteristic MCC features with positive immunohistochemistry for CD56, synaptophysin, and CK20 (perinuclear dotting). The patient opted against further imaging or lymph node biopsy and underwent Mohs micrographic surgery. To date, there has not been any evidence of recurrence at previous sites or development of new primary lesions. This case underscores the need for ongoing surveillance despite long disease-free intervals. It also stands out as the case demonstrating the longest latency/recurrence-free interval following the initial diagnosis of MCC in the literature. While most recurrences occur within the first few years post-diagnosis, our case highlights the exceptional nature of late recurrences and prompts reevaluation of surveillance protocols. Current guidelines recommend surveillance for up to 3 years post-treatment, but factors, such as patient demographics and tumor characteristics, may warrant extended monitoring periods. Emerging biomarkers, such as Merkel cell polyomavirus status and circulating tumor DNA, show promise in predicting and monitoring recurrences, but their utility in late recurrence detection requires further investigation.

PMID:39156199 | PMC:PMC11327293 | DOI:10.1002/ccr3.9340

Merkel cell polyomavirus small tumor antigen contributes to immune evasion by interfering with type I interferon signaling

Fetched: August 20th, 2024, 2:01am UTC by Denise Ohnezeit

PLoS Pathog. 2024 Aug 7;20(8):e1012426. doi: 10.1371/journal.ppat.1012426. eCollection 2024 Aug.

ABSTRACT

Merkel cell polyomavirus (MCPyV) is the causative agent of the majority of Merkel cell carcinomas (MCC). The virus has limited coding capacity, with its early viral proteins, large T (LT) and small T (sT), being multifunctional and contributing to infection and transformation. A fundamental difference in early viral gene expression between infection and MCPyV-driven tumorigenesis is the expression of a truncated LT (LTtr) in the tumor. In contrast, sT is expressed in both conditions and contributes significantly to oncogenesis. Here, we identified novel functions of early viral proteins by performing genome-wide transcriptome and chromatin studies in primary human fibroblasts. Due to current limitations in infection and tumorigenesis models, we mimic these conditions by ectopically expressing sT, LT or LTtr, individually or in combination, at different time points. In addition to its known function in cell cycle and inflammation modulation, we reveal a fundamentally new function of sT. We show that sT regulates the type I interferon (IFN) response downstream of the type I interferon receptor (IFNAR) by interfering with the interferon-stimulated gene factor 3 (ISGF3)-induced interferon-stimulated gene (ISG) response. Expression of sT leads to a reduction in the expression of interferon regulatory factor 9 (IRF9) which is a central component of the ISGF3 complex. We further show that this function of sT is conserved in BKPyV. We provide a first mechanistic understanding of which early viral proteins trigger and control the type I IFN response, which may influence MCPyV infection, persistence and, during MCC progression, regulation of the tumor microenvironment.

PMID:39110744 | PMC:PMC11333005 | DOI:10.1371/journal.ppat.1012426

Polyomavirus ALTOs, but not MTs, downregulate viral early gene expression by activating the NF-ÎºB pathway

Fetched: August 15th, 2024, 2:01am UTC by Nicholas J H Salisbury

Proc Natl Acad Sci U S A. 2024 Aug 20;121(34):e2403133121. doi: 10.1073/pnas.2403133121. Epub 2024 Aug 14.

ABSTRACT

Polyomaviruses are small, circular dsDNA viruses that can cause cancer. Alternative splicing of polyomavirus early transcripts generates large and small tumor antigens (LT, ST) that play essential roles in viral replication and tumorigenesis. Some polyomaviruses also express middle tumor antigens (MTs) or alternate LT open reading frames (ALTOs), which are evolutionarily related but have distinct gene structures. MTs are a splice variant of the early transcript whereas ALTOs are overprinted on the second exon of the LT transcript in an alternate reading frame and are translated via an alternative start codon. Merkel cell polyomavirus (MCPyV), the only human polyomavirus that causes cancer, encodes an ALTO but its role in the viral lifecycle and tumorigenesis has remained elusive. Here, we show MCPyV ALTO acts as a tumor suppressor and is silenced in Merkel cell carcinoma (MCC). Rescuing ALTO in MCC cells induces growth arrest and activates NF-ÎºB signaling. ALTO activates NF-ÎºB by binding SQSTM1 and TRAF2&3 via two N-Terminal Activating Regions (NTAR1+2), resembling Epstein-Barr virus (EBV) Latent Membrane Protein 1 (LMP1). Following activation, NF-ÎºB dimers bind the MCPyV noncoding control region (NCCR) and downregulate early transcription. Beyond MCPyV, NTAR motifs are conserved in other polyomavirus ALTOs, which activate NF-ÎºB signaling, but are lacking in MTs that do not. Furthermore, polyomavirus ALTOs downregulate their respective viral early transcription in an NF-ÎºB- and NTAR-dependent manner. Our findings suggest that ALTOs evolved to suppress viral replication and promote viral latency and that MCPyV ALTO must be silenced for MCC to develop.

PMID:39141346 | PMC:PMC11348336 | DOI:10.1073/pnas.2403133121

Permalink for 'Exploring the therapeutic modalities of targeted treatment approach for skin carcinoma: cutting-edge strategies and key insights'

Exploring the therapeutic modalities of targeted treatment approach for skin carcinoma: cutting-edge strategies and key insights

Fetched: August 14th, 2024, 2:01am UTC by Vaibhavi Meghraj Desai

Expert Opin Drug Deliv. 2024 Aug;21(8):1213-1233. doi: 10.1080/17425247.2024.2392799. Epub 2024 Aug 19.

ABSTRACT

INTRODUCTION: Skin carcinoma, including malignant melanoma, basal, squamous, and Merkel cell carcinoma, present significant healthcare challenges. Conventional treatments like surgery and chemotherapy suffer from limitations like non-specificity, toxicity, and adverse effects. The upcoming treatments are dominated by nano-sized delivery systems, which improve treatment outcomes while minimizing side effects. Moving ahead, targeted nanoparticles allow localized delivery of drugs at tumor site, ensuring minimal damage to surrounding tissues.

AREAS COVERED: This review explores various targeting strategies for specific types of skin cancers. The strategies discussed include nanocarrier-mediated targeted delivery with multiple types of ligands like aptamers, antibodies, peptides, and vitamins and their advantages in skin cancer. Upcoming cutting-edge technologies such as smart delivery systems, microneedle-assisted delivery and three-dimensional printed scaffolds have also been discussed in detail. The findings in this review are summarized from databases like PubMed, Scopus, Web of Science, ClinicalTrials.gov, NIH, and articles published between 2005 and 2024 that discuss targeted therapy for skin cancer.

EXPERT OPINION: Specific cancer-targeting strategies promise personalized treatments, improving response rates and reducing need for intensive therapies. The review highlights various challenges, their solution, and economic aspects in this dynamic field. It further emphasizes the potential for specialized strategies to revolutionize skin cancer treatment.

PMID:39136542 | DOI:10.1080/17425247.2024.2392799

Permalink for 'Avelumab as second-line or later treatment in patients with metastatic Merkel cell carcinoma: Analysis of real-world outcomes in France using the CARADERM database linked to the French national healthcare database'

Avelumab as second-line or later treatment in patients with metastatic Merkel cell carcinoma: Analysis of real-world outcomes in France using the CARADERM database linked to the French national healthcare database

Fetched: August 12th, 2024, 2:02am UTC by Laurent Mortier

Eur J Cancer. 2024 Sep;209:114261. doi: 10.1016/j.ejca.2024.114261. Epub 2024 Aug 3.

ABSTRACT

AIM: Avelumab has been approved worldwide for treatment of metastatic Merkel cell carcinoma (mMCC), a rare and aggressive skin cancer. This study evaluated outcomes in patients with mMCC in France who received avelumab as second-line or later (2L+) treatment in routine clinical practice.

METHODS: This retrospective, noninterventional study evaluated all patients diagnosed with mMCC using two databases: CARADERM (French national database of rare dermatological cancers) and SNDS (national healthcare database), identified via probabilistic linkage. Eligible patients initiated avelumab as 2L+ treatment between August 2016 and December 2019 and were followed for 24 months. The primary endpoint was overall survival (OS) at 24 months.

RESULTS: Overall, 180 patients who received 2L+ avelumab were identified (112 from CARADERM, 68 after SNDS linkage). Median age at diagnosis was 74.0 years and 177 (98.3 %) had received chemotherapy alone as first-line treatment. Median follow-up was 13.1 months. Median OS from start of avelumab was 14.6 months (95 % CI, 9.9-21.3) in the overall population, 15.9 months (95 % CI, 8.6-28.3) in CARADERM patients, and 13.3 months (95 % CI, 6.7-19.1) in non-CARADERM patients. OS rates at 12 and 24 months were 53.8 % (95 % CI, 46.2 %-60.8 %) and 40.5 % (95 % CI, 33.2 %-47.6 %), respectively. In evaluable patients (CARADERM database), median progression-free survival was 3.6 months (95 % CI, 2.7-7.5) and the objective response rate was 55.3 % (95 % CI, 45.3-65.4), including complete response in 31.9 %.

CONCLUSIONS: Real-world outcomes with 2L+ avelumab treatment for mMCC are consistent with clinical trial findings, supporting the recommendation of avelumab as a standard of care.

PMID:39128185 | DOI:10.1016/j.ejca.2024.114261

Immune Checkpoint Inhibitor Therapy for Periocular Merkel Cell Carcinoma

Fetched: August 12th, 2024, 2:02am UTC by Joshua Hohlbein

Ophthalmology. 2024 Aug 8:S0161-6420(24)00463-9. doi: 10.1016/j.ophtha.2024.08.004. Online ahead of print.

NO ABSTRACT

PMID:39127410 | DOI:10.1016/j.ophtha.2024.08.004

Mapping of Human Polyomavirus in Renal Cell Carcinoma Tissues

Fetched: August 11th, 2024, 2:02am UTC by Ghalib Mobaraki

Int J Mol Sci. 2024 Jul 27;25(15):8213. doi: 10.3390/ijms25158213.

ABSTRACT

Worldwide, the incidence of renal cell carcinoma (RCC) is rising, accounting for approximately 2% of all cancer diagnoses and deaths. The etiology of RCC is still obscure. Here, we assessed the presence of HPyVs in paraffin-embedded tissue (FFPE) resected tissue from patients with RCC by using different molecular techniques. Fifty-five FFPE tissues from 11 RCC patients were included in this study. Consensus and HPyV-specific primers were used to screen for HPyVs. Both PCR approaches revealed that HPyV is frequently detected in the tissues of RCC kidney resections. A total of 78% (43/55) of the tissues tested were positive for at least one HPyV (i.e., MCPyV, HPyV6, HPyV7, BKPyV, JCPyV, or WUyV). Additionally, 25 tissues (45%) were positive for only one HPyV, 14 (25%) for two HPyVs, 3 (5%) for three HPyVs, and 1 one (1%) tissue specimen was positive for four HPyVs. Eleven (20%) RCC specimens were completely devoid of HPyV sequences. MCPyV was found in 24/55 RCC tissues, HPyV7 in 19, and HPyV6 in 8. The presence of MCPyV and HPyV6 was confirmed by specific FISH or RNA-ISH. In addition, we aimed to confirm HPyV gene expression by IHC. Our results strongly indicate that these HPyVs infect RCC and nontumor tissues, possibly indicating that kidney tissues serve as a reservoir for HPyV latency. Whether HPyVs possibly contribute to the etiopathogenesis of RCC remains to be elucidated.

PMID:39125783 | PMC:PMC11312419 | DOI:10.3390/ijms25158213

High cardiovascular mortality risk among older merkel cell carcinoma patients

Fetched: August 11th, 2024, 2:02am UTC by Jia-Nan Huang

BMC Geriatr. 2024 Aug 9;24(1):670. doi: 10.1186/s12877-024-05222-8.

ABSTRACT

OBJECTIVE: Previous research has primarily focused on the incidence and mortality rates of Merkel cell carcinoma (MCC), neglecting the examination of cardiovascular mortality (CVM) risk among survivors, particularly older patients. This study aims to assess the risk of CVM in older individuals diagnosed with MCC.

METHODS: Data pertaining to older MCC patients were obtained from the Surveillance, Epidemiology, and End Results database (SEER). CVM risk was measured using standardized mortality ratio (SMR) and cumulative mortality. Multivariate Fine-Gray's competing risk model was utilized to evaluate the risk factors contributing to CVM.

RESULTS: Among the study population of 2,899 MCC patients, 465 (16.0%) experienced CVM during the follow-up period. With the prolongation of the follow-up duration, the cumulative mortality rate for CVM reached 27.36%, indicating that cardiovascular disease (CVD) became the second most common cause of death. MCC patients exhibited a higher CVM risk compared to the general population (SMR: 1.69; 95% CI: 1.54-1.86, p < 0.05). Notably, the SMR for other diseases of arteries, arterioles, and capillaries displayed the most significant elevation (SMR: 2.69; 95% CI: 1.16-5.29, p < 0.05). Furthermore, age at diagnosis and disease stage were identified as primary risk factors for CVM, whereas undergoing chemotherapy or radiation demonstrated a protective effect.

CONCLUSION: This study emphasizes the significance of CVM as a competing cause of death in older individuals with MCC. MCC patients face a heightened risk of CVM compared to the general population. It is crucial to prioritize cardiovascular health starting from the time of diagnosis and implement personalized CVD monitoring and supportive interventions for MCC patients at high risk. These measures are essential for enhancing survival outcomes.

PMID:39123101 | PMC:PMC11312700 | DOI:10.1186/s12877-024-05222-8

Introducing MCC-PS: a novel prognostic score for Merkel cell carcinoma

Fetched: August 7th, 2024, 2:01am UTC by Nessr Abu Rached

Front Oncol. 2024 Jul 22;14:1427740. doi: 10.3389/fonc.2024.1427740. eCollection 2024.

ABSTRACT

INTRODUCTION: Merkel cell carcinoma (MCC) is an aggressive skin cancer with a poor prognosis, which only improved with the introduction of immunotherapies. An MCC prediction model with high diagnostic accuracy is lacking. The aim was to develop an MCC prognostic score (MCC-PS) based on combinations of previously proposed risk factors.

METHODS: A multicentric, retrospective study was conducted to develop MCC-PS, which included age, neuron-specific enolase (NSE), C-reactive protein (CRP), creatinine, bilirubin, and international normalized ratio (INR). Creatinine, bilirubin, and INR were used to calculate the model of end-stage liver disease (MELD) score. A total of 98 patients were included in the study, including 36.7% with stage I according to American Joint Committee on Cancer 2018 (n = 36), 30.6% with stage II (n = 30), 25.5% with stage III (n = 25), and 7.1% with stage IV (n = 7). Survival data of MCC patients were correlated with selected laboratory parameters and risk factors. Primary endpoint was MCC-specific survival (MSS) and the secondary endpoint was progression-free survival. Several statistical methods were used to develop the prognostic score, including correlation analysis, Kaplan-Meier curves, Cox regression, and time-dependent receiver operating characteristic analysis.

RESULTS: The MCC-PS is based on the sum of the following baseline variables: elevated CRP (â‰¥5.5 mg/l), elevated NSE (â‰¥22.8 Âµg/l), MELD score â‰¥ 11, and age â‰¥ 75 years. An MELD score â‰¥ 11 was scored as 4 points, elevated NSE level as 3 points, elevated CRP level as 2 points, and age â‰¥ 75 years as 1 point. A high-risk group according to the MCC-PS was characterized by a score of 4 or more points. The high-risk group was associated with a worse prognosis than the low-risk group (1-year MSS 62%, 2-year 43.1%, 5-year 17.6% as compared to 1-year MSS 79.5%, 3-year 75%, 5-year 72%). Notably, the developed MCC-PS predicts MCC outcome measures with high accuracy (3-year MSS: area under the curve (AUC) 0.934, sensitivity 87.5% and specificity 82.2%; 5-year MSS: AUC 0.93, sensitivity 89% and specificity 82%).

CONCLUSION: MCC-PS is the first prognostic score predicting MCC outcome with a high accuracy based on five easily available laboratory parameters and patient's age. An MCC-PS of 4 or more indicates a high-risk patient associated with a poor prognosis.

PMID:39104722 | PMC:PMC11298473 | DOI:10.3389/fonc.2024.1427740

Permalink for 'Changes in Merkel cell oncoprotein antibodies after radiation therapy in curatively treated Merkel cell carcinoma and association with recurrence'

Changes in Merkel cell oncoprotein antibodies after radiation therapy in curatively treated Merkel cell carcinoma and association with recurrence

Fetched: August 6th, 2024, 2:01am UTC by Kevin X Liu

Cancer. 2024 Aug 5. doi: 10.1002/cncr.35507. Online ahead of print.

ABSTRACT

BACKGROUND: Serum antibodies to the Merkel oncoprotein (AMERK) are detectable in approximately 50% of patients with Merkel cell carcinoma (MCC) and can be used to monitor for recurrence. The objective of this study was to characterize AMERK levels in patients receiving curative-intent radiation therapy (RT) for MCC and identify associations between AMERK and recurrence.

METHODS: This was a retrospective study of patients with MCC who had baseline AMERK measurements before they received curative-intent RT from 2010 to 2020. Event-free survival (EFS) was calculated using the Kaplan-Meier method and Cox regression. The cumulative incidence of MCC-related recurrence (CIMR) was analyzed with death as a competing risk and the Gray test.

RESULTS: The authors identified 88 patients who had baseline AMERK measurements, including 52 (59%) with detectable levels. AMERK positivity was associated with younger median age (67.8 vs. 72.0 years; p = .02) and tumor site (p = 0.02), with lower rates for those who had disease in the head/neck region (17.3% vs. 44.4%). EFS (71.3% vs. 60.4%; p = .30) and CIMR (24.4% vs. 39.6%; p = .23) were more favorable in AMERK-positive patients. Two patients had recurrences in the RT field, and both were AMERK-negative at baseline. The median time to AMERK nadir after RT was 11.2 months; and, in a 6-month post-RT landmark analysis, the proportion of patients who were AMERK-positive who became negative or who had levels that decreased by â‰¥50% were not associated with EFS (87.1% vs. 85.0%; p = .90) or CIMR (12.9% vs. 15.0%; p = .62).

CONCLUSIONS: Positive AMERK baseline levels were correlated with younger age at MCC diagnosis and nonhead and neck tumor location, possibly related to the distribution of viral etiology. A specific post-RT AMERK decline correlating with EFS could not be identified.

PMID:39101686 | DOI:10.1002/cncr.35507

Current status of Merkel cell carcinoma: Epidemiology, pathogenesis and prognostic factors

Fetched: August 5th, 2024, 2:02am UTC by Zijie Li

Virology. 2024 Nov;599:110186. doi: 10.1016/j.virol.2024.110186. Epub 2024 Jul 31.

ABSTRACT

Merkel cell carcinoma (MCC) is an extremely rare cutaneous neuroendocrine cancer, with an incidence approximately 40 times lower than that of malignant melanoma; however, its significantly inferior survival rate compared to melanoma establishes MCC as the most lethal form of skin cancer. In recent years, a substantial body of literature has demonstrated a gradual increase in the incidence of MCC. Although the two factors that contribute to MCC, ultraviolet radiation and Merkel cell polyomavirus infection, have been well established, the specific pathogenesis of this disease remains unclear. Additionally, considering the high lethality and recurrence rates of MCC, as well as the absence of specific antitumor drugs, it is crucial to elucidate the factors that can accurately predict patients' outcomes. In this review, we summarized the significant advancements in the epidemiological characteristics, pathogenesis, and the factors that influence patient prognosis of MCC to enhance clinical practices and public health efforts.

PMID:39098121 | DOI:10.1016/j.virol.2024.110186

Wnt/beta-catenin activated non pilomatrical carcinoma of the skin: a case series

Fetched: August 4th, 2024, 2:01am UTC by Thibault Kervarrec

Mod Pathol. 2024 Jul 31;37(11):100586. doi: 10.1016/j.modpat.2024.100586. Online ahead of print.

ABSTRACT

Among skin epithelial tumors, recurrent mutations in the APC/CTNNB1 genes resulting in activation of the Wnt/Î²-catenin pathway have been reported predominantly in neoplasms with matrical differentiation. In the present study, we describe the morphologic, immunohistochemical, and genetic features of 16 primary cutaneous carcinomas harboring mutations activating the Wnt/Î²-catenin pathway without evidence of matrical differentiation, as well as 4 combined tumors in which a similar Wnt/Î²-catenin-activated carcinoma component was associated with Merkel cell carcinoma (MCC) or pilomatrical carcinoma. Among the pure tumor cases, 6 of 16 patients were women with a median age of 80 years (range, 58-98 years). Tumors were located on the head and neck (n = 7, 44%), upper limb (n = 4, 25%), trunk (n = 3, 18%), and leg (n = 2, 13%). Metastatic spread was observed in 4 cases resulting in death from disease in 1 patient. Microscopically, all cases were poorly differentiated neoplasms infiltrating the dermis and/or subcutaneous tissue. In 13 cases, solid "squamoid" areas were associated with a basophilic component characterized by rosette/pseudoglandular formation resulting in a biphasic appearance. Three specimens consisted only of poorly differentiated carcinoma lacking rosette formation. Immunohistochemical studies showed frequent expression of EMA (100%), BerEP4 (100%), cytokeratin 7 (94%), chromogranin A (44%), synaptophysin (82%), and cytokeratin 20 (69%). Complete loss of Rb expression was observed in all but 1 case. Nuclear Î²-catenin and CDX2 expressions were detected in all cases. Recurrent pathogenic somatic mutations were observed in APC (60%), CTNNB1 (40%), and RB1 (n = 47%). Global methylation analysis confirmed that cases with rosette formation constituted a homogeneous tumor group distinct from established skin tumor entities (pilomatrical carcinoma, MCC, and squamous cell carcinoma), although the 3 other cases lacking such morphologic features did not. In addition, we identified 4 combined neoplasms in which there was a component showing a similar poorly differentiated rosette-forming carcinoma demonstrating Rb loss and Î²-catenin activation associated with either MCC (n = 3) or pilomatrical carcinoma (n = 1). In conclusion, we describe a distinctive neoplasm, for which we propose the term "Wnt/Î²-catenin-activated rosette-forming carcinoma," morphologically characterized by the association of rosette formation, squamous and/or neuroendocrine differentiation, diffuse CDX2 expression, Rb loss, and mutations in CTNNB1/APC genes.

PMID:39094735 | DOI:10.1016/j.modpat.2024.100586

Merkel cell polyomavirus protein ALTO modulates TBK1 activity to support persistent infection

Fetched: July 30th, 2024, 2:01am UTC by Ranran Wang

PLoS Pathog. 2024 Jul 29;20(7):e1012170. doi: 10.1371/journal.ppat.1012170. eCollection 2024 Jul.

ABSTRACT

While Merkel cell polyomavirus (MCPyV or MCV) is an abundant virus frequently shed from healthy skin, it is one of the most lethal tumor viruses in immunocompromised individuals, highlighting the crucial role of host immunity in controlling MCPyV oncogenic potential. Despite its prevalence, very little is known about how MCPyV interfaces with the host immune response to maintain asymptomatic persistent infection and how inadequate control of MCPyV infection triggers MCC tumorigenesis. In this study, we discovered that the MCPyV protein, known as the Alternative Large Tumor Open Reading Frame (ALTO), also referred to as middle T, effectively primes and activates the STING signaling pathway. It recruits Src kinase into the complex of STING downstream kinase TBK1 to trigger its autophosphorylation, which ultimately activates the subsequent antiviral immune response. Combining single-cell analysis with both loss- and gain-of-function studies of MCPyV infection, we demonstrated that the activity of ALTO leads to a decrease in MCPyV replication. Thus, we have identified ALTO as a crucial viral factor that modulates the STING-TBK1 pathway, creating a negative feedback loop that limits viral infection and maintains a delicate balance with the host immune system. Our study reveals a novel mechanism by which a tumorigenic virus-encoded protein can link Src function in cell proliferation to the activation of innate immune signaling, thereby controlling viral spread, and sustaining persistent infection. Our previous findings suggest that STING also functions as a tumor suppressor in MCPyV-driven oncogenesis. This research provides a foundation for investigating how disruptions in the finely tuned virus-host balance, maintained by STING, could alter the fate of MCPyV infection, potentially encouraging malignancy.

PMID:39074144 | PMC:PMC11285941 | DOI:10.1371/journal.ppat.1012170

Neuroendocrine Neoplasms

Fetched: July 29th, 2024, 2:01am UTC by Sukhjeet Kamboj

Prim Care. 2024 Sep;51(3):549-560. doi: 10.1016/j.pop.2024.04.010. Epub 2024 May 23.

ABSTRACT

Neuroendocrine neoplasms (NENs), also known as neuroendocrine tumors (NETs), are rare tumors derived from cells with characteristics of both nerve and endocrine cells. The clinical presentation, diagnosis, and treatment of NENs vary significantly depending on the type, location, whether the neoplasm is hormonally functional, how aggressive it is, and whether it has metastasized to other parts of the body. This article provides an overview of specific types of NETs, clinical presentations and related syndromes, diagnosis, and approach to management of common NENs.

PMID:39067978 | DOI:10.1016/j.pop.2024.04.010

Profound ctDNA and radiological responses after 2 cycles of avelumab in a metastatic Merkel cell carcinoma of the head and neck

Fetched: July 29th, 2024, 2:01am UTC by Santiago Cabezas-Camarero

Oral Oncol. 2024 Oct;157:106971. doi: 10.1016/j.oraloncology.2024.106971. Epub 2024 Jul 26.

ABSTRACT

BACKGROUND: Merkel cell carcinoma (MCC) is an uncommon skin cancer that in more than 90 % of cases develops within the head and neck region. MCC is an aggressive disease with a dismal prognosis before the advent of immunotherapy. Avelumab, an anti-PDL1 agent is approved since 2017 for the treatment of advanced MCC after demonstrating a high response rate and favorable impact in survival.

METHODS: Next generation sequencing (NGS) of the primary tumor biopsy from initial diagnosis (Foundation One CDx, Roche Diagnostics) as well as from plasma samples (Foundation One Liquid, Roche Diagnostics) obtained before and during treatment with avelumab were performed.

RESULTS: We present the case of a patient with a metastatic MCC developing in the left parotid gland / pre-auricular area in an 80-year-old male with a long-lasting history of high UV exposure. After two cycles of avelumab 10 mg/kg/q2wk a near complete metabolic response and a major radiological response occurred in parallel to a brisk reduction in the ctDNA tumor fraction as well as variant-allele frequencies (VAFs) of all the mutations detected before the start of avelumab.

CONCLUSION: Avelumab may achieve rapid and major responses in metastatic MCC. Our study demonstrates that ctDNA mirrors radiological responses and may serve as an ideal companion for diagnosis and disease monitoring in MCC.

PMID:39067262 | DOI:10.1016/j.oraloncology.2024.106971

Inpatient prevalence and factors associated with Merkel Cell Carcinoma inpatient hospitalization in the United States

Fetched: July 29th, 2024, 2:01am UTC by Maci Terrell

Arch Dermatol Res. 2024 Jul 27;316(8):489. doi: 10.1007/s00403-024-03222-7.

ABSTRACT

Merkel Cell Carcinoma is a rare and aggressive cutaneous carcinoma with a propensity for metastasis and death. Our study describes the prevalence, sociodemographics and inpatient mortality of Merkel Cell Carcinoma related hospitalizations in the United States from 2011 to 2020. We conducted an observational study using the Nationwide Inpatient Sample database, which captures a 20% sample of all hospitalizations in the United States. We utilized the International Classification of Disease Clinical Modification codes from the ninth and tenth revision to identify Merkel Cell Carcinoma and demographic factors. There was a total of 28,809 cases of Merkel Cell Carcinoma in the United States from 2011 to 2020. Merkel Cell Carcinoma was associated with white race (11.4 per 100,000) and disposition of death (26.8 per 100,000). It was most prevalent in the highest quartile income (12.5 per 100,000) and Medicare as primary payer (13.0 per 100,000). Hospitalization was lowest in nonwhite races, particularly NH-Blacks and NH-Others. Inpatient mortality was significantly associated with NH-Others (odds ratio 2.18, 95% confidence interval = 1.38-3.45) and self-pay patients (odds ratio = 2.93, 95% confidence interval 1.84-4.67).This study contributes to reported socio-demographic factors related to Merkel Cell Carcinomas and brings awareness to factors associated with increased hospitalization and inpatient mortality.

PMID:39066821 | DOI:10.1007/s00403-024-03222-7

Where Are We Now with Oncolytic Viruses in Melanoma and Nonmelanoma Skin Malignancies?

Fetched: July 28th, 2024, 2:01am UTC by George Nassief

Pharmaceuticals (Basel). 2024 Jul 9;17(7):916. doi: 10.3390/ph17070916.

ABSTRACT

Skin cancer prognosis has greatly improved recently due to the introduction of immune checkpoint inhibitors (ICIs). However, many patients with advanced skin cancer still experience immunotherapy resistance and disease progression during ICI treatment, thus calling for novel therapeutics which address this treatment gap. Talimogene laherparepvec (T-VEC) has gained popularity in recent years as a viable treatment option for patients with skin cancer. In preclinical studies, T-VEC demonstrated both a direct anti-tumor effect in injected lesions as well as a systemic immune-mediated effect in non-injected lesions, which could pose additional benefits when combined with ICI therapy. Following promising results from the OPTiM trial, the Food and Drug Administration (FDA) approved the usage of T-VEC as a single agent in advanced melanoma. However, the MASTERKEY-265 trial demonstrated that adding T-VEC to pembrolizumab did not offer additional clinical benefit in patients with melanoma. Nevertheless, the promising efficacy of T-VEC and its approval by the FDA helped oncolytic viruses (OVs) gain wide attention in cancer therapy, and extensive research has been undertaken to evaluate the usage of OVs in other tumors such as sarcomas and breast cancers. Here, we provide a review of clinical results from 2022 to 2024 that investigate the efficacy and safety of OVs as a monotherapy or in combination with other therapies in skin malignancies. Furthermore, we delineate the current limitations in OV utilization and outline future directions to enhance clinical outcomes for patients with skin malignancies receiving OV-based therapies.

PMID:39065766 | PMC:PMC11279659 | DOI:10.3390/ph17070916

The Role of Oncogenic Viruses in Head and Neck Cancers: Epidemiology, Pathogenesis, and Advancements in Detection Methods

Fetched: July 28th, 2024, 2:01am UTC by Pinelopi Samara

Microorganisms. 2024 Jul 19;12(7):1482. doi: 10.3390/microorganisms12071482.

ABSTRACT

Head and neck cancers (HNCs) constitute a wide range of malignancies originating from the epithelial lining of the upper aerodigestive tract, including the oral cavity, pharynx, larynx, nasal cavity, paranasal sinuses, and salivary glands. Although lymphomas affecting this region are not conventionally classified as HNCs, they may occur in lymph nodes or mucosa-associated lymphoid tissues within the head and neck. Oncogenic viruses play a crucial role in HNC onset. Human papillomavirus (HPV) is extensively studied for its association with oropharyngeal cancers; nevertheless, other oncogenic viruses also contribute to HNC development. This review provides an overview of the epidemiology, pathogenesis, and advancements in detection methods of oncogenic viruses associated with HNCs, recognizing HPV's well-established role while exploring additional viral connections. Notably, Epstein-Barr virus is linked to nasopharyngeal carcinoma and lymphomas. Human herpesvirus 8 is implicated in Kaposi's sarcoma, and Merkel cell polyomavirus is associated with subsets of HNCs. Additionally, hepatitis viruses are examined for their potential association with HNCs. Understanding the viral contributions in the head and neck area is critical for refining therapeutic approaches. This review underlines the interaction between viruses and malignancies in this region, highlighting the necessity for ongoing research to elucidate additional mechanisms and enhance clinical outcomes.

PMID:39065250 | PMC:PMC11279059 | DOI:10.3390/microorganisms12071482

Merkel Cell Carcinoma

Fetched: July 28th, 2024, 2:01am UTC by Jennifer Strong

Hematol Oncol Clin North Am. 2024 Oct;38(5):1133-1147. doi: 10.1016/j.hoc.2024.05.013. Epub 2024 Jul 26.

ABSTRACT

Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer that is highly radiosensitive and immunogenic. Immunotherapy is the primary treatment of advanced disease, and immune checkpoint inhibitors show promise as neoadjuvant or adjuvant therapy in patients with high-risk resectable MCC. Emerging biomarkers of tumor burden are becoming increasingly important in identifying high-risk patients and in post-treatment surveillance. Further research is needed to determine the optimal duration of anti-PD-(L)1 treatment and second-line options for patients with MCC refractory to immunotherapy. This review covers the characteristics and management of MCC including recent innovations and areas of active investigation.

PMID:39060119 | PMC:PMC11423797 | DOI:10.1016/j.hoc.2024.05.013

Genomic profiles of Merkel cell carcinoma in Japan

Fetched: July 27th, 2024, 2:01am UTC by Junji Kato

J Dermatol. 2024 Sep;51(9):1259-1261. doi: 10.1111/1346-8138.17401. Epub 2024 Jul 26.

NO ABSTRACT

PMID:39058281 | DOI:10.1111/1346-8138.17401

Permalink for 'Pre-existing skin-resident CD8 and gd T cell circuits mediate immune response in Merkel cell carcinoma and predict immunotherapy efficacy'

Pre-existing skin-resident CD8 and gd T cell circuits mediate immune response in Merkel cell carcinoma and predict immunotherapy efficacy

Fetched: July 27th, 2024, 2:01am UTC by Zachary Z Reinstein

Cancer Discov. 2024 Jul 26. doi: 10.1158/2159-8290.CD-23-0798. Online ahead of print.

ABSTRACT

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer with a ~50% response rate to immune checkpoint blockade (ICB) therapy. To identify predictive biomarkers, we integrated bulk and single-cell RNA-seq with spatial transcriptomics from a cohort of 186 samples from 116 patients, including bulk RNA-seq from 14 matched pairs pre- and post-ICB. In non-responders, tumors show evidence of increased tumor proliferation, neuronal stem cell markers, and IL-1. Responders have increased type I/II interferons and pre-existing tissue resident (Trm) CD8 or Vd1 gd T cells that functionally converge with overlapping antigen-specific transcriptional programs and clonal expansion of public TCRs. Spatial transcriptomics demonstrated co-localization of T cells with B and dendritic cells, which supply chemokines and co-stimulation. Lastly, ICB significantly increased clonal expansion or recruitment of Trm and Vd1 cells in tumors specifically in responders, underscoring their therapeutic importance. These data identify potential clinically actionable biomarkers and therapeutic targets for MCC.

PMID:39058036 | DOI:10.1158/2159-8290.CD-23-0798

Permalink for 'Retrospective Single-Center Case Study of Clinical Variables and the Degree of Actinic Elastosis Associated with Rare Skin Cancers'

Retrospective Single-Center Case Study of Clinical Variables and the Degree of Actinic Elastosis Associated with Rare Skin Cancers

Fetched: July 27th, 2024, 2:01am UTC by Konstantin Drexler

Biology (Basel). 2024 Jul 16;13(7):529. doi: 10.3390/biology13070529.

ABSTRACT

(1) Background: Rare skin cancers include epithelial, neuroendocrine, and hematopoietic neoplasias as well as cutaneous sarcomas. Ultraviolet (UV) radiation and sunburns are important drivers for the incidence of certain cutaneous sarcomas; however, the pathogenetic role of UV light is less clear in rare skin cancers compared to keratinocyte cancer and melanoma. In this study, we compared the degree of actinic elastosis (AE) as a surrogate for lifetime UV exposure among selected rare skin cancers (atypical fibroxanthoma [AFX], pleomorphic dermal sarcoma [PDS], dermatofibrosarcoma protuberans [DFSP], Kaposi sarcoma [KS], Merkel cell carcinoma [MCC], and leiomyosarcoma [LMS]) while taking into account relevant clinical variables (age, sex, and body site). (2) Methods: We newly established a semi-quantitative score for the degree of AE ranging from 0 = none to 3 = total loss of elastic fibers (basophilic degeneration) and multiplied it by the perilesional vertical extent (depth), measured histometrically (tumor-associated elastosis grade (TEG)). We matched the TEG of n = 210 rare skin cancers from 210 patients with their clinical variables. (3) Results: TEG values were correlated with age and whether tumors arose on UV-exposed body sites. TEG values were significantly higher in AFX and PDS cases compared to all other analyzed rare skin cancer types. As expected, TEG values were low in DFSP and KS, while MCC cases exhibited intermediate TEG values. (4) Conclusions: High cumulative UV exposure is more strongly associated with AFX/PDS and MCC than with other rare skin cancers. These important results expand the available data associated with rare skin cancers while also offering insight into the value of differentiating among these tumor types based on their relationship with sun exposure, potentially informing preventative, diagnostic and/or therapeutic approaches.

PMID:39056721 | PMC:PMC11274094 | DOI:10.3390/biology13070529

$Permalink for 'Merkel cell carcinoma refractory to anti-PD(L)1: utility of adding ipilimumab for salvage therapy'$

Merkel cell carcinoma refractory to anti-PD(L)1: utility of adding ipilimumab for salvage therapy

Fetched: July 27th, 2024, 2:01am UTC by Tomoko Akaike

J Immunother Cancer. 2024 Jul 24;12(7):e009396. doi: 10.1136/jitc-2024-009396.

ABSTRACT

Merkel cell carcinoma (MCC) incidence has risen to approximately 3,000 cases annually in the USA. Although anti-programmed cell death (ligand) 1 (PD-(L)1) agents are now the first-line treatment for advanced MCC, approximately 50% of such patients do not persistently benefit. In PD-(L)1-refractory cases, ipilimumab (anti-cytotoxic T lymphocyte antigen-4) is often added; however, the extent of the clinical benefit of this combination is controversial. We identified one prospective study, three retrospective studies, and three case reports regarding this combination in refractory MCC. The aggregate response rate from retrospective studies was 32% (13 of 41 patients) with 4 complete responses (CR) and 9 partial responses (PR). In the prospective study, the response rate was very similar at 31% (8 of 26 patients; 4 CR, 4 PR). Response durability was highly variable (range 2 to >43 months), with patients achieving CR having greater durability. Immune-related adverse events (irAEs) were â‰¥grade III in 29% (retrospective cohort, N=41) and 36% (prospective cohort, N=50). While these aggregate data indicate adding ipilimumab should be considered in this setting, many patients with refractory MCC are ineligible due to comorbidities/irAEs, and approximately 70% will not benefit from this regimen. There is thus a significant unmet need in PD-(L)1-refractory MCC and clinical trials in this setting should be encouraged.

PMID:39053946 | PMC:PMC11284820 | DOI:10.1136/jitc-2024-009396

Permalink for 'Circulating Tumor DNA Assay Detects Merkel Cell Carcinoma Recurrence, Disease Progression, and Minimal Residual Disease: Surveillance and Prognostic Implications'

Circulating Tumor DNA Assay Detects Merkel Cell Carcinoma Recurrence, Disease Progression, and Minimal Residual Disease: Surveillance and Prognostic Implications

Fetched: July 27th, 2024, 2:01am UTC by Tomoko Akaike

J Clin Oncol. 2024 Jul 25:JCO2302054. doi: 10.1200/JCO.23.02054. Online ahead of print.

ABSTRACT

PURPOSE: Merkel cell carcinoma (MCC) is an aggressive skin cancer with a 40% recurrence rate, lacking effective prognostic biomarkers and surveillance methods. This prospective, multicenter, observational study aimed to evaluate circulating tumor DNA (ctDNA) as a biomarker for detecting MCC recurrence.

METHODS: Plasma samples, clinical data, and imaging results were collected from 319 patients. A tumor-informed ctDNA assay was used for analysis. Patients were divided into discovery (167 patients) and validation (152 patients) cohorts. Diagnostic performance, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), was assessed.

RESULTS: ctDNA showed high sensitivity, 95% (discovery; 95% CI, 87 to 99) and 94% (validation; 95% CI, 85 to 98), for detecting disease at enrollment, with corresponding specificities of 90% (95% CI, 82 to 95) and 86% (95% CI, 77 to 93). A positive ctDNA during surveillance indicated increased recurrence risk, with hazard ratios (HRs) of 6.8 (discovery; 95% CI, 2.9 to 16) and 20 (validation; 95% CI, 8.3 to 50). The PPV for clinical recurrence at 1 year after a positive ctDNA test was 69% (discovery; 95% CI, 32 to 91) and 94% (validation; 95% CI, 71 to 100), respectively. The NPV at 135 days after a negative ctDNA test was 94% (discovery; 95% CI, 90 to 97) and 93% (validation; 95% CI, 89 to 97), respectively. Patients positive for ctDNA within 4 months after treatment had higher rates of recurrence, with 1-year rates of 74% versus 21% (adjusted HR, 7.4 [95% CI, 2.7 to 20]).

CONCLUSION: ctDNA testing exhibited high prognostic accuracy in detecting MCC recurrence, suggesting its potential to reduce frequent surveillance imaging. ctDNA also identifies high-risk patients who need more frequent imaging and may be best suited for adjuvant therapy trials.

PMID:39052958 | DOI:10.1200/JCO.23.02054

Permalink for 'Analyses of combined Merkel cell carcinomas with neuroblastic components suggests that loss of T antigen expression in Merkel cell carcinoma may result in cell cycle arrest and neuroblastic transdifferentiation'

Analyses of combined Merkel cell carcinomas with neuroblastic components suggests that loss of T antigen expression in Merkel cell carcinoma may result in cell cycle arrest and neuroblastic transdifferentiation

Fetched: July 27th, 2024, 2:01am UTC by Thibault Kervarrec

J Pathol. 2024 Sep;264(1):112-124. doi: 10.1002/path.6304. Epub 2024 Jul 25.

ABSTRACT

Merkel cell carcinoma (MCC) is an aggressive skin cancer frequently caused by genomic integration of the Merkel cell polyomavirus (MCPyV). MCPyV-negative cases often present as combined MCCs, which represent a distinctive subset of tumors characterized by association of an MCC with a second tumor component, mostly squamous cell carcinoma. Up to now, only exceptional cases of combined MCC with neuroblastic differentiation have been reported. Herein we describe two additional combined MCCs with neuroblastic differentiation and provide comprehensive morphologic, immunohistochemical, transcriptomic, genetic and epigenetic characterization of these tumors, which both arose in elderly men and appeared as an isolated inguinal adenopathy. Microscopic examination revealed biphasic tumors combining a poorly differentiated high-grade carcinoma with a poorly differentiated neuroblastic component lacking signs of proliferation. Immunohistochemical investigation revealed keratin 20 and MCPyV T antigen (TA) in the MCC parts, while neuroblastic differentiation was confirmed in the other component in both cases. A clonal relation of the two components can be deduced from 20 and 14 shared acquired point mutations detected by whole exome analysis in both combined tumors, respectively. Spatial transcriptomics demonstrated a lower expression of stem cell marker genes such as SOX2 and MCM2 in the neuroblastic component. Interestingly, although the neuroblastic part lacked TA expression, the same genomic MCPyV integration and the same large T-truncating mutations were observed in both tumor parts. Given that neuronal transdifferentiation upon TA repression has been reported for MCC cell lines, the most likely scenario for the two combined MCC/neuroblastic tumors is that neuroblastic transdifferentiation resulted from loss of TA expression in a subset of MCC cells. Indeed, DNA methylation profiling suggests an MCC-typical cellular origin for the combined MCC/neuroblastomas. Â© 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

PMID:39049595 | DOI:10.1002/path.6304

Magnetic seed localization is feasible for non-palpable melanoma, Merkel cell carcinoma, and soft tissue sarcoma lesions

Fetched: July 27th, 2024, 2:01am UTC by S J C van der Burg

Eur J Surg Oncol. 2024 Jun 29;50(10):108485. doi: 10.1016/j.ejso.2024.108485. Online ahead of print.

ABSTRACT

BACKGROUND: Localization of non-palpable melanoma, Merkel cell carcinoma (MCC) and soft tissue sarcoma (STS) lesions can be difficult due to size, location, and obesity of patients or fibrosis due to previous treatments. Magnetic seed localization (MSL) is a common method to localize non-palpable breast lesions, but the feasibility of MSL for non-palpable melanoma, MCC and STS lesions has not yet been described.

METHODS: In this retrospective single center cohort study, all consecutive patients between January 2021 and October 2023 who had a resection of a non-palpable melanoma, MCC or STS lesion guided by Sirius Pintuition, a MSL technique, were included. The primary endpoint was successful lesion localization during surgery and the secondary endpoints were seed migration, negative resection margins, and complications.

RESULTS: Seventy-nine seeds were placed for 76 lesions, which were resected during 68 surgeries in 61 patients. All lesions (100 %) were localized and resected. Median time of surgery was 44 min. No seed migration was observed. A negative resection margin was achieved for 60 (78.9 %) lesions. Clavien Dindo grade â‰¥2 complications occurred in 7.4 %.

CONCLUSION: Magnetic seed localization with Sirius Pintuition is feasible for both non-palpable melanoma, MCC, and STS lesions.

PMID:39047326 | DOI:10.1016/j.ejso.2024.108485

Permalink for 'Biomarker analyses investigating disease biology and associations with outcomes in the JAVELIN Merkel 200 trial of avelumab in metastatic Merkel cell carcinoma'

Biomarker analyses investigating disease biology and associations with outcomes in the JAVELIN Merkel 200 trial of avelumab in metastatic Merkel cell carcinoma

Fetched: July 27th, 2024, 2:01am UTC by Sandra P D'Angelo

Clin Cancer Res. 2024 Jul 24. doi: 10.1158/1078-0432.CCR-23-0395. Online ahead of print.

ABSTRACT

PURPOSE: Avelumab (anti-PD-L1) became the first approved treatment for metastatic Merkel cell carcinoma (mMCC) based on results from the phase 2 JAVELIN Merkel 200 trial. We report exploratory biomarker analyses from the trial.

PATIENTS AND METHODS: Patients with mMCC (n=88) with or without prior first-line chemotherapy received avelumab 10 mg/kg every 2 weeks. Analyses included: somatic mutations, mutational signatures, and tumor mutation burden from paired whole exome sequencing; gene, gene set, and immune content from RNAseq profiles; tumor PD-L1 and CD8 status from immunohistochemistry; and CD8 status from digital pathology.

RESULTS: Tumors positive for Merkel cell polyomavirus (MCPyV) were characterized by an absence of driver mutations and a low tumor mutational burden, consistent with previous studies. A novel MCPyV-specific host gene expression signature was identified. MCPyV+ tumors had increased levels of immunosuppressive M2 macrophages in the tumor microenvironment, which appeared to correlate with PD-L1 expression; high CD8+ T-cell density in these tumors did not predict response to avelumab. Conversely, in patients with MCPyV- tumors, higher CD8+ T-cell density appeared to be associated with response. Mutations in several genes were associated with treatment outcomes. Compared with tumors sampled before chemotherapy, tumors sampled after chemotherapy had downregulated gene signatures for immune responses, including reduced expression of IFN-Î³-related pathways. Levels of activated dendritic cells in responding patients were higher in patients assessed after vs before prior chemotherapy.

CONCLUSIONS: Exploratory analyses provide insights into mMCC biology and potential associations with response to avelumab. Chemotherapy seems to negatively modulate the immune microenvironment.

PMID:39047170 | DOI:10.1158/1078-0432.CCR-23-0395

The Clinical Utility of Teledermatology in Triaging and Diagnosing Skin Malignancies: Case Series

Fetched: July 24th, 2024, 2:02am UTC by Kimberly A Sable

Cutis. 2024 May;113(5):211-213. doi: 10.12788/cutis.1000.

ABSTRACT

With the increasing utilization of telemedicine since the COVID-19 pandemic, it is critical that clinicians have an appropriate understanding of the application of virtual care resources, including teledermatology. We present a case series of 3 patients to demonstrate the clinical utility of teledermatology in reducing the time to diagnosis of various rare and/or aggressive cutaneous malignancies, including Merkel cell carcinoma, malignant melanoma, and atypical fibroxanthoma. Cases were obtained from one large Midwestern medical center during the month of July 2021. Each case presented includes a description of the initial teledermatology presentation and reviews the clinical timeline from initial consultation submission to in-person clinic visit with lesion biopsy. This case series demonstrates real-world examples of how teledermatology can be utilized to expedite the care of specific vulnerable patient populations.

PMID:39042123 | DOI:10.12788/cutis.1000

spatialGE: A user-friendly web application to democratize spatial transcriptomics analysis

Fetched: July 20th, 2024, 2:01am UTC by Oscar E Ospina

bioRxiv [Preprint]. 2024 Jul 2:2024.06.27.601050. doi: 10.1101/2024.06.27.601050.

ABSTRACT

Spatial transcriptomics (ST) is a powerful tool for understanding tissue biology and disease mechanisms. However, its potential is often underutilized due to the advanced data analysis and programming skills required. To address this, we present spatialGE, a web application that simplifies the analysis of ST data. The application spatialGE provides a user-friendly interface that guides users without programming expertise through various analysis pipelines, including quality control, normalization, domain detection, phenotyping, and multiple spatial analyses. It also enables comparative analysis among samples and supports various ST technologies. We demonstrate the utility of spatialGE through its application in studying the tumor microenvironment of melanoma brain metastasis and Merkel cell carcinoma. Our results highlight the ability of spatialGE to identify spatial gene expression patterns and enrichments, providing valuable insights into the tumor microenvironment and its utility in democratizing ST data analysis for the wider scientific community.

PMID:39005315 | PMC:PMC11244876 | DOI:10.1101/2024.06.27.601050

Permalink for 'Quality of life and patient-reported toxicities in patients with advanced Merkel cell carcinoma treated with combined nivolumab and ipilimumab with or without stereotactic body radiation therapy'

Quality of life and patient-reported toxicities in patients with advanced Merkel cell carcinoma treated with combined nivolumab and ipilimumab with or without stereotactic body radiation therapy

Fetched: July 19th, 2024, 2:01am UTC by Aasha I Hoogland

Cancer Med. 2024 Jul;13(14):e7464. doi: 10.1002/cam4.7464.

ABSTRACT

BACKGROUND: Merkel cell carcinoma is a rare skin cancer associated with poor survival. Based on a previous Phase II trial of adults with advanced Merkel cell carcinoma by Kim and colleagues (2022), there is now a strong rationale for combination therapy (i.e., nivolumab and ipilimumab) to become a treatment option for patients with advanced Merkel cell carcinoma. The goal of this paper was to report on the secondary outcome of quality of life (QOL) among patients on this trial.

METHODS: Patients receiving combined nivolumab and ipilimumab, with or without stereotactic body radiation therapy (SBRT), completed the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 prior to starting treatment and every 2 weeks thereafter. Changes in QOL during treatment and post-treatment were evaluated using piecewise random-effects mixed models. Exploratory analyses compared changes in QOL between study arms. The original trial was registered with ClinicalTrials.gov (NCT03071406).

RESULTS: Study participants (n = 50) reported no changes in overall QOL (ps > 0.05), but emotional functioning improved during treatment (p = 0.01). Cognitive and social functioning worsened post-treatment (ps < 0.01). In general, patients treated with combination therapy only (n = 25) reported no change in QOL over time, whereas patients also treated with SBRT (n = 25) consistently demonstrated worsening QOL post-treatment.

CONCLUSION: QOL is generally preserved in patients treated with combination therapy, but the addition of SBRT may worsen QOL. Combined with clinical efficacy data published previously, results support the use of combination therapy with nivolumab and ipilimumab as a treatment option for patients with advanced Merkel cell carcinoma.

PMID:39021272 | PMC:PMC11255021 | DOI:10.1002/cam4.7464

$Permalink for 'Tumor Regression Following Engineered Polyomavirus-Specific T Cell Therapy in Immune Checkpoint Inhibitor-Refractory Merkel Cell Carcinoma'$

Tumor Regression Following Engineered Polyomavirus-Specific T Cell Therapy in Immune Checkpoint Inhibitor-Refractory Merkel Cell Carcinoma

Fetched: July 19th, 2024, 2:01am UTC by Yuta Asano

medRxiv [Preprint]. 2024 Jul 5:2024.07.01.24309780. doi: 10.1101/2024.07.01.24309780.

ABSTRACT

Although immune check-point inhibitors (CPIs) revolutionized treatment of Merkel cell carcinoma (MCC), patients with CPI-refractory MCC lack effective therapy. More than 80% of MCC express T-antigens encoded by Merkel cell polyomavirus, which is an ideal target for T-cell receptor (TCR)-based immunotherapy. However, MCC often repress HLA expression, requiring additional strategies to reverse the downregulation for allowing T cells to recognize their targets. We identified TCRMCC1 that recognizes a T-antigen epitope restricted to human leukocyte antigen (HLA)-A*02:01. Seven CPI-refractory metastatic MCC patients received CD4 and CD8 T cells transduced with TCRMCC1 (TTCR-MCC1) preceded either by lymphodepleting chemotherapy or an HLA-upregulating regimen (single-fraction radiation therapy (SFRT) or systemic interferon gamma (IFNÎ³)) with concurrent avelumab. Two patients who received preceding SFRT and IFNÎ³ respectively experienced tumor regression. One experienced regression of 13/14 subcutaneous lesions with 1 'escape' lesion and the other had delayed tumor regression in all lesions after initial progression. Although TTCR-MCC1 cells with an activated phenotype infiltrated tumors including the 'escape' lesion, all progressing lesions transcriptionally lacked HLA expression. While SFRT/IFNÎ³ did not immediately upregulate tumor HLA expression, a secondary endogenous antigen-specific T cell infiltrate was detected in one of the regressing tumors and associated with HLA upregulation, indicating in situ immune responses have the potential to reverse HLA downregulation. Indeed, supplying a strong co-stimulatory signal via a CD200R-CD28 switch receptor allows TTCR-MCC1 cells to control HLA-downregulated MCC cells in a xenograft mouse model, upregulating HLA expression. Our results demonstrate the potential of TCR gene therapy for metastatic MCC and propose a next strategy for overcoming epigenetic downregulation of HLA in MCC.

PMID:39006423 | PMC:PMC11245074 | DOI:10.1101/2024.07.01.24309780

Permalink for 'ISLET-1 expression in soft tissue neoplasms reveals high sensitivity but moderate specificity for desmoplastic small round cell tumors and potential utility as a diagnostic biomarker'

ISLET-1 expression in soft tissue neoplasms reveals high sensitivity but moderate specificity for desmoplastic small round cell tumors and potential utility as a diagnostic biomarker

Fetched: July 18th, 2024, 2:02am UTC by Faizan Malik

Pathol Res Pract. 2024 Aug;260:155469. doi: 10.1016/j.prp.2024.155469. Epub 2024 Jul 14.

ABSTRACT

ISLET-1 (ISL1) is a LIM-homeodomain transcription factor. Selective ISL1 expression is shown in neuroendocrine, non-neuroendocrine, and some soft tissue tumors including desmoplastic small round cell tumor (DSRCT). We assessed the specificity of ISL1 (clone EP283, 1:500, Cell Marque) in 288 soft tissue tumors, which included 17 DSRCTs and other histologic mimics. Positive staining threshold for ISL1 was set to >10 % of neoplastic cell nuclei at moderate intensity. ISL1 IHC was positive in 15/16 (94 %) DSRCTs with 75 % showing diffuse (>50 %) expression. ISL1 was positive in 1/10 (10 %) Ewing sarcomas (EWS), 7/13 (54 %) alveolar rhabdomyosarcoma (RMS), 14/22 (63 %) embryonal RMS, 7/14 (50 %) synovial sarcomas, 15/16 (93 %) neuroblastoma, 1/5 (20 %) Wilms tumor, 2/4 (50 %) olfactory neuroblastoma, and all 9 Merkel cell carcinomas. Other tumors, including all CIC::DUX4 sarcomas, were negative except 3/27 leiomyosarcomas, and 1 each of angiosarcoma, myxoid liposarcomas, inflammatory myofibroblastic tumor, malignant peripheral nerve sheath tumor, tenosynovial giant cell tumor, dedifferentiated LPS, and 1 ectomesenchymoma. In summary, among the soft tissue tumors tested, ISL1 is a highly sensitive but moderately specific marker for DSRCT and may be useful to distinguish from round cell mimics including EWS and CIC::DUX4 sarcomas. The oncogenic role of ISL1 in these tumors warrants further investigation.

PMID:39018925 | DOI:10.1016/j.prp.2024.155469

Early postoperative infection in patient with IgM deficiency

Fetched: July 18th, 2024, 2:02am UTC by Kayen Chan

Int Wound J. 2024 Jul;21(7):e70003. doi: 10.1111/iwj.70003.

ABSTRACT

Selective IgM deficiency is a rare immunological disorder, with patients presenting with recurrent infections and allergic manifestations. However, the association with early postoperative infection has not been widely reported in the literature. We describe a rare case of a patient who had an early wound infection 1 day after excision of a Merkel cell carcinoma from his right buttock and was later found to have decreased IgM levels. Selective IgM deficiency should therefore be considered in patients presenting with recurrent infections or in patients who have previously undergone surgery and subsequently developed early infection postoperatively. In this subset of patients, extra precautions may need to be taken pre- and postoperatively to reduce the risk of developing a postoperative infection.

PMID:39016243 | PMC:PMC11253023 | DOI:10.1111/iwj.70003

Cutaneotropic Polyomavirus Abundance in the Non-lesional Skin of Keratinocyte Carcinoma Patients: A Cross-sectional Study

Fetched: July 16th, 2024, 2:01am UTC by Eray Yihui Zhou

J Am Acad Dermatol. 2024 Jul 14:S0190-9622(24)02489-7. doi: 10.1016/j.jaad.2024.06.086. Online ahead of print.

NO ABSTRACT

PMID:39009226 | DOI:10.1016/j.jaad.2024.06.086

Lack of Clinically Significant Relationships of Age or Body Mass Index with Merkel Cell Carcinoma Immunotherapy Outcomes

Fetched: July 14th, 2024, 2:01am UTC by Rian Alam

Cancers (Basel). 2024 Jul 7;16(13):2480. doi: 10.3390/cancers16132480.

ABSTRACT

Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer with a high risk of metastasis. The development of anti-PD-1/PD-L1 immunotherapy has improved outcomes for advanced MCC, yet about 50% of such patients do not achieve durable responses. This study analyzed the effects of age and body mass index (BMI) on immunotherapy response in 183 advanced MCC patients from a single-center longitudinal database. Using Fine-Gray or Cox regression models, treatment response, progression-free survival (PFS), MCC-specific survival, and overall survival (OS) were evaluated. Age showed a significant non-linear relationship with treatment response (p = 0.04), with patients much older or younger than 70 years less likely to respond. However, age was not significantly associated with PFS (p = 0.21), MCC-specific survival (p = 0.72), or OS (p = 0.36). Similarly, BMI was not significantly correlated with treatment response (p = 0.41), PFS (p = 0.52), MCC-specific survival (p = 0.78), or OS (p = 0.71). Unlike previous studies suggesting that obesity and advanced age improve outcomes in other cancers, these associations were not observed in MCC. These findings suggest that age and BMI should not influence eligibility for immunotherapy in MCC patients, emphasizing the importance of unbiased patient selection for this treatment.

PMID:39001542 | PMC:PMC11240446 | DOI:10.3390/cancers16132480

Therapeutic Approaches for Non-Melanoma Skin Cancer: Standard of Care and Emerging Modalities

Fetched: July 14th, 2024, 2:01am UTC by Stefano Sol

Int J Mol Sci. 2024 Jun 27;25(13):7056. doi: 10.3390/ijms25137056.

ABSTRACT

Skin cancer encompasses a range of cutaneous malignancies, with non-melanoma skin cancers (NMSCs) being the most common neoplasm worldwide. Skin exposure is the leading risk factor for initiating NMSC. Ultraviolet (UV) light induces various genomic aberrations in both tumor-promoting and tumor-suppressing genes in epidermal cells. In conjunction with interactions with a changed stromal microenvironment and local immune suppression, these aberrations contribute to the occurrence and expansion of cancerous lesions. Surgical excision is still the most common treatment for these lesions; however, locally advanced or metastatic disease significantly increases the chances of morbidity or death. In recent years, numerous pharmacological targets were found through extensive research on the pathogenic mechanisms of NMSCs, leading to the development of novel treatments including Hedgehog pathway inhibitors for advanced and metastatic basal cell carcinoma (BCC) and PD-1/PD-L1 inhibitors for locally advanced cutaneous squamous cell carcinoma (cSCC) and Merkel cell carcinoma (MCC). Despite the efficacy of these new drugs, drug resistance and tolerability issues often arise with long-term treatment. Ongoing studies aim to identify alternative strategies with reduced adverse effects and increased tolerability. This review summarizes the current and emerging therapies used to treat NMSC.

PMID:39000164 | PMC:PMC11241167 | DOI:10.3390/ijms25137056

Permalink for 'ASO Visual Abstract: The Role of Neoadjuvant Immunotherapy in the Management of Merkel Cell Carcinoma with Clinically Detected Regional Lymph Node Metastasis'

ASO Visual Abstract: The Role of Neoadjuvant Immunotherapy in the Management of Merkel Cell Carcinoma with Clinically Detected Regional Lymph Node Metastasis

Fetched: July 13th, 2024, 2:01am UTC by Jenny H Chang

Ann Surg Oncol. 2024 Aug;31(8):5006. doi: 10.1245/s10434-024-15547-8.

NO ABSTRACT

PMID:38853214 | DOI:10.1245/s10434-024-15547-8

Permalink for 'ASO Author Reflections: Neoadjuvant Immunotherapy for Merkel Cell Carcinoma with Clinically Detected Regional Lymph Node Metastasis?'

ASO Author Reflections: Neoadjuvant Immunotherapy for Merkel Cell Carcinoma with Clinically Detected Regional Lymph Node Metastasis?

Fetched: July 13th, 2024, 2:01am UTC by Jenny H Chang

Ann Surg Oncol. 2024 Aug;31(8):5354-5355. doi: 10.1245/s10434-024-15564-7. Epub 2024 May 31.

NO ABSTRACT

PMID:38822171 | PMC:PMC11236848 | DOI:10.1245/s10434-024-15564-7

Permalink for 'Chemoreactive 2,5-Diketopiperazines from a Penicillium sp., Structure Revision of Reported Analogues and Proposed Facile Transformation Pathways'

Chemoreactive 2,5-Diketopiperazines from a Penicillium sp., Structure Revision of Reported Analogues and Proposed Facile Transformation Pathways

Fetched: July 13th, 2024, 2:01am UTC by Quan T Khong

J Nat Prod. 2024 Jul 26;87(7):1826-1837. doi: 10.1021/acs.jnatprod.4c00478. Epub 2024 Jul 12.

ABSTRACT

Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous cancer. Two new prenylated indole 2,5-diketopiperazine alkaloids, brevianamides E1 (1) and E2 (2), were isolated from a Penicillium fungus. Both compounds showed moderate cytotoxic activity against select MCC cell lines (i.e., MCC13, MKL-1, UISO, and WaGa) in the low micromolar range. The relative and absolute configurations of 1 and 2 were determined by combined approaches, including NOESY spectroscopy, DFT ECD and DP4 plus calculations, and Marfey's reaction. Literature research and the comparison of NMR and ECD data led to the structure revision of three previously reported natural analogues, notoamides K and P and asperversiamide L. The structurally unstable 1 and 2 underwent steady interconversion under neutral aqueous conditions. Investigation of the degradation of 2 in acidic methanol solutions led to the identification of a new methoxylated derivative (6) and two new ring-opened products (7 and 8) with the rearranged, elongated, 4-methylpent-3-ene side chain. The facile transformation of 2 to 7 and 8 was promoted by the intrinsic impurity (i.e., formaldehyde) of HPLC-grade methanol through the aza-Cope rearrangement.

PMID:38995621 | DOI:10.1021/acs.jnatprod.4c00478

Possible association between polyomaviruses and gastrointestinal complications: a narrative review

Fetched: July 13th, 2024, 2:01am UTC by Piruz Shadbash

Gastroenterol Hepatol Bed Bench. 2024;17(2):121-131. doi: 10.22037/ghfbb.v17i2.2796.

ABSTRACT

Polyomaviruses are a group of small, double-stranded DNA viruses that are known to be associated with the development of certain human diseases, but there is evidence that these viruses might be associated with gastrointestinal (GI) cancers. Several polyomaviruses have been identified, such as JC polyomavirus (JCPyV), BK polyomavirus (BKPyV) and recently Merkel cell polyomavirus (MCPyV). Although the direct effects of polyomaviruses on transformation of human cells and cancer development are not clearly recognized, their association with certain human diseases including GI cancers has been proposed through several molecular and epidemiological studies. For example, JCPyV and BKPyV have been linked to colorectal cancer, as there is growing evidence of finding viral genomes in cancerous tissues. Nevertheless, the major role of JCPyV, BKPyV and MCPyV in colorectal cancer progression is still under extensive investigation, and further surveys is required to establish a conclusive cause-and-effect relationship. Understanding the role of these viruses in cancer development has significant implications for diagnosis, treatment, and prevention strategies. It seems that proving a causal link between polyomaviruses and GI cancers might provide a novel path for targeted therapies or design and development of specific therapeutic vaccines. In addition, performing research on the possible link can provide insights into the underlying molecular mechanisms of carcinogenesis, potentially leading to the identification of novel biomarkers. This review focuses on polyomaviruses, in particular a recently discovered polyomavirus, MCPyV, and their possible link with human gastrointestinal disorders.

PMID:38994506 | PMC:PMC11234488 | DOI:10.22037/ghfbb.v17i2.2796

Use of immune checkpoint inhibitors in solid organ transplant recipients with advanced cutaneous malignancies

Fetched: July 13th, 2024, 2:01am UTC by Stephanie Ji

Front Transplant. 2023 Oct 30;2:1284740. doi: 10.3389/frtra.2023.1284740. eCollection 2023.

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors (ICI) are standard of care therapy for patients with cutaneous malignancies, the most frequently diagnosed cancers in solid organ transplant (SOT) recipients. The activity and rate of allograft rejection in SOT recipients with advanced skin cancers treated with ICI is understudied.

METHODS: We conducted a retrospective analysis of SOT recipients with advanced melanoma, cutaneous squamous cell carcinoma (cSCC), and merkel cell carcinoma (MCC) who were treated with ICI. Unpublished cases from our institution and published cases from the literature were aggregated. Demographics, type of immunosuppressive therapy, type of ICI(s) administered, prior systemic therapies, tumor response to ICI, and evidence of organ rejection and/or failure were recorded. Objective response rates (ORR) and rates of graft rejection and failure are reported.

RESULTS: Ninety patients were identified; four patients from our institution and 86 unique patients from a literature review. ORR to first-line ICI for the entire cohort was 41.1% (37/90). ORR by tumor type was 31% (18/58), 64.3% (18/28), and 25.0% (1/4) for melanoma, cSCC, and MCC, respectively. The rate of graft rejection was 37.8% (34/90) with 61.8% (21/34) of these cases progressing to graft failure. Number of immunosuppressive agents (0, 1, 2, or 3) was inversely associated with rate of graft failure.

CONCLUSIONS: In this retrospective analysis, ICIs demonstrate clinical activity in SOT recipients with cutaneous malignancies; however, the rate of graft rejection is high. Treatment plans should be individualized through thorough interdisciplinary discussion. Immunosuppressive modifications may be considered prior to starting treatment, but when feasible, enrollment on clinical trials is preferred.

PMID:38993910 | PMC:PMC11235332 | DOI:10.3389/frtra.2023.1284740

PRAME Expression in Merkel Cell Carcinoma

Fetched: July 13th, 2024, 2:01am UTC by Elisabeth Miller

Am J Surg Pathol. 2024 Jul 12. doi: 10.1097/PAS.0000000000002288. Online ahead of print.

ABSTRACT

Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine tumor of the skin. Risk factors include extensive sun damage, infection with Merkel cell polyomavirus, and an immunocompromised state. PRAME, also known as preferentially expressed antigen in melanoma, is a cancer-testis antigen recently found to be a useful diagnostic tool in the workup of melanocytic neoplasms. However, the expression pattern of PRAME in Merkel cell carcinoma is unknown. In this study, we examine PRAME expression in Merkel cell carcinoma and explore its prognostic implications. The institutional archives at the University of Virginia were used to search for tumors classified as Merkel cell carcinoma from 2004 to 2022. All potential cases were reviewed to confirm the diagnosis, and electronic medical records were searched for clinical and demographic data. Tumors were subsequently immunostained for PRAME and Merkel cell polyomavirus. Cox proportional hazards regression models were used to estimate relative (all-cause) survival of PRAME positivity and MCPyV positivity in our study as well as MCC-specific survival of PRAME positivity. Univariate and multivariable models were created for each outcome related to all-cause survival. A total of 39 cases were included in the study. Twenty-eight percent (11 cases) demonstrated strong PRAME expression, and 27% of cases were positive for Merkel cell polyomavirus. There was no statistically significant correlation between PRAME expression and virus positivity. With respect to PRAME, the adjusted all-cause mortality hazard ratio was 11.4 (95% CI: 1.8, 70.8). The unadjusted MCC-specific hazard ratio was 4.6 (95% CI: 0.8, 27.5). The adjusted hazard ratio pertaining to Merkel cell polyomavirus infection was 0.25 (95% CI: 0.02, 2.96). In this limited cohort, PRAME expression appears to correlate with worse outcomes in Merkel cell carcinoma.

PMID:38992873 | DOI:10.1097/PAS.0000000000002288

Permalink for 'Merkel Cell Carcinoma With Extensive Bone Marrow Metastasis and Peripheral Blood Involvement: A Case Report With Immunohistochemical and Mutational Studies'

Merkel Cell Carcinoma With Extensive Bone Marrow Metastasis and Peripheral Blood Involvement: A Case Report With Immunohistochemical and Mutational Studies

Fetched: July 12th, 2024, 2:01am UTC by Benjamin Highland

Appl Immunohistochem Mol Morphol. 2024 Jul 11. doi: 10.1097/PAI.0000000000001214. Online ahead of print.

ABSTRACT

Merkel cell carcinoma (MCC) is a rare, highly aggressive skin cancer of neuroendocrine origin that is typically associated with either the presence of Merkel cell polyomavirus or chronic exposure to ultraviolet (UV) light. We report a case of relapsed MCC that presented with new symptoms of fatigue, back pain, and myeloid left shift identified during scheduled follow-up. The patient was found to have circulating neoplastic cells in the peripheral blood and bone marrow metastasis. Immunohistochemistry for synaptophysin, CD56, INSM-1, CK20, CD117 were positive, whereas CD34, TdT, Chromogranin, CD10, myeloperoxidase, CD3 and CD19 were negative. Flow cytometry of the peripheral blood confirmed the presence of an abnormal nonhematopoietic cell population expressing CD56 positivity. A next-generation sequencing (NGS) panel revealed the presence of variants in RB1, TP53, and other genes, some of which have not been previously described in MCC. This rare presentation highlights the challenges in the diagnosis and management of MCC.

PMID:38990715 | DOI:10.1097/PAI.0000000000001214

Permalink for 'Merkel cell polyomavirus pan-T antigen knockdown reduces cancer cell stemness and promotes neural differentiation independent of RB1'

Merkel cell polyomavirus pan-T antigen knockdown reduces cancer cell stemness and promotes neural differentiation independent of RB1

Fetched: July 12th, 2024, 2:01am UTC by Kuan Cheok Lei

J Med Virol. 2024 Jul;96(7):e29789. doi: 10.1002/jmv.29789.

ABSTRACT

Merkel cell carcinoma (MCC) is a highly aggressive skin cancer associated with integration of Merkel cell polyomavirus (MCPyV). MCPyV-encoded T-antigens (TAs) are pivotal for sustaining MCC's oncogenic phenotype, i.e., repression of TAs results in reactivation of the RB pathway and subsequent cell cycle arrest. However, the MCC cell line LoKe, characterized by a homozygous loss of the RB1 gene, exhibits uninterrupted cell cycle progression after shRNA-mediated TA repression. This unique feature allows an in-depth analysis of the effects of TAs beyond inhibition of the RB pathway, revealing the decrease in expression of stem cell-related genes upon panTA-knockdown. Analysis of gene regulatory networks identified members of the E2F family (E2F1, E2F8, TFDP1) as key transcriptional regulators that maintain stem cell properties in TA-expressing MCC cells. Furthermore, minichromosome maintenance (MCM) genes, which encodes DNA-binding licensing proteins essential for stem cell maintenance, were suppressed upon panTA-knockdown. The decline in stemness occurred simultaneously with neural differentiation, marked by the increased expression of neurogenesis-related genes such as neurexins, BTG2, and MYT1L. This upregulation can be attributed to heightened activity of PBX1 and BPTF, crucial regulators of neurogenesis pathways. The observations in LoKe were confirmed in an additional MCPyV-positive MCC cell line in which RB1 was silenced before panTA-knockdown. Moreover, spatially resolved transcriptomics demonstrated reduced TA expression in situ in a part of a MCC tumor characterized by neural differentiation. In summary, TAs are critical for maintaining stemness of MCC cells and suppressing neural differentiation, irrespective of their impact on the RB-signaling pathway.

PMID:38988206 | DOI:10.1002/jmv.29789

The Impact of DNA Tumor Viruses in low-to-middle income countries (LMICS): a literature review

Fetched: July 9th, 2024, 2:02am UTC by Bothwell Takaingofa Guzha

Tumour Virus Res. 2024 Jul 6;18:200289. doi: 10.1016/j.tvr.2024.200289. Online ahead of print.

ABSTRACT

DNA viruses are common in the human population and act as aetiological agents of cancer on a large scale globally. They include the human papillomaviruses (HPV), Epstein-Barr virus (EBV), Kaposi sarcoma-associated herpesvirus (KSHV), hepatitis viruses, and human polyomaviruses. Oncogenic viruses employ different mechanisms to induce cancer. Notably, cancer only develops in a minority of individuals who are infected, usually following protracted years of chronic infection. The human papillomaviruses (HPVs) are associated with the highest number of cancer cases, including cervical cancer and other epithelial malignancies. Hepatitis B virus (HBV) and the RNA virus hepatitis C (HCV) are significant contributors to hepatocellular cancer (HCC). Other oncoviruses include Epstein-Barr virus (EBV), Kaposi sarcoma-associated herpes virus (KSHV), human T-cell leukemia virus (HTLV-I), and Merkel cell polyomavirus (MCPyV). The identification of these infectious agents as aetiological agents for cancer has led to reductions in cancer incidence through preventive interventions such as HBV and HPV vaccination, HPV-DNA based cervical cancer screening, antiviral treatments for chronic HBV and HCV infections, and screening of blood for transfusion for HBV and HCV. Successful efforts to identify additional oncogenic viruses in human cancer may provide further understanding of the aetiology and development of cancer, and novel approaches for prevention and treatment. Cervical cancer, caused by HPV, is the leading gynaecological malignancy in LMICs, with high age-standardised incidence and mortality rates, HCC due to HBV is an important cause of cancer deaths, and the burden of other cancer attributable to infections continues to rise globally. Hence, cancers attributable to DNA viruses have become a significant global health challenge. These viruses hence warrant continued attention and interrogation as efforts to understand them further and device further preventive interventions are critical.

PMID:38977263 | PMC:PMC11298656 | DOI:10.1016/j.tvr.2024.200289

The association between infectious agents and breast cancer: a review of the epidemiologic evidence

Fetched: July 7th, 2024, 2:02am UTC by Kristen D Brantley

Breast Cancer Res Treat. 2024 Sep;207(2):235-252. doi: 10.1007/s10549-024-07388-6. Epub 2024 Jul 6.

ABSTRACT

PURPOSE: Several viruses have been casually linked to human cancers, including cervical, nasopharyngeal, liver, sarcoma, and Merkel cell carcinomas. However, the etiologic contribution of viral infections to breast cancer, the number one incident cancer among women worldwide, is not well established. Among studies exploring associations of viruses with breast cancer, potential linkages have been identified between breast cancer and five viruses: beta retrovirus, (i.e., mouse mammary tumor virus), human papillomavirus, Epstein Barr virus. bovine leukemia virus, and human cytomegalovirus.

METHODS: In this review, we provide a comprehensive evaluation of epidemiological ecologic, case-control, case-only, and cohort studies investigating these associations. We discuss results from several existing reviews and meta-analyses, evaluate epidemiological studies published in the past five years, and assess the relationship between these viruses and breast tumor clinicopathological factors.

RESULTS: The strongest epidemiological evidence for a viral role in breast cancer exists for MMTV and HPV, though limitations include lack of prospective studies for MMTV and potential detection bias in HPV studies. Viral detection challenges have limited studies of EBV and HCMV. Fewer studies have evaluated BLV, and though it has been associated with higher risk of breast cancer, sample sizes are quite small. CONCLUSION: While epidemiologic evidence exists for an association between these five viruses and breast cancer, various methodological issues and lack of prospective studies preclude robust conclusions. Future research should prioritize establishing a temporal relationship between infection and disease, minimizing misclassification of detection assays, and further exploring the influence of co-infections.

PMID:38971906 | DOI:10.1007/s10549-024-07388-6

Mast cell density in Merkel cell carcinoma and its correlation with prognostic features and MCPyV status: a pilot study

Fetched: July 6th, 2024, 2:01am UTC by Gerardo Cazzato

Clin Exp Med. 2024 Jul 5;24(1):151. doi: 10.1007/s10238-024-01366-4.

ABSTRACT

Merkel cell carcinoma (MCC) is a rare, highly aggressive, primitive neuroendocrine carcinoma of the skin, the origin of which is not yet fully understood. Numerous independent prognostic factors have been investigated in an attempt to understand which are the most important parameters to indicate in the histological diagnostic report of MCC. Of these, mast cells have only been studied in one paper before this one. We present a retrospective descriptive study of 13 cases of MCC, received at the Department of Pathology over a 20-year period (2003-2023 inclusive) on which we performed a study using whole-slide (WSI) morphometric analysis scanning platform Aperio Scanscope CS for the detection and spatial distribution of mast cells, using monoclonal anti-tryptase antibody and anti-CD34 monoclonal antibody to study the density of microvessels. In addition, we analyzed MCPyV status with the antibody for MCPyV large T-antigen (Clone CM2B4). We found statistically significant correlation between mast cell density and local recurrence/distant metastasis/death-of-disease (p = 0.008). To our knowledge, we firstly reported that MCPyV ( -) MCC shows higher mast cells density compared to MCPyV ( +) MCC, the latter well known to be less aggressive. Besides, the median vascular density did not show no significant correlation with recurrence/metastasis/death-of-disease, (p = 0.18). Despite the small sample size, this paper prompts future studies investigating the role of mast cell density in MCC.

PMID:38967728 | PMC:PMC11226501 | DOI:10.1007/s10238-024-01366-4

Merkel cell carcinoma associated with TNF inhibitor therapy: a systematic review of case reports

Fetched: July 4th, 2024, 2:01am UTC by Mohammed Almashali

Dermatol Online J. 2024 Apr 15;30(2). doi: 10.5070/D330263575.

ABSTRACT

A rare neuroendocrine skin cancer called Merkel cell carcinoma (MCC) primarily affects elderly people. The objective of this study is to comprehensively review the impact of immunosuppressive medications, particularly TNF inhibitors, on the emergence of MCC.

METHODS: PubMed, Web of Science, Science Direct, and Cochrane Library were searched. Study articles were screened by title and abstract at Rayyan Qatar Computing Research Institute, then a full-text assessment was implemented.

RESULTS: A total of eight case reports with 9 patients were included. Of the total population, seven were women and only two were men. Their age ranged from 31 to 73 years. More than half the population (5 cases) were being treated for rheumatoid arthritis. All received TNF inhibitors that were associated with the induction of MCC.

CONCLUSION: We found that it is essential for physicians to explain potential cancer risks to patients before starting long-term immunosuppressive therapy and to conduct routine checks for MCC and other side effects. TNF inhibitors (infliximab, adalimumab, etanercept, and golimumab) were all associated with MCC development. Women constituted the majority of cases and most were elderly.

PMID:38959915 | DOI:10.5070/D330263575

Systemic Therapy for Non-Melanoma Skin Cancers: Latest Advances

Fetched: July 3rd, 2024, 2:01am UTC by Spencer Lessans

Curr Oncol Rep. 2024 Jul 2. doi: 10.1007/s11912-024-01570-1. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: This review provides an update on approved and emerging systemic therapies in the treatment of locally advanced or metastatic non-melanoma skin cancers (squamous cell carcinoma, basal cell carcinoma, Merkel cell carcinoma).

RECENT FINDINGS: Many studies demonstrate the effectiveness of immunotherapy for all types of non-melanoma skin cancer. For basal cell carcinoma (BCC), hedgehog inhibitors (HHI) remain first-line but with poor tolerability. Numerous clinical trials studying both neoadjuvant and adjuvant use of anti-PD-1 and anti-PD-L1 therapies in advanced NMSC are under investigation. There is a growing number of systemic therapies available to treat non-melanoma skin cancers. The advent of immunotherapy has revolutionized the field and greatly improved survival compared to historical survival rates with cytotoxic chemotherapy.

PMID:38954315 | DOI:10.1007/s11912-024-01570-1

Dermoscopic characteristics of Merkel cell carcinoma

Fetched: July 3rd, 2024, 2:01am UTC by Dimitra Koumaki

BMC Cancer. 2024 Jul 1;24(1):785. doi: 10.1186/s12885-024-12566-2.

ABSTRACT

BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive, cutaneous tumour with high mortality and frequently delayed diagnosis. Clinically, it often manifests as a rapidly growing erythematous to purple nodule usually located on the lower extremities or face and scalp of elderly patients. There is limited available data on the dermoscopic findings of MCC, and there are no specific features that can be used to definitively diagnose MCC.

AIM OF THE STUDY: Here, we aimed to summarize existing published literature on dermatoscopic and reflectance confocal microscopy (RCM) features of MCC.

MATERIALS AND METHODS: To find relevant studies, we searched the PubMed and Scopus databases from inception to April 12, 2023. Our goal was to identify all pertinent research that had been written in English. The following search strategy was employed: (" dermoscopy" OR " dermatoscopy" OR " videodermoscopy" OR " videodermatoscopy" OR " reflectance confocal microscopy") AND " Merkel cell carcinoma". Two dermatologists, DK and GE, evaluated the titles and abstracts separately for eligibility. For inclusion, only works written in English were taken into account.

RESULTS: In total 16 articles were retrieved (68 cases). The main dermoscopic findings of MCC are a polymorphous vascular pattern including linear irregular, arborizing, glomerular, and dotted vessels on a milky red background, with shiny or non-shiny white areas. Pigmentation was lacking in all cases. The RCM images showed a thin and disarranged epidermis, and small hypo-reflective cells that resembled lymphocytes arranged in solid aggregates outlined by fibrous tissue in the dermis. Additionally, there were larger polymorphic hyper-reflective cells that likely represented highly proliferative cells.

CONCLUSION: Dermoscopic findings of MCC may play a valuable role in evaluating MCC, aiding in the early detection and differentiation from other skin lesions. Further prospective case-control studies are needed to validate these results.

PMID:38951767 | PMC:PMC11218240 | DOI:10.1186/s12885-024-12566-2

Permalink for 'Corrigendum to "Characterizing the Therapeutic Potential of a Potent BET Degrader in Merkel Cell Carcinoma" [Neoplasia, Volume 21, Issue 3 (2019) 322-330]'

Corrigendum to "Characterizing the Therapeutic Potential of a Potent BET Degrader in Merkel Cell Carcinoma" [Neoplasia, Volume 21, Issue 3 (2019) 322-330]

Fetched: June 30th, 2024, 2:01am UTC by Jae Eun Choi

Neoplasia. 2024 Sep;55:101019. doi: 10.1016/j.neo.2024.101019. Epub 2024 Jun 28.

NO ABSTRACT

PMID:38943995 | PMC:PMC11261137 | DOI:10.1016/j.neo.2024.101019

Permalink for 'Casein kinase 1alpha mediates phosphorylation of the Merkel cell polyomavirus large T antigen for beta-TrCP destruction complex interaction and subsequent degradation'

Casein kinase 1alpha mediates phosphorylation of the Merkel cell polyomavirus large T antigen for beta-TrCP destruction complex interaction and subsequent degradation

Fetched: June 29th, 2024, 2:01am UTC by Alexander M Pham

mBio. 2024 Aug 14;15(8):e0111724. doi: 10.1128/mbio.01117-24. Epub 2024 Jun 28.

ABSTRACT

Merkel cell polyomavirus (MCPyV) is a double-stranded tumor virus that is the main causative agent of Merkel cell carcinoma (MCC). The MCPyV large T antigen (LT), an essential viral DNA replication protein, maintains viral persistence by interacting with host Skp1-Cullin 1-F-box (SCF) E3 ubiquitin ligase complexes, which subsequently induces LT's proteasomal degradation, restricting MCPyV DNA replication. SCF E3 ubiquitin ligases require their substrates to be phosphorylated to bind them, utilizing phosphorylated serine residues as docking sites. The MCPyV LT unique region (MUR) is highly phosphorylated and plays a role in multiple host protein interactions, including SCF E3 ubiquitin ligases. Therefore, this domain highly governs LT stability. Though much work has been conducted to identify host factors that restrict MCPyV LT protein expression, the kinase(s) that cooperates with the SCF E3 ligase remains unknown. Here, we demonstrate that casein kinase 1 alpha (CK1Î±) negatively regulates MCPyV LT stability and LT-mediated replication by modulating interactions with the SCF Î²-TrCP. Specifically, we show that numerous CK1 isoforms (Î±, Î´, Îµ) localize in close proximity to MCPyV LT through in situ proximity ligation assays (PLA) and CK1Î± overexpression mainly resulted in decreased MCPyV LT protein expression. Inhibition of CK1Î± using short hairpin RNA (shRNA) and treatment of a CK1Î± inhibitor or an mTOR inhibitor, TORKinib, resulted in decreased Î²-TrCP interaction with LT, increased LT expression, and enhanced MCPyV replication. The expression level of the CSNK1A1 gene transcripts is higher in MCPyV-positive MCC, suggesting a vital role of CK1Î± in limiting MCPyV replication required for establishing persistent infection.

IMPORTANCE: Merkel cell polyomavirus (MCPyV) large tumor antigen is a polyphosphoprotein and the phosphorylation event is required to modulate various functions of LT, including viral replication. Therefore, cellular kinase pathways are indispensable for governing MCPyV polyomavirus infection and life cycle in coordinating with the immunosuppression environment at disease onset. Understanding the regulation mechanisms of MCPyV replication by viral and cellular factors will guide proper prevention strategies with targeted inhibitors for MCPyV-associated Merkel cell carcinoma (MCC) patients, who currently lack therapies.

PMID:38940554 | PMC:PMC11323502 | DOI:10.1128/mbio.01117-24

The Role of Oncogenic Viruses in the Pathogenesis of Sporadic Breast Cancer: A Comprehensive Review of the Current Literature

Fetched: June 27th, 2024, 2:01am UTC by Chiara Rossi

Pathogens. 2024 May 25;13(6):451. doi: 10.3390/pathogens13060451.

ABSTRACT

Breast cancer is the most common malignancy in the female sex; although recent therapies have significantly changed the natural history of this cancer, it remains a significant challenge. In the past decade, evidence has been put forward that some oncogenic viruses may play a role in the development of sporadic breast cancer; however, data are scattered and mostly reported as sparse case series or small case-control studies. In this review, we organize and report current evidence regarding the role of high-risk human papillomavirus, mouse mammary tumor virus, Epstein-Barr virus, cytomegalovirus, bovine leukemia virus, human polyomavirus 2, and Merkel cell polyomavirus in the pathogenesis of breast cancer.

PMID:38921749 | PMC:PMC11206847 | DOI:10.3390/pathogens13060451

Merkel Cell Polyomavirus targets SET/PP2A complex to promote cellular proliferation and migration

Fetched: June 26th, 2024, 2:01am UTC by Purnima Gupta

Virology. 2024 Sep;597:110143. doi: 10.1016/j.virol.2024.110143. Epub 2024 Jun 18.

ABSTRACT

Merkel Cell Carcinoma (MCC) is a rare neuroendocrine skin cancer. In our previous work, we decoded genes specifically deregulated by MCPyV early genes as opposed to other polyomaviruses and established functional importance of NDRG1 in inhibiting cellular proliferation and migration in MCC. In the present work, we found the SET protein, (I2PP2A, intrinsic inhibitor of PP2A) upstream of NDRG1 which was modulated by MCPyV early genes, both in hTERT-HK-MCPyV and MCPyV-positive (+) MCC cell lines. Additionally, MCC dermal tumour nodule tissues showed strong SET expression. Inhibition of the SET-PP2A interaction in hTERT-HK-MCPyV using the small molecule inhibitor, FTY720, increased NDRG1 expression and inhibited cell cycle regulators, cyclinD1 and CDK2. SET inhibition by shRNA and FTY720 also decreased cell proliferation and colony formation in MCPyV(+) MCC cells. Overall, these results pave a path for use of drugs targeting SET protein for the treatment of MCC.

PMID:38917692 | DOI:10.1016/j.virol.2024.110143

High-Risk Non-Melanoma Skin Cancers: Biological and Therapeutic Advances

Fetched: June 23rd, 2024, 2:01am UTC by Truelian Lee

Hematol Oncol Clin North Am. 2024 Jun 21:S0889-8588(24)00053-4. doi: 10.1016/j.hoc.2024.05.004. Online ahead of print.

ABSTRACT

Nonmelanoma skin cancers (NMSCs) are the most common cancers, with high-risk NMSCs sharing features such as poor histologic differentiation, invasion into deeper layers, and anatomic location. NMSC includes basal cell carcinoma, cutaneous squamous cell carcinoma, and Merkel cell carcinoma. Herein, the authors describe advances in understanding the genetic mechanisms of malignant transformation and the composition of tumor microenvironment for these cancers. They summarize recent therapeutic advances, including targeted therapy and immunotherapy for NMSCs. Effective skin protection against ultraviolet radiation-induced carcinogenesis remains an urgent unmet need for NMSC prevention. The authors highlight immune-based interventions as novel strategies to address this need.

PMID:38908957 | DOI:10.1016/j.hoc.2024.05.004

DNA damage stress control is a tLT- and EHMT2-dependent central feature of Merkel Cell Carcinoma

Fetched: June 23rd, 2024, 2:01am UTC by Kamel Bachiri

J Invest Dermatol. 2024 Jun 21:S0022-202X(24)01860-8. doi: 10.1016/j.jid.2024.04.034. Online ahead of print.

ABSTRACT

Merkel cell carcinoma (MCC) is an aggressive skin cancer with a high mortality rate. Merkel cell polyomavirus causes 80% of MCCs, encoding the viral oncogenes small T and truncated large T (tLT) antigens. These proteins impair the RB1-dependent G1/S checkpoint blockade and subvert the host cell epigenome to promote cancer. Whole-proteome analysis and proximal interactomics identified a tLT-dependent deregulation of DNA damage response (DDR). Our investigation revealed, to our knowledge, a previously unreported interaction between tLT and the histone methyltransferase EHMT2. T antigen knockdown reduced DDR protein levels and increased the levels of the DNA damage marker Î³H2Ax. EHMT2 normally promotes H3K9 methylation and DDR signaling. Given that inhibition of EHMT2 did not significantly change the MCC cell proteome, tLT-EHMT2 interaction could affect the DDR. With tLT, we report that EHMT2 gained DNA damage repair proximal interactors. EHMT2 inhibition rescued proliferation in MCC cells depleted for their T antigens, suggesting impaired DDR and/or lack of checkpoint efficiency. Combined tLT and EHMT2 inhibition led to altered DDR, evidenced by multiple signaling alterations. In this study, we show that tLT hijacks multiple components of the DNA damage machinery to enhance tolerance to DNA damage in MCC cells, which could explain the genetic stability of these cancers.

PMID:38908781 | DOI:10.1016/j.jid.2024.04.034

Upper and Lower Eyelid Malignancies: Differences in Clinical Presentation, Metastasis, and Treatment

Fetched: June 23rd, 2024, 2:01am UTC by M Mukarram

Arch Dermatol Res. 2024 Jun 22;316(7):429. doi: 10.1007/s00403-024-03163-1.

ABSTRACT

Approximately 5-15% of all dermatologic malignancies manifest in the upper and lower eyelids. The primary types include basal cell carcinoma, squamous cell carcinoma, and sebaceous cell carcinoma, with Merkel cell carcinoma and melanoma following closely behind. Basal cell carcinoma predominantly affects the lower eyelid, yet various other carcinomas, melanomas, metastases, and neoplasms of diverse origins can arise on both upper and lower eyelids. Risk factors such as advanced age, smoking, and notably, exposure to UV light significantly contribute to the development of these eyelid lesions. Despite the increasing incidence, research on dermatologic eyelid malignancies remains limited. However, such study is imperative given that many systemic oncologic malignancies initially present as metastatic eyelid lesions. This paper provides an in-depth exploration of eyelid anatomy, clinical presentation, diagnosis, and treatment management.Key Points: Eyelid metastases represent less than one percent of all eyelid cancers, yet they often serve as the initial indication of an underlying systemic malignancy. Early detection and treatment is crucial in improving prognosis and quality of life for patients. Treatment options encompass a range of modalities, with Mohs surgery as the gold standard for the removal of ocular tumors. Additional treatment options include local excision as well as non-surgical interventions such as radiotherapy, cryotherapy, immunotherapy, and topical medications.

PMID:38907769 | DOI:10.1007/s00403-024-03163-1

Permalink for 'Hispanic patients with Merkel Cell Carcinoma have lower mortality compared to non-Hispanic patients in the National Cancer Database'

Hispanic patients with Merkel Cell Carcinoma have lower mortality compared to non-Hispanic patients in the National Cancer Database

Fetched: June 23rd, 2024, 2:01am UTC by Winston W Liu

J Am Acad Dermatol. 2024 Jun 19:S0190-9622(24)00957-5. doi: 10.1016/j.jaad.2024.05.089. Online ahead of print.

NO ABSTRACT

PMID:38906257 | DOI:10.1016/j.jaad.2024.05.089

Permalink for 'Searching for biomarkers to help distinguish Merkel cell carcinoma from cutaneous small cell lung cancer with gene expression analysis'

Searching for biomarkers to help distinguish Merkel cell carcinoma from cutaneous small cell lung cancer with gene expression analysis

Fetched: June 20th, 2024, 2:02am UTC by Joshua D Bloomstein

Skin Res Technol. 2024 Jun;30(6):e13789. doi: 10.1111/srt.13789.

NO ABSTRACT

PMID:38898376 | PMC:PMC11186706 | DOI:10.1111/srt.13789

Incidence and Relative Survival of Patients with Merkel Cell Carcinoma in North Rhine-Westphalia, Germany, 2008-2021

Fetched: June 20th, 2024, 2:02am UTC by Andreas Stang

Cancers (Basel). 2024 Jun 6;16(11):2158. doi: 10.3390/cancers16112158.

ABSTRACT

BACKGROUND: To date, only a few population-representative studies have been carried out on the rare Merkel cell carcinoma (MCC). We provide incidence and survival estimates of MCC, including the conditional relative survival.

METHODS: We analyzed data from the cancer registry of North Rhine-Westphalia, Germany, 2008-2021, covering a population of 18 million. We included all newly diagnosed MCCs and calculated age-standardized (old European Standard population) incidence rates and unconditional and conditional relative survival.

RESULTS: Our analysis included 2164 MCC patients. The age-standardized incidence of MCC was 5.2 (men) and 3.8 (women) per million person-years. The 5-year relative survival was 58.8% (men) and 70.7% (women). Survival was lower among men than women in all age-sex groups and was highest for MCC of the upper extremity in both men (68.2%) and women (79.3%). The sex difference in survival is particularly due to the better survival of women with MCC of the head and neck. In terms of survival, the first two years are particularly critical.

CONCLUSIONS: Our data validate the worse survival among men and highlights a more favorable prognosis for MCCs located on the limbs. The first two years after diagnosis of MCC are the years with the highest excess mortality.

PMID:38893275 | PMC:PMC11171844 | DOI:10.3390/cancers16112158

Cellular Transformation by Human Cytomegalovirus

Fetched: June 20th, 2024, 2:02am UTC by Georges Herbein

Cancers (Basel). 2024 May 22;16(11):1970. doi: 10.3390/cancers16111970.

ABSTRACT

Epstein-Barr virus (EBV), Kaposi sarcoma human virus (KSHV), human papillomavirus (HPV), hepatitis B and C viruses (HBV, HCV), human T-lymphotropic virus-1 (HTLV-1), and Merkel cell polyomavirus (MCPyV) are the seven human oncoviruses reported so far. While traditionally viewed as a benign virus causing mild symptoms in healthy individuals, human cytomegalovirus (HCMV) has been recently implicated in the pathogenesis of various cancers, spanning a wide range of tissue types and malignancies. This perspective article defines the biological criteria that characterize the oncogenic role of HCMV and based on new findings underlines a critical role for HCMV in cellular transformation and modeling the tumor microenvironment as already reported for the other human oncoviruses.

PMID:38893091 | PMC:PMC11171319 | DOI:10.3390/cancers16111970

Subsequent primary malignancies following first diagnosis of Merkel cell carcinoma in black patients

Fetched: June 16th, 2024, 2:02am UTC by Luis J Borda

Arch Dermatol Res. 2024 Jun 15;316(7):387. doi: 10.1007/s00403-024-02937-x.

NO ABSTRACT

PMID:38878144 | DOI:10.1007/s00403-024-02937-x

Different prognosis in cutaneous early-onset and late-onset Merkel cell carcinoma: a population-based retrospective study

Fetched: June 13th, 2024, 2:01am UTC by Zhujun Li

Int J Dermatol. 2024 Jun 11. doi: 10.1111/ijd.17297. Online ahead of print.

ABSTRACT

BACKGROUND: Merkel cell carcinoma (MCC) is a rare and highly aggressive form of skin cancer. However, there is limited research on the clinicopathological features of early-onset MCC (EOMCC) and the differences between EOMCC and late-onset MCC (LOMCC). Our objective was to evaluate the clinicopathological features and cancer-specific survival (CSS) of EOMCC.

METHODS: Our cohort study analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2018, to December 31, 2020. Data from 1941 patients who were diagnosed with primary cutaneous MCC were included. We then divided the patients with MCC into two groups: those with EOMCC (526 patients) and those with LOMCC (1415 patients). CSS is used as the primary outcome.

RESULTS: The EOMCC group exhibited trends toward advanced tumor progression, an expanded surgical scope, increased lymph node retrieval, intensified radiotherapy, greater utilization of systemic therapy, and a better prognosis. Multivariate analysis revealed that LOMCC (HR 3.305 [2.002-5.456], P < 0.001), advanced T stage (HR 1.430 [1.139-1.797], P = 0.002), advanced N stage (HR 1.522 [1.221-1.897], P < 0.001), M1 stage (HR 2.587 [1.480-4.521], P < 0.001), and radiation (HR 0.586 [0.410-0.837], P = 0.003) were significantly associated with CSS. Among these factors, EOMCC/LOMCC was most strongly associated with CSS, indicating that LOMCC is an independent risk factor for CSS. Interestingly, we found that regional EOMCC and localized or in situ LOMCC had almost completely overlapping survival curves (Plog-rank = 0.620). Additionally, we observed that the TNM staging + age model was a more accurate predictor of CSS among MCC patients than using TNM staging alone.

CONCLUSIONS: We found that EOMCC has distinct clinicopathological features compared to LOMCC. EOMCC is associated with better CSS. The combination of TNM staging and age was more accurate for predicting patient outcomes than TNM staging alone.

PMID:38863308 | DOI:10.1111/ijd.17297

Permalink for 'Increased Risk of Keratinocyte Carcinomas, Merkel Cell Carcinoma, and Other Skin Cancers in Patients Treated With Janus Kinase 1 and 2 Inhibitor, Ruxolitinib'

Increased Risk of Keratinocyte Carcinomas, Merkel Cell Carcinoma, and Other Skin Cancers in Patients Treated With Janus Kinase 1 and 2 Inhibitor, Ruxolitinib

Fetched: June 12th, 2024, 2:01am UTC by Nadine Elias Dababneh

J Cutan Med Surg. 2024 Jun 10:12034754241258364. doi: 10.1177/12034754241258364. Online ahead of print.

NO ABSTRACT

PMID:38859667 | DOI:10.1177/12034754241258364

Metastases to the parotid glands: An institutional experience

Fetched: June 11th, 2024, 2:02am UTC by Lea Calo

Cytopathology. 2024 Jul;35(4):488-496. doi: 10.1111/cyt.13387. Epub 2024 May 16.

ABSTRACT

BACKGROUND: Metastatic lesions to the salivary gland are rare and mostly affect the parotids. Metastases represent 8% of all malignant lesions of the parotid gland. Around 80% originate from squamous cell carcinomas (SCC) of the head and neck region. Fine needle aspiration (FNA) plays a crucial role in distinguishing primary salivary gland lesions from metastases. Herein we describe our series of metastases to the parotid glands.

MATERIALS AND METHODS: We analysed 630 parotid gland FNAs over a decade including conventional and liquid-based cytology specimens. Ancillary techniques such as immunocytochemistry (ICC) were conducted on cell blocks.

RESULTS: Eighty (12.4%) cases were malignant lesions, of which 53 (63.75%) were metastases including 24% melanoma, 22.6% SCC, 19% renal carcinomas, 7.5% breast carcinomas, 11.3% lung, 9% intestinal and 1.8% testicular, malignant solitary fibrous tumour and Merkel cell carcinoma. The 53 cases, classified according to the Milan system for salivary cytopathology, belonged to 5 Suspicious for malignancy (SFM) and 48 malignant (M) categories. Forty had a known history of primary malignancy (75.4%), while 13 were suspicious to be a metastatic localisation (24.5%), distributed as 5SFM (2SCC and 3Melanoma) and 8 M. A combination of clinical history, cytomorphology and ICC identified 100% of them.

CONCLUSIONS: Fine needle aspiration plays a central role in the diagnostic workup of patients with metastatic lesions to their parotid glands, thereby defining the correct management. Diagnostic accuracy may be enhanced by applying ICC. Although melanoma and SCC are the most common histological types, several other malignancies may also metastasize to the parotid glands and should be kept into consideration.

PMID:38752464 | DOI:10.1111/cyt.13387

A retrospective case-control analysis of various comorbidities associated with Merkel Cell Carcinoma

Fetched: June 9th, 2024, 2:01am UTC by Kritin K Verma

Arch Dermatol Res. 2024 Jun 8;316(7):355. doi: 10.1007/s00403-024-03026-9.

NO ABSTRACT

PMID:38850315 | DOI:10.1007/s00403-024-03026-9

Brazilian Society of Surgical Oncology recommendations on Merkel cell carcinoma surgical treatment

Fetched: June 8th, 2024, 2:01am UTC by Matheus de Melo Lobo

J Surg Oncol. 2024 Jun 6. doi: 10.1002/jso.27728. Online ahead of print.

ABSTRACT

BACKGROUND: Merkel cell carcinoma (MCC) is a rare neuroendocrine skin cancer with poor 5-year survival rates. Surgery and radiation are the current first-line treatments for local and nodal disease.

OBJECTIVES: The Brazilian Society of Surgical Oncology developed this document aiming to guide the surgical oncology role in multimodal MCC management.

METHODS: The consensus was established in three rounds of online discussion, achieving consensus on specific topics including diagnosis, staging, treatment, and follow-up.

RESULTS: Patients suspected of having MCC should undergo immunohistochemical examination and preferably undergo pathology review by a dermatopathologist. Initial staging should be performed with dermatologic and nodal physical examination, combined with complementary imaging. Whole-body imaging, preferably with positron emission tomography (PET) or computed tomography (CT) scans, are recommended. Due to the need for multidisciplinary approaches, we recommend that all cases should be discussed in tumor boards and referred to other specialties as soon as possible, reducing potential treatment delays. We recommend that all patients with clinical stage I or II may undergo local excision associated with sentinel lymph node biopsy. The decision on margin size should consider time to recovery, patient's comorbidities, and risk factors. Patients with positive sentinel lymph nodes or the presence of risk factors should undergo postoperative radiation therapy at the primary site. Exclusive radiation is a viable option for patients with low performance. Patients with positive sentinel lymph node biopsy should undergo nodal radiation therapy or lymphadenectomy. In patients with nodal clinical disease, in addition to primary tumor treatment, nodal radiation therapy and/or lymphadenectomy are recommended. Patients with advanced disease should preferably be enrolled in clinical trials and discussed in multidisciplinary meetings. The role of surgery and radiation therapy in the metastatic/advanced setting should be discussed individually and always in tumor boards.

CONCLUSION: This document aims to standardize a protocol for initial assessment and treatment for Merkel cell carcinoma, optimizing oncologic outcomes in middle-income countries such as Brazil.

PMID:38845222 | DOI:10.1002/jso.27728

Permalink for 'The small tumor antigen of Merkel cell polyomavirus accomplishes cellular transformation by uniquely localizing to the nucleus despite the absence of a known nuclear localization signal'

The small tumor antigen of Merkel cell polyomavirus accomplishes cellular transformation by uniquely localizing to the nucleus despite the absence of a known nuclear localization signal

Fetched: June 4th, 2024, 2:01am UTC by Kaira R Thevenin

Virol J. 2024 Jun 3;21(1):125. doi: 10.1186/s12985-024-02395-x.

ABSTRACT

BACKGROUND: Merkel Cell Carcinoma (MCC) is an aggressive skin cancer that is three times deadlier than melanoma. In 2008, it was found that 80% of MCC cases are caused by the genomic integration of a novel polyomavirus, Merkel Cell Polyomavirus (MCPyV), and the expression of its small and truncated large tumor antigens (ST and LT-t, respectively). MCPyV belongs to a family of human polyomaviruses; however, it is the only one with a clear association to cancer.

METHODS: To investigate the role and mechanisms of various polyomavirus tumor antigens in cellular transformation, Rat-2 and 293A cells were transduced with pLENTI MCPyV LT-t, MCPyV ST, TSPyV ST, HPyV7 ST, or empty pLENTI and assessed through multiple transformation assays, and subcellular fractionations. One-way ANOVA tests were used to assess statistical significance.

RESULTS: Soft agar, proliferation, doubling time, glucose uptake, and serum dependence assays confirmed ST to be the dominant transforming protein of MCPyV. Furthermore, it was found that MCPyV ST is uniquely transforming, as the ST antigens of other non-oncogenic human polyomaviruses such as Trichodysplasia Spinulosa-Associated Polyomavirus (TSPyV) and Human Polyomavirus 7 (HPyV7) were not transforming when similarly assessed. Identification of structural dissimilarities between transforming and non-transforming tumor antigens revealed that the uniquely transforming domain(s) of MCPyV ST are likely located within the structurally dissimilar loops of the MCPyV ST unique region. Of all known MCPyV ST cellular interactors, 62% are exclusively or transiently nuclear, suggesting that MCPyV ST localizes to the nucleus despite the absence of a canonical nuclear localization signal. Indeed, subcellular fractionations confirmed that MCPyV ST could achieve nuclear localization through a currently unknown, regulated mechanism independent of its small size, as HPyV7 and TSPyV ST proteins were incapable of nuclear translocation. Although nuclear localization was found to be important for several transforming properties of MCPyV ST, some properties were also performed by a cytoplasmic sequestered MCPyV ST, suggesting that MCPyV ST may perform different transforming functions in individual subcellular compartments.

CONCLUSIONS: Together, these data further elucidate the unique differences between MCPyV ST and other polyomavirus ST proteins necessary to understand MCPyV as the only known human oncogenic polyomavirus.

PMID:38831469 | PMC:PMC11149282 | DOI:10.1186/s12985-024-02395-x

Liquid Biomarker Study in Melanoma and Non-Melanoma Skin Cancers

Posted: September 23rd, 2024, 11:00pm UTC

Conditions: Skin Cancer; Melanoma (Skin Cancer); Basal Cell Carcinoma of Skin; Basal Cell Carcinoma of Skin, Site Unspecified; Cutaneous Squamous Cell Carcinoma (CSCC); Merkel Cell Carcinoma of Skin
Interventions: Other: Blood draw for the laboratory assessment
Sponsors: University of Wisconsin, Madison; National Center for Advancing Translational Sciences (NCATS)
Not yet recruiting

Personalised Immunotherapy Platform (PIP-PREDICT)

Posted: August 2nd, 2024, 11:00pm UTC

Conditions: Melanoma; Cutaneous Squamous Cell Carcinoma; Basal Cell Carcinoma; Merkel Cell Carcinoma; Solid Tumor
Interventions: Other: Predictive model
Sponsors: Melanoma Institute Australia
Recruiting

Permalink for 'Identification and Characterization of Circulating Tumor Cells Before and After Treatment (Surgery and Radiotherapy) in a Cohort of Patients Treated for Resectable Stage I-III Merkel Cell Carcinoma'

Identification and Characterization of Circulating Tumor Cells Before and After Treatment (Surgery and Radiotherapy) in a Cohort of Patients Treated for Resectable Stage I-III Merkel Cell Carcinoma

Posted: June 7th, 2024, 11:00pm UTC

Conditions: Merkel Cell Carcinoma
Interventions: Other: Blood Test
Sponsors: University Hospital, Montpellier
Not yet recruiting

A Study of VET3-TGI in Patients With Solid Tumors

Posted: June 6th, 2024, 11:00pm UTC

Conditions: Solid Tumor, Adult; Microsatellite Stable Colorectal Cancer; Head and Neck Squamous Cell Carcinoma; Cervical Cancer; Kidney Cancer; Renal Cell Carcinoma; Melanoma Stage IV; Merkel Cell Carcinoma of Skin; Mesothelioma; Non-small Cell Lung Cancer
Interventions: Drug: VET3-TGI; Drug: Pembrolizumab
Sponsors: KaliVir Immunotherapeutics
Recruiting

Permalink for 'EMLA Topical Cream for Treatment of Pain in Patients Receiving Intra-Dermal Technetium 99 Injections for Lymphoscintigraphy for Skin Cancers'

EMLA Topical Cream for Treatment of Pain in Patients Receiving Intra-Dermal Technetium 99 Injections for Lymphoscintigraphy for Skin Cancers

Posted: January 25th, 2024, 1:00am UTC

Conditions: Cutaneous Melanoma; Merkel Cell Carcinoma; Skin Squamous Cell Carcinoma
Interventions: Drug: Eutectic Mixture of Local Anesthetics; Drug: Placebo Administration; Other: Questionnaire Administration
Sponsors: Ohio State University Comprehensive Cancer Center
Recruiting

Neoadjuvant Nivolumab and Relatlimab in Merkel Cell Carcinoma

Posted: November 30th, 2023, 1:00am UTC

Conditions: Merkel Cell Carcinoma
Interventions: Drug: Nivolumab 240 mg / Relatlimab 80 mg in a fixed dose combination
Sponsors: Melanoma Institute Australia; Bristol-Myers Squibb
Recruiting

A Study of CRD3874-SI in People With Solid Tumors

Posted: September 1st, 2023, 11:00pm UTC

Conditions: Sarcoma; Merkel Cell Carcinoma
Interventions: Drug: CRD3874
Sponsors: Memorial Sloan Kettering Cancer Center; Curadev Pharma
Recruiting

Intratumoral PH-762 for Cutaneous Carcinoma

Posted: August 28th, 2023, 11:00pm UTC

Conditions: Squamous Cell Carcinoma of the Skin; Malignant Melanoma of Skin; Merkel Cell Carcinoma of Skin
Interventions: Drug: PH-762
Sponsors: Phio Pharmaceuticals Inc.; Prosoft Clinical
Recruiting

Exercise to Boost Response to Checkpoint Blockade Immunotherapy

Posted: August 24th, 2023, 11:00pm UTC

Conditions: Cutaneous Melanoma; Cutaneous Squamous Cell Carcinoma; Merkel Cell Carcinoma
Interventions: Other: Exercise Test
Sponsors: AdventHealth Translational Research Institute
Recruiting

Permalink for 'Immunotherapy in Combination With Prednisone and Sirolimus for Kidney Transplant Recipients With Unresectable or Metastatic Skin Cancer'

Immunotherapy in Combination With Prednisone and Sirolimus for Kidney Transplant Recipients With Unresectable or Metastatic Skin Cancer

Posted: June 9th, 2023, 11:00pm UTC

Conditions: Clinical Stage III Cutaneous Melanoma AJCC v8; Clinical Stage III Cutaneous Merkel Cell Carcinoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Clinical Stage IV Cutaneous Merkel Cell Carcinoma AJCC v8; Metastatic Basal Cell Carcinoma; Metastatic Carcinoma in the Skin; Metastatic Melanoma; Metastatic Merkel Cell Carcinoma; Metastatic Skin Squamous Cell Carcinoma; Unresectable Basal Cell Carcinoma; Unresectable Melanoma; Unresectable Merkel Cell Carcinoma; Unresectable Skin Squamous Cell Carcinoma
Interventions: Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Biological: Ipilimumab; Procedure: Kidney Biopsy; Procedure: Magnetic Resonance Imaging; Biological: Nivolumab; Drug: Prednisone; Drug: Sirolimus
Sponsors: National Cancer Institute (NCI)
Recruiting

A Study of MQ710 With and Without Pembrolizumab in People With Solid Tumor Cancer

Posted: May 15th, 2023, 11:00pm UTC

Conditions: Cutaneous Squamous Cell Carcinoma; SCC - Squamous Cell Carcinoma; Basal Cell Carcinoma; BCC; BCC - Basal Cell Carcinoma; Melanoma; Merkel Cell Carcinoma; Sebaceous Carcinoma; Extramammary Paget Disease; Kaposi Sarcoma; Head and Neck Squamous Cell Carcinoma; HNSCC; Adnexal Carcinoma; Angiosarcoma; Cutaneous Neoplasm; Advanced Cancer; Metastatic Cancer; Refractory Cancer; Solid Tumor
Interventions: Biological: MQ719; Drug: Pembrolizumab
Sponsors: Memorial Sloan Kettering Cancer Center
Active, not recruiting

Sentinel Lymph Node Biopsy in Ocular Surface and Adnexal Cancers

Posted: April 4th, 2023, 11:00pm UTC

Conditions: Ocular Sebaceous Carcinoma; Ocular Basal Cell Carcinoma; Ocular Surface Squamous Neoplasia; Merkel Cell Carcinoma, Unspecified; Porocarcinoma; Conjunctival Melanoma
Interventions: Procedure: Sentinel Lymph Node Biopsy
Sponsors: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Recruiting

Permalink for 'Structural Description of Skin Biopsies With Dynamic Full-field Optical Coherence Tomography on Suspected Basal Cell Carcinoma Lesions, a Pilot Study (DOCTOBA)'

Structural Description of Skin Biopsies With Dynamic Full-field Optical Coherence Tomography on Suspected Basal Cell Carcinoma Lesions, a Pilot Study (DOCTOBA)

Posted: November 8th, 2022, 1:00am UTC

Conditions: Basal Cell Carcinoma; Tomography, Optical Coherence
Interventions: Other: Dynamic full-field optical coherence tomography analysis of skin biopsy or resection
Sponsors: Centre Hospitalier William Morey - Chalon sur SaÃ´ne
Completed

Chemo-immunotherapy in Patients With Resectable Merkel Cell Carcinoma Prior to Surgery

Posted: October 26th, 2022, 11:00pm UTC

Conditions: Merkel Cell Carcinoma
Interventions: Drug: Retifanlimab; Drug: Cisplatin; Drug: Etoposide
Sponsors: Gruppo Oncologico del Nord-Ovest
Recruiting

Permalink for 'A Study of a Selective T Cell Receptor (TCR) Targeting, Bifunctional Antibody-fusion Molecule STAR0602 in Participants With Advanced Solid Tumors'

A Study of a Selective T Cell Receptor (TCR) Targeting, Bifunctional Antibody-fusion Molecule STAR0602 in Participants With Advanced Solid Tumors

Posted: October 24th, 2022, 11:00pm UTC

Conditions: Advanced Solid Tumors; Genital Neoplasm, Female; Urogenital Neoplasms; Lung Neoplasm; Neoplasms by Site; Papillomavirus Infection; Epstein-Barr Virus Infections; Carcinoma; Neoplasms; Vulvar Neoplasms; Vulvar Diseases; Abdominal Neoplasm
Interventions: Drug: STAR0602
Sponsors: Marengo Therapeutics, Inc.
Recruiting

Permalink for 'Phase II Study of Peptide Receptor Radionuclide Therapy in Combination With Immunotherapy for Patients With Merkel Cell Cancer'

Phase II Study of Peptide Receptor Radionuclide Therapy in Combination With Immunotherapy for Patients With Merkel Cell Cancer

Posted: October 18th, 2022, 11:00pm UTC

Conditions: Merkel Cell Carcinoma
Interventions: Drug: Pembrolizumab; Drug: Lutetium Lu 177 dotatate
Sponsors: Weill Medical College of Cornell University
Suspended

Neoadjuvant PD-1 Blockade in Resectable Merkel Cell Carcinoma

Posted: August 10th, 2022, 11:00pm UTC

Conditions: Merkel Cell Carcinoma
Interventions: Drug: Pembrolizumab
Sponsors: Abramson Cancer Center at Penn Medicine; Merck Sharp & Dohme LLC
Recruiting

Exercise to Boost Response to Checkpoint Blockade Immunotherapy

Posted: May 3rd, 2022, 11:00pm UTC

Conditions: Cutaneous Melanoma; Cutaneous Squamous Cell Carcinoma; Merkel Cell Carcinoma
Interventions: Other: Exercise; Drug: Checkpoint Blockade, Immune
Sponsors: H. Lee Moffitt Cancer Center and Research Institute
Active, not recruiting

Personalized Neoantigen Peptide-Based Vaccine in Combination With Pembrolizumab for Treatment of Advanced Solid Tumors

Posted: March 8th, 2022, 1:00am UTC

Conditions: Anatomic Stage III Breast Cancer AJCC v8; Anatomic Stage IIIA Breast Cancer AJCC v8; Anatomic Stage IIIB Breast Cancer AJCC v8; Anatomic Stage IIIC Breast Cancer AJCC v8; Anatomic Stage IV Breast Cancer AJCC v8; Clinical Stage III Cutaneous Melanoma AJCC v8; Clinical Stage III Gastric Cancer AJCC v8; Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage III Merkel Cell Carcinoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Clinical Stage IV Gastric Cancer AJCC v8; Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IV Merkel Cell Carcinoma AJCC v8; Clinical Stage IVA Gastric Cancer AJCC v8; Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IVB Gastric Cancer AJCC v8; Clinical Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8; Locally Advanced Cervical Carcinoma; Locally Advanced Endometrial Carcinoma; Locally Advanced Gastric Adenocarcinoma; Locally Advanced Gastroesophageal Junction Adenocarcinoma; Locally Advanced Head and Neck Squamous Cell Carcinoma; Locally Advanced Hepatocellular Carcinoma; Locally Advanced Lung Non-Small Cell Carcinoma; Locally Advanced Malignant Solid Neoplasm; Locally Advanced Melanoma; Locally Advanced Merkel Cell Carcinoma; Locally Advanced Renal Cell Carcinoma; Locally Advanced Skin Squamous Cell Carcinoma; Locally Advanced Triple-Negative Breast Carcinoma; Locally Advanced Unresectable Breast Carcinoma; Locally Advanced Unresectable Cervical Carcinoma; Locally Advanced Unresectable Gastric Adenocarcinoma; Locally Advanced Unresectable Gastroesophageal Junction Adenocarcinoma; Locally Advanced Unresectable Renal Cell Carcinoma; Locally Advanced Urothelial Carcinoma; Metastatic Cervical Carcinoma; Metastatic Endometrial Carcinoma; Metastatic Gastric Adenocarcinoma; Metastatic Gastroesophageal Junction Adenocarcinoma; Metastatic Head and Neck Squamous Cell Carcinoma; Metastatic Hepatocellular Carcinoma; Metastatic Lung Non-Small Cell Carcinoma; Metastatic Malignant Solid Neoplasm; Metastatic Melanoma; Metastatic Merkel Cell Carcinoma; Metastatic Renal Cell Carcinoma; Metastatic Skin Squamous Cell Carcinoma; Metastatic Triple-Negative Breast Carcinoma; Metastatic Urothelial Carcinoma; Pathologic Stage III Cutaneous Melanoma AJCC v8; Pathologic Stage III Gastric Cancer AJCC v8; Pathologic Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage III Merkel Cell Carcinoma AJCC v8; Pathologic Stage IIIA Cutaneous Melanoma AJCC v8; Pathologic Stage IIIA Gastric Cancer AJCC v8; Pathologic Stage IIIA Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IIIB Cutaneous Melanoma AJCC v8; Pathologic Stage IIIB Gastric Cancer AJCC v8; Pathologic Stage IIIB Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IIIC Cutaneous Melanoma AJCC v8; Pathologic Stage IIIC Gastric Cancer AJCC v8; Pathologic Stage IIID Cutaneous Melanoma AJCC v8; Pathologic Stage IV Cutaneous Melanoma AJCC v8; Pathologic Stage IV Gastric Cancer AJCC v8; Pathologic Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IV Merkel Cell Carcinoma AJCC v8; Pathologic Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8; Postneoadjuvant Therapy Stage III Gastric Cancer AJCC v8; Postneoadjuvant Therapy Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8; Postneoadjuvant Therapy Stage IIIA Gastroesophageal Junction Adenocarcinoma AJCC v8; Postneoadjuvant Therapy Stage IIIB Gastroesophageal Junction Adenocarcinoma AJCC v8; Postneoadjuvant Therapy Stage IV Gastric Cancer AJCC v8; Postneoadjuvant Therapy Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8; Postneoadjuvant Therapy Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8; Postneoadjuvant Therapy Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8; Prognostic Stage III Breast Cancer AJCC v8; Prognostic Stage IIIA Breast Cancer AJCC v8; Prognostic Stage IIIB Breast Cancer AJCC v8; Prognostic Stage IIIC Breast Cancer AJCC v8; Prognostic Stage IV Breast Cancer AJCC v8; Skin Squamous Cell Carcinoma; Stage III Cervical Cancer AJCC v8; Stage III Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8; Stage III Hepatocellular Carcinoma AJCC v8; Stage III Lung Cancer AJCC v8; Stage III Renal Cell Cancer AJCC v8; Stage III Uterine Corpus Cancer AJCC v8; Stage IIIA Cervical Cancer AJCC v8; Stage IIIA Hepatocellular Carcinoma AJCC v8; Stage IIIA Lung Cancer AJCC v8; Stage IIIA Uterine Corpus Cancer AJCC v8; Stage IIIB Cervical Cancer AJCC v8; Stage IIIB Hepatocellular Carcinoma AJCC v8; Stage IIIB Lung Cancer AJCC v8; Stage IIIB Uterine Corpus Cancer AJCC v8; Stage IIIC Lung Cancer AJCC v8; Stage IIIC Uterine Corpus Cancer AJCC v8; Stage IIIC1 Uterine Corpus Cancer AJCC v8; Stage IIIC2 Uterine Corpus Cancer AJCC v8; Stage IV Cervical Cancer AJCC v8; Stage IV Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8; Stage IV Hepatocellular Carcinoma AJCC v8; Stage IV Lung Cancer AJCC v8; Stage IV Renal Cell Cancer AJCC v8; Stage IV Uterine Corpus Cancer AJCC v8; Stage IVA Cervical Cancer AJCC v8; Stage IVA Hepatocellular Carcinoma AJCC v8; Stage IVA Lung Cancer AJCC v8; Stage IVA Uterine Corpus Cancer AJCC v8; Stage IVB Cervical Cancer AJCC v8; Stage IVB Hepatocellular Carcinoma AJCC v8; Stage IVB Lung Cancer AJCC v8; Stage IVB Uterine Corpus Cancer AJCC v8; Triple-Negative Breast Carcinoma; Unresectable Cervical Carcinoma; Unresectable Endometrial Carcinoma; Unresectable Gastric Adenocarcinoma; Unresectable Gastroesophageal Junction Adenocarcinoma; Unresectable Head and Neck Squamous Cell Carcinoma; Unresectable Hepatocellular Carcinoma; Unresectable Lung Non-Small Cell Carcinoma; Unresectable Malignant Solid Neoplasm; Unresectable Melanoma; Unresectable Merkel Cell Carcinoma; Unresectable Renal Cell Carcinoma; Unresectable Skin Squamous Cell Carcinoma; Unresectable Triple-Negative Breast Carcinoma; Unresectable Urothelial Carcinoma
Interventions: Drug: Cyclophosphamide; Biological: Neoantigen Peptide Vaccine; Biological: Pembrolizumab; Biological: Sargramostim
Sponsors: Mayo Clinic
Recruiting

Permalink for 'Study of AU-007, A Monoclonal Antibody That Binds to IL-2 and Inhibits IL-2RÎ± Binding, in Patients With Unresectable Locally Advanced or Metastatic Cancer'

Study of AU-007, A Monoclonal Antibody That Binds to IL-2 and Inhibits IL-2RÎ± Binding, in Patients With Unresectable Locally Advanced or Metastatic Cancer

Posted: March 4th, 2022, 1:00am UTC

Conditions: Advanced Solid Tumor; Metastatic Cancer
Interventions: Drug: AU-007; Drug: Aldesleukin; Drug: Avelumab
Sponsors: Aulos Bioscience, Inc.
Recruiting

Comparing Radical Surgery and Radical Radiotherapy as First Definitive Treatment for Primary MCC

Posted: February 23rd, 2022, 1:00am UTC

Conditions: Merkel Cell Carcinoma
Interventions: Radiation: Radiotherapy; Procedure: Surgery
Sponsors: University of Birmingham; Efficacy and Mechanism Evaluation (EME) Programme
Completed

BOXR1030 T Cells in Subjects With Advanced GPC3-Positive Solid Tumors

Posted: November 15th, 2021, 1:00am UTC

Conditions: Hepatocellular Carcinoma; Squamous Cell Carcinoma of the Lung; Merkel Cell Carcinoma; Myxoid/Round Cell Liposarcoma
Interventions: Biological: CAR-GPC3 T Cells
Sponsors: Sotio Biotech Inc.; SOTIO Biotech AG; SOTIO Biotech a.s.
Recruiting

$Permalink for 'Hypofractionated Radiation Therapy for Merkel Cell Carcinoma'$

Hypofractionated Radiation Therapy for Merkel Cell Carcinoma

Posted: October 29th, 2021, 11:00pm UTC

Conditions: Merkel Cell Carcinoma
Interventions: Drug: Radiation therapy
Sponsors: M.D. Anderson Cancer Center
Recruiting

A Beta-only IL-2 ImmunoTherapY Study

Posted: October 21st, 2021, 11:00pm UTC

Conditions: Advanced Solid Tumor; Unresectable Solid Tumor; Clear Cell Renal Cell Carcinoma; Triple Negative Breast Cancer; Non-Small Cell Lung Cancer Squamous; Non-Small Cell Lung Cancer Non-squamous; Colorectal Cancer (MSI-H); Gastric Cancer; Cervical Cancer; Basal Cell Carcinoma; Bladder Cancer; Merkel Cell Carcinoma; Squamous Cell Carcinoma of Head and Neck; Cutaneous Squamous Cell Carcinoma; Pleural Mesothelioma; Esophageal Cancer; Endometrial Carcinoma; Solid Tumor; Solid Tumor, Adult; MSI-H Solid Malignant Tumor; Cancer With A High Tumor Mutational Burden; Epithelial Ovarian Carcinoma; Primary Peritoneal Cancer; Gastroesophageal Junction (GEJ) Cancer; Acral Melanoma; Mucosal Melanoma; Cutaneous Melanoma; DMMR Solid Malignant Tumor; Fallopian Tube Cancer; Ovarian Cancer; MSI-H Cancer; DMMR Cancer; Pancreas Adenocarcinoma (MSI-H); Skin Cancer
Interventions: Drug: MDNA11; Drug: Pembrolizumab (KEYTRUDAÂ®)
Sponsors: Medicenna Therapeutics, Inc.; Merck Sharp & Dohme LLC
Recruiting

Permalink for 'Study Comparing the Standard Administration of IO Versus the Same IO Administered Each 3 Months in Patients in Response After 6 Months of Standard IO'

Study Comparing the Standard Administration of IO Versus the Same IO Administered Each 3 Months in Patients in Response After 6 Months of Standard IO

Posted: October 14th, 2021, 11:00pm UTC

Conditions: Lung Cancer Metastatic; Renal Cell Carcinoma; Head and Neck Cancer; Triple Negative Breast Cancer; Merkel Cell Carcinoma; Hepatocellular Carcinoma; Melanoma; Urothelial Carcinoma; Colorectal Carcinoma With Microsatellite Instability; Esophageal Squamous Cell Carcinoma; Endometrial Carcinoma; Cervical Cancer; Gastric/Gastro-esophageal Junction/Esophageal Adenocarcinoma; Basal Cell Carcinoma; Squamous Skin Carcinoma
Interventions: Drug: Reduced dose intensity of IO
Sponsors: UNICANCER
Recruiting

Study of Zirconium Zr 89 Crefmirlimab Berdoxam PET/CT in Subjects With Advanced or Metastatic Malignancies

Posted: August 19th, 2021, 11:00pm UTC

Conditions: Melanoma; Merkel Cell Carcinoma, Unspecified; Renal Cell Carcinoma; Non Small Cell Lung Cancer
Interventions: Biological: zirconium Zr 89 crefmirlimab berdoxam
Sponsors: ImaginAb, Inc.
Active, not recruiting

GI-101 as a Single Agent or in Combination With Pembrolizumab, Lenvatinib or Local Radiotherapy in Advanced Solid Tumors

Posted: July 27th, 2021, 11:00pm UTC

Conditions: Advanced Solid Tumor; Metastatic Solid Tumor; Non-small Cell Lung Cancer; Head and Neck Squamous Cell Carcinoma; Renal Cell Carcinoma; Urinary Bladder Cancer; Melanoma; Sarcoma; Microsatellite Stable Colorectal Carcinoma; Merkel Cell Carcinoma; Esophageal Squamous Cell Carcinoma; Cervical Cancer; Vaginal Cancer; Vulvar Cancer
Interventions: Drug: GI-101; Drug: Pembrolizumab (KEYTRUDAÂ®); Drug: Lenvatinib; Radiation: Local Radiotherapy; Drug: GI-101A
Sponsors: GI Innovation, Inc.; Merck Sharp & Dohme LLC
Recruiting

Permalink for 'Neoadjuvant Cemiplimab in Newly Diagnosed or Recurrent Stage I-II Merkel Cell Carcinoma and Locoregionally Advanced Cutaneous Squamous Cell Carcinoma'

Neoadjuvant Cemiplimab in Newly Diagnosed or Recurrent Stage I-II Merkel Cell Carcinoma and Locoregionally Advanced Cutaneous Squamous Cell Carcinoma

Posted: July 23rd, 2021, 11:00pm UTC

Conditions: Merkel Cell Carcinoma; Cutaneous Squamous Cell Carcinoma
Interventions: Drug: Cemiplimab-Rwlc
Sponsors: H. Lee Moffitt Cancer Center and Research Institute; Regeneron Pharmaceuticals; Sanofi-Synthelabo
Recruiting

Permalink for 'A Trial to Find Out if Vidutolimod Together With Cemiplimab is Safe and if it Works in Adult Participants With Advanced Cancer or Metastatic Cancer'

A Trial to Find Out if Vidutolimod Together With Cemiplimab is Safe and if it Works in Adult Participants With Advanced Cancer or Metastatic Cancer

Posted: June 7th, 2021, 11:00pm UTC

Conditions: Merkel Cell Carcinoma; Cutaneous Squamous Cell Carcinoma; Basal Cell Carcinoma; Triple Negative Breast Cancer; Non-Small Cell Lung Cancer; Oropharynx Squamous Cell Carcinoma
Interventions: Drug: vidutolimod; Drug: cemiplimab
Sponsors: Regeneron Pharmaceuticals
Active, not recruiting

Pomalidomide and Nivolumab in People With Virus-Associated Malignancies With or Without HIV

Posted: May 26th, 2021, 11:00pm UTC

Conditions: Viral Associated Malignancies; Kaposi Sarcoma; EBV/KSHV-associated Lymphomas
Interventions: Drug: Pomalidomide; Drug: Nivolumab
Sponsors: National Cancer Institute (NCI)
Recruiting

Permalink for 'Plinabulin in Combination With Radiation/Immunotherapy in Patients With Select Advanced Cancers After Progression on PD-1 or PD-L1 Targeted Antibodies'

Plinabulin in Combination With Radiation/Immunotherapy in Patients With Select Advanced Cancers After Progression on PD-1 or PD-L1 Targeted Antibodies

Posted: May 26th, 2021, 11:00pm UTC

Conditions: Advanced Bladder Carcinoma; Advanced Lung Non-Small Cell Carcinoma; Advanced Malignant Solid Neoplasm; Advanced Melanoma; Advanced Merkel Cell Carcinoma; Advanced Renal Cell Carcinoma; Clinical Stage III Cutaneous Melanoma AJCC v8; Clinical Stage III Merkel Cell Carcinoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Clinical Stage IV Merkel Cell Carcinoma AJCC v8; Pathologic Stage III Cutaneous Melanoma AJCC v8; Pathologic Stage III Merkel Cell Carcinoma AJCC v8; Pathologic Stage IIIA Cutaneous Melanoma AJCC v8; Pathologic Stage IIIA Merkel Cell Carcinoma AJCC v8; Pathologic Stage IIIB Cutaneous Melanoma AJCC v8; Pathologic Stage IIIB Merkel Cell Carcinoma AJCC v8; Pathologic Stage IIIC Cutaneous Melanoma AJCC v8; Pathologic Stage IIID Cutaneous Melanoma AJCC v8; Pathologic Stage IV Cutaneous Melanoma AJCC v8; Pathologic Stage IV Merkel Cell Carcinoma AJCC v8; Stage III Bladder Cancer AJCC v8; Stage III Lung Cancer AJCC v8; Stage III Renal Cell Cancer AJCC v8; Stage IIIA Bladder Cancer AJCC v8; Stage IIIA Lung Cancer AJCC v8; Stage IIIB Bladder Cancer AJCC v8; Stage IIIB Lung Cancer AJCC v8; Stage IIIC Lung Cancer AJCC v8; Stage IV Bladder Cancer AJCC v8; Stage IV Lung Cancer AJCC v8; Stage IV Renal Cell Cancer AJCC v8; Stage IVA Bladder Cancer AJCC v8; Stage IVA Lung Cancer AJCC v8; Stage IVB Bladder Cancer AJCC v8; Stage IVB Lung Cancer AJCC v8
Interventions: Biological: Atezolizumab; Drug: Avelumab; Biological: Durvalumab; Biological: Nivolumab; Biological: Pembrolizumab; Drug: Plinabulin; Radiation: Radiation Therapy
Sponsors: M.D. Anderson Cancer Center
Recruiting

Neoadjuvant Lenvatinib Plus Pembrolizumab in Merkel Cell Carcinoma

Posted: May 3rd, 2021, 11:00pm UTC

Conditions: Merkel Cell Carcinoma; Neuroendocrine Carcinoma of the Skin; Trabecular Carcinoma of the Skin
Interventions: Drug: Lenvatinib Oral Product; Drug: Pembrolizumab
Sponsors: H. Lee Moffitt Cancer Center and Research Institute; Merck Sharp & Dohme LLC
Recruiting

IFx-Hu2.0 Expanded Access Program

Posted: April 21st, 2021, 11:00pm UTC

Conditions: Cutaneous Melanoma, Stage III; Cutaneous Melanoma, Stage IV; Merkel Cell Carcinoma; Cutaneous Squamous Cell Carcinoma
Interventions: Biological: IFx-Hu2.0
Sponsors: TuHURA Biosciences, Inc.
Available

Study of Avelumab and/or Radiation Therapy in People With Advanced Merkel Cell Carcinoma

Posted: March 10th, 2021, 1:00am UTC

Conditions: Merkel Cell Carcinoma
Interventions: Drug: Avelumab; Radiation: Comprehensive Ablative Radiation Therapy
Sponsors: Memorial Sloan Kettering Cancer Center; EMD Serono
Recruiting

A Clinical Trial Assessing BT-001 Alone and in Combination With Pembrolizumab in Metastatic or Advanced Solid Tumors

Posted: January 26th, 2021, 1:00am UTC

Conditions: Metastatic Cancer; Soft Tissue Sarcoma; Merkel Cell Carcinoma; Melanoma; Triple Negative Breast Cancer; Non Small Cell Lung Cancer
Interventions: Biological: BT-001; Drug: Pembrolizumab [KEYTRUDAÂ®]
Sponsors: Transgene; BioInvent International AB; Merck Sharp & Dohme LLC
Recruiting

Study of PF-07265807 in Participants With Metastatic Solid Tumors.

Posted: July 7th, 2020, 11:00pm UTC

Conditions: Neoplasm Metastasis
Interventions: Drug: PF-07265807; Drug: Sasanlimab; Drug: Axitinib
Sponsors: Pfizer
Active, not recruiting

Domatinostat in Combination With Avelumab in Patients With Advanced Merkel Cell Carcinoma Progressing on Anti-PD-(L)1

Posted: May 19th, 2020, 11:00pm UTC

Conditions: Merkel Cell Carcinoma
Interventions: Drug: domatinostat in combination with avelumab
Sponsors: 4SC AG
Completed

A Phase 1B/2 Study of RP1 in Solid Organ Transplant Patients With Advanced Cutaneous Malignancies

Posted: April 16th, 2020, 11:00pm UTC

Conditions: Cutaneous Squamous Cell Carcinoma; Merkel Cell Carcinoma; Basal Cell Carcinoma; Melanoma
Interventions: Biological: RP1, intra-tumoral injection, oncolytic virus
Sponsors: Replimune Inc.
Recruiting

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INCB099318 in Participants With Advanced Solid Tumors

Posted: February 17th, 2020, 1:00am UTC

Conditions: Advanced Solid Tumors; MSI-H/dMMR Tumors; Cutaneous Squamous Cell Carcinoma; Urothelial Carcinoma, HCC; Cervical Cancer; Esophageal Squamous Cell Carcinoma; Merkel Cell Carcinoma; Small-cell Lung Cancer; Mesothelioma; PD-L1 Amplified Tumor (9p24.1); Nasopharyngeal Carcinoma; Cyclin-dependent Kinase 12 Mutated Tumors; Basal Cell Carcinoma (Unresectable or Metastatic); Sarcomatoid Renal Cell Carcinoma; Clear Cell Ovarian or Endometrial Carcinoma; Anal Carcinoma; Squamous Cell Penile Carcinoma; DNA Polymerase Epsilon Mutated Tumors (P286R and V411L)
Interventions: Drug: INCB099318
Sponsors: Incyte Corporation
Active, not recruiting

Targeted Therapy and Avelumab in Merkel Cell Carcinoma

Posted: February 10th, 2020, 1:00am UTC

Conditions: Metastatic Merkel Cell Carcinoma
Interventions: Drug: Avelumab; Radiation: External Beam Radiation Therapy (EBRT); Radiation: Lutetium-177 (177Lu)-DOTATATE
Sponsors: Melanoma and Skin Cancer Trials Limited
Recruiting

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INCB099280 in Participants With Advanced Solid Tumors

Posted: January 27th, 2020, 1:00am UTC

Conditions: Advanced Solid Tumor; MSI-H/dMMR Tumors; Cutaneous Squamous Cell Carcinoma; Urothelial Carcinoma; Cervical Cancer; HepatoCellular Carcinoma; Esophageal Squamous Cell Carcinoma; Merkel Cell Carcinoma; Small-cell Lung Cancer; Mesothelioma; PD-L1 Amplified Tumor (9p24.1); Nasopharyngeal Carcinoma
Interventions: Drug: INCB099280
Sponsors: Incyte Corporation
Active, not recruiting

Study of SO-C101 and SO-C101 in Combination With Pembro in Adult Patients With Advanced/Metastatic Solid Tumors

Posted: January 21st, 2020, 1:00am UTC

Conditions: Thyroid Cancer; Renal Cell Carcinoma; Non Small Cell Lung Cancer; Small-cell Lung Cancer; Bladder Cancer; Melanoma; Merkel Cell Carcinoma; Skin Squamous Cell Carcinoma; Microsatellite Instability High; Triple Negative Breast Cancer; Mesothelioma; Thymic Cancer; Cervical Cancer; Biliary Tract Cancer; Hepatocellular Carcinoma; Ovarian Cancer; Gastric Cancer; Head and Neck Squamous Cell Carcinoma; Anal Cancer
Interventions: Drug: Nanrilkefusp alfa; Drug: Pembrolizumab
Sponsors: SOTIO Biotech AG; SOTIO Biotech a.s.
Active, not recruiting

LITT and Pembrolizumab in Recurrent Brain Metastasis

Posted: December 5th, 2019, 1:00am UTC

Conditions: Melanoma; Non-small Cell Lung Carcinoma (NSCLC); Renal Cell Carcinoma (RCC); Small-cell Lung Cancer; Head and Neck Squamous Cell Cancer; Classical Hodgkin Lymphoma; Primary Mediastinal Large B-Cell Lymphoma; Urothelial Carcinoma; Microsatellite Instability-High Cancer; Gastric Cancer; Esophageal Cancer; Cervical Cancer; Hepatocellular Carcinoma; Merkel Cell Carcinoma; Brain Metastases, Adult
Interventions: Combination Product: LITT + Pembrolizumab
Sponsors: University of Florida; Monteris Medical
Terminated

Immunotherapy With IFx-Hu2.0 Vaccine for Advanced Non-melanoma Skin Cancers

Posted: November 12th, 2019, 1:00am UTC

Conditions: Merkel Cell Carcinoma; Cutaneous Squamous Cell Carcinoma; Non-Melanoma Skin Cancers
Interventions: Biological: IFx-Hu2.0
Sponsors: TuHURA Biosciences, Inc.; H. Lee Moffitt Cancer Center and Research Institute; University of Southern California; Dana-Farber Cancer Institute; Huntsman Cancer Institute
Completed

Evaluating Length of Treatment With PD-1/PD-L1 Inhibitor in Advanced Solid Tumors

Posted: November 8th, 2019, 1:00am UTC

Conditions: Advanced Solid Tumors; NSCLC; Bladder Cancer; HNSCC; Renal Cancer; Melanoma; Anal Cancer; Colorectal Cancer; Cholangiocarcinoma; Gastric Cancer; Hepatocellular Carcinoma; Merkel Cell Carcinoma; Cervical Cancer
Interventions: Drug: Continue PD-1/PD-L1 Inhibitors treatment; Other: Discontinue PD-1/PD-L1-1 inhibitor
Sponsors: Jason J. Luke, MD
Recruiting

A Study of FF-10850 Topotecan Liposome Injection in Advanced Solid Tumors

Posted: August 6th, 2019, 11:00pm UTC

Conditions: Advanced Solid Tumors; Merkel Cell Carcinoma
Interventions: Drug: FF-10850 Topotecan Liposome Injection
Sponsors: Fujifilm Pharmaceuticals U.S.A., Inc.
Recruiting

Adoptive Transfer of Tumor Infiltrating Lymphocytes for Advanced Solid Cancers

Posted: May 2nd, 2019, 11:00pm UTC

Conditions: Gastric Cancer; Colorectal Cancer; Pancreatic Cancer; Sarcoma; Mesothelioma; Neuroendocrine Tumors; Squamous Cell Cancer; Merkel Cell Carcinoma; Mismatch Repair Deficiency; Microsatellite Instability
Interventions: Biological: Tumor Infiltrating Lymphocytes (TIL); Drug: Fludarabine + Cyclophosphamide combination
Sponsors: Udai Kammula
Recruiting

High-Risk Skin Cancers With Atezolizumab Plus NT-I7

Posted: April 3rd, 2019, 11:00pm UTC

Conditions: Melanoma; Merkel Cell Carcinoma; Cutaneous Squamous Cell Carcinoma
Interventions: Drug: NT-I7; Drug: atezolizumab
Sponsors: NeoImmuneTech; Immune Oncology Network
Terminated

AMPLIFYing NEOepitope-specific VACcine Responses in Progressive Diffuse Glioma

Posted: March 28th, 2019, 11:00pm UTC

Conditions: Malignant Glioma
Interventions: Drug: IDH1R132H peptide vaccine; Drug: Avelumab
Sponsors: German Cancer Research Center
Active, not recruiting

QUILT-3.063: A Study of N-803, haNK and Avelumab in Patients With Merkel Cell Carcinoma That Has Progressed After Checkpoint Therapy

Posted: February 25th, 2019, 1:00am UTC

Conditions: Merkel Cell Carcinoma
Interventions: Biological: Avelumab; Biological: N-803; Biological: haNKâ„¢
Sponsors: ImmunityBio, Inc.
Terminated

Nivolumab and Radiation Therapy or Ipilimumab as Adjuvant Therapy in Treating Patients With Merkel Cell Cancer

Posted: January 10th, 2019, 1:00am UTC

Conditions: Merkel Cell Carcinoma; Pathologic Stage IIIA Merkel Cell Carcinoma AJCC v8; Pathologic Stage IIIB Merkel Cell Carcinoma AJCC v8
Interventions: Biological: Ipilimumab; Biological: Nivolumab; Radiation: Radiation Therapy
Sponsors: Claire Verschraegen
Completed

Pembrolizumab (MK-3475) as First-line Therapy for Advanced Merkel Cell Carcinoma (MK-3475-913)

Posted: December 20th, 2018, 1:00am UTC

Conditions: Merkel Cell Carcinoma
Interventions: Drug: Pembrolizumab (MK-3475)
Sponsors: Merck Sharp & Dohme LLC
Completed

Gene-Modified Immune Cells (FH-MCVA2TCR) in Treating Patients With Metastatic or Unresectable Merkel Cell Cancer

Posted: November 20th, 2018, 1:00am UTC

Conditions: Other Skin
Interventions: Biological: Autologous MCPyV-specific HLA-A02-restricted TCR-transduced CD4+ and CD8+ T-cells FH-MCVA2TCR; Drug: Avelumab; Biological: Pembrolizumab; Biological: Interferon Gamma-1b
Sponsors: Fred Hutchinson Cancer Center; National Cancer Institute (NCI); Affini-T Therapeutics, Inc.
Active, not recruiting

Testing Pembrolizumab Versus Observation in Patients With Merkel Cell Carcinoma After Surgery, STAMP Trial

Posted: October 19th, 2018, 11:00pm UTC

Conditions: Pathologic Stage I Cutaneous Merkel Cell Carcinoma AJCC v8; Pathologic Stage II Cutaneous Merkel Cell Carcinoma AJCC v8; Pathologic Stage III Cutaneous Merkel Cell Carcinoma AJCC v8
Interventions: Other: Best Practice; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Biological: Pembrolizumab; Procedure: Positron Emission Tomography; Radiation: Radiation Therapy
Sponsors: National Cancer Institute (NCI)
Active, not recruiting

A Study to Evaluate the Safety and Tolerability of Immunotherapy Combinations in Participants With Advanced Malignancies

Posted: August 14th, 2018, 11:00pm UTC

Conditions: Non-small Cell Lung Cancer; Squamous Cell Carcinoma of the Head and Neck; Breast Cancer; Colorectal Cancer; Melanoma; Bladder Cancer; Ovarian Cancer; Endometrial Cancer; Merkel Cell Carcinoma; GastroEsophageal Cancer; Renal Cell Carcinoma; Castration-resistant Prostate Cancer
Interventions: Drug: Etrumadenant; Drug: Zimberelimab
Sponsors: Arcus Biosciences, Inc.
Completed

A Study of INCMGA00012 in Metastatic Merkel Cell Carcinoma (POD1UM-201)

Posted: July 26th, 2018, 11:00pm UTC

Conditions: Metastatic Merkel Cell Carcinoma
Interventions: Drug: Retifanlimab
Sponsors: Incyte Corporation
Completed

DOTATOC PET/CT for Imaging NET Patients

Posted: July 11th, 2018, 11:00pm UTC

Conditions: Neuroendocrine Tumors; Insulinoma; Gastrinoma; Glucagonoma; Vipoma; Pheochromocytoma; Paraganglioma; Neuroblastoma; Ganglioneuroma; Medullary Carcinoma; Pituitary Adenoma; Medulloblastoma; Merkel Cell Carcinoma; Small-cell Lung Cancer; Meningioma; Carcinoid
Interventions: Diagnostic Test: 68Ga-DOTATOC PET/CT; Diagnostic Test: 18F-FDG PET/CT
Sponsors: British Columbia Cancer Agency
Recruiting

How Microbes and Metabolism May Predict Skin Cancer Immunotherapy Outcomes

Posted: December 12th, 2017, 1:00am UTC

Conditions: Autoimmunity; Melanoma; Merkel Cell Carcinoma; Squamous Cell Carcinoma of the Skin; Basal Cell Carcinoma; Skin Cancer
Interventions: Biological: Immunotherapy
Sponsors: Washington University School of Medicine
Terminated

Testing the Addition of Radiation Therapy to Immunotherapy for Merkel Cell Carcinoma

Posted: October 9th, 2017, 11:00pm UTC

Conditions: Advanced Merkel Cell Carcinoma; Clinical Stage III Cutaneous Merkel Cell Carcinoma AJCC v8; Clinical Stage IV Cutaneous Merkel Cell Carcinoma AJCC v8; Metastatic Merkel Cell Carcinoma; Pathologic Stage III Cutaneous Merkel Cell Carcinoma AJCC v8; Pathologic Stage IIIA Cutaneous Merkel Cell Carcinoma AJCC v8; Pathologic Stage IIIB Cutaneous Merkel Cell Carcinoma AJCC v8; Pathologic Stage IV Cutaneous Merkel Cell Carcinoma AJCC v8
Interventions: Biological: Pembrolizumab; Radiation: Stereotactic Body Radiation Therapy
Sponsors: National Cancer Institute (NCI)
Active, not recruiting

Adjuvant Avelumab in Merkel Cell Cancer

Posted: September 5th, 2017, 11:00pm UTC

Conditions: Stage III Merkel Cell Carcinoma AJCC v8; Stage IIIB Merkel Cell Carcinoma AJCC v8; Stage IIIA Merkel Cell Carcinoma AJCC v8
Interventions: Drug: Avelumab; Other: Peripheral Blood Collection; Other: Placebo
Sponsors: University of Washington; EMD Serono
Active, not recruiting

Phase Ib of L-NMMA and Pembrolizumab

Posted: August 2nd, 2017, 11:00pm UTC

Conditions: Non-Small Cell Lung Cancer; Malignant Melanoma; Head and Neck Squamous Cell Carcinoma; Classical Hodgkin Lymphoma; Urothelial Carcinoma Bladder; DNA Repair-Deficiency Disorders
Interventions: Drug: L-NMMA; Drug: Pembrolizumab
Sponsors: The Methodist Hospital Research Institute
Active, not recruiting

Permalink for 'QUILT-3.055: A Study of Combination Immunotherapies in Patients Who Have Previously Received Treatment With Immune Checkpoint Inhibitors'

QUILT-3.055: A Study of Combination Immunotherapies in Patients Who Have Previously Received Treatment With Immune Checkpoint Inhibitors

Posted: July 25th, 2017, 11:00pm UTC

Conditions: Non-Small Cell Lung Cancer; Small Cell Lung Cancer; Urothelial Carcinoma; Head and Neck Squamous Cell Carcinoma; Merkel Cell Carcinoma; Melanoma; Renal Cell Carcinoma; Gastric Cancer; Cervical Cancer; Hepatocellular Carcinoma; Microsatellite Instability; Mismatch Repair Deficiency; Colorectal Cancer
Interventions: Drug: N-803 + Pembrolizumab; Drug: N-803 + Nivolumab; Drug: N-803 + Atezolizumab; Drug: N-803 + Avelumab; Drug: N-803 + Durvalumab; Drug: N-803 + Pembrolizumab + PD-L1 t-haNK; Drug: N-803 + Nivolumab + PD-L1 t-haNK; Drug: N-803 + Atezolizumab + PD-L1 t-haNK; Drug: N-803 + Avelumab + PD-L1 t-haNK; Drug: N-803 + Durvalumab + PD-L1 t-haNK
Sponsors: ImmunityBio, Inc.
Active, not recruiting

Atezolizumab and Bevacizumab in Treating Patients With Rare Solid Tumors

Posted: March 8th, 2017, 1:00am UTC

Conditions: Appendix Adenocarcinoma; Human Papillomavirus-Related Anal Squamous Cell Carcinoma; Human Papillomavirus-Related Cervical Squamous Cell Carcinoma; Human Papillomavirus-Related Squamous Cell Carcinoma of the Penis; Human Papillomavirus-Related Vulvar Squamous Cell Carcinoma; Neuroendocrine Carcinoma; Pancreatic Neuroendocrine Tumor; Recurrent Merkel Cell Carcinoma; Recurrent Nasopharynx Carcinoma; Recurrent Peritoneal Malignant Mesothelioma; Recurrent Pleural Malignant Mesothelioma; Stage III Merkel Cell Carcinoma AJCC v7; Stage III Nasopharyngeal Carcinoma AJCC v7; Stage III Pleural Malignant Mesothelioma AJCC v7; Stage IV Merkel Cell Carcinoma AJCC v7; Stage IV Nasopharyngeal Carcinoma AJCC v7; Stage IV Pleural Malignant Mesothelioma AJCC v7; Stage IVA Nasopharyngeal Carcinoma AJCC v7; Stage IVB Nasopharyngeal Carcinoma AJCC v7; Stage IVC Nasopharyngeal Carcinoma AJCC v7; Vaginal Squamous Cell Carcinoma, Not Otherwise Specified
Interventions: Drug: Atezolizumab; Biological: Bevacizumab; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study
Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI)
Active, not recruiting

Randomized Study of Nivolumab+Ipilimumab+/- SBRT for Metastatic Merkel Cell Carcinoma

Posted: March 6th, 2017, 1:00am UTC

Conditions: Merkel Cell Carcinoma; Skin Cancer
Interventions: Drug: Nivolumab; Drug: Ipilimumab; Radiation: Stereotactic Body Radiation Therapy (SBRT)
Sponsors: H. Lee Moffitt Cancer Center and Research Institute; Bristol-Myers Squibb
Active, not recruiting

$Permalink for 'Talimogene Laherparepvec and Nivolumab in Treating Patients With Refractory Lymphomas or Advanced or Refractory Non-melanoma Skin Cancers'$

Talimogene Laherparepvec and Nivolumab in Treating Patients With Refractory Lymphomas or Advanced or Refractory Non-melanoma Skin Cancers

Posted: December 1st, 2016, 1:00am UTC

Conditions: Adnexal Carcinoma; Anaplastic Large Cell Lymphoma, ALK-Negative; Anaplastic Large Cell Lymphoma, ALK-Positive; Apocrine Carcinoma; Carcinoma Arising From Cylindroma; Carcinoma Arising From Spiradenoma; Digital Papillary Adenocarcinoma; Endocrine Mucin-Producing Sweat Gland Carcinoma; Extramammary Paget Disease; Extraocular Sebaceous Carcinoma; Hidradenocarcinoma; Keratoacanthoma; Malignant Sweat Gland Neoplasm; Merkel Cell Carcinoma; Microcystic Adnexal Carcinoma; NK-Cell Lymphoma, Unclassifiable; Papillary Adenocarcinoma; Porocarcinoma; Primary Cutaneous Mucinous Carcinoma; Recurrent Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Recurrent T-Cell Non-Hodgkin Lymphoma; Refractory Anaplastic Large Cell Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Refractory Merkel Cell Carcinoma; Refractory Mycosis Fungoides; Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Skin Squamous Cell Carcinoma; Refractory T-Cell Non-Hodgkin Lymphoma; Sezary Syndrome; Signet Ring Cell Adenocarcinoma; Skin Adenoid Cystic Carcinoma; Skin Basal Cell Carcinoma; Skin Basosquamous Cell Carcinoma; Skin Squamous Cell Carcinoma; Squamoid Eccrine Ductal Carcinoma; Squamous Cell Carcinoma of Unknown Primary; Sweat Gland Carcinoma; Trichilemmal Carcinoma; Vulvar Squamous Cell Carcinoma
Interventions: Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Other: Laboratory Biomarker Analysis; Biological: Nivolumab; Procedure: Positron Emission Mammography; Biological: Talimogene Laherparepvec
Sponsors: National Cancer Institute (NCI)
Active, not recruiting

A Study of T-VEC (Talimogene Laherparepvec) With or Without Radiotherapy for Melanoma, Merkel Cell Carcinoma, or Other Solid Tumors

Posted: June 30th, 2016, 11:00pm UTC

Conditions: Melanoma; Merkel Cell Carcinoma; Other Solid Tumors
Interventions: Drug: TALIMOGENE LAHERPAREPVEC (TVEC); Radiation: Hypofractionated Radiotherapy
Sponsors: Memorial Sloan Kettering Cancer Center; Amgen
Completed

Cytotoxic T Lymphocytes in Treating Patients With Malignancies With BK and/or JC Virus

Posted: June 24th, 2015, 11:00pm UTC

Conditions: Acquired Immunodeficiency Syndrome; BK Virus Infection; Human Immunodeficiency Virus; JC Virus Infection; Malignant Neoplasm; Merkel Cell Carcinoma; Merkel Cell Polyomavirus Infection; Viral Encephalitis
Interventions: Biological: Allogeneic BK-specific Cytotoxic T-lymphocytes; Other: Laboratory Biomarker Analysis
Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI)
Recruiting

Studies of Dermatologic Diseases Biospecimen Acquisition Protocol

Posted: June 15th, 2015, 11:00pm UTC

Conditions: Dermatologic Conditions; Healthy Volunteers; Normal Volunteers; Carcinoma, Merkel Cell
Sponsors: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Recruiting

QUILT-3.009: Patients With Stage III (IIIB) or Stage (IV) Merkel Cell Carcinoma (MCC)

Posted: June 9th, 2015, 11:00pm UTC

Conditions: Stage IIIB Merkel Cell Carcinoma; Stage IV Merkel Cell Carcinoma
Interventions: Biological: aNK (NK-92); Biological: aNK (NK-92) + N-803
Sponsors: ImmunityBio, Inc.
Terminated

Avelumab in Participants With Merkel Cell Carcinoma (JAVELIN Merkel 200)

Posted: June 4th, 2014, 11:00pm UTC

Conditions: Carcinoma, Merkel Cell
Interventions: Drug: Avelumab
Sponsors: EMD Serono Research & Development Institute, Inc.
Completed

Everolimus and Vatalanib in Treating Patients With Advanced Solid Tumors

Posted: April 10th, 2008, 11:00pm UTC

Conditions: Gastrinoma; Glucagonoma; Insulinoma; Metastatic Gastrointestinal Carcinoid Tumor; Metastatic Pheochromocytoma; Pancreatic Polypeptide Tumor; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Recurrent Melanoma; Recurrent Neuroendocrine Carcinoma of the Skin; Recurrent Non-small Cell Lung Cancer; Recurrent Pheochromocytoma; Recurrent Renal Cell Cancer; Somatostatinoma; Stage III Neuroendocrine Carcinoma of the Skin; Stage IV Melanoma; Stage IV Non-small Cell Lung Cancer; Stage IV Renal Cell Cancer; Thyroid Gland Medullary Carcinoma; Unspecified Adult Solid Tumor, Protocol Specific
Interventions: Drug: everolimus; Drug: vatalanib; Other: pharmacological study; Other: laboratory biomarker analysis; Procedure: dynamic contrast-enhanced magnetic resonance imaging; Procedure: ultrasound imaging
Sponsors: Mayo Clinic
Completed

Differentiation Benign and Malignant Pancreatic Lesions

Posted: October 15th, 2024, 11:00pm UTC

Conditions: Pancreatic Tumor
Interventions: Procedure: Whipple procedure
Sponsors: First Affiliated Hospital of Chongqing Medical University
Completed

Agnostic Therapy in Rare Solid Tumors

Posted: October 14th, 2024, 11:00pm UTC

Conditions: Urachal Cancer; Parathyroid Carcinoma; Fibrolamellar Carcinoma; Angiosarcoma; Secretory Carcinoma of Breast; Anal Neoplasms; Metaplastic Breast Carcinoma; Translocation Renal Cell Carcinoma; Carcinosarcoma; Small Intestine Neoplasms; Cholangiocarcinoma; Sertoli-Leydig Cell Tumor; Adenoid Cystic Carcinoma; Mesothelioma; Neuroblastoma; Adrenal Gland Neoplasms; Penile Neoplasms; Apocrine Carcinoma; Fibrosarcoma; Cancer of Unknown Primary; Hemangioblastoma; Thyroid Neoplasms; Hepatoblastoma; Fallopian Tube Neoplasms; Leiomyosarcoma; Vaginal Neoplasms; Neurofibrosarcoma; Gallbladder Neoplasms; Osteosarcoma; Biliary Tract Neoplasms; Clear Cell Endometrial Cancer; Yolk Sac Tumor; Vulvar Neoplasms; Kaposi Sarcoma; Ovarian Epithelial Cancer; Soft Tissue Sarcoma; Urethral Neoplasms; Granulosa Cell Tumor; Primitive Neuroectodermal Tumor; Neuroendocrine Tumors; Trophoblastic Tumor
Interventions: Drug: Nivolumab
Sponsors: Instituto do Cancer do Estado de SÃ£o Paulo; Financiadora de Estudos e Projetos
Recruiting

Clinical Study of the Efficacy and Safety of BCD-263 and OpdivoÂ® As Monotherapy in Subjects with Advanced Melanoma of the Skin

Posted: October 14th, 2024, 11:00pm UTC

Conditions: Advanced Melanoma; Melanoma (Skin)
Interventions: Drug: BCD-263; Drug: Opdivo
Sponsors: Biocad
Recruiting

177Lu-TATE-RGD in Patients With SSTR2 and Integrin Î±VÎ²3 Positive Tumors

Posted: October 9th, 2024, 11:00pm UTC

Conditions: SSTR2 and Integrin Î±VÎ²3 Positive Tumors
Interventions: Drug: 177Lu-TATE-RGD
Sponsors: Peking Union Medical College Hospital
Recruiting

Permalink for 'Evaluation of a Pragmatic Approach to Adoptive Cell Therapy (ACT) Using an IL2 Analog (ANV419) vs High Dose IL2 After Tumor Infiltrating Lymphocytes (TIL) Therapy in Patients With Melanoma, NSCLC and Cervical Cancer (PragmaTIL)'

Evaluation of a Pragmatic Approach to Adoptive Cell Therapy (ACT) Using an IL2 Analog (ANV419) vs High Dose IL2 After Tumor Infiltrating Lymphocytes (TIL) Therapy in Patients With Melanoma, NSCLC and Cervical Cancer (PragmaTIL)

Posted: October 8th, 2024, 11:00pm UTC

Conditions: Melanoma; Non Small Cell Lung Cancer; Cervical Cancer
Interventions: Biological: NMA-LD regimen; Biological: Tumor infiltrating lymphocytes adoptive cell therapy (TIL-ACT) infusion; Biological: High dose IL-2; Biological: IL-2 analog
Sponsors: Vall d'Hebron Institute of Oncology; Banc de Sang i Teixits
Not yet recruiting

Study of Tebentafusp and Radioembolization in the Treatment of Metastatic Uveal Melanoma

Posted: October 4th, 2024, 11:00pm UTC

Conditions: Metastatic Uveal Melanoma; Metastatic Uveal Melanoma in the Liver
Interventions: Drug: Tebentafusp; Radiation: TheraSphereâ„¢ Yttrium-90 Trans-Arterial Radioembolization
Sponsors: University of Miami; Immunocore Ltd
Not yet recruiting

Impact of Physical Activity on Immunotherapy-induced Toxicities in Melanoma Management

Posted: October 4th, 2024, 11:00pm UTC

Conditions: Melanoma; Immunotoxicity
Interventions: Drug: Immunotherapy
Sponsors: University Hospital, Montpellier
Not yet recruiting

Tebentafusp-tebn With LDT in Metastatic UM

Posted: October 4th, 2024, 11:00pm UTC

Conditions: Metastatic Uveal Melanoma
Interventions: Drug: Tebentafusp-Tebn; Drug: GM-CSF (Sargramostim); Drug: BCNU
Sponsors: Thomas Jefferson University; Sidney Kimmel Cancer Center at Thomas Jefferson University
Not yet recruiting

Microbiota and Carcinogenesis of Small-intestine Neuroendocrine Tumors

Posted: October 3rd, 2024, 11:00pm UTC

Conditions: Small-intestine Neuroendocrine Tumors
Interventions: Other: Blood and stool sampling
Sponsors: Hospices Civils de Lyon
Not yet recruiting

Effect of LNS8801 (with or Without Pembrolizumab) on Melanoma

Posted: October 3rd, 2024, 11:00pm UTC

Conditions: Melanoma (Skin Cancer); Melanoma Stage IIIB-IV; Cutaneous Melanoma; Unresectable Melanoma
Interventions: Biological: LNS8801; Biological: Pembrolizumab; Drug: Chemotherapy (dacarbazine or temozolomide); Biological: Immunotherapy (Pembrolizumab); Biological: Immunotherapy (nivolumab and relatlimab); Biological: Immunotherapy (ipilimumab and nivolumab)
Sponsors: Linnaeus Therapeutics, Inc.; Merck Sharp & Dohme LLC
Not yet recruiting

Permalink for 'STIL101 for Injection for the Treatment of Locally Advanced, Metastatic or Unresectable Pancreatic Cancer, Colorectal Cancer, Renal Cell Cancer, Cervical Cancer and Melanoma'

STIL101 for Injection for the Treatment of Locally Advanced, Metastatic or Unresectable Pancreatic Cancer, Colorectal Cancer, Renal Cell Cancer, Cervical Cancer and Melanoma

Posted: October 3rd, 2024, 11:00pm UTC

Conditions: Locally Advanced Cervical Carcinoma; Locally Advanced Colorectal Carcinoma; Locally Advanced Malignant Solid Neoplasm; Locally Advanced Melanoma; Locally Advanced Pancreatic Ductal Adenocarcinoma; Locally Advanced Renal Cell Carcinoma; Metastatic Cervical Carcinoma; Metastatic Colorectal Carcinoma; Metastatic Malignant Solid Neoplasm; Metastatic Melanoma; Metastatic Pancreatic Ductal Adenocarcinoma; Metastatic Renal Cell Carcinoma; Stage II Pancreatic Cancer AJCC v8; Stage III Cervical Cancer AJCC v8; Stage III Colorectal Cancer AJCC v8; Stage III Pancreatic Cancer AJCC v8; Stage III Renal Cell Cancer AJCC v8; Stage IV Cervical Cancer AJCC v8; Stage IV Colorectal Cancer AJCC v8; Stage IV Pancreatic Cancer AJCC v8; Stage IV Renal Cell Cancer AJCC v8; Unresectable Cervical Carcinoma; Unresectable Colorectal Carcinoma; Unresectable Malignant Solid Neoplasm; Unresectable Melanoma; Unresectable Pancreatic Ductal Adenocarcinoma; Unresectable Renal Cell Carcinoma
Interventions: Biological: Aldesleukin; Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Cyclophosphamide; Procedure: Excisional Biopsy; Drug: Fludarabine; Procedure: Magnetic Resonance Imaging; Procedure: Standard Treatment; Biological: Therapeutic Tumor Infiltrating Lymphocytes
Sponsors: City of Hope Medical Center; National Cancer Institute (NCI)
Not yet recruiting

LND101 for Fecal Microbiota Transplantation in Combination With Immune Checkpoint Blockade in Advanced Melanoma

Posted: October 2nd, 2024, 11:00pm UTC

Conditions: Melanoma
Interventions: Drug: Standard of Care Immune Checkpoint Blockade; Drug: LND101
Sponsors: Canadian Cancer Trials Group; Canadian Institutes of Health Research (CIHR); Canadian Cancer Society (CCS); The Weston A. Price Foundation
Not yet recruiting

Artificial Intelligence Based Melanoma Early Diagnosis and Risk Prediction in Children, Adolescents and Young Adults

Posted: October 1st, 2024, 11:00pm UTC

Conditions: Melanoma (Skin Cancer); Artificial Intelligence (AI); Pediatric Cancer
Sponsors: German Cancer Research Center; UniversitÃ¤t TÃ¼bingen; University of Florence; Fundacio Clinic Barcelona; Hospital Clinic of Barcelona
Recruiting

Permalink for 'Application of Machine Learning Algorithms to Identify Optimal Candidates for Primary Tumor Resection in Patients with Metastatic Non-small Cell Neuroendocrine Tumors'

Application of Machine Learning Algorithms to Identify Optimal Candidates for Primary Tumor Resection in Patients with Metastatic Non-small Cell Neuroendocrine Tumors

Posted: October 1st, 2024, 11:00pm UTC

Conditions: Lung Cancer - Non Small Cell
Interventions: Procedure: Surgery
Sponsors: Hongquan Xing; Second Affiliated Hospital of Nanchang University
Completed

Improved Early Diagnosis in Female Pelvic Cancer With OC Detect

Posted: September 25th, 2024, 11:00pm UTC

Conditions: Ovarian Cancer; Endometrial Cancer; Breast Cancer; Lymphoma; Malignant Melanoma; Sarcoma
Sponsors: Region Skane; Linkoeping University; VOC Diagnostics
Recruiting

Permalink for 'Study of IBI3009 in Subjects With Unresectable, Locally Advanced or Metastatic Small Cell Lung Cancer and Other Neuroendocrine Carcinomas'

Study of IBI3009 in Subjects With Unresectable, Locally Advanced or Metastatic Small Cell Lung Cancer and Other Neuroendocrine Carcinomas

Posted: September 25th, 2024, 11:00pm UTC

Conditions: Small Cell Lung Cancer and Other Neuroendocrine Carcinomas
Interventions: Drug: IBI3009
Sponsors: Innovent Biologics (Suzhou) Co. Ltd.
Not yet recruiting

Precision Medicine for L/GCMN and Melanoma 1

Posted: September 23rd, 2024, 11:00pm UTC

Conditions: Melanoma (Skin Cancer); Nevi and Melanomas
Interventions: Other: Gradient Boosting Survival Analysis (GBSA),; Other: Concordance index
Sponsors: Fundacion Clinic per a la Recerca BiomÃ©dica; Hospital Clinic of Barcelona
Recruiting

Clinical-pathological Evaluation of Pit-NETs

Posted: September 23rd, 2024, 11:00pm UTC

Conditions: Pituitary; Cancer; Neuroendocrine Tumors
Interventions: Diagnostic Test: grading & staging; Diagnostic Test: PitNET morphology analysis; Diagnostic Test: Radiomics; Diagnostic Test: Molecular test: proteomics
Sponsors: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Not yet recruiting

Liquid Biomarker Study in Melanoma and Non-Melanoma Skin Cancers

Posted: September 23rd, 2024, 11:00pm UTC

Understanding the Transition from Normal Melanocytes to Nevus to Melanoma

Posted: September 20th, 2024, 11:00pm UTC

Conditions: Congenital Melanocytic Nevi; Melanoma, Skin; Nevi and Melanomas
Interventions: Genetic: Methylomics; Genetic: RNA sequencing; Genetic: Spatial transcriptomics; Genetic: Liquid biopsy
Sponsors: Fundacion Clinic per a la Recerca BiomÃ©dica; Institut National de la SantÃƒÂ© Et de la Recherche MÃƒÂ©dicale, France; University Hospital Tuebingen; University of Florence; Fondazione IRCCS Istituto Nazionale dei Tumori, Milano; University Of Perugia; German Cancer Research Center; Karolinska Institutet; Maria Sklodowska-Curie National Research Institute of Oncology; Institut Curie; Medical University of Gdansk; Princess Maxima Center for Pediatric Oncology; Catalan Institute of Oncology, Barcelona
Recruiting

Precision Medicine for L/GCMN and Melanoma 2

Posted: September 20th, 2024, 11:00pm UTC

Conditions: Melanoma (Skin Cancer); Nevi and Melanomas; Congenital Melanocytic Nevus
Interventions: Device: Breath analyzer; Device: Skin patch; Genetic: Liquid biopsy
Sponsors: Fundacion Clinic per a la Recerca BiomÃ©dica; Hospital Clinic of Barcelona
Not yet recruiting

A Feasibility Study to Investigate LATe CaRdiac ToxicIty Following ImmUnotherapy Treatment for Melanoma

Posted: September 20th, 2024, 11:00pm UTC

Conditions: Melanoma Stage III or IV
Interventions: Diagnostic Test: Lead ECG; Diagnostic Test: Transthoracic Echocardiogram; Diagnostic Test: Cardiac MRI; Diagnostic Test: Cardiac Biomarker Screening; Other: Basic Observations
Sponsors: Royal Marsden NHS Foundation Trust; Royal Brompton and Harefield NHS Foundation Trust; Royal Free Hospital NHS Foundation Trust
Not yet recruiting

MELCAYA - Novel Health Care Strategies for Melanoma in Children, Adolescents, and Young Adults - Work Package 3 (WP3)

Posted: September 19th, 2024, 11:00pm UTC

Conditions: Melanoma of Skin
Sponsors: University of Florence; Tubingen University Hospital; Maria Sklodowska-Curie National Research Institute of Oncology; Fondazione IRCCS ISTITUTO NAZIONALE TUMORI; Hospital Clinic of Barcelona; Istanbul University; University Of Perugia; German Cancer Research Center
Recruiting

Effects of Anti-PD1 Adjuvant Checkpoint Blockade Immunotherapy on Atypical/Dysplastic Nevi

Posted: September 19th, 2024, 11:00pm UTC

Conditions: Melanoma
Interventions: Drug: Nivolumab; Drug: Pembrolizumab
Sponsors: John Kirkwood; Melanoma Research Foundation
Not yet recruiting

A Study of Fianlimab, Cemiplimab, and Ipilimumab in People With Melanoma

Posted: September 13th, 2024, 11:00pm UTC

Conditions: Advanced Melanoma
Interventions: Drug: Fianlimab; Drug: Cemiplimab; Drug: Ipilimumab
Sponsors: Memorial Sloan Kettering Cancer Center; Regeneron Pharmaceuticals
Recruiting

A Clinical Study of Sorafenib Combined With Gefitinib for the Treatment of pNET

Posted: September 12th, 2024, 11:00pm UTC

Conditions: Pancreatic Neuroendocrine Neoplasm; Sorafenib; Gefitinib
Interventions: Drug: sorafenib, gefitinib
Sponsors: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Not yet recruiting

An Expanded Access Program for VO (RP1) in Combination With Nivolumab in Patients With Advanced Melanoma

Posted: September 11th, 2024, 11:00pm UTC

Conditions: Advanced Melanoma
Interventions: Biological: RP1; Biological: Nivolumab
Sponsors: Replimune Inc.
Available

Permalink for 'Integrated Pharmacokinetics (PK)/efficacy, Safety, and Immunogenicity Study to Demonstrate Similarity of JPB898, a Proposed Biosimilar to Nivolumab, to OpdivoÂ® in Combination with YervoyÂ®'

Integrated Pharmacokinetics (PK)/efficacy, Safety, and Immunogenicity Study to Demonstrate Similarity of JPB898, a Proposed Biosimilar to Nivolumab, to OpdivoÂ® in Combination with YervoyÂ®

Posted: September 9th, 2024, 11:00pm UTC

Conditions: Melanoma
Interventions: Drug: JPB898 (Induction and Maintenance); Drug: Opdivo-EU (Induction); Drug: Opdivo-US (Induction); Drug: Yervoy-EU (Induction); Drug: Opdivo-EU (Maintenance)
Sponsors: Sandoz
Not yet recruiting

Treatment of Metastatic Melanoma with Lenvatinib + Anti-PD1

Posted: September 6th, 2024, 11:00pm UTC

Conditions: Metastatic Melanoma
Sponsors: Centre Hospitalier Universitaire de Besancon
Completed

Neoadjuvant Immunotherapy of Operable Metastatic Melanoma in Real Life (GCC)

Posted: September 6th, 2024, 11:00pm UTC

Conditions: Melanoma Metastatic
Sponsors: Centre Hospitalier Universitaire de Besancon
Recruiting

Permalink for 'A Randomized, Phase 2/3 Study to Investigate the Efficacy and Safety of RP2 in Combination With Nivolumab in Immune Checkpoint Inhibitor-NaÃ¯ve Adult Patients With Metastatic Uveal Melanoma'

A Randomized, Phase 2/3 Study to Investigate the Efficacy and Safety of RP2 in Combination With Nivolumab in Immune Checkpoint Inhibitor-NaÃ¯ve Adult Patients With Metastatic Uveal Melanoma

Posted: September 2nd, 2024, 11:00pm UTC

Conditions: Metastatic Uveal Melanoma
Interventions: Biological: RP2; Biological: Ipilimumab; Biological: Nivolumab
Sponsors: Replimune Inc.
Not yet recruiting

Irinotecan Liposome in Combination With Capecitabine

Posted: August 29th, 2024, 11:00pm UTC

Conditions: Pancreatic Cancer
Interventions: Drug: Irinotecan liposome Capecitabine
Sponsors: Cancer Hospital Chinese Academy of Medical Science, Shenzhen Center
Not yet recruiting

Safety/Efficacy Study of CID-078 in Patients With Advanced Solid Tumor Malignancies

Posted: August 29th, 2024, 11:00pm UTC

Conditions: Advanced Solid Tumor; Metastatic Solid Tumor; Refractory Solid Tumor; Cancer; Lung Cancer; Triple Negative Breast Cancer; Breast Neoplasms; Neuroendocrine Tumors; Neuroendocrine Carcinoma
Interventions: Drug: CID-078 Monotherapy
Sponsors: Circle Pharma
Recruiting

USPIO Enhanced MR Imaging in CNS Tumours (UMIC)

Posted: August 27th, 2024, 11:00pm UTC

Conditions: Vestibular Schwannoma; Glioma, Astrocytic
Interventions: Diagnostic Test: USPIO enhanced MRI
Sponsors: Northern Care Alliance NHS Foundation Trust
Recruiting

Institutional Registry of Rare Diseases

Posted: August 27th, 2024, 11:00pm UTC

Conditions: Rare Diseases; Amyloidosis; Sarcoidosis; Phacomatosis; Pheochromocytoma; Paraganglioma; Von Hippel-Lindau Disease; Immunoglobulin G4-Related Disease; Demyelinating Diseases; Inborn Errors of Metabolism; Eosinophilic Gastrointestinal Disorders; Hypertrophic Cardiomyopathy; Gaucher Disease; Congenital Adrenal Hyperplasia; Hereditary Angioedema; Pulmonary Hypertension; Wilson Disease; Vascular Anomalies; Mastocytosis; Multiple Endocrine Neoplasia; Inflammatory Bowel Diseases; Prader-Willi Syndrome; Hirschsprung Disease; Cushing Syndrome
Sponsors: Hospital Italiano de Buenos Aires
Recruiting

Oral Protein Supplements for Nutritional and Quality of Life Improvement After Pancreatic Resection in Elderly Patients

Posted: August 26th, 2024, 11:00pm UTC

Conditions: Pancreatic Cancer; Cholangiocarcinoma; Intraductal Papillary Mucinous Neoplasm; Neuroendocrine Tumor; Solid Pseudopapillary Tumor
Interventions: Dietary Supplement: oral protein supplements; Genetic: placebo
Sponsors: Yonsei University
Completed

Ipilimumab and Nivolumab Followed by Adjuvant Nivolumab in Locally Advanced or Limited Metastatic Melanoma

Posted: August 22nd, 2024, 11:00pm UTC

Conditions: Melanoma
Interventions: Drug: Ipilimumab
Sponsors: European Institute of Oncology; Bristol-Myers Squibb
Active, not recruiting

Gene Expression Profiles and ctDNA for Risk Stratification in Patients With Melanoma

Posted: August 22nd, 2024, 11:00pm UTC

Conditions: Melanoma
Sponsors: European Institute of Oncology
Not yet recruiting

Preoperative Planning With PSMA-PET in Melanoma Surgery Trial

Posted: August 19th, 2024, 11:00pm UTC

Conditions: Malignant Melanoma
Interventions: Drug: 68Ga-PSMA
Sponsors: Royal Marsden NHS Foundation Trust
Not yet recruiting

Relapse-Free Survival With Adjuvant Dabrafenib/Trametinib Therapy in Patients With BRAF V600-mutated Stage III/IV Melanoma

Posted: August 16th, 2024, 11:00pm UTC

Conditions: BRAF V600 Mutated-Stage III/IV Melanoma
Sponsors: Novartis
Completed

Pancreatic Fistula After Minimally Invasive Enucleation

Posted: August 16th, 2024, 11:00pm UTC

Conditions: Pancreatic Tumor, Benign; Pancreatic Neuroendocrine Tumor; Solid Pseudopapillary Tumor of the Pancreas
Sponsors: Fudan University
Completed

The Application of the PDCA Management Model in Improving the Diagnostic Accuracy of AIG

Posted: August 16th, 2024, 11:00pm UTC

Conditions: Autoimmune Gastritis
Interventions: Behavioral: PDCA training
Sponsors: Ningbo No. 1 Hospital
Not yet recruiting

Merck Belzutifan PAS

Posted: August 15th, 2024, 11:00pm UTC

Conditions: Von Hippel Lindau Disease; Renal Cell Carcinoma
Interventions: Other: Merck Belzutifan PAS in adult patients
Sponsors: M.D. Anderson Cancer Center; Merck Sharp & Dohme LLC
Not yet recruiting

Phase 1 Study Using TRIMELVax for Stage IIIC / IV Melanoma Patients

Posted: August 15th, 2024, 11:00pm UTC

Conditions: Melanoma Stage IIIc; Melanoma Stage IV
Interventions: Biological: TRIMELVAX
Sponsors: University of Chile; Hospital del Salvador
Active, not recruiting

Permalink for 'A Single-arm, Multicenter Clinical Study of Fruquintinib Combined With Cadonilimab Injection and Temozolomide in Second-line and Subsequent Treatment of Advanced Melanoma'

A Single-arm, Multicenter Clinical Study of Fruquintinib Combined With Cadonilimab Injection and Temozolomide in Second-line and Subsequent Treatment of Advanced Melanoma

Posted: August 14th, 2024, 11:00pm UTC

Conditions: Malignant Melanoma
Interventions: Drug: Temozolomideã€Fruquintinibã€Cadonilimab
Sponsors: Fudan University
Not yet recruiting

Identification of New Candidate Genes for Hereditary Predisposition to Uveal Melanoma

Posted: August 13th, 2024, 11:00pm UTC

Conditions: Uveal Melanoma
Interventions: Genetic: Constitutional exome analysis
Sponsors: Centre Jean Perrin; Association Nationale des Patients atteints de cancers de l'oeil (A.N.P.A.C.O.)
Not yet recruiting

Assessment of PK Similarity of FYB206 in Comparison With Keytruda in Resected Stage II or III Melanoma Patients

Posted: August 13th, 2024, 11:00pm UTC

Conditions: Melanoma, Stage II; Melanoma Stage III
Interventions: Biological: pembrolizumab
Sponsors: Formycon AG
Recruiting

eFLASH for Skin Lesions of Malignant Melanomas

Posted: August 12th, 2024, 11:00pm UTC

Conditions: Metastatic Melanoma
Interventions: Radiation: Electron FLASH radiotherapy
Sponsors: University of Zurich; Varian, a Siemens Healthineers Company
Not yet recruiting

Permalink for 'Neoadjuvant Immune Checkpoint Blockade + a Prebiotic Food-enriched Dietary Intervention to Optimize Immune Response in Melanoma: NEO-PreFED'

Neoadjuvant Immune Checkpoint Blockade + a Prebiotic Food-enriched Dietary Intervention to Optimize Immune Response in Melanoma: NEO-PreFED

Posted: August 12th, 2024, 11:00pm UTC

Conditions: Melanoma
Interventions: Dietary Supplement: Prebiotic Xnack Packouts
Sponsors: M.D. Anderson Cancer Center
Not yet recruiting

Permalink for 'Collection of Liquid Biopsy Samples of Neuroendocrine Neoplasms (NEN) Patients - Collection of NET (CollectNET) 2.0, a Study by the BE-FORCE Consortium'

Collection of Liquid Biopsy Samples of Neuroendocrine Neoplasms (NEN) Patients - Collection of NET (CollectNET) 2.0, a Study by the BE-FORCE Consortium

Posted: August 7th, 2024, 11:00pm UTC

Conditions: Neuroendocrine Neoplasms
Interventions: Diagnostic Test: Shallow Whole Genome Sequencing (sWGS)-GIPXplore; Diagnostic Test: methylation-sensitive restriction enzymes (MSRE)-Single-molecule molecular inversion probes (smMIP)-seq assay
Sponsors: University Hospital, Antwerp; Universitaire Ziekenhuizen KU Leuven; Universiteit Antwerpen; KU Leuven
Recruiting

Phase II Clinical Study of Leflunomide in the Treatment of MEN-1 Neuroendocrine Tumor

Posted: August 7th, 2024, 11:00pm UTC

Conditions: Neuroendocrine Tumors
Interventions: Drug: Leflunomide Pill
Sponsors: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Recruiting

A French Multicenter Observational Retrospective Study of Rare Primary Liver Cancers

Posted: August 7th, 2024, 11:00pm UTC

Conditions: Hepatocholangiocarcinoma; Fibrolamellar Carcinoma; Hepatic Epithelioid Hemangioendothelioma; Hepatoblastoma; Hepatic Neuroendocrine Carcinoma; Hepatic Carcinosarcomas; Hepatic Cystadenoma; Hepatic Leiomyosarcomas; Hepatic Angiosarcomas; Cholangiocarcinoma
Sponsors: Federation Francophone de Cancerologie Digestive; SociÃ©tÃ© Nationale FranÃ§aise de GastroentÃ©rologie
Recruiting

A Phase 1b Trial to Evaluate Safety of MB097 in Combination With Pembrolizumab in Melanoma Patients

Posted: August 6th, 2024, 11:00pm UTC

Conditions: Melanoma
Interventions: Biological: MB097; Biological: Pembrolizumab; Drug: Vancomycin
Sponsors: Microbiotica Ltd; Merck Sharp & Dohme LLC
Not yet recruiting

Personalised Immunotherapy Platform (PIP-PREDICT)

Posted: August 2nd, 2024, 11:00pm UTC

Permalink for 'Surufatinib Combined With Serplulimab and Standard Chemotherapy as First-line Treatment in Advanced Solid Tumors With Neuroendocrine Differentiation'

Surufatinib Combined With Serplulimab and Standard Chemotherapy as First-line Treatment in Advanced Solid Tumors With Neuroendocrine Differentiation

Posted: July 31st, 2024, 11:00pm UTC

Conditions: ESCC; Biliary Tract Cancer; Gastric Cancer; Pancreas Cancer
Interventions: Drug: Surufatinib; Drug: Serplulimab; Drug: standard chemotherapy
Sponsors: RenJi Hospital
Not yet recruiting

Genetic Bases of Neuroendocrine Neoplasms in Mexican Patients

Posted: July 26th, 2024, 11:00pm UTC

Conditions: Neuroendocrine Neoplasm; Neuroendocrine Neoplasm of Gastrointestinal Tract; Neuroendocrine Neoplasm of Lung; Thymic Neuroendocrine Neoplasm; Neuroendocrine Tumor of Pancreas; Gastrointestinal Stromal Tumors; Medullary Thyroid Cancer; Paraganglioma; Pheochromocytoma; Primary Hyperparathyroidism; Pituitary Tumor; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2; Multiple Endocrine Neoplasia Type 4; Carney Complex; Carney Stratakis Dyad; Carney Triad; Cowden Syndrome; DICER1 Syndrome; Li-Fraumeni Syndrome; Lynch Syndrome; Von Hippel-Lindau Disease; Familial Isolated Pituitary Adenoma; X-Linked Acrogigantism; Neurofibromatosis 1; Tuberous Sclerosis
Sponsors: Universidad Nacional Autonoma de Mexico; Instituto Mexicano del Seguro Social; Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Recruiting

A Study of Cobolimab Plus Dostarlimab in Pediatric and Young Adult Participants With Cancer

Posted: July 26th, 2024, 11:00pm UTC

Conditions: Melanoma
Interventions: Drug: Cobolimab; Drug: Dostarlimab
Sponsors: GlaxoSmithKline
Not yet recruiting

PHP in Combination With IPI1/NIVO3 Compared to IPI3/NIVO1 Only in Patients With Uveal Melanoma Liver Metastases

Posted: July 25th, 2024, 11:00pm UTC

Conditions: Uveal Melanoma; Liver Metastases
Interventions: Device: PHP; Drug: IPI1/NIVO3; Drug: IPI3/NIVO1
Sponsors: Vastra Gotaland Region
Not yet recruiting

Head-to-head Study of 68Ga-MGS5 Versus 68Ga-DOTATATE PET/CT in Patients With Medullary Thyroid Carcinoma

Posted: July 25th, 2024, 11:00pm UTC

Conditions: Medullary Thyroid Carcinoma
Interventions: Drug: 68Ga-MGS5
Sponsors: First Affiliated Hospital of Fujian Medical University
Recruiting

Permalink for 'Generation of Organoids of Neuroendocrine Neoplasms of the Gastro-Entero-Pancreatic Tract Obtained From Patients Undergoing Surgery'

Generation of Organoids of Neuroendocrine Neoplasms of the Gastro-Entero-Pancreatic Tract Obtained From Patients Undergoing Surgery

Posted: July 25th, 2024, 11:00pm UTC

Conditions: Gastro-entero-pancreatic Neoplasms
Sponsors: Regina Elena Cancer Institute
Recruiting

Anti-VEGF Gene Therapy Trial for Vestibular Schwannoma

Posted: July 24th, 2024, 11:00pm UTC

Conditions: Vestibular Schwannoma
Interventions: Combination Product: AAVAnc80-antiVEGF via Akouos Delivery Device
Sponsors: Akouos, Inc.; Eli Lilly and Company
Recruiting

Evaluating Myelodysplastic Syndrome Risks in NET Patients Planned for Peptide Radionuclide Therapy

Posted: July 19th, 2024, 11:00pm UTC

Conditions: Myelodysplastic Syndrome; Acute Myeloid Leukemia
Interventions: Radiation: Peptide receptor radionuclide therapy (PRRT); Diagnostic Test: Blood collection
Sponsors: University Health Network, Toronto
Not yet recruiting

Pilot Trial of Intravenous Iron in Combination With Standard of Care Immunotherapy in Melanoma

Posted: July 18th, 2024, 11:00pm UTC

Conditions: Anemia, Iron Deficiency; Melanoma
Interventions: Drug: Iron dextran 1000 mg IV
Sponsors: Indiana University
Recruiting

Long-Term Follow-up of Patients Treated With Miltenyi Cell and Gene Therapies

Posted: July 18th, 2024, 11:00pm UTC

Conditions: Melanoma Stage III; B-cell Non Hodgkin Lymphoma; Pediatric ALL; Childhood Non-Hodgkin Lymphoma; Acute Lymphatic Leukemia; Chronic Lymphatic Leukemia; Melanoma Stage IV
Interventions: Biological: MB-CART19.1; Biological: MB-CART20.1; Biological: MB-CART2019.1
Sponsors: Miltenyi Biomedicine GmbH
Recruiting

Permalink for 'A Study of BL-M14D1 in Patients With Locally Advanced or Metastatic Small Cell Lung Cancer, Neuroendocrine Tumors and Other Solid Tumors'

A Study of BL-M14D1 in Patients With Locally Advanced or Metastatic Small Cell Lung Cancer, Neuroendocrine Tumors and Other Solid Tumors

Posted: July 17th, 2024, 11:00pm UTC

Conditions: Small Cell Lung Cancer; Neuroendocrine Tumors
Interventions: Drug: BL-M14D1
Sponsors: Sichuan Baili Pharmaceutical Co., Ltd.; Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.
Recruiting

Permalink for 'A Trial to Assess Efficacy, Safety, Pharmacokinetics of Octreotide Subcutaneous Injection in Patients With Gastroentero-pancreatic Neuroendocrine Tumor (GEP-NET)'

A Trial to Assess Efficacy, Safety, Pharmacokinetics of Octreotide Subcutaneous Injection in Patients With Gastroentero-pancreatic Neuroendocrine Tumor (GEP-NET)

Posted: July 17th, 2024, 11:00pm UTC

Conditions: Gastrointestinal Neuroendocrine Pancreatic Tumor
Interventions: Drug: SYHX2008 injection; Drug: Sandostatin LAR@
Sponsors: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Recruiting

18F-Fibroblast Activation Protein Inhibitor ([18F]FAPI-74) PET Imaging for Cancer Detection

Posted: July 16th, 2024, 11:00pm UTC

Conditions: Pancreatic Ductal Adenocarcinoma; Cholangiocarcinoma; Gastric Cancer; Bladder Cancer; Hepatocellular Carcinoma; Pheochromocytoma; Ovarian Cancer
Interventions: Drug: [18F]FAPI-74; Drug: [18F]FDG
Sponsors: National Cancer Institute (NCI)
Not yet recruiting

Permalink for 'Study Evaluating Tarlatamab in Chinese Participants With Advanced Small Cell Lung Cancer After Two or More Prior Lines of Treatment'

Study Evaluating Tarlatamab in Chinese Participants With Advanced Small Cell Lung Cancer After Two or More Prior Lines of Treatment

Posted: July 16th, 2024, 11:00pm UTC

Conditions: Advanced Small Cell Lung Cancer
Interventions: Drug: Tarlatamab
Sponsors: Amgen
Recruiting

Permalink for 'Testing Longer Duration Radiation Therapy Versus the Usual Radiation Therapy in Patients With Cancer That Has Spread to the Brain'

Testing Longer Duration Radiation Therapy Versus the Usual Radiation Therapy in Patients With Cancer That Has Spread to the Brain

Posted: July 15th, 2024, 11:00pm UTC

Conditions: Anatomic Stage IV Breast Cancer AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Metastatic Breast Carcinoma; Metastatic Digestive System Carcinoma; Metastatic Lung Non-Small Cell Carcinoma; Metastatic Malignant Neoplasm in the Brain; Metastatic Malignant Solid Neoplasm; Metastatic Melanoma; Metastatic Renal Cell Carcinoma; Stage IV Lung Cancer AJCC v8; Stage IV Renal Cell Cancer AJCC v8
Interventions: Procedure: Computed Tomography; Radiation: Fractionated Stereotactic Radiation Therapy; Procedure: Magnetic Resonance Imaging; Radiation: Stereotactic Radiosurgery
Sponsors: NRG Oncology; National Cancer Institute (NCI)
Recruiting

Identification of Olfactory Biomarkers of Skin Cancer From Skin Odor Samples: a Pilot Study

Posted: July 10th, 2024, 11:00pm UTC

Conditions: Identify Volatile Biomarkers Specific to Malignant Melanoma, Basal Cell Carcinoma and Squamous Cell Carcinoma; Verify That the Volatile Biomarkers Identified Derive From Metabolic Changes in Body Odour and Not Just From Changes in the Surface of Cancerous Lesions
Interventions: Other: Collection of body odor samples
Sponsors: Association pour la Recherche Clinique et Immunologique; SenseBioTek Health-Care; ESPCI Paris
Not yet recruiting

NIS to Examine the Effectiveness of TDC in Patients With Metastatic Non-squamous NSCLC and High-risk Genetic Alterations

Posted: July 10th, 2024, 11:00pm UTC

Conditions: Non-squamous Metastatic Non-Small-Cell Lung Carcinoma
Sponsors: AstraZeneca
Recruiting

In Vivo Liquid Biopsy of Melanoma Melanoma (Cytophone)

Posted: July 4th, 2024, 11:00pm UTC

Conditions: Melanoma; Circulating Tumor Cells; Metastatic Melanoma; Diagnosis
Interventions: Device: Cytophone
Sponsors: Cytoastra
Not yet recruiting

Assessment of Short Immunotherapy After Radical Surgery of High-risk Malignant Melanoma

Posted: July 4th, 2024, 11:00pm UTC

Conditions: High-risk Melanoma
Interventions: Drug: nivolumab or pembrolizumab
Sponsors: Uppsala University; Karolinska University Hospital; Skane University Hospital; Sahlgrenska University Hospital, Sweden; Norrlands University Hospital; Region Ã–rebro County; University Hospital, Linkoeping; Karlstad Central Hospital; VÃ¤stmanland County Council, Sweden; GÃ¤vle Hospital; Falu Hospital
Not yet recruiting

Irinotecan Liposomes for the Treatment of Neuroendocrine Carcinoma

Posted: July 3rd, 2024, 11:00pm UTC

Conditions: Neuroendocrine Tumors
Interventions: Drug: Irinotecan liposomes combined with cisplatin/carboplatin
Sponsors: First Affiliated Hospital Xi'an Jiaotong University
Not yet recruiting

Permalink for '[212Pb]VMT-Alpha-NET in Metastatic or Inoperable Somatostatin-Receptor Positive Gastrointestinal Neuroendocrine Tumors, Pheochromocytoma/Paragangliomas, Small Cell Lung, Renal Cell, and Head and Neck Cancers'

[212Pb]VMT-Alpha-NET in Metastatic or Inoperable Somatostatin-Receptor Positive Gastrointestinal Neuroendocrine Tumors, Pheochromocytoma/Paragangliomas, Small Cell Lung, Renal Cell, and Head and Neck Cancers

Posted: June 28th, 2024, 11:00pm UTC

Conditions: Head and Neck Tumors; Kidney Cancers; Small Cell Lung Cancers; Pheochromocytoma/Paragangliomas; Gastrointestinal Neuroendocrine Tumors; Somatostatin Receptor Positive
Interventions: Drug: 68Ga-DOTATATE; Drug: [203Pb]VMT-alpha-NET; Drug: [212Pb]VMT-alpha-NET
Sponsors: National Cancer Institute (NCI)
Not yet recruiting

Everolimus 5 mg vs 10 mg/Daily for Patients With Neuroendocrine Tumors

Posted: June 25th, 2024, 11:00pm UTC

Conditions: Neuroendocrine Tumors; Progression; Neuroendocrine Tumor Grade 1; Neuroendocrine Tumor Grade 2; Neuroendocrine Tumor of Pancreas; Neuroendocrine Tumor of the Lung; Neuroendocrine Tumor Carcinoid
Interventions: Drug: Everolimus 5 MG
Sponsors: AC Camargo Cancer Center
Recruiting

FUSA With Intratumoral PolyICLC in Regionally Advanced Resectable Melanoma

Posted: June 25th, 2024, 11:00pm UTC

Conditions: Advanced Melanoma
Interventions: Device: Echopulse or Echopulse HD; Drug: PolyICLC
Sponsors: University of Virginia; Theraclion
Recruiting

Circulating Tumour DNA Guided Adaptive BRAF and MEK Inhibitor Therapy

Posted: June 24th, 2024, 11:00pm UTC

Conditions: Melanoma
Interventions: Drug: Adaptive Therapy; Drug: Standard of Care
Sponsors: The Christie NHS Foundation Trust; University of Manchester; University of Liverpool
Not yet recruiting

Heart Analysis in GATED-PET in Patients Having a Gallium-68-DOTATOC PET/CT Exam for Oncology Indication

Posted: June 21st, 2024, 11:00pm UTC

Conditions: Cardiac Inflammation
Interventions: Other: Cardiac ECG-gated PET imaging will added
Sponsors: Central Hospital, Nancy, France
Recruiting

Permalink for 'Prebiotic Food-enriched Diet (PreFED) to Enhance the Microbiome and Response to First-line Immunotherapy in Unresectable Melanoma'

Prebiotic Food-enriched Diet (PreFED) to Enhance the Microbiome and Response to First-line Immunotherapy in Unresectable Melanoma

Posted: June 19th, 2024, 11:00pm UTC

Conditions: Unresectable Melanoma
Interventions: Other: Prebiotic Food-Enriched Diet
Sponsors: M.D. Anderson Cancer Center
Recruiting

Establishment and Standardization of a Platform for In-depth Tumour Profiling (TUPRO) in Patients With Melanoma

Posted: June 17th, 2024, 11:00pm UTC

Conditions: Melanoma
Interventions: Other: Establishment of an in-deepth tumor profiling platform
Sponsors: Reinhard Dummer
Completed

Liposomal Irinotecan Combination Regimen for First-line Treatment of Small Cell Lung Cancer

Posted: June 17th, 2024, 11:00pm UTC

Conditions: Small Cell Lung Cancer
Interventions: Drug: Irinotecan Hydrochloride Liposome Injectionï¼›Carboplatin Injectionï¼›Serplulimab Injection
Sponsors: Zhou Chengzhi; Sun Yat-sen University; Hunan Cancer Hospital; Guangdong Provincial Hospital of Traditional Chinese Medicine; First People's Hospital of Foshan; Affiliated Hospital of Youjiang Medical University for Nationalities
Not yet recruiting

Semi-automatic Segmentation Method for Determining 177Lu-DOTATATE Tumor Dosimetry

Posted: June 14th, 2024, 11:00pm UTC

Conditions: Meningioma
Interventions: Device: scintigraphy of 177Lu-DOTATATE
Sponsors: Central Hospital, Nancy, France
Not yet recruiting

Evaluation of [18F]Fluoroethyl Triazole Labelled [Tyr3]-Octreotate Analogues for the Imaging of Neuroendocrine Tumours.

Posted: June 13th, 2024, 11:00pm UTC

Conditions: Neuroendocrine Tumors
Interventions: Drug: [18F]-FET-Î²AG-TOCA
Sponsors: Imperial College London; Imperial College Healthcare NHS Trust; Royal Marsden NHS Foundation Trust; University of Manchester; The Christie NHS Foundation Trust; Invicro; Newcastle University
Completed

61Cu-NODAGA-LM3 PET/CT for the Detection of Neuroendocrine Tumors (COPPER PET in NET)

Posted: June 12th, 2024, 11:00pm UTC

Conditions: Neuroendocrine Tumors
Interventions: Drug: 61Cu-NODAGA-LM3; Other: Comparator
Sponsors: University Hospital, Basel, Switzerland
Not yet recruiting

Defining Response Criteria for PET Scans for People With Neuroendocrine Tumors

Posted: June 7th, 2024, 11:00pm UTC

Conditions: Neuroendocrine Tumors
Interventions: Diagnostic Test: positron emission tomography (PET) scans
Sponsors: Memorial Sloan Kettering Cancer Center; NeuroEndocrine Tumor Research Foundation (NETRF)
Recruiting

A Study in Advanced/Metastatic Solid Tumors With the Study Medicine (PF-07329640) When Given Alone or In Combination

Posted: June 7th, 2024, 11:00pm UTC

Conditions: Advanced or Metastatic Solid Tumors; Non-Small Cell Lung Cancer; Colorectal Cancer; Urothelial Cancer; Melanoma
Interventions: Biological: PF-07329640; Biological: sasanlimab; Biological: bevacizumab
Sponsors: Pfizer
Active, not recruiting

Permalink for 'Perioperative Surufatinib Plus Sintilimab Combined With Chemotherapy in Gastric/Gastroesophageal Junction Adenocarcinoma'

Perioperative Surufatinib Plus Sintilimab Combined With Chemotherapy in Gastric/Gastroesophageal Junction Adenocarcinoma

Posted: June 7th, 2024, 11:00pm UTC

Conditions: Gastric Cancer; Gastro Esophageal Junction Cancer
Interventions: Drug: Surufatinib; Drug: Sintilimab; Drug: Oxaliplatin; Drug: S1
Sponsors: Fudan University
Not yet recruiting

Identification and Characterization of Circulating Tumor Cells Before and After Treatment (Surgery and Radiotherapy) in a Cohort of Patients Treated for Resectable Stage I-III Merkel Cell Carcinoma

Posted: June 7th, 2024, 11:00pm UTC

Conditions: Merkel Cell Carcinoma
Interventions: Other: Blood Test
Sponsors: University Hospital, Montpellier
Not yet recruiting

A Study of VET3-TGI in Patients With Solid Tumors

Posted: June 6th, 2024, 11:00pm UTC

Hereditary Pheochromocytoma Assessment of Tumour Immunologies

Posted: June 5th, 2024, 11:00pm UTC

Conditions: Pheochromocytoma; Paraganglioma
Interventions: Procedure: Venepuncture; Procedure: Venepuncture
Sponsors: Radboud University Medical Center
Not yet recruiting

Permalink for 'Phase I Trial to Determine the Dose and Evaluate the PK of Lutetium Lu 177 Edotreotide Therapy in Pediatric Participants With SSTR-positive Tumors'

Phase I Trial to Determine the Dose and Evaluate the PK of Lutetium Lu 177 Edotreotide Therapy in Pediatric Participants With SSTR-positive Tumors

Posted: June 4th, 2024, 11:00pm UTC

Conditions: NET; Lymphoma; Solid Tumor, Childhood; Somatostatin Receptor Positive; CNS Tumor
Interventions: Drug: Lutetium Lu 177-Edotreotide; Other: Amino Acid Solution
Sponsors: ITM Solucin GmbH
Not yet recruiting

Permalink for 'The Incidence and Outcomes of Metabolically Active Brown Adipose Tissue (aBAT) in Patients With Pheochromocytoma or Paraganglioma (PPGLs)'

The Incidence and Outcomes of Metabolically Active Brown Adipose Tissue (aBAT) in Patients With Pheochromocytoma or Paraganglioma (PPGLs)

Posted: June 3rd, 2024, 11:00pm UTC

Conditions: Pheochromocytoma; Paraganglioma
Interventions: Diagnostic Test: FDG-PET Scan
Sponsors: King's College Hospital NHS Trust
Recruiting

Rural Adult and Youth Sun Protection Study

Posted: June 3rd, 2024, 11:00pm UTC

Conditions: Melanoma (Skin); Skin Cancer
Interventions: Behavioral: RAYS Intervention
Sponsors: University of Utah; Georgetown University; West Virginia University
Recruiting

Permalink for 'Dose Escalation Study of ZG006 in Participants With Advanced Small Cell Lung Cancer or Neuroendocrine Carcinoma, Followed by Dose Expansion Study in Participants With Neuroendocrine Carcinoma.'

Dose Escalation Study of ZG006 in Participants With Advanced Small Cell Lung Cancer or Neuroendocrine Carcinoma, Followed by Dose Expansion Study in Participants With Neuroendocrine Carcinoma.

Posted: June 3rd, 2024, 11:00pm UTC

Conditions: Neuroendocrine Carcinoma
Interventions: Biological: ZG006
Sponsors: Suzhou Zelgen Biopharmaceuticals Co.,Ltd
Not yet recruiting

Prospective Registry of Ocular Melanoma Eye Plaque brachyTherapy Patients

Posted: May 29th, 2024, 11:00pm UTC

Conditions: Ocular Melanoma
Interventions: Other: Data collection
Sponsors: Duke University
Recruiting

Permalink for 'Study of the Value of hPG80 (Circulating Progastrin) for the Diagnosis of Neuroendocrine Tumours in Patients With an MEN1 Mutation'

Study of the Value of hPG80 (Circulating Progastrin) for the Diagnosis of Neuroendocrine Tumours in Patients With an MEN1 Mutation

Posted: May 27th, 2024, 11:00pm UTC

Conditions: Neuroendocrine Tumors; MEN1 Mutation
Interventions: Biological: blood sample
Sponsors: Centre Hospitalier Universitaire Dijon
Recruiting

Permalink for 'First-line Anlotinib Combined With Penpulimab for Advanced Pheochromocytoma: A Single-arm, Multicenter, Prospective Phase II Study'

First-line Anlotinib Combined With Penpulimab for Advanced Pheochromocytoma: A Single-arm, Multicenter, Prospective Phase II Study

Posted: May 27th, 2024, 11:00pm UTC

Conditions: Pheochromocytoma
Interventions: Drug: Anlotinib and Penpulimab
Sponsors: Sun Yat-sen University; Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Recruiting

Permalink for 'Somatostatin-Receptors (SSTR)-Agonist [212Pb]VMT-alpha-NET in Metastatic or Inoperable SSTR+ Gastrointestinal Neuroendocrine Tumor and Pheochromocytoma/Paraganglioma Previously Treated With Systemic Targeted Radioligand Therapy'

Somatostatin-Receptors (SSTR)-Agonist [212Pb]VMT-alpha-NET in Metastatic or Inoperable SSTR+ Gastrointestinal Neuroendocrine Tumor and Pheochromocytoma/Paraganglioma Previously Treated With Systemic Targeted Radioligand Therapy

Posted: May 24th, 2024, 11:00pm UTC

Conditions: Somatostatin Receptor Positive; Gastrointestinal Neuroendocrine Tumors; Pheochromocytoma; Paragangliomas
Interventions: Drug: 68Ga-DOTATATE; Drug: [203Pb]VMT-alpha-NET; Drug: [212Pb]VMT-alpha-NET
Sponsors: National Cancer Institute (NCI)
Not yet recruiting

Safety and Tolerability Study of GIM-531 in Advanced Solid Tumors

Posted: May 23rd, 2024, 11:00pm UTC

Conditions: Melanoma Stage IV; Solid Tumor
Interventions: Drug: GIM-531; Drug: Anti-PD-1 monoclonal antibody
Sponsors: Georgiamune Inc
Recruiting

Identification of mutations in canine oral mucosal melanomas by exome sequencing and comparison with human melanomas

Fetched: October 16th, 2024, 2:01am UTC by Maria Lucia Zaidan Dagli

Sci Rep. 2024 Oct 15;14(1):24174. doi: 10.1038/s41598-024-74748-z.

ABSTRACT

Oral mucosal melanomas (OMMs) are aggressive neoplasms commonly found in dogs but rare in humans. Utilizing whole exome sequencing (WES), which focuses on protein-coding regions to reveal mutation profiles, we conducted a comparative analysis of canine OMM and human melanomas. This study involved DNA extraction, exome enrichment, and sequencing from three canine OMM cell lines (CMGD-2, CMGD-5, TLM-1), five canine OMM frozen samples, a human OMM cell line (MEMO), and a human commercial skin melanoma cell line (SK-MEL-28). The sequencing and subsequent analysis of FASTQ files yielded final variant files, leading to the identification of mutations. Our findings revealed a total of 500 mutated genes in canine OMM, including significant ones such as EP300, FAT4, JAK3, LRP1B, NCOR1, and NOTCH1. Notably, 82 shared mutations were identified between human melanomas and canine OMM genomes. These mutations were categorized based on the gene functions. The identification of these mutations provides critical insights that can pave the way for the development of novel therapeutic strategies for both canine and human OMM, offering hope for more effective treatments in the future.

PMID:39406779 | DOI:10.1038/s41598-024-74748-z

Unraveling the Microbiome's Role in Neuroendocrine Neoplasms: A New Perspective

Fetched: October 16th, 2024, 2:01am UTC by Sara Massironi

Neuroendocrinology. 2024 Oct 15:1-4. doi: 10.1159/000541678. Online ahead of print.

NO ABSTRACT

PMID:39406190 | DOI:10.1159/000541678

Primary Mast Cell Sarcoma of the Maxillary Sinus and Gingiva Mimicking Malignant Neuroendocrine Tumor: A Case Report

Fetched: October 16th, 2024, 2:01am UTC by Tzu-Chien Cheng

Head Neck Pathol. 2024 Oct 15;18(1):97. doi: 10.1007/s12105-024-01702-w.

ABSTRACT

Mast cell sarcoma (MCS) is an extremely rare and aggressive malignancy primarily affecting bones, with limited literature associating it with neuroendocrine marker expression. This report presents a rare case of MCS arising in the maxillary sinus and gingiva. A 74-year-old man presented with a progressively enlarging ulcer on the right-sided upper gingiva. Magnetic resonance imaging revealed a 3.4 cm tumor on the floor of the right maxillary sinus. The patient underwent an inferior maxillectomy and right-sided neck dissection. Microscopically, the tumor consisted of monotonous round cells with oval nuclei, vesicular chromatin, inconspicuous nucleoli, and brisk mitoses. A panel of immunohistochemical stains was initially applied to exclude common sinonasal undifferentiated neoplasms, such as sinonasal undifferentiated carcinoma, melanoma, rhabdomyosarcoma, Ewing sarcoma, and lymphoma. The tumor cells showed patchy staining for INSM1 and synaptophysin, but were negative for AE1/AE3, CAM5.2, p40, chromogranin, S100, HMB45, NKX2.2, desmin, CD45 (LCA), CD3, and CD20, with intact INI1 and BRG1 expression. No specific diagnosis could be rendered based on the staining results, leading to consideration of other rare malignancies. Additional staining revealed positivity for CD117, mast cell tryptase, CD13, CD33, CD43, and CD68, confirming the MCS diagnosis. Molecular testing for KIT mutation was negative. Subsequent bone marrow biopsy demonstrated infiltration of atypical mast cells, which led to a diagnosis of mast cell leukemia. Despite high-dose chemotherapy, the patient died three months after the initial diagnosis. The undifferentiated epithelioid morphology and unusual aberrant neuroendocrine marker expression posed significant diagnostic challenges. The major differential diagnoses were discussed in this report.

PMID:39404971 | DOI:10.1007/s12105-024-01702-w

Permalink for 'Variable anatomical features of acromegaly in the nasal cavity and paranasal sinuses: implications for endoscopic endonasal transsphenoidal surgery'

Variable anatomical features of acromegaly in the nasal cavity and paranasal sinuses: implications for endoscopic endonasal transsphenoidal surgery

Fetched: October 16th, 2024, 2:01am UTC by Kento Takahara

Acta Neurochir (Wien). 2024 Oct 15;166(1):408. doi: 10.1007/s00701-024-06307-4.

ABSTRACT

PURPOSE: Growth hormone (GH)-secreting pituitary neuroendocrine tumors (PitNETs) are the most common cause of acromegaly. The endoscopic endonasal transsphenoidal approach (EEA) is commonly employed to remove them. Although morphological differences in the nasal cavity exist between acromegaly patients and those with other types of PitNET, few quantitative studies have been performed. This study aimed to evaluate the anatomical features of the nasal cavity and paranasal sinuses in patients with acromegaly.

METHODS: Preoperative computed tomography images of the nasal cavity and paranasal sinuses were compared between 20 patients with a GH-secreting PitNET (acromegaly group) and 22 with a non-functioning PitNET (control group). In the acromegaly group, the relationships between preoperative GH and/or insulin-like growth factor 1 (IGF-1) levels and anatomical characteristics were assessed.

RESULTS: In the acromegaly group, the distance between the nostril and dorsum sellae was significantly longer and the distance between the parasellar internal carotid arteries was significantly shorter (p = 0.0022 and 0.0092, respectively). Pneumatization volume in the nasal cavity did not differ between the groups. Nasal mucosa and bony hypertrophy were observed in the acromegaly group. Preoperative GH level was correlated with the width of the piriform aperture (p = 0.0171).

CONCLUSION: The nasal and paranasal changes associated with acromegaly can make EEA challenging to perform. Widening the surgical corridor anterior to the sphenoid sinus is important in these patients.

PMID:39404864 | DOI:10.1007/s00701-024-06307-4

Permalink for 'Cancer-Associated Fibroblast Subtypes Reveal Distinct Gene Signatures in the Tumor Immune Microenvironment of Vestibular Schwannoma'

Cancer-Associated Fibroblast Subtypes Reveal Distinct Gene Signatures in the Tumor Immune Microenvironment of Vestibular Schwannoma

Fetched: October 16th, 2024, 2:01am UTC by Ji-Yong Sung

Cells. 2024 Oct 9;13(19):1669. doi: 10.3390/cells13191669.

ABSTRACT

Cancer-associated fibroblast (CAF) composition within the same organ varies across different cancer subtypes. Distinct CAF subtypes exhibit unique features due to interactions with immune cells and the tumor microenvironment. However, data on CAF subtypes in individuals with vestibular schwannoma (VS) are lacking. Therefore, we aimed to distinguish CAF subtypes at the single-cell level, investigate how stem-like CAF characteristics influence the tumor immune microenvironment, and identify CAF subtype-specific metabolic reprogramming pathways that contribute to tumor development. Data were analyzed from three patients with VS, encompassing 33,081 single cells, one bulk transcriptome cohort, and The Cancer Genome Atlas Pan-Cancer database (RNA sequencing and clinical data). Our findings revealed that antigen-presenting CAFs are linked to substantially heightened immune activity, supported by metabolic reprogramming, which differs from tumorigenesis. High expression of the stem-like CAF gene signature correlated with poor prognosis in low-grade gliomas within the pan-cancer database. This is the first study to classify CAF subtypes in VS patients and identify a therapeutic vulnerability biomarker by developing a stem-like CAF gene signature. Personalized treatments tailored to individual patients show promise in advancing precision medicine.

PMID:39404431 | DOI:10.3390/cells13191669

Management of rTTS associated with PGL using VA-ECMO and surgical resection: a case report

Fetched: October 16th, 2024, 2:01am UTC by Kechun Zhou

Front Cardiovasc Med. 2024 Sep 30;11:1468415. doi: 10.3389/fcvm.2024.1468415. eCollection 2024.

ABSTRACT

BACKGROUND: Paraganglioma (PGL) is a neuroendocrine tumor located outside the adrenal gland that can secrete catecholamines. Clinical manifestations include headaches, hypertension, and, rarely, cardiomyopathy. Among these, reverse Takotsubo cardiomyopathy (rTTS) is a rare Takotsubo cardiomyopathy (TTS) associated with a surge in catecholamines.

CASE INTRODUCTION: This article reports a case of a hypertensive patient admitted for recurrent dizziness and chest tightness. During treatment, the patient suddenly experienced chest tightness and shortness of breath, followed by refractory cardiogenic shock, and was eventually diagnosed with rTTS. The patient gradually recovered and was successfully discharged after receiving treatments, including tracheal intubation with mechanical ventilation, extracorporeal membrane oxygenation (ECMO), and surgery.

CONCLUSION: The diagnosis of rTTS is significantly aided by the presence of free plasma metanephrines and specific changes observed in cardiac ultrasound. In the treatment of severe rTTS, ECMO can serve as a crucial life support technology. Under VA-ECMO support, early resection of the PGL after accelerated preoperative preparation may be a feasible approach.

PMID:39403595 | PMC:PMC11471588 | DOI:10.3389/fcvm.2024.1468415

Duodenal ampulla neuroendocrine tumor and gastrointestinal stromal tumors in a case of neurofibromatosis type 1: a case report

Fetched: October 16th, 2024, 2:01am UTC by Tingting Zhang

Front Oncol. 2024 Sep 30;14:1336539. doi: 10.3389/fonc.2024.1336539. eCollection 2024.

ABSTRACT

Neurofibromatosis type 1 (NF-1) is commonly associated with a variety of rare tumors. However, no case of multiple gastric gastrointestinal stromal tumors (GISTs) or duodenal ampulla neuroendocrine tumors (NETs) with multiple liver metastases in a patient with NF-1 has yet been reported. Here, we describe a case of a 55-year-old female patient with NF-1 whose serum Pro-Gastrin-Releasing Peptide (pro-GRP) levels were elevated. Gastrointestinal endoscopy and biopsy showed duodenal papilla space-occupying mass, and the pathological diagnosis turned out to be neuroendocrine tumors (NETs). During surgical exploration, multiple tumors were found on the serosal surface of the stomach and numerous miliary metastases in the liver. Following histopathological examination, it was determined that the liver metastases were NF-1 and the tumors in the gastric wall were GISTs. The patient benefited from targeted therapy and had an uneventful hospital stay. In this case, we emphasize treating patients with neurofibromatosis type 1 who exhibit abdominal symptoms with a high degree of clinical suspicion and performing thorough evaluations to rule out multiple tumors.

PMID:39403336 | PMC:PMC11471724 | DOI:10.3389/fonc.2024.1336539

Permalink for 'Liver metastases in high-grade neuroendocrine neoplasms: A comparative study of hepatic tumor volume and biochemical findings in NET G3 versus NEC'

Liver metastases in high-grade neuroendocrine neoplasms: A comparative study of hepatic tumor volume and biochemical findings in NET G3 versus NEC

Fetched: October 16th, 2024, 2:01am UTC by Philipp Melhorn

J Neuroendocrinol. 2024 Oct 14:e13454. doi: 10.1111/jne.13454. Online ahead of print.

ABSTRACT

Abnormal liver blood tests and liver tumor burden are known prognostic factors in neuroendocrine neoplasms (NEN). However, the relationship between biochemical liver parameters and hepatic tumor load is largely unknown in NEN and in high-grade NEN (G3) specifically. The primary objective of this study was to correlate the biochemical parameters and liver tumor volume of patients with neuroendocrine tumors grade 3 (NET G3) or neuroendocrine carcinomas (NEC). We wanted to investigate whether patients with NET G3 with extensive liver involvement had less severely elevated laboratory liver parameters than NEC patients. In total, 46 patients with NEN were included, 31 had NEC and 15 NET G3. All patients had distant metastatic disease, with liver metastases being the most common (n = 39). Both laboratory results and semiautomatic volumetric measurements of liver tumor burden were obtainable for 34 patients at baseline and 26 patients at follow-up. Alkaline phosphatase (AP), gamma-GT (gGT), and lactate dehydrogenase (LDH) increased significantly between the two time periods (p < .01). In a regression model, liver tumor burden significantly affected several blood parameters, for example, increasing AP, gGT, LDH, and aspartate aminotransferase (ASAT) by a factor of 1.02-1.04 per unit increase (1% tumor burden; all p < .001). AP, gGT, and LDH were significantly lower in NET G3 (factor of 0.43-0.68) than in NEC. Here, we found that liver chemistries changed over the NEN disease course, correlated with hepatic tumor burden, and differed by histologic subtype. The current data can potentially guide treatment decisions, for example, with regard to integration of liver-directed therapies.

PMID:39402903 | DOI:10.1111/jne.13454

Intraoperative monitoring and early recognition of facial nerve root in vestibular schwannoma surgery

Fetched: October 16th, 2024, 2:01am UTC by Ryan Keswani

Neurosurg Rev. 2024 Oct 15;47(1):798. doi: 10.1007/s10143-024-03017-4.

ABSTRACT

The removal of vestibular schwannomas carries a risk of facial palsy. This study aims to evaluate the usefulness and technical aspects of intraoperative monitoring (IOM) for the facial nerve. A total of 96 patients who underwent surgery for vestibular schwannoma were retrospectively investigated. The cohort was divided into two groups: those with intraoperative facial nerve monitoring (IOM group) and those without IOM (non-IOM group). Preoperative and postoperative facial nerve functions were assessed using the House-Brackmann (HB) scale immediately after surgery, at discharge, and at the 1-year follow-up. HB grade I and II were classified as satisfactory outcomes, HB grade III and IV as intermediate, and HB grade V and VI as poor. Facial nerve functions were compared between the groups. Additionally, the ratio of satisfactory results was investigated in the IOM group, focusing on whether the root exit zone (REZ) was identified at an early or late stage of surgery. Among the 65 (67%) patients in the IOM group and 31 (32%) patients in the non-IOM group, there were no differences in demographic and tumor characteristics. The extent of resection varied from subtotal to gross total removal, with no statistical differences between the groups. Although facial nerve function was more favorably preserved in the non-IOM group immediately after surgery, this trend reversed at discharge and the 1-year follow-up, showing significant statistical differences. In the IOM group, more patients achieved satisfactory outcomes when the REZ was identified early compared to late during tumor resection. Intraoperative facial nerve monitoring provides more satisfactory outcomes in preserving nerve function in vestibular schwannoma surgery. Early recognition of the REZ may contribute to improved surgical outcomes.

PMID:39402283 | DOI:10.1007/s10143-024-03017-4

Prospective assessment of circulating tumor DNA in patients with metastatic uveal melanoma treated with tebentafusp

Fetched: October 16th, 2024, 2:01am UTC by Manuel Rodrigues

Nat Commun. 2024 Oct 14;15(1):8851. doi: 10.1038/s41467-024-53145-0.

ABSTRACT

Tebentafusp, a bispecific immune therapy, is the only drug that demonstrated an overall survival benefit in patients with metastatic uveal melanoma (MUM). Circulating tumor DNA (ctDNA) has emerged as a potential prognostic and predictive marker in the phase 3 IMCgp100-202 trial using multiplex PCR-based next-generation sequencing (NGS). In this study (NCT02866149), ctDNA dynamics were assessed using droplet digital PCR (ddPCR) in 69 MUM patients undergoing tebentafusp treatment. Notably, 61% of patients exhibited detectable ctDNA before treatment initiation, which was associated with shorter overall survival (median 12.9 months versus 40.5 months for patients with undetectable ctDNA; p < 0.001). Patients manifesting a 90% or greater reduction in ctDNA levels at 12 weeks demonstrated markedly prolonged overall survival (median 21.2 months versus 12.9 months; p = 0.02). Our findings highlight the potential of ddPCR-based ctDNA monitoring as an economical, pragmatic and informative approach in MUM management, offering valuable insights into treatment response and prognosis.

PMID:39402032 | DOI:10.1038/s41467-024-53145-0

Permalink for 'A machine learning model reveals expansive downregulation of ligand-receptor interactions that enhance lymphocyte infiltration in melanoma with developed resistance to immune checkpoint blockade'

A machine learning model reveals expansive downregulation of ligand-receptor interactions that enhance lymphocyte infiltration in melanoma with developed resistance to immune checkpoint blockade

Fetched: October 16th, 2024, 2:01am UTC by Sahil Sahni

Nat Commun. 2024 Oct 14;15(1):8867. doi: 10.1038/s41467-024-52555-4.

ABSTRACT

Immune checkpoint blockade (ICB) is a promising cancer therapy; however, resistance frequently develops. To explore ICB resistance mechanisms, we develop Immunotherapy Resistance cell-cell Interaction Scanner (IRIS), a machine learning model aimed at identifying cell-type-specific tumor microenvironment ligand-receptor interactions relevant to ICB resistance. Applying IRIS to deconvolved transcriptomics data of the five largest melanoma ICB cohorts, we identify specific downregulated interactions, termed resistance downregulated interactions (RDI), as tumors develop resistance. These RDIs often involve chemokine signaling and offer a stronger predictive signal for ICB response compared to upregulated interactions or the state-of-the-art published transcriptomics biomarkers. Validation across multiple independent melanoma patient cohorts and modalities confirms that RDI activity is associated with CD8 + T cell infiltration and highly manifested in hot/brisk tumors. This study presents a strongly predictive ICB response biomarker, highlighting the key role of downregulating chemotaxis-associated ligand-receptor interactions in inhibiting lymphocyte infiltration in resistant tumors.

PMID:39402030 | DOI:10.1038/s41467-024-52555-4

$Permalink for 'Intratumoral STING agonist reverses immune evasion in PD-(L)1-refractory Merkel cell carcinoma: mechanistic insights from detailed biomarker analyses'$

Intratumoral STING agonist reverses immune evasion in PD-(L)1-refractory Merkel cell carcinoma: mechanistic insights from detailed biomarker analyses

Fetched: October 16th, 2024, 2:01am UTC by Thomas Pulliam

J Immunother Cancer. 2024 Oct 14;12(10):e009803. doi: 10.1136/jitc-2024-009803.

ABSTRACT

PMID:39401968 | DOI:10.1136/jitc-2024-009803

A Case Report of Primary Neuroendocrine Carcinoma of the Anal Canal with Cancer Genome Profiling

Fetched: October 16th, 2024, 2:01am UTC by Ryuichi Morita

Intern Med. 2024 Oct 11. doi: 10.2169/internalmedicine.4289-24. Online ahead of print.

ABSTRACT

Primary neuroendocrine carcinoma (NEC) of the anal canal is a rare, highly malignant tumor with a poor prognosis. Despite the standard first-line treatment with etoposide or irinotecan combined with cisplatin, effective second-line therapies are lacking. In 2019, Japan approved cancer genome profiling (CGP) tests for solid tumors to enhance genomic understanding. We present the case of a 79-year-old woman with NEC of the anal canal, treated with etoposide, carboplatin, and amrubicin. Post-standard therapy, CGP suggested pemigatinib, a tyrosine kinase inhibitor; however, the patient died before receiving it. This case highlights the potential of personalized medicine to improve outcomes in such cases.

PMID:39401914 | DOI:10.2169/internalmedicine.4289-24

Permalink for 'Intraoperative intermittently scanned continuous glucose monitoring in the management of patients with pancreatic insulinoma'

Intraoperative intermittently scanned continuous glucose monitoring in the management of patients with pancreatic insulinoma

Fetched: October 16th, 2024, 2:01am UTC by M Magliozzo

J Endocrinol Invest. 2024 Oct 14. doi: 10.1007/s40618-024-02472-6. Online ahead of print.

ABSTRACT

INTRODUCTION: Insulinomas represent the most common functional pancreatic neuroendocrine tumors. Following preoperative localization, surgical excision is the curative treatment. It may be difficult to confirm a complete resection of insulinoma. We used intermittently scanned continuous glucose monitoring (isCGM) to record the fluctuation of interstitial glucose throughout surgery to help verify the tumor's complete surgical excision.

MATERIALS AND METHODS: In five individuals with insulinoma undergoing laparoscopic surgery we used the isCGM system (Freestyle Libre 2 Abbott) during tumor removal in order for the surgeon to understand "in real-time" the extent of tumor removal.

RESULTS: Two patients received no preoperative treatment, while three patients received medical treatment with either lanreotide (2 patients) or diazoxide (1 patient). In the non-treated patients, following tumor resection, there was a rapid interstitial glucose increase along with stabilized glucose levels thoroughly documented by intraoperative isCGM. Lanreotide treatment, on the other hand, resulted in only a minor increase in interstitial glucose. Finally, diazoxide-treated patients had a response that was intermediate between lanreotide-treated and non-treated patients.

CONCLUSION: Our findings suggest that isCGM is a useful tool to monitor the outcome of surgery during pancreatic insulinoma excision, assisting the surgical team in successfully removing the tumor. Despite the limited sample size, the results are promising, and, if validated in larger studies, they make us believe that the use of CGM systems has a definite benefit for becoming a standard in the surgical treatment of insulinomas.

PMID:39400889 | DOI:10.1007/s40618-024-02472-6

Permalink for 'The Histopathology of Chronic "Radiation Conjunctivitis" Shows Diagnostic Features Similar to Those Seen in Radiation Dermatitis, Including Radiation Fibroblasts'

The Histopathology of Chronic "Radiation Conjunctivitis" Shows Diagnostic Features Similar to Those Seen in Radiation Dermatitis, Including Radiation Fibroblasts

Fetched: October 16th, 2024, 2:01am UTC by Buravej Assavapongpaiboon

Head Neck Pathol. 2024 Oct 14;18(1):94. doi: 10.1007/s12105-024-01701-x.

ABSTRACT

PURPOSE: Radiation therapy is a treatment modality for various ocular and ocular adnexal tumors. The histopathology of chronic radiation dermatitis has been well-described. The authors present two cases demonstrating and characterizing "chronic radiation conjunctivitis" which has not been histopathologically illustrated in detail.

METHODS: Retrospective case review of two patients who received proton beam irradiation for an anterior uveal melanoma and external beam radiation for conjunctival lymphoma, and developed leukoplakia and/or thickening of the eyelid margin and symblepharon. Hematoxylin and eosin-stained sections of eyelid margin and conjunctival biopsies as well as clinical histories were reviewed.

RESULTS: Conjunctival biopsies in both cases revealed squamous epithelial metaplasia, chronic inflammation and bizarre-appearing stromal cells with hyperchromatic nuclei in a fibrotic/sclerotic stroma, consistent with chronic radiation conjunctivitis. These stromal cells are believed to be the same "radiation fibroblasts" described in chronic radiation dermatitis.

CONCLUSION: The radiation fibroblast is characteristic for the diagnosis of chronic radiation conjunctivitis, as it is in radiation dermatitis. Features of squamous metaplasia of conjunctival epithelium, keratinization, subepithelial fibrosis/sclerosis and chronic inflammation are frequently found but not specific. A detailed history and other ancillary tests help differentiate cicatrizing conjunctival conditions, and biopsy should be performed in the setting of suspicion for a secondary malignancy.

PMID:39400878 | DOI:10.1007/s12105-024-01701-x

Permalink for 'Racial and ethnic differences in healthcare access and utilization among U.S. adults with melanoma and keratinocyte carcinomas in the NIH All of Us Research Program'

Racial and ethnic differences in healthcare access and utilization among U.S. adults with melanoma and keratinocyte carcinomas in the NIH All of Us Research Program

Fetched: October 16th, 2024, 2:01am UTC by Michelle C Juarez

Arch Dermatol Res. 2024 Oct 14;316(10):686. doi: 10.1007/s00403-024-03383-5.

ABSTRACT

There is a paucity of information on racial and ethnic disparities relating to barriers to care in healthcare access and utilization in patients with cutaneous malignancies. We conducted a cross-sectional analysis of adults with melanoma, basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) in the National Institutes of Health (NIH) All of Us Research Program collected between May 2018 and July 2022. Participants included adults (aged 18 or older) with cutaneous malignancy who completed the Health Care Access and Utilization survey. We identified 5,817 adults who were diagnosed with BCC (67%), cSCC (28.9%), and melanoma (23.9%). Non-Hispanic Black (NHB) and Hispanic patients were more likely than non-Hispanic White (NHW) patients to delay a primary care visit due to cost (p = 0.005 and p = 0.015, respectively). NHB patients were also more likely to delay care due to lack of transportation (p < 0.001). NHB and Hispanic patients were more likely to place importance on seeing a provider from the same background (NHB p < 0.002; Hispanic p = 0.002) and also were more likely to report never being able to see such a provider (NHB p < 0.001; Hispanic p = 0.002). Medicaid/Medicare patients, non-college graduates, and those with lower incomes also faced increased barriers to care, including delays due to cost and transportation issues. People of color with cutaneous malignancies are more likely to delay care in seeing primary care providers due to cost or transportation issues. This study provides important insights on disproportionate healthcare usage among racial/ethnic groups that may help mitigate healthcare disparities.

PMID:39400730 | DOI:10.1007/s00403-024-03383-5

Permalink for 'Incidence and Prognostic Implications of Lymphovascular Invasion in Node-Negative Pancreatic Neuroendocrine Tumors: Results From the US Neuroendocrine Study Group'

Incidence and Prognostic Implications of Lymphovascular Invasion in Node-Negative Pancreatic Neuroendocrine Tumors: Results From the US Neuroendocrine Study Group

Fetched: October 16th, 2024, 2:01am UTC by Kota Sahara

J Surg Oncol. 2024 Oct 13. doi: 10.1002/jso.27914. Online ahead of print.

ABSTRACT

BACKGROUND: Despite the well-known prognostic role of lymph node metastasis (LNM) in pNETs, less is known about the importance of lymphovascular invasion (LVI) among patients with these tumors.

METHODS: Patients undergoing pancreatectomy for pNET between 2002 and 2020 were identified in the US Neuroendocrine Tumor Study Group database. Cox regression analysis was utilized to identify the impact of LVI on recurrence-free survival (RFS) among patients with node-negative pNET.

RESULTS: Among 853 patients who underwent resection for pNET, 214 patients (25.1%) had LNM, while 116 (13.6%) and 523 individuals (61.3%) were LVI + N0 and LVI - N0, respectively. The overall incidence of LVI among patients with N0 pNET was 18.1%; the incidence of LVI increased with increasing tumor size and Ki-67 levels (size < 2 cm and Ki-67 < 3%: 5.5%; size < 2 cm and Ki-67 â‰¥ 3%: 17.2%; size â‰¥ 2 cm and Ki-67 < 3%: 22.2%; size â‰¥ 2 cm and Ki-67 â‰¥ 3%: 43.1%, p < 0.001). Five-year RFS was highest among patients with LVI - N0 disease followed by individuals with LVI + N0 and N+ pNETs (92.8% vs. 61.6% vs. 58.3%, p < 0.001). On multivariable analysis, the presence of LVI on pathology remained independently associated with almost 2.5 times higher hazards of recurrence (HR 2.47, 05% CI 1.44-4.24) among individuals with N0 pNETs.

CONCLUSION: The incidence of LVI varied according to tumor size and Ki-67. LVI was associated with a higher likelihood of recurrence among individuals who underwent formal pancreatic resection for N0 pNETs. LVI is an important prognostic indicator among patients with node-negative pNETs.

PMID:39400348 | DOI:10.1002/jso.27914

Melanoma arising in a child with a medium-sized congenital melanocytic nevus

Fetched: October 16th, 2024, 2:01am UTC by MarÃa Victoria Montes

Medicina (B Aires). 2024;84(5):1002-1006.

ABSTRACT

Pediatric melanomas are rare and some of them may arise on giant congenital melanocytic nevi. The risk of developing melanoma on a medium-sized nevus is not clear but is thought to be very rare. Proliferative cellular nodules which mimic malignant melanoma may pose significant diagnostic challenges. We report the case of a 9-year-old patient who developed a melanoma on a medium-sized congenital melanocytic nevus on the tip of the nose, requiring a complex surgery with excellent aesthetic results.

PMID:39399944

Incidence of metastasis and survival in patients with primary uveal melanoma

Fetched: October 16th, 2024, 2:01am UTC by Carolina M Gentile

Medicina (B Aires). 2024;84(5):902-912.

ABSTRACT

INTRODUCTION: Primary uveal melanoma is the most common intraocular malignancy in adults. Almost 50% of patients die from metastatic disease despite successful local treatment. The objective was to estimate the incidence of metastasis and survival in patients with primary uveal melanoma. The second objective was to determine the independent predictors of metastasis.

METHODS: A retrospective, observational, analytical study was carried out using an ambidirectional cohort design in patients from Buenos Aires City between January 2003 to January 2020. Patients with uveal melanoma and potential clinical predictors of metastasis were identified. The density of incidence of metastasis and mortality were determined, and survival curves were analyzed (Kaplan Meir) A univariate and multivariate analysis using Cox proportional hazard models was performed.

RESULTS: 143 patients (mean age 57 SD 16) were included. The median thickness was 6.2 mm SD 3.4 mm, the mean tumor diameter was 12.6 mm (SD 3.8). 69.9% of the patients underwent conservative treatment with brachytherapy while 25.9% underwent enucleation. 19.6% presented metastasis, the median time to the event was 26.5 months. The specific mortality due to melanoma was 17.5%. Diameter greater than 12 mm and extension were predictor variables of metastasis in a multivariable model.

CONCLUSION: Although the median time to the event (metastasis) is 26.5 moths, it could occur many years after local oncological effective treatment. An early diagnosis would allow finding smaller tumors and would improve the prognosis.

PMID:39399930

Mouse developmental defects, but not paraganglioma tumorigenesis, upon conditional Complex II loss in early Sox10+ cells

Fetched: October 16th, 2024, 2:01am UTC by Elizabeth P Lewis

FASEB Bioadv. 2024 Jul 24;6(9):327-336. doi: 10.1096/fba.2024-00056. eCollection 2024 Sep.

ABSTRACT

In humans, loss of heterozygosity for defective alleles of any of the four subunits of mitochondrial tricarboxylic acid cycle enzyme succinate dehydrogenase (SDH, also Complex II of the electron transport chain) can lead to paraganglioma tumors in neuroendocrine cells. With the goal of developing mouse models of this rare disorder, we have developed various SDH conditional loss strategies. Based on recent lineage tracing studies, we hypothesized that conditional SDHC loss in early embryogenesis during migration of primordial neural crest cells that form the susceptible chromaffin cells of the adrenal medulla might induce paraganglioma. We triggered low levels of detectable SDHC loss in Sox10⁺ cells at E11.5 of mouse development. We report that, rather than developing adrenal medulla paraganglioma (pheochromocytoma), offspring survived with evidence of neural crest cell dysfunction. Phenotypes included mild lower extremity gait anomalies suggestive of neural tube closure defects and patches of unpigmented fur consistent with neural crest-derived melanocyte dysfunction. These defects were not observed in mice lacking Sdhc knockout. Our results add to existing data suggesting that, unlike humans, even early embryonic (Sox10-driven) SDHx loss is inadequate to trigger paraganglioma in mice of the genetic backgrounds that have been investigated. Instead, low levels of tricarboxylic acid cycle-deficient neural crest cells cause mild developmental defects in hind limb and melanocyte function. This new model may be of interest for studies of metabolism during early neural crest cell development.

PMID:39399478 | PMC:PMC11467736 | DOI:10.1096/fba.2024-00056

Permalink for 'Synchronous cancers of the stomach and esophagus in a patient with autoimmune gastritis and pernicious anemia: a case report and review of the literature'

Synchronous cancers of the stomach and esophagus in a patient with autoimmune gastritis and pernicious anemia: a case report and review of the literature

Fetched: October 16th, 2024, 2:01am UTC by Toshiyuki Kubo

Int Cancer Conf J. 2024 Jun 4;13(4):367-373. doi: 10.1007/s13691-024-00689-z. eCollection 2024 Oct.

ABSTRACT

Type-A gastritis/autoimmune gastritis (AIG) has gained renewed attention due to declining Helicobacter pylori infection rates and increasing eradication. AIG is associated with pernicious anemia (PA) and is prone to complicate various tumors, such as gastric cancer and neuroendocrine tumors. This report describes a case of AIG with PA in which gastric and esophageal cancers arose simultaneously. An 86-year-old woman had been diagnosed with PA and AIG 9 years earlier. As routine blood tests revealed high levels of carcinoembryonic antigen, she underwent esophagogastroduodenoscopy, which revealed a type 0-IIa lesion in the middle part of the stomach and a type 0-IIa + IIb lesion in the lower esophagus. Endoscopic submucosal dissection was performed on both lesions, since neither distant nor lymph node metastases were identified. Histological examination showed gastric tubular adenocarcinoma and esophageal squamous cell carcinoma. Immunohistology revealed that cells from neither cancer expressed gastrin, gastrin receptor, or p53. Whole-exome sequencing showed 8 gene mutations in the esophageal cancer and 6 mutations in 5 genes in the gastric cancer. The reason for the lack of p53 immunostaining was that TP53 was mutated in these cancers, although TP53 mutations differed. Thus, TP53 mutations may not be detected by immunostaining alone. When treating patients with AIG/PA, clinicians must be aware of the possibility of esophageal cancer coexisting with gastric cancer.

PMID:39398913 | PMC:PMC11465013 | DOI:10.1007/s13691-024-00689-z

Bowen's Disease Along With Intradermal Merkel Cell Carcinoma Occurring on the Dorsum of the Hand

Fetched: October 16th, 2024, 2:01am UTC by Chihiro Ishihara

Cureus. 2024 Sep 10;16(9):e69114. doi: 10.7759/cureus.69114. eCollection 2024 Sep.

ABSTRACT

Bowen's disease (BD), also known as squamous cell carcinoma (SCC) in situ, is a precancerous skin condition that can potentially progress to invasive tumors. Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine tumor typically found in sun-exposed areas of elderly Caucasians. The coexistence of BD and MCC is extremely rare, particularly when MCC is located in subcutaneous tissue rather than its typical epidermal or dermal layers. This case report presents an unusual instance of BD coexisting with subcutaneous MCC on the dorsum of the hand in an elderly Japanese male. An 87-year-old Japanese male with over 30 years of sun exposure presented with a progressively enlarging red tumor on the dorsum of his left hand. A biopsy confirmed BD, and the tumor was excised with a 5 mm margin followed by skin grafting. Histopathological examination revealed subcutaneous MCC along with BD, with MCC cells forming small nests in the dermal papillary layer. Immunohistochemistry showed positive staining for synaptophysin and CK20 in a perinuclear dot pattern, confirming the MCC diagnosis. Given the patient's advanced age and the absence of positive surgical margins, a watch-and-wait approach was adopted. The patient has been under close outpatient monitoring, and no recurrence has been observed after six months. This case highlights the rarity of subcutaneous MCC coexisting with BD, with only a few reported cases of such coexistence. The unusual subcutaneous presentation and the presence of multiple micro-nodules instead of large atypical cell clusters suggest an early-stage MCC beneath BD. The pathogenesis of this coexistence remains unclear but raises important questions regarding the relationship between sun exposure and viral factors like Merkel cell polyomavirus (MCPyV), which was not tested in this case. The findings underscore the need for comprehensive diagnostic evaluation when encountering complex or atypical skin lesions. This report emphasizes the rarity of subcutaneous MCC coexisting with BD and underscores the importance of comprehensive diagnostic assessment in unusual cases. Further research is warranted to better understand the underlying mechanisms and to guide optimal management strategies for such rare and challenging presentations.

PMID:39398756 | PMC:PMC11469582 | DOI:10.7759/cureus.69114

Glomus Tumor of the Chest Wall With Metastases to Lung

Fetched: October 16th, 2024, 2:01am UTC by Joshua A Engle

Cureus. 2024 Sep 10;16(9):e69122. doi: 10.7759/cureus.69122. eCollection 2024 Sep.

ABSTRACT

Glomus tumors are typically benign, soft tissue neoplasms composed of thermoregulatory glomus bodies. The more common varieties, such as subungual, are treated surgically and typically have a very low mortality rate. Malignant glomus tumors are very rare, and their pathogenesis is poorly understood. As such, treatment options and prognosis are unclear. We present a 67-year-old female diagnosed with a chest wall glomus tumor with biopsy-proven metastases to her lungs. Her treatment course included neoadjuvant radiation therapy followed by immunotherapy with pembrolizumab. After completion of the initial radiation therapy, imaging showed disease regression. Interval imaging after seven months of immunotherapy showed the resolution of all lung nodules with no reported concerns for disease recurrence. Pembrolizumab was discontinued due to concerns for dermatologic and renal adverse events, and the patient continues to be monitored off therapy. The metastatic glomus tumor described in this case had several unique qualities, including its initial presentation on the chest wall as an aggressive lesion, as well as its spread to multiple locations in the lungs. Glomus tumors are not normally as aggressive as seen in this case, but the genetic profile with high tumor mutational burden allowed for guided treatment. Radiation is often used as neoadjuvant treatment in higher risk glomus tumors, but the addition of immunotherapy such as pembrolizumab represents a potential avenue to manage these patients when surgery is not an option. Malignant glomus tumors are exceptionally rare occurrences that, by nature of their rarity, require protocols or therapies that are not specifically designed for their treatment. The clinical course of these tumors is difficult to predict as most cases of metastatic spread have few examples from which to draw conclusions. This case provided encouraging results for treatment with radiation and, potentially, immunotherapy. Each instance of a malignant glomus tumor and its genetic profile should be closely examined and documented so that sufficient data can be accumulated to guide treatment for this rare cancer.

PMID:39398735 | PMC:PMC11466728 | DOI:10.7759/cureus.69122

Andrew Victor Schally: Pioneering Neuroendocrinologist and Architect of Luteinizing Hormone-Releasing Hormone Analogs

Fetched: October 16th, 2024, 2:01am UTC by MiloÅ¡ GrujiÄ‡

Cureus. 2024 Sep 10;16(9):e69137. doi: 10.7759/cureus.69137. eCollection 2024 Sep.

ABSTRACT

Andrew Victor Schally is a pioneering figure in endocrinology and neuroendocrinology, whose work has fundamentally transformed the understanding and treatment of hormone-related disorders and cancer. His research, particularly in the isolation, characterization, and clinical application of hypothalamic hormones, has been instrumental in advancing medical science. Schally's early life, marked by the adversities of World War II, shaped his resilience and determination, driving him to pursue a career in medical research. His groundbreaking discovery of luteinizing hormone-releasing hormone (LHRH) and its analogs revolutionized the treatment of hormone-dependent cancers, especially advanced prostate cancer, by providing an effective alternative to surgical castration. Beyond LHRH, Schally's contributions to the development of somatostatin analogs have also had a significant impact on the management of acromegaly and neuroendocrine tumors. This article reviews Schally's life and work, emphasizing his contributions to endocrinology, particularly in the context of LHRH and its clinical applications. The review outlines his early life and education, his pioneering research on hypothalamic hormones, and the development of LHRH analogs that have become a cornerstone in the treatment of prostate cancer. Schally's ability to translate basic scientific discoveries into practical therapeutic strategies has earned him numerous accolades, including the Nobel Prize in Physiology or Medicine in 1977. His legacy continues to inspire and guide research in endocrinology and oncology, underscoring the lasting impact of his scientific achievements.

PMID:39398731 | PMC:PMC11467473 | DOI:10.7759/cureus.69137

Permalink for 'Microsatellite Instability-High and High Tumor Mutation Burden Frequencies in Urologic Malignancies Off-Label for Immune Checkpoint Inhibitors in Japan: A Retrospective Single-Institutional Cohort'

Microsatellite Instability-High and High Tumor Mutation Burden Frequencies in Urologic Malignancies Off-Label for Immune Checkpoint Inhibitors in Japan: A Retrospective Single-Institutional Cohort

Fetched: October 16th, 2024, 2:01am UTC by Hiroshi Yaegashi

Cureus. 2024 Sep 13;16(9):e69366. doi: 10.7759/cureus.69366. eCollection 2024 Sep.

ABSTRACT

Objectives Microsatellite instability-high (MSI-H) and high tumor mutation burden (TMB-high) frequencies were investigated to determine the efficacy and adverse events of pembrolizumab in patients with urologic malignancies (or their equivalents) for which immune checkpoint inhibitors (ICIs) are not covered by Japanese insurance. Methods Between February 2019 and April 2024, patients with urologic malignancies (or their equivalents) treated in our department for whom ICIs were not approved by Japanese insurance were screened with an MSI companion diagnostic kit or comprehensive genomic profiling (CGP). The efficacy of pembrolizumab therapy, presence of adverse events, and outcomes were evaluated retrospectively in patients with MSI-H or TMB-high. Results In total, 44 patients were tested, and the median age at testing was 70 years. Castration-resistant prostate cancer (CRPC) was the most common (n = 31). Overall, 49 tests were performed, including 22 MSI companion diagnostic kits and 27 CGP tests. Of the 49 tests, 1 detected MSI-H, 2 detected TMB-high, and 1 detected simultaneous MSI-H/TMB-high, with detection rates of 4.1% and 11.1% for MSI-H and TMB-high, respectively. A patient with MSI-H CRPC and neuroendocrine differentiation achieved a complete response and a prolonged duration of response to pembrolizumab without adverse events. The duration of response to pembrolizumab was shorter in a patient with TMB-high, and a CRPC patient with simultaneously detected MSI-H/TMB-high had to discontinue pembrolizumab early due to immune-related adverse events. Conclusions Despite the potential benefit of pembrolizumab, MSI-H or TMB-high was less frequently detected in urologic malignancies for which ICIs are not covered by Japanese insurance.

PMID:39398648 | PMC:PMC11471304 | DOI:10.7759/cureus.69366

Elucidating Clinical Queries for Tailored Therapy in Patients with Prolactinoma

Fetched: October 16th, 2024, 2:01am UTC by Min-Ho Lee

Endocrinol Metab (Seoul). 2024 Oct 14. doi: 10.3803/EnM.2024.2057. Online ahead of print.

ABSTRACT

Prolactinomas are the most prevalent type of pituitary neuroendocrine adenomas, primarily affecting women of reproductive age. Unlike other pituitary tumors, the first-line management has traditionally been pharmacological rather than surgical. This preference is due to the effectiveness of dopamine agonists (DAs), which typically reduce tumor size and normalize prolactin levels in most patients. However, this does not imply that there is no room for improvement; the duration of treatment and medication side effects often lead to compliance issues among patients. Recent advances in surgical techniques and molecular biology have paved the way for the development of precision medicine, allowing for more flexible and personalized treatment strategies for prolactinomas. This review aims to enhance clinical decision-making and patient care for endocrinologists by focusing on several key factors: predictive markers of DA sensitivity, clinical characteristics and suitability for transsphenoidal adenomectomy as a potential first-line treatment, factors determining the successful withdrawal of DAs after prolonged use, safety concerns during pre/post-pregnancy and breastfeeding, and determinants of tumor aggressiveness. Through tailored therapy-a patient-focused, multidisciplinary approach- we aim to improve the management of prolactinoma patients.

PMID:39397514 | DOI:10.3803/EnM.2024.2057

68Ga-DOTATATE and 18F-FDG PET/CT in a Rapidly Progressing Lymphoma

Fetched: October 16th, 2024, 2:01am UTC by Ashwin Singh Parihar

Clin Nucl Med. 2024 Oct 14. doi: 10.1097/RLU.0000000000005450. Online ahead of print.

ABSTRACT

68Ga-DOTATATE PET/CT targeting somatostatin receptors is commonly utilized in the imaging of neuroendocrine tumors. However, other malignancies such as lymphomas (both Hodgkin and non-Hodgkin) also have expression of somatostatin receptors, albeit to a lesser degree compared with the neuroendocrine tumors, and thus can be positive on a 68Ga-DOTATATE PET/CT. We describe an atypical presentation of an aggressive large B-cell lymphoma mimicking a metastatic neuroendocrine tumor at initial presentation with high somatostatin receptor expression demonstrated on the 68Ga-DOTATATE PET/CT and a rapidly progressing course on the subsequent 18F-FDG PET/CT.

PMID:39397315 | DOI:10.1097/RLU.0000000000005450

Preoperative risk factors for ileostomy-associated kidney injury in colorectal tumor surgery following ileostomy formation

Fetched: October 16th, 2024, 2:01am UTC by Emi Ota

Int J Colorectal Dis. 2024 Oct 14;39(1):160. doi: 10.1007/s00384-024-04732-6.

ABSTRACT

PURPOSE: Diverting ileostomy is related to postoperative high-output stoma (HOS) leading to kidney injury. The purpose of our study was to clarify the risk factors for ileostomy-associated kidney injury, which is kidney injury starting after the first operation to ileostomy closure after colorectal tumor surgery with diverting ileostomy.

METHODS: Between January 2013 and December 2020, 442 patients who underwent colorectal tumor surgery (cancer, neuroendocrine tumor, and leiomyosarcoma) following diverting ileostomy formation were included. We used the KDIGO (Kidney Disease Improving Global Outcomes) guidelines, which defines the acute kidney injury (AKI) to classify patients with ileostomy-associated kidney injury. The definition of AKI was (i) serum creatinine (sCr) â‰¥ 0.3 mg/dL or (ii) sCr â‰¥1.5-fold the preoperative level. Multivariate analyses were performed to identify the independent risk factors for kidney injury.

RESULTS: Kidney injury developed in 99/442 eligible patients (22.4%). Patients in the kidney injury group were older age, male sex, high American Society of Anesthesiologists Physical Status Classification System (ASA-PS) score, hypertension, cardiovascular diseases, diabetes. The preoperative hemoglobin, albumin, prognostic nutritional index (PNI), and creatinine clearance (CCr) were lower, and the maximum wound length was more extended than the non-kidney injury group. The median highest daily stoma output was significantly higher in the kidney injury group. The postoperative white blood cell (WBC) and C-reactive protein (CRP) levels were also high in the kidney injury group. The univariate analysis showed older age, male sex, high ASA-PS score, hypertension, cardiovascular diseases, and diabetes were the risk factors for kidney injury. The multivariate analysis revealed that age 70 or older, ASA-PS III/IV, hypertension, and HOS â‰¥2000 ml/day were independent risk factors for kidney injury.

CONCLUSIONS: Surgeons should consider diverting colostomy creation for patients with risk factors such as age 70 or older, ASA-PS III/IV, and hypertension.

PMID:39397177 | PMC:PMC11471691 | DOI:10.1007/s00384-024-04732-6

Permalink for 'Surgery enhances the effectiveness of peptide receptor radionuclide therapy in metastatic gastroenteropancreatic neuroendocrine tumors'

Surgery enhances the effectiveness of peptide receptor radionuclide therapy in metastatic gastroenteropancreatic neuroendocrine tumors

Fetched: October 16th, 2024, 2:01am UTC by Joseph Tobias

Surgery. 2024 Oct 11:S0039-6060(24)00705-0. doi: 10.1016/j.surg.2024.06.065. Online ahead of print.

ABSTRACT

BACKGROUND: With the advent of peptide receptor radionuclide therapy, the timing and sequence of surgery in the treatment of metastatic gastroenteropancreatic neuroendocrine tumors merits further study. We hypothesized that surgery before peptide receptor radionuclide therapy might enhance its effectiveness in patients with metastatic gastroenteropancreatic neuroendocrine tumors.

METHODS: Eighty-nine patients with metastatic well-differentiated gastroenteropancreatic neuroendocrine tumors treated with ¹⁷⁷Lutetium-dotatate peptide receptor radionuclide therapy between 2018 and 2023 were included. Fifty-six patients underwent surgery (primary tumor resection and/or liver debulking) before peptide receptor radionuclide therapy and 33 patients did not. Primary outcome was progression-free survival according to Response Evaluation Criteria in Solid Tumors. Pretreatment dotatate positron emission tomography/computed tomography was used to calculate tumor volumes.

RESULTS: The surgery and no-surgery groups were well-matched. Median progression-free survival after peptide receptor radionuclide therapy was 15.6 months (interquartile range, 9.1-22.7 months) in the no-surgery group compared with 26.1 months (interquartile range, 12.7-38.1 months) in the surgery group (P = .04). On subgroup analysis, median progression-free survival was 18.1 months (interquartile range, 11.9-38.4 months) in patients who underwent primary tumor resection only compared with 26.2 months (interquartile range, 14.0-38.1 months) in patients who underwent liver debulking (P = .04). Tumor volume was lowest in patients who underwent liver debulking (median 146.07 mL³) compared with no surgery (median 626.42 mL³) (P = .001). On univariable analysis, a tumor volume <138.8 mL³ was associated with longer progression-free survival (hazard ratio, 2.03; 95% confidence interval, 0.95-4.34, P = .05), with a median progression-free survival of 38.1 months (interquartile range, 16.9-41.3 months) compared with 17.8 months (interquartile range, 10.8-28.7 months).

CONCLUSION: Surgery may enhance the effectiveness of ¹⁷⁷Lutetium-dotatate in the treatment of metastatic well-differentiated gastroenteropancreatic neuroendocrine tumors. This positive effect may be the result of a lower tumor volume in patients after surgery. Our findings fortify the concept of using surgical debulking to improve systemic therapies such as peptide receptor radionuclide therapy.

PMID:39395860 | DOI:10.1016/j.surg.2024.06.065

Therapeutic effects of an ALK inhibitor, brigatinib, on lung large cell neuroendocrine carcinoma with EML4-ALK fusion

Fetched: October 16th, 2024, 2:01am UTC by Takayuki Suetsugu

Respir Investig. 2024 Oct 11;62(6):1157-1160. doi: 10.1016/j.resinv.2024.09.013. Online ahead of print.

ABSTRACT

A 64-year-old light-smoking woman was clinically diagnosed with lung large-cell neuroendocrine carcinoma (LCNEC) with a metastatic brain tumor. An Oncomine Dx Targeted Test using metastatic brain tissue revealed that the patient's lung cancer cells had an EML4-ALK rearrangement. Patients with LCNEC and anaplastic lymphoma kinase (ALK) gene rearrangements are rare, and there is currently no standard treatment. Based on the genomic analysis, we treated the patient with brigatinib, an ALK inhibitor. We describe here a patient with LCNEC who responded significantly to brigatinib without serious adverse events.

PMID:39395329 | DOI:10.1016/j.resinv.2024.09.013

Acetate utilization promotes hormone therapy resistance in prostate cancer through neuroendocrine differentiation

Fetched: October 16th, 2024, 2:01am UTC by Dajun Gao

Drug Resist Updat. 2024 Oct 6;77:101158. doi: 10.1016/j.drup.2024.101158. Online ahead of print.

ABSTRACT

AIMS: Tumor fatty acid (FA) metabolic plasticity plays a pivotal role in resistance to therapy and poses limitations to anticancer strategies. In this study, our aim is to uncover the role of acetate metabolism in neurodifferentiation (NED)-mediated castration-resistant prostate cancer (CRPC).

METHODS: We conducted analyses using LC-MS/MS on clinical prostate cancer tissue before and after hormone therapy. We established tumor xenograft mouse models, primary tumor cells, and human-derived organoids to detect the novel mechanism of NED and to identify potential therapies.

RESULTS: The hormone therapy-induced upregulation of acetate metabolism was mediated by acyl-CoA synthetase short-chain family member 2 (ACSS2), which increased c-MYC expression for NED induction. Notably, combined treatment with an ACSS2 inhibitor and enzalutamide significantly reduced the xenograft tumor volume.

CONCLUSION: Our findings uncovered the critical role of acetate metabolism in NED-mediated CRPC and suggest that ACSS2 inhibitors may represent a novel, low-toxicity strategy when combined with hormone therapy for treating patients with NED-mediated CRPC.

PMID:39395327 | DOI:10.1016/j.drup.2024.101158

eSOMA-DM1, a Maytansinoid-Based Theranostic Small-Molecule Drug Conjugate for Neuroendocrine Tumors

Fetched: October 16th, 2024, 2:01am UTC by Dylan Chapeau

Bioconjug Chem. 2024 Oct 12. doi: 10.1021/acs.bioconjchem.4c00413. Online ahead of print.

ABSTRACT

Background: The main challenges of conventional chemotherapy lie in its lack of selectivity and specificity, leading to significant side effects. Using a small-molecule drug conjugate (SMDC) ensures specific delivery of a cytotoxic drug to the tumor site by coupling it to a targeting vector. This promising strategy can be applied to neuroendocrine tumors (NETs) by choosing a targeting vector that binds specifically to somatostatin receptor subtype 2 (SSTR2). Additionally, incorporation of a bifunctional chelate into the molecule enables complexation of both diagnostic and therapeutic radionuclides. Thus, it facilitates monitoring of the distribution of the SMDC in the body and allows for the implementation of combination therapy. In our study, we designed eSOMA-DM1, a SMDC combining the SSTR2-targeted octreotate peptide and the cytotoxic agent DM1 via a chelate-bridged linker (N3-Py-DOTAGA). This approach warrants conjugation of the targeting vector and the drug at opposite sites to avoid undesired steric hindrance effects. Methods: Synthesis of the DM1 moiety (4) involved a three-step synthetic route, followed by the conjugation to the cyclic peptide, N3-Py-DOTAGA-d-Phe-cyclo[Cys-Tyr-d-Trp-Lys-Thr-Cys]-Thr-OH, through a copper-free click reaction, resulting in eSOMA-DM1. Subsequent labeling with [¹¹¹In]InCl3 gave a high radiochemical yield and purity. In vitro assessments of eSOMA-DM1 binding, uptake, and internalization were conducted in SSTR2-transfected U2OS cells. Ex vivo biodistribution and fluorescence imaging were performed in H69-tumor bearing mice. Results: eSOMA-DM1 exhibited an IC50 value for SSTR2 similar to the gold standard DOTA-TATE. The uptake of [¹¹¹In]In-eSOMA-DM1 in U2OS.SSTR2 cells was 1.2-fold lower than that of [¹¹¹In]In-DOTA-TATE. Tumor uptake in H69-xenografted mice was higher for [¹¹¹In]In-eSOMA-DM1 at all-time points compared to [¹¹¹In]In-DOTA-TATE. Prolonged blood circulation led to increased accumulation of [¹¹¹In]In-eSOMA-DM1 in highly vascularized tissues, such as the lungs, skin, and heart. Excretion through the kidneys, liver, and spleen was also observed. Conclusion: eSOMA-DM1 is a SMDC developed for NET showing promising characteristics in vitro. However, the in vivo results obtained with [¹¹¹In]In-eSOMA-DM1 suggest the need for adjustments to optimize its distribution.

PMID:39395152 | DOI:10.1021/acs.bioconjchem.4c00413

Permalink for 'Nutritional aspects in neuroendocrine neoplasms. bridging the gap between dietary interventions and cancer care strategies: a scoping review'

Nutritional aspects in neuroendocrine neoplasms. bridging the gap between dietary interventions and cancer care strategies: a scoping review

Fetched: October 16th, 2024, 2:01am UTC by Sara Massironi

J Endocrinol Invest. 2024 Oct 12. doi: 10.1007/s40618-024-02462-8. Online ahead of print.

ABSTRACT

PURPOSE: Neuroendocrine neoplasms (NENs) represent heterogeneous tumors arising from neuroendocrine cells in different organs. Despite growing interest in the nutritional aspects of NEN management, research in this area is limited. Aim of this review is to summarize the current state of knowledge, highlight research gaps, and underscore the significance of nutrition in the comprehensive care of NEN patients.

METHODS: We conducted an extensive bibliographic search focusing on studies (including retrospective and prospective studies, systematic reviews, case series, and guidelines) exploring the relationship between nutritional assessments, dietary interventions, micronutrient deficiencies, and their impact on NEN outcomes.

RESULTS: Significant gaps exist in current research, particularly in understanding the specific nutritional needs of NEN patients and how tailored nutritional interventions can improve clinical outcomes. Evidence suggests that a high-fat Western diet may promote the growth of NEN, while a Mediterranean diet may help lower insulin levels and strengthen the immune system, potentially preventing tumor development. The ketogenic diet and intermittent fasting may also have positive impacts. Addressing common micronutrient deficiencies, such as vitamin D and niacin, is crucial to mitigate disease progression. There's a crucial need for future studies to include a comprehensive nutritional assessment incorporating patient-reported outcomes, to fully capture the impact of nutritional strategies.

CONCLUSION: Nutritional management, an important but under-researched facet of NEN treatment, significantly improves patients' quality of life and survival. Integrating nutrition into personalized cancer care is essential, highlighting the role of nutritional strategies in optimizing patient outcomes.

PMID:39395115 | DOI:10.1007/s40618-024-02462-8

Permalink for 'Radioligand therapy in the therapeutic strategy for patients with gastro-entero-pancreatic neuroendocrine tumors: a consensus statement from the Italian Association for Neuroendocrine Tumors (Itanet), Italian Association of Nuclear Medicine (AIMN), Itali'

Radioligand therapy in the therapeutic strategy for patients with gastro-entero-pancreatic neuroendocrine tumors: a consensus statement from the Italian Association for Neuroendocrine Tumors (Itanet), Italian Association of Nuclear Medicine (AIMN), Itali

Fetched: October 16th, 2024, 2:01am UTC by Francesco Panzuto

J Endocrinol Invest. 2024 Oct 12. doi: 10.1007/s40618-024-02448-6. Online ahead of print.

ABSTRACT

PURPOSE: This paper outlines the consensus of the Italian Association for Neuroendocrine Tumors(Itanet), the Italian Association of Nuclear Medicine (AIMN), the Italian Society of Endocrinology (SIE), and the Italian Association of Medical Oncology (AIOM) on treating neuroendocrine neoplasms (NENs)with radioligand therapy (RLT).

METHODS: A list of 10 questions regarding using RLT ingastroenteropancreatic neuroendocrine tumors (GEP-NETs) was addressed after a careful review of theavailable literature. compiling information from the MEDLINE database, augmented with expert opinionsand recommendations, aligns with the latest scientific research and the author's extensive knowledge.The recommendations are evaluated using the GRADE system, showcasing the level of evidence andthe strength of the recommendations.

RESULTS AND CONCLUSIONS: Specifically, this paper focuses on thesubcategories of well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) thatexpress somatostatin receptors and are considered suitable for RLT, according to internationalguidelines.

PMID:39395114 | DOI:10.1007/s40618-024-02448-6

Changes in WHO classification of adrenal tumors and new ideas for multi-dimensional diagnosis and treatment

Fetched: October 16th, 2024, 2:01am UTC by Z Wang

Zhonghua Wai Ke Za Zhi. 2024 Oct 11;62(11):1001-1007. doi: 10.3760/cma.j.cn112139-20240531-00263. Online ahead of print.

ABSTRACT

In 2022, WHO updated the classification and concept of adrenal cortical and medullary tumors. In terms of adrenal cortical tumors, the WHO classification further standardizes the nomenclature of nodular adrenal cortical disease and refines the pathological classification of primary aldosteronism. In terms of adrenal medullary tumors, the WHO classification unifies the concepts of pheochromocytoma and paraganglioma, and reclassifies various concepts, including paraganglioma-like neuroendocrine tumors. The new standards not only cover the clinical manifestations of the disease, but also include other multiple aspects such as the histological origin of the disease, immunohistochemical manifestations, physiological mechanisms of the disease, hereditary susceptibility and prognostic factors. This article intends to explore how to improve the diagnostic and therapeutic level of adrenal tumors.

PMID:39394623 | DOI:10.3760/cma.j.cn112139-20240531-00263

$Permalink for 'Hypofractionated versus standard fractionation radiotherapy for merkel cell carcinoma'$

Hypofractionated versus standard fractionation radiotherapy for merkel cell carcinoma

Fetched: October 16th, 2024, 2:01am UTC by Lorein Gonzalez

Radiat Oncol. 2024 Oct 11;19(1):142. doi: 10.1186/s13014-024-02516-4.

ABSTRACT

PMID:39394124 | PMC:PMC11468079 | DOI:10.1186/s13014-024-02516-4

Size matters: integrating tumour volume and immune activation signatures predicts immunotherapy response

Fetched: October 16th, 2024, 2:01am UTC by Su Yin Lim

Mol Cancer. 2024 Oct 11;23(1):228. doi: 10.1186/s12943-024-02146-0.

ABSTRACT

Immune checkpoint inhibitors (ICIs) have transformed cancer treatment, providing significant benefit to patients across various tumour types, including melanoma. However, around 40% of melanoma patients do not benefit from ICI treatment, and accurately predicting ICI response remains challenging. We now describe a novel and simple approach that integrates immune-associated transcriptome signatures and tumour volume burden to better predict ICI response in melanoma patients. RNA sequencing was performed on pre-treatment (PRE) tumour specimens derived from 32 patients with advanced melanoma treated with combination PD1 and CTLA4 inhibitors. Of these 32 patients, 11 also had early during treatment (EDT, 5-15 days after treatment start) tumour samples. Tumour volume was assessed at PRE for all 32 patients, and at first computed tomography (CT) imaging for the 11 patients with EDT samples. Analysis of the Hallmark IFNÎ³ gene set revealed no association with ICI response at PRE (AUC ROC curve = 0.6404, p = 0.24, 63% sensitivity, 71% specificity). When IFNg activity was evaluated with tumour volume (ratio of gene set expression to tumour volume) using logistic regression to predict ICI response, we observed high discriminative power in separating ICI responders from non-responders (AUC = 0.7760, p = 0.02, 88% sensitivity, 67% specificity); this approach was reproduced with other immune-associated transcriptomic gene sets. These findings were further replicated in an independent cohort of 23 melanoma patients treated with PD1 inhibitor. Hence, integrating tumour volume with immune-associated transcriptomic signatures improves the prediction of ICI response, and suggest that higher levels of immune activation relative to tumour burden are required for durable ICI response.

PMID:39394099 | PMC:PMC11468211 | DOI:10.1186/s12943-024-02146-0

Update on the diagnosis of the pheochromocytoma

Fetched: October 16th, 2024, 2:01am UTC by E Achote

Hipertens Riesgo Vasc. 2024 Oct 10:S1889-1837(24)00092-8. doi: 10.1016/j.hipert.2024.08.001. Online ahead of print.

ABSTRACT

Pheochromocytoma is a rare neuroendocrine tumour that develops from chromaffin cells in the adrenal medulla and is characterised by the excessive production of catecholamines and their metabolites. Diagnostic confirmation is performed by detecting elevated levels of catecholamines and/or their metabolites in plasma or 24-h urine. In the case of moderate elevations of normetanephrine, the clonidine suppression test may be useful to differentiate between endogenous hypersecretion and false positive results. Once the biochemical diagnosis is performed, the tumour localisation is carried out using imaging techniques and sometimes with nuclear medicine imaging tests. Furthermore, in all patients with pheochromocytomas it is recommended to perform a genetic study to identify hereditary disorders that may be present in more than 30% of cases and to perform a cardiological evaluation to rule out the presence of cardiovascular involvement secondary to the catecholamine hypersecretion.

PMID:39394015 | DOI:10.1016/j.hipert.2024.08.001

Cancer of the paranasal sinuses in Germany: Data on incidence and survival from a population-based cancer registry

Fetched: October 16th, 2024, 2:01am UTC by Lisa Nachtsheim

Cancer Epidemiol. 2024 Oct 10;93:102684. doi: 10.1016/j.canep.2024.102684. Online ahead of print.

ABSTRACT

PURPOSE: This study aims to provide a broad overview of the epidemiology of cancer of the paranasal sinuses (PSC) in Germany. The data include information on incidence, staging, clinicopathological features and survival from one of the largest cancer registries in Europe.

METHODS: Population-based data on PSC diagnosed from January 1st, 2009 until December 31st, 2019 were retrieved from the German Centre for Cancer Registry Data (ZfKD). Age standardized incidence was calculated and relative survival estimates were computed by sex, histological subtype, age group and T-, N-, and M-Stage.

RESULTS: In total, 3975 cases were included in this study. The age-adjusted incidence rate (ASR) for PSC was 0.3/100,000 which remained stable during the observation period. The most frequent tumor localization was the maxillary sinus (41.9 %) and the most common histological subtype was keratinizing squamous cell carcinoma (kSCC) (44.3 %). All subtypes were predominantly found in the maxillary sinus except for adenocarcinoma and neuroendocrine carcinomas (SNEC), which were most frequently located in the ethmoidal sinus. The majority of the patients with a known T stage was diagnosed in tumor stage T4 (60.8 %). The overall 5-year relative survival (RS) for all patients with PSC was 52 %. RS dropped from 93 % for T1 stage tumors to 39 % for T4 tumors. RS was 58 % for N0 and 31 % for N+ cases, 54 % for M0 and 27 % for M1 cases.

CONCLUSION: Age-adjusted incidence for PSC is low and has been stable for the observed 11-year period. RS decreases continuously with increasing T-, N- and M-stage.

PMID:39393188 | DOI:10.1016/j.canep.2024.102684

Permalink for 'The impact of spheno-occipital synchondrosis exposure via extended endoscopic endonasal surgery on midface growth in pediatric patients'

The impact of spheno-occipital synchondrosis exposure via extended endoscopic endonasal surgery on midface growth in pediatric patients

Fetched: October 16th, 2024, 2:01am UTC by Manish Beniwal

J Neurosurg Pediatr. 2024 Oct 11:1-8. doi: 10.3171/2024.7.PEDS24174. Online ahead of print.

ABSTRACT

OBJECTIVE: Pediatric extended endonasal procedures pose significant surgical challenges. Lesions from the suprasellar region to the lower clivus necessitate extensive exposure. This study examined whether drilling the spheno-occipital synchondrosis (SOS) to remove the posterior clinoid process and dorsum sellae (DS) for greater exposure affects pediatric midfacial growth.

METHODS: From 2014 to 2020, the authors performed endoscopic endonasal surgery (EES) in 14 patients aged 12 years or younger. The lesions consisted of 11 cases of craniopharyngioma, 1 pituitary neuroendocrine tumor, 1 Rathke's cleft cyst, and 1 Langerhans cell histiocytosis. In 8 of the 14 cases, an extended EES procedure was used by exposing the SOS to remove the posterior clinoid process and DS. Measurement of the central face was based on head MRI before and after surgery. Measuring points were the sellae-nasion (SN) plane, the foremost points of the anterior maxilla (point A), and the maximum concavity point of the mandibular symphysis (point B). The authors measured and evaluated the SNA angle (angle created by the SN plane and the NA [a line connecting point A and the nasion] plane), SNB angle (angle created by the SN plane and the NB [a line connecting point B and the nasion] plane), and the ANB angle (angle created by the NA plane and the NB plane). In addition, a comparison was made with 6 pediatric cases in which transcranial surgery was performed for craniopharyngiomas.

RESULTS: In the extended EES group, the average preoperative age was 7 years, and the average postoperative age was 12 years. Mean preoperative angles in this group were 84Â° (SNA), 80.9Â° (SNB), and 3.1Â° (ANB); mean postoperative angles were 83.5Â° (SNA), 83.9Â° (SNB), and -0.4Â° (ANB). In the standard EES group, the average preoperative age was 9 years, and the average postoperative age was 14.5 years. Average preoperative angles in the standard EES group were 83Â° (SNA), 80.3Â° (SNB), and 2.7Â° (ANB); average postoperative angles were 82.7Â° (SNA), 81Â° (SNB), and 1.6Â° (ANB). In the transcranial surgery group, the average preoperative age was 4.5 years, and the average postoperative age was 9.8 years. Mean preoperative angles were 83.8Â° (SNA), 80.3Â° (SNB), and 3Â° (ANB); mean postoperative angles were 83.8Â° (SNA), 82.6Â° (SNB), and 1.2Â° (ANB). The only significant difference between groups was the postoperative ANB angle, which was negative in the extended EES group compared to the standard EES group, indicating the maxilla was positioned posteriorly compared to the mandible.

CONCLUSIONS: The measurement values of the EES groups and the transcranial surgery group exhibited minimal differences, except for a significant decrease in the postoperative ANB angle in the extended EES group compared with the standard EES group. These results show that extended EES may impact midface growth. Further research is required to understand the long-term impact of SOS exposure.

PMID:39393096 | DOI:10.3171/2024.7.PEDS24174

Tarlatamab-dlle: A New Hope for Patients with Extensive-Stage Small-Cell Lung Cancer

Fetched: October 16th, 2024, 2:01am UTC by Parveen Kumar Goyal

Curr Treat Options Oncol. 2024 Oct 11. doi: 10.1007/s11864-024-01268-3. Online ahead of print.

ABSTRACT

Lung cancer is expected to contribute to about 0.234 million new cases and about 0.125 million mortalities in the United States in the year 2024. Small cell lung cancer (SCLC), a neuroendocrine carcinoma, has lesser prevalence but is more aggressive at an extensive stage where the tumor is not only confined to hemithorax, mediastinum, and supraclavicular region but spread beyond the supraclavicular region. The prognosis of SCLC, irrespective of the limited or extensive stage, is very poor. Only a 5-10% overall survival rate in five years is expected and with extensive-stage SCLC, long-term disease-free survival is rare. In May 2024, the USFDA approved Tarlatamab-dlle, a DLL3 targeted bi-specific T-cell engager, for treating extensive-stage SCLC in adult patients, on or after platinum-based chemotherapy or on progression. Before the approval of Tarlatamab-dlle, only a few drugs, such as Atezolizumab and Durvalumab, received FDA approval for treating extensive-stage SCLC. It might be possible that Tarlatamab-dlle received accelerated FDA approval for extensive-stage SCLC, leaving some questions unanswered at this stage. This manuscript is focused on clinical, pre-clinical, and other pharmacological aspects of Tarlatamab-dlle for extensive-stage SCLC.

PMID:39392556 | DOI:10.1007/s11864-024-01268-3

Relationship between the expressions of DLL3, ASC1, TTF-1 and Ki-67: First steps of precision medicine at SCLC

Fetched: October 16th, 2024, 2:01am UTC by Samuel Silva

Oncotarget. 2024 Oct 11;15:750-763. doi: 10.18632/oncotarget.28660.

ABSTRACT

This study presents an observational, cross-sectional analysis of 64 patients diagnosed with small cell lung cancer (SCLC) at a reference laboratory for thoracic pathology between 2022 and 2024. The primary objective was to evaluate the expression of Delta-like ligand 3 (DLL3) and other neuroendocrine markers such as Chromogranin, and Synaptophysin, utilizing both traditional immunohistochemistry and digital pathology tools. Patients were primarily older adults, with a median age of over 71, and most biopsies were obtained from lung parenchyma. Immunohistochemistry (IHC) was performed using specific monoclonal antibodies, with DLL3 showing variable expression across the samples. Notably, DLL3 was expressed in 72.3% of the cases, with varied intensities and a semi-quantitative H-score applied for more nuanced analysis. ASCL1 was expressed in 97% of cases, with the majority considered low-expressors. Only 11% had high expression. TTF-1, traditionally not a conventional marker for the diagnosis of SCLC, was positive in half of the cases, suggesting its potential as a biomarker. The study underscores the significant variability in the expression of neuroendocrine markers in SCLC, with implications for both diagnosis and potential therapeutic targeting. DLL3, particularly, shows promise as a therapeutic target due to its high expression rate in the cohort. The use of digital pathology software QuPath enhanced the accuracy and depth of analysis, allowing for detailed morphometric analysis and potentially informing more personalized treatment approaches. The findings emphasize the need for further research into the role of these markers in the management and treatment of SCLC, considering the poor prognosis and high mortality rate observed in the cohort.

PMID:39392394 | PMC:PMC11468345 | DOI:10.18632/oncotarget.28660

Pituitary gigantism due to a novel AIP germline splice-site variant

Fetched: October 16th, 2024, 2:01am UTC by Elisa Lamback

Endocr Oncol. 2024 Sep 24;4(1):e240003. doi: 10.1530/EO-24-0003. eCollection 2024 Jan 1.

ABSTRACT

Pituitary gigantism is a rare pediatric disorder caused by excess growth hormone (GH) secretion. In almost 50% of cases, a genetic cause can be identified, with pathogenic variants in the aryl hydrocarbon receptor-interacting protein (AIP) gene being the most common. We present a case of an 11-year-old boy who exhibited progressive vision loss, associated with accelerated linear growth, and weight gain. On physical examination, he had enlarged hands, right eye amaurosis, and was already above his target height. Increased GH and IGF-I concentrations confirmed the diagnosis of pituitary gigantism. Magnetic resonance imaging showed a giant sellar lesion with supra- and para-sellar extensions. He underwent two surgeries which did not achieve a cure or visual improvement. Histopathological analysis revealed a sparsely granulated tumor, negative for somatostatin receptor type 2 (SST2) and an immunoreactivity score of 6 for somatostatin receptor type 5 (SST5). Our published artificial intelligence prediction model predicted an 83% chance of not responding to first-generation somatostatin receptor ligands. Pasireotide was therefore prescribed, and afterward cabergoline was added on. IGF-I concentrations decreased but did not normalize. We discovered a novel germline single nucleotide variant in the splicing donor region of intron 2 of the AIP gene (NM_003977.4:c.279+1 G>A), classified as likely pathogenic according to the American College of Medical Genetics and Genomics guidelines.

PMID:39391823 | PMC:PMC11466259 | DOI:10.1530/EO-24-0003

Immunomodulatory effects of immune cell-derived extracellular vesicles in melanoma

Fetched: October 16th, 2024, 2:01am UTC by Peng Nanru

Front Immunol. 2024 Sep 26;15:1442573. doi: 10.3389/fimmu.2024.1442573. eCollection 2024.

ABSTRACT

Melanoma, recognized as one of the most immunogenic malignancies in humans, holds paramount significance in the realm of immunotherapy. However, the emergence of drug resistance and the occurrence of adverse drug reactions underscore the pressing need to explore increasingly personalized immunotherapeutic modalities. Extracellular Vesicles (EVs), pivotal derivatives of immune cells, assume pivotal roles by encapsulating proteins, lipids, and nucleic acids within bilayer lipid structures, thereby facilitating targeted delivery to other immune cells. This orchestrated process orchestrates critical functions including antigen presentation, immune modulation, and the induction of apoptosis in tumor cells. A burgeoning body of evidence underscores the vast therapeutic potential of EVs in melanoma treatment. This comprehensive review aims to delineate the roles of EVs derived from immune cells such as dendritic cells, natural killer cells, macrophages, and T cells in the context of melanoma patients, thereby furnishing invaluable insights for the future direction of melanoma immunotherapy.

PMID:39391320 | PMC:PMC11464304 | DOI:10.3389/fimmu.2024.1442573

Permalink for 'Radiomics Analysis for Clinical Decision Support in 177Lu-DOTATATE Therapy of Metastatic Neuroendocrine Tumors using CT Images'

Radiomics Analysis for Clinical Decision Support in 177Lu-DOTATATE Therapy of Metastatic Neuroendocrine Tumors using CT Images

Fetched: October 16th, 2024, 2:01am UTC by Baharak Behmanesh

J Biomed Phys Eng. 2024 Oct 1;14(5):423-434. doi: 10.31661/jbpe.v0i0.2112-1444. eCollection 2024 Oct.

ABSTRACT

BACKGROUND: Radiomics is the computation of quantitative image features extracted from medical imaging modalities to help clinical decision support systems, which could ultimately meliorate personalized management based on individual characteristics.

OBJECTIVE: This study aimed to create a predictive model of response to peptide receptor radionuclide therapy (PRRT) using radiomics computed tomography (CT) images to decrease the dose for patients if they are not a candidate for treatment.

MATERIAL AND METHODS: In the current retrospective study, 34 patients with neuroendocrine tumors whose disease is clinically confirmed participated. Effective factors in the treatment were selected by eXtreme gradient boosting (XGBoost) and minimum redundancy maximum relevance (mRMR). Classifiers of decision trees (DT), random forest (RF), and K-nearest neighbors (KNN) with selected quantitative and clinical features were used for modeling. A confusion matrix was used to evaluate the performance of the model.

RESULTS: Out of 866 quantitative and clinical features, nine features with the XGBoost method and ten features with the mRMR pattern were selected that had the most relevance in predicting response to treatment. Selected features of the XGBoost method in integration with the RF classifier provided the highest accuracy (accuracy: 89%), and features selected by the mRMR method in combination with the RF classifier showed satisfactory performance (accuracy: 74%).

CONCLUSION: This exploratory analysis shows that radiomic features with high accuracy can effectively predict response to personalize treatment.

PMID:39391275 | PMC:PMC11462270 | DOI:10.31661/jbpe.v0i0.2112-1444

Permalink for 'High-Grade Progression, Sarcomatous Transformation, and/or Metastasis of Pituitary Neuroendocrine Neoplasms (PitNENs): The UCSF Experience'

High-Grade Progression, Sarcomatous Transformation, and/or Metastasis of Pituitary Neuroendocrine Neoplasms (PitNENs): The UCSF Experience

Fetched: October 16th, 2024, 2:01am UTC by Merryl Terry

Endocr Pathol. 2024 Oct 10. doi: 10.1007/s12022-024-09829-w. Online ahead of print.

ABSTRACT

Pituitary neuroendocrine tumors (PitNET) that metastasize comprise ~ 0.2% of adenohypophyseal tumors are aggressive and are challenging to treat. However, many non-metastatic tumors are also aggressive. Herein, we review 21 specimens from 13 patients at UCSF with metastatic PitNETs (CSF or systemic, N = 7 patients), high-grade pituitary neuroendocrine neoplasms (HG-PitNEN, N = 4 patients), and/or PitNETs with sarcomatous transformation (PitNET-ST, N = 5 patients). We subtyped cases using the World Health Organization (WHO) and International Agency for Research on Cancer (IARC) criteria for neuroendocrine neoplasms (NENs). Lineage subtypes included acidophil stem cell, null cell, thyrotroph, corticotroph, lactotroph, and gonadotroph tumors. The median Ki-67 labeling index was 25% (range 5-70%). Lack of p16 was seen in 3 cases, with overexpression in 2. Strong diffuse p53 immunopositivity was present in 3 specimens from 2 patients. Loss of Rb expression was seen in 2 cases, with ATRX loss in one. Molecular analysis in 4 tumors variably revealed TERT alterations, homozygous CDKN2A deletion, aneuploidy, and mutations in PTEN, TP53, PDGFRB, and/or PIK3CA. Eight patients (62%) died of disease, 4 were alive at the last follow-up, and 1 was lost to the follow-up. All primary tumors had worrisome features, including aggressive lineage subtype, high mitotic count, and/or high Ki-67 indices. Additional evidence of high-grade progression included immunohistochemical loss of neuroendocrine, transcription factor, and/or hormone markers. We conclude that metastatic PitNET is not the only high-grade form of pituitary NEN. If further confirmed, these histopathologic and/or molecular features could provide advanced warning of biological aggressiveness and be applied towards a future grading scheme.

PMID:39388031 | DOI:10.1007/s12022-024-09829-w

Permalink for 'Preoperative Glycosylated Hemoglobin A1C Impacts Long-Term Outcomes Following Curative-Intent Resection of Nonfunctional Gastroenteropancreatic Neuroendocrine Tumors'

Preoperative Glycosylated Hemoglobin A1C Impacts Long-Term Outcomes Following Curative-Intent Resection of Nonfunctional Gastroenteropancreatic Neuroendocrine Tumors

Fetched: October 16th, 2024, 2:01am UTC by Mu-Xing Li

J Surg Oncol. 2024 Oct 10. doi: 10.1002/jso.27951. Online ahead of print.

ABSTRACT

BACKGROUND: To investigate the impact of preoperative glycosylated hemoglobin A1C (HbA1c) among patients following curative-intent resection of nonfunctional gastroentropancreatic neuroendocrine tumors (GEP-NETs).

METHODS: Patients who underwent curative-intent resection for GEP-NETs from 2000 to 2020 were identified from the US Neuroendocrine Tumor Study Group (US-NETSG). Preoperative blood HbA1c levels were defined as high HbA1c (â‰¥ 6.5%) versus low HbA1c group (< 6.5%). Impact of HbA1c level on postoperative short-term and long-term overall (OS) were investigated.

RESULTS: A total of 130 patients with HbA1c < 6.5% and 60 patients with HbA1c â‰¥ 6.5% were included. Patients with HbA1c â‰¥ 6.5% had higher proportion of comorbidities, such as hypertension, obesity, anemia, and lower preoperative albumin levels versus patients with HbA1c < 6.5% (all p < 0.05). In addition, high level of preoperative HbA1c was associated with increased incidence of wound and infectious complications, as well as decreased long-term OS (median OS: high Hb1Ac 89.8 months vs. low Hb1Ac not reached, HR 3.487, p = 0.004) among patients with nonfunctional GEP-NETs, as well as among the subset of pancreatic NET patients (median OS: high Hb1Ac 74.3 months vs. low Hb1Ac not reached, p = 0.004), and patients with normal fasting blood glucose (< 140 mg/dL) (median OS: high Hb1Ac 75.4 months vs. low Hb1Ac not reached, p = 0.001).

CONCLUSIONS: Hb1Ac might have value as a screening tool to identify high-risk patients following surgical resection of nonfunctional GEP-NETs for consideration of more strict postoperative surveillance and treatment of elevated Hb1Ac level.

PMID:39387595 | DOI:10.1002/jso.27951

Permalink for 'Predictive Significance of Combined Plasmatic Detection of BRAF Mutations and S100B Tumor Marker in Early-Stage Malignant Melanoma'

Predictive Significance of Combined Plasmatic Detection of BRAF Mutations and S100B Tumor Marker in Early-Stage Malignant Melanoma

Fetched: October 16th, 2024, 2:01am UTC by Jiri Polivka

Cancer Med. 2024 Oct;13(19):e70313. doi: 10.1002/cam4.70313.

ABSTRACT

BACKGROUND: Melanoma is the most aggressive skin cancer with ability to recur also after early-stage tumor surgery. The aim was to identify early-stage melanoma patients at high risk of recurrence using liquid biopsy, estimating of mutated BRAF ctDNA and the level of tumor marker S100B in plasma.

METHODS: Eighty patients were enrolled in the study. BRAF V600E mutation was determined in FFPE tissue and plasma samples using ultrasensitive ddPCR with pre-amplification. The level of S100B was determined in plasma by immunoassay chemiluminescent method.

RESULTS: The best prediction of melanoma recurrence after surgery was observed in patients with combined high level of S100B (S100B^high) and ctDNA BRAFV600E (BRAF^mut) in preoperative (57.1% vs. 12.5%, p = 0.025) as well as postoperative blood samples (83.3% vs. 14.3%, resp., p = 0.001) in comparison with low S100B and BRAF wild-type. Similarly, patients with preoperative and postoperative S100B^high and BRAF^mut experienced worse prognosis (DFI p = 0.05, OS p = 0.131 and DFI p = 0.001, OS = 0.001, resp.).

CONCLUSION: We observed the benefit of the estimation of combination of S100B and ctDNA BRAF^mut in peripheral blood for identification of patients at high risk of recurrence and unfavorable prognosis.

SIGNIFICANCE: There is still no general consensus on molecular markers for deciding the appropriateness of adjuvant treatment of early-stage melanoma. We have shown for the first time that the combined determination of the ctDNA BRAF^mut oncogene (liquid biopsy) and the high level of tumor marker S100B in pre- and postoperative plasma samples can identify patients with the worst prognosis and the highest risk of tumor recurrence. Therefore, modern adjuvant therapy would be appropriate for these patients with resectable melanoma, regardless of disease stage.

PMID:39387479 | PMC:PMC11465285 | DOI:10.1002/cam4.70313

Permalink for 'Fluorescence detection of pituitary neuroendocrine tumour during endoscopic transsphenoidal surgery using bevacizumab-800CW: a non-randomised, non-blinded, single centre feasibility and dose finding trial [DEPARTURE trial]'

Fluorescence detection of pituitary neuroendocrine tumour during endoscopic transsphenoidal surgery using bevacizumab-800CW: a non-randomised, non-blinded, single centre feasibility and dose finding trial [DEPARTURE trial]

Fetched: October 16th, 2024, 2:01am UTC by I Schmidt

Eur J Nucl Med Mol Imaging. 2024 Oct 11. doi: 10.1007/s00259-024-06947-9. Online ahead of print.

ABSTRACT

PURPOSE: Achieving endocrine remission by gross total resection is challenging in pituitary neuroendocrine tumours (PitNETs) with cavernous sinus invasion. This study aims to assess the safety, feasibility, and optimal dose for intraoperative fluorescence imaging as an added instrument to discriminate PitNET from surrounding tissue using bevacizumab-800CW, targeting vascular endothelial growth factor A (VEGF-A).

METHODS: In part I, dose-escalation (0-4âˆ™5-10-25 mg) was performed in 4 groups of 3 patients with PitNETs Knosp grade 3-4. In part II, after interim analysis, the 10 mg and 25 mg groups were expanded to a total of 6 patients. Quantitative fluoroscence molecular endoscopy consisted of wide field fluorescence molecular endoscopy and multi-diameter single fiber reflectance / single fiber fluorescence spectroscopy. Mean fluorescence intensity (MFI) of the fresh surgical specimen was calculated and VEGF-staining was performed.

RESULTS: Eighteen patients were included. All doses were well tolerated. Three serious adverse events were registered, but none were tracer-related. Part I showed an adequate in-vivo tumour-to-background ratio for both 10 mg (TBR 2âˆ™00 [1âˆ™86, 2âˆ™19]) and 25 mg (TBR 2âˆ™10, [1âˆ™86, 2âˆ™58]). Part II revealed a substantially higher MFI in the 25 mg group. With both 10 mg and 25 mg a statistically significant difference between tumour and surrounding tissue was detected (p < 0âˆ™0001). All surgical specimens had VEGF-A expression.

CONCLUSION: This study demonstrates the safety and feasibility of quantitative fluorescence molecular endoscopy during PitNET surgery. Both 10 mg and 25 mg bevacizumab-800CW result in clear differentiation in-vivo, with improved contrast ex-vivo (MFI) in the 25 mg group.

TRIAL REGISTRATION: NCT04212793 / Study Details| Detection of PitNET Tissue During TSS Using Bevacizumab800CW| ClinicalTrials.gov.

PMID:39390132 | DOI:10.1007/s00259-024-06947-9

Permalink for 'Comparison of RECIST 1.1, mRECIST and PERCIST for assessment of peptide receptor radionuclide therapy treatment response in metastatic neuroendocrine tumors'

Comparison of RECIST 1.1, mRECIST and PERCIST for assessment of peptide receptor radionuclide therapy treatment response in metastatic neuroendocrine tumors

Fetched: October 16th, 2024, 2:01am UTC by Jack Zhao

Curr Probl Diagn Radiol. 2024 Oct 4:S0363-0188(24)00178-6. doi: 10.1067/j.cpradiol.2024.10.003. Online ahead of print.

ABSTRACT

PURPOSE: To compare RECIST 1.1, modified RECIST (mRECIST) and PERCIST for assessment of Peptide Receptor Radionuclide Therapy (PRRT) treatment response in metastatic neuroendocrine tumors.

MATERIALS: In this IRB-approved, HIPAA compliant retrospective study, patients treated with PRRT between July 2019 and Dec 2022 were identified. Inclusion criteria were presence of at least one pre-and one post-treatment imaging (CT, MRI, Ga 68 or Cu64 DOTATATE PET/CT) within one year of the start and end of PRRT respectively. The imaging was reviewed independently by two radiologists using RECIST 1.1, modified RECIST (mRECIST) and PERCIST criteria. Response of first post treatment scan and presence of disease progression during follow-up were recorded along with the date of best response and disease progression. Statistical analysis was performed to determine inter-reader agreement and agreement between the various response criteria using kappa statistics.

RESULTS: Best response by RECIST 1.1 was recorded in 26 patients (PR-7, SD- 13, PD- 6), by mRECIST in 22 patients (PR-7, SD- 10, PD- 5), by PERCIST in 14 patients (PR-4, SD- 3, PD- 7). Inter-reader agreement was highest for PERCIST (weighted kappa 0.921, standard error 0.078 95% CI 0.769 to 1.000) followed by RECIST 1.1 (weighted kappa 0.897, standard error 0.071 95% CI 0.758 to 1.000) and mRECIST (weighted kappa 0.883, standard error 0.079 95% CI 0.727 to 1.000).

PMID:39389807 | DOI:10.1067/j.cpradiol.2024.10.003

The third symposium on treatment-induced neuroendocrine prostate cancer: insights and future directions

Fetched: September 4th, 2024, 2:03am UTC by Yuzhuo Wang

Epigenomics. 2024 Sep 3:1-4. doi: 10.1080/17501911.2024.2391729. Online ahead of print.

ABSTRACT

Neuroendocrine prostate cancer (NEPC) is a rare and aggressive subtype of prostate cancer (PCa), emerging from advanced treatments and characterized by loss of androgen receptor (AR) signaling and neuroendocrine features, leading to rapid progression and treatment resistance. The third symposium on treatment-induced NEPC, held from 21 to 23 June 2024, at Harrison Hot Springs Resort, BC, Canada, united leading global researchers and clinicians. Sponsored by the Vancouver Prostate Centre (VPC), Canadian Institute of Health Research, Prostate Cancer Foundation Canada and Pharma Planter Inc, the event focused on the latest NEPC research and innovative treatment strategies. Co-chaired by Drs. Yuzhuo Wang and Martin Gleave, the symposium featured sessions on NEPC's historical context, molecular pathways, epigenetic regulation and the role of the tumor microenvironment and metabolism in its progression. Keynotes from experts like Dr. Himisha Beltran and Dr. Martin Gleave highlighted the complexity of NEPC. The Emerging Talent session showcased new research, pointing to the future of NEPC treatment. The symposium concluded with a consensus on the need for early detection, targeted therapies and personalized medicine to effectively combat NEPC, emphasizing the importance of global collaboration in advancing NEPC understanding and treatment.

PMID:39225130 | DOI:10.1080/17501911.2024.2391729

Pharmacologic LDH inhibition redirects intratumoral glucose uptake and improves antitumor immunity in solid tumor models

Fetched: September 4th, 2024, 2:03am UTC by Svena Verma

J Clin Invest. 2024 Sep 3;134(17):e177606. doi: 10.1172/JCI177606.

ABSTRACT

Tumor reliance on glycolysis is a hallmark of cancer. Immunotherapy is more effective in controlling glycolysis-low tumors lacking lactate dehydrogenase (LDH) due to reduced tumor lactate efflux and enhanced glucose availability within the tumor microenvironment (TME). LDH inhibitors (LDHi) reduce glucose uptake and tumor growth in preclinical models, but their impact on tumor-infiltrating T cells is not fully elucidated. Tumor cells have higher basal LDH expression and glycolysis levels compared with infiltrating T cells, creating a therapeutic opportunity for tumor-specific targeting of glycolysis. We demonstrate that LDHi treatment (a) decreases tumor cell glucose uptake, expression of the glucose transporter GLUT1, and tumor cell proliferation while (b) increasing glucose uptake, GLUT1 expression, and proliferation of tumor-infiltrating T cells. Accordingly, increasing glucose availability in the microenvironment via LDH inhibition leads to improved tumor-killing T cell function and impaired Treg immunosuppressive activity in vitro. Moreover, combining LDH inhibition with immune checkpoint blockade therapy effectively controls murine melanoma and colon cancer progression by promoting effector T cell infiltration and activation while destabilizing Tregs. Our results establish LDH inhibition as an effective strategy for rebalancing glucose availability for T cells within the TME, which can enhance T cell function and antitumor immunity.

PMID:39225102 | DOI:10.1172/JCI177606

Permalink for 'Use of Free Internal Mammary Artery Perforator Flap Harvested With Minimally Invasive Approach for Facial Reconstruction: Report of Two Cases'

Use of Free Internal Mammary Artery Perforator Flap Harvested With Minimally Invasive Approach for Facial Reconstruction: Report of Two Cases

Fetched: September 4th, 2024, 2:03am UTC by Yun Choi

Microsurgery. 2024 Sep;44(6):e31233. doi: 10.1002/micr.31233.

ABSTRACT

The internal mammary artery perforator (IMAP) flap has been widely used for chest wall and neck reconstruction. The color of its skin paddle closely resembles that of facial skin, making it attractive for facial reconstruction. However, there has been insufficient investigations reporting the use of free IMAP flap. Furthermore, even in such studies, somewhat invasive procedures, including rib cartilage resection, were employed to ensure sufficient pedicle length, potentially increasing donor morbidity. Our report presents two cases of successful facial defect reconstruction using a free IMAP flap harvested with minimal donor site damage, showing its feasibility. In the first case, a 48-year-old male underwent wide excision for a malignant melanoma on his right cheek, resulting in a 4 Ã— 4.5 cm full-thickness defect. A free IMAP flap with a 2.5 cm pedicle, was harvested without rib cartilage resection, preserving IMA main trunk, and transferred with anastomosed to the angular vessels within the defect. The second patient presented with a 4.5 Ã— 3.5 cm basal cell carcinoma on the left cheek, necessitating wide excision and leaving a 6 Ã— 5 cm defect. A free IMAP flap was harvested with the same approach and successfully reconstructed the defect with connected to the superficial temporal vessels using vascular bridge. Both patients were discharged complication-free, with no recurrence during 24 and 15 months of follow-up, respectively. They were highly satisfied with the final skin color and texture outcomes. Harvesting a free IMAP flap while minimizing donor morbidity may offer an attractive option for facial reconstruction.

PMID:39225063 | DOI:10.1002/micr.31233

Permalink for 'A case of double-negative prostate cancer with BRCA2 mutation and high tumor mutation burden treated sequentially with olaparib and pembrolizumab'

A case of double-negative prostate cancer with BRCA2 mutation and high tumor mutation burden treated sequentially with olaparib and pembrolizumab

Fetched: September 4th, 2024, 2:03am UTC by Hiroki Tanaka

IJU Case Rep. 2024 Aug 4;7(5):395-398. doi: 10.1002/iju5.12766. eCollection 2024 Sep.

ABSTRACT

INTRODUCTION: Double-negative prostate cancer, an androgen receptor-independent prostate cancer without features of neuroendocrine tumors, is refractory to treatment but could be an ideal candidate for individualized treatment.

CASE PRESENTATION: An 85-year-old patient with metastatic castration-resistant prostate cancer without prostate-specific antigen progression presented with local recurrence and liver and lung metastases 6 months after orchiectomy and apalutamide. A liver tumor biopsy led to a diagnosis of double-negative prostate cancer. FoundationOne^Â® CDx showed BRCA2 mutation and high tumor mutation burden. Olaparib and pembrolizumab were administered sequentially, and the patient responded to each treatment for 5 months until radiographic progression.

CONCLUSION: Sequential use of olaparib and pembrolizumab may be effective for double-negative prostate cancer with BRCA2 mutations and high tumor mutation burden.

PMID:39224671 | PMC:PMC11366435 | DOI:10.1002/iju5.12766

$Permalink for 'Diagnosis and Management of Aggressive/Refractory Growth Hormone-Secreting Pituitary Neuroendocrine Tumors'$

Diagnosis and Management of Aggressive/Refractory Growth Hormone-Secreting Pituitary Neuroendocrine Tumors

Fetched: September 4th, 2024, 2:03am UTC by Xiaojuan Zhang

Int J Endocrinol. 2024 Aug 26;2024:5085905. doi: 10.1155/2024/5085905. eCollection 2024.

ABSTRACT

The majority of acromegaly and gigantism are caused by growth hormone-secreting pituitary neuroendocrine tumors (PitNETs). Most cases can be cured or controlled by surgery, medical therapy, and/or radiotherapy. However, a few of these tumors are resistant to traditional therapy and always have a poor prognosis. The title aggressive/refractory is used to differentiate them from pituitary carcinomas. To date, there is no definitive conclusion on how to diagnose aggressive/refractory growth hormone-secreting PitNETs, which may have slowed the process of exploring new therapeutical strategies. We summarized the literature described diagnosis and treatment of the disease. Potential disease markers and prospective therapies were also included.

PMID:39224564 | PMC:PMC11368557 | DOI:10.1155/2024/5085905

Permalink for 'Belzutifan in Individuals with von Hippel-Lindau Retinal Hemangioblastomas: Institutional Experience and Review of the Literature'

Belzutifan in Individuals with von Hippel-Lindau Retinal Hemangioblastomas: Institutional Experience and Review of the Literature

Fetched: September 4th, 2024, 2:03am UTC by Farzad Jamshidi

Ocul Oncol Pathol. 2024 Sep;10(3):154-161. doi: 10.1159/000539434. Epub 2024 May 24.

ABSTRACT

INTRODUCTION: The systemic HIF-2 alpha inhibitor, belzutifan, has been approved for use in patients with von Hippel-Lindau disease (VHL)-associated renal cell carcinoma, central nervous system (CNS) hemangioblastomas, and pancreatic neuroendocrine tumors. This drug has also shown promise in controlling VHL retinal hemangioblastomas (RHs), but little work has been published on the use of the drug in this setting.

METHODS: We conducted a retrospective review of patients with VHL-associated RHs followed by the retina service at our institution who were treated with systemic belzutifan. Patient age, gender, genotype, presence of systemic tumors, indication for the drug, initial dose, adjusted dose, side effects, and tumor response were recorded. We also conducted a literature search for all manuscripts describing the effect of belzutifan on VHL-associated ocular tumors.

RESULTS: We identified 12 eyes of 7 patients with VHL-associated ocular tumors who were treated with belzutifan at our institution. Of these, 5 eyes of 3 patients had progressing ocular tumors when belzutifan was started. Of the 7 total patients, 2 were treated for renal cell carcinoma, 2 for CNS hemangioblastomas, 2 for RHs, and one for pancreatic neuroendocrine tumors. Initial dose was 120 mg PO daily in 6 patients and 80 mg PO daily in 1 patient. The dose was reduced in all but 1 patient due to side effects. The ocular tumors were controlled in all patients with an average follow-up of 13 months (range 4-24 months). Literature review identified 7 manuscripts that described belzutifan-mediated control of ocular tumors in patients with VHL-associated RHs in 21 patients.

CONCLUSION: The drug belzutifan shows great promise for controlling RHs and preventing vision loss in patients with VHL. Further work needs to address the optimal dose, role of the drug as a neoadjuvant therapy, and long-term efficacy and tolerability of the drug in a larger cohort of patients with ocular tumors.

PMID:39224523 | PMC:PMC11368390 | DOI:10.1159/000539434

Mixed Neuroendocrine-Squamous Cell Carcinoma of the Hand With Metastatic Dissemination: A Case Report

Fetched: September 4th, 2024, 2:03am UTC by Jubril Adepoju

Eplasty. 2024 Aug 15;24:e45. eCollection 2024.

ABSTRACT

PMID:39224411 | PMC:PMC11367163

68Ga-DOTATATE PET/CT Imaging of a Solitary Nasopharyngeal Metastasis of Merkel Cell Carcinoma

Fetched: September 4th, 2024, 2:03am UTC by Haoyuan Ding

Clin Nucl Med. 2024 Oct 1;49(10):973-974. doi: 10.1097/RLU.0000000000005283. Epub 2024 May 26.

ABSTRACT

PMID:39223731 | DOI:10.1097/RLU.0000000000005283

Unilateral amelanotic conjunctival malignant melanoma: a case report

Fetched: September 4th, 2024, 2:03am UTC by Marcelo Ayala

J Med Case Rep. 2024 Sep 3;18(1):403. doi: 10.1186/s13256-024-04729-3.

ABSTRACT

INTRODUCTION: Cutaneous malignant melanomas rarely occur in the eye, usually in the eyelids or the conjunctiva. Conjunctival malignant melanomas are even rarer. Most melanomas are dark in color as they are pigmented. However, amelanotic conjunctival malignant melanomas, a scarce variant of the cancer, can be challenging to diagnose accurately.

CASE PRESENTATION: We present two cases of white Caucasian Swedish-born women who were diagnosed with unilateral amelanotic malignant melanoma in the conjunctiva of the eye. In the first case, the patient was an 81-year-old woman who was suffering from redness and foreign body sensation in the left eye. The initial diagnosis was blepharitis. Three biopsies were taken, which showed malignant melanoma in the eyelid and the conjunctiva. Unfortunately, the eye and the rest of the orbit could not be saved, and the patient had to undergo an orbital exenteration. In the second case, the patient was a 50-year-old woman, and the tumor was localized in the temporal conjunctiva of the left eye. The initial diagnosis was pinguecula, but at the time of surgery, the physician suspected conjunctival intraepithelial neoplasia. The tumor was not completely removed, so adjuvant brachytherapy and local chemotherapy were used. The eye was preserved. No neck and/or lung metastasis was detected in either case at the time of diagnosis.

CONCLUSIONS: Conjunctival amelanotic malignant melanomas should be suspected when tumors are present in the eye and/or the eyelids. By suspecting amelanotic malignant melanoma, the delay in treatment can be shortened. Treating them as soon as possible is essential to minimize the risk of metastasis.

PMID:39223654 | DOI:10.1186/s13256-024-04729-3

Permalink for 'Deciphering genetic and nongenetic factors underlying tumour dormancy: insights from multiomics analysis of two syngeneic MRD models of melanoma and leukemia'

Deciphering genetic and nongenetic factors underlying tumour dormancy: insights from multiomics analysis of two syngeneic MRD models of melanoma and leukemia

Biol Res. 2024 Sep 3;57(1):59. doi: 10.1186/s40659-024-00540-y.

ABSTRACT

BACKGROUND: Tumour dormancy, a resistance mechanism employed by cancer cells, is a significant challenge in cancer treatment, contributing to minimal residual disease (MRD) and potential relapse. Despite its clinical importance, the mechanisms underlying tumour dormancy and MRD remain unclear. In this study, we employed two syngeneic murine models of myeloid leukemia and melanoma to investigate the genetic, epigenetic, transcriptomic and protein signatures associated with tumour dormancy. We used a multiomics approach to elucidate the molecular mechanisms driving MRD and identify potential therapeutic targets.

RESULTS: We conducted an in-depth omics analysis encompassing whole-exome sequencing (WES), copy number variation (CNV) analysis, chromatin immunoprecipitation followed by sequencing (ChIP-seq), transcriptome and proteome investigations. WES analysis revealed a modest overlap of gene mutations between melanoma and leukemia dormancy models, with a significant number of mutated genes found exclusively in dormant cells. These exclusive genetic signatures suggest selective pressure during MRD, potentially conferring resistance to the microenvironment or therapies. CNV, histone marks and transcriptomic gene expression signatures combined with Gene Ontology (GO) enrichment analysis highlighted the potential functional roles of the mutated genes, providing insights into the pathways associated with MRD. In addition, we compared "murine MRD genes" profiles to the corresponding human disease through public datasets and highlighted common features according to disease progression. Proteomic analysis combined with multi-omics genetic investigations, revealed a dysregulated proteins signature in dormant cells with minimal genetic mechanism involvement. Pathway enrichment analysis revealed the metabolic, differentiation and cytoskeletal remodeling processes involved in MRD. Finally, we identified 11 common proteins differentially expressed in dormant cells from both pathologies.

CONCLUSIONS: Our study underscores the complexity of tumour dormancy, implicating both genetic and nongenetic factors. By comparing genomic, transcriptomic, proteomic, and epigenomic datasets, our study provides a comprehensive understanding of the molecular landscape of minimal residual disease. These results provide a robust foundation for forthcoming investigations and offer potential avenues for the advancement of targeted MRD therapies in leukemia and melanoma patients, emphasizing the importance of considering both genetic and nongenetic factors in treatment strategies.

PMID:39223638 | DOI:10.1186/s40659-024-00540-y

Treatment options for a large facial lentigo maligna

Fetched: September 4th, 2024, 2:03am UTC by Jim Muir

Aust J Gen Pract. 2024 Sep;53(9):647-650. doi: 10.31128/AJGP-11-23-7024.

NO ABSTRACT

PMID:39226599 | DOI:10.31128/AJGP-11-23-7024

Melanoma imaging and diagnosis: What does the future hold?

Fetched: September 4th, 2024, 2:03am UTC by H Peter Soyer

Aust J Gen Pract. 2024 Sep;53(9):633-634. doi: 10.31128/AJGP-02-24-7156.

ABSTRACT

BACKGROUND: In Australia, artificial intelligence (AI) is increasingly being used in the field of melanoma diagnosis. Early diagnosis is arguably the most important prognostic factor for melanoma survival. The use of digital monitoring of naevi, especially dysplastic naevi, might reduce the number of biopsies needed in managing patients at risk of melanoma, especially in patients with high naevi counts.

OBJECTIVE: This article discusses advances in imaging and early diagnosis including the use of AI in this process.

DISCUSSION: The benefits of performing biopsies must be balanced with the potential to cause harm. Whole-body imaging can assist with more accurate detection of changing lesions and enable clinicians to focus on lesions where change is detected.

PMID:39226596 | DOI:10.31128/AJGP-02-24-7156

Melanoma medicine: New drugs for melanoma and the role of the general practitioner

Fetched: September 4th, 2024, 2:03am UTC by Andrea Boutros

Aust J Gen Pract. 2024 Sep;53(9):619-624. doi: 10.31128/AJGP-01-24-7129.

ABSTRACT

BACKGROUND: Following major achievements seen with drug therapies for the treatment of advanced melanoma in the last decade, they now also have an ever-increasing role for the treatment of earlier stage disease. This review outlines the current drugs used to treat melanoma, and how general practitioners (GPs) can assist in the management of patients with melanoma and the associated toxicities with treatment.

OBJECTIVE: This review summarises the evolving status of melanoma care, emphasising when to refer patients to medical oncologists as part of the multidisciplinary team. It provides guidance into recognising and managing immune-related adverse events (irAEs) associated with immunotherapy, and provides insights into the future changes in clinical practice.

DISCUSSION: Drug therapies are increasingly used for the treatment of many patients with melanoma. Early referral is crucial, and clinical trials remain the best choice for most patients. Recognition and prompt management of irAEs is vital, and collaboration between GPs and oncologists is essential for best care.

PMID:39226594 | DOI:10.31128/AJGP-01-24-7129

Melanoma overdiagnosis: What do we know and what do we do?

Fetched: September 4th, 2024, 2:03am UTC by Cliff Rosendahl

Aust J Gen Pract. 2024 Sep;53(9):612-616. doi: 10.31128/AJGP-02-24-7176.

ABSTRACT

BACKGROUND: Melanoma overdiagnosis occurs when melanomas, not destined to cause morbidity or death in a patient's lifetime, are identified and treated.

OBJECTIVE: This study considers the causes and magnitude of melanoma overdiagnosis in Australia. We also speculate about a possible benefit of overdiagnosis in Australia; namely, a reduction in excess deaths in the geographical areas where melanoma is diagnosed most frequently.

DISCUSSION: Overdiagnosis can arguably be mitigated by factors that reduce the number of lesions treated for each melanoma identified. Data from the Australian Cancer Atlas show that there is a reduction in excess deaths from melanoma in geographical areas where diagnostic rates are higher (Pearson correlation coefficient r=-0.5978, 95% CI: -0.6243 to -0.5699, P<0.0001); this being the strongest inverse correlation observed among the 20 cancer types in the Atlas. Is early diagnosis of actual life-threatening melanomas in these geographical regions impacting survival? Further research is planned.

PMID:39226593 | DOI:10.31128/AJGP-02-24-7176

Skin cancer 2

Fetched: September 4th, 2024, 2:03am UTC by David Wilkinson

Aust J Gen Pract. 2024 Sep;53(9):597. doi: 10.31128/AJGP-09-24-1234e.

NO ABSTRACT

PMID:39226592 | DOI:10.31128/AJGP-09-24-1234e

Genomic profiling and immune phenotyping of neuroendocrine bladder cancer

Fetched: September 4th, 2024, 2:03am UTC by Jingyu Zang

Clin Cancer Res. 2024 Sep 3. doi: 10.1158/1078-0432.CCR-24-1277. Online ahead of print.

ABSTRACT

PURPOSE: Neuroendocrine bladder cancer (NEBC) poses a formidable clinical challenge and attracts keen interests to explore immunotherapy as a viable treatment option. However, a comprehensive immunogenomic landscape has yet to be thoroughly investigated.

EXPERIMENTAL DESIGN: Leveraging a long-term cohort of natural NEBC cases, we employed a multimodal approach integrating genomic (n = 19), transcriptomic (n = 3), single-cell RNA sequencing (n = 1), and immunohistochemical analyses (n = 34) to meticulously characterize the immunogenicity and immunotypes of primary NEBC tumors. Clinical, pathological, medical imaging, and treatment information was retrospectively retrieved and analyzed.

RESULTS: Our study unveiled that despite a considerable mutational burden, NEBC was typically immunologically inactive, as manifested by 'immune-excluded' or 'immune-desert' microenvironment. Interestingly, a subset of mixed NEBC with concurrent urothelial bladder cancer (UBC) histology displayed an 'immune-infiltrated' phenotype with prognostic relevance. When compared to UBC, NEBC lesions were distinguished by a denser cellular composition and augmented peritumoral extracellular matrix, which might collectively impede lymphatic infiltration. As a result, single-agent immune checkpoint inhibitors demonstrated limited efficacy against NEBC, while pharmacologic immunostimulation with combination chemotherapy conferred a more favorable response.

CONCLUSIONS: These new insights derived from genomic profiling and immune phenotyping pave the way for rational immunotherapeutic interventions in NEBC patients, with the potential to ultimately reduce mortality from this otherwise fatal disease.

PMID:39226396 | DOI:10.1158/1078-0432.CCR-24-1277

Permalink for 'Bronchoscopic Interventional Therapy Combined With Pembrolizumab in the Treatment of Pulmonary Large Cell Neuroendocrine Carcinoma: A Case Report'

Bronchoscopic Interventional Therapy Combined With Pembrolizumab in the Treatment of Pulmonary Large Cell Neuroendocrine Carcinoma: A Case Report

Fetched: September 4th, 2024, 2:03am UTC by Yingyi Fan

Clin Respir J. 2024 Sep;18(9):e70009. doi: 10.1111/crj.70009.

ABSTRACT

This study reports a significant clinical outcome following the use of bronchoscopic interventional therapy combined with pembrolizumab for treating pulmonary large cell neuroendocrine carcinoma (LCNEC), showcasing a novel approach in managing this aggressive cancer.

PMID:39225701 | DOI:10.1111/crj.70009

Permalink for 'Incidence trends in upper GI cancer in young adults: a nationwide time-trend analysis using 2001-2019 United States Cancer Statistics databases'

Incidence trends in upper GI cancer in young adults: a nationwide time-trend analysis using 2001-2019 United States Cancer Statistics databases

Fetched: September 4th, 2024, 2:03am UTC by Jeff Liang

Am J Gastroenterol. 2024 Sep 3. doi: 10.14309/ajg.0000000000003068. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Upper gastrointestinal (UGI) cancers, comprised of malignancies of the esophagus, stomach, duodenum, pancreas, liver, biliary tract, and gallbladder, are the second leading cause of cancer-related mortality in the US and is associated with significant comorbidities. Recent studies show a disproportionate rise in pancreatic and stomach cancer among young adults. This study aims to use a nationwide, population-based cohort to (1) evaluate the trend of al UGI cancer as an aggregate and (2) examine the role of demographics, histology, and tumor stage in UGI cancer incidence among young adults.

METHODS: Individuals diagnosed with UGI cancer in the US from 2001-2019 were identified and obtained from the SEER-NPCR database. The primary outcomes were incidence rates of UGI cancer (calculated per 100,000, age-adjusted to the year 2000 US population), stratified by sex and age (< 55 years for young adults, and â‰¥55 years for older adults). Trends, annual percentage change (APC) and average APC (AAPC) were calculated using the parametric method. Sensitivity analysis was performed according to primary site and histology; further analysis examining race and cancer stage was performed in the young adult subgroup.

RESULTS: A total of 2,333,161 patients with UGI cancer were identified. The majority of cases were male and 14.3% were <55 years of age. Incidence of UGI cancer increased most in women < 55 years of age, driven primarily by pancreatic and stomach cancers, as well as neuroendocrine tumor and gastrointestinal stromal tumor histology. African American race and localized tumors, and malignancy with distant spread are also contributing to the disparate increase among young women. UGI mortality rates have not changed significantly in young adults.

CONCLUSION: The overall incidence rate of upper GI cancer is increasing significantly in young women compared to men. Increased endoscopic procedures and disparate exposure to risk factors are likely contributing to these trends.

PMID:39225338 | DOI:10.14309/ajg.0000000000003068

New oncological indications for liver transplantation

Fetched: September 3rd, 2024, 2:02am UTC by Massimo Leo

Rev Med Suisse. 2024 Aug 28;20(884):1478-1482. doi: 10.53738/REVMED.2024.20.884.1478.

ABSTRACT

Transplantation oncology represents a specificity of liver transplantation. Hepatocellular carcinoma is now an accepted indication with very good long-term results. Cholangiocarcinoma, hepatic -metastases from colorectal cancer and neuroendocrine tumors are emerging indications with outcome superior to those that can be achieved with systemic treatments in very selected patients.

PMID:39219389 | DOI:10.53738/REVMED.2024.20.884.1478

Rapidly Growing Leiomyoma Mimicking Schwannoma of the Saphenous Nerve in the Lower Extremity: An Unusual Case Report

Fetched: September 3rd, 2024, 2:02am UTC by Åžule GÃ¶ktÃ¼rk

J Musculoskelet Neuronal Interact. 2024 Sep 1;24(3):325-329.

ABSTRACT

Leiomyomas and schwannomas are both types of rare benign soft tissue tumours. Leiomyomas are more commonly found in the lower limbs than in the upper extremities, while schwannomas are rare peripheral nerve sheath tumours that can occur in different anatomical regions. However, they rarely occur in the saphenous nerve. This case study presents a 41-year-old female patient with a solitary mass lesion located deep in the soft tissue of the anteromedial lower extremity. The physical examination revealed a palpable, elastic-hard, mobile and non-tender mass. Magnetic resonance imaging (MRI) showed an oval-shaped subcutaneous mass on contrast-enhanced T1-weighted sections. The initial MRI images suggested a schwannoma, but the tumour was later confirmed to be a leiomyoma after total enucleation. An immunohistochemical study was performed for differential diagnosis. Solitary mass lesions in the lower extremities can be mistaken for various types of tumours and misdiagnosed and require histopathological examination and good radiological imaging for differential diagnosis. Complete surgical excision is usually a safe and effective treatment for leiomyomas.

PMID:39219331 | PMC:PMC11367172

Permalink for 'TREM2, a critical activator of pyroptosis, mediates the anti-tumor effects of piceatannol in uveal melanoma cells via caspase 3/GSDME pathwayTREM2, a critical activator of pyroptosis, mediates the anti-tumor effects of piceatannol in uveal melanoma cells'

TREM2, a critical activator of pyroptosis, mediates the anti-tumor effects of piceatannol in uveal melanoma cells via caspase 3/GSDME pathwayTREM2, a critical activator of pyroptosis, mediates the anti-tumor effects of piceatannol in uveal melanoma cells

Fetched: September 3rd, 2024, 2:02am UTC by Xudong Jiu

Int J Mol Med. 2024 Nov;54(5):96. doi: 10.3892/ijmm.2024.5420. Epub 2024 Sep 2.

ABSTRACT

Uveal melanoma (UM) is the most prevalent type of primary intraocular malignancy and is prone to metastasize, particularly to the liver. However, due to the poor understanding of the pathogenesis of UM, effective therapeutic approaches are lacking. As a phenolic compound extracted from grapes, piceatannol (PIC) exhibits antiâ€‘cancer properties. To the best of our knowledge, however, the effects of PIC on UM have not been well investigated. Therefore, in the present study, considering the impact of pyroptosis on modulating cell viability, the mechanism underlying the effects of PIC on UM cell proliferation was explored. The inhibitory effect of PIC on proliferation of UM cells was detected by cell counting kitâ€‘8 assay. Wound healing was used to investigate the effects of PIC on the migration of UM cells. Activity detecting assays were performed to test the apoptosis and oxidant level in UM cells. Western blotting and RTâ€‘qPCR were used to detect the inflammatory and pyroptotic levels of UM cell after PIC treatment. PICâ€‘treated UM cells were screened by highâ€‘throughput sequencing to detect the differential expression of RNA and differential genes. Siâ€‘TREM2 transfection was used to verify the important role of TREM2 in the effects of PIC. Immunohistochemical staining was used to observe the expressions of TREM2 and GSDMR of tumor in nude mice after PIC administration. PIC effectively inhibited proliferation ability of C918 and Mumâ€‘2b UM cell lines via enhancing apoptosis, as evidenced by enhanced activities of caspase 3 and caspase 9. In addition, treatment of UM cells with PIC attenuated cell migration in a doseâ€‘dependent manner. PIC increased reactive oxygen species levels and suppressed the activity of the antioxidant enzymes superoxide dismutase, glutathioneâ€‘Sâ€‘transferase, glutathione peroxidase and catalase. PIC inhibited inflammatory responses in C918 cells. PIC treatment upregulated ILâ€‘1Î², ILâ€‘18 and Nodâ€‘like receptor protein 3 and downregulated gasdermin D (GSDMD). RNA sequencing results revealed the activation of an unconventional pyroptosisâ€‘associated signaling pathway, namely caspase 3/GSDME signaling, following PIC treatment, which was mediated by triggering receptor expressed on myeloid cells 2 (TREM2) upregulation. As an agonist of TREM2, COG1410â€‘mediated TREM2 upregulation inhibited proliferation of C918 cells, displaying similar effects to PIC. Furthermore, PIC inhibited tumor growth via regulating the TREM2/caspase 3/GSDME pathway in a mouse model. Collectively, the present study revealed a novel mechanism underlying the inhibitory effects of PIC on UM, providing a potential treatment approach for UM in clinic.

PMID:39219277 | DOI:10.3892/ijmm.2024.5420

Primary hepatic neuroendocrine tumour: A rare clinical case

Fetched: September 3rd, 2024, 2:02am UTC by Yang Xu

Asian J Surg. 2024 Aug 31:S1015-9584(24)01869-4. doi: 10.1016/j.asjsur.2024.08.129. Online ahead of print.

NO ABSTRACT

PMID:39218747 | DOI:10.1016/j.asjsur.2024.08.129

Anti-tumor and anti-metastasis of water-soluble sulfated beta-glucan derivatives from Saccharomyces cerevisiae

Fetched: September 3rd, 2024, 2:02am UTC by Jia Li

Carbohydr Polym. 2024 Nov 15;344:122466. doi: 10.1016/j.carbpol.2024.122466. Epub 2024 Jul 6.

ABSTRACT

Traditional fungi Î²-glucan commonly possesses high molecular weight with poor water solubility, which remains significant challenge in the drug development and medical application. Water-soluble Î²-glucan with high molecular weight (dHSCG) of 560 kDa, low molecular weight (dLSCG) of 60 kDa, and sulfated derivative (SCGS) with a molecular weight of 146 kDa and sulfate degree at 2.04 were obtained through well-controlled degradation and sulfated modification from Saccharomyces cerevisiae in this study. The structural characteristics were confirmed as Î²-1,3/6-glucan by FT-IR and NMR spectroscopy. Carbohydrate microarrays and surface plasmon resonance revealed distinct and contrasting binding affinities between the natural Î²-glucans and sulfated derivatives. SCGS exhibited strong binding to FGF and VEGF, while natural Î²-glucan showed no response, suggesting its potential as a novel antitumor agent. Moreover, SCGS significantly inhibited the migration rate of the highly metastatic melanoma (B16F10) cells. The lung metastasis mouse model also demonstrated that SCGS significantly reduced and eliminated the nodules, achieving an inhibition rate of 86.7% in vivo, with a dramatic improvement in IFN-Î±, TNF-Î±, and IL-1Î² levels. Through analysis of protein content and distribution in lung tissues, the anti-tumor and anti-metastasis mechanism of SCGS involves the regulation of degrading enzymes to protect extracellular matrix (ECM), as well as the reduction of angiogenic factor release. These findings provide a foundation for exploring the potential of SCGS in the development of new anti-tumor and anti-metastasis drugs and open up a new field in cancer research.

PMID:39218533 | DOI:10.1016/j.carbpol.2024.122466

Permalink for 'The 2022 WHO classification of tumors of the pituitary gland: An update on aggressive and metastatic pituitary neuroendocrine tumors'

The 2022 WHO classification of tumors of the pituitary gland: An update on aggressive and metastatic pituitary neuroendocrine tumors

Fetched: September 3rd, 2024, 2:02am UTC by Olivera Casar-Borota

Brain Pathol. 2024 Sep 1:e13302. doi: 10.1111/bpa.13302. Online ahead of print.

ABSTRACT

The vast majority of pituitary neuroendocrine tumors (PitNETs) are benign and slow growing with a low relapse rate over many years after surgical resection. However, about 40% are locally invasive and may not be surgically cured, and about one percentage demonstrate an aggressive clinical behavior. Exceptionally, these aggressive tumors may metastasize outside the sellar region to the central nervous system and/or systemically. The 2017 (4th Edition) WHO Classification of Pituitary Tumors abandoned the terminology "atypical adenoma" for tumors previously considered to have potential for a more aggressive behavior since its prognostic value was not established. The 2022 (5th Edition) WHO Classification of the Pituitary Tumors emphasizes the concept that morphological features distinguish indolent tumors from locally aggressive ones, however, the proposed histological subtypes are not consistent with the real life clinical characteristics of patients with aggressive tumors/carcinomas. So far, no single clinical, radiological or histological parameter can determine the risk of growth or malignant progression. Novel promising molecular prognostic markers, such as mutations in ATRX, TP53, SF3B1, and epigenetic DNA modifications, will need to be verified in larger tumor cohorts. In this review, we provide a critical analysis of the WHO guidelines for prognostic stratification and diagnosis of aggressive and metastatic PitNETs. In addition, we discuss the new WHO recommendations for changing ICD-O and ICD-11 codes for PitNET tumor behavior from a neoplasm either "benign" or "unspecified, borderline, or uncertain behavior" to "malignant" neoplasm regardless of the clinical presentation, histopathological subtype, and tumor location. We encourage multidisciplinary initiatives for integrated clinical, histological and molecular classification, which would enable early recognition of these challenging tumors and initiation of more appropriate and aggressive treatments, ultimately improving the outcome.

PMID:39218431 | DOI:10.1111/bpa.13302

Fractional differentiation based image enhancement for automatic detection of malignant melanoma

Fetched: September 3rd, 2024, 2:02am UTC by Basmah Anber

BMC Med Imaging. 2024 Sep 2;24(1):231. doi: 10.1186/s12880-024-01400-7.

ABSTRACT

Recent improvements in artificial intelligence and computer vision make it possible to automatically detect abnormalities in medical images. Skin lesions are one broad class of them. There are types of lesions that cause skin cancer, again with several types. Melanoma is one of the deadliest types of skin cancer. Its early diagnosis is at utmost importance. The treatments are greatly aided with artificial intelligence by the quick and precise diagnosis of these conditions. The identification and delineation of boundaries inside skin lesions have shown promise when using the basic image processing approaches for edge detection. Further enhancements regarding edge detections are possible. In this paper, the use of fractional differentiation for improved edge detection is explored on the application of skin lesion detection. A framework based on fractional differential filters for edge detection in skin lesion images is proposed that can improve automatic detection rate of malignant melanoma. The derived images are used to enhance the input images. Obtained images then undergo a classification process based on deep learning. A well-studied dataset of HAM10000 is used in the experiments. The system achieves 81.04% accuracy with EfficientNet model using the proposed fractional derivative based enhancements whereas accuracies are around 77.94% when using original images. In almost all the experiments, the enhanced images improved the accuracy. The results show that the proposed method improves the recognition performance.

PMID:39223468 | DOI:10.1186/s12880-024-01400-7

Permalink for 'Insulinoma-associated protein-1 (INSM-1) is a useful diagnostic marker for the evaluation of primary thymic neuroendocrine neoplasms: an immunohistochemical study of 27 cases'

Insulinoma-associated protein-1 (INSM-1) is a useful diagnostic marker for the evaluation of primary thymic neuroendocrine neoplasms: an immunohistochemical study of 27 cases

Fetched: September 3rd, 2024, 2:02am UTC by David Suster

Virchows Arch. 2024 Sep 3. doi: 10.1007/s00428-024-03904-7. Online ahead of print.

ABSTRACT

Insulinoma-associated protein 1 (INSM1) immunohistochemistry has been established as a sensitive and reliable immunohistochemical marker for detecting neuroendocrine differentiation in tumors across various organ systems. However, this marker has not been adequately investigated in primary thymic neuroendocrine tumors. We have studied a series of 27 cases of primary neuroendocrine carcinomas of the thymus, including 3 typical carcinoids, 18 atypical carcinoids, 4 large cell neuroendocrine carcinomas, and 2 small cell carcinomas. Immunostaining on whole tissue sections for INSM-1 was evaluated. Results of immunostaining for chromogranin and synaptophysin were also evaluated. 26/27 tumors (96%) demonstrated nuclear positivity for INSM1. 18 tumors (67%) showed strong and diffuse nuclear staining (3 +), 3 tumors (11%) moderate (2 +) nuclear staining, and 5 tumors (19%) showed weak (1 +) nuclear staining. The average percentage of tumor cells positive for INSM1 was 76%. Only one tumor, a small cell carcinoma, was negative. All tumors were positive for synaptophysin, and 26/27 (96%) were positive for chromogranin A. This study confirms that INSM1 immunohistochemistry is a sensitive marker of neuroendocrine differentiation in primary thymic neuroendocrine neoplasms and demonstrates similar performance characteristics compared to other organ systems. The nuclear staining with this marker offers the advantage of eliminating some of the ambiguity in the interpretation sometimes encountered with other markers. An added advantage is the consistent staining across the entire spectrum of neuroendocrine tumors of this organ.

PMID:39223347 | DOI:10.1007/s00428-024-03904-7

Trends in Invasive Melanoma Thickness in Norway, 1983-2019

Fetched: September 3rd, 2024, 2:02am UTC by Raju Rimal

Acta Derm Venereol. 2024 Sep 2;104:adv26110. doi: 10.2340/actadv.v104.26110.

ABSTRACT

Monitoring melanoma incidence time trends by tumour thickness is essential to understanding the evolution of melanoma occurrence and guiding prevention strategies. To assess long-term incidence trends, tumour thickness was extracted from pathology reports in the Cancer Registry of Norway (1983-2007) and the Norwegian Melanoma Registry (2008-2019), n = 45,635 patients. Across all anatomic sites, T1 (â‰¤ 1 mm) incidence increased most (men annual percentage change [AAPC] = 4.6, 95% confidence interval [95% CI] 4.2-5.0; women AAPC = 3.2, 95% CI 2.8-3.6); the increase was steep until 1989/90, followed by a plateau, and a further steep increase from 2004/05. Increased incidence was also observed for T2 (>1.0-2.0) melanoma (men AAPC = 2.8, 95% CI 2.4-3.2; women AAPC = 1.5, 95% CI 1.1-1.9), and T3 (>2.0-4.0) in men (AAPC = 1.4, 95% CI 0.9-1.9). T4 (>4.0) melanoma followed a similar overall pattern (men AAPC = 1.3, 95% CI 0.9-1.7, head/neck, upper limbs, and trunk; women AAPC = 0.9, 95% CI 0.4-1.4, upper limbs and trunk). Men had the highest T3 and T4 incidence and the sex difference increased with age. Regarding birth cohorts, age-specific incidence increased in all T categories in the oldest age groups, while stabilizing in younger patients born after 1950. Overall, the steep increase in T1 melanoma was not accompanied by a decrease in thick melanoma.

PMID:39221835 | DOI:10.2340/actadv.v104.26110

Autoimmune gastritis studies and gastric cancer: True renaissance or bibliometric illusion

Fetched: September 3rd, 2024, 2:02am UTC by Vasily Isakov

World J Gastroenterol. 2024 Aug 28;30(32):3783-3790. doi: 10.3748/wjg.v30.i32.3783.

ABSTRACT

A bibliometric analysis of studies dedicated to autoimmune gastritis (AIG) recently published demonstrated a noteworthy surge in publications over the last three years. This can be explained by numerous publications from different regions of the world reporting the results of several studies that stimulated reassessment of our view of AIG as a precancerous condition. Follow-up studies and retrospective analyses showed that the risk of gastric cancer (GC) in AIG patients is much lower than expected if the patients ever being infected with Helicobacter pylori (H. pylori) were excluded. The low prevalence of precancerous lesions, such as the incomplete type of intestinal metaplasia, may explain the low risk of GC in AIG patients because the spasmolytic polypeptide-expressing metaplasia commonly observed in AIG does not involve clonal reprogramming of the gastric gland and can be considered as an adaptive change rather than a true precancerous lesion. However, changes in gastric secretion due to the progression of gastric atrophy during the course of AIG cause changes in the gastric mic-robiome, stimulating the growth of bacterial species such as streptococci, which may promote the development of precancerous lesions and GC. Thus, Streptococcus anginosus exhibited a robust proinflammatory response and induced the gastritis-atrophy-metaplasia-dysplasia sequence in mice, reproducing the well-established process for carcinogenesis associated with H. pylori. Prospective studies in H. pylori-naÃ¯ve patients evaluating gastric microbiome changes during the long-term course of AIG might provide an explanation for the enigmatic increase in GC incidence in the last decades in younger cohorts, which has been reported in economically developed countries.

PMID:39221066 | PMC:PMC11362875 | DOI:10.3748/wjg.v30.i32.3783

Permalink for 'Enucleation of insulinoma using laparoscopic distal pancreatectomy with a focus on vascular and splenic preservation: a case report'

Enucleation of insulinoma using laparoscopic distal pancreatectomy with a focus on vascular and splenic preservation: a case report

Fetched: September 3rd, 2024, 2:02am UTC by Luis F Marcial-Cuevas

J Surg Case Rep. 2024 Aug 30;2024(8):rjae561. doi: 10.1093/jscr/rjae561. eCollection 2024 Aug.

ABSTRACT

Insulinomas represent <10% of pancreatic tumors. It is a functional neuroendocrine tumor that can cause recurrent and severe episodes of loss of consciousness due to hypoglycemia. Surgical removal is the only curative treatment. The selection of the optimal surgical technique must be individualized for each patient. Currently, there are emerging innovations in less invasive techniques that reduce morbidity. We present the case of a 23-year-old woman who underwent enucleation of an insulinoma localized at the tip of the pancreatic tail after laparoscopic surgery, with a focus on vascular and splenic preservation. The tumor was safely identified during surgery and enucleated without injury to the spleen and adjacent vascular structures or postoperative complications.

PMID:39220171 | PMC:PMC11364455 | DOI:10.1093/jscr/rjae561

Permalink for 'Primary coexisting adenocarcinoma of the colon and neuroendocrine tumor of the duodenum: A case report and review of the literature'

Primary coexisting adenocarcinoma of the colon and neuroendocrine tumor of the duodenum: A case report and review of the literature

Fetched: September 3rd, 2024, 2:02am UTC by Song Fei

World J Gastrointest Surg. 2024 Aug 27;16(8):2724-2734. doi: 10.4240/wjgs.v16.i8.2724.

ABSTRACT

BACKGROUND: Neuroendocrine tumors (NETs) arise from the body's diffuse endocrine system. Coexisting primary adenocarcinoma of the colon and NETs of the duodenum (D-NETs) is a rare occurrence in clinical practice. The classification and treatment criteria for D-NETs combined with a second primary cancer have not yet been determined.

CASE SUMMARY: We report the details of a case involving female patient with coexisting primary adenocarcinoma of the colon and a D-NET diagnosed by imaging and surgical specimens. The tumors were treated by surgery and four courses of chemotherapy. The patient achieved a favorable clinical prognosis.

CONCLUSION: Coexisting primary adenocarcinoma of the colon and D-NET were diagnosed by imaging, laboratory indicators, and surgical specimens. Surgical resection combined with chemotherapy was a safe, clinically effective, and cost-effective treatment.

PMID:39220064 | PMC:PMC11362920 | DOI:10.4240/wjgs.v16.i8.2724

Superior and inferior vena cava syndrome caused by a rare lung cancer: A case report

Fetched: September 3rd, 2024, 2:02am UTC by Amey Joshi

Clin Case Rep. 2024 Aug 30;12(9):e9391. doi: 10.1002/ccr3.9391. eCollection 2024 Sep.

ABSTRACT

Superior vena cava syndrome (SVCS) is commonly caused by mediastinal malignancies. Early identification through clinical signs and imaging is critical to avoid complications including cerebral and laryngeal edema, and cardiogenic shock. We present a case of large cell neuroendocrine carcinoma causing superior and inferior vena cava compression that responded well to radiotherapy and chemotherapy.

PMID:39219783 | PMC:PMC11364610 | DOI:10.1002/ccr3.9391

What is behind the declining incidence of melanoma in younger Australians?

Fetched: September 2nd, 2024, 2:01am UTC by Anne E Cust

Med J Aust. 2024 Sep 2;221(5):246-247. doi: 10.5694/mja2.52411.

NO ABSTRACT

PMID:39217599 | DOI:10.5694/mja2.52411

Changes in the incidence of melanoma in Australia, 2006-2021, by age group and ancestry: a modelling study

Fetched: September 2nd, 2024, 2:01am UTC by David C Whiteman

Med J Aust. 2024 Sep 2;221(5):251-257. doi: 10.5694/mja2.52404.

ABSTRACT

OBJECTIVES: To estimate the incidence of melanoma in Australia among people with ancestries associated with low, moderate, or high risk of melanoma, by sex and 5-year age group; to establish whether age-specific incidence rates by ancestry risk group have changed over time.

STUDY DESIGN: Modelling study; United States (SEER database) melanoma incidence rates for representative ancestral populations and Australian census data (2006, 2011, 2016, 2021) used to estimate Australian melanoma incidence rates by ancestry-based risk.

SETTING, PARTICIPANTS: Australia, 2006-2021.

MAIN OUTCOME MEASURES: Age-specific invasive melanoma incidence rates, and average annual percentage change (AAPC) in age-specific melanoma rates, by ancestry-based risk group, sex, and 5-year age group.

RESULTS: The proportion of people in Australia who reported high risk (European) ancestry declined from 85.3% in 2006 to 71.1% in 2021. The estimated age-standardised melanoma incidence rate was higher for people with high risk ancestry (2021: males, 82.2 [95% confidence interval {CI}, 80.5-83.8] cases per 100 000 population; females, 58.5 [95% CI, 57.0-59.9] cases per 100 000 population) than for all Australians (males, 67.8 [95% CI, 66.5-69.2] cases per 100 000 population; females, 45.4 [95% CI, 44.3-46.5] cases per 100 000 population). AAPCs were consistently positive for Australians aged 50 years or older, both overall and for people with high risk ancestry, but were statistically significant only for some age groups beyond 65 years. AAPCs were negative for people aged 34 years or younger, but were generally not statistically significant.

CONCLUSIONS: Melanoma incidence has declined in some younger age groups in Australia, including among people with high risk ancestry. Social and behavioural changes over the same period that lead to lower levels of ultraviolet radiation exposure probably contributed to these changes.

PMID:39217597 | DOI:10.5694/mja2.52404

Permalink for 'Solid-state electron-mediated z-scheme heterostructured semiconductor nanomaterials induce dual programmed cell death for melanoma therapy'

Solid-state electron-mediated z-scheme heterostructured semiconductor nanomaterials induce dual programmed cell death for melanoma therapy

Fetched: September 2nd, 2024, 2:01am UTC by Yiping Ren

J Nanobiotechnology. 2024 Aug 31;22(1):526. doi: 10.1186/s12951-024-02770-4.

ABSTRACT

The programmed cell death (PCD) pathway removes functionally insignificant, infection-prone, or potentially tumorigenic cells, underscoring its important role in maintaining the stability of the internal environment and warding off cancer and a host of other diseases. PCD includes various forms, such as apoptosis, copper death, iron death, and cellular pyroptosis. However, emerging solid-state electron-mediated Z-scheme heterostructured semiconductor nanomaterials with high electron-hole (e-h⁺) separation as a new method for inducing PCD have not been well studied. We synthesize the Bi2S3-Bi2O3-Au-PEG nanorods (BB-A-P NRs) Z-scheme heterostructured semiconductor has a higher redox capacity and biocompatibility. Firstly, the BB-A-P NRs are excited by near-infrared (NIR) light, which mimics the action of catalase by supplying oxygen (O2) and converting it to a single-linear state of oxygen (¹O2) via e-h⁺ transfer. Secondly, they react with hydrogen peroxide (H2O2) and water (H2O) in tumor to produce hydroxyl radicals (â€¢OH), inducing apoptosis. Intriguingly, the Caspase-1/Gasdermin D (GSDMD)-dependent conventional pyroptosis pathway induced cellular pyroptosis activated by apoptosis and reactive oxygen species (ROS) which causes the intense release of damage associated molecular patterns (DAMPs), leading to the inflammatory death of tumor cells. This, in turn, activates the immunological environment to achieve immunogenic cell death (ICD). BB-A-P enables computed tomography imaging, which allows for visualization of the treatment. BB-A-P activated dual PCD can be viewed as an effective mode of cell death that coordinates the intracellular environment, and the various pathways are interrelated and mutually reinforcing which shows promising therapeutic effects and provides a new strategy for eliminating anoxic tumors.

PMID:39217372 | PMC:PMC11365183 | DOI:10.1186/s12951-024-02770-4

Permalink for 'Longitudinal multiomics analysis of aggressive pituitary neuroendocrine tumors: comparing primary and recurrent tumors from the same patient, reveals genomic stability and heterogeneous transcriptomic profiles with alterations in metabolic pathways'

Longitudinal multiomics analysis of aggressive pituitary neuroendocrine tumors: comparing primary and recurrent tumors from the same patient, reveals genomic stability and heterogeneous transcriptomic profiles with alterations in metabolic pathways

Fetched: September 2nd, 2024, 2:01am UTC by Keiko Taniguchi-Ponciano

Acta Neuropathol Commun. 2024 Aug 31;12(1):142. doi: 10.1186/s40478-024-01796-x.

ABSTRACT

Pituitary neuroendocrine tumors (PitNET) represent the vast majority of sellar masses. Some behave aggressively, growing rapidly and invading surrounding tissues, with high rates of recurrence and resistance to therapy. Our aim was to establish patterns of genomic, transcriptomic and methylomic evolution throughout time in primary and recurrent tumors from the same patient. Therefore, we performed transcriptome- and exome-sequencing and methylome microarrays of aggressive, primary, and recurrent PitNET from the same patient. Primary and recurrent tumors showed a similar exome profile, potentially indicating a stable genome over time. In contrast, the transcriptome of primary and recurrent PitNET was dissimilar. Gonadotroph, silent corticotroph, as well as metastatic corticotroph and a somatotroph PitNET expressed genes related to fatty acid biosynthesis and metabolism, phosphatidylinositol signaling, glycerophospholipid and phospholipase D signaling, respectively. Diacylglycerol kinase gamma (DGKG), a key enzyme in glycerophospholipid metabolism and phosphatidylinositol signaling pathways, was differentially expressed between primary and recurrent PitNET. These alterations did not seem to be regulated by DNA methylation, but rather by several transcription factors. Molecular docking showed that dasatinib, a small molecule tyrosine kinase inhibitor used in the treatment of chronic lymphocytic and acute lymphoblastic leukemia, could target DGKG. Dasatinib induced apoptosis and decreased proliferation in GH3 cells. Our data indicate that pituitary tumorigenesis could be driven by transcriptomically heterogeneous clones, and we describe alternative pharmacological therapies for aggressive and recurrent PitNET.

PMID:39217365 | PMC:PMC11365143 | DOI:10.1186/s40478-024-01796-x

Transoral diode laser-assisted resection of a tongue base schwannoma

Fetched: September 2nd, 2024, 2:01am UTC by Mavra Sarwar

BMJ Case Rep. 2024 Aug 31;17(8):e260536. doi: 10.1136/bcr-2024-260536.

ABSTRACT

Schwannomas are benign peripheral nerve sheath tumours with a low risk of malignant transformation. About 25%-40% are in the head and neck region with the posterior third of the tongue being a rather rare site of its growth, and a lesion at this site is understandably difficult to approach and treat. Being benign and encapsulated, surgical excision is in the mainstay of treatment. Symptoms can range from a globus pharyngeus and dysphagia to airway compromise depending on the size and site. Traditionally, a paramedian lip split approach with paramedian mandibulotomy and mandible swing may be used. However, some recent reports of the use of carbon dioxide laser and robotic surgery for tongue base lesions are seen in the literature. Our case report is a unique addition to the management strategies for such tongue base lesions as we employed diode 980 nm laser using a minimally invasive transoral approach with a successful outcome.

PMID:39216893 | DOI:10.1136/bcr-2024-260536

Prolactin Secreting Pituitary Carcinoma and the Role of Peptide Receptor Radionuclide Therapy: A Brief Report

Fetched: September 2nd, 2024, 2:01am UTC by Nitish Agarwal

Neurol India. 2024 Jul 1;72(4):871-876. doi: 10.4103/neurol-india.Neurol-India-D-24-00529. Epub 2024 Aug 31.

ABSTRACT

Pituitary carcinoma is a rare entity comprising 0.1-0.2% of all pituitary tumors and presents significant diagnostic and therapeutic challenges. Intraspinal drop metastasis in these tumors is even rarer. We report a case of a prolactin secreting pituitary carcinoma with intracranial metastasis and multiple intraspinal drop metastasis. This is the first case where 68Gallium labelled [1,4,7,10 - tetraazacyclododecane - 1,4,7,10 - tetraacetic acid] -1- NaI3 - octreotide (68Ga-DOTANOC) whole-body positron emission tomography-computed tomography (PET-CT) has been used in a case of malignant prolactinoma, in an attempt to ascertain the somatostatin receptor (SSTR) expression on tumor cells. Through this paper, we suggest that SSTR targeted radionuclide therapy could have a potential role in aggressive pituitary tumors and pituitary carcinomas similar to the promising role of lutetium-labelled peptides in inoperable or metastasized gastroentero-pancreatic neuroendocrine tumors (GEP-NETs).

PMID:39216050 | DOI:10.4103/neurol-india.Neurol-India-D-24-00529

Facial Nerve Preserving Subtotal Excision for Large Vestibular Schwannoma: An Institution-Based Functional Outcome Study

Fetched: September 2nd, 2024, 2:01am UTC by Santhosh K S Annayappa

Neurol India. 2024 Jul 1;72(4):811-816. doi: 10.4103/neurol-india.NI_951_20. Epub 2024 Aug 31.

ABSTRACT

BACKGROUND: The ideal goal of treatment for medium to large vestibular schwannoma is complete tumor removal with preservation of all cranial nerves. However, despite the advancements in microsurgery and intraoperative monitoring, the risk of facial nerve dysfunction following total resection varies between 31% and 57%. Currently, the goal of treatment for large tumors is shifting from total excision to facial nerve preservation.

OBJECTIVE: To evaluate the facial nerve outcome in patients who underwent subtotal excision with or without subsequent gamma knife radiosurgery for large vestibular schwannomas in our institute.

METHODS AND MATERIAL: All patients who underwent primary surgery for large vestibular schwannomas between January 2012 and December 2016 were analyzed retrospectively. Cases where total excision was not done and a residue was left behind to prevent facial nerve injury during surgery were included in the study.

RESULTS: A total of 52 patients who met the inclusion criteria were analyzed. At final follow-up, 70% of patients had good facial nerve function (H-B grade 1 and 2). In patients with normal facial nerve function preoperatively, 81% (25/31) of them had good facial nerve outcomes (H-B grade 1 and 2), whereas in patients with preexisting facial nerve deficits, nearly 62% (13/21) of them either maintained or had improvement in their facial nerve grades.

CONCLUSION: Good facial nerve outcomes and tumor control rate is obtained by subtotal excision of VS followed by upfront or delayed GKRS; however, there is a need for long-term follow-up to detect recurrences in these slow-growing tumors.

PMID:39216039 | DOI:10.4103/neurol-india.NI_951_20

Permalink for 'Real-World Study of Lanreotide Autogel in Routine Practice in Patients with Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs) in Hong Kong and Taiwan'

Real-World Study of Lanreotide Autogel in Routine Practice in Patients with Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs) in Hong Kong and Taiwan

Fetched: September 2nd, 2024, 2:01am UTC by Jen-Shi Chen

Oncol Ther. 2024 Aug 31. doi: 10.1007/s40487-024-00302-6. Online ahead of print.

ABSTRACT

INTRODUCTION: There is a lack of data on the efficacy, effectiveness, and safety of lanreotide autogel in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) of Chinese ethnicity. This non-interventional, retrospective study evaluated the effectiveness and safety of lanreotide autogel in patients of Chinese ethnicity with GEP-NETs in clinical practice.

METHODS: Patient charts were abstracted from five hospitals in Hong Kong and Taiwan (July-September 2021), where lanreotide autogel is approved for treating GEP-NETs. Included patients were adults with unresectable, metastatic, or locally advanced GEP-NETs who received a first injection (index) of lanreotide autogel 120 mg between 01 January 2017 and 30 June 2020 (planned sample size: N = 30). Follow-up ran from index to a maximum of 48 (Â± 4) weeks or until disease progression, start of new antitumor treatment, or death. The primary endpoint was progression-free survival (PFS) rate at week 48 (Â±4), and secondary endpoints included PFS rate at week 24 (Â±4), estimated using Kaplan-Meier analyses. All analyses were descriptive.

RESULTS: Of 27 patients enrolled, 22 (81.5%) had 48 weeks of follow-up. Tumors of pancreatic origin were the most common (73.9%). PFS rate was 0.96 (95% confidence interval: 0.72 - 0.99) at 24 weeks and 0.82 (0.53-0.94) at 48 weeks. Overall, 74.1% patients experienced â‰¥ 1 treatment-emergent adverse event; none were serious. No deaths were reported.

CONCLUSIONS: Lanreotide autogel was well tolerated and showed good tumor control rate in a real-world setting. These findings align with results from previous studies in Caucasian, Japanese, and Korean patients, thus supporting lanreotide autogel for treating patients with GEP-NETs of Chinese ethnicity.

PMID:39215958 | DOI:10.1007/s40487-024-00302-6

Neuroendocrine tumor masquerading as hepatic hydatid cyst

Fetched: September 2nd, 2024, 2:01am UTC by Arpit Shastri

Indian J Gastroenterol. 2024 Aug 31. doi: 10.1007/s12664-024-01677-0. Online ahead of print.

NO ABSTRACT

PMID:39215897 | DOI:10.1007/s12664-024-01677-0

$Permalink for 'Correction to: Entinostat in patients with relapsed or refractory abdominal neuroendocrine tumors'$

Correction to: Entinostat in patients with relapsed or refractory abdominal neuroendocrine tumors

Fetched: September 2nd, 2024, 2:01am UTC

Oncologist. 2024 Aug 31:oyae199. doi: 10.1093/oncolo/oyae199. Online ahead of print.

NO ABSTRACT

PMID:39215827 | DOI:10.1093/oncolo/oyae199

Robot-Assisted Right S3 Segmentectomy of a Neuroendocrine Tumor

Fetched: September 2nd, 2024, 2:01am UTC by Purab D Kothari

Innovations (Phila). 2024 Aug 31:15569845241272237. doi: 10.1177/15569845241272237. Online ahead of print.

NO ABSTRACT

PMID:39215659 | DOI:10.1177/15569845241272237

Identification of Immune Checkpoint Inhibitor-Induced Diabetes

Fetched: September 1st, 2024, 2:01am UTC by Karina N Ruiz-Esteves

JAMA Oncol. 2024 Aug 29:e243104. doi: 10.1001/jamaoncol.2024.3104. Online ahead of print.

ABSTRACT

IMPORTANCE: Immune checkpoint inhibitors (ICIs) have revolutionized cancer care; however, accompanying immune-related adverse events (irAEs) confer substantial morbidity and occasional mortality. Life-threatening irAEs may require permanent cessation of ICI, even in patients with positive tumor response. Therefore, it is imperative to comprehensively define the spectrum of irAEs to aid individualized decision-making around the initiation of ICI therapy.

OBJECTIVE: To define incidence, risk factors, and clinical spectrum of an irreversible and life-threatening irAE: ICI-induced diabetes.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study, conducted at an academic integrated health care system examined 14 328 adult patients treated with ICIs, including 64 patients who developed ICI-induced diabetes, from July 2010 to January 2022. The data were analyzed from 2022 to 2023. Cases of ICI-induced diabetes were manually confirmed; detailed clinical phenotyping was performed at diagnosis and 1-year follow-up. For 862 patients, genotyping data were available, and polygenic risk for type 1 diabetes was determined.

MAIN OUTCOMES AND MEASURES: For ICI-induced diabetes cases and controls, demographic characteristics, comorbidities, tumor category, and ICI category were compared. Among ICI-induced diabetes cases, markers of glycemic physiology were examined at diagnosis and 1-year follow-up. For patients with available genotyping, a published type 1 diabetes polygenic score (T1D GRS2) was calculated.

RESULTS: Of 14 328 participants, 6571 (45.9%) were women, and the median (range) age was 66 (8-106) years. The prevalence of ICI-induced diabetes among ICI-treated patients was 0.45% (64 of 14 328), with an incidence of 124.8 per 100 000 person-years. Preexisting type 2 diabetes (odds ratio [OR], 5.91; 95% CI, 3.34-10.45) and treatment with combination ICI (OR, 2.57; 95% CI, 1.44-4.59) were significant clinical risk factors of ICI-induced diabetes. T1D GRS2 was associated with ICI-induced diabetes risk, with an OR of 4.4 (95% CI, 1.8-10.5) for patients in the top decile of T1D GRS2, demonstrating a genetic association between spontaneous autoimmunity and irAEs. Patients with ICI-induced diabetes were in 3 distinct phenotypic categories based on autoantibodies and residual pancreatic function, with varying severity of initial presentation.

CONCLUSIONS AND RELEVANCE: The results of this analysis of 14 328 ICI-treated patients followed up from ICI initiation determined the incidence, risk factors and clinical spectrum of ICI-induced diabetes. Widespread implementation of this approach across organ-specific irAEs may enhance diagnosis and management of these conditions, and this becomes especially pertinent as ICI treatment rapidly expands to treat a wide spectrum of cancers and is used at earlier stages of treatment.

PMID:39207773 | PMC:PMC11362970 | DOI:10.1001/jamaoncol.2024.3104

Permalink for 'Feasibility of a deep-inspiration breath-hold [18F]AlF-NOTA-LM3 PET/CT imaging on upper-abdominal lesions in NET patients: in comparison with respiratory-gated PET/CT'

Feasibility of a deep-inspiration breath-hold [18F]AlF-NOTA-LM3 PET/CT imaging on upper-abdominal lesions in NET patients: in comparison with respiratory-gated PET/CT

Fetched: September 1st, 2024, 2:01am UTC by Haiqiong Zhang

EJNMMI Phys. 2024 Aug 29;11(1):75. doi: 10.1186/s40658-024-00677-5.

ABSTRACT

PURPOSES: To explore the clinical feasibility and efficacy of a deep inspiration breath-hold (BH) PET/CT using [¹⁸F]AlF-NOTA-LM3 on upper abdominal lesions in patients with neuroendocrine tumors (NETs).

METHODS: Twenty-three patients underwent a free-breath (FB) whole-body PET/CT, including a 10 min/bed scan for the upper abdomen with a vital signal monitoring for respiratory gating (RG) followed by a 20-second BH PET/CT covering the same axial range. For the upper abdomen bed, the following PET series was reconstructed: a 2-min FB PET; RG PET (6 bins); a 20-second and 15-second BH PET (BH_15 and BH_20). Semi-quantitative analysis was performed to compare liver SUVmean, lesion SUVmax, MTV, its percentage difference and target-to-background ratio (TBR) between both BH PET and RG PET images. Subgroup analysis considered lesion location, MTV and SUVmax. A 5-point Likert scale was used to perform visual analysis and any missed or additional lesions were identified compared with RG PET.

RESULTS: Quantitative analysis on overall lesions (n = 78) revealed higher SUVmax and TBR, and smaller MTV for both BH PET compared to FB and RG PET, with lesion location-specific variations. Neither significant difference was observed in all metrics between RG and FB PET in larger lesions, nor in MTV in lower-uptake lesions. However, both BH PET significantly enhanced these measurements. In the visual analysis, both BH PET showed noninferior performance to RG PET, and were evaluated clinically acceptable. Additional and missed lesions were observed in FB and both BH PET compared with RG PET, but didn't alter the clinical management. The BH_15 PET showed comparable performance to BH_20 PET in any comparison.

CONCLUSION: The BH PET/CT using [¹⁸F]AlF-NOTA-LM3 is effective in detecting upper abdominal lesions, offering more accurate quantitative measurements. Using a novel PET/CT scanner, a 15-second BH PET can provide comparable and superior performance to RG PET, indicating potential feasibility in clinical routines.

PMID:39207609 | PMC:PMC11362407 | DOI:10.1186/s40658-024-00677-5

Central nervous system metastasis in melanoma patients: a retrospective cohort study, 2015-2019

Fetched: September 1st, 2024, 2:01am UTC by Aria Wei

Arch Dermatol Res. 2024 Aug 29;316(8):582. doi: 10.1007/s00403-024-03246-z.

NO ABSTRACT

PMID:39207606 | DOI:10.1007/s00403-024-03246-z

Nail technicians as partners in early melanoma detection: bridging the knowledge gap

Fetched: September 1st, 2024, 2:01am UTC by Kritin K Verma

Arch Dermatol Res. 2024 Aug 29;316(8):586. doi: 10.1007/s00403-024-03342-0.

NO ABSTRACT

PMID:39207598 | DOI:10.1007/s00403-024-03342-0

Treatment of malignant melanoma with coxsackievirus A21 (V937): An emerging oncolytic virotherapy

Fetched: September 1st, 2024, 2:01am UTC by Goranit Sakunchotpanit

Exp Dermatol. 2024 Sep;33(9):e15169. doi: 10.1111/exd.15169.

ABSTRACT

Despite rising melanoma incidence in recent decades, there is a trend towards overall decreased mortality, reflecting multiple factors including improved treatment options for metastatic disease. While local treatments are the mainstay for early-stage melanoma, metastatic disease necessitates systemic treatment, with oncolytic virotherapy emerging as a promising option. For this review, articles were retrieved from PubMed from 1964 through 2024. We conducted title, abstract and full-text screening in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify articles describing the use of coxsackievirus A21 (V937), either as monotherapy or as part of combination therapy for malignant melanoma. Fifteen articles met inclusion criteria, offering preclinical and clinical data on V937's efficacy in reducing tumour burden. In addition to reporting manageable safety profiles, clinical trial data examining intratumoral V937 combination therapy with pembrolizumab and ipilimumab also endorsed favourable objective response rates compared to immune checkpoint inhibitor monotherapy (47% vs. 38% and 21% vs. 10%, respectively). In contrast, intravenous V937 monotherapy failed to yield additional benefit in a cohort of patients with Stage IIIC/IV melanoma (n = 3) despite achieving detectable levels in tumour tissue (1 Ã— 10⁹ TCID50). Although small subsets of patients experienced severe adverse effects and study design limitations imposed constraints on collected data, evidence for the efficacy of V937 remains encouraging. With few clinical trials evaluating V937 in melanoma, additional data is required before routine usage in standard treatment for metastatic lesions.

PMID:39207089 | DOI:10.1111/exd.15169

Permalink for 'An aggressive Cushing's syndrome originating from a rare thymic neuroendocrine tumor, controlled successfully with fluconazole and octreotide therapy before surgery'

An aggressive Cushing's syndrome originating from a rare thymic neuroendocrine tumor, controlled successfully with fluconazole and octreotide therapy before surgery

Fetched: September 1st, 2024, 2:01am UTC by Sinem Kargun

J Cancer Res Ther. 2024 Aug 16. doi: 10.4103/jcrt.jcrt_644_22. Online ahead of print.

ABSTRACT

Cushing's syndromes (CSs) due to the thymic neuroendocrine tumors are rarely seen. Here, a case of ectopic CS originating from an atypical neuroendocrine tumor has been presented. A 49-year-old woman was hospitalized with symptoms of fatigue, chest pressure, dyspnea, muscle weakness, and resistant hypertension. There was marked hyperpigmentation in the whole-body surface suggestive of adrenocorticotropic hormone (ACTH) excess and there were physical features of CS. There was deep hypokalemia. Basal hormone profile, dexamethasone suppression tests, midnight cortisol, and 24-hour urine cortisol levels were suggestive of ectopic CS. The pituitary magnetic resonance imaging revealed a 5 mm cystic lesion and the patient refused inferior petrosal sinus sampling. Thorax computerized tomography showed an anterior mediastinal mass. A fluorodeoxyglucose-positron emission tomography showed the same mediastinal lesion (suvmax: 11.4), and no other tumor focus was detected. There was an aggressive cortisol excess causing acute respiratory distress syndrome, making it difficult to perform the surgery. We immediately started fluconazole and octreotide therapy and were successful in lowering the cortisol level. Then a complete resection of the tumor had been able to be surgically performed and tumor cells showed strong cytoplasmic immunopositivity with ACTH. A definitive diagnosis of "ACTH secreting atypical thymic carcinoid tumor" was rendered based on the histopathological and immunohistochemical features. There was only surrounding vessel invasion, and no lymphoid or other organ metastases were detected. As there were surrounding vessel invasions, a two-cycle regimen cisplatin-etoposide chemotherapy and radiotherapy were employed. After surgical and medical therapy, the cortisol and ACTH levels turned to normal. The patient is in biochemical and clinical remission and has no tumor recurrence yet. Ectopic ACTH-producing thymic carcinoids are rare but life-threatening tumors because of the underlying malignancy and severe hypercortisolemia. It is important to consider this disease and perform appropriate treatment at the right time. Today, surgery is the standard therapeutic modality if it is possible to perform, but there is not a clear and constant recommendation for nonsurgical therapeutic modalities. Further studies are needed for the optimal treatment strategies.

PMID:39207033 | DOI:10.4103/jcrt.jcrt_644_22

Permalink for 'Administration of intratumoral GD2-directed interleukin-2 immunocytokine and local radiation therapy to activate immune rejection of spontaneous canine melanoma: Erratum'

Administration of intratumoral GD2-directed interleukin-2 immunocytokine and local radiation therapy to activate immune rejection of spontaneous canine melanoma: Erratum

Fetched: September 1st, 2024, 2:01am UTC

Melanoma Res. 2024 Oct 1;34(5):473. doi: 10.1097/CMR.0000000000000996. Epub 2024 Aug 28.

NO ABSTRACT

PMID:39206844 | DOI:10.1097/CMR.0000000000000996

The death rate for melanoma remained unchanged in the USA during the coronavirus disease 2019 pandemic

Fetched: September 1st, 2024, 2:01am UTC by Camilla Mattiuzzi

Melanoma Res. 2024 Oct 1;34(5):472. doi: 10.1097/CMR.0000000000000987. Epub 2024 Aug 28.

NO ABSTRACT

PMID:39206843 | DOI:10.1097/CMR.0000000000000987

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Rare Cancer News & Clinical Trials » Endocrine/Neuroendocrine

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Endocrine/Neuroendocrine (571 unread)

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