Rare Cancer News & Clinical Trials » Endocrine/Neuroendocrine

Endocrine/Neuroendocrine (534 unread)

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Ectopic Cushing's syndrome in a patient with metastatic Merkel cell carcinoma: A case report

Fetched: September 27th, 2022, 5:01am GMT by Avraham Ishay

World J Clin Cases. 2022 Aug 6;10(22):7989-7993. doi: 10.12998/wjcc.v10.i22.7989.

ABSTRACT

BACKGROUND: Ectopic Cushing syndrome (ECS) is a rare condition commonly associated with neuroendocrine tumors (NET), mainly bronchial carcinoids. The association of paraneoplastic syndrome with Merkle cell carcinoma (MCC) is limited to individual case reports.

CASE SUMMARY: In this article we report an unusual and striking presentation of ECS in a patient with known metastatic MCC. An elderly patient presented with new onset severe hypertension, hyperglycemia and hypokalemia, muscle wasting, and peripheral edema. A diagnosis of adrenocorticotropic hormone dependent, non-pituitary, Cushing syndrome was established. Medical therapy inhibiting adrenal function was promptly started but unfortunately the patient survived only a few days after diagnosis.

CONCLUSION: The occurrence of an aggressive form of ECS in patients with NET should be recognized as an ominous event. To our knowledge, the association of this complication in a patient with MCC had not been reported.

PMID:36158508 | PMC:PMC9372868 | DOI:10.12998/wjcc.v10.i22.7989

Therapeutic Potential of 5'-Methylschweinfurthin G in Merkel Cell Polyomavirus-Positive Merkel Cell Carcinoma

Fetched: September 24th, 2022, 5:01am GMT by Emily J Koubek

Viruses. 2022 Aug 23;14(9):1848. doi: 10.3390/v14091848.

ABSTRACT

Merkel cell carcinoma (MCC) is a rare but aggressive form of skin cancer predominantly caused by the human Merkel cell polyomavirus (MCPyV). Treatment for MCC includes excision and radiotherapy of local disease, and chemotherapy or immunotherapy for metastatic disease. The schweinfurthin family of natural compounds previously displayed potent and selective growth inhibitory activity against the NCI-60 panel of human-derived cancer cell lines. Here, we investigated the impact of schweinfurthin on human MCC cell lines. Treatment with the schweinfurthin analog, 5'-methylschweinfurth G (MeSG also known as TTI-3114), impaired metabolic activity through induction of an apoptotic pathway. MeSG also selectively inhibited PI3K/AKT and MAPK/ERK pathways in the MCPyV-positive MCC cell line, MS-1. Interestingly, expression of the MCPyV small T (sT) oncogene selectively sensitizes mouse embryonic fibroblasts to MeSG. These results suggest that the schweinfurthin family of compounds display promising potential as a novel therapeutic option for virus-induced MCCs.

PMID:36146655 | PMC:PMC9506461 | DOI:10.3390/v14091848

Polycomb Directed Cell Fate Decisions in Development and Cancer

Fetched: September 23rd, 2022, 5:01am GMT by Beatriz German

Epigenomes. 2022 Sep 6;6(3):28. doi: 10.3390/epigenomes6030028.

ABSTRACT

The polycomb group (PcG) proteins are a subset of transcription regulators highly conserved throughout evolution. Their principal role is to epigenetically modify chromatin landscapes and control the expression of master transcriptional programs to determine cellular identity. The two mayor PcG protein complexes that have been identified in mammals to date are Polycomb Repressive Complex 1 (PRC1) and 2 (PRC2). These protein complexes selectively repress gene expression via the induction of covalent post-translational histone modifications, promoting chromatin structure stabilization. PRC2 catalyzes the histone H3 methylation at lysine 27 (H3K27me1/2/3), inducing heterochromatin structures. This activity is controlled by the formation of a multi-subunit complex, which includes enhancer of zeste (EZH2), embryonic ectoderm development protein (EED), and suppressor of zeste 12 (SUZ12). This review will summarize the latest insights into how PRC2 in mammalian cells regulates transcription to orchestrate the temporal and tissue-specific expression of genes to determine cell identity and cell-fate decisions. We will specifically describe how PRC2 dysregulation in different cell types can promote phenotypic plasticity and/or non-mutational epigenetic reprogramming, inducing the development of highly aggressive epithelial neuroendocrine carcinomas, including prostate, small cell lung, and Merkel cell cancer. With this, EZH2 has emerged as an important actionable therapeutic target in such cancers.

PMID:36135315 | PMC:PMC9497807 | DOI:10.3390/epigenomes6030028

Antibody-Drug Conjugates for Melanoma and Other Skin Malignancies

Fetched: September 21st, 2022, 5:02am GMT by Rachel Goodman

Curr Treat Options Oncol. 2022 Sep 20. doi: 10.1007/s11864-022-01018-3. Online ahead of print.

ABSTRACT

While most skin malignancies are successfully treated with surgical excision, advanced and metastatic skin malignancies still often have poor long-term outcomes despite therapeutic advances. Antibody-drug conjugates (ADCs) serve as a potentially promising novel therapeutic approach to treat advanced skin cancers as they combine antibody-associated antigen specificity with cytotoxic anti-tumor effects, thereby maximizing efficacy and minimizing systemic toxicity. While no ADCs have gained regulatory approval for advanced skin cancers, several promising agents are undergoing preclinical and clinical investigation. In addition to identifying and validating skin cancer antigen targets, the key to maximizing therapeutic success is the careful development of each component of the ADC complex: antibodies, cytotoxic drugs, and linkers. It is the optimization of each of these components that will be integral in overcoming resistance, maximizing safety, and improving long-term clinical outcomes.

PMID:36125618 | DOI:10.1007/s11864-022-01018-3

HIV-related Merkel cell carcinoma: A report of three cases from the UK

Fetched: September 17th, 2022, 5:03am GMT by Evdoxia Panou

Int J STD AIDS. 2022 Sep 13:9564624221123872. doi: 10.1177/09564624221123872. Online ahead of print.

ABSTRACT

Merkel cell carcinoma (MCC) of the skin is a rare, aggressive and often fatal neuroendocrine skin cancer. The incidence of MCC has significantly increased in the last decades. Factors that have been associated with the development of MCC include infection with Merkel Cell polyomavirus (MCPyV), ultraviolet exposure, hematologic malignancies and immunosuppression.We present three cases of patients living with HIV who were diagnosed with MCC. HIV cases associated with MCC have been rarely reported and to our knowledge, not yet before in the UK.

PMID:36112903 | DOI:10.1177/09564624221123872

Permalink for 'Combined nivolumab and ipilimumab with or without stereotactic body radiation therapy for advanced Merkel cell carcinoma: a randomised, open label, phase 2 trial'

Combined nivolumab and ipilimumab with or without stereotactic body radiation therapy for advanced Merkel cell carcinoma: a randomised, open label, phase 2 trial

Fetched: September 16th, 2022, 5:02am GMT by Sungjune Kim

Lancet. 2022 Sep 24;400(10357):1008-1019. doi: 10.1016/S0140-6736(22)01659-2. Epub 2022 Sep 12.

ABSTRACT

BACKGROUND: Merkel cell carcinoma is among the most aggressive and lethal of primary skin cancers, with a high rate of distant metastasis. Anti-programmed death receptor 1 (anti-PD-1) and programmed death ligand 1 (PD-L1) monotherapy is currently standard of care for unresectable, recurrent, or metastatic Merkel cell carcinoma. We assessed treatment with combined nivolumab plus ipilimumab, with or without stereotactic body radiotherapy (SBRT) in patients with advanced Merkel cell carcinoma as a first-line therapy or following previous treatment with anti-PD-1 and PD-L1 monotherapy.

METHODS: In this randomised, open label, phase 2 trial, we randomly assigned adults from two cancer sites in the USA (one in Florida and one in Ohio) to group A (combined nivolumab and ipilimumab) or group B (combined nivolumab and ipilimumab plus SBRT) in a 1:1 ratio. Eligible patients were aged at least 18 years with histologically proven advanced stage (unresectable, recurrent, or stage IV) Merkel cell carcinoma, a minimum of two tumour lesions measureable by CT, MRI or clinical exam, and tumour tissue available for exploratory biomarker analysis. Patients were stratified by previous immune-checkpoint inhibitor (ICI) status to receive nivolumab 240 mg intravenously every 2 weeks plus ipilimumab 1 mg/kg intravenously every 6 weeks (group A) or the same schedule of combined nivolumab and ipilimumab with the addition of SBRT to at least one tumour site (24 Gy in three fractions at week 2; group B). Patients had to have at least two measurable sites of disease so one non-irradiated site could be followed for response. The primary endpoint was objective response rate (ORR) in all randomly assigned patients who received at least one dose of combined nivolumab and ipilimumab. ORR was defined as the proportion of patients with a complete response or partial response per immune-related Response Evaluation Criteria in Solid Tumours. Response was assessed every 12 weeks. Safety was assessed in all patients. This trial is registered with ClinicalTrials.gov, NCT03071406.

FINDINGS: 50 patients (25 in both group A and group B) were enrolled between March 14, 2017, and Dec 21, 2021, including 24 ICI-naive patients (13 [52%] of 25 group A patients and 11 [44%] of 25 group B patients]) and 26 patients with previous ICI (12 [48%] of 25 group A patients and 14 [56%] of 25 group B patients]). One patient in group B did not receive SBRT due to concerns about excess toxicity. Median follow-up was 14·6 months (IQR 9·1-26·5). Two patients in group B were excluded from the analysis of the primary endpoint because the target lesions were irradiated and so the patients were deemed non-evaluable. Of the ICI-naive patients, 22 (100%) of 22 (95% CI 82-100) had an objective response, including nine (41% [95% CI 21-63]) with complete response. Of the patients who had previously had ICI exposure, eight (31%) of 26 patients (95% CI 15-52) had an objective response and four (15% [5-36]) had a complete response. No significant differences in ORR were observed between groups A (18 [72%] of 25 patients) and B (12 [52%] of 23 patients; p=0·26). Grade 3 or 4 treatment-related adverse events were observed in 10 (40%) of 25 patients in group A and 8 (32%) of 25 patients in group B.

INTERPRETATION: First-line combined nivolumab and ipilimumab in patients with advanced Merkel cell carcinoma showed a high ORR with durable responses and an expected safety profile. Combined nivolumab and ipilimumab also showed clinical benefit in patients with previous anti-PD-1 and PD-L1 treatment. Addition of SBRT did not improve efficacy of combined nivolumab and ipilimumab. The combination of nivolumab and ipilimumab represents a new first-line and salvage therapeutic option for advanced Merkel cell carcinoma.

FUNDING: Bristol Myers Squibb Rare Population Malignancy Program.

PMID:36108657 | DOI:10.1016/S0140-6736(22)01659-2

Combined nivolumab and ipilimumab in non-resectable Merkel cell carcinoma

Fetched: September 16th, 2022, 5:02am GMT by Philippe Saiag

Lancet. 2022 Sep 24;400(10357):976-977. doi: 10.1016/S0140-6736(22)01749-4. Epub 2022 Sep 12.

NO ABSTRACT

PMID:36108656 | DOI:10.1016/S0140-6736(22)01749-4

Permalink for 'Cutaneous Merkel cell carcinoma (MCC): A report from the 16th Annual Meeting for Multicenter Merkel Interest Group - A supplementation to the new European guidelines 2022 on MCC'

Cutaneous Merkel cell carcinoma (MCC): A report from the 16th Annual Meeting for Multicenter Merkel Interest Group - A supplementation to the new European guidelines 2022 on MCC

Fetched: September 15th, 2022, 5:02am GMT by Ettore Minutilli

Eur J Cancer. 2022 Sep 9;175:107-109. doi: 10.1016/j.ejca.2022.07.008. Online ahead of print.

NO ABSTRACT

PMID:36099669 | DOI:10.1016/j.ejca.2022.07.008

m6A modification of mRNA in skin diseases

Fetched: September 15th, 2022, 5:02am GMT by Zhuoxian Yan

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2022 Aug 28;47(8):1154-1162. doi: 10.11817/j.issn.1672-7347.2022.210332.

ABSTRACT

N6-methyladenosine (m6A) is the predominant post-transcriptional modification for eukaryotic mRNA. It's regulated by methyltransferases, demethylases, and m6A binding proteins, and plays an important role in regulating splicing, translation, and degradation of mRNA. Skin diseases, especially immune skin diseases and skin tumors, have a complicated pathogenesis and are refractory to treatment, seriously affecting the patient quality of life. Recent studies have revealed that m6A and its regulatory proteins can affect the development of numerous skin diseases. The m6A modification was found to be involved in skin accessory development, including hair follicle and sweat gland formation. The level of m6A modification was significantly altered in a variety of skin diseases including melanoma, cutaneous squamous cell carcinoma, Merkel cell carcinoma, and psoriasis, and affected a variety of biological processes including cell proliferation and differentiation migration. The m6A and its regulatory proteins may become potential molecular markers or therapeutic targets for skin diseases, and have promising clinical applications in early diagnosis, efficacy determination, prognosis prediction, and gene therapy of skin diseases.

PMID:36097784 | DOI:10.11817/j.issn.1672-7347.2022.210332

Correction: Nationwide multidisciplinary consensus on the clinical management of Merkel cell carcinoma: a Delphi panel

Fetched: September 13th, 2022, 5:01am GMT

J Immunother Cancer. 2022 Sep;10(9):e004742corr1. doi: 10.1136/jitc-2022-004742corr1.

NO ABSTRACT

PMID:36096539 | PMC:PMC9472105 | DOI:10.1136/jitc-2022-004742corr1

Skin manifestations of neuroendocrine neoplasms: review of the literature

Fetched: September 13th, 2022, 5:01am GMT by Irena Walecka

Postepy Dermatol Alergol. 2022 Aug;39(4):656-661. doi: 10.5114/ada.2021.112073. Epub 2022 Jan 18.

ABSTRACT

Neuroendocrine neoplasms (NENs) are a heterogeneous group of rare tumours derived from peptidergic neurons and specialized neuroendocrine cells capable of secreting various peptides or amines. These cells may be present in endocrine tissue or diffused in the tissues of the digestive or respiratory system. The article reviews the characteristic features of NENs, with particular emphasis on skin manifestations, such as necrolytic migratory erythema (NME), tongue inflammation, angular cheilitis, venous thrombosis and alopecia in glucagonoma; "flushing", "lion face", pellagra skin symptoms, "scleroderma-like features without Raynaud's phenomenon" in carcinoid tumours. The paper also presents the clinical picture of the neuroendocrine tumour of the skin - Merkel cell carcinoma. The aim of this study was to draw attention to the need for precise and comprehensive diagnosis of the patients, with particular emphasis on skin lesions as a revelator of neuroendocrine tumours. This management allows for the early implementation of appropriate treatment.

PMID:36090712 | PMC:PMC9454360 | DOI:10.5114/ada.2021.112073

Hyperpigmented nodule on a young Black man

Fetched: September 13th, 2022, 5:01am GMT by Dinah T Hodge

JAAD Case Rep. 2022 Jul 4;27:153-155. doi: 10.1016/j.jdcr.2022.05.044. eCollection 2022 Sep.

NO ABSTRACT

PMID:36090385 | PMC:PMC9449643 | DOI:10.1016/j.jdcr.2022.05.044

Pitx2 is a useful marker of midgut-derived neuroendocrine tumours - an immunohistochemical study of 224 cases

Fetched: September 13th, 2022, 5:01am GMT by Jiri Soukup

Histopathology. 2022 Sep 12. doi: 10.1111/his.14789. Online ahead of print.

ABSTRACT

Pitx2 is a transcription factor responsible for establishment of the right-left axis and development of the gut and pituitary. In mouse embryos, Pitx2 is expressed in the greater curvature of the stomach and midgut. Previously, Pitx2 was studied in pituitary neuroendocrine tumours but not in other NETs. Pitx2 expression was immunohistochemically assessed in whole sections and tissue microarrays in a cohort of 224 neuroendocrine neoplasms, and was analysed in 29 cases. The cohort included 18 cauda equina NETs, 38 paragangliomas, 98 cases of primary visceral NETs from different organs, 23 metastases of visceral NETs and 47 neuroendocrine carcinomas (NECs). Pitx2 expression was observed in 29.5% (29 of 98) NETs and 14.9% (7 of 47) NECs, but was not observed in any paraganglioma or cauda equina NET. Pitx2 was observed only in tumours of midgut-derived organs, including the small intestine (100%, 20 of 20), appendix (88.9%, eight of nine) and large intestine (9.1%, one of 11 - only caecal NET). The NETs of remaining locations were negative. Pitx2 was 96.7% sensitive and 100% specific for NETs of midgut origin. In NECs, Pitx2 positivity was observed in goblet cell adenocarcinoma (75%, three of four), medullary thyroid carcinoma (42.9, three of seven) and one Merkel cell carcinoma (25%, one of four). In metastatic NETs, Pitx2 was observed in all the tumours originating in the small intestine (n = 17) or caecum (n = 1). No positivity was observed in tumours from other locations (four pancreas, one lung). We observed no correlation between immunoreactivity and mRNA expression. Thus, Pitx2 immunohistochemistry can be helpful in assessing the midgut origin of NETs.

PMID:36089904 | DOI:10.1111/his.14789

Permalink for 'Primary cutaneous SMARCA4-deficient undifferentiated malignant neoplasm: first two cases with clinicopathologic and molecular comparison to eight visceral counterparts'

Primary cutaneous SMARCA4-deficient undifferentiated malignant neoplasm: first two cases with clinicopathologic and molecular comparison to eight visceral counterparts

Fetched: September 11th, 2022, 5:01am GMT by Eleanor Russell-Goldman

Mod Pathol. 2022 Sep 9. doi: 10.1038/s41379-022-01152-1. Online ahead of print.

ABSTRACT

SMARCA4-deficient undifferentiated malignant neoplasms (SD-UMN) comprise a group of aggressive tumors with epithelioid morphology that are characterized by loss of function of SMARCA4, a component of the SWI/SNF chromatin remodeling complex. SD-UMN was first recognized in the thoracic cavity but is now appreciated to occur at multiple anatomic sites. A notable exception has been skin. Here we report the first two cases of primary cutaneous SD-UMN and compare their features to a cohort of eight visceral cases arising in lung, gastrointestinal tract, and gallbladder. Evidence for a bona fide cutaneous origin included extensive clinical, radiologic, and serologic analyses that failed to identify a metastatic source as well as the molecular identification of a UV-associated mutational pattern. The cutaneous cases showed strikingly similar morphologic, immunohistochemical, and molecular features to the visceral cases, strongly suggesting that they belong to this family of tumors. In addition to biallelic inactivation of SMARCA4, both cutaneous tumors also showed biallelic inactivation of TP53 and CDKN2A, findings which also appear common in visceral cases. One patient died of disease at 18 months after diagnosis, consistent with the aggressive nature of this tumor. Our results expand the anatomic spectrum of SD-UMN, adding this entity to an already challenging differential diagnosis that includes melanoma, squamous cell carcinoma, Merkel cell carcinoma, epithelioid sarcoma, and others. Given the potentially aggressive nature of SD-UMN, the timely and accurate diagnosis of this entity may have implications for prognosis and therapy.

PMID:36085356 | DOI:10.1038/s41379-022-01152-1

Utilization of Sentinel Lymph Node Biopsy for Merkel Cell Carcinoma

Fetched: September 11th, 2022, 5:01am GMT by Melika Marani

J Am Acad Dermatol. 2022 Sep 6:S0190-9622(22)02638-X. doi: 10.1016/j.jaad.2022.09.002. Online ahead of print.

NO ABSTRACT

PMID:36084788 | DOI:10.1016/j.jaad.2022.09.002

Diagnostic Test Accuracy of 18 F-FDG PET or PET/CT in Merkel Cell Carcinoma

Fetched: September 9th, 2022, 5:02am GMT by Sung Ryul Shim

Clin Nucl Med. 2022 Oct 1;47(10):843-848. doi: 10.1097/RLU.0000000000004321. Epub 2022 Jul 6.

ABSTRACT

OBJECTIVE: The purpose of the current study was to evaluate the diagnostic accuracies of 18 F-FDG PET or PET/CT for diagnosis of Merkel cell carcinoma (MCC) through a systematic review and meta-analysis.

METHODS: The PubMed, Cochrane database, and EMBASE database, from January 1990 to January 31, 2022, were searched for studies evaluating diagnostic performance of 18 F-FDG PET or PET/CT for MCC. We determined the sensitivities and specificities across studies, calculated positive and negative likelihood ratios (LR+ and LR-), and constructed summary receiver operating characteristic curves.

RESULTS: Across 9 studies (259 patients), the pooled sensitivity of 18 F-FDG PET or PET/CT was 0.91 (95% confidence interval [CI], 0.85-0.95) and a pooled specificity of 0.93 (95% CI, 0.86-0.97). Likelihood ratio syntheses gave an overall LR+ of 14.0 (95% CI, 6.6-29.6) and LR- of 0.09 (95% CI, 0.05-0.17). The pooled diagnostic odds ratio was 153 (95% CI, 57-416).

CONCLUSION: 18 F-FDG PET/CT showed an excellent performance for diagnosis of MCC. The likelihood ratio scattergram indicated that 18 F-FDG PET or PET/CT is useful for exclusion and confirmation of MCC. Further large multicenter studies would be necessary to substantiate the diagnostic accuracy of 18 F-FDG PET or PET/CT for MCC patients.

PMID:35777979 | DOI:10.1097/RLU.0000000000004321

Reddish painless rapidly growing tumor of the upper eyelid with a smooth surface: Merkel cell carcinoma

Fetched: September 9th, 2022, 5:02am GMT by B Holbach

Ophthalmologie. 2022 Sep;119(9):875. doi: 10.1007/s00347-022-01699-z. Epub 2022 Aug 2.

NO ABSTRACT

PMID:35925363 | DOI:10.1007/s00347-022-01699-z

Delivery of Online Adaptive MRI-Guided Radiation Therapy for a Deaf Patient

Fetched: September 6th, 2022, 5:02am GMT by Lauren C Linkowski

Cureus. 2022 Aug 1;14(8):e27558. doi: 10.7759/cureus.27558. eCollection 2022 Aug.

ABSTRACT

MRI-guided radiation therapy (MRgRT) enables real-time imaging during treatment and daily online adaptive planning. It is particularly useful for areas of treatment that have been previously excluded or restricted from ablative doses due to potential damage to adjacent normal tissue. In certain cases, ablative doses to metastatic lesions may be justified and treated with MRgRT using video-assisted gated breath-hold adjustments throughout delivery. The workflow relies on patient biofeedback and auditory cues. A 74-year-old deaf male with a history of prostate cancer status post prostatectomy was found to have an enlarged cervical lymph node, which was excised with histopathology demonstrating Merkel cell carcinoma. Approximately one year after treatment with two cycles of pembrolizumab, which was subsequently discontinued due to toxicity, surveillance imaging demonstrated an enlarging left adrenal nodule. It was initially stable for an additional seven months with pembrolizumab rechallenge but was again found enlarged on subsequent imaging. The patient underwent MRg stereotactic body radiation therapy (MRgSBRT) to a total dose of 60 Gy in five fractions to this isolated site of progression. The patient was equipped with mirrored glasses to view the tracking structure with respect to gating the boundary structure, and the traditional reliance on verbal cues for coaching was reimagined to rely on visual cues instead. Follow-up positron emission tomography/CT (PET/CT) two weeks after treatment demonstrated interval resolution of the left adrenal metastatic nodule and a return to symmetric bilateral adrenal gland metabolic activity. The necessary MRgSBRT treatment for single metastatic lesions near normal tissue structures relies on verbal cues and coaching. However, deaf patients are unable to receive this treatment according to the traditional workflow model. Unique opportunities exist for the implementation of culturally competent care for the Deaf community, relying more heavily on visual cues, in radiation oncology practice.

PMID:36059359 | PMC:PMC9429821 | DOI:10.7759/cureus.27558

Permalink for 'Implication of IL6-positive Cancer-associated Fibroblasts in Merkel Cell Carcinoma Pathogenesis: A Possible Modulator of Immune Microenvironment'

Implication of IL6-positive Cancer-associated Fibroblasts in Merkel Cell Carcinoma Pathogenesis: A Possible Modulator of Immune Microenvironment

Fetched: August 31st, 2022, 5:02am GMT by Zhenlong Zheng

Anticancer Res. 2022 Sep;42(9):4359-4369. doi: 10.21873/anticanres.15936.

ABSTRACT

BACKGROUND/AIM: The role of cancer-associated fibroblasts (CAFs) in the pathogenesis of Merkel cell carcinoma (MCC) remains unknown. This study aimed to investigate the clinicopathological significance of CAF subpopulations and their association with tumor-infiltrating lymphocytes (TILs) in patients with MCC.

MATERIALS AND METHODS: Clinicopathological features and the status of microenvironment fibrosis (MF) around tumor masses were evaluated in 20 MCC patient and tissue sections. Alpha-smooth muscle actin (α-SMA)-positive CAFs (α-SMA⁺CAFs), interleukin-6-positive CAFs (IL6⁺CAFs), CD4-positive TILs (CD4⁺TILs), and CD8-positive TILs (CD8⁺TILs) in MCC tissue samples were investigated using immunohistochemistry.

RESULTS: In a total of 20 MCC patients, high-MF was detected in 12 (60%) patients which was significantly associated with worse progression-free survival (p=0.048), but not with overall survival. CD4⁺/CD8⁺ TILs were frequently detected in MCC tissues. High-intra-tumoral CD8⁺TIL was significantly associated with better overall and progression-free survival (p=0.04 and p=0.015) in our cohort. High-αSMA⁺ CAFs were detected in 11 (55.0%) patients and high-IL6⁺CAFs in 10 (50.0%) patients. A negative association was found between high-IL6⁺CAF and high-intra-tumoral CD8⁺TILs (p=0.005). Patients with high IL6⁺CAFs showed worse overall/progression-free survival than patients with low-IL6⁺CAFs (p=0.022 and p=0.035).

CONCLUSION: IL6⁺CAFs may largely influence the tumor immune microenvironment of MCC by modulating distinct T-cell populations and functions. This study provides a possible therapeutic target to overcome resistance to immune therapies in MCC.

PMID:36039447 | DOI:10.21873/anticanres.15936

Metachronous Testicular Metastases from Merkel Cell Carcinoma (MCC): A Case Report and Literature Review

Fetched: August 31st, 2022, 5:02am GMT by Alice Laffi

Am J Case Rep. 2022 Aug 29;23:e936552. doi: 10.12659/AJCR.936552.

ABSTRACT

BACKGROUND Merkel cell carcinoma (MCC) is a rare neuroendocrine neoplasm. The immunotherapy era has dramatically changed MCC prognosis, but unresponsive and progressive diseases after anti- programmed death-ligand 1 (PDL1) treatment still represent a challenge. MCC can metastasize in virtually every anatomical site, also during immunotherapy, and the reasons for primary resistance are debated. Testes are a rare metastatic site, accounting only 0.04% of autoptic detections in patients with more common malignancies. We report a case of a patient with metachronous and bilateral testes metastases after a previous radically treated MCC. CASE REPORT A 57-year-old man underwent radical surgery for left knee MCC. The oncologic follow-up was negative until 4 years later when the patient developed a right testis lesion. The patient underwent right orchiectomy for the suspicion of testicular primary malignancy, but the pathologist report revealed MCC metastasis. Subsequent radiologic assessment detected new bone metastases. The patient was treated with immunotherapy, experiencing a complete response. After 20 months of treatment, a further assessment revealed a new single left testis metastasis. A left orchiectomy was performed and immunotherapy was continued, maintaining a complete response. CONCLUSIONS There are few reports that MCC can be associated with uncommon metastases in testicular tissue. The present case suggests the testis represents another "sanctuary" site for the metastasizing process and host immune response. Considering the dramatic impact of immunotherapy in MCC prognosis, the study of these rare cases may aid the understanding of intrinsic resistance mechanisms to anti-PDL1, which affects a percentage of MCC patients.

PMID:36031755 | DOI:10.12659/AJCR.936552

Synergistic targeting of the PI3K/mTOR and MAPK/ERK pathways in Merkel cell carcinoma

Fetched: August 26th, 2022, 5:02am GMT by Arturo Temblador

Tumour Virus Res. 2022 Aug 22;14:200244. doi: 10.1016/j.tvr.2022.200244. Online ahead of print.

ABSTRACT

Merkel cell carcinoma (MCC) is an aggressive type of skin cancer, which is caused either by integration of the oncogenic Merkel cell polyomavirus (MCPyV) or by accumulation of UV-light induced mutations. Since the response to immune-checkpoint inhibitors is limited, new therapeutic agents need to be explored. Previous studies have shown that MCC cell lines and xenografts are sensitive to MLN0128, a dual mTOR1/2 inhibitor. Prompted by these results and considering that the PI3K/mTOR and MAPK/ERK pathways are the most commonly deregulated pathways in cancer, the combination of MLN0128 with the MEK1/2 inhibitor trametinib was investigated. Importantly, the combined targeting showed to be synergistic in MCC cell lines and induced alterations in the protein levels of downstream elements of the targeted pathways. This synergistic activity implies a reduction in the dose of each inhibitor necessary to reach the same effect that when used as single agents. Therefore, this is a promising approach to improve the clinical management of MCC and to overcome the limited efficacy of single drug regimens owed to the appearance of toxicity or drug resistance.

PMID:36007768 | PMC:PMC9449649 | DOI:10.1016/j.tvr.2022.200244

Permalink for 'Dataset for the Reporting of Merkel Cell Carcinoma: Recommendations From the International Collaboration on Cancer Reporting (ICCR)'

Dataset for the Reporting of Merkel Cell Carcinoma: Recommendations From the International Collaboration on Cancer Reporting (ICCR)

Fetched: August 25th, 2022, 5:02am GMT by Klaus J Busam

Am J Surg Pathol. 2022 Aug 25. doi: 10.1097/PAS.0000000000001959. Online ahead of print.

ABSTRACT

Accurate and complete pathology reports are critical for the optimal management of cancer patients. Protocols for the pathologic reporting of Merkel cell carcinoma (MCC) have been developed independently by the Royal College of Pathologists (UK) and the College of American Pathologists. In this study, data elements for pathologic reporting of MCC were analyzed by an international panel of pathologists and clinicians with the aim of developing a common, internationally agreed upon dataset useful for clinical practice. The International Collaboration on Cancer Reporting expert review panel developed a protocol containing "core" (required) and "noncore" (recommended) elements. Core elements were defined as those that had evidentiary support and were unanimously agreed upon by the review panel as essential for the clinical management, staging, and/or assessment of prognosis in patients with MCC. Noncore elements were those considered to be clinical of interest, but with lesser degrees of supportive evidence or nonactionable implications. Ten core data elements for pathology reports on primary MCC were defined. Development and agreement on this evidence-based protocol at an international level was accomplished in a timely and efficient manner. The template developed for melanoma reporting was used as a structural base for this initiative. It is applicable to, and may facilitate the development of, protocols for other tumor types. Widespread utilization of an internationally agreed upon structured pathology dataset for MCC can be expected to lead to improved patient management. It should also facilitate collaborative clinical research.

PMID:36001458 | DOI:10.1097/PAS.0000000000001959

Permalink for 'Real-world clinical outcomes with avelumab in patients with Merkel cell carcinoma treated in the USA: a multicenter chart review study'

Real-world clinical outcomes with avelumab in patients with Merkel cell carcinoma treated in the USA: a multicenter chart review study

Fetched: August 20th, 2022, 5:02am GMT by Shailender Bhatia

J Immunother Cancer. 2022 Aug;10(8):e004904. doi: 10.1136/jitc-2022-004904.

ABSTRACT

BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive, cutaneous neuroendocrine neoplasm with annual incidence rates of 0.13-1.6 cases/100,000/year worldwide as of 2018. Chemotherapy for metastatic MCC (mMCC) has high objective response rates (ORRs), but responses are not durable and overall survival (OS) is poor. Avelumab (anti-programmed death-ligand 1) has demonstrated meaningful survival benefit and durable responses in clinical trials for mMCC. This study investigated real-world clinical outcomes in avelumab-treated patients with advanced (stage IIIB/IV) MCC in US academic medical centers.

METHODS: We conducted a retrospective chart review of patients with advanced MCC who initiated avelumab between March 1, 2017, and July 31, 2019, at six US academic centers. Data were requested for eligible patients from index date through December 31, 2020. Descriptive analyses were conducted to assess demographic and clinical characteristics, real-world ORR (rwORR), real-world duration of response, real-world progression-free survival (rwPFS), and OS.

RESULTS: Ninety patients with advanced MCC (82%, stage IV; 18%, stage IIIB) received avelumab. Median follow-up was 20.8 months (95% CI: 19.1 to 24.2). Median age was 68 years (range, 48-83), and the majority of patients were men (58%) and white (93%). The primary tumor was most commonly located on the lower limb (38%), with metastases mostly located in lymph nodes (68%), lung (52%), and viscera (52%). Approximately 42% and 26% of patients had an Eastern Cooperative Oncology Group performance status of 2 and 3, respectively. Seventy-three patients (81%) received avelumab as first-line treatment of advanced MCC, while 17 (19%) received avelumab as second-line or later treatment. The median duration of avelumab treatment was 13.5 months (95% CI: 6.4 to 30.6), with 42% of patients still receiving avelumab by the end of follow-up. Patients with avelumab treatment had an rwORR of 73% (95% CI: 64 to 83), median rwPFS of 24.4 months (95% CI: 8.31 to not estimable (NE)), and median OS of 30.7 months (95% CI: 11.2 to NE).

CONCLUSIONS: This real-world study of patients with advanced MCC demonstrated that avelumab treatment resulted in a high response rate with durable responses and prolonged survival. The study findings validate the results demonstrated in prospective clinical trials and other observational studies.

PMID:35981787 | PMC:PMC9394192 | DOI:10.1136/jitc-2022-004904

Readability of online patient education materials for Merkel cell carcinoma

Fetched: August 18th, 2022, 5:02am GMT by Yue Zhang

Arch Dermatol Res. 2022 Aug 17. doi: 10.1007/s00403-022-02381-9. Online ahead of print.

ABSTRACT

The Internet is a significant source of information for patients. According to the National Institutes of Health, patient education materials (PEMs) should be at or below an eighth-grade reading level. Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer that affects patients over 50 with rising incidence. Unfortunately, US adults aged 65 + have the least proficiency in health literacy. This study assessed the readability of online PEMs and factors that contribute to readability. We retrieved 50 PEM websites and extracted primary content. A readability software package calculated six readability statistics and generated a consensus standard readability. Overall, only eight articles had a standard reading level of eighth-grade level or below (16%). The median standard reading level was at the 11th-grade level. We also examined MCC PEMs from cancer treatment institution websites (N = 20). We determined whether they contained institution-specific information, meaning they contained text information about the institution-specific expertise and specialist team. Websites containing this information (N = 13) had a significantly higher reading level than websites that did not (N = 7) in five of six readability metrics (p < 0.05). We concluded that MCC PEMs with institution-specific information led to significantly higher reading level scores. We propose that such information may increase cognitive load, as patients are learning about their disease and treatment and contending with the institution-specific information. The Cognitive Load Theory principles of intrinsic load (learning the material relevant to the disease and treatment) and extraneous load (institution-specific information and increased reading level) are constrained by limited working memory. Working memory decreases with age; hence, the patient demographic most sensitive to increased extraneous load tends to overlap with that of MCC. As patients typically read pages linked from their search engine, we suggest moving institution-specific information to another page, separate from the PEMs.

PMID:35976406 | DOI:10.1007/s00403-022-02381-9

Permalink for 'Discovery of novel druggable pockets on polyomavirus VP1 through crystallographic fragment-based screening to develop capsid assembly inhibitors'

Discovery of novel druggable pockets on polyomavirus VP1 through crystallographic fragment-based screening to develop capsid assembly inhibitors

Fetched: August 18th, 2022, 5:02am GMT by Evgenii M Osipov

RSC Chem Biol. 2022 Apr 29;3(8):1013-1027. doi: 10.1039/d2cb00052k. eCollection 2022 Aug 3.

ABSTRACT

Polyomaviruses are a family of ubiquitous double-stranded DNA viruses many of which are human pathogens. These include BK polyomavirus which causes severe urinary tract infection in immunocompromised patients and Merkel cell polyomavirus associated with aggressive cancers. The small genome of polyomaviruses lacks conventional drug targets, and no specific drugs are available at present. Here we focus on the main structural protein VP1 of BK polyomavirus which is responsible for icosahedral capsid formation. To provide a foundation towards rational drug design, we crystallized truncated VP1 pentamers and subjected them to a high-throughput screening for binding drug-like fragments through a direct X-ray analysis. To enable a highly performant screening, rigorous optimization of the crystallographic pipeline and processing with the latest generation PanDDA2 software were necessary. As a result, a total of 144 binding hits were established. Importantly, the hits are well clustered in six surface pockets. Three pockets are located on the outside of the pentamer and map on the regions where the 'invading' C-terminal arm of another pentamer is attached upon capsid assembly. Another set of three pockets is situated within the wide pore along the five-fold axis of the VP1 pentamer. These pockets are situated at the interaction interface with the minor capsid protein VP2 which is indispensable for normal functioning of the virus. Here we systematically analyse the three outside pockets which are highly conserved across various polyomaviruses, while point mutations in these pockets are detrimental for viral replication. We show that one of the pockets can accommodate antipsychotic drug trifluoperazine. For each pocket, we derive pharmacophore features which enable the design of small molecules preventing the interaction between VP1 pentamers and therefore inhibiting capsid assembly. Our data lay a foundation towards a rational development of first-in-class drugs targeting polyomavirus capsid.

PMID:35974998 | PMC:PMC9347357 | DOI:10.1039/d2cb00052k

Application of immune enhanced organoids in modeling personalized Merkel cell carcinoma research

Fetched: August 17th, 2022, 5:02am GMT by Steven D Forsythe

Sci Rep. 2022 Aug 16;12(1):13865. doi: 10.1038/s41598-022-17921-6.

ABSTRACT

Merkel cell carcinoma (MCC) is a rare neuroendocrine cutaneous cancer, with incidence of less than 1/100,000, low survival rates and variable response to chemotherapy or immunotherapy. Herein we explore the application of patient tumor organoids (PTOs) in modeling personalized research in this rare malignancy. Unsorted and non-expanded MCC tumor cells were isolated from surgical specimens and suspended in an ECM based hydrogel, along with patient matched blood and lymph node tissue to generate immune enhanced organoids (iPTOs). Organoids were treated with chemotherapy or immunotherapy agents and efficacy was determined by post-treatment viability. Nine specimens from seven patients were recruited from December 2018-January 2022. Establishment rate was 88.8% (8/9) for PTOs and 77.8% (7/9) for iPTOs. Histology on matched patient tissues and PTOs demonstrated expression of MCC markers. Chemotherapy response was exhibited in 4/6 (66.6%) specimens with cisplatin and doxorubicin as the most effective agents (4/6 PTO sets) while immunotherapy was not effective in tested iPTO sets. Four specimens from two patients demonstrated resistance to pembrolizumab, correlating with the corresponding patient's treatment response. Routine establishment and immune enhancement of MCC PTOs is feasible directly from resected surgical specimens allowing for personalized research and exploration of treatment regimens in the preclinical setting.

PMID:35974123 | PMC:PMC9380677 | DOI:10.1038/s41598-022-17921-6

AdAPT-001, an oncolytic adenovirus armed with a TGF-β trap, overcomes in vivo resistance to PD-L1-immunotherapy

Fetched: August 16th, 2022, 5:01am GMT by Christopher Larson

Am J Cancer Res. 2022 Jul 15;12(7):3141-3147. eCollection 2022.

ABSTRACT

Monoclonal antibodies targeting the programmed cell death protein-1/programmed cell death-ligand 1 (PD-1/PD-L1) and cytotoxic T lymphocyte-associated protein-4 (CTLA-4) axes have permanently changed the therapeutic landscape for multiple tumor types previously associated with a dismal prognosis such as melanoma, non-small cell lung cancer, renal cell carcinoma, bladder cancer, head and neck squamous cell carcinoma, MSI-high colorectal carcinoma, Merkel cell carcinoma, and Hodgkin lymphoma. However, only a subset of patients initially benefits from these inhibitors, and increasing clinical experience indicates that in a substantial proportion of initial responders, lethal secondary resistance ultimately develops months or years later. In this paper we evaluated combination therapy with a Phase 1 oncolytic adenovirus called AdAPT-001, armed with a TGF-β "trap" that binds to and neutralizes the immunosuppressive cytokine, TGF-β, and a checkpoint inhibitor, anti-PD-L1, in PD-L1 resistant tumors. The study, which was performed in an immunocompetent syngeneic ADS-12 mouse model, demonstrated that the combination of AdAPT-001 with PD-L1 blockade reversed PD-L1 resistance, potentially representing a future paradigm shift for patients that are primarily or secondarily resistant to checkpoint inhibitors.

PMID:35968324 | PMC:PMC9360241

Distinct radiation responses in virus-positive and virus-negative Merkel cell carcinoma

Fetched: August 12th, 2022, 5:01am GMT by Mona M Ahmed

J Invest Dermatol. 2022 Aug 8:S0022-202X(22)01732-8. doi: 10.1016/j.jid.2022.07.015. Online ahead of print.

NO ABSTRACT

PMID:35952731 | DOI:10.1016/j.jid.2022.07.015

Permalink for 'Racial and Ethnic Healthcare Disparities in Skin Cancer in the United States: A Review of Existing Inequities, Contributing Factors, and Potential Solutions'

Racial and Ethnic Healthcare Disparities in Skin Cancer in the United States: A Review of Existing Inequities, Contributing Factors, and Potential Solutions

Fetched: August 10th, 2022, 5:01am GMT by Kimberly Shao

J Clin Aesthet Dermatol. 2022 Jul;15(7):16-22.

ABSTRACT

OBJECTIVE: Racial and ethnic health disparities affect the diagnosis and management of melanoma and nonmelanoma skin cancers, leading to deleterious outcomes. Non-Hispanic White patients make up the majority of skin cancers cases, yet racial and ethnic minorities have poorer prognoses and outcomes. The skin cancer literature is fragmented with regards to potential contributors to these healthcare disparities. In this article, we provide a comprehensive review of the skin cancer literature to briefly quantify racial and ethnic inequities, highlight contributing factors, and propose practical changes that can be made.

METHODS: A PubMed search was completed to identify articles related to racial and ethnic health care disparities in the context of melanoma, basal cell carcinoma, squamous cell carcinoma, Merkel cell carcinoma, and dermatofibrosarcoma protuberans.

RESULTS: Relative to non-Hispanic White patients, patients of racial and ethnic minorities have differing clinical presentations of skin cancers and genetic risk factors. Insurance, access to specialty care, cultural beliefs, and available educational resources further contribute to racial and ethnic disparities.

LIMITATIONS: We are limited to the level of detail provided in the existing literature, and at some times are unable to distinguish race of Hispanic populations. We also acknowledge that there are different nationalities grouped under these broad labels as well as multi-racial populations that may not be accounted for.

CONCLUSION: Awareness of and familiarization with innate factors and potentially more modifiable contributors can help inform efforts to close the observed gap in racial and ethnic inequities.

PMID:35942012 | PMC:PMC9345197

Glypican-3 (GPC3) is associated with MCPyV-negative status and impaired outcome in Merkel cell carcinoma

Fetched: August 9th, 2022, 5:01am GMT by Sujatha Muralidharan

Oncotarget. 2022 Aug 3;13:960-967. doi: 10.18632/oncotarget.28260. eCollection 2022.

ABSTRACT

INTRODUCTION: Merkel cell carcinoma (MCC) is an aggressive skin cancer, related to the Merkel Cell Polyomavirus (MCPyV) in 80% of cases. Immune checkpoint inhibitors provide sustained benefit in about 50% of MCC patients with advanced disease. Glypican-3 (GPC3) is an oncofetal tumor antigen that is an attractive target for chimeric antigen receptor T cell therapy due to its highly restricted expression on normal tissue and high prevalence in several solid tumors. GPC3 is known to be expressed in MCC but its association with tumor characteristics or prognosis has not been reported. We investigated MCC GPC3 expression by immunohistochemistry (IHC) and its association with tumor characteristics, MCPyV status, and patient outcome.

METHODS: The GC33 antibody clone was validated for GPC3 IHC staining of tumor specimens in comparison to an established GPC3 IHC antibody. An MCC tissue microarray was stained for GPC3 by IHC using GC33 antibody. Association of GPC3+ IHC with baseline characteristics, MCPyV status (qPCR) and outcome (death from MCC/recurrence) were assessed.

RESULTS: Forty-two of 62 samples (67.7%) were GPC3+. GPC3 expression was more frequently observed in females (p = 0.048) and MCPyV-negative tumors (p = 0.021). By multivariate analysis, GPC3 expression was associated with increased death from disease (CSS) (hazard ratio [HR] 4.05, 95% CI 1.06-15.43), together with advanced age (HR 4.85, 95% CI 1.39-16.9) and male gender (HR 4.64, 95% CI 1.31-16.41).

CONCLUSIONS: GPC3 expression is frequent in MCC tumors, especially MCPyV-negative cases, and is associated with increased risk of death. High prevalence of surface GPC3 makes it a putative drug target.

PMID:35937502 | PMC:PMC9348696 | DOI:10.18632/oncotarget.28260

SATB2 Expression in Human Tumors

Fetched: August 3rd, 2022, 5:01am GMT by David Dum

Arch Pathol Lab Med. 2022 Aug 2. doi: 10.5858/arpa.2021-0317-OA. Online ahead of print.

ABSTRACT

CONTEXT.—: Special AT-rich sequence-binding protein 2 (SATB2) induces local chromatin loops to facilitate transcription. SATB2 immunostaining is commonly used as a marker for colorectal adenocarcinoma and osteosarcoma.

OBJECTIVE.—: To extend our knowledge on the diagnostic value of SATB2 analysis in a comprehensive set of human tumors.

DESIGN.—: Tissue microarrays with 15 012 samples from 120 tumor types and 608 samples of 76 different normal tissues were analyzed.

RESULTS.—: SATB2 positivity was found in 89 of 120 different tumor types (74%), including 59 of 120 (49%) with at least 1 moderately positive tumor and 38 of 120 tumor types (32%) with at least 1 strongly positive tumor. Expression was frequent in adenomas (44/42-47/44; 94%-96% positive), adenocarcinomas (1747 of 2023; 86%) and various subtypes of neuroendocrine neoplasms (3/7-12/12; 43%-100%) of the colorectum and appendix, Merkel cell carcinoma (25 of 34, 74%), osteosarcomas (15 of 25; 60%), and papillary renal cell carcinoma (RCC) (121 of 235; 52%). Associations to clinicopathologic tumor features were assessed in colorectal and kidney cancers. In colorectal cancer, weak SATB2 expression was linked to high pT (P < .001), nodal metastasis (P < .001), right-sided tumor location (P < .001), microsatellite instability (P < .001), and BRAF mutations (P = .02). In papillary RCC, low SATB2 expression was associated with high pT (P = .02), distant metastasis (P = .04), and reduced tumor-specific survival (P = .04). In clear cell RCC, low SATB2 expression was linked to high pT (P < .001), high Union for International Cancer Control stage (P < .001), high Thoenes grade (P = .02), and reduced recurrence-free survival (P = .02).

CONCLUSIONS.—: Strong SATB2 expression argues for a colorectal origin within adenocarcinomas and neuroendocrine neoplasms. Weak SATB2 expression reflects progression and poor prognosis in colorectal and kidney cancer.

PMID:35917493 | DOI:10.5858/arpa.2021-0317-OA

Permalink for 'Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of nonmelanoma skin cancer'

Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of nonmelanoma skin cancer

Fetched: July 29th, 2022, 5:01am GMT by Ann W Silk

J Immunother Cancer. 2022 Jul;10(7):e004434. doi: 10.1136/jitc-2021-004434.

ABSTRACT

Nonmelanoma skin cancers (NMSCs) are some of the most commonly diagnosed malignancies. In general, early-stage NMSCs have favorable outcomes; however, a small subset of patients develop resistant, advanced, or metastatic disease, or aggressive subtypes that are more challenging to treat successfully. Recently, immune checkpoint inhibitors (ICIs) have been approved by the US Food and Drug Administration (FDA) for the treatment of Merkel cell carcinoma (MCC), cutaneous squamous cell carcinoma (CSCC), and basal cell carcinoma (BCC). Although ICIs have demonstrated activity against NMSCs, the routine clinical use of these agents may be more challenging due to a number of factors including the lack of predictive biomarkers, the need to consider special patient populations, the management of toxicity, and the assessment of atypical responses. With the goal of improving patient care by providing expert guidance to the oncology community, the Society for Immunotherapy of Cancer (SITC) convened a multidisciplinary panel of experts to develop a clinical practice guideline (CPG). The expert panel drew on the published literature as well as their own clinical experience to develop recommendations for healthcare professionals on important aspects of immunotherapeutic treatment for NMSCs, including staging, biomarker testing, patient selection, therapy selection, post-treatment response evaluation and surveillance, and patient quality of life (QOL) considerations, among others. The evidence- and consensus-based recommendations in this CPG are intended to provide guidance to cancer care professionals treating patients with NMSCs.

PMID:35902131 | PMC:PMC9341183 | DOI:10.1136/jitc-2021-004434

Permalink for 'ASO Visual Abstract: An Internally Validated Prognostic Risk Score Model for Disease-Specific Survival in Clinical Stage I and II Merkel Cell Carcinoma'

ASO Visual Abstract: An Internally Validated Prognostic Risk Score Model for Disease-Specific Survival in Clinical Stage I and II Merkel Cell Carcinoma

Fetched: July 28th, 2022, 5:01am GMT by Adrienne B Shannon

Ann Surg Oncol. 2022 Oct;29(11):7045-7046. doi: 10.1245/s10434-022-12293-7.

NO ABSTRACT

PMID:35896923 | DOI:10.1245/s10434-022-12293-7

Activation of Oncogenic and Immune-Response Pathways Is Linked to Disease-Specific Survival in Merkel Cell Carcinoma

Fetched: July 28th, 2022, 5:01am GMT by Benjamin Sundqvist

Cancers (Basel). 2022 Jul 23;14(15):3591. doi: 10.3390/cancers14153591.

ABSTRACT

BACKGROUND: Merkel cell carcinoma (MCC) is a rare but highly aggressive neuroendocrine carcinoma of the skin with a poor prognosis. Improving the prognosis of MCC by means of targeted therapies requires further understanding of the mechanisms that drive tumor progression. In this study, we aimed to identify the genes, processes, and pathways that play the most crucial roles in determining MCC outcomes.

METHODS: We investigated transcriptomes generated by RNA sequencing of formalin-fixed paraffin-embedded tissue samples of 102 MCC patients and identified the genes that were upregulated among survivors and in patients who died from MCC. We subsequently cross-referenced these genes with online databases to investigate the functions and pathways they represent. We further investigated differential gene expression based on viral status in patients who died from MCC.

RESULTS: We found several novel genes associated with MCC-specific survival. Genes upregulated in patients who died from MCC were most notably associated with angiogenesis and the PI3K-Akt and MAPK pathways; their expression predominantly had no association with viral status in patients who died from MCC. Genes upregulated among survivors were largely associated with antigen presentation and immune response.

CONCLUSION: This outcome-based discrepancy in gene expression suggests that these pathways and processes likely play crucial roles in determining MCC outcomes.

PMID:35892849 | PMC:PMC9331388 | DOI:10.3390/cancers14153591

Permalink for 'Short-Interval, Low-Dose Peptide Receptor Radionuclide Therapy in Combination with PD-1 Checkpoint Immunotherapy Induces Remission in Immunocompromised Patients with Metastatic Merkel Cell Carcinoma'

Short-Interval, Low-Dose Peptide Receptor Radionuclide Therapy in Combination with PD-1 Checkpoint Immunotherapy Induces Remission in Immunocompromised Patients with Metastatic Merkel Cell Carcinoma

Fetched: July 28th, 2022, 5:01am GMT by Alexandra Aicher

Pharmaceutics. 2022 Jul 14;14(7):1466. doi: 10.3390/pharmaceutics14071466.

ABSTRACT

Merkel cell carcinoma (MCC) is a neuroendocrine skin cancer of the elderly, with high metastatic potential and poor prognosis. In particular, the primary resistance to immune checkpoint inhibitors (ICI) in metastatic (m)MCC patients represents a challenge not yet met by any efficient treatment modality. Herein, we describe a novel therapeutic concept with short-interval, low-dose ¹⁷⁷Lutetium (Lu)-high affinity (HA)-DOTATATE [¹⁷⁷Lu]Lu-HA-DOTATATE peptide receptor radionuclide therapy (SILD-PRRT) in combination with PD-1 ICI to induce remission in patients with ICI-resistant mMCC. We report on the initial refractory response of two immunocompromised mMCC patients to the PD-L1 inhibitor avelumab. After confirming the expression of somatostatin receptors (SSTR) on tumor cells by [⁶⁸Ga]Ga-HA-DOTATATE-PET/CT (PET/CT), we employed low-dose PRRT (up to six treatments, mean activity 3.5 GBq per cycle) at 3-6 weeks intervals in combination with the PD-1 inhibitor pembrolizumab to restore responsiveness to ICI. This combination enabled the synergistic application of PD-1 checkpoint immunotherapy with low-dose PRRT at more frequent intervals, and was very well tolerated by both patients. PET/CTs demonstrated remarkable responses at all metastatic sites (lymph nodes, distant skin, and bones), which were maintained for 3.6 and 4.8 months, respectively. Both patients eventually succumbed with progressive disease after 7.7 and 8 months, respectively, from the start of treatment with SILD-PRRT and pembrolizumab. We demonstrate that SILD-PRRT in combination with pembrolizumab is safe and well-tolerated, even in elderly, immunocompromised mMCC patients. The restoration of clinical responses in ICI-refractory patients as proposed here could potentially be used not only for patients with mMCC, but many other cancer types currently treated with PD-1/PD-L1 inhibitors.

PMID:35890361 | PMC:PMC9323617 | DOI:10.3390/pharmaceutics14071466

Viral Encoded miRNAs in Tumorigenesis: Theranostic Opportunities in Precision Oncology

Fetched: July 28th, 2022, 5:01am GMT by Rodney Hull

Microorganisms. 2022 Jul 18;10(7):1448. doi: 10.3390/microorganisms10071448.

ABSTRACT

About 15% of all human cancers have a viral etiology. Although progress has been made, understanding the viral oncogenesis and associated molecular mechanisms remain complex. The discovery of cellular miRNAs has led to major breakthroughs. Interestingly, viruses have also been discovered to encode their own miRNAs. These viral, small, non-coding miRNAs are also known as viral-miRNAs (v-miRNAs). Although the function of v-miRNAs largely remains to be elucidated, their role in tumorigenesis cannot be ignored. V-miRNAs have also been shown to exploit the cellular machinery to benefit viral replication and survival. Although the discovery of Hepatitis C virus (HCV), and its viral miRNAs, is a work in progress, the existence of HPV-, EBV-, HBV-, MCPyV- and KSHV-encoded miRNA has been documented. V-miRNAs have been shown to target host factors to advance tumorigenesis, evade and suppress the immune system, and deregulate both the cell cycle and the apoptotic machinery. Although the exact mechanisms of v-miRNAs-induced tumorigenesis are still unclear, v-miRNAs are active role-players in tumorigenesis, viral latency and cell transformation. Furthermore, v-miRNAs can function as posttranscriptional gene regulators of both viral and host genes. Thus, it has been proposed that v-miRNAs may serve as diagnostic biomarkers and therapeutic targets for cancers with a viral etiology. Although significant challenges exist in their clinical application, emerging reports demonstrate their potent role in precision medicine. This review will focus on the roles of HPV-, HCV-, EBV-, HBV-, MCPyV-, and KSHV-produced v-miRNAs in tumorigenesis, as effectors in immune evasion, as diagnostic biomarkers and as novel anti-cancer therapeutic targets. Finally, it will discuss the challenges and opportunities associated with v-miRNAs theranostics in precision oncology.

PMID:35889167 | PMC:PMC9321719 | DOI:10.3390/microorganisms10071448

The Role of Citrate Homeostasis in Merkel Cell Carcinoma Pathogenesis

Fetched: July 28th, 2022, 5:01am GMT by Konstantin Drexler

Cancers (Basel). 2022 Jul 14;14(14):3425. doi: 10.3390/cancers14143425.

ABSTRACT

Merkel cell carcinoma (MCC) is a rare but highly aggressive tumor of the skin with a poor prognosis. The factors driving this cancer must be better understood in order to discover novel targets for more effective therapies. In the search for targets, we followed our interest in citrate as a central and critical metabolite linked to fatty acid synthesis in cancer development. A key to citrate uptake in cancer cells is the high expression of the plasma membrane citrate transporter (pmCiC), which is upregulated in the different adenocarcinoma types tested so far. In this study, we show that the pmCiC is also highly expressed in Merkel cell carcinoma cell lines by western blot and human tissues by immunohistochemistry staining. In the presence of extracellular citrate, MCC cells show an increased proliferation rate in vitro; a specific pmCiC inhibitor (Na⁺-gluconate) blocks this citrate-induced proliferation. Furthermore, the 3D in vivo Chick Chorioallantoic Membrane (CAM) model showed that the application of Na⁺-gluconate also decreases Merkel cell carcinoma growth. Based on our results, we conclude that pmCiC and extracellular citrate uptake should be considered further as a potential novel target for the treatment of Merkel cell carcinoma.

PMID:35884486 | PMC:PMC9325124 | DOI:10.3390/cancers14143425

Malignant Eyelid Lesions

Fetched: July 27th, 2022, 5:01am GMT by Harkaran Rana

2022 Jul 14. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan–.

ABSTRACT

Malignant eyelid lesions can be identified by the eye care provider, primary care provider, or dermatologist during a routine exam. The most common malignancies of the eyelid include basal cell carcinoma, squamous cell carcinoma, sebaceous cell carcinoma, melanoma, and Merkel cell carcinoma.

Other eyelid malignancies exist, but these are rare and beyond the scope of this article. It is crucial to remember that any cutaneous malignancy can occur in the periocular region, and physicians should perform a thorough history and physical exam with all new patients.

The patient history should include questions regarding predisposing factors, duration, and rate of lesion growth, symptoms of tenderness, discharge, or bleeding, combined with careful clinical observation. A past medical history of skin cancer, UV exposure, and non-healing or recurrent cutaneous lesions should heighten suspicion of periorbital skin malignancy. Examination under magnification using a slit-lamp or dermoscopy is helpful in better characterization of any suspicious lesion. Notably, dermoscopy can reduce the need for unnecessary surgical procedures.

When there is a suspicion of malignancy, a referral should be made for a biopsy and histopathological analysis. When indicated, treatment consists of surgical excision, radiotherapy, chemotherapy, immunotherapy, cryosurgery, or laser treatments.

PMID:35881732 | Bookshelf:NBK582127

$Permalink for 'A Retrospective Study of Ipilimumab Plus Nivolumab in Anti-PD-L1/PD-1 Refractory Merkel Cell Carcinoma'$

A Retrospective Study of Ipilimumab Plus Nivolumab in Anti-PD-L1/PD-1 Refractory Merkel Cell Carcinoma

Fetched: July 26th, 2022, 5:01am GMT by Sophia Z Shalhout

J Immunother. 2022 Sep 1;45(7):299-302. doi: 10.1097/CJI.0000000000000432. Epub 2022 Jul 26.

ABSTRACT

Merkel cell carcinoma (MCC) is a very rare but highly aggressive cutaneous neuroendocrine carcinoma and is associated with chronic exposure to ultraviolet light and the Merkel cell polyoma virus. The incidence rate of MCC is increasing and MCC is associated with high rates of recurrence and mortality. Immune checkpoint inhibitors (ICIs) offer durable responses and significant clinical benefit with 2 agents-avelumab (anti-PD-L1) and pembrolizumab (anti-PD-1)-currently approved by the U.S. Food and Drug Administration for the treatment of advanced MCC. Despite the advances in systemic therapy options for MCC, ~50% of patients with advanced MCC treated with ICI progress on therapy. There is a paucity of studies assessing second-line systemic therapy following primary/acquired resistance to ICIs. Current management in this setting remains a clinical challenge especially in trial ineligible patients. We evaluated objective response to ipilimumab plus nivolumab in metastatic MCC refractory to anti-PD-(L)1 therapy. Thirty-one percent of patients experienced a grade III or grade IV immune-related adverse event (irAE) due to ipilimumab plus nivolumab. No patients (0/13) achieved a complete or partial response via RECISTv1.1/irRECIST. Twenty-three percent (3/13) of patients achieved stable disease as the best overall response but progressed shortly thereafter. The median progression-free survival was 1.3 months (90% CI 1.1-1.5) from the initiation of ipi-nivo. The median overall survival was 4.7 months (95% CI 3-17). This study suggests limited, if any, clinical benefit of ipi-nivo in patients with advanced anti-PD-L1/anti-PD-1 refractory MCC.

PMID:35877101 | DOI:10.1097/CJI.0000000000000432

Permalink for 'An Internally Validated Prognostic Risk-Score Model for Disease-Specific Survival in Clinical Stage I and II Merkel Cell Carcinoma'

An Internally Validated Prognostic Risk-Score Model for Disease-Specific Survival in Clinical Stage I and II Merkel Cell Carcinoma

Fetched: July 23rd, 2022, 5:01am GMT by Adrienne B Shannon

Ann Surg Oncol. 2022 Oct;29(11):7033-7044. doi: 10.1245/s10434-022-12201-z. Epub 2022 Jul 22.

ABSTRACT

BACKGROUND: Merkel cell carcinoma (MCC) is a rare cutaneous malignancy for which factors predictive of disease-specific survival (DSS) are poorly defined.

METHODS: Patients from six centers (2005-2020) with clinical stage I-II MCC who underwent sentinel lymph node (SLN) biopsy were included. Factors associated with DSS were identified using competing-risks regression analysis. Risk-score modeling was established using competing-risks regression on a training dataset and internally validated by point assignment to variables.

RESULTS: Of 604 patients, 474 (78.5%) and 128 (21.2%) patients had clinical stage I and II disease, respectively, and 189 (31.3%) had SLN metastases. The 5-year DSS rate was 81.8% with a median follow-up of 31 months. Prognostic factors associated with worse DSS included increasing age (hazard ratio [HR] 1.03, p = 0.046), male sex (HR 3.21, p = 0.021), immune compromise (HR 2.46, p = 0.013), presence of microsatellites (HR 2.65, p = 0.041), and regional nodal involvement (1 node: HR 2.48, p = 0.039; ≥2 nodes: HR 2.95, p = 0.026). An internally validated, risk-score model incorporating all of these factors was developed with good performance (AUC 0.738). Patients with ≤ 4.00 and > 4.00 points had 5-year DSS rates of 89.4% and 67.2%, respectively. Five-year DSS for pathologic stage I/II patients with > 4.00 points (n = 49) was 79.8% and for pathologic stage III patients with ≤ 4.00 points (n = 62) was 90.3%.

CONCLUSIONS: A risk-score model, including patient and tumor factors, based on DSS improves prognostic assessment of patients with clinically localized MCC. This may inform surveillance strategies and patient selection for adjuvant therapy trials.

PMID:35867209 | DOI:10.1245/s10434-022-12201-z

Merkel Cell Carcinoma of the Upper Eye Lid with Atypical Clinical Appearance

Fetched: July 23rd, 2022, 5:01am GMT by Benjamin Roschinski

Klin Monbl Augenheilkd. 2022 Jul;239(7):899-904. doi: 10.1055/a-1864-9772. Epub 2022 Jul 20.

ABSTRACT

Merkel cell carcinoma (MCC) is a rare aggressive neuroendocrine skin tumor that occurs mainly in the sun-exposed head and neck region, but rarely in the eyelid region. Early lymphogenic spread often leads to locoregional metastases, which is why early diagnosis is crucial. Classically, periocular MCC presents as a reddish-livid nodule in elderly patients, a visual diagnosis. However, given its low incidence and variable appearance, diagnosis can also be challenging. In both cases presented here, the MCC presented as a skin-colored swelling. In patient 1, the tumor showed a partially deep subaponeurotic localization and mimicked a B-cell lymphoma histopathologically, whereas in patient 2 it imitated a diffuse chalazion clinically. After immunohistochemical characterization and exclusion of metastases, the initial clinically benign appearing lesions in both patients were classified as CK20 negative MCC. The extensive upper eyelid defects were reconstructed by Cutler-Beard plastic surgery, a particular challenge in patient 1 given the oculus unicus situation. Our two cases demonstrate that Merkel cell carcinomas not only manifest as deep red cherry-shaped tumors, but can be skin-colored and mimic benign changes when atypical in location or infiltration pattern.

PMID:35858601 | DOI:10.1055/a-1864-9772

High prevalence of p16 staining in malignant tumors

Fetched: July 22nd, 2022, 5:01am GMT by Noémi De Wispelaere

PLoS One. 2022 Jul 21;17(7):e0262877. doi: 10.1371/journal.pone.0262877. eCollection 2022.

ABSTRACT

p16 (CDKN2A) is a member of the INK4 class of cell cycle inhibitors, which is often dysregulated in cancer. However, the prevalence of p16 expression in different cancer types is controversial. 15,783 samples from 124 different tumor types and 76 different normal tissue types were analyzed by immunohistochemistry in a tissue microarray format. p16 was detectable in 5,292 (45.0%) of 11,759 interpretable tumors. Except from adenohypophysis in islets of Langerhans, p16 staining was largely absent in normal tissues. In cancer, highest positivity rates were observed in uterine cervix squamous cell carcinomas (94.4%), non-invasive papillary urothelial carcinoma, pTaG2 (100%), Merkel cell carcinoma (97.7%), and small cell carcinomas of various sites of origin (54.5%-100%). All 124 tumor categories showed at least occasional p16 immunostaining. Comparison with clinico-pathological data in 128 vulvar, 149 endometrial, 295 serous ovarian, 396 pancreatic, 1365 colorectal, 284 gastric, and 1245 urinary bladder cancers, 910 breast carcinomas, 620 clear cell renal cell carcinomas, and 414 testicular germ cell tumors revealed only few statistically significant associations. Comparison of human papilloma virus (HPV) status and p16 in 497 squamous cell carcinomas of different organs revealed HPV in 80.4% of p16 positive and in 20.6% of p16 negative cancers (p<0.0001). It is concluded, that a positive and especially strong p16 immunostaining is a feature for malignancy which may be diagnostically useful in lipomatous, urothelial and possibly other tumors. The imperfect association between p16 immunostaining and HPV infection with high variability between different sites of origin challenges the use of p16 immunohistochemistry as a surrogate for HPV positivity, except in tumors of cervix uteri and the penis.

PMID:35862385 | PMC:PMC9302831 | DOI:10.1371/journal.pone.0262877

Cabozantinib for the treatment of solid tumors: a systematic review

Fetched: July 19th, 2022, 5:02am GMT by Pablo Maroto

Ther Adv Med Oncol. 2022 Jul 13;14:17588359221107112. doi: 10.1177/17588359221107112. eCollection 2022.

ABSTRACT

BACKGROUND: Cabozantinib is approved, in various settings, for the treatment of renal cell carcinoma, medullary thyroid cancer, and hepatocellular carcinoma, and it has been investigated for the treatment of other cancers. With the available evidence and the real-world performance of cabozantinib compared with clinical trial data, we performed a systematic review of cabozantinib monotherapy as treatment for solid tumors in adults.

METHODS: This study was designed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and registered with PROSPERO (CRD42020144680). We searched for clinical and observational studies of cabozantinib monotherapy for solid tumors using Embase, MEDLINE, and Cochrane databases (October 2020), and screened relevant congress abstracts. Eligible studies reported clinical or safety outcomes, or biomarker data. Small studies (n < 25) and studies of cabozantinib combination therapies were excluded. Quality was assessed using National Institute for Health and Care Excellence methodology, and study characteristics were described qualitatively.

RESULTS: Of 2888 citations, 114 were included (52 randomized studies, 29 observational studies, 32 nonrandomized phase I or II studies or pilot trials, and 1 analysis of data from a randomized study and a nonrandomized study). Beyond approved indications, other tumors studied were castration-resistant prostate cancer, urothelial carcinoma, Ewing sarcoma, osteosarcoma, uveal melanoma, non-small-cell lung cancer, Merkel cell carcinoma, glioblastoma, pheochromocytomas and paragangliomas, cholangiocarcinoma, gastrointestinal stromal tumor, colorectal cancer, salivary gland cancer, carcinoid and pancreatic neuroendocrine tumors, and breast, endometrial and ovarian cancers. The most common adverse events were hypertension, diarrhea, and fatigue.

CONCLUSION: The identified evidence demonstrates the positive efficacy/effectiveness of cabozantinib monotherapy in various solid tumor types, with safety findings being consistent with those observed with other VEGFR-targeting tyrosine kinase inhibitors. When available, real-world findings were consistent with the data reported from clinical trials. A limitation of this review is the high proportion of abstracts; however, this allowed us to capture the most up-to-date findings.

PMID:35847482 | PMC:PMC9284205 | DOI:10.1177/17588359221107112

Permalink for 'Immunoinformatics- and Bioinformatics-Assisted Computational Designing of a Novel Multiepitopes Vaccine Against Cancer-Causing Merkel Cell Polyomavirus'

Immunoinformatics- and Bioinformatics-Assisted Computational Designing of a Novel Multiepitopes Vaccine Against Cancer-Causing Merkel Cell Polyomavirus

Fetched: July 16th, 2022, 5:01am GMT by Nahlah Makki Almansour

Front Microbiol. 2022 Jun 28;13:929669. doi: 10.3389/fmicb.2022.929669. eCollection 2022.

ABSTRACT

Merkel cell polyomavirus (MCV) contains double-stranded DNA as its genome and is the fifth polyomavirus that infects humans. The virus causes Merkel cell carcinoma (aggressive skin cancer). Till present, no proper drug or vaccines are available to treat/prevent the virus infection and stop the emergence of Merkel cell carcinoma. In this study, computational vaccine design strategies were applied to design a chimeric-epitopes vaccine against the virus. The complete proteome comprised of four proteins was filtered through various vaccine candidacy parameters and as such two proteins, namely, capsid protein VP1 and capsid protein VP2, were considered as good vaccine targets. Furthermore, they harbor safe and potential B and T cell epitopes, which can be used in a chimeric multiepitopes-based vaccine design. The epitopes of the vaccine have maximum world population coverage of 95.04%. The designed vaccine structure was modeled in 3D that reported maximum residues in favored regions (95.7%) of the Ramachandran plot. The interactions analysis with different human immune receptors like TLR3, MHC-I, and MHC-II illustrated vaccine's good binding affinity and stable dynamics. The structural deviations of the vaccine receptor(s) complexes are within 5 Å, where majority of the receptors residues remain in good equilibrium in the simulation time. Also, the vaccine was found to form between 60 and 100 hydrogen bonds to receptors. The vaccine stimulated strong immune responses in addition to interferon and cytokines. The strength of vaccine-receptor(s) binding was further affirmed by binding energies estimation that concluded <-150.32 kcal/mol of net binding energy. All these findings suggest the vaccine as a promising candidate that needs further experimental testing to disclose its real immune protective efficacy. Furthermore, the designed vaccine might accelerate vaccine development against the MCV and could save time and expenses.

PMID:35836414 | PMC:PMC9273964 | DOI:10.3389/fmicb.2022.929669

Therapeutic targets for vaccination in polyomavirus-driven Merkel cell carcinoma

Fetched: July 15th, 2022, 5:01am GMT by Tejas P Joshi

Dermatol Ther. 2022 Jul;35(7):e15580. doi: 10.1111/dth.15580. Epub 2022 May 26.

NO ABSTRACT

PMID:35560970 | DOI:10.1111/dth.15580

Milademetan is a highly potent MDM2 inhibitor in Merkel cell carcinoma

Fetched: July 9th, 2022, 5:01am GMT by Varsha Ananthapadmanabhan

JCI Insight. 2022 Jul 8;7(13):e160513. doi: 10.1172/jci.insight.160513.

ABSTRACT

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine carcinoma of the skin with 2 etiologies. Merkel cell polyomavirus (MCPyV) integration is present in about 80% of all MCC. Virus-positive MCC (MCCP) tumors have few somatic mutations and usually express WT p53 (TP53). By contrast, virus-negative MCC (MCCN) tumors present with a high tumor mutational burden and predominantly UV mutational signature. MCCN tumors typically contain mutated TP53. MCCP tumors express 2 viral proteins: MCPyV small T antigen and a truncated form of large T antigen. MCPyV ST specifically activates expression of MDM2, an E3 ubiquitin ligase of p53, to inhibit p53-mediated tumor suppression. In this study, we assessed the efficacy of milademetan, a potent, selective, and orally available MDM2 inhibitor in several MCC models. Milademetan reduced cell viability of WT p53 MCC cell lines and triggered a rapid and sustained p53 response. Milademetan showed a dose-dependent inhibition of tumor growth in MKL-1 xenograft and patient-derived xenograft models. Here, along with preclinical data for the efficacy of milademetan in WT p53 MCC tumors, we report several in vitro and in vivo models useful for future MCC studies.

PMID:35801592 | PMC:PMC9310528 | DOI:10.1172/jci.insight.160513

Reversal of viral and epigenetic HLA class I repression in Merkel cell carcinoma

Fetched: July 2nd, 2022, 5:01am GMT by Patrick C Lee

J Clin Invest. 2022 Jul 1;132(13):e151666. doi: 10.1172/JCI151666.

ABSTRACT

Cancers avoid immune surveillance through an array of mechanisms, including perturbation of HLA class I antigen presentation. Merkel cell carcinoma (MCC) is an aggressive, HLA-I-low, neuroendocrine carcinoma of the skin often caused by the Merkel cell polyomavirus (MCPyV). Through the characterization of 11 newly generated MCC patient-derived cell lines, we identified transcriptional suppression of several class I antigen presentation genes. To systematically identify regulators of HLA-I loss in MCC, we performed parallel, genome-scale, gain- and loss-of-function screens in a patient-derived MCPyV-positive cell line and identified MYCL and the non-canonical Polycomb repressive complex 1.1 (PRC1.1) as HLA-I repressors. We observed physical interaction of MYCL with the MCPyV small T viral antigen, supporting a mechanism of virally mediated HLA-I suppression. We further identify the PRC1.1 component USP7 as a pharmacologic target to restore HLA-I expression in MCC.

PMID:35775490 | PMC:PMC9246387 | DOI:10.1172/JCI151666

Lyon IARC Polyomavirus Displays Transforming Activities in Primary Human Cells

Fetched: July 1st, 2022, 5:01am GMT by Assunta Venuti

J Virol. 2022 Jul 27;96(14):e0206121. doi: 10.1128/jvi.02061-21. Epub 2022 Jun 30.

ABSTRACT

Several studies reported the presence of a recently discovered polyomavirus (PyV), Lyon IARC PyV (LIPyV), in human and domestic animal specimens. LIPyV has some structural similarities to well-established animal and human oncogenic PyVs, such as raccoon PyV and Merkel cell PyV (MCPyV), respectively. In this study, we demonstrate that LIPyV early proteins immortalize human foreskin keratinocytes. LIPyV LT binds pRb, accordingly cell cycle checkpoints are altered in primary human fibroblasts and keratinocytes expressing LIPyV early genes. Mutation of the pRb binding site in LT strongly affected the ability of LIPyV ER to induced HFK immortalization. LIPyV LT also binds p53 and alters p53 functions activated by cellular stresses. Finally, LIPyV early proteins activate telomerase reverse transcriptase (hTERT) gene expression, via accumulation of the Sp1 transcription factor. Sp1 recruitment to the hTERT promoter is controlled by its phosphorylation, which is mediated by ERK1 and CDK2. Together, these data highlight the transforming properties of LIPyV in in vitro experimental models, supporting its possible oncogenic nature. IMPORTANCE Lyon IARC PyV is a recently discovered polyomavirus that shows some structural similarities to well-established animal and human oncogenic PyVs, such as raccoon PyV and Merkel cell PyV, respectively. Here, we show the capability of LIPyV to efficiently promote cellular transformation of primary human cells, suggesting a possible oncogenic role of this virus in domestic animals and/or humans. Our study identified a novel virus-mediated mechanism of activation of telomerase reverse transcriptase gene expression, via accumulation of the Sp1 transcription factor. In addition, because the persistence of infection is a key event in virus-mediated carcinogenesis, it will be important to determine whether LIPyV can deregulate immune-related pathways, similarly to the well-established oncogenic viruses.

PMID:35770990 | PMC:PMC9327700 | DOI:10.1128/jvi.02061-21

Merkel cell carcinoma of the anorectum: a case report and review of the literature

Fetched: June 29th, 2022, 5:01am GMT by Abraham C van Wyk

Clin J Gastroenterol. 2022 Aug;15(4):740-745. doi: 10.1007/s12328-022-01648-y. Epub 2022 Jun 28.

ABSTRACT

Merkel cell carcinoma is a highly aggressive neuroendocrine carcinoma that most commonly arises in sun-exposed skin. Established risk factors include advanced age, fair skin, chronic ultraviolet light exposure and immunosuppression. Merkel cell polyomavirus infection is implicated in a subset of cases. Primary extracutaneous Merkel cell carcinoma is exceedingly rare. We report a case of Merkel cell carcinoma of the anorectum in a 44-year-old woman of Indian descent with no apparent risk factors. She presented with rectal bleeding and worsening perineal discomfort. A polypoid tumor was identified in the anal canal. No cutaneous lesions were detected. Histopathology revealed a small round blue cell tumor with neuroendocrine features. Immunohistochemistry for CK20, synaptophysin, CD56, neurofilament and SATB2 were positive while CK7, CDX2 and TTF1 were negative. Polymerase chain reaction and immunohistochemistry were negative for Merkel cell polyomavirus. Merkel cell carcinoma should be considered in the differential diagnosis of a high grade neuroendocrine carcinoma at an unusual site such as the anorectum in this case. Correct diagnosis of Merkel cell carcinoma at an extracutaneous site is crucial because it should prompt careful evaluation for a skin primary and it may make the patient eligible for immune checkpoint inhibitor therapy.

PMID:35764912 | DOI:10.1007/s12328-022-01648-y

Serum neuron-specific enolase independently predicts outcome of Merkel cell carcinoma patients

Fetched: June 29th, 2022, 5:01am GMT by Thilo Gambichler

Br J Dermatol. 2022 Jun 28. doi: 10.1111/bjd.21717. Online ahead of print.

NO ABSTRACT

PMID:35762290 | DOI:10.1111/bjd.21717

CK20/CK7 Double Negative Merkel Cell Carcinoma In-Situ: A Case Report

Fetched: June 25th, 2022, 5:01am GMT by W Mark Richardson

J Cutan Pathol. 2022 Jun 24. doi: 10.1111/cup.14284. Online ahead of print.

ABSTRACT

An 83-year-old male with a history of both melanoma and non-melanoma skin cancers presented with a light pink non-ulcerated slightly raised 0.6 × 0.5-cm papule on his left lower extremity. Biopsy specimen revealed a proliferation of intraepidermal round blue cells. On immunohistochemical staining, CD56, chromogranin, and pancytokeratin were faintly positive within the lesional population, while synaptophysin was strongly positive. CD45, CK5/6, CK7, CK20, Melan-A, SOX10, and TTF-1 stains were negative. There was no dermal component identified. A Merkel cell polyomavirus stain was negative. Distant metastases and other in situ pathologies were excluded and a diagnosis of Merkel cell carcinoma in situ (MMCIS) was made. The majority of MCCIS lesions reported in the literature have been discovered amongst other non-melanoma neoplasms. Our findings of an MCCIS with purely intraepidermal involvements without the association with another squamous cell neoplasm is rare finding.

PMID:35748574 | DOI:10.1111/cup.14284

Merkel Cell Carcinoma Display PIEZO2 Immunoreactivity

Fetched: June 25th, 2022, 5:01am GMT by Yolanda García-Mesa

J Pers Med. 2022 May 28;12(6):894. doi: 10.3390/jpm12060894.

ABSTRACT

As an essential component of mechano-gated ion channels, critically required for mechanotransduction in mammalian cells, PIEZO2 is known to be characteristically expressed by Merkel cells in human skin. Here, we immunohistochemically investigated the occurrence of Piezo channels in a case series of Merkel cell carcinoma. A panel of antibodies was used to characterize Merkel cells, and to detect PIEZO2 expression. All analyzed tumors displayed PIEZO2 in nearly all cells, showing two patterns of immunostaining: membranous and perinuclear dot-like. PIEZO2 co-localized with cytokeratin 20, chromogranin A, synaptophysin and neurofilament. Moreover, neurofilament immunoreactive structures resembling nerve-Merkel cell contacts were occasionally found. PIEZO2 was also detected in cells of the sweat ducts. The role of PIEZO2 in Merkel cell carcinoma is still unknown, but it could be related with the mechanical regulation of the tumor biology or be a mere vestige of the Merkel cell derivation.

PMID:35743679 | PMC:PMC9224776 | DOI:10.3390/jpm12060894

Permalink for 'Identifying Candidates for Immunotherapy among Patients with Non-Melanoma Skin Cancer: A Review of the Potential Predictors of Response'

Identifying Candidates for Immunotherapy among Patients with Non-Melanoma Skin Cancer: A Review of the Potential Predictors of Response

Fetched: June 25th, 2022, 5:01am GMT by Enrico Zelin

J Clin Med. 2022 Jun 11;11(12):3364. doi: 10.3390/jcm11123364.

ABSTRACT

BACKGROUND: Non-melanoma skin cancer (NMSC) stands as an umbrella term for common cutaneous malignancies, including basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), together with rarer cutaneous cancers, such as Merkel cell carcinoma (MCC) and other forms of adnexal cancers. The majority of NMSCs can be successfully treated with surgery or radiotherapy, but advanced and metastatic stages may require systemic approaches such as immunotherapy with immune checkpoint inhibitors (ICIs).

SUMMARY: Since immunotherapy is not effective in all patients and can potentially lead to severe adverse effects, an important clinical question is how to properly identify those who could be suitable candidates for this therapeutic choice. In this paper, we review the potential features and biomarkers used to predict the outcome of ICIs therapy for NMSCs. Moreover, we analyze the role of immunotherapy in special populations, such as the elderly, immunocompromised patients, organ transplant recipients, and subjects suffering from autoimmune conditions.

KEY MESSAGES: Many clinical, serum, histopathological, and genetic features have been investigated as potential predictors of response in NMSCs treated with ICIs. Although this field of research is very promising, definitive, cost-effective, and reproducible biomarkers are still lacking and further efforts are needed to validate the suggested predictors in larger cohorts.

PMID:35743435 | PMC:PMC9225110 | DOI:10.3390/jcm11123364

PET-CT in Clinical Adult Oncology-VI. Primary Cutaneous Cancer, Sarcomas and Neuroendocrine Tumors

Fetched: June 25th, 2022, 5:01am GMT by Gabriel C Fine

Cancers (Basel). 2022 Jun 8;14(12):2835. doi: 10.3390/cancers14122835.

ABSTRACT

PET-CT is an advanced imaging modality with many oncologic applications, including staging, therapeutic assessment, restaging and surveillance for recurrence. The goal of this series of six review articles is to provide practical information to providers and imaging professionals regarding the best use of PET-CT for specific oncologic indications, the potential pitfalls and nuances that characterize these applications, and guidelines for image interpretation. Tumor-specific clinical information and representative PET-CT images are provided. The current, sixth article in this series addresses PET-CT in an evaluation of aggressive cutaneous malignancies, sarcomas and neuroendocrine tumors. A discussion of the role of FDG PET for all types of tumors in these categories is beyond the scope of this review. Rather, this article focuses on the most common malignancies in adult patients encountered in clinical practice. It also focuses on Food and Drug Agency (FDA)-approved and clinically available radiopharmaceuticals rather than research tracers or those requiring a local cyclotron. This information will serve as a guide to primary providers for the appropriate role of PET-CT in managing patients with cutaneous malignancies, sarcomas and neuroendocrine tumors. The nuances of PET-CT interpretation as a practical guide for imaging providers, including radiologists, nuclear medicine physicians and their trainees, are also addressed.

PMID:35740501 | PMC:PMC9221374 | DOI:10.3390/cancers14122835

Amyloid deposition with a granulomatous reaction in a resection specimen: A clue for a preexisting Merkel cell carcinoma

Fetched: June 24th, 2022, 5:01am GMT by Aimi T Rothrock

J Cutan Pathol. 2022 Sep;49(9):787-790. doi: 10.1111/cup.14282. Epub 2022 Jul 5.

ABSTRACT

Merkel cell carcinoma (MCC) is an aggressive, highly metastatic, cutaneous neuroendocrine malignancy with poor prognosis. Here, we describe a MCC excision specimen with a rare case of tumor-associated amyloid deposition in the absence of residual tumor cells. A 72-year-old man presented with a lesion of 5-6 months' duration on his left elbow, clinically thought to be a ganglion cyst. The biopsy specimen revealed a Stage IIA MCC with classic histomorphologic and immunophenotypic findings, with tumor extending to the tissue edges. The patient underwent wide local excision with negative margins and a negative sentinel lymph node biopsy. Although the patient did not receive any presurgical chemotherapy, immunotherapy, or targeted therapy, the re-excision specimen showed only amphophilic, feathery deposits that were salmon-pink with Congo red stain and further confirmed as amyloid by electron microscopy; there were no residual carcinoma cells. Amyloid deposition in MCC has been described in rare case reports. Our case was extraordinary in that there was only amyloid deposition and an associated granulomatous reaction, without identifiable MCC cells. This case demonstrates that amyloid deposition may be evidence of a prior MCC at the site of a prior procedure and may warrant careful evaluation for residual MCC.

PMID:35734844 | DOI:10.1111/cup.14282

Diagnosis and treatment of Merkel cell carcinoma: European consensus-based interdisciplinary guideline - Update 2022

Fetched: June 23rd, 2022, 5:01am GMT by Marie-Léa Gauci

Eur J Cancer. 2022 Aug;171:203-231. doi: 10.1016/j.ejca.2022.03.043. Epub 2022 Jun 19.

ABSTRACT

Merkel cell carcinoma (MCC) is a rare skin cancer, accounting for less than 1% of all cutaneous malignancies. It is found predominantly in white populations and risk factors include advanced age, ultraviolet exposure, male sex, immunosuppression, such as AIDS/HIV infection, haematological malignancies or solid organ transplantation, and Merkel cell polyomavirus infection. MCC is an aggressive tumour with 26% of cases presenting lymph node involvement at diagnosis and 8% with distant metastases. Five-year overall survival rates range between 48% and 63%. Two subsets of MCC have been characterised with distinct molecular pathogenetic pathways: ultraviolet-induced MCC versus virus-positive MCC, which carries a better prognosis. In both subtypes, there are alterations in the retinoblastoma protein and p53 gene structure and function. MCC typically manifests as a red nodule or plaque with fast growth, most commonly on sun exposed areas. Histopathology (small-cell neuroendocrine appearance) and immunohistochemistry (CK20 positivity and TTF-1 negativity) confirm the diagnosis. The current staging systems are the American Joint Committee on Cancer/Union for international Cancer control 8th edition. Baseline whole body imaging is encouraged to rule out regional and distant metastasis. For localised MCC, first-line treatment is surgical excision with postoperative margin assessment followed by adjuvant radiation therapy (RT). Sentinel lymph node biopsy is recommended in all patients with MCC without clinically detectable lymph nodes or distant metastasis. Adjuvant RT alone, eventually combined with complete lymph nodes dissection is proposed in case of micrometastatic nodal involvement. In case of macroscopic nodal involvement, the standard of care is complete lymph nodes dissection potentially followed by post-operative RT. Immunotherapy with anti-PD-(L)1 antibodies should be offered as first-line systemic treatment in advanced MCC. Chemotherapy can be used when patients fail to respond or are intolerant for anti-PD-(L)1 immunotherapy or clinical trials.

PMID:35732101 | DOI:10.1016/j.ejca.2022.03.043

Merkel Cell Carcinoma on the Forearm: A Case Report and Literature Review

Fetched: June 22nd, 2022, 5:01am GMT by Yaqi Tan

Clin Cosmet Investig Dermatol. 2022 Jun 14;15:1087-1090. doi: 10.2147/CCID.S361844. eCollection 2022.

ABSTRACT

Merkel cell carcinoma (MCC) is a rare cutaneous growth with aggressive nature. It mostly affects on the head and neck of white men aged 65 years old and immunosuppressed patients. Limited cases were reported in Asian patients. Loco-regional metastases with the regional lymph nodes involvement were common. The treatment methods include complete surgical excision and radiotherapy. Topical imiquimod and biologics are promising therapies. Here, we present a case of MCC occurring in a 76-year-old Chinese woman.

PMID:35726233 | PMC:PMC9206517 | DOI:10.2147/CCID.S361844

Epidemiological characteristics of malignant eyelid tumors at a referral hospital in Japan

Fetched: June 22nd, 2022, 5:01am GMT by Hiroshi Goto

Jpn J Ophthalmol. 2022 Jul;66(4):343-349. doi: 10.1007/s10384-022-00926-z. Epub 2022 Jun 7.

ABSTRACT

PURPOSE: To clarify the incidence and demographic characteristics of malignant eyelid tumors diagnosed in a single institute in Japan.

STUDY DESIGN: Retrospective, observational case series METHODS: Patients with malignant eyelid tumors diagnosed histopathologically at Tokyo Medical University Hospital between 1995 and 2019 were reviewed retrospectively. The incidence and demographic profile of malignant eyelid tumors were analyzed. The number of benign eyelid tumors diagnosed histopathologically during the same period was also counted.

RESULTS: A total of 412 patients with histopathologically proven malignant eyelid tumors were included. The most common malignant eyelid tumor was sebaceous carcinoma (n = 180, 44%), followed by basal cell carcinoma (n = 148, 36%), squamous cell carcinoma (n = 35, 9%), lymphoma (n = 28, 7%), Merkel cell carcinoma (n = 11, 3%) and others (n = 10, 2%). Mean age of all patients with malignant eyelid tumor at the time of diagnosis was 71.0 ± 13.0 years. For sebaceous carcinoma, the proportion of female patients was significantly higher than that of male patients (P = 0.0283) and the proportion of involvement of upper eyelid was significantly higher than that of lower eyelid (P = 0.0001). On the other hand, there was no sex predominance in basal cell carcinoma and squamous cell carcinoma. The proportion of involvement of lower eyelid was significantly higher than of upper eyelid in basal cell carcinoma (P = 0.001) and squamous cell carcinoma (P = 0.0012). There were 1433 patients with benign eyelid tumors accounting for 78% of all eyelid tumors during the study period.

CONCLUSIONS: Sebaceous carcinoma is the major malignant eyelid tumor in Japan and is more frequent in women than in men. Epidemiology of malignant eyelid tumors may be affected by the trend of population age structure associated with the recent population aging.

PMID:35670924 | DOI:10.1007/s10384-022-00926-z

Intralymphatic Histiocytosis Associated with Osteoarthritis: A Case Report

Fetched: June 21st, 2022, 5:01am GMT by Taehan Koo

Ann Dermatol. 2022 Jun;34(3):225-227. doi: 10.5021/ad.2022.34.3.225. Epub 2022 May 20.

ABSTRACT

Intralymphatic histiocytosis (ILH) is a rare cutaneous condition with uncertain pathogenesis. It is characterized by dilated lymphatic vessels that contain histiocytes within their lumina. Although the etiology of ILH remains unknown, it has been associated with various inflammatory and neoplastic diseases, such as rheumatoid arthritis (RA), reaction to metal joint implants and Merkel cell carcinoma, breast cancer and colon cancer. An 83-year-old female presented with an erythematous patch on the left forearm that had appeared six months previous. She had suffered from osteoarthritis (OA) and the cutaneous lesion was located in the vicinity of the affected joint. Skin biopsy from the lesion showed dilated dermal vessels and some ectatic vessels that contained many mononuclear histiocytes. Based on the clinical and histopathological findings, we diagnosed her with ILH with OA. Two sessions of intralesional triamcinolone acetonide injection (5 mg/ml) were administered to treat the skin lesion, which gradually improved over a period of a few months. We here report a rare case of ILH associated with degenerative OA.

PMID:35721336 | PMC:PMC9171188 | DOI:10.5021/ad.2022.34.3.225

Neuroendocrine Neoplasia of the Female Genital Tract

Fetched: June 19th, 2022, 5:01am GMT by Karen L Talia

Surg Pathol Clin. 2022 Jun;15(2):407-420. doi: 10.1016/j.path.2022.02.012. Epub 2022 May 18.

ABSTRACT

Neuroendocrine neoplasia is relatively uncommon in the female genital tract (FGT) and occurs at any site, most often the ovary and cervix. A unified dichotomous nomenclature, introduced by the World Health Organization Classification of Tumors in all fifth edition volumes, divides neuroendocrine neoplasms (NENs) into well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). The term carcinoid tumor is retained in the ovary and represents the commonest FGT NEN. NEC is most common in the cervix and is usually admixed with another human papillomavirus-associated epithelial neoplasm. Despite shared neuroendocrine differentiation, NET and NEC show diverse etiology, morphology, and clinical behavior.

PMID:35715168 | DOI:10.1016/j.path.2022.02.012

Permalink for 'Oncologic outcomes of patients with lymph node-positive Merkel cell carcinoma with unknown primary: a retrospective cohort study'

Oncologic outcomes of patients with lymph node-positive Merkel cell carcinoma with unknown primary: a retrospective cohort study

Fetched: June 19th, 2022, 5:01am GMT by Jane Yuet Ching Hui

J Am Acad Dermatol. 2022 Jun 14:S0190-9622(22)01005-2. doi: 10.1016/j.jaad.2022.06.015. Online ahead of print.

NO ABSTRACT

PMID:35714787 | DOI:10.1016/j.jaad.2022.06.015

Skin cancers under Janus kinase inhibitors: A World Health Organization drug safety database analysis

Fetched: June 17th, 2022, 5:01am GMT by Cédric Jalles

Therapie. 2022 May 7:S0040-5957(22)00092-0. doi: 10.1016/j.therap.2022.04.005. Online ahead of print.

ABSTRACT

BACKGROUND: Janus kinase (JAK) inhibitors are targeted therapies with a potential imunomodulatory and anti-inflammatory effect, indicated in various dysimmune pathologies. Skin cancers have been reported to occur in patients treated with JAK inhibitors. However, drug safety in clinical trials did not confirm that risk, but these studies are performed on controlled population and in a limited time of follow up.

OBJECTIVES: The aim of this study is to evaluate in real life condition if a disproportionality signal exists between JAK inhibitors treatment and skin cancers.

METHODS: We performed cases/non cases analysis in VigiBase® (the World Health Organization international database of suspected adverse drug reaction) using information component to search for a disproportionality signal of skin cancers from JAK inhibitor. We extracted all reports of skin cancers from the French Pharmacovigilance database occurring since 1978 up to 31^st December 2019 for the three existing JAK inhibitors on market: ruxolitinib, tofacitinib and baricitinib. Only melanoma, squamous cell carcinoma and Merkel cell carcinoma were analyzed, according to the pathophysiology of these cancers and their link with immunosuppression.

RESULTS: A disproportionality signal was found positive for squamous cell carcinoma with ruxolitinib (IC025=3.92) and tofacitinib (IC025=0.82), for melanoma with ruxolitinib (IC025=0.81) and tofacitinib (IC025=0.74), and Merkel cell carcinoma with ruxolitinib (IC025=4) and tofactinib (IC025=1.01) and only for Merkel cell carcinoma with baricitinib (IC025=0.53). Moreover, Merkel cell carcinoma, a very rare skin cancer more prevalent in immunodepressed patients was particularly represented in our sample and was associated with a significant disproportionality signal with all the studied JAK inhibitors.

CONCLUSION: Our study shows that JAK inhibitors could be associated with an extra risk to develop skin cancers. Could an anti-viral or immunovigilance disruption mechanism brought by JAK inhibitors explain an over-risk with Merkel cell carcinoma, which were notably represented in our sample? Considering pharmacovigilance method limitations, further pharmacoepidemiological studies are required to assess a causal link between JAK inhibitors treatment and skin cancers development.

PMID:35710462 | DOI:10.1016/j.therap.2022.04.005

Intracranial extraosseous dural-based Ewing's sarcoma with fluid-haematocrit levels: imaging findings of a rare tumour

Fetched: June 17th, 2022, 5:01am GMT by Sudipta Mohakud

BMJ Case Rep. 2022 Jun 14;15(6):e247056. doi: 10.1136/bcr-2021-247056.

ABSTRACT

Extraosseous dural-based primary Ewing's sarcoma of the central nervous system is a rare tumour posing a diagnostic challenge. On cross-sectional radiological imaging, the lesion has an extra-axial location with heterogeneous appearance. These lesions are usually multicystic with internal haemorrhage causing fluid-haematocrit levels. It mimics conditions like an aneurysmal bone cyst, microcystic meningioma, telangiectatic osteosarcoma or cystic metastasis. Exclusion of primary Ewing's sarcoma or malignancy elsewhere in the body is required to rule out a secondary. Surgery along with adjuvant chemotherapy and focal radiotherapy is the preferred mode of treatment. Due to the presence of non-specific small round blue cells on H&E stain, these tumours are also confused with lymphoma, osteosarcoma, rhabdomyosarcoma, Merkel cell carcinoma, ependymoblastoma and neuroendocrine carcinoma. Immunohistochemistry provides a definitive diagnosis. A high degree of suspicion in the preoperative scans is crucial for prognostication and early management of this aggressive tumour leading to improved patient survival.

PMID:35701017 | PMC:PMC9198795 | DOI:10.1136/bcr-2021-247056

Merkel cell carcinoma

Fetched: June 17th, 2022, 5:01am GMT by Morten Kristoffer Nyrud

Tidsskr Nor Laegeforen. 2022 Jun 13;142(9). doi: 10.4045/tidsskr.21.0693. Print 2022 Jun 14.

ABSTRACT

Merkel cell carcinoma is an uncommon but aggressive tumour with a high metastatic potential. A rapidly growing, non-tender cutaneous tumour on sun-exposed areas of the body in older patients should raise suspicion of the condition. It may be necessary to combine the patient history with clinical, radiological and pathological findings in order to make the correct diagnosis. Excision with a 1-2 cm margin, direct closure and simultaneous sentinel-node biopsy should be performed without delay. Adjuvant radiation therapy of the tumour site may be relevant. After the diagnosis is made, assessment and treatment should take place in hospitals with special experience of the condition.

PMID:35699540 | DOI:10.4045/tidsskr.21.0693

Merkel cell carcinoma with pleural effusion

Fetched: June 16th, 2022, 5:01am GMT by María J Soler-Sempere

Arch Bronconeumol. 2021 Nov;57(11):715-717. doi: 10.1016/j.arbr.2021.09.007. Epub 2021 Sep 10.

NO ABSTRACT

PMID:35699019 | DOI:10.1016/j.arbr.2021.09.007

Nationwide multidisciplinary consensus on the clinical management of Merkel cell carcinoma: a Delphi panel

Fetched: June 15th, 2022, 5:01am GMT by Francesca Spada

J Immunother Cancer. 2022 Jun;10(6):e004742. doi: 10.1136/jitc-2022-004742.

ABSTRACT

Merkel cell carcinoma (MCC) is a rare and highly aggressive cutaneous neuroendocrine carcinoma. The MCC incidence rate has rapidly grown over the last years, with Italy showing the highest increase among European countries. This malignancy has been the focus of active scientific research over the last years, focusing mainly on pathogenesis, new therapeutic trials and diagnosis. A national expert board developed 28 consensus statements that delineated the evolution of disease management and highlighted the paradigm shift towards the use of immunological strategies, which were then presented to a national MCC specialists panel for review. Sixty-five panelists answered both rounds of the questionnaire. The statements were divided into five areas: a high level of agreement was reached in the area of guidelines and multidisciplinary management, even if in real life the multidisciplinary team was not always represented by all the specialists. In the diagnostic pathway area, imaging played a crucial role in diagnosis and initial staging, planning for surgery or radiation therapy, assessment of treatment response and surveillance of recurrence and metastases. Concerning diagnosis, the usefulness of Merkel cell polyomavirus is recognized, but the agreement and consensus regarding the need for cytokeratin evaluation appears greater. Regarding the areas of clinical management and follow-up, patients with MCC require customized treatment. There was a wide dispersion of results and the suggestion to increase awareness about the adjuvant radiation therapy. The panelists unanimously agreed that the information concerning avelumab provided by the JAVELIN Merkel 200 study is adequate and reliable and that the expanded access program data could have concrete clinical implications. An immunocompromised patient with advanced MCC can be treated with immunotherapy after multidisciplinary risk/benefit assessment, as evidenced by real-world analysis and highlighted in the guidelines. A very high consensus regarding the addition of radiotherapy to treat the ongoing focal progression of immunotherapy was observed. This paper emphasizes the importance of collaboration and communication among the interprofessional team members and encourages managing patients with MCC within dedicated multidisciplinary teams. New insights in the treatment of this challenging cancer needs the contribution of many and different experts.

PMID:35701070 | PMC:PMC9198700 | DOI:10.1136/jitc-2022-004742

Cytology coupled with immunocytochemistry identifies Merkel cell carcinoma: A rare intruder in the cerebrospinal fluid

Fetched: June 15th, 2022, 5:01am GMT by Reetu Kundu

Cytopathology. 2022 Jul;33(4):530-533. doi: 10.1111/cyt.13127. Epub 2022 Apr 28.

ABSTRACT

Merkel cell carcinoma is an uncommon aggressive skin tumour which is well known for its recurrence and metastasis. Leptomeningeal metastasis involving the cerebrospinal fluid is extremely rare. The diagnosis may easily be missed as it simulates other much more common small round blue cell tumours. A patient history with a primary diagnosis may not always be available. Awareness and cytomorphological vigilance with judicious employment of appropriate immunomarkers on limited cerebrospinal fluid samples is indispensable for reaching the correct diagnosis. The tumour cells are usually monotonous small round cells, singly scattered or arranged in loosely cohesive clusters. Cells have round to elongated nuclei with coarsely granular chromatin, nuclear moulding in places and scanty basophilic cytoplasm. A limited immunocytochemistry panel employing CK20 and CD56, for which the tumour is positive, is confirmatory. We herein present a case of infiltration of cerebrospinal fluid by Merkel cell carcinoma.

PMID:35416339 | DOI:10.1111/cyt.13127

Editorial: Environment and Skin Cancer

Fetched: June 14th, 2022, 5:01am GMT by Nabiha Yusuf

Front Oncol. 2022 May 27;12:924225. doi: 10.3389/fonc.2022.924225. eCollection 2022.

NO ABSTRACT

PMID:35692782 | PMC:PMC9186106 | DOI:10.3389/fonc.2022.924225

Addiction of Merkel cell carcinoma to MUC1-C identifies a potential new target for treatment

Fetched: June 12th, 2022, 5:01am GMT by Yoshihiro Morimoto

Oncogene. 2022 Jul;41(27):3511-3523. doi: 10.1038/s41388-022-02361-3. Epub 2022 Jun 10.

ABSTRACT

Merkel cell carcinoma (MCC) is an aggressive malignancy with neuroendocrine (NE) features, limited treatment options, and a lack of druggable targets. There is no reported involvement of the MUC1-C oncogenic protein in MCC progression. We show here that MUC1-C is broadly expressed in MCCs and at higher levels in Merkel cell polyomavirus (MCPyV)-positive (MCCP) relative to MCPyV-negative (MCCN) tumors. Our results further demonstrate that MUC1-C is expressed in MCCP, as well as MCCN, cell lines and regulates common sets of signaling pathways related to RNA synthesis, processing, and transport in both subtypes. Mechanistically, MUC1-C (i) interacts with MYCL, which drives MCC progression, (ii) is necessary for expression of the OCT4, SOX2, KLF4, MYC, and NANOG pluripotency factors, and (iii) induces the NEUROD1, BRN2 and ATOH1 NE lineage dictating transcription factors. We show that MUC1-C is also necessary for MCCP and MCCN cell survival by suppressing DNA replication stress, the p53 pathway, and apoptosis. In concert with these results, targeting MUC1-C genetically and pharmacologically inhibits MCC self-renewal capacity and tumorigenicity. These findings demonstrate that MCCP and MCCN cells are addicted to MUC1-C and identify MUC1-C as a potential target for MCC treatment.

PMID:35688945 | PMC:PMC9249628 | DOI:10.1038/s41388-022-02361-3

Neuronal intermediate filament paraneoplastic autoimmunity complicating avelumab therapy of Merkel cell carcinoma

Fetched: June 10th, 2022, 5:01am GMT by Alessandro Dinoto

J Neuroimmunol. 2022 Jul 15;368:577882. doi: 10.1016/j.jneuroim.2022.577882. Epub 2022 May 5.

ABSTRACT

A 67-years-old woman developed subacute oculomotor nerve palsy and cerebellar gait instability while receiving avelumab as immunotherapy for Merkel cell carcinoma. Brain MRI revealed oculomotor nerve T2/FLAIR hyperintensity and contrast enhancement, CSF cell number and protein concentration were slightly increased. Antibodies against intracellular and surface antigens were excluded through commercial assays, but home-made immunohistochemistry on rat brain sections showed a "neurofilament-like" pattern. Antibodies against neuronal intermediate filament (NIF-IgG) were thus tested and resulted positive in both serum and CSF, confirming the diagnosis of NIF-IgG autoimmunity. Avelumab was discontinued and treatment with steroids and intravenous immunoglobulins led to partial improvement.

PMID:35580403 | DOI:10.1016/j.jneuroim.2022.577882

$Permalink for 'Talimogene laherparepvec resulting in near-complete response in a patient with treatment-refractory Merkel cell carcinoma'$

Talimogene laherparepvec resulting in near-complete response in a patient with treatment-refractory Merkel cell carcinoma

Fetched: June 7th, 2022, 5:02am GMT by Michael A Cilento

Australas J Dermatol. 2022 Aug;63(3):e222-e225. doi: 10.1111/ajd.13881. Epub 2022 Jun 6.

ABSTRACT

Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous tumour of neuroendocrine cell origin, which can grow rapidly and metastasise early. Localised disease is treated with surgery and radiotherapy. Disease that reaches a more advanced stage can be treated with a variety of different treatment modalities including surgery, radiotherapy, chemotherapy, radionuclide therapy, immunotherapy, and intralesional therapy. We report a case of a patient who had exhausted all local and systemic treatment options and who subsequently had an exceptional response to intralesional injection of Talimogene laherparepvec (TVEC).

PMID:35666757 | DOI:10.1111/ajd.13881

Gender and immunosuppression impact on Merkel cell carcinoma diagnosis and prognosis. A population based cohort study

Fetched: June 7th, 2022, 5:02am GMT by E Keeling

Skin Health Dis. 2021 Dec 8;2(1):e80. doi: 10.1002/ski2.80. eCollection 2022 Mar.

ABSTRACT

BACKGROUND: Merkel cell carcinoma (MCC), a rare cutaneous neuroendocrine endocrine tumour is increasing in incidence, and continues to carry a poor prognosis.

OBJECTIVES: The objectives of this study were to examine all Irish cases of MCC from 1 January 1994 over 2 decades, focusing on gender and organ transplantation recipients (OTRs). Cases were identified from the National Cancer Registry of Ireland. Covariates of interest included age, body site, period of diagnosis, deprivation-status and history of non-melanoma skin cancer (NMSC).

RESULTS: In total 314 MCC cases were identified. A female predominance was noted (53.8%). Comparison between age-standardised rates between the earliest period (1994-1996) with the latest period (2012-2014) showed an increase of 105% in total. The trend in age-standardised incidence rates were noted to be increasing significantly (p = 0.0004). Average age at diagnosis was 77.6 years (male 75.1 years, female 79.7 years). Overall, the majority of MCC cases presented on the head and neck (n = 170, 54.1%). Differences in anatomical location of MCCs were noted between genders. Males were found to be more likely to have a history of previous NMSCs (males n = 73 [57.9%], females n = 53 [42.1%]). Thirty-one percentage of patients died from MCC, average survival was 3.5 years in those who died of this malignancy. Ten organ transplant recipients developed MCC. OTR who developed MCC were diagnosed at a younger average age of 65.1 years. Standardized incidence ratio for MCC in OTR was 59.96. A higher proportion of OTR died from MCC (70%), with a shorter median survival of 0.14 years. In competing risks regression, gender was not significantly associated with risk of dying, females having a non-significantly higher hazard of dying. Organ transplant recipients and patients from less deprived areas were at greater risk of dying from MCC.

CONCLUSIONS: This population based study provides epidemiological, clinical and outcome data for MCC over a 20-year period.

PMID:35665203 | PMC:PMC9060007 | DOI:10.1002/ski2.80

Permalink for 'Sentinel lymph node biopsy in Merkel cell carcinoma: rates and predictors of compliance with National Comprehensive Cancer Network guidelines'

Sentinel lymph node biopsy in Merkel cell carcinoma: rates and predictors of compliance with National Comprehensive Cancer Network guidelines

Fetched: June 7th, 2022, 5:02am GMT by Daniel J Lewis

J Am Acad Dermatol. 2022 Jun 1:S0190-9622(22)00898-2. doi: 10.1016/j.jaad.2022.05.054. Online ahead of print.

NO ABSTRACT

PMID:35660413 | DOI:10.1016/j.jaad.2022.05.054

MOC-31 Antibody Immunolabeling During Mohs Surgery

Fetched: June 7th, 2022, 5:02am GMT by Edward Bae

Dermatol Surg. 2022 Jun 1;48(6):595-600. doi: 10.1097/DSS.0000000000003446. Epub 2022 Apr 5.

ABSTRACT

BACKGROUND: Ber-EP4 is an antibody that labels basal cell carcinoma (BCC) by targeting epithelial cell adhesion molecule (Ep-CAM). MOC-31, a monoclonal mouse antibody, also targets Ep-CAM and is currently used to differentiate several extracutaneous epithelial tumors. However, the utility of MOC-31 has not been fully described in cutaneous tumors and in Mohs micrographic surgery (MMS).

OBJECTIVE: To evaluate MOC-31 labeling in BCC and other cutaneous tumors and to compare immunolabeling intensity of MOC-31 and Ber-EP4 in BCCs.

MATERIALS AND METHODS: Nineteen permanently fixed and 29 frozen BCC specimens and 23 other cutaneous tumors were labeled with MOC-31; labeling intensity of tumors, epidermis, and adnexal structures were recorded. In a separate study, a blinded dermatopathologist compared labeling intensities of 8 BCC specimens, each labeled with MOC-31 and Ber-EP4.4.

RESULTS: MOC-31 labeled all BCCs. Eccrine coils and follicular bulbs did label variably, although this did not detract utility of MOC-31. Five of thirteen cutaneous squamous cell carcinomas and one of two Merkel cell carcinomas demonstrated MOC-31 positivity. MOC-31 and Ber-EP4 labeled BCCs similarly.

CONCLUSION: MOC-31, an antibody directed against Ep-CAM, is sensitive for BCCs in frozen specimens encountered in MMS and permanently fixed specimen. In addition, MOC-31 demonstrated comparable immunolabeling characteristics with Ber-EP4 for BCCs.

PMID:35384902 | DOI:10.1097/DSS.0000000000003446

Human polyomavirus-associated skin diseases

Fetched: June 3rd, 2022, 5:01am GMT by Steffi Silling

Hautarzt. 2022 Jun;73(6):426-433. doi: 10.1007/s00105-022-04993-8. Epub 2022 Apr 28.

ABSTRACT

Of the 15 currently known human polyomaviruses (HPyV), eight have been found on healthy skin. Merkel cell polyomavirus (MCPyV), HPyV6, HPyV7, and to a lesser extent Saint Louis polyomavirus (STLPyV) are considered part of the human cutaneous virome. The most important cutaneous polyomavirus, MCPyV, causes the majority of Merkel cell carcinomas (MCC). MCC is a rare but very aggressive malignant skin tumor that affects both immunocompetent and immunosuppressed patients. A steady increase in incidence rates of this skin tumor has been observed in recent decades. MCC occurs primarily on sunlight-exposed skin of fair-skinned individuals. Risk factors for MCC development include immunosuppression and advanced age. In immunocompromised individuals, primary infection with trichodysplasia spinulosa-associated polyomavirus (TSPyV) can cause the very rare skin disease trichodysplasia spinulosa (TS). Keratin spines (spicules), mainly in the center of the face, clinically characterize this disease. Skin lesions associated with further HPyV have been described exclusively in immunocompromised individuals. For HPyV6 and HPyV7, cases of epithelial proliferation and pruritic dyskeratotic dermatitis have been published. HPyV9 and New Jersey polyomavirus (NJPyV-13) were each found in different skin lesions of individual patients. The role of these polyomaviruses in the development of the skin lesions is still unclear.

PMID:35482045 | DOI:10.1007/s00105-022-04993-8

Permalink for 'Large Cell Neuroendocrine Carcinoma of the Skin/Conjunctiva: A Series of 6 Cases including 1 Combined Case With Squamous Cell Carcinoma'

Large Cell Neuroendocrine Carcinoma of the Skin/Conjunctiva: A Series of 6 Cases including 1 Combined Case With Squamous Cell Carcinoma

Fetched: June 2nd, 2022, 5:14am GMT by Keisuke Goto

Am J Dermatopathol. 2022 May 30. doi: 10.1097/DAD.0000000000002229. Online ahead of print.

ABSTRACT

This study sought to reveal the clinicopathologic characteristics of large cell neuroendocrine carcinoma (LCNEC) of the skin/conjunctiva. The retrieved patients included 3 men and 3 women with a median age of 85 (63-95) years. All lesions occurred on the face, including the ears, with a median tumor size of 11.5 (7-65) mm. Lymph node metastasis was observed in 5 (83%) of 6 cases, and distant metastasis was noted in 2 (33%). One patient (17%) who had a 13-mm-sized tumor died of the tumor 13 months after excision. All tumors were mainly located in the dermis, and one of them also exhibited intraepithelial spreading. The cytology resembled that of an LCNEC in other organs. No adnexal differentiation was observed. Five cases were of the pure type, but one had a component of squamous cell carcinoma. Immunoreactivities for CAM5.2, CK7, CK19, BerEP4, epithelial membrane antigen, neuron-specific enolase, synaptophysin, c-KIT, GATA3, and bcl-2 were frequently present, but CK20, neurofilament, Merkel cell polyomavirus large T antigen, mammaglobin, estrogen receptor, HER2, and TTF1 were completely negative in all cases. Mutant-pattern immunostaining of p53, PTEN, and Rb was frequently observed. The Ki67 rate exceeded 70% in all cases. LCNEC of the skin/conjunctiva is a morphologically-defined group of primary cutaneous/conjunctival neuroendocrine neoplasm, although it may be heterogeneous similar to other-site LCNEC or Merkel cell carcinoma. This study highlighted the predominant location for the face, high metastatic and lethal potential, possible combination with other tumor components, and frequent mutant-type immunoexpressions of p53, PTEN, and Rb in this tumor group.

PMID:35642978 | DOI:10.1097/DAD.0000000000002229

Small DNA tumor viruses and human cancer: Preclinical models of virus infection and disease

Fetched: June 1st, 2022, 5:01am GMT by Megan E Spurgeon

Tumour Virus Res. 2022 May 27;14:200239. doi: 10.1016/j.tvr.2022.200239. Online ahead of print.

ABSTRACT

Human tumor viruses cause various human cancers that account for at least 15% of the global cancer burden. Among the currently identified human tumor viruses, two are small DNA tumor viruses: human papillomaviruses (HPVs) and Merkel cell polyomavirus (MCPyV). The study of small DNA tumor viruses (adenoviruses, polyomaviruses, and papillomaviruses) has facilitated several significant biological discoveries and established some of the first animal models of virus-associated cancers. The development and use of preclinical in vivo models to study HPVs and MCPyV and their role in human cancer is the focus of this review. Important considerations in the design of animal models of small DNA tumor virus infection and disease, including host range, cell tropism, choice of virus isolates, and the ability to recapitulate human disease, are presented. The types of infection-based and transgenic model strategies that are used to study HPVs and MCPyV, including their strengths and limitations, are also discussed. An overview of the current models that exist to study HPV and MCPyV infection and neoplastic disease are highlighted. These comparative models provide valuable platforms to study various aspects of virus-associated human disease and will continue to expand knowledge of human tumor viruses and their relationship with their hosts.

PMID:35636683 | PMC:PMC9194455 | DOI:10.1016/j.tvr.2022.200239

Permalink for 'Merkel cell carcinoma and immune evasion: Merkel cell polyomavirus small T-antigen induced surface changes can be reverted by therapeutic intervention'

Merkel cell carcinoma and immune evasion: Merkel cell polyomavirus small T-antigen induced surface changes can be reverted by therapeutic intervention

Fetched: June 1st, 2022, 5:01am GMT by Tabea Schlemeyer

J Invest Dermatol. 2022 May 28:S0022-202X(22)00404-3. doi: 10.1016/j.jid.2022.04.029. Online ahead of print.

ABSTRACT

Merkel cell polyomavirus is the causative agent for most Merkel cell carcinomas (MCCs). This highly aggressive skin cancer shows rapid progression, with metastasis being a significant challenge for patient therapy. Virus-positive MCCs show low mutation rates, and tumor cell proliferation is dependent on viral oncoproteins small T antigen (sT) and large T antigen. Although the role of sT and large T antigen in early events of tumorigenesis has been extensively studied, their role in tumor progression has been scarcely addressed. In this study, we investigate the possible mechanisms of how Merkel cell polyomavirus oncoproteins, particularly sTs, contribute to metastasis. We show that sT specifically affects selectin ligand binding and processing by altering the presentation of multiple MCC surface molecules, thereby influencing initial metastasis events and tumor cell immune recognition. Furthermore, we show that sT regulates the surface antigen CD47, which inhibits phagocytosis by macrophages. By applying either sT short hairpin RNAs, CD47-targeted small interfering RNAs, or a therapeutic anti-CD47 antibody, we show that immune recognition of MCC cells can be restored. Thus, CD47 is a promising therapeutic target on MCC cells. Blocking the CD47‒SIRPα interaction effectively promotes phagocytosis of MCC cells and might be a promising combinatorial immunotherapy approach together with PD-1/PD-L1 axis in MCC treatment.

PMID:35636504 | DOI:10.1016/j.jid.2022.04.029

Effects of Oxaliplatin on Facial Sensitivity to Cool Temperatures and TRPM8 Expressing Trigeminal Ganglion Neurons in Mice

Fetched: June 1st, 2022, 5:01am GMT by Robert M Caudle

Front Pain Res (Lausanne). 2022 May 11;3:868547. doi: 10.3389/fpain.2022.868547. eCollection 2022.

ABSTRACT

The chemotherapeutic agent oxaliplatin is commonly used to treat colorectal cancer. Although effective as a chemotherapeutic, it frequently produces painful peripheral neuropathies. These neuropathies can be divided into an acute sensitivity to cool temperatures in the mouth and face, and chronic neuropathic pain in the limbs and possible numbness. The chronic neuropathy also includes sensitivity to cool temperatures. Neurons that detect cool temperatures are reported to utilize Transient Receptor Potential Cation Channel, Subfamily M, Member 8 (TRPM8). Therefore, we investigated the effects of oxaliplatin on facial nociception to cool temperatures (18°C) in mice and on TRPM8 expressing trigeminal ganglion (TRG) neurons. Paclitaxel, a chemotherapeutic that is used to treat breast cancer, was included for comparison because it produces neuropathies, but acute cool temperature sensitivity in the oral cavity or face is not typically reported. Behavioral testing of facial sensitivity to 18°C indicated no hypersensitivity either acutely or chronically following either chemotherapeutic agent. However, whole cell voltage clamp experiments in TRPM8 expressing TRG neurons indicated that both oxaliplatin and paclitaxel increased Hyperpolarization-Activated Cyclic Nucleotide-Gated channel (HCN), voltage gated sodium channel (Nav), and menthol evoked TRPM8 currents. Voltage gated potassium channel (Kv) currents were not altered. Histological examination of TRPM8 fibers in the skin of the whisker pads demonstrated that the TRPM8 expressing axons and possible Merkel cell-neurite complexes were damaged by oxaliplatin. These findings indicate that oxaliplatin induces a rapid degeneration of TRG neuron axons that express TRPM8, which prevents evoked activation of the sensitized neurons and likely leads to reduced sensitivity to touch and cool temperatures. The changes in HCN, Nav, and TRPM8 currents suggest that spontaneous firing of action potentials may be increased in the deafferented neurons within the ganglion, possibly producing spontaneously induced cooling or nociceptive sensations.

PMID:35634452 | PMC:PMC9130462 | DOI:10.3389/fpain.2022.868547

Permalink for 'Clinical-Pathological Evaluation and Prognostic Analysis of 228 Merkel Cell Carcinomas Focusing on Tumor-Infiltrating Lymphocytes, MCPYV Infection and ALK Expression'

Clinical-Pathological Evaluation and Prognostic Analysis of 228 Merkel Cell Carcinomas Focusing on Tumor-Infiltrating Lymphocytes, MCPYV Infection and ALK Expression

Fetched: May 31st, 2022, 5:01am GMT by Federica Santoro

Endocr Pathol. 2022 Jun;33(2):289-303. doi: 10.1007/s12022-022-09716-2. Epub 2022 May 12.

ABSTRACT

Merkel cell carcinoma is a rare and aggressive primary neuroendocrine carcinoma of the skin, whose pathogenesis can be traced back to UV radiation damage or Merkel cell polyomavirus (MCPyV) infection. Despite some improvements on the characterization of the disease partly due to its increased incidence, crucial pathogenetic and prognostic factors still need to be refined. A consecutive series of 228 MCC from three hospitals in Turin was collected with the aim of both analyzing the apparent increase in MCC incidence in our area and investigating the distribution and prognostic role of clinical-pathological parameters, with a focus on MCPyV status, ALK tumor expression and tumor infiltrating lymphocytes (TILs). Review of morphology and conventional immunohistochemical staining was possible in 191 cases. In 50 cases, the expression of the novel neuroendocrine marker INSM1 was additionally assessed. Fourteen cases of MCC of unknown primary skin lesion were identified and separately analyzed. While confirming an exponential trend in MCC incidence in the last decades and providing a description of histological and cytological features of a large series of MCC, the present study concludes that 1) INSM1 is a highly sensitive marker in both skin and lymph node primary MCC; 2) positive MCPyV status, brisk TILs and lower tumor size and thickness are independent positive prognostic parameters, and the combination of the former two may provide a novel tool for prognostic stratification; 3) ALK is expressed 87% of MCC and associated with positive viral status, and could represent a prognostic biomarker, if validated in larger series.

PMID:35551625 | PMC:PMC9135831 | DOI:10.1007/s12022-022-09716-2

Permalink for 'Toward the Identification of Natural Antiviral Drug Candidates against Merkel Cell Polyomavirus: Computational Drug Design Approaches'

Toward the Identification of Natural Antiviral Drug Candidates against Merkel Cell Polyomavirus: Computational Drug Design Approaches

Fetched: May 29th, 2022, 5:01am GMT by Amer H Asseri

Pharmaceuticals (Basel). 2022 Apr 20;15(5):501. doi: 10.3390/ph15050501.

ABSTRACT

Merkel cell carcinoma (MCC) is a rare form of aggressive skin cancer mainly caused by Merkel cell polyomavirus (MCPyV). Most MCC tumors express MCPyV large T (LT) antigens and play an important role in the growth-promoting activities of oncoproteins. Truncated LT promotes tumorigenicity as well as host cell proliferation by activating the viral replication machinery, and inhibition of this protein in humans drastically lowers cellular growth linked to the corresponding cancer. Our study was designed with the aim of identifying small molecular-like natural antiviral candidates that are able to inhibit the proliferation of malignant tumors, especially those that are aggressive, by blocking the activity of viral LT protein. To identify potential compounds against the target protein, a computational drug design including molecular docking, ADME (absorption, distribution, metabolism, and excretion), toxicity, molecular dynamics (MD) simulation, and molecular mechanics generalized Born surface area (MM-GBSA) approaches were applied in this study. Initially, a total of 2190 phytochemicals isolated from 104 medicinal plants were screened using the molecular docking simulation method, resulting in the identification of the top five compounds having the highest binding energy, ranging between -6.5 and -7.6 kcal/mol. The effectiveness and safety of the selected compounds were evaluated based on ADME and toxicity features. A 250 ns MD simulation confirmed the stability of the selected compounds bind to the active site (AS) of the target protein. Additionally, MM-GBSA analysis was used to determine the high values of binding free energy (ΔG bind) of the compounds binding to the target protein. The five compounds identified by computational approaches, Paulownin (CID: 3084131), Actaealactone (CID: 11537736), Epigallocatechin 3-O-cinnamate (CID: 21629801), Cirsilineol (CID: 162464), and Lycoricidine (CID: 73065), can be used in therapy as lead compounds to combat MCPyV-related cancer. However, further wet laboratory investigations are required to evaluate the activity of the drugs against the virus.

PMID:35631328 | PMC:PMC9146542 | DOI:10.3390/ph15050501

Use of Thiazide Diuretics and Risk of All Types of Skin Cancers: An Updated Systematic Review and Meta-Analysis

Fetched: May 29th, 2022, 5:01am GMT by Surapon Nochaiwong

Cancers (Basel). 2022 May 23;14(10):2566. doi: 10.3390/cancers14102566.

ABSTRACT

BACKGROUND: The use of thiazide diuretics is associated with skin cancer risk; however, whether this applies to all skin cancer types is unclear.

METHODS: In this meta-analysis, we searched multiple electronic databases and gray literature up to 10 April 2022, with no language restrictions, to identify relevant randomized controlled trials (RCTs) and non-randomized studies (cohort, case-control) that investigated the association between thiazide diuretics and skin cancer. The primary outcomes of interest were malignant melanoma and non-melanoma skin cancer (basal cell carcinoma [BCC], squamous cell carcinoma [SCC]). Secondary outcomes included other skin cancers (lip cancer, Merkel cell carcinoma, malignant adnexal skin tumors, oral cavity cancer, and precursors of skin cancer). We used a random-effects meta-analysis to estimate pooled adjusted odds ratios (ORs) and 95% confidence intervals (CIs).

RESULTS: Thirty non-randomized studies (17 case-control, 13 cohort, no RCTs) were included. Thiazide diuretic users had a higher risk of malignant melanoma (17 studies; n = 10,129,196; pooled adjusted OR, 1.10; 95% CI, 1.04-1.15; p < 0.001; strength of evidence, very low; very small harmful effect), BCC (14 studies; n = 19,780,476; pooled adjusted OR, 1.05; 95% CI, 1.02-1.09; p = 0.003; strength of evidence, very low; very small harmful effect), and SCC (16 studies; n = 16,387,862; pooled adjusted OR, 1.35; 95% CI, 1.22-1.48; p < 0.001; strength of evidence, very low; very small harmful effect) than non-users. Thiazide diuretic use was also associated with a higher risk of lip cancer (5 studies; n = 161,491; pooled adjusted OR, 1.92; 95% CI, 1.52-2.42; p < 0.001; strength of evidence, very low; small harmful effect), whereas other secondary outcomes were inconclusive.

CONCLUSIONS: Thiazide diuretics are associated with the risk of all skin cancer types, including malignant melanoma; thus, they should be used with caution in clinical practice.

PMID:35626169 | PMC:PMC9140049 | DOI:10.3390/cancers14102566

Development of metastatic Merkel cell carcinoma following the excision of same-sided recurrent auricular melanoma

Fetched: May 28th, 2022, 5:01am GMT by Jake K Cartwright

Clin Case Rep. 2022 May 22;10(5):e05891. doi: 10.1002/ccr3.5891. eCollection 2022 May.

ABSTRACT

Merkel cell carcinoma (MCC) is a rare neuroendocrine malignancy of the skin that is highly aggressive and often metastasizes early. MCC is diagnosed based on histopathological findings and is most commonly treated with surgical resection, which may be accompanied by chemotherapy and/or radiation. This report describes a 55-year-old male patient with the history of recurrent malignant melanoma of the right pinna and subsequent excision. Three years following the excision of melanoma, he presented with a lesion to the right forehead as well as a right-sided neck mass that were found to be metastatic Merkel cell carcinoma.

PMID:35620264 | PMC:PMC9124612 | DOI:10.1002/ccr3.5891

Permalink for 'Clinicopathological Features, MCPyV Status and Outcomes of Merkel Cell Carcinoma in Solid-Organ Transplant Recipients: A Retrospective, Multicenter Cohort Study'

Clinicopathological Features, MCPyV Status and Outcomes of Merkel Cell Carcinoma in Solid-Organ Transplant Recipients: A Retrospective, Multicenter Cohort Study

Fetched: May 25th, 2022, 5:01am GMT by C Ferrándiz-Pulido

J Eur Acad Dermatol Venereol. 2022 May 24. doi: 10.1111/jdv.18256. Online ahead of print.

ABSTRACT

BACKGROUND: The proportion of Merkel cell carcinomas (MCCs) in solid-organ transplant recipients (SOTR) harbouring Merkel cell polyomavirus (MCPyV) is unknown, as are factors affecting their outcomes.

OBJECTIVE: To describe clinicopathological features of MCC in SOTR, investigate the tumoral MCPyV-status and identify factors associated with tumour outcomes.

METHODS: Retrospective, international, cohort-study. MCPyV-status was investigated by immunohistochemistry and polymerase chain reaction.

RESULTS: A total of 30 SOTR and 44 consecutive immunocompetent patients with MCC were enrolled. SOTR were younger at diagnosis (69 vs. 78 years, P < 0.001). Thirty-three percent of SOTR MCCs were MCPyV-positive vs. 91% of immunocompetent MCCs (P = 0.001). Solid-organ transplantation was associated with an increased cumulative incidence of progression (SHR: 3.35 [1.57-7.14], P = 0.002), MCC-specific mortality (SHR: 2.55 [1.07-6.06], P = 0.034) and overall mortality (HR: 3.26 [1.54-6.9], P = 0.002). MCPyV-positivity and switching to an mTOR inhibitor (mTORi) after MCC diagnosis were associated with an increased incidence of progression (SHR: 4.3 [1.5-13], P = 0.008 and SHR: 3.6 [1.1-12], P = 0.032 respectively) in SOTR.

LIMITATIONS: Retrospective design and heterogeneity of SOTR cohort.

CONCLUSIONS: MCPyV appears to play a less prominent role in the aetiopathogenesis of MCC in SOTR. SOTR have a worse prognosis than their immunocompetent counterparts and switching to an mTORi after the diagnosis of MCC does not improve progression.

PMID:35607918 | DOI:10.1111/jdv.18256

$Permalink for 'Characterization of clinical outcomes after shorter course hypofractionated and standard-course radiotherapy for stage I-III curatively-treated Merkel cell carcinoma'$

Characterization of clinical outcomes after shorter course hypofractionated and standard-course radiotherapy for stage I-III curatively-treated Merkel cell carcinoma

Fetched: May 22nd, 2022, 5:01am GMT by Kevin X Liu

Radiother Oncol. 2022 Aug;173:32-40. doi: 10.1016/j.radonc.2022.05.012. Epub 2022 May 17.

ABSTRACT

BACKGROUND: Limited data exists regarding the efficacy of curative hypofractionated radiotherapy (hypo-RT) regimens compared to conventionally-fractionated radiotherapy (conv-RT) for Merkel cell carcinoma (MCC).

METHODS: A retrospective analysis of 241 patients diagnosed with non-metastatic MCC from 2005-2021 and who received RT at Dana-Farber/Brigham & Women's Cancer Center. The primary outcome was cumulative incidence of in-field locoregional relapse using Gray's test with competing risks of death and isolated out-of-field recurrence. Secondary outcomes included overall survival (OS) and MCC-specific survival using log-rank tests, and risk factors of recurrence using Cox-proportional hazards regression.

RESULTS: There were 50 (20.6 %) and 193 (79.4 %) courses of hypo-RT and conv-RT, respectively. The hypo-RT cohort was older (≥73 years at diagnosis: 78.0 % vs 41.5 %, p < 0.01), and received a lower equivalent total RT dose in 2 Gy per fraction (<50 Gy: 58.0 % vs 5.2 %, p < 0.01). Median follow-up was 65.1 months (range: 1.2-194.5) for conv-RT and 25.0 months (range: 1.6-131.3) for hypo-RT cohorts. Two-year cumulative incidence of in-field locoregional relapse was low in both groups (1.1 % conv-RT vs 4.1 % hypo-RT, p = 0.114). While two-year OS was lower for the hypo-RT group (62.6 % vs 84.4 %, p = 0.0008), two-year MCC-specific survival was similar (84.7 % vs 86.6 %, p = 0.743). On multivariable analysis, immunosuppression, clinical stage III disease, and lymphovascular invasion were associated with any-recurrence when controlling for sex, age, and hypo-RT.

CONCLUSIONS AND RELEVANCE: There was no difference in cumulative incidence of in-field locoregional relapse or MCC-specific survival between hypo-RT and conv-RT. Prospective studies are needed to confirm hypo-RT as an efficacious treatment option for MCC.

PMID:35595174 | DOI:10.1016/j.radonc.2022.05.012

Permalink for 'Patterns of Recurrence and Prognosis in Pathologic Stage I and II Merkel Cell Carcinoma: A multi-center, retrospective cohort analysis'

Patterns of Recurrence and Prognosis in Pathologic Stage I and II Merkel Cell Carcinoma: A multi-center, retrospective cohort analysis

Fetched: May 21st, 2022, 5:01am GMT by Andrew D Tieniber

J Am Acad Dermatol. 2022 May 16:S0190-9622(22)00813-1. doi: 10.1016/j.jaad.2022.05.019. Online ahead of print.

NO ABSTRACT

PMID:35588924 | DOI:10.1016/j.jaad.2022.05.019

This Month in JAAD International: June 2022: Merkel cell carcinoma management and outcomes

Fetched: May 20th, 2022, 5:01am GMT by Jonathan Kantor

J Am Acad Dermatol. 2022 Jun;86(6):1233. doi: 10.1016/j.jaad.2022.04.005. Epub 2022 Apr 12.

NO ABSTRACT

PMID:35427681 | DOI:10.1016/j.jaad.2022.04.005

Response to comment on "Merkel cell carcinoma: An updated review of pathogenesis, diagnosis, and treatment options."

Fetched: May 15th, 2022, 5:01am GMT by Loren E Hernandez

Dermatol Ther. 2022 Jul;35(7):e15581. doi: 10.1111/dth.15581. Epub 2022 May 26.

NO ABSTRACT

PMID:35560755 | DOI:10.1111/dth.15581

Merkel cell polyomavirus large T antigen binding to pRb promotes skin hyperplasia and tumor development

Fetched: May 15th, 2022, 5:01am GMT by Megan E Spurgeon

PLoS Pathog. 2022 May 13;18(5):e1010551. doi: 10.1371/journal.ppat.1010551. eCollection 2022 May.

ABSTRACT

Clear evidence supports a causal link between Merkel cell polyomavirus (MCPyV) and the highly aggressive human skin cancer called Merkel cell carcinoma (MCC). Integration of viral DNA into the human genome facilitates continued expression of the MCPyV small tumor (ST) and large tumor (LT) antigens in virus-positive MCCs. In MCC tumors, MCPyV LT is truncated in a manner that renders the virus unable to replicate yet preserves the LXCXE motif that facilitates its binding to and inactivation of the retinoblastoma tumor suppressor protein (pRb). We previously developed a MCPyV transgenic mouse model in which MCC tumor-derived ST and truncated LT expression were targeted to the stratified epithelium of the skin, causing epithelial hyperplasia, increased proliferation, and spontaneous tumorigenesis. We sought to determine if any of these phenotypes required the association between the truncated MCPyV LT and pRb. Mice were generated in which K14-driven MCPyV ST/LT were expressed in the context of a homozygous RbΔLXCXE knock-in allele that attenuates LT-pRb interactions through LT's LXCXE motif. We found that many of the phenotypes including tumorigenesis that develop in the K14-driven MCPyV transgenic mice were dependent upon LT's LXCXE-dependent interaction with pRb. These findings highlight the importance of the MCPyV LT-pRb interaction in an in vivo model for MCPyV-induced tumorigenesis.

PMID:35560034 | PMC:PMC9132321 | DOI:10.1371/journal.ppat.1010551

Mass Spectrometry Based Identification of Novel HLA Class I Restricted Peptides in Merkel Cell Carcinoma

Fetched: May 14th, 2022, 5:01am GMT by Suzanna Rachimi

FASEB J. 2022 May;36 Suppl 1. doi: 10.1096/fasebj.2022.36.S1.R3864.

ABSTRACT

Highly polymorphic class I human leukocyte antigen (HLA-I) molecules present endogenous peptides to CD8+ T cells, an essential part of immune regulation. This mechanism allows for the presentation of thousands of epitopes per allele and individual. Liquid chromatography-mass spectrometry (LC-MS/MS) is a high throughput method that can be utilized to identify endogenously processed and presented peptides. Merkel cell carcinoma (MCC) is a rare and aggressive form of neuroendocrine skin cancer. A major subtype of this cancer is caused by the Merkel cell Polyomavirus (MCPyV), so MCPyV+ MCC is an informative model system to explore virally derived cancer-specific epitopes. MCC, however, often downregulates or eliminates HLA-I antigen presentation to evade recognition by the immune system. We hypothesized that reversing the mechanisms of immune evasion will allow us to detect novel epitopes. Here, we used optimized LC-MS/MS methods to characterize the immunopeptidome of MCC in a native and perturbed state. First, we compared the immunopeptidome of primary tumor samples and tumor-derived MCC cell lines. Peptide identities presented on primary tumors and tumor-derived cell lines overlapped by 50% or more, indicating that the tumor-derived cell lines retain their innate tumor properties and are a useful model to study immune presentation in MCC. Next, we investigated mechanisms to restore HLA-I presentation in MCC, such as IFNγ treatment and knockout or inhibition of components of the Polycomb repressive complex (PRC1.1). We found that IFNγ treatment increased peptide yield up to 8-fold across seven cell lines while also increasing presentation on HLA-B alleles. Using tandem mass tag labeling, we observed relative quantitative changes in the immunopeptidome of an MCPyV+ cell line when PRC1.1 components were knocked down. We discovered increased HLA-I presentation upon USP7 inhibitor treatment in comparison to the control. In contrast to IFNγ treatment, USP7 inhibition did not alter the fraction of observed peptides assigned to alleles. Finally, use of High Field Asymmetric Ion Mobility Spectrometry (FAIMS) to analyze samples with reinstated HLA presentation enabled identification of a number of novel antigens, including three MCPyV viral epitopes. The immunogenicity of these viral peptides was determined by ELISpot assays with peripheral blood mononuclear cells (PBMCs). These findings can be translated into medical treatments for patients diagnosed with this cancer.

PMID:35555650 | DOI:10.1096/fasebj.2022.36.S1.R3864

The immunogenetics of viral antigen response is associated with subtype-specific glioma risk and survival

Fetched: May 14th, 2022, 5:01am GMT by Geno Guerra

Am J Hum Genet. 2022 Jun 2;109(6):1105-1116. doi: 10.1016/j.ajhg.2022.04.011. Epub 2022 May 11.

ABSTRACT

Glioma is a highly fatal cancer with prognostically significant molecular subtypes and few known risk factors. Multiple studies have implicated infections in glioma susceptibility, but evidence remains inconsistent. Genetic variants in the human leukocyte antigen (HLA) region modulate host response to infection and have been linked to glioma risk. In this study, we leveraged genetic predictors of antibody response to 12 viral antigens to investigate the relationship with glioma risk and survival. Genetic reactivity scores (GRSs) for each antigen were derived from genome-wide-significant (p < 5 × 10^-8) variants associated with immunoglobulin G antibody response in the UK Biobank cohort. We conducted parallel analyses of glioma risk and survival for each GRS and HLA alleles imputed at two-field resolution by using data from 3,418 glioma-affected individuals subtyped by somatic mutations and 8,156 controls. Genetic reactivity scores to Epstein-Barr virus (EBV) ZEBRA and EBNA antigens and Merkel cell polyomavirus (MCV) VP1 antigen were associated with glioma risk and survival (Bonferroni-corrected p < 0.01). GRSZEBRA and GRSMCV were associated in opposite directions with risk of IDH wild-type gliomas (ORZEBRA = 0.91, p = 0.0099/ORMCV = 1.11, p = 0.0054). GRSEBNA was associated with both increased risk for IDH mutated gliomas (OR = 1.09, p = 0.040) and improved survival (HR = 0.86, p = 0.010). HLA-DQA1^∗03:01 was significantly associated with decreased risk of glioma overall (OR = 0.85, p = 3.96 × 10^-4) after multiple testing adjustment. This systematic investigation of the role of genetic determinants of viral antigen reactivity in glioma risk and survival provides insight into complex immunogenomic mechanisms of glioma pathogenesis. These results may inform applications of antiviral-based therapies in glioma treatment.

PMID:35550063 | PMC:PMC9247888 | DOI:10.1016/j.ajhg.2022.04.011

Health literacy strategies to improve engagement of Merkel cell carcinoma patients in their care

Fetched: May 12th, 2022, 5:01am GMT by Kelsey Ouyang

J Plast Reconstr Aesthet Surg. 2022 Jul;75(7):2387-2440. doi: 10.1016/j.bjps.2022.04.064. Epub 2022 Apr 29.

NO ABSTRACT

PMID:35545493 | DOI:10.1016/j.bjps.2022.04.064

To the Editor: Patient and County-Level Factors Associated with Late Stage Merkel Cell Carcinoma at Diagnosis

Fetched: May 11th, 2022, 5:01am GMT by Payal Shah

J Invest Dermatol. 2022 May 7:S0022-202X(22)00373-6. doi: 10.1016/j.jid.2022.03.034. Online ahead of print.

NO ABSTRACT

PMID:35537549 | DOI:10.1016/j.jid.2022.03.034

The Efficacy of Immune Checkpoint Inhibitors in Rare Tumors: A Systematic Review of Published Clinical Trials

Fetched: May 10th, 2022, 5:01am GMT by Deniz Can Guven

Crit Rev Oncol Hematol. 2022 Jun;174:103700. doi: 10.1016/j.critrevonc.2022.103700. Epub 2022 May 6.

ABSTRACT

The immune checkpoint inhibitors (ICIs) entered treatment algorithms in most tumors. However, the data on the efficacy is limited in rare tumors with no phase III studies. We systemically reviewed the clinical trials evaluating the ICI efficacy in rare tumors and included a total of 47 clinical trials in this review. The ICIs demonstrated over 30% response rates in Merkel cell carcinoma and squamous cell carcinoma of the skin and became the standard of care. Additionally, the ICI efficacy was promising in thymic epithelial tumors and gestational trophoblastic neoplasia. In contrast, the ICI efficacy is limited in most sarcomas, germ cell tumors and low-grade neuroendocrine tumors. The ICI efficacy seemed to be improved with combinations targeting tumor microenvironment in sarcomas. The available evidence on ICI efficacy in rare tumors denote a need for better patient selection and novel combination strategies to improve outcomes.

PMID:35533815 | DOI:10.1016/j.critrevonc.2022.103700

Permalink for 'BOXR1030, an anti-GPC3 CAR with exogenous GOT2 expression, shows enhanced T cell metabolism and improved anti-cell line derived tumor xenograft activity'

BOXR1030, an anti-GPC3 CAR with exogenous GOT2 expression, shows enhanced T cell metabolism and improved anti-cell line derived tumor xenograft activity

Fetched: May 5th, 2022, 5:01am GMT by Taylor L Hickman

PLoS One. 2022 May 4;17(5):e0266980. doi: 10.1371/journal.pone.0266980. eCollection 2022.

ABSTRACT

PURPOSE: The solid tumor microenvironment (TME) drives T cell dysfunction and inhibits the effectiveness of immunotherapies such as chimeric antigen receptor-based T cell (CAR T) cells. Early data has shown that modulation of T cell metabolism can improve intratumoral T cell function in preclinical models.

EXPERIMENTAL DESIGN: We evaluated GPC3 expression in human normal and tumor tissue specimens. We developed and evaluated BOXR1030, a novel CAR T therapeutic co-expressing glypican-3 (GPC3)-targeted CAR and exogenous glutamic-oxaloacetic transaminase 2 (GOT2) in terms of CAR T cell function both in vitro and in vivo.

RESULTS: Cell surface expression of tumor antigen GPC3 was observed by immunohistochemical staining in tumor biopsies from hepatocellular carcinoma, liposarcoma, squamous lung cancer, and Merkel cell carcinoma patients. Compared to control GPC3 CAR alone, BOXR1030 (GPC3-targeted CAR T cell that co-expressed GOT2) demonstrated superior in vivo efficacy in aggressive solid tumor xenograft models, and showed favorable attributes in vitro including an enhanced cytokine production profile, a less-differentiated T cell phenotype with lower expression of stress and exhaustion markers, an enhanced metabolic profile and increased proliferation in TME-like conditions.

CONCLUSIONS: Together, these results demonstrated that co-expression of GOT2 can substantially improve the overall antitumor activity of CAR T cells by inducing broad changes in cellular function and phenotype. These data show that BOXR1030 is an attractive approach to targeting select solid tumors. To this end, BOXR1030 will be explored in the clinic to assess safety, dose-finding, and preliminary efficacy (NCT05120271).

PMID:35507536 | PMC:PMC9067639 | DOI:10.1371/journal.pone.0266980

Complete response of Merkel cell carcinoma with talimogene laherparepvec (TVEC) monotherapy

Fetched: May 5th, 2022, 5:01am GMT by Fiore Casale

Dermatol Online J. 2022 Jan 15;28(1). doi: 10.5070/D328157059.

ABSTRACT

Merkel cell carcinoma (MCC) is a rare neuroendocrine neoplasm, warranting surgical excision with sentinel lymph node biopsy. In later stages, adjuvant chemotherapy and radiation are required owing to its aggressive malignant behavior. We describe a 62-year-old woman who presented with multifocal recurrence of MCC and was not a candidate for immunotherapy or surgery. The patient underwent four treatments of intratumoral talimogene laherparepvec (TVEC) and demonstrated a complete response with no histologic evidence of remaining MCC on four scouting biopsies. Although TVEC therapy is currently approved for the treatment of advanced stage melanoma, it is still being investigated in MCC. This case supports the use of TVEC as monotherapy in select patients with locally advanced MCC who are not candidates for surgery or systemic immunotherapy.

PMID:35499413 | DOI:10.5070/D328157059

Hemato-Oncological Diseases as Risk Factor for Recurrence or Metastasis of Pleomorphic Dermal Sarcoma

Fetched: May 3rd, 2022, 5:01am GMT by Doris Helbig

Front Oncol. 2022 Apr 14;12:873771. doi: 10.3389/fonc.2022.873771. eCollection 2022.

ABSTRACT

BACKGROUND: Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are increasingly common sarcomas of the skin with a genetic UV signature. Immunosuppression is a known risk factor for developing other UV-induced skin cancers such as cutaneous squamous cell carcinoma (cSCC), basal cell carcinoma (BCC), and Merkel cell carcinoma with increased mortality. In case reports or small case series of AFX/PDS patients, immunosuppression has been hypothesized as a risk factor for the development of distant metastases. The aim of the present study was to analyze immunosuppression as a risk factor for AFX/PDS in a large patient cohort.

METHODS: A cohort of 164 patients with AFX/PDS (47 AFX and 117 PDS) was collected between 2003 and 2021 and analyzed for clinicopathological data with a special focus on immunosuppression.

RESULTS: Of all patients, 29.9% had any kind of immunosuppression; 6.4% of the AFX and 12.0% of the PDS patients had underlying hemato-oncological diseases. Patients with immunosuppression due to an underlying hemato-oncological disease had a significantly increased risk of progressing to (p = 0.010) and developing distant organ metastases (p = 0.000).

CONCLUSIONS: Immunosuppression seems to be a risk factor for developing AFX/PDS with worse clinical outcomes. Therefore, immunosuppression, especially underlying hemato-oncological diseases, should be considered in the treatment and follow-up care of patients with AFX/PDS.

PMID:35494063 | PMC:PMC9050200 | DOI:10.3389/fonc.2022.873771

Permalink for 'Epstein-Barr Virus, But Not Human Papillomavirus, Is Associated With Preinvasive and Invasive Ocular Surface Squamous Neoplasias in Zambian Patients'

Epstein-Barr Virus, But Not Human Papillomavirus, Is Associated With Preinvasive and Invasive Ocular Surface Squamous Neoplasias in Zambian Patients

Fetched: May 3rd, 2022, 5:01am GMT by Peter Julius

Front Oncol. 2022 Apr 14;12:864066. doi: 10.3389/fonc.2022.864066. eCollection 2022.

ABSTRACT

BACKGROUND: The etiopathogenesis of ocular surface squamous neoplasia (OSSN) is not fully understood. We assessed the frequency of oncogenic viruses in OSSN by immunohistochemistry (IHC) and polymerase chain reaction (PCR) for human papillomavirus (HPV), Epstein-Barr virus (EBV), Merkel cell polyomavirus (MCPyV), Kaposi sarcoma virus, and adenovirus. Cases from Zambia were prospectively enrolled using a cross-sectional study design between November 2017 and March 2020.

METHODS: Demographic and clinical data [age, sex, HIV status, antiretroviral therapy (ART) history, CD4 count, plasma viral load] and tumor biopsies were collected from 243 consenting patients. Tumor samples were bisected, and half was used for DNA isolation, while the other half was formalin fixed and paraffin embedded (FFPE) for histopathology analysis. The expressions of latent EBV nuclear antigen 1 (EBNA1), CDKN2A/p16INK4A (p16), and MCPyV large T-antigen (LT) were tested by IHC. Multiplex PCR was used to detect 16 HPV genotypes and four other DNA tumor viruses [Kaposi's sarcoma-associated herpesvirus (KSHV), EBV, MCPyV, and adenovirus]. Relationships between HIV status, viral DNA and protein expression, and tumor grades were determined by statistical analysis.

RESULTS: OSSN tumors from patients were 29.6% preinvasive and 70.4% invasive. Patients presented with unilateral tumors that were 70.4% late stage (T3/T4). OSSN patients were HIV positive (72.8%). IHC on 243 FFPE biopsies resulted in the detection of EBNA1 (EBV), p16 high-risk HPV (HR-HPV), and MCPyV LT expression in 89.0%, 4.9%, and 0.0%, respectively. EBNA1 was expressed in all grades of preinvasive [cornea-conjunctiva intraepithelial neoplasia (CIN)1, 100%; CIN2, 85.7%; CIN3, 95.8%; and carcinoma in situ (CIS), 83.8%] and in invasive (89.2%) OSSN. PCR on 178 samples detected EBV, HR-HPV, and MCPyV in 80.3%, 9.0%, and 13.5% of tumors, respectively. EBV was detected in all grades of preinvasive and invasive OSSN. EBV detection was associated with high HIV viral loads (p = 0.022). HR-HPV was detected in 0.0% CIN1, 0.0% CIN2, 5.6% CIN3, 13.0% CIS, and 7.0% invasive OSSN.

CONCLUSIONS: Our findings of EBV DNA and EBNA1 protein in all the grades of preinvasive and especially invasive OSSN are consistent with a potential causal role for EBV in OSSN. A role of HPV in OSSN was not clearly established in this study.

PMID:35494029 | PMC:PMC9047892 | DOI:10.3389/fonc.2022.864066

Permalink for 'Lymph node ratio predicts efficacy of postoperative radiation therapy in nonmetastatic Merkel cell carcinoma: A population-based analysis'

Lymph node ratio predicts efficacy of postoperative radiation therapy in nonmetastatic Merkel cell carcinoma: A population-based analysis

Fetched: April 30th, 2022, 5:01am GMT by Giuseppe Lamberti

Cancer Med. 2022 Apr 29. doi: 10.1002/cam4.4773. Online ahead of print.

ABSTRACT

BACKGROUND: After radical resection of a nonmetastatic Merkel cell carcinoma (M0 MCC), postoperative radiation therapy (RT) is recommended as it improves survival. However, the role of RT in specific subgroups of M0 MCC is unclear. We sought to identify whether there is a differential survival benefit from RT in specific M0 MCC patient subgroups.

METHODS: M0 MCC patients from the Surveillance, Epidemiology, and End Results (SEER) database registry were collected. The best prognostic age, tumor size, and lymph node ratio (LNR, ratio between positive lymph nodes and resected lymph nodes) cutoffs were calculated. The primary endpoint was overall survival (OS).

RESULTS: A total of 5644 M0 MCC patients (median age 77 years, 62% male) were included: 4022 (71%) node-negative (N0) and 1551 (28%) node-positive (N+). Overall, 2682 patients (48%) received RT. Age > 76.5 years, tumor size >13.5 mm, and LNR >0.215 were associated with worse OS. RT was associated with longer OS in the M0 MCC, N0, and N+ group and independently associated with a 25%, 27%, and 26% reduction in the risk for death, respectively. RT benefit on survival was increased in tumor size >13.5 mm in the N0 group and LNR >0.215 in the N+ group. No OS benefit from RT was observed in T4 tumors (N0 and N+ groups).

CONCLUSIONS: RT was associated with improved survival in M0 MCC, irrespective of the nodal status. LNR >0.215 is a useful prognostic factor for clinical decision-making and for stratification and interpretation of clinical trials.

PMID:35485165 | DOI:10.1002/cam4.4773

Merkel cell carcinoma in Taiwan: A rare tumour with a better prognosis in those harbouring Merkel cell polyomavirus

Fetched: April 30th, 2022, 5:01am GMT by S W Chen

Malays J Pathol. 2022 Apr;44(1):61-66.

ABSTRACT

Merkel cell carcinoma (MCC) is a rare malignant cutaneous neuroendocrine tumour affecting mainly elderly patients and is more common in the West than in Asia. It is associated with Merkel cell polyomavirus (MCPyV), immunosuppression, and ultraviolet light. In this study, we retrospectively investigated the first series of MCC from Taiwan and identified 19 cases from three tertiary centres. All patients were males with a median age of 67.5. Twelve (63%) cases occurred in the extremities, with one unique case presenting initially as nodal metastasis of unknown primary. Immunohistochemically, the great majority of tumours expressed CK20 (89%), synaptophysin (89%), and INSM1 (84%), with none positive for TTF1. Eleven (58%) cases were positive for MCPyV by immunohistochemistry (clone CM2B4). All patients were treated with excision, including four with additional radiotherapy and one with radiotherapy and chemotherapy. Nodal status and treatment modalities significantly affected survival. The median survival time of MCPyV-positive cases was much longer than the negative cases (median 40 vs. 10 months). In summary, we presented the first report on the clinicopathological features of MCC in Taiwan, with 58% cases associated with MCPyV. The prognosis of patients with MCPyV-positive tumours was better than those negative for MCPyV.

PMID:35484887

Neoadjuvant PD-1 Blockade in Resectable Merkel Cell Carcinoma

Posted: August 10th, 2022, 2:00pm GMT

Condition: Merkel Cell Carcinoma
Intervention: Drug: Pembrolizumab
Sponsors: Abramson Cancer Center of the University of Pennsylvania; Merck Sharp & Dohme LLC
Not yet recruiting

Immunological Variables Associated to ICI Toxicity in Cancer Patients

Posted: June 23rd, 2022, 2:00pm GMT

Conditions: Breast Cancer; Melanoma; Non Small Cell Lung Cancer; Non-melanoma Skin Cancer; Gastrointestinal Cancer; Head and Neck Cancer; Renal Cell Carcinoma; Small Cell Lung Cancer; Mesothelioma, Malignant; Bladder Cancer; Merkel Cell Carcinoma; Hepatocellular Carcinoma; MSI-H Colorectal Cancer
Intervention: Drug: Checkpoint Blockade, Immune
Sponsor: Jules Bordet Institute
Recruiting

Permalink for 'Study To Evaluate The Safety, Tolerability And Immunogenicity Of 4 mg Of ITI-3000 In Patients With Polyomavirus-Positive Merkel Cell Carcinoma (MCC)'

Study To Evaluate The Safety, Tolerability And Immunogenicity Of 4 mg Of ITI-3000 In Patients With Polyomavirus-Positive Merkel Cell Carcinoma (MCC)

Posted: June 16th, 2022, 2:00pm GMT

Condition: Merkel Cell Carcinoma
Intervention: Drug: ITI-3000
Sponsor: Immunomic Therapeutics, Inc.
Recruiting

Exercise to Boost Response to Checkpoint Blockade Immunotherapy

Posted: May 3rd, 2022, 2:00pm GMT

Conditions: Cutaneous Melanoma; Cutaneous Squamous Cell Carcinoma; Merkel Cell Carcinoma
Interventions: Other: Excerise; Drug: Checkpoint Blockade, Immune
Sponsor: H. Lee Moffitt Cancer Center and Research Institute
Recruiting

L19IL2/L19TNF in Skin Cancer Patients

Posted: April 15th, 2022, 2:00pm GMT

Conditions: BCC - Basal Cell Carcinoma; SCC - Squamous Cell Carcinoma; Merkel Cell Carcinoma; Keratoacanthoma of Skin; Malignant Adnexal Tumors of the Skin (MATS); Tumors From Cutaneous T-cell Lymphoma (CTCL); Kaposi Sarcoma
Intervention: Drug: L19IL2/L19TNF
Sponsor: Philogen S.p.A.
Not yet recruiting

Permalink for 'Personalized Neoantigen Peptide-Based Vaccine in Combination With Pembrolizumab for the Treatment of Advanced Solid Tumors, The PNeoVCA Study'

Personalized Neoantigen Peptide-Based Vaccine in Combination With Pembrolizumab for the Treatment of Advanced Solid Tumors, The PNeoVCA Study

Posted: March 8th, 2022, 3:00pm GMT

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; National Cancer Institute (NCI)
Recruiting

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

Posted: March 4th, 2022, 3:00pm GMT

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

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

Posted: November 15th, 2021, 3:00pm GMT

Conditions: Hepatocellular Carcinoma; Squamous Cell Carcinoma of the Lung; Merkel Cell Carcinoma; Myxoid/Round Cell Liposarcoma
Intervention: Biological: CAR-GPC3 T Cells
Sponsors: SOTIO, LLC; SOTIO Biotech
Recruiting

FT538 in Combination With Monoclonal Antibodies in Advanced Solid Tumors

Posted: October 6th, 2021, 2:00pm GMT

Condition: Solid Tumor, Adult
Interventions: Drug: FT538; Drug: Cyclophosphamide; Drug: Fludarabine; Combination Product: Monoclonal antibody - Dose Escalation; Combination Product: Monoclonal antibody - Dose Expansion
Sponsor: Fate Therapeutics
Recruiting

Study of 89Zr-Df-crefmirlimab PET/CT in Subjects With Advanced or Metastatic Malignancies

Posted: August 19th, 2021, 2:00pm GMT

Conditions: Melanoma; Merkel Cell Carcinoma, Unspecified; Renal Cell Carcinoma; Non Small Cell Lung Cancer
Intervention: Biological: zirconium Zr 89 crefmirlimab berdoxam
Sponsor: ImaginAb, Inc.
Recruiting

Neoadjuvant Cemiplimab in Stage I-II Merkel Cell Carcinoma: Safety and Biomarker Analysis

Posted: July 23rd, 2021, 2:00pm GMT

Condition: Merkel Cell Carcinoma
Intervention: Drug: Cemiplimab-Rwlc
Sponsors: H. Lee Moffitt Cancer Center and Research Institute; Regeneron Pharmaceuticals; Sanofi-Synthelabo
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, 2:00pm GMT

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
Sponsor: M.D. Anderson Cancer Center
Recruiting

IFx-Hu2.0 Expanded Access Program

Posted: April 21st, 2021, 2:00pm GMT

Conditions: Cutaneous Melanoma, Stage III; Cutaneous Melanoma, Stage IV; Merkel Cell Carcinoma; Cutaneous Squamous Cell Carcinoma
Intervention: Biological: IFx-Hu2.0
Sponsor: Morphogenesis, Inc.
Available

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

Posted: March 10th, 2021, 3:00pm GMT

Condition: 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, 3:00pm GMT

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

Improving Patient and Caregiver Understanding of Risks and Benefits of Immunotherapy for Advanced Cancer

Posted: December 17th, 2020, 3:00pm GMT

Conditions: Stage IV Melanoma; Advanced Lung Cancer; Stage IV Non-Small Cell Lung Cancer; Unresectable Non-Small Cell Lung Carcinoma; Unresectable Stage III Non-Small Cell Lung Cancer; Small Cell Lung Cancer Extensive Stage; Stage IV Merkel Cell Carcinoma; Stage IV Cutaneous Squamous Cell Carcinoma; Stage IV Basal Cell Carcinoma; Stage IV Breast Cancer; Stage IV Colorectal Cancer; Stage IV Gastric Cancer; Stage IV Esophageal Cancer; Stage IV Hepatocellular Cancer; Stage IV Renal Cell Carcinoma; Stage IV Bladder Cancer; Stage IV Head and Neck Squamous Cell Carcinoma; Stage IV Cervical Cancer; Stage IV Endometrial Cancer; Stage IV Mesothelioma; Immunotherapy; Immune Checkpoint Inhibitors
Interventions: Other: Educational Video and QPL List; Other: Usual Care
Sponsors: Massachusetts General Hospital; Conquer Cancer Foundation
Recruiting

Immunotherapy Adjuvant Trial in Patients With Stage I-III Merkel Cell Carcinoma

Posted: March 2nd, 2020, 3:00pm GMT

Conditions: Merkel Cell Carcinoma; Merkel Cell Carcinoma, Stage I; Merkel Cell Carcinoma, Stage II; Merkel Cell Carcinoma, Stage III; Neuroendocrine Tumors; Carcinoma Neuroendocrine Skin
Interventions: Drug: Avelumab; Drug: Placebo
Sponsor: Melanoma and Skin Cancer Trials Limited
Recruiting

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

Posted: February 17th, 2020, 3:00pm GMT

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)
Intervention: Drug: INCB099318
Sponsor: Incyte Corporation
Recruiting

Targeted Therapy and Avelumab in Merkel Cell Carcinoma

Posted: February 10th, 2020, 3:00pm GMT

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

A Study to Evaluate the Safety and Pharmacokinetics of OC-001 in Patients With Locally Advanced or Metastatic Cancers

Posted: February 7th, 2020, 3:00pm GMT

Conditions: Cancer; Neoplasms; Metastatic Cancer; Triple Negative Breast Cancer; Gastric Cancer; Cervical Cancer; Ovarian Cancer; Hepatocellular Carcinoma; Squamous Cell Carcinoma of Head and Neck; Urothelial Carcinoma; Urothelial Neoplasm; Non Small Cell Lung Cancer; Renal Cell Carcinoma; Locally Advanced Solid Tumor; Locally Advanced Malignant Neoplasm; Squamous Cell Carcinoma; Sarcoma; Merkel Cell Carcinoma; Bladder Cancer
Interventions: Drug: OC-001; Drug: OC-001 in Combination
Sponsor: Ocellaris Pharma, Inc.
Recruiting

TAEK-VAC-HerBy Vaccine for Brachyury and HER2 Expressing Cancer

Posted: January 29th, 2020, 3:00pm GMT

Conditions: Chordoma; Breast Cancer; Gastric/Gastroesophageal Junction Cancer; Ovarian Cancer; Prostate Cancer; Colorectal Cancer; Pancreatic Cancer; Hepatocellular Cancer; Merkel Cell Cancer; Small Cell Lung Cancer
Intervention: Biological: TAEK-VAC-HerBy
Sponsor: Bavarian Nordic
Recruiting

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

Posted: January 21st, 2020, 3:00pm GMT

Conditions: Thyroid; 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: SO-C101; Drug: pembrolizumab
Sponsors: SOTIO Biotech AG; SOTIO a.s.
Recruiting

LITT and Pembrolizumab in Recurrent Brain Metastasis

Posted: December 5th, 2019, 3:00pm GMT

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
Intervention: Combination Product: LITT + Pembrolizumab
Sponsors: University of Florida; Monteris Medical
Recruiting

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

Posted: November 12th, 2019, 3:00pm GMT

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

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

Posted: November 8th, 2019, 3:00pm GMT

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
Sponsor: Antoinette J Wozniak, MD
Recruiting

Safety, PK and Efficacy of ONC-392 in Monotherapy and in Combination of Anti-PD-1 in Advanced Solid Tumors and NSCLC

Posted: October 28th, 2019, 2:00pm GMT

Conditions: Non Small Cell Lung Cancer; Advanced Solid Tumor; Metastatic Melanoma; Metastatic Head and Neck Carcinoma; Metastatic Renal Cell Carcinoma; Metastatic Colorectal Cancer; Sarcomas; Metastatic Prostate Cancer; Ovarian Cancer; Small Cell Lung Cancer; Metastatic Breast Cancer; Merkel Cell Carcinoma; Pancreas Cancer; Gastric Cancer; Esophageal Cancer; Gastroesophageal Junction Adenocarcinoma; Cervical Cancer
Interventions: Drug: ONC-392; Drug: Pembrolizumab; Drug: Osimertinib
Sponsors: OncoC4, Inc.; National Cancer Institute (NCI)
Recruiting

Focused Ultrasound Ablation and PD-1 Antibody Blockade in Advanced Solid Tumors

Posted: October 4th, 2019, 2:00pm GMT

Conditions: Melanoma; Breast Cancer; Merkel Cell Carcinoma; Squamous Cell Cancer; Non Small Cell Lung Cancer; Cervical Cancer; Urothelial Carcinoma; Ovarian Cancer; Hepatocellular Carcinoma; Small-cell Lung Cancer; Microsatellite Instability High; Gastric Cancer; Esophageal Cancer
Interventions: Device: Echopulse; Drug: Poly ICLC; Drug: Standard of Care PD-1 Therapy
Sponsors: Craig L Slingluff, Jr; Theraclion
Recruiting

Phase II Multicenter Study of Talimogene Laherparepvec in Classic or Endemic Kaposi Sarcoma

Posted: August 22nd, 2019, 2:00pm GMT

Condition: Kaposi Sarcoma
Intervention: Drug: Talimogene laherparepvec
Sponsor: Assistance Publique - Hôpitaux de Paris
Recruiting

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

Posted: August 6th, 2019, 2:00pm GMT

Condition: Advanced Solid Tumors
Intervention: Drug: FF-10850 Topotecan Liposome Injection
Sponsor: Fujifilm Pharmaceuticals U.S.A., Inc.
Recruiting

Adoptive Transfer of Tumor Infiltrating Lymphocytes for Advanced Solid Cancers

Posted: May 2nd, 2019, 2:00pm GMT

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
Sponsor: Udai Kammula
Recruiting

Navtemadlin (KRT-232) With or Without Anti-PD-1/Anti-PD-L1 for the Treatment of Patients With Merkel Cell Carcinoma

Posted: December 26th, 2018, 3:00pm GMT

Condition: Merkel Cell Carcinoma
Interventions: Drug: KRT-232; Drug: Avelumab
Sponsor: Kartos Therapeutics, Inc.
Recruiting

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

Posted: November 20th, 2018, 3:00pm GMT

Condition: Other Skin
Interventions: Biological: Autologous MCPyV-specific HLA-A02-restricted TCR-transduced CD4+ and CD8+ T-cells FH-MCVA2TCR; Drug: Avelumab; Biological: Pembrolizumab; Radiation: Radiation Therapy
Sponsors: Fred Hutchinson Cancer Center; National Cancer Institute (NCI); bluebird bio
Recruiting

Adjuvant Avelumab in Merkel Cell Cancer

Posted: September 5th, 2017, 2:00pm GMT

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
Recruiting

Phase I Dose Escalation Study for VIP152 in Patients With Advanced Cancer

Posted: December 21st, 2015, 3:00pm GMT

Condition: Neoplasms
Interventions: Drug: VIP152 (BAY 1251152); Drug: VIP152 (BAY 1251152) 30 mg; Drug: Keytruda; Drug: VIP152 (BAY 1251152) 15 mg
Sponsor: Vincerx Pharma, Inc.
Recruiting

Permalink for 'Metronomic Temozolomide in Unfit NENs Patients Metronomic Temozolomide in Unfit Patients With Advanced Neuroendocrine Neoplasms (NENs): MeTe Study'

Metronomic Temozolomide in Unfit NENs Patients Metronomic Temozolomide in Unfit Patients With Advanced Neuroendocrine Neoplasms (NENs): MeTe Study

Posted: September 26th, 2022, 2:00pm GMT

Conditions: Neuroendocrine Tumors; Frailty; Chemotherapy Effect
Intervention: Drug: Temozolomide capsule
Sponsor: European Institute of Oncology
Recruiting

EUS-FNI for MEN1-related Pancreatic Neuroendocrine Tumors

Posted: September 26th, 2022, 2:00pm GMT

Conditions: Multiple Endocrine Neoplasia Type 1; Pancreatic Neuroendocrine Tumor
Intervention: Procedure: EUS-guided fine-needle injection
Sponsor: Guangxi Medical University
Recruiting

Pre-planning Mathematical Models in EUS-guided Laser Ablation of Pancreatic Lesions

Posted: September 22nd, 2022, 2:00pm GMT

Condition: Pancreatic Neoplasms
Intervention: Device: The medical device used in this study is a 980 nm wavelength diode laser with maximum output of 30 W (EUFOTON Laser Spectrum).
Sponsors: Campus Bio-Medico University; Politecnico di Milano
Not yet recruiting

A Phase 1/2 Study of Oral MRT-2359 in Selected Cancer Patients

Posted: September 19th, 2022, 2:00pm GMT

Conditions: Phase 1; NSCLC; SCLC; High-grade Neuroendocrine Cancer of Any Primary Site; DLBCL; Tumor With L-MYC and N-MYC Amplification; Phase 2; NSCLC With High or Low L-MYC or N-MYC Expression; SCLC With High or Low L-MYC or N-MYC Expression; Solid Tumors With L-MYC or N-MYC Amplification
Intervention: Drug: Oral MRT-2359
Sponsor: Monte Rosa Therapeutics, Inc
Not yet recruiting

Permalink for 'A Study of Safety and Efficacy of KFA115 Alone and KFA115 in Combination With Tislelizumab in Patients With Select Advanced Cancers'

A Study of Safety and Efficacy of KFA115 Alone and KFA115 in Combination With Tislelizumab in Patients With Select Advanced Cancers

Posted: September 19th, 2022, 2:00pm GMT

Conditions: Carcinoma, Non-Small-Cell Lung; Cutaneous Melanoma; Carcinoma, Renal Cell; Carcinoma, Ovarian Epithelial; Nasopharyngeal Carcinoma; Carcinoma, Thymic; Anal Cancer; Mesothelioma; Esophagogastric Cancer; High Microsatellite Instability Colorectal Carcinoma; Squamous Cell Carcinoma of Head and Neck
Interventions: Drug: KFA115; Drug: tislelizumab
Sponsor: Novartis Pharmaceuticals
Not yet recruiting

A Study to Learn About the Study Medicine Called PF-07799544 in People With Advanced Solid Tumors

Posted: September 13th, 2022, 2:00pm GMT

Conditions: Melanoma; Glioma; Thyroid Cancer; Non-Small Cell Lung Cancer; Malignant Neoplasms; Brain Neoplasms; Colorectal Cancer
Interventions: Drug: PF-07799544; Drug: PF-07284890; Drug: PF-07799933; Drug: encorafenib
Sponsor: Pfizer
Not yet recruiting

Circulating Tumour Cells as Biomarkers to Predict Prostate Cancer Metastasis for Treatment Stratification of Cancer

Posted: September 9th, 2022, 2:00pm GMT

Condition: Prostate Cancer
Intervention: Diagnostic Test: CTC Blood Test
Sponsors: Queen Mary University of London; University College London Hospitals
Recruiting

Evaluation of the 18F-PSMA Positron Emission Tomography (PET)/CT in Patients With Medullary Thyroid Cancer

Posted: September 9th, 2022, 2:00pm GMT

Conditions: Medullary Thyroid Cancer; Medullary Thyroid Carcinoma; Thyroid Carcinoma, Medullary; Thyroid Cancer, Medullary
Intervention: Drug: 18F-PSMA-1007
Sponsor: University Medical Center Groningen
Not yet recruiting

Evaluation of the Results of Simultaneous Pancreatic and Hepatic Resections for Metastatic Neuroendocrine Tumors.

Posted: September 5th, 2022, 2:00pm GMT

Condition: Tumor of Pancreas
Intervention:
Sponsor: University Hospital, Strasbourg, France
Recruiting

Biomarker Identification of Radionuclide Therapy-induced Radiation Responses

Posted: August 24th, 2022, 2:00pm GMT

Condition: Neuroendocrine Tumors
Intervention: Drug: Lutathera
Sponsor: Erasmus Medical Center
Not yet recruiting

Assessment of Compliance With Monitoring Conducted by a Physician in Person or by a Nurse in Remote Monitoring

Posted: August 15th, 2022, 2:00pm GMT

Conditions: Stage I Testicular Seminoma; Stage I Testicular Nonseminomatous Germ Cell Tumor; Gastrointestinal Stromal Tumors; Ovarian Germ Cell Tumor; Adenocarcinoma, Clear Cell; Borderline Ovarian Tumor; Sex Cord-Stromal Tumor; Mucinous Adenocarcinoma of Ovary; Carcinoma, Small Cell; Carcinosarcoma, Ovarian; Serous Tumor of Ovary; Glioma; Neuroendocrine Tumors; Aggressive Fibromatosis of Abdominal Wall (Disorder)
Intervention: Other: Oncological Follow-up
Sponsors: Centre Oscar Lambret; Canceropôle Nord Ouest; Groupement Interrégional de Recherche Clinique et d'Innovation
Not yet recruiting

Neoadjuvant PD-1 Blockade in Resectable Merkel Cell Carcinoma

Posted: August 10th, 2022, 2:00pm GMT

Condition: Merkel Cell Carcinoma
Intervention: Drug: Pembrolizumab
Sponsors: Abramson Cancer Center of the University of Pennsylvania; Merck Sharp & Dohme LLC
Not yet recruiting

Dexmedetomidine Infusion on Intraoperative Propofol,Fentanyl Requirements in Spine Surgery for Pediatric Cancer Patients

Posted: August 9th, 2022, 2:00pm GMT

Conditions: Spine Cancer; Anesthesia
Interventions: Drug: Precedex Injectable Product; Drug: Saline
Sponsor: Children's Cancer Hospital Egypt 57357
Recruiting

Permalink for 'Study of RYZ101 Compared With SOC in Pts With Inoperable SSTR+ Well-differentiated GEP-NET That Has Progressed Following 177Lu-SSA Therapy'

Study of RYZ101 Compared With SOC in Pts With Inoperable SSTR+ Well-differentiated GEP-NET That Has Progressed Following 177Lu-SSA Therapy

Posted: July 28th, 2022, 2:00pm GMT

Conditions: GEP-NET; Gastroenteropancreatic Neuroendocrine Tumor; Gastroenteropancreatic Neuroendocrine Tumor Disease; Neuroendocrine Tumors; Carcinoid; Carcinoid Tumor; Pancreatic NET
Interventions: Drug: RYZ101; Drug: Everolimus 10 mg; Drug: Sunitinib 37.5 MG; Drug: Octreotide LAR 60 MG Injection; Drug: Lanreotide 120Mg Sa Susp Inj Syringe
Sponsor: RayzeBio, Inc.
Recruiting

Study of Factors Associated With Significant MYoCArdian Uptake on 68Ga-DOTATOC PET Scans for Oncology

Posted: July 28th, 2022, 2:00pm GMT

Condition: Oncologic Disorders
Intervention:
Sponsor: Central Hospital, Nancy, France
Not yet recruiting

Imaging and Genomic Biomarkers to Predict Response in Prostate Cancer

Posted: July 28th, 2022, 2:00pm GMT

Condition: Prostate Cancer
Interventions: Radiation: External beam radiation therapy; Radiation: Prostate brachytherapy boost; Drug: Androgen deprivation therapy; Diagnostic Test: Positron emission tomography (PET)/magnetic resonance imaging (MRI)
Sponsor: University of Wisconsin, Madison
Not yet recruiting

Artificial Intelligence in EUS for Diagnosing Pancreatic Solid Lesions

Posted: July 27th, 2022, 2:00pm GMT

Conditions: Pancreatic Ductal Adenocarcinoma; Pancreatitis, Chronic; Pancreatic Neuroendocrine Tumor; Autoimmune Pancreatitis
Intervention: Diagnostic Test: EUS-AI model
Sponsors: Huazhong University of Science and Technology; The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School; LanZhou University
Not yet recruiting

177Lu-DOTA-EB-TATE in Untreated (Naïve) Adult Patients With Advanced, Well- Differentiated Neuroendocrine Tumors

Posted: July 26th, 2022, 2:00pm GMT

Condition: Neuroendocrine Tumors
Interventions: Drug: 177Lu-DOTA-EB-TATE; Other: Amino Acid Solution
Sponsors: Molecular Targeting Technologies, Inc.; ClinSmart
Recruiting

Permalink for 'A Single-arm Trial of Atezolizumab/Platinum/Etoposide for the Treatment of Advanced Large-cell Neuroendocrine Cancer of the Lung'

A Single-arm Trial of Atezolizumab/Platinum/Etoposide for the Treatment of Advanced Large-cell Neuroendocrine Cancer of the Lung

Posted: July 22nd, 2022, 2:00pm GMT

Condition: Large Cell Neuroendocrine Carcinoma of the Lung
Intervention: Drug: Atezolizumab
Sponsors: Technische Universität Dresden; Roche Pharma AG
Recruiting

Permalink for 'Phase I, Open-Label, Study of Tumor Infiltrating Lymphocytes Engineered With Membrane Bound IL15 Plus Acetazolamide in Adult Patients With Metastatic Melanoma'

Phase I, Open-Label, Study of Tumor Infiltrating Lymphocytes Engineered With Membrane Bound IL15 Plus Acetazolamide in Adult Patients With Metastatic Melanoma

Posted: July 22nd, 2022, 2:00pm GMT

Conditions: Tumor; Metastatic Melanoma; Melanoma
Interventions: Drug: OBX-115; Drug: Acetazolamide; Drug: Cyclophosphamide; Drug: Furosemide; Drug: Mesna; Drug: Fludarabine Phosphate
Sponsor: M.D. Anderson Cancer Center
Recruiting

Nivolumab and DAY101 for Treatment of Craniopharyngioma in Children and Young Adults

Posted: July 19th, 2022, 2:00pm GMT

Conditions: Craniopharyngioma, Child; Craniopharyngioma; Recurrent Craniopharyngioma
Interventions: Drug: Nivolumab; Drug: DAY101
Sponsors: Sabine Mueller, MD, PhD; Bristol-Myers Squibb; Day One Biopharmaceuticals, Inc.
Recruiting

A Study Comparing Treatment With Lutetium[177Lu] Oxodotreotide Injection to Octreotide LAR in Patients With GEP-NETs

Posted: July 15th, 2022, 2:00pm GMT

Condition: Neuroendocrine Tumors
Interventions: Drug: Lutetium[177Lu] Oxodotreotide Injection; Drug: Octreotide LAR
Sponsor: Sinotau Pharmaceutical Group
Not yet recruiting

A Study to Find the Best Dose of ASP5354 to Show Lymph Nodes in People With Breast Cancer or Melanoma During Surgery

Posted: July 14th, 2022, 2:00pm GMT

Conditions: Sentinel Lymph Node Biopsy; Breast Cancer; Melanoma
Intervention: Drug: pudexacianinium chloride
Sponsor: Astellas Pharma Inc
Recruiting

68Ga-DOTATOC Radio-Guided Surgery With β-Probe in GEP-NET

Posted: July 7th, 2022, 2:00pm GMT

Conditions: Neuroendocrine Tumor Carcinoid; Neuroendocrine Tumor of Pancreas; Gep Net
Intervention:
Sponsor: European Institute of Oncology
Recruiting

Postmortem Evaluation of Adrenal and Other Endocrine Tumors in Patients With Sudden Death

Posted: July 7th, 2022, 2:00pm GMT

Conditions: Primary Aldosteronism; Adrenal Cushing Syndrome; Pheochromocytoma; Endocrine Neoplasia
Interventions: Diagnostic Test: Adrenal aldosterone synthase (CYP11B2) staining; Diagnostic Test: Adrenal cortisol synthase (CYP11B1) staining; Diagnostic Test: Histopathological analysis
Sponsors: Helsinki University Central Hospital; Finnish Institute for Health and Welfare; University of Helsinki; Tampere University Hospital; Tampere University
Recruiting

BioMEL- Diagnostic and Prognostic Factors in Melanoma.

Posted: July 6th, 2022, 2:00pm GMT

Conditions: Melanoma; Melanoma in Situ; Dysplastic Nevi; Mole (Dermatology); Image; Mutation
Intervention: Diagnostic Test: Imaging
Sponsor: Region Skane
Recruiting

TARGETed Therapy Drug MONITOring in DIGestive Oncology

Posted: July 4th, 2022, 2:00pm GMT

Conditions: Digestive Cancer; Metastatic Colorectal Cancer; Hepatocellular Carcinoma; GIST; Neuroendocrine Tumors
Intervention: Other: Blood sampling to build population pharmacokinetics model
Sponsor: UNICANCER
Recruiting

Permalink for 'FAPi Radioligand OpeN-Label, Phase 1 Study to Evaluate Safety, Tolerability and DosImetry of [Lu-177]-PNT6555; A Dose Escalation Study for TReatment of Patients With Select Solid Tumors (FRONTIER)'

FAPi Radioligand OpeN-Label, Phase 1 Study to Evaluate Safety, Tolerability and DosImetry of [Lu-177]-PNT6555; A Dose Escalation Study for TReatment of Patients With Select Solid Tumors (FRONTIER)

Posted: June 27th, 2022, 2:00pm GMT

Conditions: Pancreatic Ductal Adenocarcinoma; Colorectal Cancer; Esophageal Cancer; Melanoma (Skin); Soft Tissue Sarcoma
Interventions: Drug: [Ga-68]-PNT6555; Drug: [Lu-177]-PNT6555
Sponsor: POINT Biopharma
Recruiting

Endoscopic Methods for Small Rectal Neuroendocrine Tumors