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Permalink for 'The Genomic Landscape of Merkel Cell Carcinoma and Clinicogenomic Biomarkers of Response to Immune Checkpoint Inhibitor Therapy.'

The Genomic Landscape of Merkel Cell Carcinoma and Clinicogenomic Biomarkers of Response to Immune Checkpoint Inhibitor Therapy.

Fetched: September 27th, 2020, 5:01am GMT

The Genomic Landscape of Merkel Cell Carcinoma and Clinicogenomic Biomarkers of Response to Immune Checkpoint Inhibitor Therapy.

Clin Cancer Res. 2019 10 01;25(19):5961-5971

Authors: Knepper TC, Montesion M, Russell JS, Sokol ES, Frampton GM, Miller VA, Albacker LA, McLeod HL, Eroglu Z, Khushalani NI, Sondak VK, Messina JL, Schell MJ, DeCaprio JA, Tsai KY, Brohl AS

Abstract
PURPOSE: Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy, which has demonstrated sensitivity to immune checkpoint inhibitor therapy. Here, we perform the largest genomics study in MCC to date to characterize the molecular landscape and evaluate for clinical and molecular correlates to immune checkpoint inhibitor response.
EXPERIMENTAL DESIGN: Comprehensive molecular profiling was performed on 317 tumors from patients with MCC, including the evaluation of oncogenic mutations, tumor mutational burden (TMB), mutational signatures, and the Merkel cell polyomavirus (MCPyV). For a subset of 57 patients, a retrospective analysis was conducted to evaluate for clinical and molecular correlates to immune checkpoint inhibitor response and disease survival.
RESULTS: Genomic analyses revealed a bimodal distribution in TMB, with 2 molecularly distinct subgroups. Ninety-four percent (n = 110) of TMB-high specimens exhibited an ultraviolet light (UV) mutational signature. MCPyV genomic DNA sequences were not identified in any TMB-high cases (0/117), but were in 63% (110/175) of TMB-low cases. For 36 evaluable patients treated with checkpoint inhibitors, the overall response rate was 44% and response correlated with survival at time of review (100% vs. 20%, P < 0.001). Response rate was 50% in TMB-high/UV-driven and 41% in TMB-low/MCPyV-positive tumors (P = 0.63). Response rate was significantly correlated with line of therapy: 75% in first-line, 39% in second-line, and 18% in third-line or beyond (P = 0.0066). PD-1, but not PD-L1, expression was associated with immunotherapy response (77% vs. 21%, P = 0.00598, for PD-1 positive and negative, respectively).
CONCLUSIONS: We provide a comprehensive genomic landscape of MCC and demonstrate clinicogenomic associates of immunotherapy response.

PMID: 31399473 [PubMed - indexed for MEDLINE]

Merkel Cell Carcinoma of the Digit.

Fetched: September 27th, 2020, 5:01am GMT

Merkel Cell Carcinoma of the Digit.

Ann Plast Surg. 2019 08;83(2):169-171

Authors: Persitz J, Atzmon R, Keren T, Avisar E

Abstract
Merkel cell carcinoma (MCC) is a biologically aggressive neuroendocrine tumor of the skin. There are roughly 1500 new cases of MCC diagnosed every year in the United States, with an increased incidence over the past 15 years reaching up to 8%. Epidemiological studies show that the highest MCC incidence is seen in men older than 65 years, with a ratio of 0.23 per 10,000 among whites. Merkel cell carcinoma of the skin most commonly presents as a single, rapidly growing, flesh-colored, painless mass. Because MCC is uncommon, histopathological examination is usually delayed. Because of the high mortality rate associated with this aggressive tumor, a multidisciplinary panel is recommended to ensure high-quality coordinated care. The choice of treatment option depends on disease characteristics, staging at presentation, regional lymph node involvement, comorbidities, and performance status of the patient. We report a case of MCC to alert medical professionals of this potentially fatal tumor, as early diagnosis and treatment may improve morbidity and mortality rates.

PMID: 31008795 [PubMed - indexed for MEDLINE]

Merkel Cell Polyomavirus Large T Antigen Unique Domain Regulates Its Own Protein Stability and Cell Growth.

Fetched: September 25th, 2020, 5:01am GMT

Merkel Cell Polyomavirus Large T Antigen Unique Domain Regulates Its Own Protein Stability and Cell Growth.

Viruses. 2020 Sep 18;12(9):

Authors: Nwogu N, Ortiz LE, Kwun HJ

Abstract
Merkel cell polyomavirus (MCV) is the only known human oncogenic virus in the polyomaviridae family and the etiological agent of most Merkel cell carcinomas (MCC). MCC is an aggressive and highly metastatic skin cancer with a propensity for recurrence and poor prognosis. Large tumor antigen (LT), is an essential oncoprotein for MCV transcription, viral replication, and cancer cell proliferation. MCV LT is a short-lived protein that encodes a unique domain: MCV LT unique regions (MURs). These domains consist of phosphorylation sites that interact with multiple E3 ligases, thus limiting LT expression and consequently, viral replication. In this study, we show that MURs are necessary for regulating LT stability via multiple E3 ligase interactions, resulting in cell growth arrest. While expression of wild-type MCV LT induced a decrease in cellular proliferation, deletion of the MUR domains resulted in increased LT stability and cell proliferation. Conversely, addition of MURs to SV40 LT propagated E3 ligase interactions, which in turn, reduced SV40 LT stability and decreased cell growth activity. Our results demonstrate that compared to other human polyomaviruses (HPyVs), MCV LT has evolved to acquire the MUR domains that are essential for MCV LT autoregulation, potentially leading to viral latency and MCC.

PMID: 32962090 [PubMed - in process]

Avelumab: search for combinations of immune checkpoint inhibition with chemotherapy.

Fetched: September 23rd, 2020, 5:01am GMT

Avelumab: search for combinations of immune checkpoint inhibition with chemotherapy.

Expert Opin Biol Ther. 2020 Sep 21;:

Authors: Hamilton G

Abstract
INTRODUCTION: Immune checkpoint inhibition (ICI) has proved successful for selected tumors and a subpopulation of patients. The human monoclonal IgG1 antibody (mAB) avelumab capable of mediating antibody-dependent cytotoxicity (ADCC) lysis is directed to programmed death ligand-1 (PD-L1) of tumor cells and is tested in trials aiming to improve ICI in combination with chemotherapeutic drugs. Areas covered: This article presents an overview of the current trials to enhance ICI regimens using avelumab in combination with chemotherapeutics, antiangiogenetic drugs and immunomodulators. Predictive factors for this kind of immunochemotherapy are discussed. Expert opinion: Clinical data demonstrate that avelumab shows efficacy in cancer patients against Merkel cell carcinoma (MCC), renal cell carcinoma (RCC) and urothelial cancers as single agent. Furthermore, avelumab in combination with axitinib in RCC increases survival and exhibits activity in combination with docetaxel in urothelial carcinoma. However, several other immunochemotherapy trials for ovarian cancer, gastric cancer and non-small lung cancer (NSCLC) showed no activity due to factors disfavoring administration of immunotherapy combos.

PMID: 32954871 [PubMed - as supplied by publisher]

Avelumab for advanced Merkel cell carcinoma in the Netherlands: a real-world cohort.

Fetched: September 21st, 2020, 5:01am GMT

Avelumab for advanced Merkel cell carcinoma in the Netherlands: a real-world cohort.

J Immunother Cancer. 2020 Sep;8(2):

Authors: Levy S, Aarts MJB, Eskens FALM, Keymeulen KBMI, Been LB, Grünhagen D, van Akkooi A, Jalving M, Tesselaar MET

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) is associated with high recurrence rates and poor survival when metastatic disease is present. The immune checkpoint inhibitor avelumab has shown high response rates (RRs) and durable responses in patients with advanced MCC (aMCC) in clinical trials. To date, only results from clinical trials, patients treated in an expanded access program and very small numbers of patients have been reported. In this study, detailed real-world efficacy and toxicity data of avelumab in patients with aMCC are reported.
METHODS: Patients with aMCC treated in four dedicated referral centers in the Netherlands were analyzed from February 2017 until December 2019. Patients were included if they had received at least one administration of avelumab, regardless of previous lines of therapy. Patient data were collected retrospectively from patient records. Primary endpoints were response rate (RR) and duration of response (DOR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity.
RESULTS: Fifty-four patients received avelumab. Eight (15%) patients had locally advanced disease (laMCC). In 40 (74%) patients, avelumab was first-line treatment, these included all patients with laMCC. The median follow-up was 8.9 (range 0.5-35.9) months. RR was 57% (n=31) with 24% (n=13) of patients achieving a complete response. The median DOR was 8.4 (range 1.3-22.1) months and 23 (43%) patients had an ongoing response at the end of the study. The median PFS was 8.6 (95% CI 1.6-15.5) months, and the median OS was 25.8 (95% CI 9.1-42.4) months. Six (11%) patients experienced grade 3 toxicity. No grade 4-5 toxicity was seen.
CONCLUSIONS: In this real-world cohort, clinical efficacy and toxicity outcomes in clinical practice were in line with results from clinical trials and showed relatively high RRs and durable responses in patients with aMCC.

PMID: 32948651 [PubMed - as supplied by publisher]

Health-related quality of life trajectory of treatment-naive patients with Merkel cell carcinoma receiving avelumab.

Fetched: September 19th, 2020, 5:01am GMT

Health-related quality of life trajectory of treatment-naive patients with Merkel cell carcinoma receiving avelumab.

Future Oncol. 2020 Sep 17;:

Authors: Bharmal M, Nolte S, Lebbé C, Mortier L, Brohl AS, Fazio N, Grob JJ, Pusceddu S, Hanna GJ, Hassel JC, Kiecker F, Ellers-Lenz B, Bajars M, Güzel G, Nghiem P, Hunger M, Schlichting M, Henry-Szatkowski M, D'Angelo SP

Abstract
Aim: To evaluate changes in health-related quality of life (HRQoL) in a Phase II trial (NCT02155647) of treatment-naive patients with metastatic Merkel cell carcinoma treated with avelumab (15-month follow-up). Materials & methods: Mixed-effect Models for Repeated Measures were applied to HRQoL data (FACT-M; EQ-5D-5L) to assess changes over time. Clinically derived progression-free survival was compared with HRQoL deterioration-free survival. Results: Overall, we saw relative stability in HRQoL among 116 included patients, with nonprogression associated with statistically and clinically meaningful better HRQoL compared with progressive disease. Deterioration-free survival rates (49-72% at 6 months, 40-58% at 12 months) were consistently higher/better compared with progression-free survival rates (41/31% at 6/12 months). Conclusion: These findings show unique longitudinal HRQoL data for treatment-naive metastatic Merkel cell carcinoma patients treated with avelumab. Clinical trial registration: NCT02155647 (ClinicalTrials.gov).

PMID: 32938212 [PubMed - as supplied by publisher]

[Aberrant expression of ALK and clinicopathological features in Merkel cell carcinoma].

Fetched: September 19th, 2020, 5:01am GMT

[Aberrant expression of ALK and clinicopathological features in Merkel cell carcinoma].

Zhonghua Bing Li Xue Za Zhi. 2020 Sep 08;49(9):931-933

Authors: Yuan LL, Chen XW, Wang L, Tang XB

PMID: 32892561 [PubMed - indexed for MEDLINE]

Permalink for 'Merkel Cell Carcinoma of the Head and Neck Compared to Other Anatomical Sites in a Real-World Setting: Importance of Surgical Therapy for Facial Tumors.'

Merkel Cell Carcinoma of the Head and Neck Compared to Other Anatomical Sites in a Real-World Setting: Importance of Surgical Therapy for Facial Tumors.

Fetched: September 19th, 2020, 5:01am GMT

Merkel Cell Carcinoma of the Head and Neck Compared to Other Anatomical Sites in a Real-World Setting: Importance of Surgical Therapy for Facial Tumors.

Facial Plast Surg. 2020 Jun;36(3):249-254

Authors: Kirchberger MC, Heppt MV, Schuler G, Berking C, Heinzerling L

Abstract
Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin tumor with a high propensity for nodal involvement, local recurrence, and distant metastases. Up to 50% of MCC arises on head and neck (HN), which may impede oncological treatment due to insufficiently wide excisions and a lower rate of sentinel lymph node detection due to more complicated lymph drainage. Several studies have compared the clinical outcome of HN-MCC with those of non-head and neck (NHN) MCC yielding inconsistent results. This single-center, retrospective analysis compared the clinical outcome of 26 HN-MCC patients with 30 NHN-MCC patients. Overall survival (OS) and disease-free survival (DFS) were calculated with the Kaplan-Meier method assuming proportional hazards. The mean resection margins were 1.6 and 2.0 cm for the HN and NHN cohort, respectively. Local relapses were more frequently observed in patients with HN-MCC (19 vs. 10%). Patients with HN-MCC had a median OS of 4.3 years compared with 7.5 years in patients with NHN-MCC (p = 0.277). The median OS by tumor stage was 11, 3, 2, and 3 years in stage I, II, III, and IV disease, respectively (p = 0.009). The median DFS in HN-MCC was 10 years and not reached in the cohort with NHN-MCC patients (p = 0.939). Our data suggest a trend toward poorer outcomes of HN-MCC compared with NHN-MCC. Patients with MCC on the head and neck carry a higher risk for local relapse, requiring resolute surgical treatment also in facial localizations at early stages.

PMID: 31887750 [PubMed - indexed for MEDLINE]

Complete response to avelumab and IL-15 superagonist N-803 with Abraxane in Merkel cell carcinoma: a case study.

Fetched: September 13th, 2020, 5:01am GMT

Complete response to avelumab and IL-15 superagonist N-803 with Abraxane in Merkel cell carcinoma: a case study.

J Immunother Cancer. 2020 Sep;8(2):

Authors: Drusbosky L, Nangia C, Nguyen A, Szeto C, Newton Y, Spilman P, Reddy SB

Abstract
Merkel cell carcinoma (MCC) is a rare aggressive form of skin cancer originating in neuroendocrine cells. The antiprogrammed death ligand 1 (PD-L1) monoclonal antibody (mAb) avelumab has been approved for treatment of MCC, but options are limited, should it be ineffective as a monotherapy. Combined therapy with low/moderate dose nab-paclitaxel and an interleukin 15 (IL-15)-based therapeutic such as the IL-15 'superagonist' N-803 may increase response by activation of the immune system. The case of a 71-year-old man diagnosed with MCC who achieved and maintained a complete response (CR) by treatment with the anti-PD-L1 mAb avelumab in combination with IL-15 superagonist N-803 and nab-paclitaxel (Abraxane) is presented. Avelumab treatment alone resulted in a response in a para-aortic lesion, but not the other tumor masses. N-803 was added, followed by nab-paclitaxel; CT showed a decrease in the size of the abdominal mass at 1 month, near resolution at 3 months and CR at 5 months. Abraxane was discontinued after the first CR on CT, and the patient continues on avelumab/N-803 treatment and maintains a CR. Combination of avelumab with low/moderate-dose chemotherapy and an immune enhancer such as N-803 may offer a viable treatment option for MCC patients for whom avelumab therapy alone was not effective.

PMID: 32913030 [PubMed - in process]

Permalink for 'Efficacy and safety of first-line avelumab in patients with advanced non-small cell lung cancer: results from a phase Ib cohort of the JAVELIN Solid Tumor study.'

Efficacy and safety of first-line avelumab in patients with advanced non-small cell lung cancer: results from a phase Ib cohort of the JAVELIN Solid Tumor study.

Fetched: September 12th, 2020, 5:00am GMT

Efficacy and safety of first-line avelumab in patients with advanced non-small cell lung cancer: results from a phase Ib cohort of the JAVELIN Solid Tumor study.

J Immunother Cancer. 2020 Sep;8(2):

Authors: Verschraegen CF, Jerusalem G, McClay EF, Iannotti N, Redfern CH, Bennouna J, Chen FL, Kelly K, Mehnert J, Morris JC, Taylor M, Spigel D, Wang D, Grote HJ, Zhou D, Munshi N, Bajars M, Gulley JL

Abstract
INTRODUCTION: Avelumab, an antiprogrammed death ligand-1 antibody, is approved as a monotherapy for treatment of metastatic Merkel cell carcinoma and advanced urothelial carcinoma, and in combination with axitinib for advanced renal cell carcinoma. We report the efficacy and safety of first-line avelumab in advanced non-small cell lung cancer (NSCLC).
METHODS: In a phase I expansion cohort of the JAVELIN Solid Tumor trial, patients with treatment-naive, metastatic, or recurrent NSCLC received 10 mg/kg avelumab intravenously every 2 weeks. Endpoints included best overall response, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.
RESULTS: Overall, 156 patients were enrolled and treated. Median duration of follow-up was 18.6 months (range, 15 to 23 months). The objective response rate was 19.9% (95% CI, 13.9 to 27.0), including complete response in 3 (1.9%) and partial response in 28 (17.9%). Median DOR was 12.0 months (95% CI, 6.9 to not estimable). Median PFS was 4.0 months (95% CI, 2.7 to 5.4) and the 6-month PFS rate was 38.5% (95% CI, 30.7 to 46.3). Median OS was 14.1 months (95% CI, 11.3 to 16.9) and the 12-month OS rate was 56.6% (95% CI, 48.2 to 64.1). Treatment-related adverse events (TRAEs) occurred in 107 patients (68.6%), including grade ≥3 TRAEs in 19 (12.2%). Immune-related adverse events and infusion-related reactions occurred in 31 (19.9%) and 40 patients (25.6%), respectively. No treatment-related deaths occurred.
CONCLUSION: Avelumab showed antitumor activity with a tolerable safety profile as a first-line treatment in patients with advanced NSCLC. These data support further investigation of avelumab in the phase III JAVELIN Lung 100 study.
TRIAL REGISTRATION DETAILS: ClinicalTrials.gov NCT01772004; registered January 21, 2013.

PMID: 32907924 [PubMed - in process]

Permalink for 'Current and Future Trends in Molecular Biomarkers for Diagnostic, Prognostic, and Predictive Purposes in Non-Melanoma Skin Cancer.'

Current and Future Trends in Molecular Biomarkers for Diagnostic, Prognostic, and Predictive Purposes in Non-Melanoma Skin Cancer.

Fetched: September 11th, 2020, 5:01am GMT

Current and Future Trends in Molecular Biomarkers for Diagnostic, Prognostic, and Predictive Purposes in Non-Melanoma Skin Cancer.

J Clin Med. 2020 Sep 04;9(9):

Authors: Nikolouzakis TK, Falzone L, Lasithiotakis K, Krüger-Krasagakis S, Kalogeraki A, Sifaki M, Spandidos DA, Chrysos E, Tsatsakis A, Tsiaoussis J

Abstract
Skin cancer represents the most common type of cancer among Caucasians and presents in two main forms: melanoma and non-melanoma skin cancer (NMSC). NMSC is an umbrella term, under which basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and Merkel cell carcinoma (MCC) are found along with the pre-neoplastic lesions, Bowen disease (BD) and actinic keratosis (AK). Due to the mild nature of the majority of NMSC cases, research regarding their biology has attracted much less attention. Nonetheless, NMSC can bear unfavorable characteristics for the patient, such as invasiveness, local recurrence and distant metastases. In addition, late diagnosis is relatively common for a number of cases of NMSC due to the inability to recognize such cases. Recognizing the need for clinically and economically efficient modes of diagnosis, staging, and prognosis, the present review discusses the main etiological and pathological features of NMSC as well as the new and promising molecular biomarkers available including telomere length (TL), telomerase activity (TA), CpG island methylation (CIM), histone methylation and acetylation, microRNAs (miRNAs), and micronuclei frequency (MNf). The evaluation of all these aspects is important for the correct management of NMSC; therefore, the current review aims to assist future studies interested in exploring the diagnostic and prognostic potential of molecular biomarkers for these entities.

PMID: 32899768 [PubMed]

Complete response with neoadjuvant avelumab in Merkel cell carcinoma - A case report.

Fetched: September 11th, 2020, 5:01am GMT

Complete response with neoadjuvant avelumab in Merkel cell carcinoma - A case report.

Oral Oncol. 2019 12;99:104350

Authors: Abdallah N, Nagasaka M, Chowdhury T, Raval K, Hotaling J, Sukari A

Abstract
Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine skin malignancy. We report here a case of localized MCC achieving pathologic complete response upon treatment with avelumab in the neoadjuvant setting. Preclinical and clinical studies have revealed a close relationship between MCC and the immune system, thus supporting a role for PD-1/PD-L1 inhibitors in MCC. This neoadjuvant use of PD-1/PD-L1 inhibitors can avoid potentially disfiguring surgery in MCC. As the incidence of MCC is rising, clinical trials are needed to evaluate the efficacy and safety of immunotherapy in resectable disease.

PMID: 31277904 [PubMed - indexed for MEDLINE]

COVID-19 in a patient with advanced Merkel cell carcinoma receiving immunotherapy.

Fetched: September 11th, 2020, 5:01am GMT

COVID-19 in a patient with advanced Merkel cell carcinoma receiving immunotherapy.

Immunotherapy. 2020 Sep 09;:

Authors: da Costa CM, de Souza ZS, Real Salgues AC, Harada G, Marino Rodrigues Ayres PP, Vieira Nunes DB, Katz A, Munhoz RR

Abstract
Background: Little is known about the 2019 novel coronavirus disease (COVID-19) course and outcomes in patients receiving immunotherapy. Here we describe a metastatic Merkel cell carcinoma patient with a severe acute respiratory syndrome coronavirus 2 infection while receiving pembrolizumab. Case presentation: A 66-year-old man, with a metastatic Merkel cell carcinoma receiving pembrolizumab, presented with fever. Chest computed tomography (CT) showed pulmonary ground-glass opacities, suggesting viral or immuno-related etiology. On day 7, the patient was hospitalized due to dyspnea and worsening of the radiological findings. Real time polymerase chain reaction (RT-PCR) testing confirmed COVID-19. The patient developed acute respiratory distress syndrome and acute kidney injury. Hydroxychloroquine was administered for 5 days, but discontinued after supraventricular extrasystoles. Clinical improvement allowed the patient's discharge after 81 days of hospitalization. Conclusion: A careful evaluation of oncologic patients receiving immunotherapy during the COVID-19 pandemic is of utmost importance.

PMID: 32900245 [PubMed - as supplied by publisher]

Permalink for 'The presence of Merkel cell carcinoma polyomavirus is associated with a distinct phenotype in neoplastic Merkel cell carcinoma cells and their tissue microenvironment.'

The presence of Merkel cell carcinoma polyomavirus is associated with a distinct phenotype in neoplastic Merkel cell carcinoma cells and their tissue microenvironment.

Fetched: September 10th, 2020, 5:01am GMT

The presence of Merkel cell carcinoma polyomavirus is associated with a distinct phenotype in neoplastic Merkel cell carcinoma cells and their tissue microenvironment.

PLoS One. 2020;15(7):e0232517

Authors: Mendoza MD, Santonja C, Gonzalez-Vela C, Concha A, Iglesias Pena N, Andrés-Esteban EM, Vaque JP, Cereceda L, Pajares R, Kutzner H, Requena L, Piris MA

Abstract
AIMS: Merkel cell carcinoma (MCC) is an aggressive primary neuroendocrine tumor of the skin, associated with Merkel cell polyomavirus (MCPyV) in 49-89% of cases, depending on the country of origin and the techniques of detection. The presence of MCPyV defines heterogeneity in MCC; MCPyV-negative cases bear a much higher mutational load, with a distinct ultraviolet signature pattern featuring C > T transitions, as a consequence of exposure to ultraviolet light radiation. MCC stroma has not been thoroughly studied, although MCC patients benefit from therapy targeting PD1/PDL1.
METHODS AND RESULTS: In this study, using Tissue Microarrays and immunohistochemistry, we have analyzed a series of 219 MCC cases in relation to the presence of MCPyV, and confirmed that the presence of MCPyV is associated with changes not only in the neoplastic cells, but also in the composition of the tumor stroma. Thus, MCPyV, found in 101/176 (57,4%) analyzable cases, exhibits changes in its tumor morphology, the density of the inflammatory infiltrate, the phenotype of the neoplastic cells, and the cell composition of the tumor stroma. MCPyV presence is negatively correlated with a higher level of p53 expression, and associated with a very high frequency (86%) of HLA-I expression loss, a higher apoptotic index, and a stroma richer in T-cells, cytotoxic T-cells, macrophages, PDL1-positive macrophages, and B-cells.
CONCLUSIONS: Our findings provide evidence of the basic heterogeneity of MCC, supporting the hypothesis that the presence of MCPyV may induce a rich inflammatory response, which is at least partially avoided through loss of HLA-I antigen expression. On the other hand, MCPyV-negative cases show a much higher frequency of stronger p53 expression and, probably, p53 alterations.

PMID: 32687503 [PubMed - indexed for MEDLINE]

Dissection of Merkel cell formation in hairy and glabrous skin reveals a common requirement for FGFR2-mediated signalling.

Fetched: September 10th, 2020, 5:01am GMT

Dissection of Merkel cell formation in hairy and glabrous skin reveals a common requirement for FGFR2-mediated signalling.

Exp Dermatol. 2019 04;28(4):374-382

Authors: Nguyen MB, Valdes VJ, Cohen I, Pothula V, Zhao D, Zheng D, Ezhkova E

Abstract
Merkel cells are mechanosensory cells involved in tactile discrimination. Merkel cells have been primarily studied in the murine back skin, where they are found in specialized structures called touch domes located around primary hair follicles. Yet, little is known about the morphogenesis of Merkel cells in areas of the skin devoid of hair, such as the glabrous paw skin. Here, we describe Merkel cell formation in the glabrous paw skin during embryogenesis. We first found in the glabrous paw skin that Merkel cells were specified at E15.5, 24 hours later, compared to in the back skin. Additionally, by performing lineage-tracing experiments, we found that unlike in the back skin, SOX9(+) cells do not give rise to Merkel cells in the glabrous paw skin. Finally, we compared the transcriptomes of Merkel cells in the back and the glabrous paw skin and showed that they are similar. Genetic and transcriptome studies showed that the formation of Merkel cells in both regions was controlled by similar regulators. Among them was FGFR2, an upstream factor of MAPK signalling that was reported to have a critical function in Merkel cell formation in the back skin. Here, we showed that FGFR2 is also required for Merkel cell development in the glabrous paw skin. Taken together, our results demonstrate that Merkel cells in the murine back skin and glabrous paw skin are similar, and even though their formation is controlled by a common genetic programme, their precursor cells might differ.

PMID: 30758073 [PubMed - indexed for MEDLINE]

There is still a place for tumour-targeted therapies in Merkel cell carcinoma in the era of immune checkpoint inhibitors.

Fetched: September 9th, 2020, 5:01am GMT

There is still a place for tumour-targeted therapies in Merkel cell carcinoma in the era of immune checkpoint inhibitors.

Br J Dermatol. 2020 Sep 06;:

Authors: Samimi M, Becker J

PMID: 32892361 [PubMed - as supplied by publisher]

Merkel Cell Carcinoma: A Description of 11 Cases.

Fetched: September 7th, 2020, 5:01am GMT

Merkel Cell Carcinoma: A Description of 11 Cases.

Actas Dermosifiliogr. 2020 Sep 01;:

Authors: García-Zamora E, Vela Ganuza M, Martín-Alcalde J, Miñano Medrano R, Pinedo Moraleda F, López-Estebaranz JL

Abstract
Merkel cell carcinoma (MCC) is a malignant neuroendocrine tumor. Metastasis or lymph node spread is often detected at diagnosis. We performed a descriptive, retrospective study of patients diagnosed with MMC at Hospital Universitario Fundación Alcorcón in the Community of Madrid, Spain between January 1998 and December 2018. Eleven patients (7 men [63%] and 4 women [36%]; mean age, 77.6 years) were diagnosed with MCC during this 21-year period; 45% of patients had stage IIIB disease (pTNM) at diagnosis. All patients but one underwent local surgery, and lymphovascular invasion was detected in 7 cases. Eight patients received adjuvant therapy after surgery (radiation therapy in 5 cases and chemotherapy in 3). Six patients (54%) died of MCC (mean survival, 14.5 months). MCC is an uncommon malignant tumor with an annual incidence of around 0.18 to 0.41 cases per 100 000 inhabitants; this is similar to the rate of 0.29 to 0.32 cases per 100 000 inhabitants a year detected in our series. Results with avelumab, a drug recently approved for the treatment of metastatic MCC; have been promising.

PMID: 32888930 [PubMed - as supplied by publisher]

Impact of Tumor-Infiltrating Lymphocytes on Overall Survival in Merkel Cell Carcinoma.

Fetched: September 6th, 2020, 5:01am GMT

Impact of Tumor-Infiltrating Lymphocytes on Overall Survival in Merkel Cell Carcinoma.

Oncologist. 2020 Sep 04;:

Authors: Butala A, Jain V, Reddy VK, Sebro RA, Song Y, Karakousis G, Mitchell TC, Lukens JN, Shabason JE

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine carcinoma of the skin. As the clinical course can be variable, prognostic markers are needed to better stratify patients. Prior literature, composed of small series with limited sample size, has demonstrated that tumor-infiltrating lymphocytes (TILs) are an important prognostic marker in MCC. To validate these findings on a population level, we sought to analyze and report the prognostic value of TILs in a large national data set.
MATERIALS AND METHODS: A retrospective observational cohort study was conducted of patients with nonmetastatic MCC from 2010 to 2015 using the National Cancer Database. Individual variables trending toward significance using a univariable analysis were included in a multivariable Cox proportional hazards model to assess their independent effect on overall survival (OS). TILs were subclassified into none, nonbrisk, and brisk and the survival analysis was performed. Propensity score-weighted multivariable analysis (PS MVA) was performed to adjust for additional confounding.
RESULTS: A total of 2,182 patients met inclusion criteria: 611 (28.0%) were identified as having TILs present, and 1,571 (72.0%) had TILs absent in the tumor. On MVA, subdivision of TIL status into nonbrisk (hazard ratio [HR], 0.750; 95% confidence interval [CI], 0.602-0.933) and brisk (HR, 0.499; 95% CI, 0.338-0.735) was associated with incrementally improved OS compared with no TILs. The association of nonbrisk and brisk TILs with improved OS was retained on PS MVA (Nonbrisk: HR, 0.720; 95% CI, 0.550-0.944; Brisk: HR, 0.483; 95% CI, 0.286-0.814).
CONCLUSION: The presence of nonbrisk and brisk TILs is associated with incrementally improved OS in patients with nonmetastatic MCC in a large national data set. This pathologic feature can aid with risk stratification, estimation of prognosis, and, importantly, decision-making with respect to treatment intensification in high-risk patients.
IMPLICATIONS FOR PRACTICE: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine carcinoma of the skin with variable clinical course. Prognostic markers are thus needed to better stratify patients at presentation. This analysis represents the largest retrospective observational cohort study of patients with nonmetastatic MCC using the National Cancer Database. It demonstrates that increasing degrees of tumor infiltration by lymphocytes (nonbrisk and brisk, respectively) are associated with incrementally improved survival. This manuscript will impact modern practice by improving our understanding of pathologic findings that aid with risk stratification, estimation of prognosis, and, importantly, decision-making with respect to treatment intensification in high-risk patients. Intensification may include offering adjuvant radiation therapy to the primary site after wide excision despite small (<1 cm) tumor size, to the nodal basin in sentinel lymph node-negative patients, or offering closer follow-up with routine imaging to rule out recurrent or metastatic disease.

PMID: 32886418 [PubMed - as supplied by publisher]

Oncologic outcomes of patients with Merkel Cell Carcinoma (MCC): A multi-institutional cohort study.

Fetched: September 5th, 2020, 5:01am GMT

Oncologic outcomes of patients with Merkel Cell Carcinoma (MCC): A multi-institutional cohort study.

Am J Surg. 2020 Aug 22;:

Authors: Bleicher J, Asare EA, Flores S, Bowles TL, Bowen GM, Hyngstrom JR

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine tumor that primarily affects elderly patients. Despite aggressive treatment, overall survival (OS) remains low.
METHODS: This study is a multi-institutional, retrospective review of 102 patients with MCC. We evaluated OS, disease-specific survival (DSS), and risk factors for recurrence.
RESULTS: Median age of patients was 71.46% of patients recurred. Patients with stage I disease had median 5-year OS of 59.3%, compared to 68.1% DSS. For stage III, median 5-year OS was 46.0% vs 58.2% DSS. Disease stage and advanced age were risk factors for recurrence and decreased OS. Immunocompromised status and disease stage were the strongest predictors of DSS.
CONCLUSIONS: DSS is significantly better than OS for patients with MCC. Many elderly patients with newly diagnosed MCC have low remaining life expectancy, regardless of their MCC diagnosis. Patient age and overall health status should be considered to personalize care plans for patients with MCC.

PMID: 32878692 [PubMed - as supplied by publisher]

Merkel Cell Polyomavirus in Merkel Cell Carcinoma: Integration Sites and Involvement of the KMT2D Tumor Suppressor Gene.

Fetched: September 5th, 2020, 5:01am GMT

Merkel Cell Polyomavirus in Merkel Cell Carcinoma: Integration Sites and Involvement of the KMT2D Tumor Suppressor Gene.

Viruses. 2020 Aug 31;12(9):

Authors: Arora R, Choi JE, Harms PW, Chandrani P

Abstract
Merkel cell carcinoma (MCC) is an uncommon, lethal cancer of the skin caused by either Merkel cell polyomavirus (MCPyV) or UV-linked mutations. MCPyV is found integrated into MCC tumor genomes, accompanied by truncation mutations that render the MCPyV large T antigen replication incompetent. We used the open access HPV Detector/Cancer-virus Detector tool to determine MCPyV integration sites in whole-exome sequencing data from five MCC cases, thereby adding to the limited published MCPyV integration site junction data. We also systematically reviewed published data on integration for MCPyV in the human genome, presenting a collation of 123 MCC cases and their linked chromosomal sites. We confirmed that there were no highly recurrent specific sites of integration. We found that chromosome 5 was most frequently involved in MCPyV integration and that integration sites were significantly enriched for genes with binding sites for oncogenic transcription factors such as LEF1 and ZEB1, suggesting the possibility of increased open chromatin in these gene sets. Additionally, in one case we found, for the first time, integration involving the tumor suppressor gene KMT2D, adding to previous reports of rare MCPyV integration into host tumor suppressor genes in MCC.

PMID: 32878339 [PubMed - in process]

The Role of the JC Virus in Central Nervous System Tumorigenesis.

Fetched: September 4th, 2020, 5:01am GMT

The Role of the JC Virus in Central Nervous System Tumorigenesis.

Int J Mol Sci. 2020 Aug 28;21(17):

Authors: Ahye N, Bellizzi A, May D, Wollebo HS

Abstract
Cancer is the second leading cause of mortality worldwide. The study of DNA tumor-inducing viruses and their oncoproteins as a causative agent in cancer initiation and tumor progression has greatly enhanced our understanding of cancer cell biology. The initiation of oncogenesis is a complex process. Specific gene mutations cause functional changes in the cell that ultimately result in the inability to regulate cell differentiation and proliferation effectively. The human neurotropic Polyomavirus JC (JCV) belongs to the family Polyomaviridae and it is the causative agent of progressive multifocal leukoencephalopathy (PML), which is a fatal neurodegenerative disease in an immunosuppressed state. Sero-epidemiological studies have indicated JCV infection is prevalent in the population (85%) and that initial infection usually occurs during childhood. The JC virus has small circular, double-stranded DNA that includes coding sequences for viral early and late proteins. Persistence of the virus in the brain and other tissues, as well as its potential to transform cells, has made it a subject of study for its role in brain tumor development. Earlier observation of malignant astrocytes and oligodendrocytes in PML, as well as glioblastoma formation in non-human primates inoculated with JCV, led to the hypothesis that JCV plays a role in central nervous system (CNS) tumorigenesis. Some studies have reported the presence of both JC viral DNA and its proteins in several primary brain tumor specimens. The discovery of new Polyomaviruses such as the Merkel cell Polyomavirus, which is associated with Merkel cell carcinomas in humans, ignited our interest in the role of the JC virus in CNS tumors. The current evidence known about JCV and its effects, which are sufficient to produce tumors in animal models, suggest it can be a causative factor in central nervous system tumorigenesis. However, there is no clear association between JCV presence in CNS and its ability to initiate CNS cancer and tumor formation in humans. In this review, we will discuss the correlation between JCV and tumorigenesis of CNS in animal models, and we will give an overview of the current evidence for the JC virus's role in brain tumor formation.

PMID: 32872288 [PubMed - in process]

[MERKEL CELL CARCINOMA: A RETROSPECTIVE STUDY].

Fetched: August 29th, 2020, 5:01am GMT

[MERKEL CELL CARCINOMA: A RETROSPECTIVE STUDY].

Harefuah. 2020 Aug;159(8):550-553

Authors: Samuel Duek O, Ben Naftali Y, Ullmann Y

Abstract
BACKGROUND: Merkel Cell Carcinoma (MCC) is an aggressive neuroendocrine skin cancer. Though rare, in recent decades its prevalence has increased, and its incidence has tripled.
OBJECTIVES: To describe a cohort of MCC patients treated at a referral center in northern Israel, and to compare their characteristics and course of illness to cases reported in the literature.
METHODS: A retrospective review of 18 MCC patients treated in the Plastic Surgery Department at the Rambam Health Care Campus between the years 2011-2016. Patient demographics, medical history, histological findings, systemic involvement, adjuvant therapy, recurrence and survival rates parameters were collected and analyzed.
RESULTS: Study group patients were predominantly elderly, mostly men, and mainly Caucasian. A few were immunocompromised. Melanoma and MCC are known to be linked, and indeed, about a quarter of the patients suffered previously from melanoma. Diabetes, although not described as an MCC risk factor, has accounted for about 50% of cases, more than 5 times its prevalence in the general population. Tumor and metastases distribution were similar to the literature. Metastases were found in about 20% of cases at diagnosis. In one third of the patients, lymph nodes were already involved during surgery, with recurrence rates of 50%, and 40% mortality in five years.
CONCLUSIONS: Study results, for the first time, imply that there might be an association between diabetes and MCC. A link that could explain the rise of MCC incidence in recent decades. In addition, treatment guidelines were defined for metastatic disease which include the novel immunotherapy as a central component in treatment; hopefully, to improve patients' prognosis in this life-threatening disease.

PMID: 32852152 [PubMed - in process]

Permalink for 'High-resolution analysis of Merkel Cell Polyomavirus in Merkel Cell Carcinoma reveals distinct integration patterns and suggests NHEJ and MMBIR as underlying mechanisms.'

High-resolution analysis of Merkel Cell Polyomavirus in Merkel Cell Carcinoma reveals distinct integration patterns and suggests NHEJ and MMBIR as underlying mechanisms.

Fetched: August 26th, 2020, 5:01am GMT

High-resolution analysis of Merkel Cell Polyomavirus in Merkel Cell Carcinoma reveals distinct integration patterns and suggests NHEJ and MMBIR as underlying mechanisms.

PLoS Pathog. 2020 08;16(8):e1008562

Authors: Czech-Sioli M, Günther T, Therre M, Spohn M, Indenbirken D, Theiss J, Riethdorf S, Qi M, Alawi M, Wülbeck C, Fernandez-Cuesta I, Esmek F, Becker JC, Grundhoff A, Fischer N

Abstract
Merkel Cell Polyomavirus (MCPyV) is the etiological agent of the majority of Merkel Cell Carcinomas (MCC). MCPyV positive MCCs harbor integrated, defective viral genomes that constitutively express viral oncogenes. Which molecular mechanisms promote viral integration, if distinct integration patterns exist, and if integration occurs preferentially at loci with specific chromatin states is unknown. We here combined short and long-read (nanopore) next-generation sequencing and present the first high-resolution analysis of integration site structure in MCC cell lines as well as primary tumor material. We find two main types of integration site structure: Linear patterns with chromosomal breakpoints that map closely together, and complex integration loci that exhibit local amplification of genomic sequences flanking the viral DNA. Sequence analysis suggests that linear patterns are produced during viral replication by integration of defective/linear genomes into host DNA double strand breaks via non-homologous end joining, NHEJ. In contrast, our data strongly suggest that complex integration patterns are mediated by microhomology-mediated break-induced replication, MMBIR. Furthermore, we show by ChIP-Seq and RNA-Seq analysis that MCPyV preferably integrates in open chromatin and provide evidence that viral oncogene expression is driven by the viral promoter region, rather than transcription from juxtaposed host promoters. Taken together, our data explain the characteristics of MCPyV integration and may also provide a model for integration of other oncogenic DNA viruses such as papillomaviruses.

PMID: 32833988 [PubMed - indexed for MEDLINE]

High-grade Neuroendocrine Carcinomas of the Vulva: A Clinicopathologic Study of 16 Cases.

Fetched: August 24th, 2020, 5:01am GMT

High-grade Neuroendocrine Carcinomas of the Vulva: A Clinicopathologic Study of 16 Cases.

Am J Surg Pathol. 2020 Aug 20;:

Authors: Chen PP, Ramalingam P, Alvarado-Cabrero I, Euscher ED, Nagarajan P, Lawson BC, Malpica A

Abstract
Vulvar high-grade neuroendocrine carcinomas (HGNECs) are rare and primarily thought to represent Merkel cell carcinoma (MCC). We present the clinicopathologic features of 16 such cases, the largest series to date. Patients were most often White, postmenopausal, and symptomatic from a palpable vulvar mass/nodule. Tumors ranged from 0.7 to 6 cm and most commonly involved the labium majus. Majority of the cases were pure HGNECs (15/16) with small cell (SC) morphology (14/16); 2 were large cell neuroendocrine carcinomas, of which 1 was combined with moderately differentiated adenocarcinoma. All tumors expressed synaptophysin. Of the 14 HGNECs with SC morphology, 6 were CK20-positive MCCs with characteristic CAM5.2 and neurofilament (NF) expression. Five of these MCCs were positive for Merkel cell polyoma virus large T-antigen (MCPyVLTAg). In contrast, 6 HGNECs with SC morphology were negative for CK20, NF, and MCPyVLTAg and classified as SCNECs. High-risk human papilloma virus was positive in all SCNECs and negative in all MCCs. One case of HGNEC with SC morphology could not be entirely characterized due to lack of tissue for ancillary testing. Five of 12 (42%) cases had a discrepant diagnosis initially rendered. Most patients (10/15) presented with International Federation of Gynecology and Obstetrics stage III or IV disease. Usual sites of metastasis included inguinal lymph node, liver, bone, and lung. Twelve patients underwent surgery with adjuvant chemotherapy and/or radiation therapy, 1 received adjuvant immunotherapy, and 1 patient received neoadjuvant chemotherapy followed by surgery and adjuvant radiation therapy. Median overall survival was 24 months (range: 7 to 103 mo), and overall 5-year survival was 12% (95% confidence interval: 1% to 39%). In summary, vulvar HGNECs are rare, aggressive neoplasms that can be further subclassified into MCC, SCNEC, and large cell neuroendocrine carcinoma. CK20, CAM5.2, NF, TTF-1, MCPyVLTAg, and high-risk human papilloma virus facilitate the distinction of MCC from SCNEC. Proper identification of vulvar HGNECs is critical for patient management.

PMID: 32826525 [PubMed - as supplied by publisher]

Cutaneous viral infections associated with ultraviolet radiation exposure.

Fetched: August 22nd, 2020, 5:01am GMT

Cutaneous viral infections associated with ultraviolet radiation exposure.

Int J Cancer. 2020 Aug 20;:

Authors: Zhao Y, Amorrortu RP, Fenske NA, Cherpelis B, Messina JL, Sondak VK, Giuliano AR, Schell MJ, Waterboer T, Pawlita M, McKay-Chopin S, Gheit T, Tommasino M, Rollison DE

Abstract
The complex interplay between ultraviolet radiation (UVR) and cutaneous viral infections in the context of cancer etiology is challenging to unravel, given the limited information on the independent association between UVR and cutaneous viral infections. Using multiple biomarkers of infection with 21 types of cutaneous human papillomavirus (HPV) and 4 types of polyomaviruses (HPyV), we investigated cross-sectional associations with recent UVR exposure, using skin pigmentation measured by spectrophotometer. Age- and sex- adjusted associations between UVR and viral seropositivity, viral DNA present in eyebrow hairs (EBH) and skin swabs (SSW) were estimated using logistic regression. Beta-HPV seropositivity was associated with viral DNA positivity in EBH (OR = 1.40, 95% CI = 1.05-1.88) and SSW (OR = 1.86, 95% CI = 1.25-2.74). Similar associations were observed for Merkel cell polyomavirus. Participants in the highest tertile of UVR exposure were more likely to be seropositive for beta-HPV (OR = 1.81, 95% = 1.16-2.38), and have beta-HPV DNA in EBH (OR = 1.57, 95% CI = 1.06-2.33) and SSW (OR = 2.22, 95% CI = 1.25-3.96), compared to participants with the lowest tertile of UVR exposure. UVR exposure was positively associated with three different markers of beta-HPV infection. Therefore, future studies of HPV associated KC development should address more directly the role of HPV and UVR exposure as potential co-carcinogens. This article is protected by copyright. All rights reserved.

PMID: 32818302 [PubMed - as supplied by publisher]

[Personalized medicine in the treatment of periocular tumors : Targeted treatment and use of immune checkpoint inhibitors].

Fetched: August 12th, 2020, 5:01am GMT

[Personalized medicine in the treatment of periocular tumors : Targeted treatment and use of immune checkpoint inhibitors].

Ophthalmologe. 2020 Jun;117(6):521-527

Authors: Rokohl AC, Koch KR, Mor JM, Loreck N, Schlaak M, Mauch C, Bechrakis NE, Mohi A, Kakkassery V, Heindl LM

Abstract
The aim of this article is to provide an overview on the current state of personalized medicine in the systemic treatment of selected periocular tumors, such as basal cell carcinoma, Merkel cell carcinoma and conjunctival melanoma. This article therefore provides an extensive current literature review from PubMed including the current guidelines and standard operating procedures (SOP). As 90% of basal cell carcinomas have a pathologic activation of the sonic hedgehog pathway, vismodegib is a new treatment option for inoperable or metastatic basal cell carcinoma and for patients with Gorlin-Goltz syndrome. A novel approach of systemic medicine for the treatment of metastatic Merkel cell carcinoma is immunotherapy using the immune checkpoint inhibitor avelumab. Other personalized immunotherapies, such as the checkpoint inhibitors pembrolizumab and nivolumab, the tyrosine kinase inhibitor pazopanib and the role of the hedgehog pathway in Merkel cell carcinomas are the subject of current research and will certainly play an important role in future treatment. In the narrow sense personalized medicine has only come true for metastatic conjunctival melanomas: systemic treatment with BRAF, MEK and/or checkpoint inhibitors is initiated only when a BRAF mutation is detected in the tumor or metastatic tissue. Systemic immunotherapy with the checkpoint inhibitors pembrolizumab and nivolumab can also be used as a treatment option in metastatic conjunctival melanomas. In summary, personalized medicine is a subject of current research and provides many new targeted treatment options especially for periocular malignancies; however, it also involves many great challenges in the development and implementation of new techniques and therapies.

PMID: 31938823 [PubMed - indexed for MEDLINE]

The changing paradigm of managing Merkel cell carcinoma in Australia: An expert commentary.

Fetched: August 8th, 2020, 5:01am GMT

The changing paradigm of managing Merkel cell carcinoma in Australia: An expert commentary.

Asia Pac J Clin Oncol. 2020 Aug 05;:

Authors: Kok DL, Wang A, Xu W, Chua MST, Guminski A, Veness M, Howle J, Tothill R, Kichendasse G, Poulsen M, Sandhu S, Fogarty G

Abstract
Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine tumor of the skin with an estimated disease-associated mortality of 15-33%. Australia has a higher incidence of MCC compared to the rest of the world, thought to be due to a higher ultraviolet index. The Australian MCC population is distinct from the MCC population of the Northern hemisphere, characterized by a predominantly viral negative etiology with high tumor mutational burden. The optimal management of MCC and the choice of treatment modality vary significantly across the world and even between institutions within Australia. Historically, the treatment for MCC has been resection followed by radiotherapy (RT), though definitive RT is an alternative treatment used commonly in Australia. The arrival of immune checkpoint inhibitors and the mounting evidence that MCC is a highly immunogenic disease is transforming the treatment landscape for MCC. Australia is playing a key role in the further development of treatment options for MCC with two upcoming Australian/New Zealand investigator-initiated clinical trials that will explore the interplay of RT and immunotherapy in the treatment of early and late stage MCC.

PMID: 32757453 [PubMed - as supplied by publisher]

Merkel Cell Polyomavirus Small T Antigen Activates Non-Canonical NF-κB Signaling to Promote Tumorigenesis.

Fetched: August 7th, 2020, 5:01am GMT

Merkel Cell Polyomavirus Small T Antigen Activates Non-Canonical NF-κB Signaling to Promote Tumorigenesis.

Mol Cancer Res. 2020 Aug 04;:

Authors: Zhao J, Jia Y, Shen S, Kim J, Wang X, Lee E, Brownell I, Cho-Vega JH, Lewis C, Homsi J, Sharma RR, Wang RC

Abstract
Multiple human polyomaviruses (HPyVs) can infect the skin, but only Merkel Cell Polyomavirus (MCPyV) has been implicated in the development of a cancer, Merkel Cell Carcinoma (MCC). While expression of HPyV6, HPyV7, and MCPyV small T antigens (sT) all induced a senescence associated secretory phenotype (SASP), MCPyV sT uniquely activated non-canonical NF-κB (ncNF-κB), instead of canonical NF-κB signaling, to evade p53-mediated cellular senescence. Through its large T stabilization domain, MCPyV sT activated ncNF-κB signaling both by inducing H3K4 trimethylation-mediated increases of NFKB2 and RELB transcription and also by promoting NFKB2 stabilization and activation through FBXW7 inhibition. Non-canonical NF-κB signaling was required for SASP cytokine secretion, which promoted the proliferation of MCPyV sT expressing cells through autocrine signaling. Virus-positive MCC cell lines and tumors showed ncNF-κB pathway activation and SASP gene expression, and the inhibition of ncNF-κB signaling prevented VP-MCC cell growth in vitro and in xenografts. We identify MCPyV sT induced ncNF-κB signaling as an essential tumorigenic pathway in MCC. Implications: This work is the first to identify the activation of non-canonical NF-κB (ncNF-κB) signaling by any polyomavirus and its critical role in MCC tumorigenesis.

PMID: 32753470 [PubMed - as supplied by publisher]

Non-Melanoma Skin Cancers: Biological and Clinical Features.

Fetched: August 7th, 2020, 5:01am GMT

Non-Melanoma Skin Cancers: Biological and Clinical Features.

Int J Mol Sci. 2020 Jul 29;21(15):

Authors: Cives M, Mannavola F, Lospalluti L, Sergi MC, Cazzato G, Filoni E, Cavallo F, Giudice G, Stucci LS, Porta C, Tucci M

Abstract
Non-melanoma skin cancers (NMSCs) include basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and Merkel cell carcinoma (MCC). These neoplasms are highly diverse in their clinical presentation, as well as in their biological evolution. While the deregulation of the Hedgehog pathway is commonly observed in BCC, SCC and MCC are characterized by a strikingly elevated mutational and neoantigen burden. As result of our improved understanding of the biology of non-melanoma skin cancers, innovative treatment options including inhibitors of the Hedgehog pathway and immunotherapeutic agents have been recently investigated against these malignancies, leading to their approval by regulatory authorities. Herein, we review the most relevant biological and clinical features of NMSC, focusing on innovative treatment approaches.

PMID: 32751327 [PubMed - in process]

Reprogramming of cellular metabolic pathways by human oncogenic viruses.

Fetched: August 7th, 2020, 5:01am GMT

Reprogramming of cellular metabolic pathways by human oncogenic viruses.

Curr Opin Virol. 2019 12;39:60-69

Authors: Purdy JG, Luftig MA

Abstract
Oncogenic viruses, like all viruses, relies on host metabolism to provide the metabolites and energy needed for virus replication. Many DNA tumor viruses and retroviruses will reprogram metabolism during infection. Additionally, some viral oncogenes may alter metabolism independent of virus replication. Virus infection and cancer development share many similarities regarding metabolic reprogramming as both processes demand increased metabolic activity to produce biomass: cell proliferation in the case of cancer and virion production in the case of infection. This review discusses the parallels in metabolic reprogramming between human oncogenic viruses and oncogenesis.

PMID: 31766001 [PubMed - indexed for MEDLINE]

Permalink for 'Time-Varying Clearance and Impact of Disease State on the Pharmacokinetics of Avelumab in Merkel Cell Carcinoma and Urothelial Carcinoma.'

Time-Varying Clearance and Impact of Disease State on the Pharmacokinetics of Avelumab in Merkel Cell Carcinoma and Urothelial Carcinoma.

Fetched: August 7th, 2020, 5:01am GMT

Time-Varying Clearance and Impact of Disease State on the Pharmacokinetics of Avelumab in Merkel Cell Carcinoma and Urothelial Carcinoma.

CPT Pharmacometrics Syst Pharmacol. 2019 06;8(6):415-427

Authors: Wilkins JJ, Brockhaus B, Dai H, Vugmeyster Y, White JT, Brar S, Bello CL, Neuteboom B, Wade JR, Girard P, Khandelwal A

Abstract
Avelumab, a human anti-programmed death ligand 1 immunoglobulin G1 antibody, has shown efficacy and manageable safety in multiple tumors. A two-compartment population pharmacokinetic model for avelumab incorporating intrinsic and extrinsic covariates and time-varying clearance (CL) was identified based on data from 1,827 patients across three clinical studies. Of 14 tumor types, a decrease in CL over time was more notable in metastatic Merkel cell carcinoma and squamous cell carcinoma of the head and neck, which had maximum decreases of 32.1% and 24.7%, respectively. The magnitude of reduction in CL was higher in responders than in nonresponders. Significant covariate effects of baseline weight, baseline albumin, and sex were identified on both CL and central distribution volume. Significant covariate effects of black/African American race, C-reactive protein, and immunogenicity were found on CL. None of the covariate or time-dependent effects were clinically important or warranted dose adjustment.

PMID: 30980481 [PubMed - indexed for MEDLINE]

Severe fistulizing pancreatitis in a patient with Merkel cell carcinoma treated with avelumab.

Fetched: August 4th, 2020, 5:01am GMT

Severe fistulizing pancreatitis in a patient with Merkel cell carcinoma treated with avelumab.

Eur J Gastroenterol Hepatol. 2020 Sep;32(9):1266-1267

Authors: Khurana S, Chi Zhang H, Peng Y, Lu Y, Wang Y

PMID: 32740281 [PubMed - in process]

Permalink for 'Somatostatin Receptors in Merkel-Cell Carcinoma: A Therapeutic Opportunity Using Somatostatin Analog Alone or in Association With Checkpoint Inhibitors Immunotherapy. A Case Report.'

Somatostatin Receptors in Merkel-Cell Carcinoma: A Therapeutic Opportunity Using Somatostatin Analog Alone or in Association With Checkpoint Inhibitors Immunotherapy. A Case Report.

Fetched: August 2nd, 2020, 5:01am GMT

Somatostatin Receptors in Merkel-Cell Carcinoma: A Therapeutic Opportunity Using Somatostatin Analog Alone or in Association With Checkpoint Inhibitors Immunotherapy. A Case Report.

Front Oncol. 2020;10:1073

Authors: Guida M, D'Alò A, Mangia A, Di Pinto F, Sonnessa M, Albano A, Sciacovelli A, Asabella AN, Fucci L

Abstract
Background: Merkel-cell carcinoma (MCC) is a rare, highly aggressive skin cancer typically involving elderly people. Surgery is usually the first treatment for primary tumor. In adjuvant setting, radiotherapy is effective in reducing local recurrence and in improving overall survival. Regarding advanced disease, systemic chemotherapy ended up disappointing results whereas antiPD1/antiPD-L1 immunotherapy recently gave relevant clinical benefits. Interestingly, about the half of MCC patients expresses high somatostatin receptors (SRs) to possibly represent a target for the therapeutic use of somatostatin analogs (SSAs). Nevertheless, SSAs have been little studied in MCC and cases treated with SSAs in association with checkpoint inhibitor immunotherapy have not been published yet. Case Report: We report the case of a 73-year-old man affected by metastatic MCC of right arm previously treated with surgery and adjuvant radio and chemotherapy. Three years later the patient presented loco-regional relapse involving lateral-cervical, mediastinal, and submandibular lymph nodes with high value of chromogranin A and neuron specific enolase. Due to the high expression of SRs at octreoscan and immunoistochemistry, patient started octreotide 30 mg i.m. every 28 days with a good control of disease for about 2 years. A widespread progression of disease was reported afterwards. The patient started the antiPD-L1 avelumab immunotherapy, only recently available in Italy, while still taking SSA. The patient showed an impressive regression of the disease after only four cycles of avelumab until complete remission. Conclusions: SSA could be a valid therapeutic option in patients with MCC with high SR expression. When combined with PD-1/PD-L1 immune-checkpoint inhibition, SSA is likely to enhance antiproliferative activity. Our case report provides the rationale to conduct a prospective trial and translational research to verify the efficacy and safety of combined SSA and checkpoint inhibitors for advanced MCC.

PMID: 32733801 [PubMed]

Molecular detection of Merkel cell polyomavirus in basal cell carcinoma and perilesional tissue: a cross-sectional study.

Fetched: August 2nd, 2020, 5:01am GMT

Molecular detection of Merkel cell polyomavirus in basal cell carcinoma and perilesional tissue: a cross-sectional study.

An Bras Dermatol. 2020 Jul - Aug;95(4):527-528

Authors: Gonçalves MTV, Varella RB, Almeida NKO, Guimarães MAAM, Luz FB

PMID: 32499100 [PubMed - indexed for MEDLINE]

Breaking avelumab resistance with combined ipilimumab and nivolumab in metastatic Merkel cell carcinoma?

Fetched: August 2nd, 2020, 5:01am GMT

Breaking avelumab resistance with combined ipilimumab and nivolumab in metastatic Merkel cell carcinoma?

Ann Oncol. 2019 10 01;30(10):1667-1668

Authors: Glutsch V, Kneitz H, Goebeler M, Gesierich A, Schilling B

PMID: 31350554 [PubMed - indexed for MEDLINE]

Permalink for 'Heterogeneity of programmed death-ligand expression in a case of Merkel cell carcinoma exhibiting complete regression after multiple metastases.'

Heterogeneity of programmed death-ligand expression in a case of Merkel cell carcinoma exhibiting complete regression after multiple metastases.

Fetched: August 2nd, 2020, 5:01am GMT

Heterogeneity of programmed death-ligand expression in a case of Merkel cell carcinoma exhibiting complete regression after multiple metastases.

Br J Dermatol. 2019 05;180(5):1228-1229

Authors: Nakamura M, Magara T, Kobayashi Y, Kato H, Watanabe S, Morita A

PMID: 30431150 [PubMed - indexed for MEDLINE]

High Prevalence of Human Polyomavirus 7 in Cholangiocarcinomas and Adjacent Peritumoral Hepatocytes: Preliminary Findings.

Fetched: August 1st, 2020, 5:01am GMT

High Prevalence of Human Polyomavirus 7 in Cholangiocarcinomas and Adjacent Peritumoral Hepatocytes: Preliminary Findings.

Microorganisms. 2020 Jul 27;8(8):

Authors: Klufah F, Mobaraki G, Chteinberg E, Alharbi RA, Winnepenninckx V, Speel EJM, Rennspiess D, Olde Damink SW, Neumann UP, Kurz AK, Samarska I, Zur Hausen A

Abstract
Cholangiocarcinoma (CCA) is a rare biliary-duct malignancy with poor prognosis. Recently, the presence of the human polyomavirus 6 (HPyV6) has been reported in the bile of diverse hepatobiliary diseases, particularly in the bile of CCA patients. Here, we investigated the presence of novel HPyVs in CCA tissues using diverse molecular techniques to assess a possible role of HPyVs in CCA. Formalin-Fixed Paraffin-Embedded (FFPE) tissues of 42 CCA patients were included in this study. PCR-based screening for HPyVs was conducted using degenerated and HPyV-specific primers. Following that, we performed FISH, RNA in situ hybridization (RNA-ISH), and immunohistochemistry (IHC) to assess the presence of HPyVs in selected tissues. Of all 42 CCAs, 25 (59%) were positive for one HPyV, while 10 (24%) CCAs were positive for 2 HPyVs simultaneously, and 7 (17%) were negative for HPyVs. Of the total 35 positive CCAs, 19 (45%) were positive for HPyV7, 4 (9%) for HPyV6, 2 (5%) for Merkel cell polyomavirus (MCPyV), 8 (19%) for both HPyV7/MCPyV, and 2 (5%) for both HPyV6/HPyV7 as confirmed by sequencing. The presence of viral nucleic acids was confirmed by specific FISH, while the RNA-ISH confirmed the presence of HPyV6 on the single-cell level. In addition, expression of HPyV7, HPyV6, and MCPyV proteins were confirmed by IHC. Our results strongly indicate that HPyV7, HPyV6, and MCPyV infect bile duct epithelium, hepatocytes, and CCA cells, which possibly suggest an indirect role of these viruses in the etiopathogenesis of CCA. Furthermore, the observed hepatotropism of these novel HPyV, in particular HPyV7, might implicate a role of these viruses in other hepatobiliary diseases.

PMID: 32726909 [PubMed]

Imaging of Merkel Cell Carcinoma: What Imaging Experts Should Know.

Fetched: August 1st, 2020, 5:01am GMT

Imaging of Merkel Cell Carcinoma: What Imaging Experts Should Know.

Radiographics. 2019 Nov-Dec;39(7):2069-2084

Authors: Akaike G, Akaike T, Fadl SA, Lachance K, Nghiem P, Behnia F

Abstract
Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neuroendocrine tumor with a higher mortality rate than melanoma. Approximately 40% of MCC patients have nodal or distant metastasis at initial presentation, and one-third of patients will develop distant metastatic disease over their clinical course. Although MCC is rare, its incidence has been steadily increasing. Furthermore, the immunogenicity of MCC and its diagnostic and therapeutic application have made MCC one of the most rapidly developing topics in dermatology and oncology. Owing to the aggressive and complex nature of MCC, a multidisciplinary approach is necessary for management of this tumor, including dermatologists, surgeons, radiation oncologists, medical oncologists, pathologists, radiologists, and nuclear medicine physicians. Imaging plays a crucial role in diagnosis, planning for surgery or radiation therapy, and assessment of treatment response and surveillance. However, MCC is still not well recognized among radiologists and nuclear medicine physicians, likely owing to its rarity. The purpose of this review is to raise awareness of MCC among imaging experts by describing the epidemiology, pathophysiology, and clinical features of MCC and current clinical management with a focus on the role of imaging. The authors highlight imaging findings characteristic of MCC, as well as the clinical significance of CT, MRI, sentinel lymph node mapping, fluorine 18 fluorodeoxyglucose PET/CT, and other nuclear medicine studies such as bone scintigraphy and somatostatin receptor scintigraphy. ©RSNA, 2019.

PMID: 31697628 [PubMed - indexed for MEDLINE]

Fine needle aspiration cytology of a recurrent hand swelling.

Fetched: July 31st, 2020, 5:01am GMT

Fine needle aspiration cytology of a recurrent hand swelling.

Cytopathology. 2019 09;30(5):558-559

Authors: Kapatia G, Peddinti RS, Radotra BD, Dey P

PMID: 30953596 [PubMed - indexed for MEDLINE]

Permalink for 'Narrow excision margins are appropriate for Merkel cell carcinoma when combined with adjuvant radiation: Analysis of 188 cases of localized disease and proposed management algorithm.'

Narrow excision margins are appropriate for Merkel cell carcinoma when combined with adjuvant radiation: Analysis of 188 cases of localized disease and proposed management algorithm.

Fetched: July 29th, 2020, 5:01am GMT

Narrow excision margins are appropriate for Merkel cell carcinoma when combined with adjuvant radiation: Analysis of 188 cases of localized disease and proposed management algorithm.

J Am Acad Dermatol. 2020 Jul 22;:

Authors: Tarabadkar ES, Fu T, Lachance K, Hippe DS, Pulliam T, Thomas H, Li J, Lewis C, Doolittle-Amieva C, Byrd D, Kampp J, Parvanthaneni U, Nghiem P

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) management typically includes surgery with or without adjuvant radiation therapy (aRT). Major challenges include determining surgical margin size and whether aRT is indicated.
OBJECTIVE: To assess the association of aRT, surgical margin size, and MCC local recurrence.
METHODS: Analysis of 188 MCC cases presenting without clinical nodal involvement.
RESULTS: aRT-treated patients tended to have higher-risk tumors (larger diameter, positive microscopic margins, immunosuppression) yet had fewer local recurrences (LR) than patients treated with surgery only (1% vs. 15%; p=0.001). For patients who underwent surgery alone, 7 of 35 (20%) treated with narrow margins (defined as ≤1.0 cm) developed LR, whereas 0 of 13 patients treated with surgical margins >1.0 cm developed LR (p=0.049). For aRT-treated patients, local control was excellent regardless of surgical margin size; only 1% recurred in each group (1 of 70 with narrow margins ≤1 cm and 1 of 70 with margins >1 cm, p=0.56).
LIMITATIONS: This was a retrospective study.
CONCLUSIONS: Among patients treated with aRT, local control was superb even if significant risk factors were present and margins were narrow. We propose an algorithm for managing primary MCC that integrates risk factors and optimizes local control while minimizing morbidity.

PMID: 32711093 [PubMed - as supplied by publisher]

Merkel Cell Polyomavirus T Antigens Induce Merkel Cell-Like Differentiation in GLI1-Expressing Epithelial Cells.

Fetched: July 29th, 2020, 5:01am GMT

Merkel Cell Polyomavirus T Antigens Induce Merkel Cell-Like Differentiation in GLI1-Expressing Epithelial Cells.

Cancers (Basel). 2020 Jul 21;12(7):

Authors: Kervarrec T, Samimi M, Hesbacher S, Berthon P, Wobser M, Sallot A, Sarma B, Schweinitzer S, Gandon T, Destrieux C, Pasqualin C, Guyétant S, Touzé A, Houben R, Schrama D

Abstract
Merkel cell carcinoma (MCC) is an aggressive skin cancer frequently caused by the Merkel cell polyomavirus (MCPyV). It is still under discussion, in which cells viral integration and MCC development occurs. Recently, we demonstrated that a virus-positive MCC derived from a trichoblastoma, an epithelial neoplasia bearing Merkel cell (MC) differentiation potential. Accordingly, we hypothesized that MC progenitors may represent an origin of MCPyV-positive MCC. To sustain this hypothesis, phenotypic comparison of trichoblastomas and physiologic human MC progenitors was conducted revealing GLI family zinc finger 1 (GLI1), Keratin 17 (KRT 17), and SRY-box transcription factor 9 (SOX9) expressions in both subsets. Furthermore, GLI1 expression in keratinocytes induced transcription of the MC marker SOX2 supporting a role of GLI1 in human MC differentiation. To assess a possible contribution of the MCPyV T antigens (TA) to the development of an MC-like phenotype, human keratinocytes were transduced with TA. While this led only to induction of KRT8, an early MC marker, combined GLI1 and TA expression gave rise to a more advanced MC phenotype with SOX2, KRT8, and KRT20 expression. Finally, we demonstrated MCPyV-large T antigens' capacity to inhibit the degradation of the MC master regulator Atonal bHLH transcription factor 1 (ATOH1). In conclusion, our report suggests that MCPyV TA contribute to the acquisition of an MC-like phenotype in epithelial cells.

PMID: 32708246 [PubMed]

Clinical Benefit of Baseline Imaging in Merkel Cell Carcinoma: Analysis of 584 Patients.

Fetched: July 28th, 2020, 5:01am GMT

Clinical Benefit of Baseline Imaging in Merkel Cell Carcinoma: Analysis of 584 Patients.

J Am Acad Dermatol. 2020 Jul 21;:

Authors: Singh N, Alexander NA, Lachance K, Lewis CW, McEvoy A, Akaike G, Byrd D, Behnia S, Bhatia S, Paulson KG, Nghiem P

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) guidelines derive from melanoma and do not recommend baseline cross-sectional imaging for most patients. However, MCC is more likely to have metastasized at diagnosis than melanoma.
OBJECTIVE: To determine how often baseline imaging identifies clinically occult MCC in newly diagnosed patients with and without palpable nodal involvement.
METHODS: Analysis of 584 MCC patients with a cutaneous primary, baseline imaging, no evident distant metastases, and sufficient staging data.
RESULTS: Among 492 patients with clinically uninvolved regional nodes, 13.2% were upstaged by imaging (8.9% in regional nodes, 4.3% in distant sites). Among 92 patients with clinically involved regional nodes, 10.8% were upstaged to distant metastatic disease. Large (>4cm) and small (<1cm) primary tumors were both frequently upstaged (29.4% and 7.8%, respectively). PET-CT upstaged patients more often (16.8% of 352), than CT alone (6.9% of 231; p=0.0006).
LIMITATIONS: This was a retrospective study.
CONCLUSIONS: In clinically node-negative patients, baseline imaging revealed occult metastatic MCC at a higher rate than reported for melanoma (13.2% vs. <1%). Although imaging is already recommended for clinically node-positive MCC patients, these data suggest that baseline imaging is also indicated for clinically node-negative patients because upstaging is frequent and markedly alters management and prognosis.

PMID: 32707254 [PubMed - as supplied by publisher]

Correction to: Merkel Cell Carcinoma Outcomes: Does AJCC8 Underestimate Survival?

Fetched: July 25th, 2020, 5:01am GMT

Correction to: Merkel Cell Carcinoma Outcomes: Does AJCC8 Underestimate Survival?

Ann Surg Oncol. 2020 Jul 22;:

Authors: Farley CR, Perez MC, Soelling SJ, Delman KA, Harit A, Wuthrick EJ, Messina JL, Sondak VK, Zager JS, Lowe MC

Abstract
C.R. Farley and M.C. Perez contributed equally to this publication and are co-first authors. J.S. Zager and M.C. Lowe contributed equally to this publication and are co-corresponding authors.

PMID: 32699930 [PubMed - as supplied by publisher]

Structure of Merkel cell polyomavirus capsid and interaction with its glycosaminoglycan attachment receptor.

Fetched: July 25th, 2020, 5:01am GMT

Structure of Merkel cell polyomavirus capsid and interaction with its glycosaminoglycan attachment receptor.

J Virol. 2020 Jul 22;:

Authors: Bayer NJ, Januliene D, Zocher G, Stehle T, Moeller A, Blaum BS

Abstract
Merkel cell polyomavirus (MCPyV) is a human double-stranded DNA tumor virus. MCPyV cell entry is unique among the polyomavirus family as it requires the engagement of two types of glycans, sialylated oligosaccharides and sulfated glycosaminoglycans (GAGs). Here, we present crystallographic and cryo-electron microscopic structures of the icosahedral MCPyV capsid and analysis of its glycan interactions via NMR spectroscopy. While sialic acid binding is specific for α2-3-linked sialic acid and mediated by the exposed apical loops of the major capsid protein VP1, a broad range of GAG oligosaccharides bind to recessed regions between VP1 capsomers. Individual VP1 capsomers are tethered to one another by an extensive disulfide network that differs in architecture from previously-described interactions for other PyVs. An unusual C-terminal extension in MCPyV VP1 projects from the recessed capsid regions. Mutagenesis experiments show that this extension is dispensable for receptor interaction.IMPORTANCEThe MCPyV genome was found to be clonally integrated in 80% of Merkel cell carcinoma (MCC), a rare but aggressive form of human skin cancer, strongly suggesting that this virus is tumorigenic. In the metastasizing state the course of disease is often fatal, especially in immunocompromised individuals, as reflected by the high mortality rate of 33-46% and low 5-year survival rate (< 45%). The high seroprevalence of about 60% makes MCPyV a serious healthcare burden and illustrates the need for targeted treatments. In this study we present the first high-resolution structural data of this human tumor virus and demonstrate that the full capsid is required for the essential interaction with its GAG receptor(s). Together this data can be used as a basis for future strategies in drug development.

PMID: 32699083 [PubMed - as supplied by publisher]

Permalink for 'Histone H3K27 dimethyl loss is highly specific for malignant peripheral nerve sheath tumor and distinguishes true PRC2 loss from isolated H3K27 trimethyl loss.'

Histone H3K27 dimethyl loss is highly specific for malignant peripheral nerve sheath tumor and distinguishes true PRC2 loss from isolated H3K27 trimethyl loss.

Fetched: July 25th, 2020, 5:01am GMT

Histone H3K27 dimethyl loss is highly specific for malignant peripheral nerve sheath tumor and distinguishes true PRC2 loss from isolated H3K27 trimethyl loss.

Mod Pathol. 2019 10;32(10):1434-1446

Authors: Marchione DM, Lisby A, Viaene AN, Santi M, Nasrallah M, Wang LP, Williams EA, Larque AB, Chebib I, Garcia BA, Wojcik JB

Abstract
Malignant peripheral nerve sheath tumors contain loss of histone H3K27 trimethylation (H3K27me3) due to driver mutations affecting the polycomb repressive complex 2 (PRC2). Consequently, loss of H3K27me3 staining has served as a diagnostic marker for this tumor type. However, recent reports demonstrate H3K27me3 loss in numerous other tumors, including some in the differential diagnosis of malignant peripheral nerve sheath tumor. Since these tumors lose H3K27me3 through mechanisms distinct from PRC2 loss, we set out to determine whether loss of dimethylation of H3K27, which is also catalyzed by PRC2, might be a more specific marker of PRC2 loss and malignant peripheral nerve sheath tumor. Using mass spectrometry, we identify a near complete loss of H3K27me2 in malignant peripheral nerve sheath tumors and cell lines. Immunohistochemical analysis of 72 malignant peripheral nerve sheath tumors, seven K27M-mutant gliomas, 43 ependymomas, and 10 Merkel cell carcinomas demonstrates that while H3K27me3 loss is common across these tumor types, H3K27me2 loss is limited to malignant peripheral nerve sheath tumors and is highly concordant with H3K27me3 loss (33/34 cases). Thus, increased specificity does not come at the cost of greatly reduced sensitivity. To further compare H3K27me2 and H3K27me3 immunohistochemistry, we investigated 42 melanomas and 54 synovial sarcomas, histologic mimics of malignant peripheral nerve sheath tumor with varying degrees of H3K27me3 loss in prior reports. While global H3K27me3 loss was not seen in these tumors, weak and limited H3K27me3 staining was common. By contrast, H3K27me2 staining was more clearly retained in all cases, making it a superior binary classifier. This was confirmed by digital image analysis of stained slides. Our findings indicate that H3K27me2 loss is highly specific for PRC2 loss and that PRC2 loss is a rarer phenomenon than H3K27me3 loss. Consequently, H3K27me2 loss is a superior diagnostic marker for malignant peripheral nerve sheath tumor.

PMID: 31175328 [PubMed - indexed for MEDLINE]

Utility of Ber-EP4 and MOC-31 in Basaloid Skin Tumor Detection.

Fetched: July 25th, 2020, 5:01am GMT

Utility of Ber-EP4 and MOC-31 in Basaloid Skin Tumor Detection.

Appl Immunohistochem Mol Morphol. 2019 09;27(8):584-588

Authors: Gill P, Naugler C, Abi Daoud MS

Abstract
Ber-EP4 has been the traditional immunostain used for the detection of basaloid skin tumors. Recently, MOC-31 has shown be superior to Ber-EP4 in the detection of basosquamous basal cell carcinoma (BCC) and many centers are now using both Ber-EP4 and MOC-31 antibodies together to detect these lesions. The objective of this study was to compare the utility of using both Ber-EP4 and MOC-31 immunostains in the detection of basaloid skin tumors and to better characterize the previously unknown staining properties of MOC-31 in cutaneous lesions. To do this, 76 basaloid skin tumors stained with both Ber-EP4 and MOC-31 were obtained. Diagnoses included basosquamous BCC, Merkel cell carcinoma, adenoid cystic carcinoma, microcystic adnexal carcinoma, sebaceous carcinoma, trichoepithelioma, trichoblastoma, sebaceous adenoma, sebaceoma, and follicular induction overlying dermatofibroma. The distribution and intensity of Ber-EP4 and MOC-31 staining in these lesions was scored. These scores were analyzed using a truth table, χ test, and Pearson correlation tests. The overall mean and SD of the scores were also obtained. Overall, we found Ber-EP4 and MOC-31 to be statistically equivalent immunostains for the diagnosis of basaloid skin tumors. We recommend the use of only one of these antibodies and favor MOC-31 for the detection of basaloid skin tumors. We also describe MOC-31 staining properties in different cutaneous lesions.

PMID: 29629953 [PubMed - indexed for MEDLINE]

Permalink for 'Exploring the Prognostic Role of Ki67 Proliferative Index in Merkel Cell Carcinoma of the Skin: Clinico-Pathologic Analysis of 84 Cases and Review of the Literature.'

Exploring the Prognostic Role of Ki67 Proliferative Index in Merkel Cell Carcinoma of the Skin: Clinico-Pathologic Analysis of 84 Cases and Review of the Literature.

Fetched: July 24th, 2020, 5:01am GMT

Exploring the Prognostic Role of Ki67 Proliferative Index in Merkel Cell Carcinoma of the Skin: Clinico-Pathologic Analysis of 84 Cases and Review of the Literature.

Endocr Pathol. 2020 Jul 22;:

Authors: La Rosa S, Bonzini M, Sciarra A, Asioli S, Maragliano R, Arrigo M, Foschini MP, Righi A, Maletta F, Motolese A, Papotti M, Sessa F, Uccella S

Abstract
The exact prediction of outcome of patients with Merkel cell carcinoma (MCC) of the skin is difficult to determine, although several attempts have been made to identify clinico-pathologic prognostic factors. The Ki67 proliferative index is a well-known marker routinely used to define the prognosis of patients with neuroendocrine neoplasms. However, its prognostic value has been poorly investigated in MCC, and available published results are often contradictory mainly because restricted to small series in the absence of standardized methods for Ki67 evaluation. For this reason, we explored the potential prognostic role of Ki67 proliferative index in a large series of MCCs using the WHO standardized method of counting positive cells in at least 500 tumor cells in hot spot areas on camera-captured printed images. In addition, since MCC may be considered as the cutaneous counterpart of digestive neuroendocrine carcinomas (NECs), we decided to stratify MCCs using the available and efficient Ki67 threshold of 55%, which was found prognostic in digestive NECs. This choice was also supported by the Youden index analysis. In addition, we analyzed the prognostic value of other clinico-pathologic parameters using both univariate and multivariate analysis. Ki67 index appeared significantly associated with prognosis at univariate analysis together with stage IV, lack of MCPyV, and p63 expression, but not at the multivariate analysis, where survival resulted independently influenced by p63 expression and tumor stage, only.

PMID: 32696301 [PubMed - as supplied by publisher]

$Permalink for 'Palliative single-fraction whole liver radiation therapy for diffuse liver metastases from metastatic Merkel cell carcinoma.'$

Palliative single-fraction whole liver radiation therapy for diffuse liver metastases from metastatic Merkel cell carcinoma.

Fetched: July 20th, 2020, 5:01am GMT

Palliative single-fraction whole liver radiation therapy for diffuse liver metastases from metastatic Merkel cell carcinoma.

J Dermatol. 2020 Jul 17;:

Authors: Andruska N, Mahapatra L, Brenneman R, Hernandez-Aya LF, MacArthur KM, Baumann BC

PMID: 32681575 [PubMed - as supplied by publisher]

Permalink for 'Merkel Cell Polyomavirus Small Tumor Antigen Activates Matrix Metallopeptidase-9 Gene Expression for Cell Migration and Invasion.'

Merkel Cell Polyomavirus Small Tumor Antigen Activates Matrix Metallopeptidase-9 Gene Expression for Cell Migration and Invasion.

Fetched: July 18th, 2020, 5:01am GMT

Merkel Cell Polyomavirus Small Tumor Antigen Activates Matrix Metallopeptidase-9 Gene Expression for Cell Migration and Invasion.

J Virol. 2020 Jul 15;:

Authors: Nwogu N, Ortiz LE, Whitehouse A, Kwun HJ

Abstract
Merkel cell polyomavirus (MCV) small T antigen (sT) is the main oncoprotein for the development of Merkel cell carcinoma (MCC). MCC is a rare, clinically aggressive neuroendocrine tumor of the skin with a high propensity for local, regional, and distant spread. The dysregulation of matrix metalloproteinase-9 (MMP-9) has been implicated in multiple essential roles in the development of various malignant tumor cell invasion and metastasis. Previously, MCV sT was shown to induce the migratory and invasive phenotype of MCC cells through the transcriptional activation of the sheddase molecule, ADAM 10 (A disintegrin and metalloprotease domain-containing protein 10). In this study, we show that MCV sT protein stimulates differential expression of epithelial-mesenchymal transition (EMT)-associated genes, including MMP-9 and Snail. This effect is dependent on the presence of the large T stabilization domain (LSD), which is known to be responsible for cell transformation through targeting of promiscuous E3 ligases, including FBW7, a known MMP-9 and Snail regulator. Chemical treatments of MMP-9 markedly inhibited MCV sT-induced cell migration and invasion. These results suggest that MCV sT contributes to the activation of MMP-9 as a result of FBW7 targeting, and increases the invasive potential of cells, which can be used for targeted therapeutic intervention.IMPORTANCE Merkel cell carcinoma (MCC) is the most aggressive cutaneous tumor without clearly defined treatment. Although MCC has a high propensity for metastasis, little is known about the underlying mechanisms that drive MCC invasion and metastatic progression. MMP-9 has shown to play a detrimental role in many metastatic human cancers, including melanoma and other non-melanoma skin cancers. Our study shows that MCV sT-mediated MMP-9 activation is driven through the LSD, a known E3 ligase targeting domain, in MCC. MMP-9 may serve as the biochemical culprit to target and develop a novel approach for the treatment of metastatic MCC.

PMID: 32669331 [PubMed - as supplied by publisher]

[Merkel cell carcinoma in face: a case report].

Fetched: July 18th, 2020, 5:01am GMT

[Merkel cell carcinoma in face: a case report].

Zhonghua Kou Qiang Yi Xue Za Zhi. 2020 Mar 09;55(3):185-186

Authors: Yue L, Huo HY, Zhang YH, Yang W

PMID: 32193915 [PubMed - indexed for MEDLINE]

Current concepts and approaches to merkel cell carcinoma.

Fetched: July 17th, 2020, 5:01am GMT

Current concepts and approaches to merkel cell carcinoma.

Arch Dermatol Res. 2020 Jul 14;:

Authors: Babadzhanov M, Doudican N, Wilken R, Stevenson M, Pavlick A, Carucci J

Abstract
Merkel cell carcinoma (MCC) is an aggressive and rare cutaneous cancer of the mechanoreceptor unit of the skin with a neuroendocrine origin. MCC incidence has been on the rise over the past two decades. Risk factors include old age, chronic UV exposure, and immunosuppression. Although MCC is a cutaneous malignancy that is often misdiagnosed as a benign nodule at the time of diagnosis, it has an aggressive disease course due to its high recurrence and metastatic potential. The PD-1/PD-L1 checkpoint blockade has recently shown promising results in the management of advanced MCC. Avelumab and pembrolizumab are considered the new standard of care for metastatic MCC. Despite advances in the field, studies are needed to elucidate the role of immunotherapy for patients who are resistant to treatment. Most ongoing clinical trials aim to assess the efficacy of checkpoint inhibitor combination therapies. This article reviews the most current literature on the surgical and medical management of MCC.

PMID: 32666149 [PubMed - as supplied by publisher]

MCPyV Large T Antigen-Induced Atonal Homolog 1 Is a Lineage-Dependency Oncogene in Merkel Cell Carcinoma.

Fetched: July 17th, 2020, 5:01am GMT

MCPyV Large T Antigen-Induced Atonal Homolog 1 Is a Lineage-Dependency Oncogene in Merkel Cell Carcinoma.

J Invest Dermatol. 2020 01;140(1):56-65.e3

Authors: Fan K, Gravemeyer J, Ritter C, Rasheed K, Gambichler T, Moens U, Shuda M, Schrama D, Becker JC

Abstract
Despite the fact that the transcription factor ATOH1 is a master regulator of Merkel cell development, its role in Merkel cell carcinoma (MCC) carcinogenesis remains controversial. Here, we provide several lines of evidence that ATOH1 is a lineage-dependent oncogene in MCC. Luciferase assays revealed binding of ATOH1 and subsequent activation to the promoter of miR-375, which is one of the most abundant microRNAs in MCCs. Overexpression of ATOH1 in variant MCC cell lines and fibroblasts induced miR-375 expression, whereas ATOH1 knockdown in classical MCC cell lines reduced miR-375 expression. Moreover, ATOH1 overexpression in these cells changed their growth characteristics from adherent to suspension and/orspheroidal growth, that is, resembling the neuroendocrine growth pattern of classical MCC cell lines. Notably, ectopic expression of different Merkel cell polyomavirus (MCPyV)-derived truncated large T antigens induced ATOH1 expression in fibroblasts, which was paralleled by miR-375 expression and similar morphologic changes. In summary, MCPyV-associated carcinogenesis is likely to induce the characteristic neuroendocrine features of MCC via induction of ATOH1; thus, ATOH1 can be regarded as a lineage-dependent oncogene in MCC.

PMID: 31283928 [PubMed - indexed for MEDLINE]

Effect of Sentinel Lymph Node Biopsy and LVI on Merkel Cell Carcinoma Prognosis and Treatment.

Fetched: July 16th, 2020, 5:00am GMT

Effect of Sentinel Lymph Node Biopsy and LVI on Merkel Cell Carcinoma Prognosis and Treatment.

Laryngoscope. 2020 Jul 14;:

Authors: Harounian JA, Molin N, Galloway TJ, Ridge D, Bauman J, Farma J, Reddy S, Lango MN

Abstract
OBJECTIVE: Prognostic factors and optimal treatment approaches for Merkel cell carcinoma (MCC) remain uncertain. This study evaluated the influences of sentinel lymph node (SLN) biopsy and lymphovascular invasion (LVI) on treatment planning and prognosis.
STUDY DESIGN: Retrospective cohort study.
METHODS: Stage 1 to 3 MCC patients treated 2005 to 2018. Predictors of nodal radiation were tested using logistic regression. Predictors of recurrence-free, disease-specific, and overall survival were tested in Cox proportional hazard models.
RESULTS: Of 122 patients, 99 were without clinically apparent nodal metastases. Of these, 76 (77%) underwent excision and SLN biopsy; 29% had metastasis in SLNs, including 20% of MCCs 1 cm or less. Primary tumor diameter, site, patient age, gender, and immunosuppressed status were not significantly associated with an involved SLN. Among patients who underwent SLN biopsy, 13 of 21 (62%) MCCs with LVI had cancer in SLNs compared with 14 of 44 (25.5%) without LVI (P = .003). Although local radiation was common, nodal radiation was infrequently employed in SLN negative (pathologic N0) patients (21.8% vs. 76.2% for patients with SLN metastases, P = .0001). Survival of patients with positive SLNs was unfavorable, regardless of completion lymphadenectomy and/or adjuvant radiation. After accounting for tumor (T) and node (N) classification, age, immunosuppression, and primary site, a positive SLN and LVI were independently associated with worse survival (LVI/recurrence-free survival [RFS]: hazard ratio [HR] 2.3 (1.04-5, P = .04; LVI/disease-specific survival [DSS]: HR 5.2 (1.8-15, P = .007); N1a vs. pN0/RFS HR 3.6 (1.42-9.3, P = .007); DSS HR5.0 (1.3-19, P = .17).
CONCLUSION: SLN biopsy assists in risk stratification and radiation treatment planning in MCC. LVI and disease in SLNs, independently associated with worse survival, constitute markers of high-risk disease warranting consideration for investigational studies.
LEVEL OF EVIDENCE: III Laryngoscope, 2020.

PMID: 32663337 [PubMed - as supplied by publisher]

Primary Merkel Cell Carcinoma: A Retrospective Analysis of 31 Cases in Poland.

Fetched: July 14th, 2020, 5:00am GMT

Primary Merkel Cell Carcinoma: A Retrospective Analysis of 31 Cases in Poland.

Dermatol Ther (Heidelb). 2020 Jul 11;:

Authors: Ciążyńska M, Szczepaniak K, Pabianek M, Nejc D, Reich A, Ułańska M, Owczarek W, Skibińska M, Narbutt J, Lesiak A

Abstract
INTRODUCTION: Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous neuroendocrine cancer that typically arises in sun-exposed areas of the skin, especially in the elderly. Significant advances have recently been made regarding skin cancers, but data on cases of MCC are rather limited as these patients are frequently grouped together with other non-melanoma skin cancers (NMSC). Here, we performed an analysis of the clinical profile of patients with MCC in Poland to identify major factors influencing the prognosis.
METHODS: Approximately 13,000 pathology and medical records were examined to identify patients with MCC diagnosed between 2010 and 2019. The management and outcomes of patients with histologically confirmed MCC were retrospectively evaluated.
RESULTS: Thirty-one patients diagnosed with MCC were identified. The tumor occurred predominantly in women (61.3%) and in the elderly (mean 75.6 years). Twenty-nine patients had locoregional MCC and two had metastatic MCC at the time of diagnosis. Patients in stage I disease had excellent prognosis. In stages II and III, respectively 22.2% and 50.0% of patients developed metastases. Among patients who received chemotherapy with cisplatin and etoposide, 17% achieved partial remission with progression-free survival (PFS) of 8.0 months, and a further 50% achieved stable disease with PFS of 4.0, 4.5, and 4.5 months respectively. In 6 (19.4%) patients MCC coexisted with chronic lymphocytic leukemia (CLL). In all six cases CLL preceded MCC development.
CONCLUSIONS: Female gender, tumor-free resection margins, and local disease were found to be independent prognostic factors in MCC progression. Patients with hematological malignancies, immunosuppression, and those with immune deficiencies should be closely followed up as they are predisposed to develop MCC.

PMID: 32654000 [PubMed - as supplied by publisher]

Jejunal metastasis of Merkel cell carcinoma: case report.

Fetched: July 11th, 2020, 5:01am GMT

Jejunal metastasis of Merkel cell carcinoma: case report.

G Chir. 2019 Jul-Aug;40(4):364-367

Authors: Mancini S, Solinas L, Leone L, Battaglia B, Notarangelo MG, Hassan R, Di Cosimo C, Angeloni R, Belardi A, Cosentino L, Bakacs A, Sagnotta A

Abstract
Merkel cell carcinoma (MCC) of the skin is a rare but aggressive cutaneous neuroendocrine-derived malignancy that predominantly affects elderly white males. The presence of distant nodal metastases significantly impacts survival. Typical metastatic sites of MCC are liver, bone, brain and skin. Gastrointestinal metastases are uncommon and small bowel is the most common site followed by stomach. We report a case of symptomatic MCC jejunal metastasis.

PMID: 32011994 [PubMed - indexed for MEDLINE]

Merkel Cell Polyomavirus Small Tumour Antigen Activates the p38 MAPK Pathway to Enhance Cellular Motility.

Fetched: July 10th, 2020, 5:01am GMT

Merkel Cell Polyomavirus Small Tumour Antigen Activates the p38 MAPK Pathway to Enhance Cellular Motility.

Biochem J. 2020 Jul 08;:

Authors: Dobson SJ, Anene A, Boyne JR, Mankouri J, Macdonald A, Whitehouse A

Abstract
Merkel cell carcinoma (MCC) is an aggressive skin cancer with high rates of recurrence and metastasis. Merkel cell polyomavirus (MCPyV) is associated with the majority of MCC cases. MCPyV-induced tumourigenesis is largely dependent on the expression of the small tumour antigen (ST). Recent findings implicate MCPyV ST expression in the highly metastatic nature of MCC by promoting cell motility and migration, through differential expression of cellular proteins that lead to microtubule destabilisation, filopodium formation and breakdown of cell-cell junctions. However, the molecular mechanisms which dysregulate these cellular processes are yet to be fully elucidated. Here we demonstrate that MCPyV ST expression activates p38 MAPK signalling to drive cell migration and motility. Notably, MCPyV ST-mediated p38 MAPK signalling occurs through MKK4, as opposed to the canonical MKK3/6 signalling pathway. In addition, our results indicate that an interaction between MCPyV ST and the cellular phospatase subunit PP4C is essential for its effect on p38 MAPK signalling. These results provide novel opportunities for the treatment of metastatic MCC given the intense interest in p38 MAPK inhibitors as therapeutic agents.

PMID: 32639530 [PubMed - as supplied by publisher]

Use of Intraoperative Radioguidance in Recurrent Merkel Carcinoma.

Fetched: July 10th, 2020, 5:01am GMT

Use of Intraoperative Radioguidance in Recurrent Merkel Carcinoma.

Case Rep Surg. 2020;2020:1789185

Authors: Beniey M, Destrempes N, Coulombe G, El Khoury M, Nassif E

Abstract
Merkel cell carcinoma is a rapidly progressive nonmelanoma skin cancer with a high risk of recurrence. When recurrence occurs, it is associated with poor prognosis and there is a lack of guidelines for the management of such cases. This article describes a challenging case in which the innovative use of iodine-125 radioactive seeds permitted us to precisely identify and resect two nonpalpable recurrent nodules. The safety and accuracy of the surgical procedure were compromised by the presence of scar tissue following two past resections and two courses of radiotherapy. Radioactive seed localization is a well-known procedure in breast cancer, demonstrating potential for an extended application in other cancer types and in complex clinical situations.

PMID: 32637182 [PubMed]

Merkel Cell Polyomavirus and Merkel Cell Carcinoma.

Fetched: July 10th, 2020, 5:01am GMT

Merkel Cell Polyomavirus and Merkel Cell Carcinoma.

Cancers (Basel). 2020 Jul 03;12(7):

Authors: Pietropaolo V, Prezioso C, Moens U

Abstract
Viruses are the cause of approximately 15% of all human cancers. Both RNA and DNA human tumor viruses have been identified, with Merkel cell polyomavirus being the most recent one to be linked to cancer. This virus is associated with about 80% of Merkel cell carcinomas, a rare, but aggressive cutaneous malignancy. Despite its name, the cells of origin of this tumor may not be Merkel cells. This review provides an update on the structure and life cycle, cell tropism and epidemiology of the virus and its oncogenic properties. Putative strategies to prevent viral infection or treat virus-positive Merkel cell carcinoma patients are discussed.

PMID: 32635198 [PubMed]

Merkel cell carcinoma: a prompt diagnosis to increase survival.

Fetched: July 10th, 2020, 5:01am GMT

Merkel cell carcinoma: a prompt diagnosis to increase survival.

J Eur Acad Dermatol Venereol. 2019 Dec;33(12):e478-e480

Authors: Chessa MA, Malosso M, Pepe F, Patrizi A, Telo S, Ambrosini V, Fanti S, Magnano M, Baraldi C, Corti B, Filippi F, Vaccari S, Pileri A, Bardazzi F

PMID: 31310359 [PubMed - indexed for MEDLINE]

Permalink for 'PD-1 (PDCD1) promoter methylation in Merkel cell carcinoma: prognostic relevance and relationship with clinico-pathological parameters.'

PD-1 (PDCD1) promoter methylation in Merkel cell carcinoma: prognostic relevance and relationship with clinico-pathological parameters.

Fetched: July 8th, 2020, 5:01am GMT

PD-1 (PDCD1) promoter methylation in Merkel cell carcinoma: prognostic relevance and relationship with clinico-pathological parameters.

Mod Pathol. 2019 09;32(9):1359-1372

Authors: Ricci C, Morandi L, Righi A, Gibertoni D, Maletta F, Ambrosi F, Agostinelli C, Uccella S, Asioli S, Sessa F, Pellilli M, Maragliano R, La Rosa S, Papotti MG, Asioli S

Abstract
Merkel cell carcinoma is an aggressive neuroendocrine skin tumor, for which several non-conclusive prognostic factors of adverse clinical behavior have been reported. As promoter methylation of the immune checkpoint receptor CD279/PD-1/PDCD1(mPDCD1) has been shown to be a prognostic factor in different cancers, we investigated its role in Merkel cell carcinoma. mPDCD1was assessed retrospectively in a cohort of 69 Merkel cell carcinoma patients from the University of Bologna, University of Turin and University of Insubria. Kaplan-Meier curves and log-rank tests were calculated for all variables. To assess the influence of mPDCD1, the Cox proportional hazards model and different Royston-Parmar models were evaluated. High PDCD1 methylation (mPDCD1high) was associated with a higher overall mortality at both the univariate analysis (log rank test: χ2 = 5.17, p = 0.023; permutation test: p = 0.023) and the multivariate analysis (HR = 2.111, p = 0.042). The other variables associated with a higher overall mortality at the multivariate analysis were clinical stage III-IV (HR = 2.357, p = 0.008), size > 2 cm (HR = 2.248, p = 0.031) and Merkel cell polyomavirus (HR = 0.397, p = 0.015). Further, mPDCD1high was strongly associated with older age (81 vs 76 years, p = 0.042), absence of immune cells (92.6%, p < 0.001), no expression of PD-L1 by immune cells (70.4%, p = 0.041) and by both immune and tumor cells (70.4%, p = 0.001). mPDCD1 is a valid prognostic parameter in patients affected by Merkel cell carcinoma. In addition, it could provide an estimate of the global PD-1/PD-L1 expression with potentially relevant implications from a therapeutic point of view.

PMID: 30976104 [PubMed - indexed for MEDLINE]

Permalink for 'B7-H3 Expression in Merkel Cell Carcinoma-Associated Endothelial Cells Correlates with Locally Aggressive Primary Tumor Features and Increased Vascular Density.'

B7-H3 Expression in Merkel Cell Carcinoma-Associated Endothelial Cells Correlates with Locally Aggressive Primary Tumor Features and Increased Vascular Density.

Fetched: July 8th, 2020, 5:01am GMT

B7-H3 Expression in Merkel Cell Carcinoma-Associated Endothelial Cells Correlates with Locally Aggressive Primary Tumor Features and Increased Vascular Density.

Clin Cancer Res. 2019 06 01;25(11):3455-3467

Authors: Aung PP, Parra ER, Barua S, Sui D, Ning J, Mino B, Ledesma DA, Curry JL, Nagarajan P, Torres-Cabala CA, Efstathiou E, Hoang AG, Wong MK, Wargo JA, Lazar AJ, Rao A, Prieto VG, Wistuba I, Tetzlaff MT

Abstract
PURPOSE: Merkel cell carcinoma (MCC) is an aggressive cutaneous malignancy whose pathogenesis and prognosis are related to the integrity of the host immune system. Despite promising clinical responses to immune-checkpoint blockade, response and resistance remain unpredictable, underscoring a critical need to delineate novel prognostic biomarkers and/or therapeutic targets for this disease.Experimental Design: Expression of immune-regulatory markers (PD-L2, B7-H3, B7-H4, IDO-1, ICOS, TIM3, LAG3, VISTA, and OX-40) was assessed using singlet chromogenic IHC in 10 primary MCCs. Multiplex immunofluorescence quantified CD31 and B7-H3 expression in 52 primary and 25 metastatic MCCs. B7-H3 and CD31 expressions were tabulated as a series of independent (X,Y) cell centroids. A spatial G-function, calculated based on the distribution of distances of B7-H3+ (X,Y) cell centroids around the CD31+ (X,Y) cell centroids, was used to estimate a colocalization index equivalent to the percentage of CD31-positive cell centroids that overlap with a B7-H3-positive cell centroid.
RESULTS: Primary and metastatic MCCs exhibit a dynamic range of colocalized CD31 and B7-H3 expression. Increasing colocalized expression of B7-H3 with CD31 significantly associated with increased tumor size (P = 0.0060), greater depth of invasion (P = 0.0110), presence of lymphovascular invasion (P = 0.0453), and invasion beyond skin (P = 0.0428) in primary MCC. Consistent with these findings, increasing colocalized expression of B7-H3 and CD31 correlated with increasing vascular density in primary MCC, but not metastatic MCC.
CONCLUSIONS: Our results demonstrate that colocalized expression of B7-H3/CD31 is a poor prognostic indicator and suggest therapies targeting B7-H3 may represent an effective approach to augmenting immune-activating therapies for MCC.

PMID: 30808776 [PubMed - indexed for MEDLINE]

Polyomaviruses of the skin: integrating molecular and clinical advances in an emerging class of viruses.

Fetched: July 8th, 2020, 5:01am GMT

Polyomaviruses of the skin: integrating molecular and clinical advances in an emerging class of viruses.

Br J Dermatol. 2019 06;180(6):1302-1311

Authors: Sheu JC, Tran J, Rady PL, Dao H, Tyring SK, Nguyen HP

Abstract
BACKGROUND: Human polyomaviruses (HPyVs) are small, nonenveloped, double-stranded DNA viruses that express tumour antigen proteins. Fourteen species of polyomaviruses have been discovered in humans, and since the 2008 discovery of the first cutaneous polyomavirus - Merkel cell polyomavirus (MCPyV) - six more species have been detected in the skin: trichodysplasia spinulosa-associated polyomavirus (TSPyV), HPyV6, HPyV7, HPyV9, HPyV10 and HPyV13. Of these cutaneous species, only MCPyV, TSPyV, HPyV6 and HPyV7 have been definitively associated with diseases of the skin, most commonly in immunocompromised individuals. MCPyV is a predominant aetiology in Merkel cell carcinomas. TSPyV is one of the aetiological factors of trichodysplasia spinulosa. HPyV6 and HPyV7 have been recently linked to pruritic skin eruptions. The roles of HPyV9, HPyV10 and HPyV13 in pathogenesis, if any, are still unknown, but their molecular features have provided some insight into their functional biology.
RESULTS: In this review, we summarize the known molecular mechanisms, clinical presentation and targeted therapies of each of the eight cutaneous HPyVs.
CONCLUSIONS: We hope that heightened awareness and clinical recognition of HPyVs will lead to increased reports of HPyV-associated diseases and, consequently, a more robust understanding of how to diagnose and treat these conditions.

PMID: 30585627 [PubMed - indexed for MEDLINE]

A multidisciplinary consensus on the morphological and functional responses to immunotherapy treatment.

Fetched: July 7th, 2020, 5:00am GMT

A multidisciplinary consensus on the morphological and functional responses to immunotherapy treatment.

Clin Transl Oncol. 2020 Jul 04;:

Authors: Leon-Mateos L, Garcia-Velloso MJ, García-Figueiras R, Rodriguez-Moreno JF, Vercher-Conejero JL, Sánchez M, Perez Gracia JL, Simo-Perdigo M, Gorospe L

Abstract
The implementation of immunotherapy has radically changed the treatment of oncological patients. Currently, immunotherapy is indicated in the treatment of patients with head and neck tumors, melanoma, lung cancer, bladder tumors, colon cancer, cervical cancer, breast cancer, Merkel cell carcinoma, liver cancer, leukemia and lymphomas. However, its efficacy is restricted to a limited number of cases. The challenge is, therefore, to identify which subset of patients would benefit from immunotherapy. To this end, the establishment of immunotherapy response criteria and predictive and prognostic biomarkers is of paramount interest. In this report, a group of experts of the Spanish Society of Medical Oncology (SEOM), the Spanish Society of Medical Radiology (SERAM), and Spanish Society of Nuclear Medicine and Molecular Imaging (SEMNIM) provide an up-to-date review and a consensus guide on these issues.

PMID: 32623581 [PubMed - as supplied by publisher]

Mohs micrographic surgery: a treatment method for many non-melanocytic skin cancers.

Fetched: July 7th, 2020, 5:00am GMT

Mohs micrographic surgery: a treatment method for many non-melanocytic skin cancers.

Dermatol Online J. 2020 Apr 15;26(4):

Authors: Dokic Y, Nguyen QL, Orengo I

Abstract
Mohs micrographic surgery (MMS) is a breakthrough surgical technique that has changed the management of neoplasms in dermatology. Through continued practice and evolution, MMS now can successfully treat a variety of rare non-melanocytic cutaneous malignancies for which achieving remission and the optimal aesthetic result after surgery was previously challenging. Mohs micrographic surgery has utility for conditions besides melanoma. Herein, we discuss this versatility of Mohs micrographic surgery. Specifically, Mohs micrographic surgery can be successfully used for cases such as dermatofibrosarcoma protuberans, atypical fibroxanthomas, extramammary Paget disease, Merkel cell carcinoma, sebaceous carcinoma, and microcystic adnexal carcinoma.

PMID: 32621679 [PubMed - in process]

[Merkel cell carcinoma in chronic lymphocytic leukemia : Successful treatment with PD-L 1 inhibition, avelumab and chlorambucil].

Fetched: July 3rd, 2020, 5:01am GMT

[Merkel cell carcinoma in chronic lymphocytic leukemia : Successful treatment with PD-L 1 inhibition, avelumab and chlorambucil].

Hautarzt. 2020 Jul;71(7):553-556

Authors: Dücker P, Hüning S, Rohde S, Lorenzen J, Nashan D

Abstract
We report the case of an 85-year-old chronic lymphocytic leukemia patient with a local metastatic MCVPyV-negative Merkel cell carcinoma at initial diagnosis. Therapy comprised surgical excision and radiotherapy but without lymphadenectomy. Six months after the primary diagnosis, liver metastases were detected. They responded to the PD-L1 inhibitor avelumab for more than 15 months. Thus, we postulate a synergistic effect of combined therapy with chlorambucil and avelumab through a mutual improvement of immune function, from which both diseases benefit.

PMID: 32394077 [PubMed - indexed for MEDLINE]

Molecular Mechanisms of Merkel Cell Polyomavirus Transformation and Replication.

Fetched: July 2nd, 2020, 5:01am GMT

Molecular Mechanisms of Merkel Cell Polyomavirus Transformation and Replication.

Annu Rev Virol. 2020 Jun 30;:

Authors: Liu W, You J

Abstract
Viral infection underlies a significant share of the global cancer burden. Merkel cell polyomavirus (MCPyV) is the newest member of the human oncogenic virus family. Its discovery over a decade ago marked the beginning of an exciting era in human tumor virology. Since then, significant evidences have emerged to support the etiologic role of MCPyV in Merkel cell carcinoma (MCC), an extremely lethal form of skin cancer. MCPyV infection is widespread in the general population. MCC diagnoses have tripled over the past 20 years, but effective treatments are currently lacking. In this review, we highlight recent discoveries that have shaped our understanding of MCPyV oncogenic mechanism and host cellular tropism, as well as the molecular events occurring in the viral infectious life cycle. These insights will guide future efforts in developing novel virus-targeted therapeutic strategies for treating the devastating human cancers associated with this new tumorigenic virus. Expected final online publication date for the Annual Review of Virology, Volume 7 is September 29, 2020. Please see [www.annualreviews.org] for revised estimates.

PMID: 32603631 [PubMed - as supplied by publisher]

Periocular skin cancer: Diagnosis and management.

Fetched: July 2nd, 2020, 5:01am GMT

Periocular skin cancer: Diagnosis and management.

Dis Mon. 2020 Jun 26;:101046

Authors: Moran JM, Phelps PO

Abstract
The periocular region sees high rates of cancer compared to the rest of the body and can be affected by several unique tumors. Treatment typically involves surgical excision, although adjunctive therapies and prognosis vary depending on the diagnosis. Basal cell carcinoma (BCC) is the most common malignancy affecting this region and should be excised promptly. This is followed by squamous cell carcinoma, which is often mistaken for BCC but is treated similarly. Melanoma is less common but more deadly, with relatively high rates of metastasis and death. Rare tumors that may be found in this region include sebaceous carcinoma, Merkel cell carcinoma, and microcystic adnexal carcinoma. While uncommon, these tumors are associated with poor outcomes and frequent recurrence. Recognition of periocular skin cancer is an important skill for primary care physicians, as prompt diagnosis and treatment can be sight or life-saving.

PMID: 32600650 [PubMed - as supplied by publisher]

Bone marrow involvement with Merkel cell carcinoma.

Fetched: July 2nd, 2020, 5:01am GMT

Bone marrow involvement with Merkel cell carcinoma.

BMJ Case Rep. 2020 Jun 28;13(6):

Authors: Khan A, Adil S, Estalilla OC, Jubelirer S

Abstract
Merkel cell carcinoma (MCC) is a rare but highly aggressive cutaneous tumour. Most tumours occur in the head and neck, extremities or torso and 36% of them involve the face. Bone marrow involvement in MCC is rare and to our knowledge only nine cases reported in the English literature. Bone marrow biopsy is not usually performed to stage MCC; thus, the true incidence of bone marrow involvement may be under-reported. The majority of the cases reported in the literature have some form of immunosuppression, which suggests a strong association. We report a case of extensive bone marrow involvement from MCC in an 80-year-old Caucasian woman with a history of rheumatoid arthritis treated with adalimumab, methotrexate and prednisone. It may be prudent to include bone marrow biopsy in the staging of MCC in immune-compromised patients.

PMID: 32595130 [PubMed - in process]

Association of Programmed Death 1 Protein Ligand (PD-L1) Expression With Prognosis in Merkel Cell Carcinoma.

Fetched: June 27th, 2020, 5:01am GMT

Association of Programmed Death 1 Protein Ligand (PD-L1) Expression With Prognosis in Merkel Cell Carcinoma.

Front Med (Lausanne). 2020;7:198

Authors: Hanna GJ, Kacew AJ, Tanguturi AR, Grote HJ, Vergara V, Brunkhorst B, Rabinowits G, Thakuria M, LeBoeuf NR, Ihling C, DeCaprio JA, Lorch JH

Abstract
Background: Merkel cell carcinoma (MCC) is a rare neuroendocrine skin cancer. Prior to the advent of immunotherapy, treatment options were limited. In our study, we evaluate the impact of tumor cell PD-L1 expression and tumor immune microenvironment on survival in MCC patients who were not treated with immune checkpoint inhibitors. Methods: Clinical data and tissue samples were collected from 78 patients with confirmed MCC treated at Dana-Farber Cancer Institute. Specimens were analyzed for the distribution of PD-L1 by immunohistochemistry staining (IHC) and standardized analysis. Results were correlated with survival data. Results: In this study, membrane and cytoplasmic MCC tumor cell staining for PD-L1 was detected in 22.4% (15 of 67) of cases and PD-L1 staining of intratumoral microvessels and PD-L1 positive immune cells at the infiltrative margins of the tumor in 92.5% (62 of 67) of cases. In patients untreated with immune checkpoint inhibitors, median overall survival was not different for patients based on PD-L1 expression (PD-L1+ 64 months vs. PD-L1- not reached; HR = 1.26, 95% CI: 0.46-3.45; p = 0.60). Conclusion: PD-L1 expression is frequently detected in MCC tumor cells and tumor microenvironment. PD-L1 expression did not affect prognosis in this cohort that had not received PD-1/L1 blockade.

PMID: 32582722 [PubMed]

Insulinoma-associated protein 1 immunostaining for various types of neuroendocrine tumors on FNA smears.

Fetched: June 25th, 2020, 5:00am GMT

Insulinoma-associated protein 1 immunostaining for various types of neuroendocrine tumors on FNA smears.

Cancer Cytopathol. 2020 Jun 23;:

Authors: Hou T, Gan Q, Joseph CT, Sun X, Gong Y

Abstract
BACKGROUND: Insulinoma-associated protein 1 (INSM1) has recently emerged as a reliable nuclear immunostaining marker for detecting neuroendocrine tumors (NETs) in paraffin-embedded surgical samples and cytologic cell blocks, but the reliability of INSM1 staining on cytologic smears is understudied. This study investigated the performance of INSM1 staining on cytologic smears for the detection of various NETs in comparison with chromogranin (CG) and synaptophysin (SYN).
METHODS: INSM1, CG, and SYN were stained on cytologic smears of 70 NETs, including 20 pancreatic NETs, 10 lung carcinoid tumors, 11 small cell lung carcinomas (SCLCs), 10 medullary thyroid carcinomas, 10 Merkel cell carcinomas, 4 thymic atypical carcinoid tumors, and 5 olfactory neuroblastomas. The detection rate, the percentage of positive cells, and the staining intensity were recorded.
RESULTS: The overall detection rate of INSM1 (94%) was higher than the rates of CG (79%) and SYN (89%). The detection rate of INSM1 was higher than the rates of CG and SYN in SCLC, Merkel cell carcinoma, and olfactory neuroblastoma; higher than the rate of CG and equal to the rate of SYN in pancreatic NETs and medullary thyroid carcinoma; equal to the rate of CG and higher than the rate of SYN in thymic atypical carcinoid tumors; and equal to the rate of CG and lower than the rate of SYN in lung carcinoid tumors. INSM1 staining was easier to interpret than CG and SYN staining, especially in high-grade NETs.
CONCLUSIONS: INSM1 can be reliably stained on cytologic smears and outperforms CG and SYN in the verification of clinically or radiologically suspected NETs.

PMID: 32573984 [PubMed - as supplied by publisher]

The Role of Age and Merkel Cell Polyomavirus in Oral Cavity Cancers.

Fetched: June 25th, 2020, 5:00am GMT

The Role of Age and Merkel Cell Polyomavirus in Oral Cavity Cancers.

Otolaryngol Head Neck Surg. 2020 Jun 23;:194599820932553

Authors: Windon M, Fakhry C, Rooper L, Ha P, Schoppy D, Miles B, Koch W, Vosler P, Eisele D, D'Souza G

Abstract
The incidence of oral tongue cancer, the majority subsite of oral cavity cancer, is rising among young people with less exposure to tobacco and alcohol. Viral causes have been proposed, including Merkel cell polyomavirus (MCPyV). We evaluated patient and tumor characteristics among 126 incident oral cavity cancers (OCCs). Consistent with generational norms, younger patients had less exposure to tobacco and a greater number of oral sexual partners than older OCCs. In addition, younger patients were more likely to present at an earlier stage and with cancer arising from the oral tongue (each P < .05). A subset of 44 cases was centrally tested for MCPyV large T antigen expression by immunohistochemistry. In the presence of controls, none of the tumors expressed MCPyV. These findings exclude consideration of MCPyV as an etiologic factor in OCC and may generate hypotheses for future examinations of the factors underlying the rise in oral tongue cancers.

PMID: 32571145 [PubMed - as supplied by publisher]

Decreased survival and increased recurrence in Merkel cell carcinoma significantly linked with immunosuppression.

Fetched: June 22nd, 2020, 5:01am GMT

Decreased survival and increased recurrence in Merkel cell carcinoma significantly linked with immunosuppression.

J Surg Oncol. 2020 Jun 20;:

Authors: Bryant MK, Ward C, Gaber CE, Strassle PD, Ollila DW, Laks S

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) is a rare and aggressive form of skin cancer. It is an immunogenic tumor as evident by its association with Polyomavirus, immunotherapy response, and increased prevalence in the immunosuppressed population.
OBJECTIVE: We sought to evaluate the impact of known clinicopathological determinants and immunosuppression on the risk of recurrence and mortality of MCC patients.
METHODS: A retrospective, observational cohort study of patients diagnosed and/or treated with MCC at two tertiary academic institutions. We compared clinicopathological determinants, treatment modalities, and immunosuppression status on clinical outcomes of recurrence, disease-specific survival, and overall survival.
RESULTS: We evaluated 90 patients within our study and 34% had a cancer recurrence during follow-up. Patients with recurrence were significantly more likely to be immunosuppressed (32% vs 5%; P = .001). Estimated 5-year recurrence was 43%, and immunosuppressed patients were significantly more likely to recur (Hazard ratio [HR] 3.67 [1.80-7.51]; P < .0001). Immunosuppressed patients had significantly elevated cancer-specific mortality (HR 6.11[1.61-23.26]; P = .008).
LIMITATIONS: Retrospective review with a prolonged observation period and changing treatment modalities.
CONCLUSION: Immunocompromised patients had a threefold increased incidence of 5-year mortality and over twofold increased incidence of any recurrence as non-immunocompromised patients. Patients' immunosuppressive status should be considered when making decisions regarding treatment, surveillance, and prognostication.

PMID: 32562583 [PubMed - as supplied by publisher]

p110δ PI3K as a therapeutic target of solid tumours.

Fetched: June 21st, 2020, 5:01am GMT

p110δ PI3K as a therapeutic target of solid tumours.

Clin Sci (Lond). 2020 Jun 26;134(12):1377-1397

Authors: Xenou L, Papakonstanti EA

Abstract
From the time of first characterization of PI3K as a heterodimer made up of a p110 catalytic subunit and a regulatory subunit, a wealth of evidence have placed the class IA PI3Ks at the forefront of drug development for the treatment of various diseases including cancer. The p110α isoform was quickly brought at the centre of attention in the field of cancer research by the discovery of cancer-specific gain-of-function mutations in PIK3CA gene in a range of human solid tumours. In contrast, p110δ PI3K was placed into the spotlight of immunity, inflammation and haematologic malignancies because of the preferential expression of this isoform in leucocytes and the rare mutations in PIK3CD gene. The last decade, however, several studies have provided evidence showing that the correlation between the PIK3CA mutations and the response to PI3K inhibition is less clear than originally considered, whereas concurrently an unexpected role of p110δ PI3K in solid tumours has being emerging. While PIK3CD is mostly non-mutated in cancer, the expression levels of p110δ protein seem to act as an intrinsic cancer-causing driver in various solid tumours including breast, prostate, colorectal and liver cancer, Merkel-Cell carcinoma, glioblastoma and neurobalstoma. Furthermore, p110δ selective inhibitors are being studied as potential single agent treatments or as combination partners in attempt to improve cancer immunotherapy, with both strategies to shown great promise for the treatment of several solid tumours. In this review, we discuss the evidence implicating the p110δ PI3K in human solid tumours, their impact on the current state of the field and the potential of using p110δ-selective inhibitors as monotherapy or combined therapy in different cancer contexts.

PMID: 32556179 [PubMed - in process]

The Evolution of Care of Cancers of the Head and Neck Region: State of the Science in 2020.

Fetched: June 19th, 2020, 5:01am GMT

The Evolution of Care of Cancers of the Head and Neck Region: State of the Science in 2020.

Cancers (Basel). 2020 Jun 11;12(6):

Authors: Yan F, Knochelmann HM, Morgan PF, Kaczmar JM, Neskey DM, Graboyes EM, Nguyen SA, Ogretmen B, Sharma AK, Day TA

Abstract
Cancers that arise in the head and neck region are comprised of a heterogeneous group of malignancies that include carcinogen- and human papillomavirus (HPV)-driven mucosal squamous cell carcinoma as well as skin cancers such as cutaneous squamous cell carcinoma, basal cell carcinoma, melanoma, and Merkel cell carcinoma. These malignancies develop in critical areas for eating, talking, and breathing and are associated with substantial morbidity and mortality despite advances in treatment. Understanding of advances in the management of these various cancers is important for all multidisciplinary providers who care for patients across the cancer care continuum. Additionally, the recent Coronavirus Disease 2019 (COVID-19) pandemic has necessitated adaptations to head and neck cancer care to accommodate the mitigation of COVID-19 risk and ensure timely treatment. This review explores advances in diagnostic criteria, prognostic factors, and management for subsites including head and neck squamous cell carcinoma and the various forms of skin cancer (basal cell carcinoma, cutaneous squamous cell carcinoma, Merkel cell carcinoma, and melanoma). Then, this review summarizes emerging developments in immunotherapy, radiation therapy, cancer survivorship, and the delivery of care during the COVID-19 era.

PMID: 32545409 [PubMed]

Merkel cell carcinoma with divergent differentiation.

Fetched: June 18th, 2020, 5:01am GMT

Merkel cell carcinoma with divergent differentiation.

Clin Exp Dermatol. 2020 Apr;45(3):327-332

Authors: Gaitskell K, Nassar S, Ibrahim H

Abstract
Merkel cell carcinoma (MCC) is a rare primary neuroendocrine carcinoma of the skin, usually occurring at sun-exposed sites in elderly people. Divergent differentiation in MCC, although rare, has been reported in previous case series. We describe two new cases of MCC with divergent differentiation. Patient 1 was a 96-year-old man with a scalp lesion; on biopsy, the morphology and immunoprofile suggested MCC with divergent squamous differentiation. Patient 2 was an 87-year-old woman with a lesion on her leg, originally reported as squamous cell carcinoma, later showing extensive local recurrence. On review, primary histology showed an MCC with divergent differentiation, most likely trichilemmal carcinoma; the recurrence showed only MCC. These cases illustrate that MCC is capable of divergent differentiation, including squamous and adnexal morphologies. Correct diagnosis is essential for appropriate prognosis and management, as later recurrence or metastases may only show the Merkel cell component.

PMID: 31580510 [PubMed - indexed for MEDLINE]

Neoadjuvant Checkpoint Inhibitor Therapy for Merkel Cell Carcinoma.

Fetched: June 14th, 2020, 5:01am GMT

Neoadjuvant Checkpoint Inhibitor Therapy for Merkel Cell Carcinoma.

J Clin Oncol. 2020 Jun 12;:JCO2000752

Authors: Brohl AS, Sondak VK

Abstract
A 78-year-old man presented with rapidly enlarging lymph nodes in the right preauricular region and neck. Needle biopsy revealed a cytokeratin 20-positive, high-grade neuroendocrine neoplasm consistent with Merkel cell carcinoma (MCC). Cross-sectional imaging disclosed a 5.2-cm intraparotid mass and extensive adenopathy in the ipsilateral cervical and submental chains (Figs 1A and 1C), without distant metastatic disease. A skin examination did not reveal a primary lesion (hence, stage IIIA, T0N1bM0). The patient's history was notable for hypertension, diet-controlled diabetes type II, high cholesterol, and a past history of numerous cutaneous basal and squamous cell carcinomas. He was quite active but reported discomfort from the bulk of the tumors. The patient was evaluated by the surgical oncology team, who believed that the parotid mass and cervical adenopathy were technically resectable but that resection carried a substantial risk of morbidity because of the potential need to sacrifice the facial and/or spinal accessory nerves and because of a likely margin-positive (R1 or R2) result. He was referred to the medical oncology team to discuss management options for regionally advanced, "borderline-resectable" MCC.

PMID: 32530767 [PubMed - as supplied by publisher]

The Clinical Utility of Neuron-Specific Enolase (NSE) Serum Levels as a Biomarker for Merkel Cell Carcinoma (MCC).

Fetched: June 14th, 2020, 5:01am GMT

The Clinical Utility of Neuron-Specific Enolase (NSE) Serum Levels as a Biomarker for Merkel Cell Carcinoma (MCC).

Ann Surg Oncol. 2020 Jun 11;:

Authors: van Veenendaal LM, Bertolli E, Korse CM, Klop WMC, Tesselaar MET, van Akkooi ACJ

Abstract
BACKGROUND: No adequate biomarker for Merkel cell carcinoma (MCC) has been identified. Serum neuron-specific enolase (NSE) has been tested and is commonly used as a biomarker for several other small cell malignancies. However, the role of NSE in MCC is still unclear. The purpose of this study was to investigate the role of NSE as a biomarker in MCC.
METHODS: A prospective cohort of MCC patients was analyzed using Kaplan-Meier curves with log-rank test, ROC curves, Cox regression, and mixed models. A separate evaluation was performed for patients treated with immunotherapy.
RESULTS: Eighty-four patients were included [47 males, median age 71 years, stages I & II, III, and IV MCC in respectively 39 (46%), 42 (50%), and 4 (3%) patients at time of diagnosis] with 565 NSE samples (median 15; interquartile range 12.6-22 ng/ml). Baseline NSE had no association with prognosis. NSE correlated with extent of disease (P = 0.01) and increased with 15 ng/ml per class (no tumor load, localized MCC, regional or distant metastases, respectively). NSE was able to detect progression (AUC 0.89). A NSE of 18.2 ng/ml was considered the most optimal level for clinical use (sensitivity 91%, specificity 78%, PPV 48%, NPV 98%). During immunotherapy (N = 23; 248 NSE values), all complete responders (N = 10) had a normalized NSE (< 18.2 ng/ml), all partial responders (N = 5) had a decreasing NSE. In nonresponders (N = 8), all NSE levels remained elevated.
CONCLUSIONS: NSE could be a valuable biomarker in MCC. NSE correlates with extent of disease; it is able to rule out progression and distinguishes responders from nonresponders during immunotherapy.

PMID: 32529274 [PubMed - as supplied by publisher]

Medically inoperable Merkel cell carcinoma of the head and neck treated with stereotactic body radiation therapy: a case report.

Fetched: June 14th, 2020, 5:01am GMT

Medically inoperable Merkel cell carcinoma of the head and neck treated with stereotactic body radiation therapy: a case report.

Ann Palliat Med. 2020 Jun 02;:

Authors: Zhu JW, Doerwald-Munoz L, Lee JW

Abstract
Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine tumour of the skin. MCC is the second most common cause of death from non-melanoma skin cancer and the most aggressive cutaneous malignancy. An 88-year-old male presented with a large, bleeding skin tumour located on the right temple and pre-auricular region. A biopsy confirmed MCC; immunohistochemistry (IHC) was positive for synaptophysin and CK20. The patient was assessed by a head and neck surgical oncologist and not deemed to have operable disease due to medical co-morbidities and extent of disease. The patient underwent a single fraction of electron treatment, followed by stereotactic body radiation therapy (SBRT) to a total dose of 40 Gy in 5 fractions over 2 weeks. Bleeding stopped and the patient tolerated treatment well with no reported side effects other than fatigue. There was symptomatic improvement within 2 weeks and a complete clinical response within 4 weeks of treatment. There are limited data on the use of radiotherapy in unresected/ inoperable MCC. For elderly, medically frail patients who cannot undergo surgery, SBRT may be an option to alleviate symptoms and control the tumour in a relatively short number of treatments; further study is warranted.

PMID: 32527130 [PubMed - as supplied by publisher]

Survival Analysis in Patients with Metastatic Merkel Cell Carcinoma Treated with Avelumab.

Fetched: June 12th, 2020, 5:00am GMT

Survival Analysis in Patients with Metastatic Merkel Cell Carcinoma Treated with Avelumab.

Adv Ther. 2019 09;36(9):2327-2341

Authors: Lanitis T, Proskorovsky I, Ambavane A, Hunger M, Zheng Y, Bharmal M, Phatak H

Abstract
INTRODUCTION: Complex underlying risk functions associated with immuno-oncology treatments have led to exploration of different methods (parametric survival, spline, landmark, and cure-fraction models) to estimate long-term survival outcomes. The objective of this study was to examine differences in estimated short- and long-term survival in previously treated metastatic Merkel cell carcinoma (mMCC) patients receiving avelumab, when using alternative extrapolation approaches.
METHODS: Efficacy data from the phase 2 JAVELIN Merkel 200 trial (part A) with at least 12 months of follow-up were analyzed. Standard parametric survival analyses and analyses of overall survival (OS) as a function of surrogate outcomes comprised of response (landmark analyses) and progression-free survival plus post-progression survival (PFS + PPS) were used to project OS. Overall survival throughout lifetime was projected and compared with the observed OS data with at least 24 months of follow-up.
RESULTS: Estimated OS from all three approaches provided a good fit to the observed OS curve from at least 12 months of follow-up. However, performance compared with OS data from at least 24 months showed that the landmark approach followed by PFS + PPS provided a better fit to the data as compared to standard parametric analysis. Mean life expectancy estimated with avelumab was 2.48 years with best-fitting parametric function (a log-normal distribution), 3.15 years with the landmark approach, and 3.54 years with PFS + PPS.
CONCLUSION: Although standard parametric survival analysis may provide a good fit to short-term survival, it appears to underestimate the long-term survival benefits associated with avelumab in mMCC. Extrapolations based on surrogate outcomes of response or progression predict OS outcomes from longer follow-up better and appear to provide more clinically plausible projections.
FUNDING: EMD Serono Inc, Rockland, MA, a business of Merck KGaA, Darmstadt, Germany.

PMID: 31350728 [PubMed - indexed for MEDLINE]

$Permalink for 'Pre-treated anti-PD-1 refractory Merkel cell carcinoma successfully treated with the combination of PD-1/PD-L1 axis inhibitors and TVEC: a report of two cases.'$

Pre-treated anti-PD-1 refractory Merkel cell carcinoma successfully treated with the combination of PD-1/PD-L1 axis inhibitors and TVEC: a report of two cases.

Fetched: June 11th, 2020, 5:01am GMT

Pre-treated anti-PD-1 refractory Merkel cell carcinoma successfully treated with the combination of PD-1/PD-L1 axis inhibitors and TVEC: a report of two cases.

Ann Oncol. 2019 08 01;30(8):1399-1400

Authors: Knackstedt R, Sussman TA, McCahon L, Song JM, Funchain P, Gastman B

PMID: 31250007 [PubMed - indexed for MEDLINE]

The landscape of host genetic factors involved in infection to common viruses and SARS-CoV-2.

Fetched: June 10th, 2020, 5:01am GMT

The landscape of host genetic factors involved in infection to common viruses and SARS-CoV-2.

medRxiv. 2020 May 30;:

Authors: Kachuri L, Francis SS, Morrison M, Bossé Y, Cavazos TB, Rashkin SR, Ziv E, Witte JS

Abstract
Introduction: Humans and viruses have co-evolved for millennia resulting in a complex host genetic architecture. Understanding the genetic mechanisms of immune response to viral infection provides insight into disease etiology and informs public health interventions.
Methods: We conducted a comprehensive study linking germline genetic variation and gene expression with antibody response to 28 antigens for 16 viruses using serological data from 7924 participants in the UK Biobank cohort. Using test results from 2010 UK Biobank subjects, we also investigated genetic determinants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
Results: Signals in human leukocyte antigen (HLA) class II region dominated the landscape of viral antibody response, with 40 independent loci and 14 independent classical alleles, 7 of which exhibited pleiotropic effects across viral families. Genome-wide association analyses discovered 7 novel genetic loci associated with viral antibody response (P<5.0×10-8), including FUT2 (19q13.33) for human polyomavirus BK (BKV), STING1 (5q31.2) for Merkel cell polyomavirus (MCV), as well as CXCR5 (11q23.3) and TBKBP1 (17q21.32) for human herpesvirus 7. Transcriptome-wide association analyses identified 114 genes associated with response to viral infection, 12 outside of the HLA region, including ECSCR: P=5.0×10-15 (MCV), NTN5: P=1.1×10-9 (BKV), and P2RY13: P=1.1×10-8 (Epstein-Barr virus nuclear antigen). We also demonstrated pleiotropy between viral response genes and complex diseases, such as C4A expression in varicella zoster virus and schizophrenia. Finally, our analyses of SARS-CoV-2 revealed the first genome-wide significant infection susceptibility signal in EHF, an epithelial-specific transcriptional repressor implicated in airway disease. Targeted analyses of expression quantitative trait loci suggest a possible role for tissue-specific ACE2 expression in modifying SARS-CoV-2 susceptibility.
Conclusions: Our study confirms the importance of the HLA region in host response to viral infection and elucidates novel genetic determinants of host-virus interaction. Our results may have implications for complex disease etiology and COVID-19.

PMID: 32511533 [PubMed]

Sentinel lymph node biopsy in clinically node-negative Merkel cell carcinoma: the Westmead Hospital experience.

Fetched: June 10th, 2020, 5:01am GMT

Sentinel lymph node biopsy in clinically node-negative Merkel cell carcinoma: the Westmead Hospital experience.

ANZ J Surg. 2019 05;89(5):520-523

Authors: Jenkins LN, Howle JR, Veness MJ

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy with a propensity to metastasize to regional lymph nodes. Sentinel lymph node biopsy (SLNB) in patients with clinically node-negative MCC has been utilized to identify patients with subclinical nodal metastases. This study aims to review the accuracy of SLNB in MCC and to evaluate the impact of SLNB on management.
METHODS: Patients with clinically node-negative MCC who underwent SLNB were identified from a prospective database of patients treated at the Westmead Hospital, Sydney, between 1998 and 2017. Data from these patients were reviewed and analysed.
RESULTS: Forty-one patients were identified: 28 men and 13 women, median age 70 years. Median duration of follow-up was 27 months. Sixteen (39%) patients had a positive SLNB and all underwent nodal treatment which consisted of radiotherapy (n = 13), completion lymphadenectomy and adjuvant radiotherapy (n = 2), and completion lymphadenectomy alone (n = 1). Following negative SLNB, 24 of 25 patients did not undergo further nodal treatment. The false-negative rate was 16% as three patients developed in-field nodal recurrence subsequent to a negative SLNB. At last follow-up, 29 patients had no evidence of disease, six were alive with disease and three had died from other causes. Three SLN-positive patients have died of MCC.
CONCLUSION: SLNB has a high rate of positivity and can improve the accuracy of staging and prognostication in MCC, and guide management. The relatively low risk of a false-negative SLNB justifies close observation in SLNB-negative patients.

PMID: 30959572 [PubMed - indexed for MEDLINE]

Merkel cells of human oral mucosa express the pluripotent stem cell transcription factor Sox2.

Fetched: June 6th, 2020, 5:01am GMT

Merkel cells of human oral mucosa express the pluripotent stem cell transcription factor Sox2.

Histol Histopathol. 2020 May 04;:18231

Authors: García-Caballero L, Caneiro J, Gándara M, González-Ortega N, Cepeda-Emiliani A, Gude F, Collado M, Beiras A, Gallego R

Abstract
Merkel cells are neuroendocrine cells associated to a neural sensitive ending and localized primarily in the epidermis, although they are also found in oral mucosa. Sox2 or SRY-box2 is a key transcription factor important in the maintenance of embryonic neural crest stem cell pluripotency. Sox2 has been described in Merkel cells of skin and in Merkel cell carcinomas, but not specifically in oral Merkel cells. The aims of the present study were to analyze the density of Merkel cells in human oral mucosa and to study the expression of Sox2 in these cells. For these purposes, immunohistochemical analyses for Sox2 and CK20 (the best marker for Merkel cells) were automatically performed on sections of normal human oral mucosa. Double immunofluorescence for Sox2 and CK20 was also performed. To analyze the density of Merkel cells, CK20 positive cells were counted in each sample and the length of the epithelial apical edge was measured (cells/mm). Merkel cells, demonstrated by CK20 immunoreactivity, were found in 95% of oral mucosa specimens studied (n=21). Mean density of Merkel cells in oral mucosa was 1.71±2.34 cells/mm. Sox2 immunoreactivity was found in the nuclei of scattered cells located at the basal layer. Serial sections immunostained for Sox2 and CK20 showed that Sox2-positive cells of oral mucosa coexpressed CK20, confirming that they were Merkel cells. Immunofluorescence for Sox2 and CK20 showed colocalization of both markers, demonstrating that virtually all oral Merkel cells expressed Sox2. This transcription factor could play a role in Merkel cell maturation and maintenance.

PMID: 32495847 [PubMed - as supplied by publisher]

Inhibition of PI3K by copanlisib exerts potent antitumor effects on Merkel cell carcinoma cell lines and mouse xenografts.

Fetched: June 4th, 2020, 5:01am GMT

Inhibition of PI3K by copanlisib exerts potent antitumor effects on Merkel cell carcinoma cell lines and mouse xenografts.

Sci Rep. 2020 Jun 01;10(1):8867

Authors: Fang B, Kannan A, Zhao S, Nguyen QH, Ejadi S, Yamamoto M, Camilo Barreto J, Zhao H, Gao L

Abstract
Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine skin cancer with steadily increasing incidence and poor prognosis. Despite recent success with immunotherapy, 50% of patients still succumb to their diseases. To date, there is no Food and Drug Administration-approved targeted therapy for advanced MCC. Aberrant activation of phosphatidylinositide-3-kinase (PI3K)/AKT/mTOR pathway is frequently detected in MCC, making it an attractive therapeutic target. We previously found PI3K pathway activation in human MCC cell lines and tumors and demonstrated complete clinical response in a Stage IV MCC patient treated with PI3K inhibitor idelalisib. Here, we found that both PI3K-α and -δ isoforms are abundantly expressed in our MCC cell lines and clinical samples; we therefore examined antitumor efficacy across a panel of five PI3K inhibitors with distinctive isoform-specificities, including idelalisib (PI3K-δ), copanlisib (PI3K-α/δ), duvelisib (PI3K-γ/δ), alpelisib (PI3K-α), and AZD8186 (PI3K-β/δ). Of these, copanlisib exerts the most potent antitumor effects, markedly inhibiting cell proliferation, survival, and tumor growth by suppressing PI3K/mTOR/Akt activities in mouse models generated from MCC cell xenografts and patient-derived tumor xenografts. These results provide compelling preclinical evidence for application of copanlisib in advanced MCC with aberrant PI3K activation for which immunotherapy is insufficient, or patients who are unsuitable for immunotherapy.

PMID: 32483262 [PubMed - in process]

Selective reactivation of STING signaling to target Merkel cell carcinoma.

Fetched: June 4th, 2020, 5:01am GMT

Selective reactivation of STING signaling to target Merkel cell carcinoma.

Proc Natl Acad Sci U S A. 2020 Jun 01;:

Authors: Liu W, Kim GB, Krump NA, Zhou Y, Riley JL, You J

Abstract
Merkel cell carcinoma (MCC) is a lethal skin cancer that metastasizes rapidly. Few effective treatments are available for patients with metastatic MCC. Poor intratumoral T cell infiltration and activation are major barriers that prevent MCC eradication by the immune system. However, the mechanisms that drive the immunologically restrictive tumor microenvironment remain poorly understood. In this study, we discovered that the innate immune regulator stimulator of IFN genes (STING) is completely silenced in MCCs. To reactivate STING in MCC, we developed an application of a human STING mutant, STINGS162A/G230I/Q266I, which we found to be readily stimulated by a mouse STING agonist, DMXAA. This STING molecule was efficiently delivered to MCC cells via an AAV vector. Introducing STINGS162A/G230I/Q266I expression and stimulating its activity by DMXAA in MCC cells reactivates their antitumor inflammatory cytokine/chemokine production. In response to MCC cells with restored STING, cocultured T cells expressing MCPyV-specific T cell receptors (TCRs) show increased cytokine production, migration toward tumor cells, and tumor cell killing. Our study therefore suggests that STING deficiency contributes to the immune suppressive nature of MCCs. More importantly, DMXAA stimulation of STINGS162A/G230I/Q266I causes robust cell death in MCCs as well as several other STING-silenced cancers. Because tumor antigens and DNA released by dying cancer cells have the potential to amplify innate immune response and activate antitumor adaptive responses, our finding indicates that targeted delivery and activation of STINGS162A/G230I/Q266I in tumor cells holds great therapeutic promise for the treatment of MCC and many other STING-deficient cancers.

PMID: 32482869 [PubMed - as supplied by publisher]

Psychometric Properties of EQ-5D-5L Scoring Algorithms for the United Kingdom in Metastatic Merkel Cell Carcinoma.

Fetched: June 4th, 2020, 5:01am GMT

Psychometric Properties of EQ-5D-5L Scoring Algorithms for the United Kingdom in Metastatic Merkel Cell Carcinoma.

Value Health. 2019 10;22(10):1170-1177

Authors: Bharmal M, Hunger M, Schlichting M

Abstract
BACKGROUND: Currently, there are 4 EQ-5D-5L scoring algorithms available for the United Kingdom that can be used to derive a utility score.
OBJECTIVES: To perform a psychometric validation of the EQ-5D utility score in patients with metastatic Merkel cell carcinoma (mMCC) and to compare 4 EQ-5D-5L value sets currently available for the United Kingdom.
METHODS: Data collected in the phase 2 trial JAVELIN Merkel 200 were analyzed, in which 88 patients with mMCC were treated with avelumab. Utility scores were calculated using the EQ-5D-5L valuation set by Devlin et al and 3 further algorithms that are based on EQ-5D-3L valuations. Criterion validity was assessed by Pearson correlations between utility and other HRQoL scales. Responsiveness was assessed by correlating change in utility scores with change in HRQoL scales and percentage change in tumor size. Effect sizes for change from baseline in utility were calculated in subgroups of patients with improving and deteriorating health based on clinically relevant changes in various external anchors.
RESULTS: Devlin utilities were up to 0.10 points higher than utilities calculated from EQ-5D-3L valuations. Large correlations (0.45-0.72; P < .01) between utility and the EuroQol Visual Analogue Scale and FACT-G total, physical, and functional scores were found for all 4 algorithms. Large correlations between these measures were also found for change from baseline scores. In patients with health improvements, effect sizes were larger for the 3 EQ-5D-3L-based algorithms, whereas the Devlin utilities had larger effect sizes for health deteriorations, probably because of different levels of baseline utility.
CONCLUSIONS: The English National Institute for Health and Care Excellence currently recommends use of the 3L valuation sets. Our analyses show that all 4 scoring algorithms have good and similar psychometric properties in patients with mMCC.

PMID: 31563260 [PubMed - indexed for MEDLINE]

The Landmark Series: Non-melanoma Skin Cancers.

Fetched: June 4th, 2020, 5:01am GMT

The Landmark Series: Non-melanoma Skin Cancers.

Ann Surg Oncol. 2020 Jan;27(1):22-27

Authors: Lee AY, Berman RS

Abstract
Surgery with or without radiation has always been the mainstay of treatment for patients with non-melanoma skin cancers, including basal cell carcinoma, squamous cell carcinoma, and Merkel cell carcinoma. Until recently, there were no effective systemic therapies for patients with advanced disease. This review will focus on the landmark clinical trials that led to Food and Drug Administration (FDA) approval of Vismodegib for advanced basal cell carcinoma (ERIVANCE BCC) and pembrolizumab for advanced Merkel cell carcinoma (KEYNOTE-017). These trials have not only changed the landscape for patients with metastatic disease but also notably for patients with locally advanced disease that is either unresectable or resectable with high morbidity. Additional mention is made for the clinical trial that led to FDA approval of cemiplimab for advanced cutaneous squamous cell carcinoma (EMPOWER-CSCC-1), which is already changing practice patterns, but for which longer-term data are still needed.

PMID: 31549317 [PubMed - indexed for MEDLINE]

Management of primary skin cancer during a pandemic: Multidisciplinary recommendations.

Fetched: June 3rd, 2020, 5:01am GMT

Management of primary skin cancer during a pandemic: Multidisciplinary recommendations.

Cancer. 2020 Jun 01;:

Authors: Baumann BC, MacArthur KM, Brewer JD, Mendenhall WM, Barker CA, Etzkorn JR, Jellinek NJ, Scott JF, Gay HA, Baumann JC, Manian FA, Devlin PM, Michalski JM, Lee NY, Thorstad WL, Wilson LD, Perez CA, Miller CJ

Abstract
During the coronavirus disease 2019 (COVID-19) pandemic, providers and patients must engage in shared decision making regarding the pros and cons of early versus delayed interventions for localized skin cancer. Patients at highest risk of COVID-19 complications are older; are immunosuppressed; and have diabetes, cancer, or cardiopulmonary disease, with multiple comorbidities associated with worse outcomes. Physicians must weigh the patient's risk of COVID-19 complications in the event of exposure against the risk of worse oncologic outcomes from delaying cancer therapy. Herein, the authors have summarized current data regarding the risk of COVID-19 complications and mortality based on age and comorbidities and have reviewed the literature assessing how treatment delays affect oncologic outcomes. They also have provided multidisciplinary recommendations regarding the timing of local therapy for early-stage skin cancers during this pandemic with input from experts at 11 different institutions. For patients with Merkel cell carcinoma, the authors recommend prioritizing treatment, but a short delay can be considered for patients with favorable T1 disease who are at higher risk of COVID-19 complications. For patients with melanoma, the authors recommend delaying the treatment of patients with T0 to T1 disease for 3 months if there is no macroscopic residual disease at the time of biopsy. Treatment of tumors ≥T2 can be delayed for 3 months if the biopsy margins are negative. For patients with cutaneous squamous cell carcinoma, those with Brigham and Women's Hospital T1 to T2a disease can have their treatment delayed for 2 to 3 months unless there is rapid growth, symptomatic lesions, or the patient is immunocompromised. The treatment of tumors ≥T2b should be prioritized, but a 1-month to 2-month delay is unlikely to worsen disease-specific mortality. For patients with squamous cell carcinoma in situ and basal cell carcinoma, treatment can be deferred for 3 months unless the individual is highly symptomatic.

PMID: 32478867 [PubMed - as supplied by publisher]

The curious case of Merkel cell carcinoma: epigenetic youth and lack of pluripotency.

Fetched: June 3rd, 2020, 5:01am GMT

The curious case of Merkel cell carcinoma: epigenetic youth and lack of pluripotency.

Epigenetics. 2020 May 30;:1-6

Authors: Chteinberg E, Vogt J, Kolarova J, Bormann F, van den Oord J, Speel EJ, Winnepenninckx V, Kurz AK, Zenke M, Siebert R, Hausen AZ

Abstract
Merkel cell carcinoma (MCC) is a very rare, but highly aggressive skin cancer which occurs mainly in elderly patients. MCC cells show an expression pattern of three cell lineages: epithelial, neuroendocrine, and B-cell progenitor. This trilinear expression pattern suggests stemness activity in MCC. The etiopathogenesis of MCC is either linked to the Merkel cell polyomavirus (MCPyV) or in a smaller proportion (20%) to high levels of UV-induced somatic mutations. Both viral presence and accumulation of mutations have been shown to be associated with accelerated DNA methylation Age (DNAmAge) compared to chronological age. The MCC DNAmAge was significantly lower compared to the chronological age, which was irrespective of the viral presence or mutational burden. Although these features indicate some aspects of stemness in MCC cells, gene-expression-based pluripotency testing did not provide evidence for pluripotency of MCC cells.

PMID: 32475296 [PubMed - as supplied by publisher]

Permalink for 'ASO Author Reflections: Neuron-Specific Enolase as a Valuable Biomarker for Patients with Merkel Cell Carcinoma in the Era of Immunotherapy.'

ASO Author Reflections: Neuron-Specific Enolase as a Valuable Biomarker for Patients with Merkel Cell Carcinoma in the Era of Immunotherapy.

Fetched: June 2nd, 2020, 5:01am GMT

ASO Author Reflections: Neuron-Specific Enolase as a Valuable Biomarker for Patients with Merkel Cell Carcinoma in the Era of Immunotherapy.

Ann Surg Oncol. 2020 May 30;:

Authors: van Veenendaal LM, van Akkooi ACJ

PMID: 32474817 [PubMed - as supplied by publisher]

Permalink for 'Patient Experiences with Avelumab in Treatment-Naïve Metastatic Merkel Cell Carcinoma: Longitudinal Qualitative Interview Findings from JAVELIN Merkel 200, a Registrational Clinical Trial.'

Patient Experiences with Avelumab in Treatment-Naïve Metastatic Merkel Cell Carcinoma: Longitudinal Qualitative Interview Findings from JAVELIN Merkel 200, a Registrational Clinical Trial.

Fetched: June 1st, 2020, 5:00am GMT

Patient Experiences with Avelumab in Treatment-Naïve Metastatic Merkel Cell Carcinoma: Longitudinal Qualitative Interview Findings from JAVELIN Merkel 200, a Registrational Clinical Trial.

Patient. 2020 May 30;:

Authors: Lambert J, Marrel A, D'Angelo SP, Burgess MA, Chmielowski B, Fazio N, Gambichler T, Grob JJ, Lebbé C, Robert C, Russell J, Güzel G, Bharmal M

Abstract
BACKGROUND AND OBJECTIVE: Avelumab is approved for the treatment of metastatic Merkel cell carcinoma, a rare aggressive skin cancer with a poor prognosis. The aim of this qualitative study embedded in a clinical trial was to explore patient experiences while receiving avelumab.
METHODS: All treatment-naïve patients with metastatic Merkel cell carcinoma entering part B of the phase II, open-label, international, JAVELIN Merkel 200 trial (NCT02155647) were invited to participate in optional semi-structured phone interviews before avelumab administration (baseline) and at weeks 13 and 25. Interviews were conducted by trained professionals, audio-recorded, transcribed and analysed. Key concepts identified at baseline were assessed during follow-up interviews.
RESULTS: Twenty-nine patients completed the baseline interview; 19 had at least one follow-up interview. Baseline interviews described the patients' challenging journeys before being correctly diagnosed with Merkel cell carcinoma, the negative psychological burden of living with a symptomless disease and the hope for avelumab to be a successful therapy. During the trial, most patients reported an increased or continued sense of hope and willingness to fight metastatic Merkel cell carcinoma. Patients who self-reported disease improvement (n = 12) also reported stability or improvement in physical well-being and ability to do daily activities, having more energy, worrying less and being optimistic. Six patients who reported their condition as stable (n = 4) or worsened (n = 3) reported a worsening of physical well-being. Nine patients reported fatigue/tiredness on the day of and after receiving avelumab. Baseline and longitudinal experiences were similar across countries.
CONCLUSIONS: This study suggests that patients experience perceptible benefits in physical and psychological well-being following treatment success with first-line avelumab in metastatic Merkel cell carcinoma.

PMID: 32472503 [PubMed - as supplied by publisher]

Neoadjuvant Immunotherapy: Making Strides.

Fetched: May 31st, 2020, 5:01am GMT

Neoadjuvant Immunotherapy: Making Strides.

Cancer Discov. 2020 May 28;:

Authors:

Abstract
Neoadjuvant immune checkpoint inhibition is gaining ground as a treatment strategy for early-stage, operable cancers. The list of potentially responsive tumor types now includes Merkel cell carcinoma; recent findings from an arm of the I-SPY2 trial also support the utility of this approach in HER2-negative breast cancer.

PMID: 32467341 [PubMed - as supplied by publisher]

Risk of rare cancers among solid organ transplant recipients.

Fetched: May 30th, 2020, 5:01am GMT

Risk of rare cancers among solid organ transplant recipients.

J Natl Cancer Inst. 2020 May 27;:

Authors: D'Arcy ME, Castenson D, Lynch CF, Kahn AR, Morton LM, Shiels MS, Pfeiffer RM, Engels EA

Abstract
BACKGROUND: Immunosuppressed solid organ transplant recipients [SOTRs] have elevated rates of certain rare cancers caused by viruses. Evaluating risk of rare cancers among SOTRs may provide etiological clues for additional cancers linked to poor immunity and viral infections.
METHODS: We performed a cohort study of 262,455 SOTRs (1987-2014) from the US SOTR registry linked to 17 population-based cancer registries. First cancers in SOTRs were categorized using an established classification scheme based on site and histology. Standardized incidence ratios (SIRs) compared risk in SOTRs to the general population. We used Poisson regression to calculate incidence rate ratios (IRRs) according to immune-related SOTR characteristics, including time since transplant (i.e., duration of immunosuppression). All statistical tests are two-sided.
RESULTS: We examined 694 distinct cancer subtypes, with 33 manifesting statistically significantly elevated SIRs (Bonferroni p < 7.2 x 10-5). All 33 are rare (incidence <6 per 100,000 person-years) and several have known viral etiology (e.g. Merkel cell carcinoma (SIR = 24.7, 95%CI = 20.8 to 29.1). Additional cancers that were increased include squamous cell carcinomas (SCCs) of the lip (SIR range = 18.3-19.8), eye/adnexa (SIR = 13.8, 95%CI = 7.9 to 22.3), salivary gland (SIR = 9.3, 95%CI = 6.1 to 13.5), and nasal cavity/sinuses (SIR = 4.5, 95%CI = 2.8 to 6.8); sebaceous adenocarcinoma (SIR = 34.3, 95%CI = 26.3 to 44.0); malignant fibrous histiocytoma (15.4); and subtypes of bladder, kidney, lung, and colon cancer (SIR range = 3.2-13.3). Incidence of several cancers increased over time since transplant (ptrend<0.05), including SCCs of the lip, salivary gland, and anogenital sites.
CONCLUSIONS: SOTRs experience elevated rates of several rare cancers. Because some of these cancers exhibit aggressive behavior with poor outcomes, it is important to further characterize the role of immunity and the potential involvement of oncogenic viruses to improve prevention and treatment.

PMID: 32462187 [PubMed - as supplied by publisher]

CME Part I: Immune checkpoint inhibitors to treat cutaneous malignancies.

Fetched: May 30th, 2020, 5:01am GMT

CME Part I: Immune checkpoint inhibitors to treat cutaneous malignancies.

J Am Acad Dermatol. 2020 May 24;:

Authors: Barrios DM, Do MH, Phillips GS, Postow MA, Akaike T, Nghiem P, Lacouture ME

Abstract
As the incidence of cutaneous malignancies continue to rise and their treatment with immunotherapy expands, dermatologists and their patients are more likely to encounter these agents. While blockade of immune checkpoint target proteins (CTLA-4, PD-1, PD-L1) generates an anti-tumor response in a substantial fraction of patients, there is a critical need for reliable predictive biomarkers, as well as approaches to address refractory disease. This article reviews the indications, efficacy, safety profile and evidence supporting checkpoint inhibition as therapeutics for metastatic melanoma, cutaneous squamous cell carcinoma, and Merkel cell carcinoma. Pivotal studies resulting in the approval of ipilimumab, pembrolizumab, nivolumab, cemiplimab and avelumab by regulatory agencies for various cutaneous malignancies, as well as ongoing clinical research trials, are discussed.

PMID: 32461079 [PubMed - as supplied by publisher]

Monitoring response of advanced Merkel cell carcinoma to Avelumab with 18F-FDG PET/CT.

Fetched: May 27th, 2020, 5:01am GMT

Monitoring response of advanced Merkel cell carcinoma to Avelumab with 18F-FDG PET/CT.

Eur J Nucl Med Mol Imaging. 2019 May;46(5):1197-1198

Authors: Vellani C, D'Ambrosio D, Licata L, Vacchieri I, Bernardo A, Trifirò G

PMID: 30535745 [PubMed - indexed for MEDLINE]

Advanced Merkel Cell Carcinoma - A Focus on Medical Drug Therapy.

Fetched: May 26th, 2020, 5:01am GMT

Advanced Merkel Cell Carcinoma - A Focus on Medical Drug Therapy.

Dermatol Ther. 2020 May 23;:e13675

Authors: Wollina U, Koch A, Cardoso JC

Abstract
Merkel cell carcinoma (MCC) is a rare but aggressive non-melanoma skin cancer with significant morbidity and mortality. Treatment of choice for primary and locoregional MCC is complete surgical removal with sentinel lymphonodectomy and post-surgical radiotherapy of tumor basin and locoregional lymph nodes. In non-resectable and advanced tumors, drug therapy is indicated. While cytotoxic chemotherapy has resulted in higher response rates, overall survival remained nearly unaffected. With a better insight into tumor development and biology, new treatment s became available. Immune checkpoint inhibitors result in durable responses with a better safety profile that classical combined chemotherapy. Combinations of immune checkpoint inhibitors with and without radiotherapy help to overcome acquired drug-resistance. New compounds for vaccination and oral use are on the horizon. Despite all progress, treatment of MCC remains a challenge that needs close interdisciplinary teamwork. This article is protected by copyright. All rights reserved.

PMID: 32447821 [PubMed - as supplied by publisher]

The Role of Anti-PD-1/PD-L1 in the Treatment of Skin Cancer.

Fetched: May 26th, 2020, 5:01am GMT

The Role of Anti-PD-1/PD-L1 in the Treatment of Skin Cancer.

BioDrugs. 2020 May 23;:

Authors: Patrinely JR, Dewan AK, Johnson DB

Abstract
Skin cancers remain the most common group of cancers globally, and the incidence continues to rise. Although localized skin cancers tend to have excellent outcomes following surgical excisions, the less common cases that become surgically unresectable or metastatic have been associated with poor prognosis and suboptimal treatment responses to cytotoxic chemotherapy. Development of monoclonal antibodies to programmed cell death-1 receptor and its ligand (PD-1/PD-L1) have transformed the management of metastatic melanoma, squamous cell carcinoma, and Merkel cell carcinoma. These agents, as monotherapies, are associated with response rates of approximately 40-60%, many of which persist durably. Further efficacy is observed with combination immunotherapy in advanced melanoma. Early reports suggest similar activity in locally advanced or metastatic basal cell carcinoma. In this review, we describe common molecular features of skin cancers that may render them particularly susceptible to anti-PD-1/PD-L1 and detail results from key clinical trials of these agents across skin cancers. Overall, the superior response rates of skin cancer to anti-PD-1/PD-L1 compared with other solid tumor types are likely due, at least in part, to a high mutational burden and, in Merkel cell carcinoma, viral etiology. Although melanoma has been rigorously studied in the setting of anti-PD-1/PD-L1 treatment, more research is needed for the other skin cancer types to establish toxicity profiles, responses, and quality-of-life outcomes.

PMID: 32447657 [PubMed - as supplied by publisher]

Permalink for 'Correction: Efficacy and safety of avelumab treatment in patients with metastatic Merkel cell carcinoma: experience from a global expanded access program.'

Correction: Efficacy and safety of avelumab treatment in patients with metastatic Merkel cell carcinoma: experience from a global expanded access program.

Fetched: May 23rd, 2020, 5:01am GMT

Correction: Efficacy and safety of avelumab treatment in patients with metastatic Merkel cell carcinoma: experience from a global expanded access program.

J Immunother Cancer. 2020 May;8(1):

Authors:

PMID: 32434786 [PubMed - in process]

Permalink for 'Update on the psychometric properties and minimal important difference (MID) thresholds of the FACT-M questionnaire for use in treatment-naïve and previously treated patients with metastatic Merkel cell carcinoma.'

Update on the psychometric properties and minimal important difference (MID) thresholds of the FACT-M questionnaire for use in treatment-naïve and previously treated patients with metastatic Merkel cell carcinoma.

Fetched: May 22nd, 2020, 5:01am GMT

Update on the psychometric properties and minimal important difference (MID) thresholds of the FACT-M questionnaire for use in treatment-naïve and previously treated patients with metastatic Merkel cell carcinoma.

Health Qual Life Outcomes. 2020 May 19;18(1):145

Authors: Bharmal M, Nolte S, Henry-Szatkowski M, Hennessy M, Schlichting M

Abstract
OBJECTIVES: For valid and reliable assessment of patients' Health-Related Quality of Life (HRQoL), it is crucial to use psychometrically robust instruments. In the context of rare diseases such as Merkel cell carcinoma (MCC), validated disease-specific instruments are often not available. The Functional Assessment of Cancer Therapy - Melanoma (FACT-M) was originally developed for use in melanoma. Its psychometric performance for use in MCC and minimal important difference (MID) thresholds have been previously reported based on a cohort of metastatic MCC patients who had disease progression following one or more prior line of chemotherapy (NCT02155647 Part A; n = 70). Since then, new data from the phase II JAVELIN Merkel 200 trial among treatment-naïve patients are available (NCT02155647 Part B; n = 102). This study aims to increase accuracy and precision of previously established psychometric properties and MID thresholds of FACT-M in metastatic MCC patients.
METHODS: Published qualitative research suggests that patients with metastatic MCC had similar experiences and described similar concepts associated with their disease independent of whether they were treatment naïve or had prior treatment. Therefore, it was deemed appropriate to pool FACT-M data from Part A (previously treated) and Part B (treatment-naïve) cohorts for this study. Construct validity was assessed by evaluating item-factor correlations (convergent validity) and known-groups validity using ECOG performance status 0 versus 1. Concurrent validity was assessed using EQ-5D items. Internal consistency reliability was assessed using Cronbach's α. Anchor- and distribution-based approaches were used to derive MID thresholds.
RESULTS: Overall, psychometric tests based on various validity (convergent, known-groups, concurrent) and reliability (Cronbach α) analyses confirmed previous findings in that FACT-M performs well in MCC patients. MID thresholds derived from this study are largely in line with previously established thresholds with some minor adjustments.
CONCLUSIONS: In the context of rare diseases, which often have limited data available for psychometric testing, a reasonably large MCC patient sample was available for this study, enhancing accuracy and precision of previously established FACT-M psychometric properties and MID thresholds with only small deviations for use in metastatic MCC patients. Results suggest that the FACT-M is suitable for Merkel cell carcinoma regardless of patients' treatment status.
TRIAL REGISTRATION: This study is a pre-planned post-hoc analysis conducted on data collected in Part A and Part B of the JAVELIN Merkel 200 trial. This trial was registered on 2 June 2014 with ClinicalTrials.gov as NCT02155647.

PMID: 32430019 [PubMed - in process]

Merkel Cell Carcinoma - Current Controversies and Future Directions.

Fetched: May 22nd, 2020, 5:01am GMT

Merkel Cell Carcinoma - Current Controversies and Future Directions.

Clin Oncol (R Coll Radiol). 2019 11;31(11):789-796

Authors: Steven N, Lawton P, Poulsen M

Abstract
Merkel cell carcinoma is a rare, aggressive neuroendocrine skin malignancy. Evidence for management comes from case series and single-arm trials. Optimal outcomes require assessment of the patient in a multidisciplinary team setting. Rapid diagnosis and staging are essential for locoregional control and may reduce metastasis. Sentinel lymph node biopsy (SLNB) adds prognostic information. FDG-positron emission tomography has high sensitivity and specificity and affects management in a quarter of cases. Surgical excision and radiotherapy provide good locoregional control even with positive margins. Wide surgical margins are needed if adjuvant radiotherapy is not used. It is uncertain whether adjuvant radiotherapy or elective surgery for uninvolved nodes or for patients selected by positive SLNB improves survival. Total doses of 50 Gy provide high levels of control for microscopic disease but at least 60 Gy should be given for macroscopic disease. Chemotherapy can be given safely with radiotherapy, but the benefit of adjuvant chemotherapy remains uncertain. Trials of adjuvant immune therapy are underway. Unresectable primaries might be controlled with radiotherapy alone or combination systemic therapy, radiotherapy and surgery. Metastatic disease often responds to chemotherapy, but the response duration can be short. Immunity is central to disease control. Immune checkpoint inhibitor treatment resulted in high response rates in chemotherapy-naive patients and lower rates in chemotherapy-refractory patients. Durable responses are observed.

PMID: 31594644 [PubMed - indexed for MEDLINE]

FT516 in Combination With Monoclonal Antibodies in Advanced Solid Tumors

Posted: September 16th, 2020, 2:00pm GMT

Condition: Solid Tumor, Adult
Interventions: Drug: FT516; Drug: Avelumab; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: IL-2
Sponsor: Fate Therapeutics
Recruiting

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

Posted: May 19th, 2020, 2:00pm GMT

Condition: Merkel Cell Carcinoma
Intervention: Drug: domatinostat in combination with avelumab
Sponsor: 4SC AG
Recruiting

Immunotherapy Merkel Adjuvant Trial

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
Not yet recruiting

Permalink for 'Phase-II Study of Lu177DOTATOC in Adults With STTR(+)Pulmonary, Pheochromocytoma, Paraganglioma, Unknown Primary, Thymus NETs (PUTNET), or Any Other Non-.GEP-NET.'

Phase-II Study of Lu177DOTATOC in Adults With STTR(+)Pulmonary, Pheochromocytoma, Paraganglioma, Unknown Primary, Thymus NETs (PUTNET), or Any Other Non-.GEP-NET.

Posted: February 19th, 2020, 3:00pm GMT

Conditions: Pulmonary Neuroendocrine Neoplasm; Pheochromocytoma; Paraganglioma; Thymus Carcinoid; Unknown Primary Tumors; Neuroendocrine Tumors; Neuroendocrine Skin Carcinoma; Neuroendocrine Breast Tumor; Neuroendocrine Carcinoma Metastatic; Neuroendocrine Neoplasm of Ovary
Intervention: Drug: 177Lu-DOTATOC
Sponsor: Excel Diagnostics and Nuclear Oncology Center
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
Not yet 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
Not yet 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

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

Posted: January 27th, 2020, 3:00pm GMT

Conditions: Advanced Solid Tumor; MSI-H/dMMR Tumors; Cutaneous Squamous Cell Carcinoma; Urothelial Carcinoma; Cervical Cancer; HepatoCellular Carcinoma; Esophageal Squamous Cell Carcinoma; Merkel Cell Carcinoma; Small-cell Lung Cancer; Mesothelioma; PD-L1 Amplified Tumor (9p24.1); Nasopharyngeal Carcinoma
Intervention: Drug: INCB099280
Sponsor: Incyte Corporation
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 MCC or cSCC

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

Conditions: Merkel Cell Carcinoma; Cutaneous Squamous Cell Carcinoma
Intervention: Biological: IFx-Hu2.0
Sponsors: Morphogenesis, Inc.; H. Lee Moffitt Cancer Center and Research Institute; University of Southern California
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

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

Posted: February 25th, 2019, 3:00pm GMT

Condition: Merkel Cell Carcinoma
Interventions: Biological: Avelumab; Biological: N-803; Biological: haNK™
Sponsors: NantKwest, Inc.; NantCell, Inc.
Recruiting

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

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

Condition: Merkel Cell Carcinoma
Intervention: Drug: Pembrolizumab (MK-3475)
Sponsor: Merck Sharp & Dohme Corp.
Recruiting

Intratumoral AST-008 Combined With Pembrolizumab in Patients With Advanced Solid Tumors

Posted: September 26th, 2018, 2:00pm GMT

Conditions: Advanced or Metastatic Solid Tumors; Advanced or Metastatic Melanoma; Advanced or Metastatic Head and Neck Squamous Cell Carcinoma; Advanced or Metastatic Cutaneous Squamous Cell Carcinoma; Advanced or Metastatic Merkel Cell Carcinoma
Interventions: Drug: AST-008; Biological: Pembrolizumab; Biological: Cemiplimab
Sponsor: Exicure, Inc.
Recruiting

Lymph Node Identification in Skin Malignancy Using ICG Transcutaneously Study

Posted: June 4th, 2018, 2:00pm GMT

Conditions: Malignant Melanoma; Merkel Cell Carcinoma
Intervention: Diagnostic Test: Visionsense™ VS3 - Stereoscopic High Definition Visualisation System (VS3-3DHD)
Sponsor: University Hospital Inselspital, Berne
Recruiting

Safety and Efficacy of Ad-p53 Combined With Checkpoint Inhibitor in Head and Neck Cancer

Posted: June 4th, 2018, 2:00pm GMT

Conditions: Solid Tumor; Lymphoma
Intervention: Drug: Ad-p53
Sponsor: MultiVir, Inc.
Recruiting

Permalink for 'A Study of NKTR-262 in Combination With Bempegaldesleukin (NKTR-214) and With Bempegaldesleukin Plus Nivolumab in Patients With Locally Advanced or Metastatic Solid Tumor Malignancies'

A Study of NKTR-262 in Combination With Bempegaldesleukin (NKTR-214) and With Bempegaldesleukin Plus Nivolumab in Patients With Locally Advanced or Metastatic Solid Tumor Malignancies

Posted: February 19th, 2018, 3:00pm GMT

Conditions: Melanoma; Merkel Cell Carcinoma; Triple Negative Breast Cancer; Head and Neck Squamous Cell Carcinoma; Renal Cell Carcinoma; Colorectal Cancer; Sarcoma
Interventions: Drug: NKTR-262; Drug: bempegaldesleukin; Drug: nivolumab
Sponsor: Nektar Therapeutics
Recruiting

QUILT-3.055: A Study of ALT-803 in Combination With PD-1/PD-L1 Checkpoint Inhibitor in Patients With Advanced Cancer

Posted: July 25th, 2017, 2:00pm GMT

Conditions: Non-Small Cell Lung Cancer; Small Cell Lung Cancer; Urothelial Carcinoma; Head and Neck Squamous Cell Carcinoma; Merkel Cell Carcinoma; Melanoma; Renal Cell Carcinoma; Gastric Cancer; Cervical Cancer; Hepatocellular Carcinoma; Microsatellite Instability; Mismatch Repair Deficiency; Colorectal Cancer
Interventions: Drug: N-803 + Pembrolizumab; Drug: N-803 + Nivolumab; Drug: N-803 + Atezolizumab; Drug: N-803 + Avelumab; Drug: N-803 + Durvalumab; Drug: N-803 + Pembrolizumab + PD-L1 t-haNK; Drug: N-803 + Nivolumab + PD-L1 t-haNK; Drug: N-803 + Atezolizumab + PD-L1 t-haNK; Drug: N-803 + Avelumab + PD-L1 t-haNK; Drug: N-803 + Durvalumab + PD-L1 t-haNK
Sponsor: Altor BioScience
Recruiting

Phase 1 Study of CK-301 (Cosibelimab) as a Single Agent in Subjects With Advanced Cancers

Posted: July 11th, 2017, 2:00pm GMT

Conditions: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Malignant Mesothelioma, Advanced; Head and Neck Cancer; Melanoma; Merkel Cell Carcinoma; Renal Cell Carcinoma; Urothelial Carcinoma; Classical Hodgkin Lymphoma; Cutaneous Squamous Cell Carcinoma; Non Hodgkin Lymphoma; Endometrial Cancer
Intervention: Drug: CK-301 (cosibelimab)
Sponsors: Checkpoint Therapeutics, Inc.; Novotech (Australia) Pty Limited
Recruiting

Permalink for 'Phase 1/2 Study Exploring the Safety, Tolerability, and Efficacy of INCAGN01876 Combined With Immune Therapies in Advanced or Metastatic Malignancies'

Phase 1/2 Study Exploring the Safety, Tolerability, and Efficacy of INCAGN01876 Combined With Immune Therapies in Advanced or Metastatic Malignancies

Posted: April 24th, 2017, 2:00pm GMT

Conditions: Advanced Malignancies; Metastatic Cancer
Interventions: Drug: INCAGN01876; Drug: Nivolumab; Drug: Ipilimumab
Sponsor: Incyte Biosciences International Sàrl
Recruiting

Atezolizumab and Bevacizumab in Treating Patients With Rare Solid Tumors

Posted: March 8th, 2017, 3:00pm GMT

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

Permalink for 'A Study of the Safety, Tolerability and Pharmacokinetics of ABBV-368 as a Single Agent and Combination in Subjects With Locally Advanced or Metastatic Solid Tumors'

A Study of the Safety, Tolerability and Pharmacokinetics of ABBV-368 as a Single Agent and Combination in Subjects With Locally Advanced or Metastatic Solid Tumors

Posted: March 7th, 2017, 3:00pm GMT

Condition: Advanced Solid Tumors Cancer
Interventions: Drug: ABBV-368; Drug: ABBV-181
Sponsor: AbbVie
Recruiting

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

Posted: March 6th, 2017, 3:00pm GMT

Conditions: Merkel Cell Carcinoma; Skin Cancer
Interventions: Drug: Nivolumab; Drug: Ipilimumab; Radiation: Stereotactic Body Radiation Therapy (SBRT)
Sponsors: H. Lee Moffitt Cancer Center and Research Institute; Bristol-Myers Squibb
Recruiting

A Study of Budigalimab (ABBV-181) in Participants With Advanced Solid Tumors

Posted: December 22nd, 2016, 3:00pm GMT

Condition: Advanced Solid Tumors
Interventions: Drug: Venetoclax; Drug: Rovalpituzumab Tesirine; Drug: ABBV-181
Sponsor: AbbVie
Recruiting

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

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

Posted: December 1st, 2016, 3:00pm GMT

Conditions: Adenoid Cystic Carcinoma; Adnexal Carcinoma; Apocrine Carcinoma; Extraocular Cutaneous Sebaceous Carcinoma; Hidradenocarcinoma; Keratoacanthoma; Malignant Sweat Gland Neoplasm; Merkel Cell Carcinoma; Microcystic Adnexal Carcinoma; NK-Cell Lymphoma, Unclassifiable; Paget Disease; Papillary Adenocarcinoma; Porocarcinoma; Primary Cutaneous Mucinous Carcinoma; Recurrent Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Recurrent T-Cell Non-Hodgkin Lymphoma; Refractory Anaplastic Large Cell Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Refractory Merkel Cell Carcinoma; Refractory Mycosis Fungoides; Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Skin Squamous Cell Carcinoma; Refractory T-Cell Non-Hodgkin Lymphoma; Sezary Syndrome; Signet Ring Cell Carcinoma; Skin Basal Cell Carcinoma; Skin Basosquamous Cell Carcinoma; Skin Squamous Cell Carcinoma; Spiradenocarcinoma; Squamous Cell Carcinoma of Unknown Primary; Stage III Skin Cancer; Stage IV Skin Cancer; Sweat Gland Carcinoma; Trichilemmal Carcinoma; Vulvar Squamous Cell Carcinoma
Interventions: Other: Laboratory Biomarker Analysis; Biological: Nivolumab; Biological: Talimogene Laherparepvec
Sponsor: National Cancer Institute (NCI)
Recruiting

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

Posted: June 30th, 2016, 2:00pm GMT

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

Permalink for 'A Phase 1/2 Study of In Situ Vaccination With Tremelimumab and IV Durvalumab Plus PolyICLC in Subjects With Advanced, Measurable, Biopsy-accessible Cancers'

A Phase 1/2 Study of In Situ Vaccination With Tremelimumab and IV Durvalumab Plus PolyICLC in Subjects With Advanced, Measurable, Biopsy-accessible Cancers

Posted: December 31st, 2015, 3:00pm GMT

Conditions: Head and Neck Squamous Cell Carcinoma; Breast Cancer; Sarcoma; Merkel Cell Carcinoma; Cutaneous T-Cell Lymphoma; Melanoma; Renal Cancer; Bladder Cancer; Prostate Cancer; Testicular Cancer; Solid Tumor
Interventions: Drug: Durvalumab; Drug: Tremelimumab; Drug: Poly ICLC
Sponsors: Ludwig Institute for Cancer Research; MedImmune LLC; Cancer Research Institute, New York City
Recruiting

Permalink for 'An Investigational Immuno-therapy Study to Investigate the Safety and Effectiveness of Nivolumab, and Nivolumab Combination Therapy in Virus-associated Tumors'

An Investigational Immuno-therapy Study to Investigate the Safety and Effectiveness of Nivolumab, and Nivolumab Combination Therapy in Virus-associated Tumors

Posted: July 2nd, 2015, 2:00pm GMT

Condition: Various Advanced Cancer
Interventions: Drug: Nivolumab; Drug: Ipilimumab; Drug: Relatlimab; Drug: Daratumumab
Sponsors: Bristol-Myers Squibb; Ono Pharmaceutical Co. Ltd
Recruiting

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

Posted: June 24th, 2015, 2:00pm GMT

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

Studies of Dermatologic Diseases Biospecimen Acquisition Protocol

Posted: June 15th, 2015, 2:00pm GMT

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

Cognitive Function in Patients Treated for Metastatic Melanoma With Immune Checkpoint Inhibitors

Posted: September 25th, 2020, 2:00pm GMT

Conditions: Metastatic Melanoma; Cognitive Impairment; Fatigue; Sleep; Depression, Anxiety; Quality of Life; Inflammation; Sickness Behavior; Cancer-related Cognitive Impairment
Intervention:
Sponsors: Aarhus University Hospital; University of Aarhus
Not yet recruiting

Ph 2 Study of IL2 With Ipilimumab Followed by Nivolumab in Stage 3 or 4 Melanoma Patients

Posted: September 24th, 2020, 2:00pm GMT

Conditions: Melanoma Stage III; Melanoma Stage IV; Inoperable Disease
Interventions: Drug: Interleukin-2; Drug: Ipilimumab; Drug: Nivolumab
Sponsors: H. Lee Moffitt Cancer Center and Research Institute; Clinigen
Recruiting

Permalink for 'Testing the Addition of the Anti-cancer Drug, Tazemetostat, to the Usual Treatment (Dabrafenib and Trametinib) for Metastatic Melanoma That Has Progressed on the Usual Treatment'

Testing the Addition of the Anti-cancer Drug, Tazemetostat, to the Usual Treatment (Dabrafenib and Trametinib) for Metastatic Melanoma That Has Progressed on the Usual Treatment

Posted: September 22nd, 2020, 2:00pm GMT

Conditions: Clinical Stage IV Cutaneous Melanoma AJCC v8; Metastatic Malignant Neoplasm in the Central Nervous System; Metastatic Melanoma; Pathologic Stage IV Cutaneous Melanoma AJCC v8
Interventions: Drug: Dabrafenib Mesylate; Drug: Tazemetostat Hydrobromide; Drug: Trametinib Dimethyl Sulfoxide
Sponsor: National Cancer Institute (NCI)
Not yet recruiting

Fatigue and Quality of Life in Patients With Neuroendocrine Neoplasia

Posted: September 21st, 2020, 2:00pm GMT

Condition: Neuroendocrine Tumors (NET) Health Related Qualito of Life (HRQoL)
Intervention: Drug: Somatostatin analog
Sponsor: University of Aarhus
Recruiting

Al18F-NOTA-octreotide PET Imaging in Neuroendocrine Tumors

Posted: September 17th, 2020, 2:00pm GMT

Condition: Neuroendocrine Tumors
Interventions: Drug: Al18F-NOTA-octreotide; Device: PET/CT; Device: PET/MR
Sponsors: Universitaire Ziekenhuizen Leuven; University Hospital, Antwerp; University Hospital, Ghent; NETwerk, Belgium
Recruiting

Lutathera in People With Pancreatic Neuroendocrine Tumors That Have Spread to the Liver

Posted: September 10th, 2020, 2:00pm GMT

Conditions: Pancreatic Neuroendocrine Tumors; Liver-Dominant Metastatic Pancreatic Neuroendocrine Tumors
Intervention: Drug: 177Lu-DOTATATE
Sponsor: Memorial Sloan Kettering Cancer Center
Recruiting

Telotristat With Lutathera in Neuroendocrine Tumors

Posted: September 10th, 2020, 2:00pm GMT

Condition: Neuroendocrine Tumors
Interventions: Drug: Telotristat (Low-Dose); Drug: Telotristat (High-Dose)
Sponsors: Aman Chauhan; Lexicon Pharmaceuticals
Not yet recruiting

A FIH Study of PF-07284890 in Participants With BRAF V600 Mutant Solid Tumors With and Without Brain Involvement

Posted: September 10th, 2020, 2:00pm GMT

Conditions: Malignant Melanoma; Carcinoma, Non-Small-Cell Lung; Brain Neoplasms, Primary; Brain Neoplasms; Malignant Neoplasms
Interventions: Drug: PF-07284890; Drug: Binimetinib; Drug: Midazolam
Sponsor: Pfizer
Not yet recruiting

A Phase 1 Study of GNR-051 in Subjects With Advanced Malignancies

Posted: September 10th, 2020, 2:00pm GMT

Condition: Non-Small Cell Lung Cancer (NSCLC), Renal Cell Carcinoma (RCC), Malignant Melanoma (MEL)
Intervention: Biological: GNR-051
Sponsor: AO GENERIUM
Recruiting

Permalink for 'Title: Phase II Trial of Olaparib (LYNPARZA) Plus Durvalumab (IMFINZI) in EGFR-Mutated Adenocarcinomas That Transform to Small Cell Lung Cancer (SCLC) and Other Neuroendocrine Tumors.'

Title: Phase II Trial of Olaparib (LYNPARZA) Plus Durvalumab (IMFINZI) in EGFR-Mutated Adenocarcinomas That Transform to Small Cell Lung Cancer (SCLC) and Other Neuroendocrine Tumors.

Posted: September 4th, 2020, 2:00pm GMT

Conditions: EGFR-Mutated Non-Small-Cell Lung Carcinoma; Small Cell/Neuroendocrine
Interventions: Drug: Olaparib; Drug: Durvalumab
Sponsor: National Cancer Institute (NCI)
Not yet recruiting

Neoadjuvant Immunotherapy With Tavo + Electroporation in Combination With Nivo. in Melanoma Patients

Posted: August 26th, 2020, 2:00pm GMT

Condition: Melanoma
Interventions: Drug: Tavo; Drug: Nivolumab; Device: OncoSec Medical Electroporation Therapy System
Sponsors: H. Lee Moffitt Cancer Center and Research Institute; OncoSec Medical Incorporated
Recruiting

A Clinical Study to Assess the Combination of Two Drugs (177Lu-DOTATATE and Nivolumab) in Neuroendocrine Tumours

Posted: August 25th, 2020, 2:00pm GMT

Conditions: Neuroendocrine Tumours (NET); Neuroendocrine Carcinomas (NEC)
Interventions: Drug: 177Lu-Dotatate; Drug: Nivolumab
Sponsors: Fundación de investigación HM; Syntax for Science, S.L
Recruiting

A Trial of Cabozantinib in Patients With Advanced, Low Proliferative NEN G3

Posted: August 24th, 2020, 2:00pm GMT

Conditions: Neuroendocrine Tumors; Neuroendocrine Carcinoma
Intervention: Drug: Cabozantinib
Sponsor: Karsten Gavenis
Not yet recruiting

Post-Authorization Safety Study (PASS) of LysaKare® in Adult Gastroenteropancreatic Neuroendocrine Tumor (GEP-NET) Patients

Posted: August 24th, 2020, 2:00pm GMT

Condition: Gastroenteropancreatic Neuroendocrine Tumors
Intervention: Drug: arginine/lysine
Sponsor: Advanced Accelerator Applications
Not yet recruiting

Pancreatic Radiofrequency Under High Echo-endoscopy in the Management of Pancreatic Neuroendocrine Tumors

Posted: August 20th, 2020, 2:00pm GMT

Conditions: Neuroendocrine Tumor of Pancreas (Disorder); Neuroendocrine Tumor Grade 1
Intervention: Procedure: Radiofrequency ablation
Sponsor: Institut Paoli-Calmettes
Not yet recruiting

Bone Loss in Melanoma Survivors Receiving Immunotherapy

Posted: August 18th, 2020, 2:00pm GMT

Conditions: Clinical Stage III Cutaneous Melanoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Pathologic Stage III Cutaneous Melanoma AJCC v8; Pathologic Stage IIIA Cutaneous Melanoma AJCC v8; Pathologic Stage IIIB Cutaneous Melanoma AJCC v8; Pathologic Stage IIIC Cutaneous Melanoma AJCC v8; Pathologic Stage IIID Cutaneous Melanoma AJCC v8; Pathologic Stage IV Cutaneous Melanoma AJCC v8
Interventions: Procedure: Biospecimen Collection; Procedure: Dual X-ray Absorptiometry
Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI)
Not yet recruiting

Permalink for 'Testing the Addition of an Anti-cancer Drug, BAY 1895344, to Usual Chemotherapy for Advanced Stage Solid Tumors, With a Specific Focus on Patients With Small Cell Lung Cancer, Poorly Differentiated Neuroendocrine Cancer, and Pancreatic Cancer'

Testing the Addition of an Anti-cancer Drug, BAY 1895344, to Usual Chemotherapy for Advanced Stage Solid Tumors, With a Specific Focus on Patients With Small Cell Lung Cancer, Poorly Differentiated Neuroendocrine Cancer, and Pancreatic Cancer

Posted: August 17th, 2020, 2:00pm GMT

Conditions: Metastatic Lung Small Cell Carcinoma; Metastatic Malignant Solid Neoplasm; Metastatic Neuroendocrine Carcinoma; Metastatic Pancreatic Adenocarcinoma; Stage III Lung Cancer AJCC v8; Stage III Pancreatic Cancer AJCC v8; Stage IIIA Lung Cancer AJCC v8; Stage IIIB Lung Cancer AJCC v8; Stage IIIC Lung Cancer AJCC v8; Stage IV Lung Cancer AJCC v8; Stage IV Pancreatic Cancer AJCC v8; Stage IVA Lung Cancer AJCC v8; Stage IVB Lung Cancer AJCC v8; Unresectable Lung Small Cell Carcinoma; Unresectable Malignant Solid Neoplasm; Unresectable Neuroendocrine Carcinoma; Unresectable Pancreatic Adenocarcinoma
Interventions: Drug: ATR Kinase Inhibitor BAY1895344; Drug: Liposomal Irinotecan; Drug: Topotecan Hydrochloride
Sponsor: National Cancer Institute (NCI)
Not yet recruiting

Testing the Combination of the Anti-cancer Drugs XL184 (Cabozantinib) and Nivolumab in Patients With Advanced Cancer and HIV

Posted: August 17th, 2020, 2:00pm GMT

Conditions: Advanced Differentiated Thyroid Gland Carcinoma; Advanced Head and Neck Carcinoma; Advanced Hepatocellular Carcinoma; Advanced Kaposi Sarcoma; Advanced Lung Non-Small Cell Carcinoma; Advanced Lung Small Cell Carcinoma; Advanced Malignant Solid Neoplasm; Advanced Melanoma; Advanced Ovarian Carcinoma; Advanced Prostate Carcinoma; Advanced Renal Cell Carcinoma; Advanced Thyroid Gland Medullary Carcinoma; Advanced Urothelial Carcinoma; 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; Castration-Resistant Prostate Carcinoma; Clinical Stage III Cutaneous Melanoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; HIV Infection; Metastatic Differentiated Thyroid Gland Carcinoma; Metastatic Head and Neck Carcinoma; Metastatic Hepatocellular Carcinoma; Metastatic Kaposi Sarcoma; Metastatic Lung Non-Small Cell Carcinoma; Metastatic Lung Small Cell Carcinoma; Metastatic Malignant Solid Neoplasm; Metastatic Melanoma; Metastatic Ovarian Carcinoma; Metastatic Prostate Carcinoma; Metastatic Renal Cell Carcinoma; Metastatic Thyroid Gland Medullary Carcinoma; Metastatic Triple-Negative Breast Carcinoma; Metastatic Urothelial Carcinoma; Pathologic Stage III Cutaneous Melanoma AJCC v8; Pathologic Stage IIIA Cutaneous Melanoma AJCC v8; Pathologic Stage IIIB Cutaneous Melanoma AJCC v8; Pathologic Stage IIIC Cutaneous Melanoma AJCC v8; Pathologic Stage IIID Cutaneous Melanoma AJCC v8; Pathologic Stage IV Cutaneous Melanoma 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; Recurrent Differentiated Thyroid Gland Carcinoma; Recurrent Head and Neck Carcinoma; Recurrent Hepatocellular Carcinoma; Recurrent Kaposi Sarcoma; Recurrent Lung Non-Small Cell Carcinoma; Recurrent Lung Small Cell Carcinoma; Recurrent Malignant Solid Neoplasm; Recurrent Melanoma; Recurrent Ovarian Carcinoma; Recurrent Prostate Carcinoma; Recurrent Renal Cell Carcinoma; Recurrent Thyroid Gland Medullary Carcinoma; Recurrent Triple-Negative Breast Carcinoma; Recurrent Urothelial Carcinoma; Refractory Differentiated Thyroid Gland Carcinoma; Stage III Differentiated Thyroid Gland Carcinoma AJCC v8; Stage III Hepatocellular Carcinoma AJCC v8; Stage III Lung Cancer AJCC v8; Stage III Ovarian Cancer AJCC v8; Stage III Prostate Cancer AJCC v8; Stage III Renal Cell Cancer AJCC v8; Stage III Thyroid Gland Medullary Carcinoma AJCC v8; Stage IIIA Hepatocellular Carcinoma AJCC v8; Stage IIIA Lung Cancer AJCC v8; Stage IIIA Ovarian Cancer AJCC v8; Stage IIIA Prostate Cancer AJCC v8; Stage IIIA1 Ovarian Cancer AJCC v8; Stage IIIA2 Ovarian Cancer AJCC v8; Stage IIIB Hepatocellular Carcinoma AJCC v8; Stage IIIB Lung Cancer AJCC v8; Stage IIIB Ovarian Cancer AJCC v8; Stage IIIB Prostate Cancer AJCC v8; Stage IIIC Lung Cancer AJCC v8; Stage IIIC Ovarian Cancer AJCC v8; Stage IIIC Prostate Cancer AJCC v8; Stage IV Differentiated Thyroid Gland Carcinoma AJCC v8; Stage IV Hepatocellular Carcinoma AJCC v8; Stage IV Lung Cancer AJCC v8; Stage IV Ovarian Cancer AJCC v8; Stage IV Prostate Cancer AJCC v8; Stage IV Renal Cell Cancer AJCC v8; Stage IV Thyroid Gland Medullary Carcinoma AJCC v8; Stage IVA Differentiated Thyroid Gland Carcinoma AJCC v8; Stage IVA Hepatocellular Carcinoma AJCC v8; Stage IVA Lung Cancer AJCC v8; Stage IVA Ovarian Cancer AJCC v8; Stage IVA Prostate Cancer AJCC v8; Stage IVA Thyroid Gland Medullary Carcinoma AJCC v8; Stage IVB Differentiated Thyroid Gland Carcinoma AJCC v8; Stage IVB Hepatocellular Carcinoma AJCC v8; Stage IVB Lung Cancer AJCC v8; Stage IVB Ovarian Cancer AJCC v8; Stage IVB Prostate Cancer AJCC v8; Stage IVB Thyroid Gland Medullary Carcinoma AJCC v8; Stage IVC Thyroid Gland Medullary Carcinoma AJCC v8; Triple-Negative Breast Carcinoma
Interventions: Drug: Cabozantinib S-malate; Biological: Nivolumab
Sponsor: National Cancer Institute (NCI)
Not yet recruiting

Postoperative Pancreatitis and Its Correlation With Clinically Relevant Pancreatic Fistula in Pancreaticoduodenectomy

Posted: August 14th, 2020, 2:00pm GMT

Condition: Pancreas Disease
Intervention:
Sponsor: Asian Institute of Gastroenterology, India
Recruiting

Imaging Properties of PET Radiotracer [18F]3F-PHPG in Patients With Neuroendocrine Tumors

Posted: August 12th, 2020, 2:00pm GMT

Condition: Neuroendocrine Tumors
Interventions: Drug: 3-[18F]Fluoro-para-hydroxyphenethylguanidine; Drug: [123I] metaiodobenzylguanidine; Diagnostic Test: Positron emission tomography/computed tomography scan; Diagnostic Test: Planar scintigraphy scan; Diagnostic Test: Single photon emission computed tomography/computed tomography scan
Sponsor: University of Michigan Rogel Cancer Center
Not yet recruiting

Serial Tumour Biopsies and Blood Biomarkers in Melanoma

Posted: July 30th, 2020, 2:00pm GMT

Condition: Melanoma
Interventions: Procedure: Surgery; Procedure: Venepuncture
Sponsors: The Christie NHS Foundation Trust; University of Manchester
Recruiting

Impact of Peptides and Chelators on Somatostatin Receptor Antagonists

Posted: July 29th, 2020, 2:00pm GMT

Condition: Neuroendocrine Tumors
Interventions: Diagnostic Test: 68Ga-NODAGA-LM3 and 68Ga-DOTA-LM3 PET/CT; Diagnostic Test: 68Ga-NODAGA-JR11 and 68Ga-DOTA-JR11 PET/CT; Diagnostic Test: 68Ga-NODAGA-LM3 and 68Ga-NODAGA-JR11 PET/CT; Diagnostic Test: 68Ga-DOTA-LM3 and 68Ga-DOTA-JR11 PET/CT
Sponsor: Peking Union Medical College Hospital
Not yet recruiting

Permalink for 'A Clinical Performance Study to Validate the Use of Novel Molecular Diagnostic Assays for the Detection of Cancer Biomarkers in Peripheral Blood and Primary Tumor Tissue of Patients With Recurrent/Metastatic HNSCC, Metastatic NSCLC or Metastatic Melanoma'

A Clinical Performance Study to Validate the Use of Novel Molecular Diagnostic Assays for the Detection of Cancer Biomarkers in Peripheral Blood and Primary Tumor Tissue of Patients With Recurrent/Metastatic HNSCC, Metastatic NSCLC or Metastatic Melanoma

Posted: July 29th, 2020, 2:00pm GMT

Conditions: Head and Neck Squamous Cell Carcinoma; Non Small Cell Lung Cancer; Melanoma
Intervention: Diagnostic Test: PD-L1 Kit
Sponsors: Pharmassist Ltd; University of Athens
Recruiting

Natural History Study of Children and Adults With Neuroendocrine Neoplasms (NEN)s

Posted: July 27th, 2020, 2:00pm GMT

Conditions: Neuroendocrine Tumors; Carcinoma, Neuroendocrine
Intervention:
Sponsor: National Cancer Institute (NCI)
Recruiting

Assessment of What Patients and Healthcare Providers Value

Posted: July 23rd, 2020, 2:00pm GMT

Conditions: Gastric Adenocarcinoma; Pancreatic Adenocarcinoma; Pancreatic Neuroendocrine Carcinoma
Intervention: Other: Survey Administration
Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI)
Recruiting

Permalink for 'Prospective Evaluation of a Program for Early Identification of Needs and Multidisciplinary Intervention in Supportive Care in Digestive Oncology - DISSPO Parcours Dig' Study'

Prospective Evaluation of a Program for Early Identification of Needs and Multidisciplinary Intervention in Supportive Care in Digestive Oncology - DISSPO Parcours Dig' Study

Posted: July 20th, 2020, 2:00pm GMT

Conditions: Non-colorectal Cancer (Esophagus, Stomach, Liver/Bile Ducts, Pancreas, Neuroendocrine Carcinoma); Colorectal With Associated Risk Factors
Intervention: Other: multidisciplinary assessment and intervention
Sponsor: Institut Curie
Not yet recruiting

Nutrition in Gastrointestinal Tumors

Posted: July 17th, 2020, 2:00pm GMT

Conditions: Pancreatic Cancer; Oesophageal Cancer; Colon Cancer; Liver Cancer; Rectal Cancer; Bile Duct Cancer; GIST, Malignant; Neuroendocrine Tumors; Small Intestine Cancer; Gastric Cancer
Intervention: Other: No intervention - observational study only
Sponsor: University Medicine Greifswald
Recruiting

Study in Patients With Advanced Cancers Associated With Expression of DLL3 Who Have Failed Standard Available Therapy

Posted: July 15th, 2020, 2:00pm GMT

Condition: Small-cell Lung Cancer
Intervention: Drug: HPN328
Sponsor: Harpoon Therapeutics
Not yet recruiting

Cancer and Blood Pressure Management, CARISMA Study

Posted: July 10th, 2020, 2:00pm GMT

Conditions: Cardiovascular Disorder; Chronic Kidney Disease; Metastatic Renal Cell Carcinoma; Metastatic Thyroid Gland Medullary Carcinoma; Stage IV Renal Cell Cancer AJCC v8; Stage IV Thyroid Gland Medullary Carcinoma AJCC v8; Stage IVA Thyroid Gland Medullary Carcinoma AJCC v8; Stage IVB Thyroid Gland Medullary Carcinoma AJCC v8; Stage IVC Thyroid Gland Medullary Carcinoma AJCC v8
Interventions: Other: Best Practice; Other: Blood Pressure Measurement; Other: Clinical Management; Other: Quality-of-Life Assessment; Other: Questionnaire Administration
Sponsors: ECOG-ACRIN Cancer Research Group; National Cancer Institute (NCI)
Not yet recruiting

Rediscovering Biomarkers for the Diagnosis and Early Treatment Response in NEN (REBORN)

Posted: July 9th, 2020, 2:00pm GMT

Conditions: Neuroendocrine Tumors; Neuroendocrine Neoplasm; Neuroendocrine Tumor Grade 1; Neuroendocrine Tumor Grade 2; Neuroendocrine Carcinoma
Intervention: Drug: Somatostatin analog; chemotherapy
Sponsor: University of Roma La Sapienza
Not yet recruiting

Postoperative Adjuvant Treatment of Completely Resected Mucosal Melanoma Phase II Study

Posted: July 8th, 2020, 2:00pm GMT

Condition: Mucosal Melanoma
Interventions: Combination Product: Toripalimab; Combination Product: Temozolomide
Sponsor: Beijing Cancer Hospital
Recruiting

Permalink for 'Using Biomarkers to Help Guide Safe Immunotherapy Discontinuation in Patients With Unresectable Stage IIIB-IV Melanoma, The PET-Stop Trial'

Using Biomarkers to Help Guide Safe Immunotherapy Discontinuation in Patients With Unresectable Stage IIIB-IV Melanoma, The PET-Stop Trial

Posted: July 8th, 2020, 2:00pm GMT

Conditions: Advanced Melanoma; Clinical Stage III Cutaneous Melanoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Melanoma of Unknown Primary; Pathologic Stage IIIB Cutaneous Melanoma AJCC v8; Pathologic Stage IIIC Cutaneous Melanoma AJCC v8; Pathologic Stage IIID Cutaneous Melanoma AJCC v8; Pathologic Stage IV Cutaneous Melanoma AJCC v8; Unresectable Acral Lentiginous Melanoma; Unresectable Melanoma; Unresectable Mucosal Melanoma
Interventions: Biological: Ipilimumab; Biological: Nivolumab; Other: Patient Observation; Biological: Pembrolizumab
Sponsors: ECOG-ACRIN Cancer Research Group; National Cancer Institute (NCI)
Recruiting

Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers

Posted: July 7th, 2020, 2:00pm GMT

Conditions: Bladder Carcinoma; Cervical Carcinoma; Cholangiocarcinoma; Hematopoietic and Lymphoid Cell Neoplasm; Hepatocellular Carcinoma; Malignant Adrenal Gland Neoplasm; Malignant Brain Neoplasm; Malignant Pleural Neoplasm; Malignant Skin Neoplasm; Malignant Solid Neoplasm; Malignant Testicular Neoplasm; Malignant Thymus Neoplasm; Neuroendocrine Neoplasm; Thyroid Gland Carcinoma; Urothelial Carcinoma
Interventions: Procedure: Computed Tomography; Drug: Gallium Ga 68 FAPi-46; Procedure: Positron Emission Tomography
Sponsor: Jonsson Comprehensive Cancer Center
Not yet recruiting

Next Generation Sequencing-Based Stratification of Front Line Treatment of HighGrade Neuroendocrine Carcinoma

Posted: June 30th, 2020, 2:00pm GMT

Condition: Large-Cell Neuroendocrine Carcinoma
Interventions: Other: Treatment Specific for Non-Small Cell Carcinoma/Adenocarcinoma; Other: Treatment for Small Cell Lung Cancer
Sponsor: Aman Chauhan
Not yet recruiting

A Study of the Safety and Tolerance of CAN04 in Combination With Pembrolizumab in Subjects With Solid Tumors

Posted: June 30th, 2020, 2:00pm GMT

Conditions: Carcinoma, Non-Small-Cell Lung; Urothelial Carcinoma; Malignant Melanoma; Head and Neck Squamous Cell Carcinoma
Interventions: Drug: CAN04; Drug: Pembrolizumab
Sponsor: Cantargia AB
Recruiting

Registry on NEN Patients and COVID-19

Posted: June 23rd, 2020, 2:00pm GMT

Conditions: Neuroendocrine Tumors; COVID-19
Intervention:
Sponsor: European Institute of Oncology
Recruiting

A Diagnostic Imaging Study of 64Cu-SARTATE Using PET on Patients With Known or Suspected Neuroendocrine Tumors

Posted: June 19th, 2020, 2:00pm GMT

Condition: Neuroendocrine Tumors
Intervention: Drug: 64Cu-SARTATE
Sponsor: Clarity Pharmaceuticals Ltd
Not yet recruiting

PDL1 Expression in Cancer (PECan Study).

Posted: June 19th, 2020, 2:00pm GMT

Conditions: Non-small Cell Lung Cancer; Melanoma
Intervention: Diagnostic Test: [99mTc]-NM01 SPECT
Sponsors: Guy's and St Thomas' NHS Foundation Trust; NanoMab
Not yet recruiting

Neuroendocrine and Adrenal Tumors

Posted: June 16th, 2020, 2:00pm GMT

Conditions: Neuroendocrine Tumors; Adrenal Tumor
Intervention: Other: No intervention
Sponsor: University of Pennsylvania
Not yet recruiting

A Trial Aiming to Assess the Safety and Activity of the Combination of Cabozantinib Plus Lanreotide in GEP and NET

Posted: June 12th, 2020, 2:00pm GMT

Conditions: Metastatic Well Differentiated Neuroendocrine Neoplasm; Neuroendocrine Tumors
Interventions: Drug: Cabozantinib; Drug: Lanreotide
Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Recruiting

Permalink for 'A Study to Test Different Doses of BI 764532 in Patients With Small Cell Lung Cancer and Other Neuroendocrine Tumours That Are Positive for Delta-Like Ligand 3 (DLL3).'

A Study to Test Different Doses of BI 764532 in Patients With Small Cell Lung Cancer and Other Neuroendocrine Tumours That Are Positive for Delta-Like Ligand 3 (DLL3).

Posted: June 12th, 2020, 2:00pm GMT

Condition: Patients With Small Cell Lung Carcinoma and Other Neoplasms
Intervention: Drug: BI 764532
Sponsor: Boehringer Ingelheim
Recruiting

Cabozantinib in High Grade Neuroendocrine Neoplasms

Posted: June 2nd, 2020, 2:00pm GMT

Condition: High Grade Neuroendocrine Neoplasms
Interventions: Drug: Cabozantinib; Procedure: Blood for plasma biomarkers
Sponsors: Washington University School of Medicine; Exelixis
Not yet recruiting

Permalink for 'Infliximab or Vedolizumab in Treating Immune Checkpoint Inhibitor-Related Colitis in Patients With Genitourinary Cancer or Melanoma'

Infliximab or Vedolizumab in Treating Immune Checkpoint Inhibitor-Related Colitis in Patients With Genitourinary Cancer or Melanoma

Posted: May 29th, 2020, 2:00pm GMT

Conditions: Colitis; Lung Non-Small Cell Carcinoma; Malignant Genitourinary System Neoplasm; Malignant Solid Neoplasm; Melanoma
Interventions: Biological: Infliximab; Biological: Vedolizumab
Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI)
Recruiting

Trial of Cabozantinib Plus Atezolizumab in Advanced and Progressive Neoplasms of the Endocrine System. The CABATEN Study

Posted: May 25th, 2020, 2:00pm GMT

Conditions: Neuroendocrine Tumor; Anaplastic Thyroid Cancer; Adenocarcinoma; Pheochromocytoma; Paraganglioma
Intervention: Drug: Cabozantinib 40 mg
Sponsors: Grupo Espanol de Tumores Neuroendocrinos; Ipsen; Roche Pharma AG
Not yet recruiting

Permalink for 'Testing the Addition of an Anticancer Drug, Olaparib, to the Usual Chemotherapy (Temozolomide) for Advanced Neuroendocrine Cancer'

Testing the Addition of an Anticancer Drug, Olaparib, to the Usual Chemotherapy (Temozolomide) for Advanced Neuroendocrine Cancer

Posted: May 20th, 2020, 2:00pm GMT

Conditions: Advanced Adrenal Gland Pheochromocytoma; Advanced Paraganglioma; Metastatic Adrenal Gland Pheochromocytoma; Metastatic Paraganglioma; Unresectable Adrenal Gland Pheochromocytoma; Unresectable Paraganglioma
Interventions: Drug: Olaparib; Other: Quality-of-Life Assessment; Drug: Temozolomide
Sponsor: National Cancer Institute (NCI)
Not yet recruiting

A Pilot Study of 5-Aminolevulinic Acid (5-ALA) to Enhance Visualization of Pituitary Adenomas

Posted: May 18th, 2020, 2:00pm GMT

Condition: Pituitary Adenoma
Intervention: Drug: 5-aminolevulinic acid
Sponsors: Massachusetts General Hospital; NX Development Corp
Not yet recruiting

X-ray Psoralen Activated Cancer Therapy in Head and Neck, Breast, Sarcoma and Melanoma

Posted: May 15th, 2020, 2:00pm GMT

Condition: Advanced Cancer
Intervention: Combination Product: X-PACT
Sponsor: Immunolight, LLC
Not yet recruiting

Neoadjuvant PRRT With 177Lu-DOTATATE Followed by Surgery for Resectable PanNET

Posted: May 13th, 2020, 2:00pm GMT

Condition: Neuroendocrine Tumors
Intervention: Drug: 177Lu-Dotatate
Sponsor: IRCCS San Raffaele
Recruiting

OH2 Injection in Solid Tumors

Posted: May 13th, 2020, 2:00pm GMT

Conditions: Solid Tumor; Melanoma
Interventions: Biological: OH2 injection; Drug: Keytruda
Sponsor: Wuhan Binhui Biotechnology Co., Ltd.
Recruiting

177Lu-DOTA-TATE and Olaparib in Somatostatin Receptor Positive Tumours

Posted: May 5th, 2020, 2:00pm GMT

Conditions: Clinical Trial, Phase I; Neuroendocrine Tumors; Thymoma; Mesothelioma
Intervention: Drug: 177Lu-DOTA-TATE + olaparib
Sponsors: Vastra Gotaland Region; Advanced Accelerator Applications
Recruiting

Binimetinib and Nivolumab for the Treatment of Locally Advanced Unresectable or Metastatic BRAF V600 Wildtype Melanoma

Posted: May 5th, 2020, 2:00pm GMT

Conditions: Clinical Stage III Cutaneous Melanoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Locally Advanced Cutaneous Melanoma; Metastatic Cutaneous Melanoma; Pathologic Stage III Cutaneous Melanoma AJCC v8; Pathologic Stage IIIA Cutaneous Melanoma AJCC v8; Pathologic Stage IIIB Cutaneous Melanoma AJCC v8; Pathologic Stage IIIC Cutaneous Melanoma AJCC v8; Pathologic Stage IIID Cutaneous Melanoma AJCC v8; Pathologic Stage IV Cutaneous Melanoma AJCC v8; Unresectable Cutaneous Melanoma
Interventions: Drug: Binimetinib; Biological: Nivolumab; Other: Questionnaire Administration
Sponsor: Jonsson Comprehensive Cancer Center
Not yet recruiting

Cohort of Well-differentiated Grade 3 Neuroendocrine Digestive Tumors

Posted: April 28th, 2020, 2:00pm GMT

Condition: Neuroendocrine Tumors
Intervention: Drug: platinum chemotherapy
Sponsors: Assistance Publique - Hôpitaux de Paris; Ipsen
Recruiting

Interaction Between Host, Microenvironment and Immunity on Gastrointestinal Neoplasms

Posted: April 27th, 2020, 2:00pm GMT

Condition: Gastrointestinal Neoplasms
Interventions: Biological: Blood sampling; Procedure: Liver biopsy; Biological: Stool collect
Sponsor: Assistance Publique - Hôpitaux de Paris
Not yet recruiting

TheraSphere Selective Internal Radiation Therapy (SIRT) as Treatment for Neuroendocrine Tumours With Liver Mets

Posted: April 27th, 2020, 2:00pm GMT

Conditions: Neuroendocrine Tumors; Liver Metastases
Intervention: Radiation: TheraSpheres Selective Internal Radiation Therapy (SIRT)
Sponsors: Imperial College London; Biocompatibles UK Ltd, a BT International group company
Recruiting

The Tolerance,Pharmacokinetic Characteristics,Safety and Efficacy of ScTIL210 in the Treatment of Melanoma

Posted: April 22nd, 2020, 2:00pm GMT

Condition: Melanoma
Intervention: Biological: Super circulating tumor infiltrating lymphocytes(ScTIL)
Sponsor: Beijing Cancer Hospital
Not yet recruiting

Atypical MOLes and Melanoma Early Detection Study (MoleMed)

Posted: April 20th, 2020, 2:00pm GMT

Conditions: Melanoma; Melanoma (Skin); Moles; Nevus; Nevus, Blue; Nevus, Pigmented; Nevus, Spitz; Nevi, Spindle Cell; Nevi, Dysplastic; Dysplastic Nevus Syndrome; Mucosal Melanoma; Mucosal Melanosis
Intervention: Procedure: Non-invasive adhesive system (patch)
Sponsors: Russian Academy of Medical Sciences; Blokhin's Russian Cancer Research Center
Recruiting

Magnetic Resonance Imaging (MRI) With Hyperpolarized Pyruvate (13C) as Diagnostic Tool in Advanced Prostate Cancer

Posted: April 15th, 2020, 2:00pm GMT

Conditions: Prostate Cancer; Advanced Prostate Carcinoma
Interventions: Drug: Hyperpolarized C13; Procedure: Magnetic Resonance Imaging (MRI)
Sponsors: Rahul Aggarwal; National Cancer Institute (NCI)
Recruiting

LunG and Melanoma canceR pAtients coVId19 Disease (GRAVID)

Posted: April 14th, 2020, 2:00pm GMT

Conditions: Covid-19; Lung Cancer
Intervention:
Sponsor: Spanish Lung Cancer Group
Recruiting

Permalink for 'Study of Capecitabine-Temozolomide(CapTem) With Yttrium-90 in Patients With Unresectable Metastatic Grade 2 Neuroendocrine Tumors'

Study of Capecitabine-Temozolomide(CapTem) With Yttrium-90 in Patients With Unresectable Metastatic Grade 2 Neuroendocrine Tumors

Posted: April 8th, 2020, 2:00pm GMT

Conditions: Neuroendocrine Tumor Grade 2; Neuroendocrine Tumors
Interventions: Drug: Capecitabine Oral Product; Drug: Temozolomide Oral Product; Combination Product: transarterial radioembolization
Sponsor: University of Pennsylvania
Not yet recruiting

Portal Vein Resection in Pancreatic Neuroendocrine Tumours

Posted: April 7th, 2020, 2:00pm GMT

Conditions: Pancreas Neoplasm; Neuroendocrine Tumors
Intervention: Procedure: Portal vein resection / reconstruction
Sponsor: Royal Free Hospital NHS Foundation Trust
Not yet recruiting

Copper Cu 64 Dotatate for the Detection, Localization and Monitoring of SSTR Expressing (NETs)

Posted: April 6th, 2020, 2:00pm GMT

Condition: Neuroendocrine Tumors
Intervention: Diagnostic Test: Copper Cu 64 Dotatate
Sponsor: Curium US LLC
Available

Permalink for 'Impact of Time-Restricted Eating on Metabolic and Neuroendocrine Homeostasis, Inflammation and Oxidative Stress in Metabolic Syndrome'

Impact of Time-Restricted Eating on Metabolic and Neuroendocrine Homeostasis, Inflammation and Oxidative Stress in Metabolic Syndrome

Posted: March 31st, 2020, 2:00pm GMT

Conditions: Metabolic Syndrome; Overweight or Obesity; PreDiabetes; Weight Loss; Quality of Life
Intervention: Behavioral: Time-Restricted Eating
Sponsors: Nicolaus Copernicus University; Salk Institute for Biological Studies; University of California, San Diego; Center for Obesity and Metabolic Disorders Treatment Bydgoszcz
Recruiting

Permalink for 'Chemotherapy For Metastatic Grade 3 Poorly Differentiated NEuroendocrine Carcinoma Of GastroEnteroPancreatic And Unknown Primary'

Chemotherapy For Metastatic Grade 3 Poorly Differentiated NEuroendocrine Carcinoma Of GastroEnteroPancreatic And Unknown Primary

Posted: March 27th, 2020, 2:00pm GMT

Condition: Neuroendocrine Carcinoma
Interventions: Drug: FOLFOXIRI Protocol; Drug: Cisplatin injection
Sponsors: Federation Francophone de Cancerologie Digestive; National Cancer Institute, France
Not yet recruiting

Mobile Application to Collect PRO Data in NET Patients

Posted: March 27th, 2020, 2:00pm GMT

Condition: Neuroendocrine Neoplasms (Tumours)
Intervention:
Sponsors: King's College Hospital NHS Trust; Ampersand Health Ltd; Neuroendocrine Cancer UK
Not yet recruiting

Gallium-68 Labeled LM3 PET/CT in Neuroendocrine Tumors

Posted: March 24th, 2020, 2:00pm GMT

Condition: Neuroendocrine Tumors
Interventions: Diagnostic Test: Gallium-68 NODAGA-LM3 PET/CT; Diagnostic Test: Gallium-68 DOTA-LM3 PET/CT; Diagnostic Test: Gallium-68 DOTATATE PET/CT
Sponsor: Peking Union Medical College Hospital
Recruiting

National Cancer Institute "Cancer Moonshot Biobank"

Posted: March 19th, 2020, 2:00pm GMT

Conditions: Acute Myeloid Leukemia; Castration-Resistant Prostate Carcinoma; Clinical Stage III Cutaneous Melanoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8; Hematopoietic and Lymphoid Cell Neoplasm; Lung Non-Small Cell Carcinoma; Lung Small Cell Carcinoma; Malignant Solid Neoplasm; Pathologic Stage III Cutaneous Melanoma AJCC v8; Pathologic Stage IIIA Cutaneous Melanoma AJCC v8; Pathologic Stage IIIB Cutaneous Melanoma 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 Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8; Refractory Plasma Cell Myeloma; Stage III Lung Cancer AJCC v8; Stage IIIA Lung Cancer AJCC v8; Stage IIIB Lung Cancer AJCC v8; Stage IIIC Lung Cancer AJCC v8; Stage IV Colorectal Cancer AJCC v8; Stage IV Lung Cancer AJCC v8; Stage IV Prostate Cancer AJCC v8; Stage IVA Colorectal Cancer AJCC v8; Stage IVA Lung Cancer AJCC v8; Stage IVA Prostate Cancer AJCC v8; Stage IVB Colorectal Cancer AJCC v8; Stage IVB Lung Cancer AJCC v8; Stage IVB Prostate Cancer AJCC v8; Stage IVC Colorectal Cancer AJCC v8
Interventions: Procedure: Biospecimen Collection; Other: Medical Chart Review
Sponsor: National Cancer Institute (NCI)
Recruiting

Immunotherapy Merkel Adjuvant Trial

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

Phase 2 Trial of Voyager V1 in Combination With Cemiplimab in Cancer Patients

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

Conditions: Melanoma; Hepatocellular Carcinoma; Non Small Cell Lung Cancer; Endometrial Cancer
Interventions: Biological: VV1; Biological: Cemiplimab
Sponsors: Vyriad, Inc.; Regeneron Pharmaceuticals
Recruiting

Permalink for 'Tipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial'

Tipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial

Posted: February 26th, 2020, 3:00pm GMT

Conditions: Recurrent Adrenal Gland Pheochromocytoma; Recurrent Ectomesenchymoma; Recurrent Ependymoma; Recurrent Ewing Sarcoma; Recurrent Hepatoblastoma; Recurrent Kidney Wilms Tumor; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Glioma; Recurrent Medulloblastoma; Recurrent Melanoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Rhabdoid Tumor; Recurrent Rhabdoid Tumor of the Kidney; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Recurrent Thyroid Gland Carcinoma; Recurrent WHO Grade II Glioma; Refractory Adrenal Gland Pheochromocytoma; Refractory Ependymoma; Refractory Ewing Sarcoma; Refractory Hepatoblastoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Glioma; Refractory Medulloblastoma; Refractory Melanoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Peripheral Primitive Neuroectodermal Tumor; Refractory Rhabdoid Tumor; Refractory Rhabdoid Tumor of the Kidney; Refractory Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma; Refractory Thyroid Gland Carcinoma; Refractory WHO Grade II Glioma
Intervention: Drug: Tipifarnib
Sponsor: National Cancer Institute (NCI)
Recruiting

Database ITANET - ENETS Registry

Posted: February 24th, 2020, 3:00pm GMT

Condition: Gastro-entero Pancreatic Neuroendocrine Tumors
Intervention:
Sponsor: Italian Association Neuroendocrine Tumors
Recruiting

Permalink for 'A Study of Selpercatinib (LY3527723) in Participants With Advanced Solid Tumors Including RET Fusion-positive Solid Tumors, Medullary Thyroid Cancer and Other Tumors With RET Activation'

A Study of Selpercatinib (LY3527723) in Participants With Advanced Solid Tumors Including RET Fusion-positive Solid Tumors, Medullary Thyroid Cancer and Other Tumors With RET Activation

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

Conditions: Solid Tumor; Medullary Thyroid Cancer
Intervention: Drug: Selpercatinib
Sponsors: Eli Lilly and Company; Loxo Oncology, Inc. a wholly owned subsidiary of Eli Lilly and Company
Recruiting

$Permalink for 'Hypofractionated Proton Therapy for Benign Intracranial Brain Tumors, the HiPPI Study'$

Hypofractionated Proton Therapy for Benign Intracranial Brain Tumors, the HiPPI Study

Posted: February 20th, 2020, 3:00pm GMT

Conditions: Grade I Meningioma; Grade II Meningioma; Grade III Meningioma; Intracranial Neoplasm; Nerve Sheath Neoplasm; Pituitary Gland Adenoma; Schwannoma
Interventions: Radiation: Hypofractionated Radiation Therapy; Radiation: Photon Beam Radiation Therapy; Radiation: Proton Beam Radiation Therapy; Other: Quality-of-Life Assessment; Other: Questionnaire Administration
Sponsors: Emory University; National Cancer Institute (NCI)
Recruiting

Phase-II Study of Lu177DOTATOC in Adults With STTR(+)Pulmonary, Pheochromocytoma, Paraganglioma, Unknown Primary, Thymus NETs (PUTNET)

Posted: February 19th, 2020, 3:00pm GMT

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

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

Efficacy of Neoadjuvant Chemotherapy in Terms of DFS in Patients With Localized Digestive Neuroendocrine Carcinomas

Posted: February 13th, 2020, 3:00pm GMT

Conditions: Neuroendocrine Carcinoma; Digestive Cancer
Interventions: Drug: Neoadjuvant treatment; Drug: Adjuvant treatment
Sponsors: GERCOR - Multidisciplinary Oncology Cooperative Group; Fondation ARCAD
Not yet recruiting

Effect of Dexmedetomidine on Brain Homeostasis and Neurocognitive Outcome

Posted: February 12th, 2020, 3:00pm GMT

Conditions: Brain Tumor; Metabolic Disturbance; Inflammatory Response; Oxygen Deficiency
Interventions: Drug: Dexmedetomidine; Other: Normal saline
Sponsor: Georgia Tsaousi
Recruiting

Targeted Therapy and Avelumab in Merkel Cell Carcinoma

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

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

Study Comparing Lymphoseek® vs. Albumin Nanocolloid in Head and Neck, Melanoma and Breast Cancer

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

Conditions: Head Cancer; Neck Cancer; Melanoma; Breast Cancer
Interventions: Drug: Lymphoseek; Drug: Nanocoll
Sponsor: Anna Cruceta
Not yet recruiting

18F-MFBG PET Imaging of the Norepinephrine Transporter in Neural Crest and Neuroendocrine Tumors

Posted: February 6th, 2020, 3:00pm GMT

Conditions: Neural Crest Tumor; Neuroendocrine Tumors
Interventions: Drug: (18F)MFBG; Device: PET/CT; Other: Venous blood samples
Sponsor: Universitaire Ziekenhuizen Leuven
Recruiting

Permalink for 'Tumor Necrosis Factor (TNF) and Glucocorticoid Antagonist for Gulf War Illness (GWI)-Associated Multi-symptom Disease Homeostasis Reset'

Tumor Necrosis Factor (TNF) and Glucocorticoid Antagonist for Gulf War Illness (GWI)-Associated Multi-symptom Disease Homeostasis Reset

Posted: February 5th, 2020, 3:00pm GMT

Condition: Gulf War Illness
Interventions: Drug: Etanercept; Drug: Mifepristone
Sponsors: Nova Southeastern University; RTI International; Rochester General Hospital
Recruiting

Evaluation of Acupuncture Effects for Complications After Surgery of Cerebellopontine Angle Tumor in Skull Base

Posted: January 31st, 2020, 3:00pm GMT

Conditions: Acupuncture; Tumor, Brain; Skull Base Tumor; Cerebellopontine Angle Tumor; Complication of Treatment; Quality of Life; Neuromuscular Blockade
Intervention:
Sponsor: Taipei Veterans General Hospital, Taiwan
Recruiting

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

Posted: January 27th, 2020, 3:00pm GMT

Natural History of Medullary Thyroid Cancer to Inform Advanced Disease Management

Posted: January 3rd, 2020, 3:00pm GMT

Conditions: Advanced Thyroid Gland Medullary Carcinoma; Stage III Thyroid Gland Medullary Carcinoma AJCC v8; Stage IV Thyroid Gland Medullary Carcinoma AJCC v8; Stage IVA Thyroid Gland Medullary Carcinoma AJCC v8; Stage IVB Thyroid Gland Medullary Carcinoma AJCC v8; Stage IVC Thyroid Gland Medullary Carcinoma AJCC v8
Interventions: Other: Blood Pressure Measurement; Other: Questionnaire Administration
Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI)
Recruiting

Permalink for 'A Study of Anlotinib and AK105 Injection in Subjects With Gastrointestinal Tumors, Urinary System Tumors, Neuroendocrine Tumors'

A Study of Anlotinib and AK105 Injection in Subjects With Gastrointestinal Tumors, Urinary System Tumors, Neuroendocrine Tumors

Posted: December 20th, 2019, 3:00pm GMT

Condition: Gastrointestinal Tumors, Urinary System Tumors, Neuroendocrine Tumors
Interventions: Drug: AK105; Drug: Anlotinib
Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Recruiting

A Study to Evaluate the Safety, Tolerability and Pharmacokinetics of HH2710 in Patient With Advanced Tumors

Posted: December 13th, 2019, 3:00pm GMT

Conditions: Advanced Tumors; Melanoma; Non-Small-Cell Lung Cancer; Erdheim-Chester Disease; Other RAS/RAF/MEK/ERK Mutated Tumors
Intervention: Drug: HH2710
Sponsor: ShangHai HaiHe Pharmaceutical
Recruiting

Study of INBRX-106 in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)

Posted: December 13th, 2019, 3:00pm GMT

Conditions: Solid Tumor; Non-Small Cell Lung Cancer; Melanoma; Head and Neck Cancer; Gastric Cancer; Renal Cell Carcinoma; Urothelial Carcinoma
Interventions: Drug: INBRX-106 - Hexavalent OX40 agonist antibody; Drug: Pembrolizumab
Sponsors: Inhibrx, Inc.; Merck Sharp & Dohme Corp.
Recruiting

Personalized CAPTEM Radiopeptide Therapy of Advanced, Non-resectable Neuroendocrine Cancer

Posted: December 11th, 2019, 3:00pm GMT

Condition: Neuroendocrine Tumors
Intervention: Drug: 177Lu-DOTATOC
Sponsors: University of Warmia and Mazury; Maria Sklodowska-Curie Institute - Oncology Center; The Medical University of Warsaw; Poland; The Diagnostic and Therapeutic Center Gammed; Poland; National Center for Research and Development, Poland
Recruiting

Granzyme B PET Imaging Drug as a Predictor of Immunotherapy Response in Melanoma or NSCLC Participants

Posted: November 19th, 2019, 3:00pm GMT

Conditions: Melanoma; Non-Small Cell Lung Cancer
Intervention: Drug: Single Arm
Sponsors: Cytosite Biopharma Inc.; Massachusetts General Hospital; University of Alabama at Birmingham
Recruiting

Adoptive Tumor-infiltrating Lymphocyte Transfer With Nivolumab for Melanoma

Posted: November 18th, 2019, 3:00pm GMT

Condition: Advanced Melanoma
Intervention: Drug: Combination of TIL Transfer with anti-PD-1 Therapy and low dose IL-2
Sponsors: University Hospital, Basel, Switzerland; GMP network of Basel
Not yet recruiting

Permalink for 'A Phase II Study on Adjuvant Vaccination With Dendritic Cells Loaded With Autologous Tumor Homogenate in Resected Stage IV Rare Cancers.'

A Phase II Study on Adjuvant Vaccination With Dendritic Cells Loaded With Autologous Tumor Homogenate in Resected Stage IV Rare Cancers.

Posted: November 18th, 2019, 3:00pm GMT

Conditions: Head Neck Tumors; Neuroendocrine Tumors; Soft Tissue Sarcoma; Rare Cancer; Vaccination
Interventions: Biological: Autologous DC vaccine; Drug: Interleukin-2
Sponsor: Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
Recruiting

Immunotherapy With IFx-Hu2.0 Vaccine for Advanced MCC or cSCC

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

A Study of ZN-c3 in Participants With Solid Tumors

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

Conditions: Solid Tumor; Epithelial Ovarian Cancer; Fallopian Tube Cancer; Peritoneal Cancer; Triple Negative Breast Cancer; Small Cell Lung Cancer; Metastatic Breast Cancer; Malignant Melanoma; Non Small Cell Lung Cancer; Urothelial Carcinoma
Interventions: Drug: ZN-c3; Drug: Talazoparib; Drug: Pembrolizumab
Sponsor: K-Group Beta
Recruiting

Tamoxifen for Well Differentiated Neurodendocrine Tumors and Hormone Receptor Positive Expression

Posted: October 10th, 2019, 2:00pm GMT

Conditions: Neuroendocrine Tumors; Progesterone Receptor Positive Tumor; Estrogen Receptor Positive Tumor
Intervention: Drug: Tamoxifen 20 mg
Sponsor: H. Lee Moffitt Cancer Center and Research Institute
Recruiting

Communicating With Patients on Cancer Resistance to Treatment: the Development of a Communication Tool. (HECTOR)

Posted: October 7th, 2019, 2:00pm GMT

Conditions: Metastatic Uveal Melanoma; Triple Negative Breast Cancer; Luminal B Breast Cancer; Pediatric Cancer
Interventions: Behavioral: Questionnaires; Behavioral: Semi-structured individual interviews; Other: Focus Group; Other: DELPHI Consensus Method
Sponsor: Institut Curie
Not yet recruiting

68-Ga DOTATATE PET/MRI in the Diagnosis and Management of Somatostatin Receptor Positive CNS Tumors.

Posted: September 9th, 2019, 2:00pm GMT

Conditions: CNS Tumors; Meningioma; Esthesioneuroblastoma; Hemangioblastoma; Medulloblastoma; Paraganglioma; Pituitary Adenoma
Intervention: Diagnostic Test: Ga68-DOTATATE-PET/MRI
Sponsors: Weill Medical College of Cornell University; Novartis Pharmaceuticals
Recruiting

Testing the Combination of XL184 (Cabozantinib), Nivolumab, and Ipilimumab for Poorly Differentiated Neuroendocrine Tumors

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

Conditions: Metastatic Large Cell Neuroendocrine Carcinoma; Metastatic Neuroendocrine Carcinoma; Metastatic Neuroendocrine Neoplasm; Metastatic Small Cell Carcinoma
Interventions: Drug: Cabozantinib; Drug: Cabozantinib S-malate; Biological: Ipilimumab; Biological: Nivolumab
Sponsor: National Cancer Institute (NCI)
Recruiting

Permalink for 'Testing the Addition of a New Anti-cancer Drug, Radium-223 Dichloride, to the Usual Treatment (Cabozantinib) for Advanced Renal Cell Cancer That Has Spread to the Bone, the RadiCaL Study'

Testing the Addition of a New Anti-cancer Drug, Radium-223 Dichloride, to the Usual Treatment (Cabozantinib) for Advanced Renal Cell Cancer That Has Spread to the Bone, the RadiCaL Study

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

Conditions: Advanced Renal Cell Carcinoma; Chromophobe Renal Cell Carcinoma; Clear Cell Renal Cell Carcinoma; Collecting Duct Carcinoma; Kidney Medullary Carcinoma; Metastatic Malignant Neoplasm in the Bone; Papillary Renal Cell Carcinoma; Stage IV Renal Cell Cancer AJCC v8; Unclassified Renal Cell Carcinoma
Interventions: Drug: Cabozantinib; Drug: Cabozantinib S-malate; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Radiation: Radium Ra 223 Dichloride
Sponsor: National Cancer Institute (NCI)
Recruiting

Enterade in Carcinoid/Non-Carcinoid Syndrome Neuroendocrine Tumor Patients With Quality of Life Limiting Bowel Frequency

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

Conditions: Neuroendocrine Tumor; Carcinoid Syndrome
Interventions: Dietary Supplement: Enterade®; Other: Functional Assessment of Chronic Illness Therapy for Patients with Diarrhea (version 4.0)
Sponsors: Vanderbilt-Ingram Cancer Center; Entrinsic Health Solutions, Inc.
Recruiting

A Personalized NeoAntigen Cancer Vaccine Combined With Anti-PD-1 in Melanoma

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

Condition: Melanoma (Skin)
Interventions: Drug: Peptide; Drug: Anti-PD-1; Drug: rhGM-CSF; Drug: Imiquimod 5% Topical Cream
Sponsor: Xiangya Hospital of Central South University
Recruiting

Permalink for 'Collision of a pancreatic ductal adenocarcinoma and a pancreatic neuroendocrine tumor associated with multiple endocrine neoplasm type 1.'

Collision of a pancreatic ductal adenocarcinoma and a pancreatic neuroendocrine tumor associated with multiple endocrine neoplasm type 1.

Fetched: September 22nd, 2020, 5:01am GMT

Collision of a pancreatic ductal adenocarcinoma and a pancreatic neuroendocrine tumor associated with multiple endocrine neoplasm type 1.

Clin J Gastroenterol. 2020 Sep 20;:

Authors: Ohno A, Fujimori N, Miki M, Oono T, Igarashi H, Matsuda R, Koga Y, Oda Y, Ohtsuka T, Nakamura M, Ito T, Ogawa Y

Abstract
A 54-year-old man with pancreatic head tumor had undergone pancreaticoduodenectomy and was diagnosed with pancreatic neuroendocrine tumor (P-NET) associated with sporadic multiple endocrine neoplasm type 1. Five years after the resection, P-NET recurred and liver metastases were observed. He was treated with a somatostatin analog. Eleven years after the resection, computed tomography revealed a new pancreatic hypodense and hypovascular mass adjacent to the P-NET that was diagnosed as pancreatic adenocarcinoma via endoscopic ultrasound-guided fine-needle aspiration. He underwent a total remnant pancreatectomy. Pathological examination showed that the lesion was constituted by a pancreatic ductal adenocarcinoma (PDAC) and a neuroendocrine tumor. Additionally, the invasive ductal carcinoma collided with the neuroendocrine tumor. Both PDAC and P-NET cells were observed in the collision area. We could observe the onset of PDAC during the treatment of P-NET. Moreover, we are the first to report the case of a collision of pancreatic endocrine and exocrine tumors diagnosed preoperatively.

PMID: 32951175 [PubMed - as supplied by publisher]

Permalink for 'Letter regarding "Nonhypervascular pancreatic neuroendocrine tumors: Spectrum of MDCT imaging findings and differentiation from pancreatic ductal adenocarcinoma".'

Letter regarding "Nonhypervascular pancreatic neuroendocrine tumors: Spectrum of MDCT imaging findings and differentiation from pancreatic ductal adenocarcinoma".

Fetched: September 22nd, 2020, 5:01am GMT

Letter regarding "Nonhypervascular pancreatic neuroendocrine tumors: Spectrum of MDCT imaging findings and differentiation from pancreatic ductal adenocarcinoma".

Eur J Radiol. 2020 Sep 11;132:109282

Authors: Ren S, Wang Z

PMID: 32950797 [PubMed - as supplied by publisher]

Permalink for 'MicroRNA-139-5p modulates the growth and metastasis of malignant melanoma cells via the PI3K/AKT signaling pathway by binding to IGF1R.'

MicroRNA-139-5p modulates the growth and metastasis of malignant melanoma cells via the PI3K/AKT signaling pathway by binding to IGF1R.

Fetched: September 17th, 2020, 5:01am GMT

MicroRNA-139-5p modulates the growth and metastasis of malignant melanoma cells via the PI3K/AKT signaling pathway by binding to IGF1R.

Cell Cycle. 2019 Dec;18(24):3513-3524

Authors: Yang C, Xia Z, Zhu L, Li Y, Zheng Z, Liang J, Wu L

Abstract
The relation between microRNAs (miRNAs) and malignant melanoma has been demonstrated in previous studies, while there was little research about miR-139-5p and malignant melanoma. The aim of this study is to investigate the ability of miR-139-5p in malignant melanoma cells via the modulation of the PI3K/AKT signaling pathway by targeting IGF1R. MiR-139-5p expression in malignant melanoma tissues and 5 malignant melanoma cell lines was detected. The melanoma cells were transfected with miR-139-5p mimic negative control (NC) sequence, miR-139-5p mimic, IGF1R overexpressed recombinant plasmid NC or IGF1R overexpressed sequence. The expression of Akt signaling pathway-related protein was evaluated. The biological functions in malignant melanoma cells were evaluated by a string of experiments. MiR-139-5p expressed a poor level in tissues and cell lines of malignant melanoma. Overexpressed miR-139-5p suppressed the cell proliferation, migration, and invasion, and contributed to the promoted apoptosis of malignant melanoma cells by decreasing IGF1R. MiR-139-5p down-regulated the IGF1R expression, and IGF1R accelerated the activation of the PI3K/AKT signaling pathway. miR-139-5p reversed the promotive impacts of IGF1R on the PI3K/AKT signaling pathway. The study validates that miR-139-5p could suppress malignant melanoma progression through the repression of the PI3K/AKT signaling pathway by down-regulating IGF1R. Therefore, miR-139-5p could pave a new way for the treatment of malignant melanoma.

PMID: 31724454 [PubMed - indexed for MEDLINE]

Permalink for 'Appearance of cutaneous melanoma and subcutaneous metastases in metastatic gastric carcinoma undergoing chemotherapy with oral 5-fluorouracil prodrug.'

Appearance of cutaneous melanoma and subcutaneous metastases in metastatic gastric carcinoma undergoing chemotherapy with oral 5-fluorouracil prodrug.

Fetched: September 17th, 2020, 5:01am GMT

Appearance of cutaneous melanoma and subcutaneous metastases in metastatic gastric carcinoma undergoing chemotherapy with oral 5-fluorouracil prodrug.

Anticancer Drugs. 2019 11;30(10):1055-1057

Authors: De Giorgi V, Scarfì F, Trane L, Silvestri F, Maida P, Gori A, Covarelli P

Abstract
Metastatic skin lesions of gastric cancers usually appear as nonspecific, firm, and hyperpigmented nodules. However, they occasionally present as unusual skin manifestations that mimic other skin disorders. We describe a case of multiple cutaneous metastases from gastric cancer resembling sebaceous cysts with a synchronous melanoma, in a patient after fluoropyrimidine-based systemic chemotherapy. Melanoma occurring as a second cancer has been recognized in patients having undergone previous chemotherapy or radiation for another cancer. We can assume that the capecitabine-based chemotherapy may have played a role in the development of the melanocytic neoplasm. Our observation adds extra evidence to the link between fluoropyrimidine-based immunosuppression and the induction of melanocytes' proliferation and transformation. For these reasons, it is advisable to require dermatological checkups for patients undergoing chemotherapy treatments in order to identify suspicious melanocytic lesions as soon as possible.

PMID: 31609761 [PubMed - indexed for MEDLINE]

Overcoming the resistance to BRAF inhibitor by the double BRAF and MEK inhibitions in advanced melanoma: a case report.

Fetched: September 17th, 2020, 5:01am GMT

Overcoming the resistance to BRAF inhibitor by the double BRAF and MEK inhibitions in advanced melanoma: a case report.

Anticancer Drugs. 2019 11;30(10):1052-1054

Authors: Kattan J, Kattan C, Farhat F, Assi T

Abstract
The advent of BRAF and MEK inhibitors changed the landscape of the management of BRAF mutated melanoma patients. In this article, we report the case of a 51-year-old man with BRAF mutated locally advanced cutaneous melanoma of the head who demonstrated a limited response to initial anti-BRAF monotherapy followed by extensive surgery. Anti-PD1 therapy failed to reverse the disease progression. However, subsequent double inhibition of the BRAF and MEK pathways induced a fast and remarkable tumour response.

PMID: 31490286 [PubMed - indexed for MEDLINE]

Melanogenic inhibitory effects of Triangularin in B16F0 melanoma cells, in vitro and molecular docking studies.

Fetched: September 17th, 2020, 5:01am GMT

Melanogenic inhibitory effects of Triangularin in B16F0 melanoma cells, in vitro and molecular docking studies.

Bioorg Med Chem. 2019 08 15;27(16):3722-3728

Authors: Santi MD, Peralta MA, Puiatti M, Cabrera JL, Ortega MG

Abstract
The lack of secure therapies for hyperpigmentation disorders, without serious adverse effects, and the latest reports relating melanogenic disorders with development of neurodegenerative diseases, encourage the continuing search for new drugs for the treatment of such disorders. In this sense, the plant kingdom is an important source of bioactive natural products with great potential for the research and development of new therapeutics. The present study evaluated the anti-melanogenic activity of the natural methoxylated chalcone, 2',6'-dihydroxy-4'-methoxy-3'-methylchalcone (Triangularin, T), on diphenolase activity from mushroom tyrosinase and on murine B16F0 melanoma cell model. In addition, molecular modelling studies were carried out in order to understand the inhibitory activity observed. T showed a potent anti-melanogenic activity being more active than kojic acid (KA) on tyrosinase isolated of both sources and on intracellular tyrosinase. Molecular docking studies displayed important interactions between T and the active site of tyrosinase. Our results suggest that T may be useful for the treatment of hyperpigmentary disorders.

PMID: 31272835 [PubMed - indexed for MEDLINE]

Immunotherapy for cancer in people living with HIV: safety with an efficacy signal from the series in real life experience.

Fetched: September 17th, 2020, 5:01am GMT

Immunotherapy for cancer in people living with HIV: safety with an efficacy signal from the series in real life experience.

AIDS. 2019 09 01;33(11):F13-F19

Authors: Spano JP, Veyri M, Gobert A, Guihot A, Perré P, Kerjouan M, Brosseau S, Cloarec N, Montaudié H, Helissey C, Flament T, Gounant V, Lavolé A, Poizot-Martin I, Katlama C

Abstract
OBJECTIVE: To report efficacy and tolerance of nivolumab or pembrolizumab, PD-1 inhibitors, in people living with HIV (PLWHIV) and cancer.
DESIGN: Series of PLWHIV cancer patients treated with anti-PD1 agents in real-life clinical practice.
METHODS: From May 2014 to January 2019, 575 HIV-infected patients have been discussed in the French CANCERVIH national multidisciplinary board and included in the network database. Twenty-three patients were treated with immune checkpoint inhibitors in daily practice. We report the demographic characteristics, CD4 T-cell counts, HIV viral loads, safety and efficacy data of these 23 PLWHIV treated in routine practice with nivolumab or pembrolizumab for nonsmall cell lung cancer (n = 21), melanoma (n = 1) and head and neck cancer (n = 1) retrospectively collected from the database CANCERVIH network. The median CD4 T-cell count at treatment initiation was 370 cells/μl (IQR: 125-1485). HIV viral load was undetectable in all patients.
RESULTS: As of 29 April 2019, with a median follow-up of 10.8 months (2.0-27.7), the median number of injections was 6 (IQR: 4-18). Only two grade 3 adverse reactions were reported (no toxic deaths or immune-related deaths). Among the 23 patients, a partial response was observed in five patients (22%), a stabilization for five (22%) and a progression in 13 (57%). Only one patient experienced a positive HIV viral load, but this occurred following ART interruption.
CONCLUSION: Treatment with PD-1 inhibitors seems to have an efficacy signal and be well tolerated in PLWHIV, including impact on CD4 lymphocyte count and HIV load, that should be monitored during treatment course (regarding real-life experience).

PMID: 31259762 [PubMed - indexed for MEDLINE]

An unusual skin reaction in uveal melanoma during treatment with nivolumab: extragenital lichen sclerosus.

Fetched: September 17th, 2020, 5:01am GMT

An unusual skin reaction in uveal melanoma during treatment with nivolumab: extragenital lichen sclerosus.

Anticancer Drugs. 2019 10;30(9):969-972

Authors: Veronesi G, Scarfì F, Misciali C, Tartari F, Melotti B, Patrizi A, Dika E

Abstract
Antibodies directed against programmed death receptor 1 emerged as beneficial immune-checkpoint inhibitor therapy in many different types of cancer. However, programmed death receptor 1 is critical in promoting self-tolerance and the most common toxicities of checkpoint inhibitors are immune-related adverse events. We present a 48-year-old woman affected by metastatic uveal melanoma treated with nivolumab (3 mg/kg every 2 weeks). The patient had no previous history of autoimmune disease or dermatologic conditions. At the fourth month of treatment, on cutaneous examination, she presented multiple whitish vitiligo-like patches on the trunk, axillae, hands and face. Diagnosis of melanoma-associated leukoderma vitiliginous reaction was made. Over the following months, the melanoma-associated leukoderma lesions slowly progressed with cigarette paper-like appearance and indurated texture. A skin biopsy leaded the diagnosis of extragenital lichen sclerosus. To the best of our knowledge, this is the first reported case of extragenital lichen sclerosus on previous melanoma-associated leukoderma lesions related to nivolumab monotherapy. The increase in clinical experience with anti programmed death receptor 1 enhances the knowledge about adverse effects associated with these immunotherapies and allows to compare therapeutic strategies.

PMID: 31205068 [PubMed - indexed for MEDLINE]

Permalink for 'Simulation stress model of the undersea environment activates the central nervous, neuroendocrine and immune systems and anxiety in rats.'

Simulation stress model of the undersea environment activates the central nervous, neuroendocrine and immune systems and anxiety in rats.

Fetched: September 17th, 2020, 5:01am GMT

Simulation stress model of the undersea environment activates the central nervous, neuroendocrine and immune systems and anxiety in rats.

Undersea Hyperb Med. 2020 Third Quarter;47(3):445-453

Authors: Tang Y, Zou YX, Fan W, Chen SH, Fang YQ, Liu LN, Sun Y, Giao Y

Abstract
The present study was designed to assess the stress responses to a simulation model of the undersea environment that is similar to some undersea working conditions such as submarine rescue, underwater salvage and underwater construction. Restraint, hyperbaric air and immersion were chosen to produce the simulation stress model in rats for four hours. Rats were randomized into five groups: control group, restraint (R) group, hyperbaric air (H) group, restraint plus hyperbaric air (RH) group, and restraint plus hyperbaric air plus immersion (RHI) group. The results showed that the responses to the simulation stress model of the undersea environment induced by R, H, RH and RHI involved the upregulated norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) of the central nervous system (CNS), upregulated adrenocorticotropic hormone (ACTH), corticosterone (CORT) and blood glucose of the neuroendocrine system, upregulated interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) of the immune system, and increased anxiety in rats. Compared with hyperbaric air, restraint tended to activate stronger stress responses. Conclusively, this work established a simulation stress model of the undersea environment induced by restraint, hyperbaric air and immersion. It further provided experimental data of such a model that showed significant activation of the CNS, neuroendocrine and immune systems and anxiety in rats. In this experiment we provided an experimental basis for undersea work such as working aboard a submarine.

PMID: 32931671 [PubMed - in process]

Three pathologies in one: band adhesion strangulating neuroendocrine tumour-containing Meckel's diverticulum.

Fetched: September 17th, 2020, 5:01am GMT

Three pathologies in one: band adhesion strangulating neuroendocrine tumour-containing Meckel's diverticulum.

ANZ J Surg. 2020 Sep 15;:

Authors: Ma JLG, Jayasekera H, Pilgrim C

PMID: 32931617 [PubMed - as supplied by publisher]

Driver mutations occur frequently in metastases of well-differentiated small intestinal neuroendocrine tumours.

Fetched: September 17th, 2020, 5:01am GMT

Driver mutations occur frequently in metastases of well-differentiated small intestinal neuroendocrine tumours.

Histopathology. 2020 Sep 15;:

Authors: Samsom KG, Levy S, van Veenendaal LM, Roepman P, Kodach LL, Steeghs N, Valk GD, Dercksen MW, Kuhlmann KFD, Verbeek WHM, Meijer GA, Tesselaar MET, van den Berg JG

Abstract
AIMS: This study aims to investigate the clinicopathological significance of driver mutations in metastatic well-differentiated SI-NETs METHODS AND RESULTS: Whole genome sequencing (WGS) of 35 and next generation sequencing (NGS) of 8 metastatic SI-NETs was performed. Biopsies were obtained between 2015 and 2019. Tumours were classified using the 2019 WHO classification. WGS included assessment of somatic mutations in all cancer related driver genes, tumour mutational burden (TMB) and microsatellite status. NGS entailed a cancer hotspot panel of 58 genes. Our cohort consisted of 21% G1, 60% G2 and 19% G3 SI-NETs. Driver mutations were identified in approximately 50% of SI-NETs. In total 27 driver mutations were identified, of which 74% in tumour suppressor genes (e.g. TP53, RB1, CDKN1B) and 22% in proto-oncogenes (e.g. KRAS, NRAS, MET). Allelic loss of chromosome 18 (63%), complete loss of CDKN2A and CDKN1B (both 6%) and CDKN1B mutations (9%) were most common. Potential targetable genetic alterations were detected in 21% of metastasized SI-NETs. All tumours were microsatellite stable and showed low TMB (median 1.10, IQR 0.87-1.35). Ki67 proliferation index was significantly associated with the presence of driver mutations (p=0.015).
CONCLUSION: Driver mutations occur in 50% of metastasized SI-NETs and their presence is associated with high Ki67 proliferation index. The identification of targetable mutations render these patients potentially eligible for targeted therapy.

PMID: 32931025 [PubMed - as supplied by publisher]

Permalink for 'ASSOCIATION BETWEEN OBJECTIVE RESPONSE RATE AND OVERALL SURVIVAL IN METASTATIC NEUROENDOCRINE TUMORS TREATED WITH RADIOEMBOLIZATION: A SYSTEMATIC LITERATURE REVIEW AND REGRESSION ANALYSIS.'

ASSOCIATION BETWEEN OBJECTIVE RESPONSE RATE AND OVERALL SURVIVAL IN METASTATIC NEUROENDOCRINE TUMORS TREATED WITH RADIOEMBOLIZATION: A SYSTEMATIC LITERATURE REVIEW AND REGRESSION ANALYSIS.

Fetched: September 17th, 2020, 5:01am GMT

ASSOCIATION BETWEEN OBJECTIVE RESPONSE RATE AND OVERALL SURVIVAL IN METASTATIC NEUROENDOCRINE TUMORS TREATED WITH RADIOEMBOLIZATION: A SYSTEMATIC LITERATURE REVIEW AND REGRESSION ANALYSIS.

Expert Rev Anticancer Ther. 2020 Sep 15;:

Authors: Pollock RF, Brennan VK, Peters R, Paprottka PM

Abstract
OBJECTIVES Neuroendocrine tumors (NETs) are a heterogeneous group of cancers arising from neuroendocrine cells. The aim was to model objective response rate (ORR) as a predictor of overall survival (OS) in patients with metastatic NETs (mNETs) treated with radioembolization (RE). METHODS Randomized controlled trials and observational studies of RE treatment of mNETs were identified by systematic literature review (SLR). Pooled ORR and OS estimates were calculated and a weighted generalized linear model (GLM) of ORR as a predictor of OS was derived, stratified by ORR assessment criteria and RE type (Yttrium-90 resin or glass microspheres). RESULTS The SLR identified 32 observational studies. Mean ORR was 41% (95% confidence interval 38-45%). The Yttrium-90 resin and glass microspheres GLMs accounted for 59% and 57% of OS deviance, respectively. ORR was a significant predictor of OS in the resin microspheres model (p<0.001), but not the glass microspheres model (p=0.11). CONCLUSIONS A weighted GLM showed a significant relationship between ORR and OS in patients with mNETs treated with Yttrium-90 resin microspheres. ORR could therefore potentially be used as an OS surrogate in future trials of Yttrium-90 resin microspheres. Further research is needed to confirm the relationship between ORR and OS and the difference between resin and glass microspheres.

PMID: 32930618 [PubMed - as supplied by publisher]

Permalink for 'One decade of 'Bench-to-Bedside' peptide receptor radionuclide therapy with indigenous [177Lu]Lu-DOTATATE obtained through 'Direct' neutron activation route: lessons learnt including practice evolution in an Indian setting.'

One decade of 'Bench-to-Bedside' peptide receptor radionuclide therapy with indigenous [177Lu]Lu-DOTATATE obtained through 'Direct' neutron activation route: lessons learnt including practice evolution in an Indian setting.

Fetched: September 17th, 2020, 5:01am GMT

One decade of 'Bench-to-Bedside' peptide receptor radionuclide therapy with indigenous [177Lu]Lu-DOTATATE obtained through 'Direct' neutron activation route: lessons learnt including practice evolution in an Indian setting.

Am J Nucl Med Mol Imaging. 2020;10(4):178-211

Authors: Basu S, Chakraborty S, Parghane RV, Kamaldeep, Ranade R, Thapa P, Asopa RV, Sonawane G, Nabar S, Shimpi H, Chandak A, Vimalnath KV, Ostwal V, Ramaswamy A, Bhandare M, Chaudhari V, Shrikhande SV, Sirohi B, Dash A, Banerjee S

Abstract
The present treatise chronicles one decade of experience pertaining to clinical PRRT services in a large-volume tertiary cancer care centre in India delivering over 4,000 therapies, an exemplar of successful PRRT programme employing indigenous 177Lutetium production and resources. For the purpose of systematic discussion, we have sub-divided the communication into 3 specific parts: (a) Radiopharmaceutical aspects that describes 177Lutetium production through 'Direct' Neutron Activation Route and the subsequent radiolabeling procedures, (b) The specific clinical nuances and finer learning points (apart from the routine standard procedure) based upon clinical experience and how it has undergone practice evolution in our setting and (c) Dosimetry results with this indigenous product and radiation safety/health physics aspects involved in PRRT services. Initiated in 2010 at our centre, the PRRT programme is a perfect example of affordable quality health care delivery, with indigenous production of the radionuclide (177Lu) in the reactor and subsequent radiolabeling of the radiopharmaceutical ([177Lu]Lu-DOTATATE) at the hospital radiopharmacy unit of the centre, which enabled catering to the needs of a large number of patients of progressive, metastatic and advanced Neuroendocrine Neoplasms (NENs) and related malignancies.

PMID: 32929396 [PubMed]

Permalink for 'Interesting case of an abdominal wall Merkel cell carcinoma highlighting the importance of developing an Australian clinical practice guideline.'

Interesting case of an abdominal wall Merkel cell carcinoma highlighting the importance of developing an Australian clinical practice guideline.

Fetched: September 17th, 2020, 5:01am GMT

Interesting case of an abdominal wall Merkel cell carcinoma highlighting the importance of developing an Australian clinical practice guideline.

BMJ Case Rep. 2020 Sep 13;13(9):

Authors: Nassour AJ, Ashrafi D, Lah K, Sivananthan S

Abstract
A 66-year-old Australian male farmer was referred for management of an asymptomatic, rapidly expanding, anterior abdominal wall mass. It was firm and well circumscribed. There were no overlying skin changes, constitutional symptoms or weight loss. His medical history included small bowel obstruction and resection from a Meckel's diverticulitis and a 40-pack-year smoking history. Core biopsy was suggestive of a neuroendocrine tumour and Gallium-68-Dodecane-Tetraacetic-Acid (68GaTate) positron emission tomography revealed an avid solitary lesion confined to the subcutaneous space in the left anterior abdominal wall. Wide local excision was performed, and histopathology revealed Merkel cell carcinoma (MCC). Although classically regarded as a primary cutaneous neuroendocrine tumour, MCC may originate from the subcutaneous fat without obvious skin involvement. Older patients with asymptomatic, rapidly enlarging lesions, particularly if immunosuppressed, with significant ultraviolet sunlight exposure, should raise a high index of suspicion for MCC. Like melanoma, non-metastatic MCC should be treated aggressively for best prognosis.

PMID: 32928821 [PubMed - in process]

Permalink for 'Isolation and Characterization of Two Novel Colorectal Cancer Cell Lines, Containing a Subpopulation with Potential Stem-Like Properties: Treatment Options by MYC/NMYC Inhibition.'

Isolation and Characterization of Two Novel Colorectal Cancer Cell Lines, Containing a Subpopulation with Potential Stem-Like Properties: Treatment Options by MYC/NMYC Inhibition.

Fetched: September 17th, 2020, 5:01am GMT

Isolation and Characterization of Two Novel Colorectal Cancer Cell Lines, Containing a Subpopulation with Potential Stem-Like Properties: Treatment Options by MYC/NMYC Inhibition.

Cancers (Basel). 2020 Sep 10;12(9):

Authors: Schulte Am Esch JSA, Windmöller BA, Hanewinkel J, Storm J, Förster C, Wilkens L, Krüger M, Kaltschmidt B, Kaltschmidt C

Abstract
Cancer stem cells (CSC) are crucial mediators of cancer relapse. Here, we isolated two primary human colorectal cancer cell lines derived from a rectal neuroendocrine carcinoma (BKZ-2) and a colorectal adenocarcinoma (BKZ-3), both containing subpopulations with potential stem-like properties. Protein expression of CSC-markers prominin-1 and CD44 antigen was significantly higher for BKZ-2 and BKZ-3 in comparison to well-established colon carcinoma cell lines. High sphere-formation capacity further confirmed the existence of a subpopulation with potential stem-like phenotype. Epithelial-mesenchymal transition markers as well as immune checkpoint ligands were expressed more pronounced in BKZ-2. Both cell populations demonstrated N-myc proto-oncogene (NMYC) copy number gain. Myc proto-oncogene (MYC)/NMYC activity inhibitor all-trans retinoic acid (ATRA) significantly reduced the number of tumor spheres for both and the volume of BKZ-2 spheres. In contrast, the sphere volume of ATRA-treated BKZ-3 was increased, and only BKZ-2 cell proliferation was reduced in monolayer culture. Treatment with KJ-Pyr-9, a specific inhibitor of MYC/NMYC-myc-associated factor X interaction, decreased survival by the induction of apoptosis of both. In summary, here, we present the novel colorectal cancer cell lines BKZ-2 and BKZ-3 as promising cellular in vitro models for colorectal carcinomas and identify the MYC/NMYC molecular pathway involved in CSC-induced carcinogenesis with relevant therapeutic potential.

PMID: 32927768 [PubMed]

Combined microscope and endoscopy total resection of primary pineal malignant melanoma: case report and literature review.

Fetched: September 17th, 2020, 5:01am GMT

Combined microscope and endoscopy total resection of primary pineal malignant melanoma: case report and literature review.

J Cancer Res Clin Oncol. 2020 Oct;146(10):2589-2594

Authors: Zhang J, Xiong Z, Chen J

Abstract
BACKGROUND: Primary pineal malignant melanoma (PPMM) is a rare entity of primary central nervous system melanomas, with only 26 cases reported in the literature to date.
CASE PRESENTATION: We report the case of a 65-year-old male with a PPMM who has prolonged survival of more than 104 weeks after combined microsurgical and endoscopic total resection. This is the first report: combined microscope and endoscopy total resection; PPMM in China; PPMM with total resection alone.
CONCLUSION: Combined microscope and endoscopy total resection is beneficial to prolong the survival of patients. But the best approach to treatment needs verification from more clinical cases in future.

PMID: 32700108 [PubMed - indexed for MEDLINE]

"How We Do It" - A Practical Approach to Percutaneous Adrenal Ablation Techniques.

Fetched: September 17th, 2020, 5:01am GMT

"How We Do It" - A Practical Approach to Percutaneous Adrenal Ablation Techniques.

Tech Vasc Interv Radiol. 2020 Jun;23(2):100676

Authors: Manchec B, Koethe Y, Schiro B, Peña C, Gandhi R

Abstract
Incidental adrenal masses are common and are found in 4% of the CT scans.1 While clinical history, laboratory results, and imaging characteristics are typically sufficient for diagnosis of an adrenal lesion, a biopsy is sometimes warranted. In some cases, adrenal mass ablation is subsequently indicated. This article serves as a brief but comprehensive review of preprocedural work-up and planning before an adrenal mass ablation, as well as a discussion on ablation techniques, associated challenges and solutions, and management of expected and unexpected outcomes.

PMID: 32591192 [PubMed - indexed for MEDLINE]

Melanoma of unknown primary in the pancreas: should it be considered primary?

Fetched: September 17th, 2020, 5:01am GMT

Melanoma of unknown primary in the pancreas: should it be considered primary?

BMC Surg. 2020 Apr 16;20(1):76

Authors: Jin Y, Ran C, Li F, Cheng N

Abstract
BACKGROUND: Malignant melanoma is characterized as highly malignant due to its rapid growth and early metastasis. Metastatic melanoma from occult primary is rare. Melanoma of unknown primary in pancreas are even rear. But it is a biologically ill-defined and clinically understudied concept.
CASE PRESENTATION: In this report, a 43-year-old man was diagnosed with pancreatic carcinoma. Extended total pancreatectomy together with portal vein reconstruction and extensive lymphadenectomy were performed in our hospital. The patient was diagnosed with pancreatic malignant melanoma after pathological examination. He was still alive 20 months after the operation without any evidence of recurrence.
CONCLUSION: The described case highlights the possibility of primary pancreatic malignant melanoma and the treatment strategies of this rare carcinoma.

PMID: 32299408 [PubMed - indexed for MEDLINE]

Sentinel node tumor burden in prediction of prognosis in melanoma patients.

Fetched: September 17th, 2020, 5:01am GMT

Sentinel node tumor burden in prediction of prognosis in melanoma patients.

Clin Exp Metastasis. 2020 04;37(2):365-376

Authors: Palve J, Ylitalo L, Luukkaala T, Jernman J, Korhonen N

Abstract
Recent data have demonstrated no survival benefit to immediate completion lymph node dissection (CLND) for positive sentinel node (SN) disease in melanoma. It is important to identify parameters in positive SNs, which predict prognosis in melanoma patients. These might provide prognostic value in staging systems and risk models by guiding high-risk patients' adjuvant therapy in clinical practice. In this retrospective study of university hospital melanoma database we analyzed tumor burden and prognosis in patients with positive SNs. Patients were stratified by the diameter of tumor deposit, distribution of metastatic focus in SN, ulceration and number of metastatic SNs. These were incorporated in Cox proportional hazard regression models. Predictive ability was assessed using Akaike information criterion and Harrell's concordance index. A total of 110 patients had positive SN and 104 underwent CLND. Twenty-two (21%) patients had non-SN metastatic disease on CLND. The 5-year melanoma specific survival for CLND-negative patients was 5.00 years (IQR 3.23-5.00, range 0.72-5.00) compared to 3.69 (IQR 2.28-4.72, range 1.01-5.00) years in CLND-positive patients (HR 2.82 (95% CI 1.17-6.76, p = 0.020).The models incorporating distribution of metastatic focus and the largest tumor deposit in SN had highest predictive ability. According to Cox proportional hazard regression models, information criterions and c-index, the diameter of tumor deposit > 4 mm with multifocal location in SN despite of number of metastatic SN were the most important parameters. According to the diameter of tumor deposit and distribution of metastatic focus in SN, adequate stratification of positive SN patients was possible and risk classes for patients were identified.

PMID: 32076905 [PubMed - indexed for MEDLINE]

Permalink for 'Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study.'

Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study.

Fetched: September 15th, 2020, 5:00am GMT

Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study.

Lancet Oncol. 2020 Sep 10;:

Authors: Marabelle A, Fakih M, Lopez J, Shah M, Shapira-Frommer R, Nakagawa K, Chung HC, Kindler HL, Lopez-Martin JA, Miller WH, Italiano A, Kao S, Piha-Paul SA, Delord JP, McWilliams RR, Fabrizio DA, Aurora-Garg D, Xu L, Jin F, Norwood K, Bang YJ

Abstract
BACKGROUND: Tumour mutational burden (TMB) has been retrospectively correlated with response to immune checkpoint blockade. We prospectively explored the association of high tissue TMB (tTMB-high) with outcomes in ten tumour-type-specific cohorts from the phase 2 KEYNOTE-158 study, which assessed the anti-PD-1 monoclonal antibody pembrolizumab in patients with selected, previously treated, advanced solid tumours.
METHODS: In the multi-cohort, open-label, non-randomised, phase 2 KEYNOTE-158 study, patients were enrolled from 81 academic facilities and community-based institutions across 21 countries in Africa, the Americas, Asia, and Europe. Eligible patients were aged 18 years or older, had a histologically or cytologically confirmed advanced (ie, unresectable or metastatic, or both) incurable solid tumour (eligible tumour types were anal, biliary, cervical, endometrial, mesothelioma, neuroendocrine, salivary, small-cell lung, thyroid, and vulvar), progression on or intolerance to one or more lines of standard therapy, had measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1) assessed by independent central radiological review, Eastern Cooperative Oncology Group performance status of 0 or 1, life expectancy of at least 3 months, adequate organ function, and a tumour sample for biomarker analysis. Participants were given pembrolizumab 200 mg intravenously every 3 weeks for up to 35 cycles. Tissue TMB (tTMB) was assessed in formalin-fixed paraffin-embedded tumour samples using the FoundationOne CDx assay (Foundation Medicine, Cambridge, MA, USA). The prespecified definition of tTMB-high status was at least 10 mutations per megabase. The primary endpoint was the proportion of patients with an objective response (complete or partial response) as per Response Evaluation Criteria in Solid Tumours (version 1.1) by independent central review. This prespecified analysis assessed the association between antitumour activity and tTMB in treated patients with evaluable tTMB data. Efficacy was assessed in all participants who received at least one dose of pembrolizumab, had evaluable tTMB data, and were enrolled at least 26 weeks before data cutoff (June 27, 2019), and safety was assessed in all participants who received at least one dose of pembrolizumab and had tTMB-high status. KEYNOTE-158 is registered at ClinicalTrials.gov, NCT02628067, and is ongoing.
FINDINGS: Between Jan 15, 2016, and June 25, 2019, 1073 patients were enrolled. 1066 participants were treated as of data cutoff (June 27, 2019), of whom 805 (76%) were evaluable for TMB, and 105 (13%) of 805 had tTMB-high status and were assessed for safety. 1050 (98%) of 1066 patients enrolled by at least 26 weeks before data cutoff, of whom 790 (75%) were evaluable for TMB and included in efficacy analyses. 102 (13%) of these 790 patients had tTMB-high status (≥10 mutations per megabase), and 688 (87%) patients had non-tTMB-high status (<10 mutations per megabase). Median study follow-up was 37·1 months (IQR 35·0-38·3). Objective responses were observed in 30 (29%; 95% CI 21-39) of 102 patients in the tTMB-high group and 43 (6%; 5-8) of 688 in the non-tTMB-high group. 11 (10%) of 105 patients had treatment-related serious adverse events. 16 (15%) participants had a grade 3-5 treatment-related adverse event, of which colitis was the only such adverse event that occurred in more than one patient (n=2). One patient had fatal pneumonia that was assessed by the investigator to be treatment related.
INTERPRETATION: tTMB-high status identifies a subgroup of patients who could have a robust tumour response to pembrolizumab monotherapy. tTMB could be a novel and useful predictive biomarker for response to pembrolizumab monotherapy in patients with previously treated recurrent or metastatic advanced solid tumours.
FUNDING: Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc.

PMID: 32919526 [PubMed - as supplied by publisher]

Risk Factors in Pancreatic Adenocarcinoma: the Interrelation with Familial History and Predictive Role on Survival.

Fetched: September 14th, 2020, 5:01am GMT

Risk Factors in Pancreatic Adenocarcinoma: the Interrelation with Familial History and Predictive Role on Survival.

J Gastrointestin Liver Dis. 2020 Sep 09;29(3):391-398

Authors: Petrusel L, Bilibou M, Drug V, Leucuta DC, Seicean R, Cainap C, Seicean A

Abstract
BACKGROUND AND AIMS: Pancreatic cancer is associated with poor survival and quality of life. In Romania the prognostic influence of known risk factors for pancreatic adenocarcinoma, such as age, smoking, chronic pancreatitis, diabetes mellitus, and obesity is little known. Their importance in developing cancer in families with a history of adenocarcinoma is less studied. This study aims to assess the risk factors in pancreatic ductal adenocarcinoma, in familial pancreatic adenocarcinoma, in neuroendocrine tumors and to evaluate their predictive role on survival.
METHODS: We performed a prospective bicentric study of patients with pancreatic tumors detected in transabdominal imaging; we assessed the risk factors and their possible association with survival.
RESULTS: 312 pancreatic cancer patients (279 with pancreatic ductal adenocarcinoma and 24 patients with neuroendocrine tumors, and nine patients with other malignant types) and 312 controls were included. The median body mass index was significantly higher in patients with neuroendocrine tumors. Positive family history for pancreatic cancer was found in 4% of patients with pancreatic cancer. The risk for familial pancreatic carcinoma was associated with the presence of new-onset diabetes (OR: 4.64, p=0.018). The multivariate logistic analysis suggested that advanced age (OR: 1.67), smoking (OR: 1.67), low body mass index (OR: 12.07), and diabetes (OR: 3.91) were risk factors for pancreatic cancer. The overall survival analysis after adjustment for age and tumor stage showed only advanced tumoral stage (HR=1.6, p=0.003) and metastasis as independent predicting factors (HR=1.67, p<0.001).
CONCLUSION: Our study suggests that diabetes, smoking, underweight, and age over 60 years are risk factors for pancreatic cancer. Patients with a family history of pancreatic cancer, especially those with new-onset diabetes, should be followed carefully and considered for screening. Only an advanced tumor stage was associated with poor overall survival for patients with pancreatic ductal adenocarcinoma.

PMID: 32919422 [PubMed - as supplied by publisher]

Primary glomus tumour of the pituitary gland: diagnostic challenges of a rare and potentially aggressive neoplasm.

Fetched: September 14th, 2020, 5:01am GMT

Primary glomus tumour of the pituitary gland: diagnostic challenges of a rare and potentially aggressive neoplasm.

Virchows Arch. 2020 Sep 12;:

Authors: Quah BL, Donofrio CA, La Rosa S, Brouland JP, Cossu G, Djoukhadar I, Mayers H, Shenjere P, Pereira M, Pathmanaban ON, Murtaza MO, Gattamaneni R, Roncaroli F, Karabatsou K

Abstract
Primary non-neuroendocrine tumours of the pituitary gland and sella are rare lesions often challenging to diagnose. We describe two cases of clinically aggressive primary glomus tumour of the pituitary gland. The lesions occurred in a 63-year-old male and a 30-year-old female who presented with headache, blurred vision and hypopituitarism. Neuroimaging demonstrated large sellar and suprasellar tumours invading the surrounding structures. Histologically, the lesions were characterised by angiocentric sheets and nests of atypical cells that expressed vimentin, smooth muscle actin and CD34. Perivascular deposition of collagen IV was also a feature. Case 2 expressed synaptophysin. INI-1 (SMARCB1) expression was preserved. Both lesions were mitotically active and demonstrated a Ki-67 labelling index of 30%. Next-generation sequencing performed in case 1 showed no mutations in the reading frame of 37 commonly mutated oncogenes, including BRAF and KRAS. Four pituitary glomus tumours have previously been reported, none of which showed features of malignant glomus tumour. Similar to our two patients, three previous examples displayed aggressive behaviour.

PMID: 32918169 [PubMed - as supplied by publisher]

Home parenteral nutrition in neuroendocrine tumour intestinal failure: improved quality of life and longevity.

Fetched: September 14th, 2020, 5:01am GMT

Home parenteral nutrition in neuroendocrine tumour intestinal failure: improved quality of life and longevity.

BMJ Support Palliat Care. 2020 Sep 11;:

Authors: Sagar VM, Shah T, Malhi H, Parkinson S, Shetty S, Cooper SC

Abstract
BACKGROUND: Neuroendocrine tumours (NETs) are neoplastic yet behave differently to typical cancers. Despite often being slow growing, they can lead to significant gastrointestinal complications including intestinal failure (IF). The use of home parenteral nutrition (HPN) in neoplastic conditions is rising, primarily for palliation and bridging through treatments for cancer, but remains a challenging decision with a paucity of high-grade evidence-based guidance.
METHODS: A retrospective analysis of patients with NET on HPN was performed. Data collected included the cause of IF, complications encountered with HPN and changes in nutritional assessments.
RESULTS: Eight patients were identified, all with metastatic NET. Median weight improved following HPN commencement and line sepsis was the sole complication. All patients had stabilisation and optimisation of nutritional and hydration status.
CONCLUSIONS: HPN is commenced to improve or maintain patients' nutritional status during often lifelong treatment. The principle aim in providing HPN was to improve survival and quality of life. While NETs are cancers, our case series demonstrates the potential of HPN to actively support longer term survival in the subgroup of patients who develop IF.

PMID: 32917652 [PubMed - as supplied by publisher]

Permalink for 'Efficacy of mistletoe extract as a complement to standard treatment in advanced pancreatic cancer: study protocol for a multicentre, parallel group, double-blind, randomised, placebo-controlled clinical trial (MISTRAL).'

Efficacy of mistletoe extract as a complement to standard treatment in advanced pancreatic cancer: study protocol for a multicentre, parallel group, double-blind, randomised, placebo-controlled clinical trial (MISTRAL).

Fetched: September 14th, 2020, 5:01am GMT

Efficacy of mistletoe extract as a complement to standard treatment in advanced pancreatic cancer: study protocol for a multicentre, parallel group, double-blind, randomised, placebo-controlled clinical trial (MISTRAL).

Trials. 2020 Sep 11;21(1):783

Authors: Wode K, Hök Nordberg J, Kienle GS, Elander NO, Bernhardson BM, Sunde B, Sharp L, Henriksson R, Fransson P

Abstract
BACKGROUND: Most pancreatic cancer patients present with advanced stage at diagnosis with extremely short expected survival and few treatment options. A multimodal palliative approach is necessary for symptom relief and optimisation of health-related quality of life. In a recent open-label trial of mistletoe extract for advanced pancreatic cancer patients not eligible for chemotherapy, promising results on improved overall survival and better health-related quality of life were reported. The objective of the present study is to assess the value of mistletoe extract as a complement to standard treatment (palliative chemotherapy or best supportive care) in advanced pancreatic cancer patients with regard to overall survival and health-related quality of life.
METHODS: The trial is prospective, randomised, double-blind, multicentre, parallel group and placebo-controlled. In total, 290 participants are randomly assigned to placebo or mistletoe extract given subcutaneously in increasing dosage from 0.01 to 20 mg three times per week for 9 months. Stratification is performed for site and palliative chemotherapy. Main inclusion criteria are advanced pancreatic cancer and Eastern Cooperative Oncology Group performance status 0 to 2; main exclusion criteria are life expectancy less than 4 weeks and neuroendocrine tumour of the pancreas. Two ancillary studies on sub-sets of participants are nested in the trial: a biomarker study collecting blood samples and a cross-sectional qualitative study with semi-structured face-to-face interviews.
DISCUSSION: To our knowledge, this is the first placebo-controlled randomised trial assessing the impact of mistletoe extract as a complement to standard treatment on overall survival and health-related quality of life in patients with advanced pancreatic cancer. The presented trial with its two nested ancillary studies exploring biomarkers and patient experiences is expected to give new insights into the treatment of advanced pancreatic cancer.
TRIAL REGISTRATION: EU Clinical Trial Register, EudraCT Number 2014-004552-64 . Registered on 19 January 2016. ClinicalTrials.gov NCT02948309 . Registered on 28 October 2016.

PMID: 32917288 [PubMed - as supplied by publisher]

Permalink for 'Clinicopathological heterogeneity between primary and metastatic sites of gastroenteropancreatic neuroendocrine neoplasm.'

Clinicopathological heterogeneity between primary and metastatic sites of gastroenteropancreatic neuroendocrine neoplasm.

Fetched: September 14th, 2020, 5:01am GMT

Clinicopathological heterogeneity between primary and metastatic sites of gastroenteropancreatic neuroendocrine neoplasm.

Diagn Pathol. 2020 Sep 11;15(1):108

Authors: Shi H, Jiang C, Zhang Q, Qi C, Yao H, Lin R

Abstract
BACKGROUND: Chromogranin A (CgA), synaptophysin (Syn) and the Ki-67 index play significant roles in diagnosis or the evaluation of the proliferative activity of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). However, little is known about whether these biological markers change during tumor metastasis and whether such changes have effect on prognosis.
METHODS: We analyzed 35 specimens of both primary and metastatic tumor from 779 patients who had been diagnosed as GEP-NENs at Wuhan Union Hospital from August 2011 to October 2019. The heterogeneity of CgA, Syn and Ki-67 index was evaluated by immunohistochemical analysis.
RESULTS: Among these 779 patients, the three most common sites of NENs in the digestive tract were the pancreas, rectum and stomach. Metastases were found in 311 (39.9%) patients. Among the 35 patients with both primary and metastatic pathological specimens, differences in the Ki-67 level were detected in 54.3% of the patients, while 37.1% showed a difference in CgA and only 11.4% showed a difference in Syn. Importantly, due to the difference in the Ki-67 index between primary and metastatic lesions, the WHO grade was changed in 8.6% of the patients. In addition, a Kaplan-Meier survival analysis showed that patients with Ki-67 index variation had a shorter overall survival (p = 0.0346), while neither Syn variation nor CgA variation was related to patient survival (p = 0.7194, p = 0.4829).
CONCLUSIONS: Our data indicate that primary and metastatic sites of GEP-NENs may exhibit pathological heterogeneity. Ki-67 index variation is closely related to the poor prognosis of patients with tumor metastasis, but neither Syn variation nor CgA variation is related to patient prognosis. Therefore, clinicopathologic evaluation of the primary tumor and metastatic sites could be helpful for predicting the prognosis.

PMID: 32917216 [PubMed - as supplied by publisher]

Clinicopathological Features of Gastroenteropancreatic Neuroendocrine Neoplasms.

Fetched: September 9th, 2020, 5:01am GMT

Clinicopathological Features of Gastroenteropancreatic Neuroendocrine Neoplasms.

J Coll Physicians Surg Pak. 2020 Aug;30(8):863-867

Authors: Sekerci A, Turk HM, Demir T, Seker M, Akcakaya A, Arici DS

Abstract
ABSTRACT Objective: To describe the clinical, pathological and survival characteristics of Turkish patients with gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs).
STUDY DESIGN: Descriptive study.
PLACE AND DURATION OF STUDY: Bezmialem Vakif University School of Medicine Hospital from April 2012 to September 2018.
METHODOLOGY: Sixty-one patients with GEP-NENs were analysed in retrospect for the clinical, pathological and survival characteristics. The Kaplan-Meier method was used for survival analysis and the Log-rank test was performed to analyse the comparisons between the groups.
RESULTS: Forty-five of the 61 GEP-NENs patients (73.8%) were neuroendocrine tumor (NET) and 26.2% of patients were neuroendocrine carcinoma (NEC). The mean age of patients was 55.5 ± 11.3 years. The most frequent localisation of tumors was stomach (34.4%), and the most common symptom was abdominal pain (27.9%). The rate of distant metastases was 31.1% at diagnosis and 63.9% of the patients were operated. The median follow-up period was 27 months. The rate of three-years overall survival (OS) was 88.5% and the five-years OS rate was 86.9%. The variables that can significantly influence the OS rate were high grade (grade 3; p= 0.005), Ki-67 proliferation index (Ki-67 >20%; p= 0.002) and distant metastases (p= 0.018).
CONCLUSION: GEP-NENs may develop anywhere in the digestive tract. Approximately one-third of the patients may be metastatic due to delay in diagnosis. Key Words: Gastroenteropancreatic neuroendocrine tumor, Neuroendocrine cancers, Neuroendocrine neoplasms.

PMID: 32893801 [PubMed - in process]

[Gastric signet ring cell neuroendocrine tumor: report of a case].

Fetched: September 9th, 2020, 5:01am GMT

[Gastric signet ring cell neuroendocrine tumor: report of a case].

Zhonghua Bing Li Xue Za Zhi. 2020 Sep 08;49(9):941-943

Authors: Xu C, Li HX, Zhu Y, Pan BJ, Zhang ZH

PMID: 32892564 [PubMed - in process]

A tool to predict survival in stage IV entero-pancreatic NEN.

Fetched: September 9th, 2020, 5:01am GMT

A tool to predict survival in stage IV entero-pancreatic NEN.

J Endocrinol Invest. 2020 Sep 06;:

Authors: Tarquini M, Ambrosio MR, Albertelli M, de Souza PB, Gafà R, Gagliardi I, Carnevale A, Franceschetti P, Zatelli MC

Abstract
PURPOSE: Well-differentiated stage IV neuroendocrine neoplasms (NEN) have an extremely heterogeneous, unpredictable clinical behavior. Survival prognostic markers, such as the recently proposed NEP-Score, would be very useful for better defining therapeutic strategies. We aim to verify NEP-Score applicability in an independent cohort of stage IV well-differentiated (WD) gastroentero-pancreatic (GEP) NEN, and identify a derivate prognostic marker taking into account clinical and pathological characteristics at diagnosis.
METHODS: Age, site of primary tumor, primary tumor surgery, symptoms, Ki67, timing of metastases of 27 patients (10 females; mean age at diagnosis 60.2 ± 2.9 years) with stage IV WD GEP NEN were evaluated to calculate the NEP-Score at the end of follow-up (NEP-T). We calculated the NEP-Score at diagnosis (NEP-D), which does not consider the appearance of new metastases during follow-up. Patients were subdivided according to whether they were alive or not at the end of follow-up (EOF) and an NEP-Score threshold was investigated to predict survival.
RESULTS: Mean NEP-T and mean NEP-D were significantly lower in 15 live patients as compared to 12 deceased patients (p < 0.01) at EOF. We identified an NEP-D = 116 as the cutoff that significantly predicts survival. No gender differences were identified.
CONCLUSIONS: In our series, we confirmed NEP-Score applicability. In addition, we propose NEP-D as a simple, quick and cheap prognostic score that can help clinicians in decision making. NEP-D threshold can predict NEN aggressiveness and may be used to define the best personalized therapeutic strategy.

PMID: 32892316 [PubMed - as supplied by publisher]

The immunohistochemical, DNA methylation, and chromosomal copy number profile of cauda equina paraganglioma is distinct from extra-spinal paraganglioma.

Fetched: September 9th, 2020, 5:01am GMT

The immunohistochemical, DNA methylation, and chromosomal copy number profile of cauda equina paraganglioma is distinct from extra-spinal paraganglioma.

Acta Neuropathol. 2020 Sep 06;:

Authors: Ramani B, Gupta R, Wu J, Barreto J, Bollen AW, Tihan T, Mummaneni PV, Ames C, Clark A, Oberheim Bush NA, Butowski N, Phillips D, King BE, Bator SM, Treynor EC, Zherebitskiy V, Quinn PS, Walker JB, Pekmezci M, Sullivan DV, Hofmann JW, Sloan EA, M Chang S, Berger MS, Solomon DA, Perry A

Abstract
Paragangliomas are neuroendocrine tumors of the autonomic nervous system that are variably clinically functional and have a potential for metastasis. Up to 40% occur in the setting of a hereditary syndrome, most commonly due to germline mutations in succinate dehydrogenase (SDHx) genes. Immunohistochemically, paragangliomas are characteristically GATA3-positive and cytokeratin-negative, with loss of SDHB expression in most hereditary cases. In contrast, the rare paragangliomas arising in the cauda equina (CEP) or filum terminale region have been shown to be hormonally silent, clinically indolent, and have variable keratin expression, suggesting these tumors may represent a separate pathologic entity. We retrospectively evaluated 17 CEPs from 11 male and 6 female patients with a median age of 38 years (range 21-82), none with a family history of neuroendocrine neoplasia. Six of the 17 tumors demonstrated prominent gangliocytic or ganglioneuromatous differentiation. By immunohistochemistry, none of the CEPs showed GATA3 positivity or loss of SDHB staining; all 17 CEPs were cytokeratin positive. Genome-wide DNA methylation profiling was performed on 12 of the tumors and compared with publicly available genome-wide DNA methylation data. Clustering analysis showed that CEPs form a distinct epigenetic group, separate from paragangliomas of extraspinal sites, pheochromocytomas, and other neuroendocrine neoplasms. Copy number analysis revealed diploid genomes in the vast majority of CEPs, whereas extraspinal paragangliomas were mostly aneuploid with recurrent trisomy 1q and monosomies of 1p, 3, and 11, none of which were present in the cohort of CEP. Together, these findings indicate that CEPs likely represent a distinct entity. Future genomic studies are needed to further elucidate the molecular pathogenesis of these tumors.

PMID: 32892244 [PubMed - as supplied by publisher]

Pancreatic neuroendocrine carcinoma G3 may be heterogeneous and could be classified into two distinct groups.

Fetched: September 9th, 2020, 5:01am GMT

Pancreatic neuroendocrine carcinoma G3 may be heterogeneous and could be classified into two distinct groups.

Pancreatology. 2020 Aug 08;:

Authors: Tanaka H, Hijioka S, Hosoda W, Ueno M, Kobayashi N, Ikeda M, Ito T, Kodama Y, Morizane C, Notohara K, Taguchi H, Kitano M, Komoto I, Tsuji A, Hashigo S, Kanno A, Miyabe K, Takagi T, Ishii H, Kojima Y, Yoshitomi H, Yanagimoto H, Furuse J, Mizuno N

Abstract
BACKGROUND/OBJECTIVES: Pancreatic neuroendocrine carcinoma (PanNEC)-G3 often presents along with genetic abnormalities such as KRAS, RB1, and TP53 mutations. However, the association between these genetic findings and response to chemotherapy and prognosis has not been clarified. This study aimed to clarify the clinicopathological features of PanNEC-G3.
METHODS: We performed a subgroup analysis of the Japanese PanNEN-G3 study (multicenter, retrospective study), which revealed that Rb loss and KRAS mutation were predictors of the response to platinum-based regimen in PanNEN-G3. We re-classified WHO grades of PanNENs using the 2017 WHO classification and then analyzed the clinicopathological features and prognostic factors in 49 patients with PanNEC-G3.
RESULTS: The rates of Rb loss and KRAS mutation in PanNEC-G3 were 54.5% and 48.7%, respectively. Patients with Rb loss and/or KRAS mutation showed a higher response rate to first-line platinum-based regimen than those without Rb loss or KRAS mutation (object response rate 70.0% vs 33.3%, odds ratio 9.22; 95% CI 1.26-67.3, P = 0.029), but tended to have shorter overall survival rates than those without Rb loss or KRAS mutation (median 239 vs 473 days, hazard ratio 2.11; 95% CI 0.92-4.86, P = 0.077).
CONCLUSIONS: Patients with PanNEC-G3 have varied clinical outcomes for platinum-based regimen. When grouped based on Rb loss and KRAS mutation, there seemed to be two groups with distinct prognoses and responses to the platinum-based regimen. PanNEC-G3 could, therefore, be classified into two distinct groups based on immunohistochemical and genetic findings.

PMID: 32891532 [PubMed - as supplied by publisher]

[Analysis of treatment and prognosis of 59 cases of vulvar melanoma].

Fetched: September 9th, 2020, 5:01am GMT

[Analysis of treatment and prognosis of 59 cases of vulvar melanoma].

Zhonghua Fu Chan Ke Za Zhi. 2020 Jun 25;55(6):395-401

Authors: Yuan GW, Li XG, Li N, Yao HW, Wu LY

Abstract
Objective: To assess the treatment and prognosis of vulvar melanoma. Methods: A total of 59 cases of primary vulvar melanoma admitted to Cancer Hospital of Peking Union Medical College, Chinese Academy of Medical Sciences from January 1st, 1981 to November 30th, 2019 were collected. The clinical characteristics, treatment, survival and prognostic factors of vulvar melanoma were analyzed retrospectively. The end date of follow-up was January 15th, 2020.The median follow-up time was 26.0 months (range:2-198 months). Results: (1) Clinical characteristics: the median age of 59 patients with vulvar melanoma was 56 years old (range:18-83 years old). According to the American Joint Committee on Cancer stage manual, there were 18, 7, 26 and 8 cases of stage Ⅰ, Ⅱ, Ⅲ and Ⅳ respectively. The lesion of 38 cases was single and the other 21 cases were multiple. The largest diameter of the tumor ranged from 0.3 to 17.0 cm.The surface of the lesion was ulcerated in 17 cases. (2) Treatment: a total of 59 cases with vulvar melanoma, 56 patients received surgery, 36 cases of them received radical resection of vulva and 20 received local extended resection of vulvar tumor due to unilateral vulva lesion. Three patients did not receive surgery,one received chemotherapy combined with interferon, one received interferon, and one received radiotherapy. Lymph node management: among the 56 patients treated by surgery, 37 patients received inguinal lymphadenectomy, 24 (65%, 24/37) of whom were confirmed with inguinal lymph node metastasis by postoperative pathological examination. Inguinal lymph nodes enlargement were not found in 19 cases by preoperative imaging and clinical examination. In these 19 patients, three patients received inguinal lymph node biopsy, among them, one (1/3) patient was confirmed with inguinal lymph node metastasis by postoperative pathological examination, and the remaining 16 patients did not receive inguinal lymph node surgery. Postoperative adjuvant treatment: among the 56 patients who received surgery, 31 received adjuvant chemotherapy，one received adjuvant radiotherapy, four received interferon therapy, 17 received combination therapy including chemotherapy, and three did not receive postoperative adjuvant therapy. (3) Survival:during the follow-up period, the median survival time of 59 patients with vulvar melanoma was 30.0 months (range:2.0-198.0 months). The 3-year survival rate was 42.5%, and the 5-year survival rate was 23.8%. The median survival time of stage Ⅰ, Ⅱ, Ⅲ and Ⅳ were 72.0, 45.0, 24.0 and 23.0 months, respectively. The difference among stage Ⅰ, Ⅱ and stage Ⅲ, Ⅳ were statistically significant （P<0.01）. The median survival time of patients undergoing radical resection of the vulva (35.0 months) and local enlarged tumor resection (29.0 months) were significantly longer than that of patients without surgery (9.0 months, P<0.01). The median survival time of the patients who underwent inguinal lymphadenectomy, lymph node biopsy and those who did not undergo surgery were 35.0, 32.0 and 30.0 months, respectively. There were no significant differences among the 3 groups (P>0.05). The median survival time of postoperative adjuvant chemotherapy patients (49.0 months) were significantly longer than that of postoperative adjuvant radiotherapy, interferon,and combination therapy including chemotherapy (9.0, 14.0 and 26.0 months, respectively, all P<0.01). (4) Prognostic factors: the univariate analysis showed that stage, vulvar operation and postoperative adjuvant treatment were the risk factors affecting the prognosis of patients with vulvar melanoma (P<0.01). Multivariate analysis revealed that stage alone was an independent risk factor affecting the prognosis of patients with vulvar melanoma (P<0.01). Conclusions: The prognosis of patients with vulvar melanoma is poor, and stage is an independent prognostic factor.Surgery combined with postoperative adjuvant chemotherapy may achieve relatively good results.

PMID: 32842246 [PubMed - indexed for MEDLINE]

Is radical ever too radical?

Fetched: September 9th, 2020, 5:01am GMT

Is radical ever too radical?

Am J Surg. 2020 08;220(2):282-283

Authors: Rose JB

PMID: 32507270 [PubMed - indexed for MEDLINE]

Long non-coding RNA MIAT promotes the growth of melanoma via targeting miR-150.

Fetched: September 9th, 2020, 5:01am GMT

Long non-coding RNA MIAT promotes the growth of melanoma via targeting miR-150.

Hum Cell. 2020 Jul;33(3):819-829

Authors: Zhu L, Wang Y, Yang C, Li Y, Zheng Z, Wu L, Zhou H

Abstract
Melanoma is a common skin cancer and it can lead to high mortality probably by early invasion and metastasis. LncRNA MIAT is involved in tumor proliferation, invasion and epithelial-to-mesenchymal transition (EMT). However, the roles of MIAT in melanoma still require further investigation. Thus, the aim of the study is to investigate the roles of MIAT in melanoma, especially the effects of MIAT on EMT of melanoma cancer cells. The results showed that the expression of MIAT was significantly upregulated in melanoma tissue and cells compared with the normal skin and normal melanocytes; moreover, miR-150 was confirmed as a target of MIAT. Furthermore, knockdown of MIAT inhibited cell proliferation and invasion in melanoma cancer cells and transfection of miR-150 inhibitors partial abrogated the anti-tumor effects of MIAT siRNA. In addition, MIAT siRNA also inhibited the EMT of melanoma cells, while miR-150 inhibitors can reverse the effects of MIAT siRNA. Finally, knockdown of MIAT also inhibited the carcinogenic effects of melanoma in vivo by targeting miR-150. In conclusion, we reported that MIAT promotes the proliferation, invasion and EMT of melanoma cells via targeting miR-150, which suggested that MIAT might be a therapeutic target for the treatment of melanoma.

PMID: 32300960 [PubMed - indexed for MEDLINE]

Oculomotor Neurofibroma: A Different Histology Implying an Unsatisfying Clinical Outcome.

Fetched: September 9th, 2020, 5:01am GMT

Oculomotor Neurofibroma: A Different Histology Implying an Unsatisfying Clinical Outcome.

World Neurosurg. 2020 07;139:31-38

Authors: Matano F, di Russo P, Okano A, Passeri T, Penet N, Fava A, Camara B, Polivka M, Giammattei L, Froelich S

Abstract
BACKGROUND: Tumors arising from oculomotor nerve are rare, with few cases reported in the literature. Generally, whereas schwannomas are well encapsulated tumors, neurofibromas tend to invade the entire nerve fibers. These differences influence surgical resection and neurological clinical outcome, with neurofibroma often requiring the sacrifice of the nerve. Accordingly, an incorrect preoperative diagnosis can lead to incomplete patient counseling before surgery.
CASE DESCRIPTION: We report 2 cases: a patient with oculomotor schwannoma and a patient with oculomotor neurofibroma. After tumor resection, the patient with a diagnosis of schwannoma recovered with 3rd nerve palsy, while patient with the neurofibroma developed a complete oculomotor nerve deficit. For each patient, surgical strategy and neurological outcome are elucidated in relation with differences in preoperative magnetic resonance imaging and histology.
CONCLUSIONS: To the best of our knowledge, this is the first report of an oculomotor neurofibroma. When an oculomotor nerve tumor is suspected, a careful preoperative evaluation of magnetic resonance imaging guides in distinguishing the different histology, in selecting the treatment strategy, and in correctly informing the patient on expected postoperative neurologic outcome.

PMID: 32289509 [PubMed - indexed for MEDLINE]

Adrenalectomy for non-neuroblastic pathology in children.

Fetched: September 9th, 2020, 5:01am GMT

Adrenalectomy for non-neuroblastic pathology in children.

Pediatr Surg Int. 2020 Feb;36(2):129-135

Authors: Traynor MD, Sada A, Thompson GB, Moir CR, Bancos I, Farley DR, Dy BM, Lyden ML, Habermann EB, McKenzie TJ

Abstract
BACKGROUND: Adrenalectomy for non-neuroblastic pathologies in children is rare with limited data on outcomes. We reviewed our experience of adrenalectomy in this unique population.
METHODS: Retrospective study of children (age ≤ 18) who underwent adrenalectomy with non-neuroblastic pathology from 1988 to 2018. Clinical and operative details of patients were abstracted. Outcomes included length of stay and 30-day postoperative morbidity.
RESULTS: Forty children underwent 50 adrenalectomies (12 right-sided, 18 left-sided, 10 bilateral). Six patients (15%) presented with an incidental adrenal mass while 4 (10%) had masses found on screening for genetic mutations or prior malignancy. The remaining 30 (75%) presented with symptoms of hormonal excess. Nineteen patients (48%) underwent genetic evaluation and 15 (38%) had genetic predispositions. Diagnoses included 9 patients (23%) with pheochromocytoma, 8 (20%) with adrenocortical adenoma, 8 (20%) with adrenocortical carcinoma, 7 (18%) with adrenal hyperplasia, 2 (5%) with metastasis, and 6 (14%) with additional benign pathologies. Of 50 adrenalectomies, twenty-five (50%) were laparoscopic. Median hospital length of stay was 3 days (range 0-11). Post-operative morbidity rate was 17% with the most severe complication being Clavien-Dindo grade II.
CONCLUSION: Adrenalectomy for non-neuroblastic pathology can be done with low morbidity. Its frequent association with genetic mutations and syndromes requires surgeons to have knowledge of appropriate pre-operative testing and post-operative surveillance.

PMID: 31691026 [PubMed - indexed for MEDLINE]

Natural Killer Cell Recruitment and Activation Are Regulated by CD47 Expression in the Tumor Microenvironment.

Fetched: September 9th, 2020, 5:01am GMT

Natural Killer Cell Recruitment and Activation Are Regulated by CD47 Expression in the Tumor Microenvironment.

Cancer Immunol Res. 2019 09;7(9):1547-1561

Authors: Nath PR, Pal-Nath D, Mandal A, Cam MC, Schwartz AL, Roberts DD

Abstract
Elevated CD47 expression in some cancers is associated with decreased survival and limited clearance by phagocytes expressing the CD47 counterreceptor SIRPα. In contrast, elevated CD47 mRNA expression in human melanomas was associated with improved survival. Gene-expression data were analyzed to determine a potential mechanism for this apparent protective function and suggested that high CD47 expression increases recruitment of natural killer (NK) cells into the tumor microenvironment. The CD47 ligand thrombospondin-1 inhibited NK cell proliferation and CD69 expression in vitro Cd47 -/- NK cells correspondingly displayed augmented effector phenotypes, indicating an inhibitory function of CD47 on NK cells. Treating human NK cells with a CD47 antibody that blocks thrombospondin-1 binding abrogated its inhibitory effect on NK cell proliferation. Similarly, treating wild-type mice with a CD47 antibody that blocks thrombospondin-1 binding delayed B16 melanoma growth, associating with increased NK cell recruitment and increased granzyme B and interferon-γ levels in intratumoral NK but not CD8+ T cells. However, B16 melanomas grew faster in Cd47 -/- than in wild-type mice. Melanoma-bearing Cd47 -/- mice exhibited decreased splenic NK cell numbers, with impaired effector protein expression and elevated exhaustion markers. Proapoptotic gene expression in Cd47-/- NK cells was associated with stress-mediated increases in mitochondrial proton leak, reactive oxygen species, and apoptosis. Global gene-expression profiling in NK cells from tumor-bearing mice identified CD47-dependent transcriptional responses that regulate systemic NK activation and exhaustion. Therefore, CD47 positively and negatively regulates NK cell function, and therapeutic antibodies that block inhibitory CD47 signaling can enhance NK immune surveillance of melanomas.

PMID: 31362997 [PubMed - indexed for MEDLINE]

Permalink for 'Immune-Checkpoint Protein VISTA Regulates Antitumor Immunity by Controlling Myeloid Cell-Mediated Inflammation and Immunosuppression.'

Immune-Checkpoint Protein VISTA Regulates Antitumor Immunity by Controlling Myeloid Cell-Mediated Inflammation and Immunosuppression.

Fetched: September 9th, 2020, 5:01am GMT

Immune-Checkpoint Protein VISTA Regulates Antitumor Immunity by Controlling Myeloid Cell-Mediated Inflammation and Immunosuppression.

Cancer Immunol Res. 2019 09;7(9):1497-1510

Authors: Xu W, Dong J, Zheng Y, Zhou J, Yuan Y, Ta HM, Miller HE, Olson M, Rajasekaran K, Ernstoff MS, Wang D, Malarkannan S, Wang L

Abstract
Immune-checkpoint protein V-domain immunoglobulin suppressor of T-cell activation (VISTA) controls antitumor immunity and is a valuable target for cancer immunotherapy. This study identified a role of VISTA in regulating Toll-like receptor (TLR) signaling in myeloid cells and controlling myeloid cell-mediated inflammation and immunosuppression. VISTA modulated the polyubiquitination and protein expression of TRAF6. Consequently, VISTA dampened TLR-mediated activation of MAPK/AP-1 and IKK/NF-κB signaling cascades. At cellular levels, VISTA regulated the effector functions of myeloid-derived suppressor cells and tolerogenic dendritic cell (DC) subsets. Blocking VISTA augmented their ability to produce proinflammatory mediators and diminished their T cell-suppressive functions. These myeloid cell-dependent effects resulted in a stimulatory tumor microenvironment that promoted T-cell infiltration and activation. We conclude that VISTA is a critical myeloid cell-intrinsic immune-checkpoint protein and that the reprogramming of tolerogenic myeloid cells following VISTA blockade promotes the development of T cell-mediated antitumor immunity.

PMID: 31340983 [PubMed - indexed for MEDLINE]

SLAMF6 as a Regulator of Exhausted CD8+ T Cells in Cancer.

Fetched: September 9th, 2020, 5:01am GMT

SLAMF6 as a Regulator of Exhausted CD8+ T Cells in Cancer.

Cancer Immunol Res. 2019 09;7(9):1485-1496

Authors: Yigit B, Wang N, Ten Hacken E, Chen SS, Bhan AK, Suarez-Fueyo A, Katsuyama E, Tsokos GC, Chiorazzi N, Wu CJ, Burger JA, Herzog RW, Engel P, Terhorst C

Abstract
The tumor microenvironment in leukemia and solid tumors induces a shift of activated CD8+ cytotoxic T cells to an exhausted state, characterized by loss of proliferative capacity and impaired immunologic synapse formation. Efficient strategies and targets need to be identified to overcome T-cell exhaustion and further improve overall responses in the clinic. Here, we took advantage of the Eμ-TCL1 chronic lymphocytic leukemia (CLL) and B16 melanoma mouse models to assess the role of the homophilic cell-surface receptor SLAMF6 as an immune-checkpoint regulator. The transfer of SLAMF6+ Eμ-TCL1 cells into SLAMF6-/- recipients, in contrast to wild-type (WT) recipients, significantly induced expansion of a PD-1+ subpopulation among CD3+CD44+CD8+ T cells, which had impaired cytotoxic functions. Conversely, administering anti-SLAMF6 significantly reduced the leukemic burden in Eμ-TCL1 recipient WT mice concomitantly with a loss of PD-1+CD3+CD44+CD8+ T cells with significantly increased effector functions. Anti-SLAMF6 significantly reduced leukemic burden in the peritoneal cavity, a niche where antibody-dependent cellular cytotoxicity (ADCC) is impaired, possibly through activation of CD8+ T cells. Targeting of SLAMF6 affected tumor growth not only in B cell-related leukemia and lymphomas but also in nonhematopoietic tumors such as B16 melanoma, where SLAMF6 is not expressed. In vitro exhausted CD8+ T cells showed increased degranulation when anti-human SLAMF6 was added in culture. Taken together, anti-SLAMF6 both effectively corrected CD8+ T-cell dysfunction and had a direct effect on tumor progression. The outcomes of our studies suggest that targeting SLAMF6 is a potential therapeutic strategy.

PMID: 31315913 [PubMed - indexed for MEDLINE]

MERTK Acts as a Costimulatory Receptor on Human CD8+ T Cells.

Fetched: September 9th, 2020, 5:01am GMT

MERTK Acts as a Costimulatory Receptor on Human CD8+ T Cells.

Cancer Immunol Res. 2019 Sep;7(9):1472-1484

Authors: Peeters MJW, Dulkeviciute D, Draghi A, Ritter C, Rahbech A, Skadborg SK, Seremet T, Carnaz Simões AM, Martinenaite E, Halldórsdóttir HR, Andersen MH, Olofsson GH, Svane IM, Rasmussen LJ, Met Ö, Becker JC, Donia M, Desler C, Thor Straten P

Abstract
The TAM family of receptor tyrosine kinases (TYRO3, AXL, and MERTK) is known to be expressed on antigen-presenting cells and function as oncogenic drivers and as inhibitors of inflammatory responses. Both human and mouse CD8+ T cells are thought to be negative for TAM receptor expression. In this study, we show that T-cell receptor (TCR)-activated human primary CD8+ T cells expressed MERTK and the ligand PROS1 from day 2 postactivation. PROS1-mediated MERTK signaling served as a late costimulatory signal, increasing proliferation and secretion of effector and memory-associated cytokines. Knockdown and inhibition studies confirmed that this costimulatory effect was mediated through MERTK. Transcriptomic and metabolic analyses of PROS1-blocked CD8+ T cells demonstrated a role of the PROS1-MERTK axis in differentiation of memory CD8+ T cells. Finally, using tumor-infiltrating lymphocytes (TIL) from melanoma patients, we show that MERTK signaling on T cells improved TIL expansion and TIL-mediated autologous cancer cell killing. We conclude that MERTK serves as a late costimulatory signal for CD8+ T cells. Identification of this costimulatory function of MERTK on human CD8+ T cells suggests caution in the development of MERTK inhibitors for hematologic or solid cancer treatment.

PMID: 31266785 [PubMed - indexed for MEDLINE]

Evolutionary Routes in Metastatic Uveal Melanomas Depend on MBD4 Alterations.

Fetched: September 9th, 2020, 5:01am GMT

Evolutionary Routes in Metastatic Uveal Melanomas Depend on MBD4 Alterations.

Clin Cancer Res. 2019 09 15;25(18):5513-5524

Authors: Rodrigues M, Mobuchon L, Houy A, Alsafadi S, Baulande S, Mariani O, Marande B, Ait Rais K, Van der Kooij MK, Kapiteijn E, Gassama S, Gardrat S, Barnhill RL, Servois V, Dendale R, Putterman M, Tick S, Piperno-Neumann S, Cassoux N, Pierron G, Waterfall JJ, Roman-Roman S, Mariani P, Stern MH

Abstract
PURPOSE: Uveal melanomas (UM) are genetically simple tumors carrying few copy number alterations (CNA) and a low mutation burden, except in rare MBD4-deficient, hypermutated cases. The genomics of uveal melanoma metastatic progression has not been described. We assessed the genetic heterogeneity of primary and metastatic MBD4-proficient and -deficient uveal melanomas.Experimental Design: We prospectively collected 75 metastatic and 16 primary samples from 25 consecutive uveal melanoma patients, and performed whole-exome sequencing.
RESULTS: MBD4-proficient uveal melanomas contained stable genomes at the nucleotide level, acquiring few new single nucleotide variants (SNVs; 16 vs. 13 in metastases and primary tumors, respectively), and no new driver mutation. Five CNAs were recurrently acquired in metastases (losses of 1p, 6q, gains of 1q, 8q, and isodisomy 3). In contrast, MBD4-deficient uveal melanomas carried more than 266 SNVs per sample, with high genetic heterogeneity and TP53, SMARCA4, and GNAS new driver mutations. SNVs in MBD4-deficient contexts were exploited to unveil the timeline of oncogenic events, revealing that metastatic clones arose early after tumor onset. Surprisingly, metastases were not enriched in monosomy 3, a previously defined metastatic risk genomic feature. Monosomy 3 was associated with shorter metastatic-free interval compared with disomy 3 rather than higher rate of relapse.
CONCLUSIONS: MBD4-proficient uveal melanomas are stable at the nucleotide level, without new actionable alterations when metastatic. In contrast, MBD4 deficiency is associated with high genetic heterogeneity and acquisition of new driver mutations. Monosomy 3 is associated with time to relapse rather than rate of relapse, thus opening avenues for a new genetic prognostic classification of uveal melanomas.

PMID: 31227496 [PubMed - indexed for MEDLINE]

Merkel Cell Carcinoma: A Description of 11 Cases.

Fetched: September 7th, 2020, 5:01am GMT

Merkel Cell Carcinoma: A Description of 11 Cases.

Actas Dermosifiliogr. 2020 Sep 01;:

Authors: García-Zamora E, Vela Ganuza M, Martín-Alcalde J, Miñano Medrano R, Pinedo Moraleda F, López-Estebaranz JL

PMID: 32888930 [PubMed - as supplied by publisher]

Molecular profiling of neuroendocrine tumours to predict response and toxicity to peptide receptor radionuclide therapy.

Fetched: September 7th, 2020, 5:01am GMT

Molecular profiling of neuroendocrine tumours to predict response and toxicity to peptide receptor radionuclide therapy.

Lancet Oncol. 2020 Sep;21(9):e431-e443

Authors: Bodei L, Schöder H, Baum RP, Herrmann K, Strosberg J, Caplin M, Öberg K, Modlin IM

Abstract
Peptide receptor radionuclide therapy (PRRT) is a type of radiotherapy that targets peptide receptors and is typically used for neuroendocrine tumours (NETs). Some of the key challenges in its use are the prediction of efficacy and toxicity, patient selection, and response optimisation. In this Review, we assess current knowledge on the molecular profile of NETs and the strategies and tools used to predict, monitor, and assess the toxicity of PRRT. The few mutations in tumour genes that can be evaluated (eg, ATM and DAXX) are limited to pancreatic NETs and are most likely not informative. Assays that are transcriptomic or based on genes are effective in the prediction of radiotherapy response in other cancers. A blood-based assay for eight genes (the PRRT prediction quotient [PPQ]) has an overall accuracy of 95% for predicting responses to PRRT in NETs. No molecular markers exist that can predict the toxicity of PRRT. Candidate molecular targets include seven single nucleotide polymorphisms (SNPs) that are susceptible to radiation. Transcriptomic evaluations of blood and a combination of gene expression and specific SNPs, assessed by machine learning with algorithms that are tumour-specific, might yield molecular tools to enhance the efficacy and safety of PRRT.

PMID: 32888472 [PubMed - as supplied by publisher]

Evaluation of 111In-Pentetreotide SPECT imaging correction for GEP-NET.

Fetched: September 7th, 2020, 5:01am GMT

Evaluation of 111In-Pentetreotide SPECT imaging correction for GEP-NET.

J Nucl Med Technol. 2020 Sep 04;:

Authors: Kanzaki T, Takahashi Y, Higuchi T, Zhang X, Mogi N, Suto T, Tsushima Y

Abstract
Purpose: The number of patients with the extremely rare disease GEP-NET (gastroenteropancreatic neuroendocrine tumor) has increased rapidly in recent years. In-111-pentetreotide single photon emission computed tomography (111In-pentetreotide SPECT) in somatostatin receptor scintigraphy (SRS) has been used for the assessment of GEP-NET patients. To diagnose GEP-NET, appropriate selection of the image correction parameters is of critical importance. Correction methods may improve the 111In-pentetreotide SPECT image quality, but there is currently no standard technique. The purpose of this study was to determine the optimal correction parameter settings for 111In-pentetreotide SPECT imaging. Materials and Methods: A phantom study produced scan images with a tumor-to-background ratio as high as 16:1. Triple energy window was used for scatter correction (SC), and computed tomography-based attenuation correction was used for attenuation correction (AC). Correlation analysis was performed in four groups: no correction (NC), SC, AC, and combined SC with AC corrections (CC). 111In-pentetreotide SPECT results of twenty patients (13 men and 7 women; age range, 37-81 years) randomly selected patients with confirmed GEP-NET were analyzed, using data collected four hours after injection of 111 MBq 111In-pentetreotide. Emission data were reconstructed using ordered subset expectation maximization (OSEM) reconstruction, with different settings. Different combinations of the correction parameters were used to analyze the contrast to noise ratios (CNR) obtained with the phantom. In the clinical study, 20 GEP-NET patients evaluated the GEP-NET lesion CNR by four different image correction methods obtained from 111In-pentetreotide SPECT images: 1) NC, 2) SC, 3) AC, and 4) CC. NC was employed as a reference method. Results: The phantom study revealed that the optimal energy window in the photopeak for SRS was 171 keV ± 10% and 245 keV ± 7.5%, and the optimal OSEM reconstruction conditions were 8 subsets and 6 iterations. Among the OSEM collection conditions, CC produced a signiﬁcantly higher CNR than NC or SC (p<0.05). In the clinical study, CC was found to increase the CNR (p<0.05).　 Conclusion: CC improves the correction in 111In-pentetreotide SPECT studies, compared with NC, providing better contrast and sharper outlines of lesions and organs.

PMID: 32887762 [PubMed - as supplied by publisher]

Circulating miRNA Increases the Diagnostic Accuracy of Chromogranin A in Metastatic Pancreatic Neuroendocrine Tumors.

Fetched: September 7th, 2020, 5:01am GMT

Circulating miRNA Increases the Diagnostic Accuracy of Chromogranin A in Metastatic Pancreatic Neuroendocrine Tumors.

Cancers (Basel). 2020 Sep 02;12(9):

Authors: Kövesdi A, Kurucz PA, Nyírő G, Darvasi O, Patócs A, Butz H

Abstract
Chromogranin A (CgA) is the most widely accepted biomarker for neuroendocrine tumors (NET) but its diagnostic accuracy is dependent on tumor type and the use of proton-pump inhibitors (PPI). We investigated the diagnostic value of circulating miRNAs along with CgA in pancreatic neuroendocrine tumors (pNET). 74 serum samples from patients with pNET (n = 25, nonfunctioning), pheochromocytoma/paraganglioma (PPGL, n = 20), healthy individuals with normal CgA (n = 29) including 10 samples from 5 healthy individuals with and without current PPI treatment were collected. MiRNA expression profiles were determined using next-generation sequencing, followed by validation with individual TaqMan assays. A global downregulation of miRNAs was observed in patients with NET compared to controls. MiRNA expression of 33 miRNAs was able to discriminate tumor samples from controls. No miRNA alone could be considered as an applicable biomarker for pNET or PPGL. However, using a logistic model, the combination of a set of miRNAs increased the discriminatory role of CgA irrespective of PPI treatment. In pNET patients with normal CgA level our regression model yielded high (89.4%) diagnostic accuracy (AUC: 0.904, sensitivity: 66.6%, specificity: 96.5%). A set of miRNAs increased the diagnostic utility of CgA in pNET even in patients with low CgA.

PMID: 32887459 [PubMed - as supplied by publisher]

Overview of Radiolabeled Somatostatin Analogs for Cancer Imaging and Therapy.

Fetched: September 7th, 2020, 5:01am GMT

Overview of Radiolabeled Somatostatin Analogs for Cancer Imaging and Therapy.

Molecules. 2020 Sep 02;25(17):

Authors: Eychenne R, Bouvry C, Bourgeois M, Loyer P, Benoist E, Lepareur N

Abstract
Identified in 1973, somatostatin (SST) is a cyclic hormone peptide with a short biological half-life. Somatostatin receptors (SSTRs) are widely expressed in the whole body, with five subtypes described. The interaction between SST and its receptors leads to the internalization of the ligand-receptor complex and triggers different cellular signaling pathways. Interestingly, the expression of SSTRs is significantly enhanced in many solid tumors, especially gastro-entero-pancreatic neuroendocrine tumors (GEP-NET). Thus, somatostatin analogs (SSAs) have been developed to improve the stability of the endogenous ligand and so extend its half-life. Radiolabeled analogs have been developed with several radioelements such as indium-111, technetium-99 m, and recently gallium-68, fluorine-18, and copper-64, to visualize the distribution of receptor overexpression in tumors. Internal metabolic radiotherapy is also used as a therapeutic strategy (e.g., using yttrium-90, lutetium-177, and actinium-225). With some radiopharmaceuticals now used in clinical practice, somatostatin analogs developed for imaging and therapy are an example of the concept of personalized medicine with a theranostic approach. Here, we review the development of these analogs, from the well-established and authorized ones to the most recently developed radiotracers, which have better pharmacokinetic properties and demonstrate increased efficacy and safety, as well as the search for new clinical indications.

PMID: 32887456 [PubMed - as supplied by publisher]

Clinical and pathological characteristics and prognosis of 132 cases of rectal neuroendocrine tumors.

Fetched: September 5th, 2020, 5:01am GMT

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Clinical and pathological characteristics and prognosis of 132 cases of rectal neuroendocrine tumors.

World J Gastrointest Oncol. 2020 Aug 15;12(8):893-902

Authors: Yu YJ, Li YW, Shi Y, Zhang Z, Zheng MY, Zhang SW

Abstract
BACKGROUND: Neuroendocrine tumors (NETs) frequently occur in the gastrointestinal tract, lung, and pancreas, and the rectum and appendix are the sites with the highest incidence. Epidemiology statistics show that an estimated 8000 people every year in the United States are diagnosed with NETs occurring in the gastrointestinal tract, including the stomach, intestine, appendix, colon, and rectum. The pathological changes and clinical symptoms of NETs are not specific, and therefore they are frequently misdiagnosed.
AIM: To investigate the clinical symptoms, pathological characteristics, treatment, and prognosis of rectal neuroendocrine tumors (RNETs) by analyzing the clinical and pathological data of 132 RNET cases at our hospital.
METHODS: All RNETs were graded according to Ki-67 positivity and mitotic events. The tumors were staged as clinical stages I, II, III, and IV according to infiltrative depth and tumor size. COX proportional hazard model was used to assess the main risk factors for survival.
RESULTS: These 132 RNETs included 83 cases of G1, 21 cases of G2, and 28 cases of G3 (neuroendocrine carcinoma) disease. Immunohistochemical staining showed that 89.4% of RNETs were positive for synaptophysin and 39.4% positive for chromogranin A. There were 19, 85, 23, and 5 cases of clinical stages I, II, III, and IV, respectively. The median patient age was 52.96 years. The diameter of tumor, depth of invasion, and pathological grade were the main reference factors for the treatment of RNETs. The survival rates at 6, 12, 36, and 60 mo after operation were 98.5%, 94.6%, 90.2%, and 85.6%, respectively. Gender, tumor size, tumor grade, lymph node or distant organ metastasis, and radical resection were the main factors associated with prognosis of RNETs. Multivariate analysis showed that tumor size and grade were independent prognostic factors.
CONCLUSION: The clinical symptoms of RNETs are not specific, and they are easy to misdiagnose. Surgery is the main treatment method. The grade and stage of RNETs are the main indices to evaluate prognosis.

PMID: 32879666 [PubMed]

Gastric neuroendocrine tumor: A practical literature review.

Fetched: September 5th, 2020, 5:01am GMT

Gastric neuroendocrine tumor: A practical literature review.

World J Gastrointest Oncol. 2020 Aug 15;12(8):850-856

Authors: Roberto GA, Rodrigues CMB, Peixoto RD, Younes RN

Abstract
Gastric neuroendocrine tumors are gastric neoplasms originating from enterochromaffin type cells and are inserted in a larger group, named gastroenteropancreatic neuroendocrine tumors. They are considered rare and variable in terms of their clinical, morphological and functional characteristics and may be indolent or aggressive. They are classified into types I, II and III, according to their pathophysiology, behavior and treatment. Their diagnosis occurs, in most cases, incidentally during upper digestive endoscopies, presenting as simple gastric polyps. Most cases (type I and type II) are related to hypergastrinemia, can be multiple and are treated by endoscopic resection, whenever possible. The use of somatostatin analogs for tumor control may be one of the options for therapy, in addition to total or subtotal gastrectomy for selected cases. Adjuvant chemotherapy is only reserved for poorly differentiated neuroendocrine carcinomas. Although rare, gastric neuroendocrine tumors have an increasing incidence over the years, therefore deserving more comprehensive studies on its adequate treatment. The present study reviews and updates management recommendations for gastric neuroendocrine tumors.

PMID: 32879663 [PubMed]

One size does not fit all for pancreatic cancers: A review on rare histologies and therapeutic approaches.

Fetched: September 5th, 2020, 5:01am GMT

One size does not fit all for pancreatic cancers: A review on rare histologies and therapeutic approaches.

World J Gastrointest Oncol. 2020 Aug 15;12(8):833-849

Authors: Niger M, Prisciandaro M, Antista M, Monica MAT, Cattaneo L, Prinzi N, Manglaviti S, Nichetti F, Brambilla M, Torchio M, Corti F, Pusceddu S, Coppa J, Mazzaferro V, de Braud F, Di Bartolomeo M

Abstract
Exocrine pancreatic neoplasms represent up to 95% of pancreatic cancers (PCs) and are widely recognized among the most lethal solid cancers, with a very poor 5-year survival rate of 5%-10%. The remaining < 5% of PCs are neuroendocrine tumors that are usually characterized by a better prognosis, with a median overall survival of 3.6 years. The most common type of PC is pancreatic ductal adenocarcinoma (PDAC), which accounts for roughly 85% of all exocrine PCs. However up to 10% of exocrine PCs have rare histotypes, which are still poorly understood. These subtypes can be distinguished from PDAC in terms of pathology, imaging, clinical presentation and prognosis. Additionally, due to their rarity, any knowledge regarding these specific histotypes is mostly based on case reports and a small series of retrospective analyses. Therefore, treatment strategies are generally deduced from those used for PDAC, even if these patients are often excluded or not clearly represented in clinical trials for PDAC. For these reasons, it is essential to collect as much information as possible on the management of PC, as assimilating it with PDAC may lead to the potential mistreatment of these patients. Here, we report the most significant literature regarding the epidemiology, typical presentation, possible treatment strategies, and prognosis of the most relevant histotypes among rare PCs.

PMID: 32879662 [PubMed]

Gastrointestinal neuroendocrine tumors in 2020.

Fetched: September 5th, 2020, 5:01am GMT

Gastrointestinal neuroendocrine tumors in 2020.

World J Gastrointest Oncol. 2020 Aug 15;12(8):791-807

Authors: Ahmed M

Abstract
Gastrointestinal neuroendocrine tumors are rare slow-growing tumors with distinct histological, biological, and clinical characteristics that have increased in incidence and prevalence within the last few decades. They contain chromogranin A, synaptophysin and neuron-specific enolase which are necessary for making a diagnosis of neuroendocrine tumor. Ki-67 index and mitotic index correlate with cellular proliferation. Serum chromogranin A is the most commonly used biomarker to assess the bulk of disease and monitor treatment and is raised in both functioning and non-functioning neuroendocrine tumors. Most of the gastrointestinal neuroendocrine tumors are non-functional. World Health Organization updated the classification of neuroendocrine tumors in 2017 and renamed mixed adenoneuroendocrine carcinoma into mixed neuroendocrine neoplasm. Gastric neuroendocrine tumors arise from enterochromaffin like cells. They are classified into 4 types. Only type I and type II are gastrin dependent. Small intestinal neuroendocrine tumor is the most common small bowel malignancy. More than two-third of them occur in the terminal ileum within 60 cm of ileocecal valve. Patients with small intestinal neuroendrocrine tumors frequently show clinical symptoms and develop distant metastases more often than those with neuroendocrine tumors of other organs. Duodenal and jejuno-ileal neuroendocrine tumors are distinct biologically and clinically. Carcinoid syndrome generally occurs when jejuno-ileal neuroendocrine tumors metastasize to the liver. Appendiceal neuroendocrine tumors are generally detected after appendectomy. Colonic neuroendocrine tumors generally present as a large tumor with local or distant metastasis at the time of diagnosis. Rectal neuroendocrine tumors are increasingly being diagnosed since the implementation of screening colonoscopy in 2000. Gastrointestinal neuroendocrine tumors are diagnosed and staged by endoscopy with biopsy, endoscopic ultrasound, serology of biomarkers, imaging studies and functional somatostatin scans. Various treatment options are available for curative and palliative treatment of gastrointestinal neuroendocrine tumors.

PMID: 32879660 [PubMed]

Outcomes of over-the-scope clip application in various gastrointestinal indications: experience from a tertiary care in India.

Fetched: September 5th, 2020, 5:01am GMT

Outcomes of over-the-scope clip application in various gastrointestinal indications: experience from a tertiary care in India.

Ann Gastroenterol. 2020 Sep-Oct;33(5):473-479

Authors: Chavan R, Nabi Z, Karayampudi A, Jagtap N, Asif S, Yaralagadda R, Basha J, Lakhtakia S, Tandan M, Ramchandani M, Reddy DN

Abstract
Background: Recent advances in endoscopic tools and techniques have allowed the minimally invasive management of iatrogenic gastrointestinal (GI) perforations and bleedings. However, surgery may be required in cases with larger defects and bleeding refractory to conventional endoscopic modalities. The use of over-the-scope clips (OTSC) has been shown to improve the outcomes in these patients compared with conventional treatment modalities. In this study, we evaluated the safety and efficacy of OTSC for different indications in the GI tract.
Methods: The data of consecutive patients in whom OTSC was utilized for different indications between February 2017 and October 2019 were analyzed retrospectively. The following outcomes were recorded: technical and clinical success, and adverse events related to the procedure.
Results: Thirty-six patients (22 male, mean age 52.673±14.97 years, range 11-72 years) underwent OTSC application. Indications for OTSC were: GI defects (perforation n=13, fistula n=5); esophageal metallic stent fixing n=9; GI bleeding n=8; and neuroendocrine tumor endotherapy n=1. The average size of the defect was 15.88±8.01 mm. The technical and clinical success rates were 88.89% and 83.33%, respectively. There were 4 (11.1%) technical failures: colonic perforations n=2; duodenal ulcer bleeding n=1; and esophageal metal stent fixation n=1. There were 2 (9.5%) adverse events, including 1 partial duodenal obstruction and 1 delayed bleeding.
Conclusions: The use of OTSC is safe, easy and effective for various indications in the GI tract. Prospective trials are required to see if the use of OTSC is cost effective as a primary endoscopic treatment method in these cases.

PMID: 32879593 [PubMed]

Permalink for '[Pulmonary Blastoma with the Differentiation of Adenocarcinoma and Large Cell Neuroendocrine Carcinoma in an Adult Patient;Report of a Case].'

[Pulmonary Blastoma with the Differentiation of Adenocarcinoma and Large Cell Neuroendocrine Carcinoma in an Adult Patient;Report of a Case].

Fetched: September 5th, 2020, 5:01am GMT

[Pulmonary Blastoma with the Differentiation of Adenocarcinoma and Large Cell Neuroendocrine Carcinoma in an Adult Patient;Report of a Case].

Kyobu Geka. 2020 Sep;73(9):712-715

Authors: Kou Y, Yamazaki N, Tanaka H, Sonobe M

Abstract
A 63-year-old man was pointed out a mass lesion in his chest X-ray at a medical checkup and referred to our hospital for further examination. Chest computed tomography showed a 4 cm-diameter tumor in the left upper lobe. He was diagnosed with adenocarcinoma by bronchoscopic biopsy. Therefore, we performed left upper lobectomy. The tumor was diagnosed as pulmonary blastoma with the differentiation of adenocarcinoma and large cell neuroendocrine carcinoma.

PMID: 32879279 [PubMed - indexed for MEDLINE]

Oncologic outcomes of patients with Merkel Cell Carcinoma (MCC): A multi-institutional cohort study.

Fetched: September 5th, 2020, 5:01am GMT

Oncologic outcomes of patients with Merkel Cell Carcinoma (MCC): A multi-institutional cohort study.

Am J Surg. 2020 Aug 22;:

Authors: Bleicher J, Asare EA, Flores S, Bowles TL, Bowen GM, Hyngstrom JR

PMID: 32878692 [PubMed - as supplied by publisher]

[Research progress of anti-angiogenic drugs in the treatment of small cell lung cancer].

Fetched: September 3rd, 2020, 5:01am GMT

[Research progress of anti-angiogenic drugs in the treatment of small cell lung cancer].

Zhonghua Zhong Liu Za Zhi. 2020 Aug 23;42(8):624-628

Authors: Wang J, Li K

Abstract
Small cell lung cancer (SCLC), a special type of lung cancer, is a highly malignant neuroendocrine tumor with strong invasiveness and rapid progression. SCLC is sensitive to radiotherapy and chemotherapy, so radiotherapy and chemotherapy have been the main first-line treatment of SCLC. However, it is easy to develop drug resistance after treatment. Therefore, the study of anti-angiogenic therapy has attracted more and more attention. At present, anti-angiogenic drugs mainly focus on four categories: monoclonal antibodies (such as bevacizumab), endogenous angiogenesis inhibitors (such as endostar), anti-angiogenic fusion protein (such as aflibercept) and small molecular tyrosine kinase inhibitors (such as anlotinib). There are still some bottlenecks in the research and clinical application of antiangiogenic drugs. It is the right direction to explore better combination therapy and effective dual-field and multi-target drugs.

PMID: 32867452 [PubMed - in process]

Permalink for 'Efficacy and safety of osilodrostat in patients with Cushing's disease (LINC 3): a multicentre phase III study with a double-blind, randomised withdrawal phase.'

Efficacy and safety of osilodrostat in patients with Cushing's disease (LINC 3): a multicentre phase III study with a double-blind, randomised withdrawal phase.

Fetched: September 3rd, 2020, 5:01am GMT

Efficacy and safety of osilodrostat in patients with Cushing's disease (LINC 3): a multicentre phase III study with a double-blind, randomised withdrawal phase.

Lancet Diabetes Endocrinol. 2020 09;8(9):748-761

Authors: Pivonello R, Fleseriu M, Newell-Price J, Bertagna X, Findling J, Shimatsu A, Gu F, Auchus R, Leelawattana R, Lee EJ, Kim JH, Lacroix A, Laplanche A, O'Connell P, Tauchmanova L, Pedroncelli AM, Biller BMK, LINC 3 investigators

Abstract
BACKGROUND: Cushing's disease is a rare endocrine disorder characterised by cortisol overproduction with severe complications. Therapies for cortisol reduction are often necessary. Here we report the outcomes from the pivotal phase III study of osilodrostat (a potent oral inhibitor of cytochrome P450 11B1, mitochondrial [11β-hydroxylase]; Novartis Pharma AG, Basel, Switzerland) in patients with Cushing's disease.
METHODS: LINC 3 was a prospective, multicentre, open-label, phase III study with a double-blind randomised withdrawal period, that comprised four periods. Patients aged 18-75 years, with confirmed persistent or recurrent Cushing's disease (defined as mean 24-h urinary free cortisol [UFC] concentration >1·5 times the upper limit of normal [ULN] and morning plasma adrenocorticotropic hormone above the lower limit of normal) who had previously had pituitary surgery or irradiation, or were newly diagnosed and who refused surgery or were not surgical candidates, were recruited from 66 hospital sites and private clinical practices in 19 countries. In period 1, open-label osilodrostat was initiated in all participants and adjusted every 2 weeks (1-30 mg twice daily; film-coated tablets for oral administration) on the basis of mean 24-h UFC concentration and safety until week 12. In period 2, weeks 13-24, osilodrostat was continued at the therapeutic dose determined during period 1. In period 3, beginning at week 26, participants who had a mean 24-h UFC concentration of less than or equal to the ULN at week 24, without up-titration after week 12, were randomly assigned (1:1), via an interactive-response technology, stratified by osilodrostat dose at week 24 and history of pituitary irradiation, to continue osilodrostat or switch to placebo for 8 weeks. Participants and investigators were masked to treatment assignment. Ineligible participants continued open-label osilodrostat. In period 4, weeks 35-48, all participants were given open-label osilodrostat until core-study end. The primary objective was to compare the efficacy of osilodrostat versus placebo at the end of period 3. The primary endpoint was the proportion of participants who had been randomly assigned to treatment or placebo with a complete response (ie, mean 24-h UFC concentration of ≤ULN) at the end of the randomised withdrawal period (week 34), without up-titration during this period. The key secondary endpoint was the proportion of participants with a complete response at the end of the single-arm, open-label period (ie, period 2, week 24) without up-titration during weeks 13-24. Analysis was by intention-to-treat for all patients who received at least one dose of osilodrostat (full analysis set; key secondary endpoint) or randomised treatment (randomised analysis set; primary endpoint) and safety was assessed in all enrolled patients who received at least one dose of osilodrostat and had at least one post-baseline safety assessment. LINC 3 is registered with ClinicalTrials.gov, NCT02180217, and is now complete.
FINDINGS: Between Nov 12, 2014, and March 22, 2017, 202 patients were screened and 137 were enrolled. The median age was 40·0 years (31·0-49·0) and 106 (77%) participants were female. 72 (53%) participants were eligible for randomisation during the withdrawal phase, of whom 36 were assigned to continue osilodrostat and 35 were assigned to placebo; one patient was not randomly assigned due to investigator decision and continued open-label osilodrostat. More patients maintained a complete response with osilodrostat versus with placebo at week 34 (31 [86%] vs ten [29%]; odds ratio 13·7 [95% CI 3·7-53·4]; p<0·0001). At week 24, 72 (53%; 95% CI 43·9-61·1) of 137 patients maintained a complete response without up-titration after week 12. Most common adverse events (ie, occurred in >25% of participants) were nausea (57 [42%]), headache (46 [34%]), fatigue (39 [28%]), and adrenal insufficiency (38 [28%]). Hypocortisolism occurred in 70 (51%) patients and adverse events related to adrenal hormone precursors occurred in 58 (42%) patients. One patient died, unrelated to study drug, after the core study phase.
INTERPRETATION: Twice-daily osilodrostat rapidly reduced mean 24-h UFC and sustained this reduction alongside improvements in clinical signs of hypercortisolism; it was also generally well tolerated. Osilodrostat is an effective new treatment option that is approved in Europe for the treatment of endogenous Cushing's syndrome and in the USA for Cushing's disease.
FUNDING: Novartis Pharma AG.

PMID: 32730798 [PubMed - indexed for MEDLINE]

Towards the automatic detection of skin lesion shape asymmetry, color variegation and diameter in dermoscopic images.

Fetched: September 3rd, 2020, 5:01am GMT

Towards the automatic detection of skin lesion shape asymmetry, color variegation and diameter in dermoscopic images.

PLoS One. 2020;15(6):e0234352

Authors: Ali AR, Li J, O'Shea SJ

Abstract
Asymmetry, color variegation and diameter are considered strong indicators of malignant melanoma. The subjectivity inherent in the first two features and the fact that 10% of melanomas tend to be missed in the early diagnosis due to having a diameter less than 6mm, deem it necessary to develop an objective computer vision system to evaluate these criteria and aid in the early detection of melanoma which could eventually lead to a higher 5-year survival rate. This paper proposes an approach for evaluating the three criteria objectively, whereby we develop a measure to find asymmetry with the aid of a decision tree which we train on the extracted asymmetry measures and then use to predict the asymmetry of new skin lesion images. A range of colors that demonstrate the suspicious colors for the color variegation feature have been derived, and Feret's diameter has been utilized to find the diameter of the skin lesion. The decision tree is 80% accurate in determining the asymmetry of skin lesions, and the number of suspicious colors and diameter values are objectively identified.

PMID: 32544197 [PubMed - indexed for MEDLINE]

Management of pigmented skin lesions during pregnancy.

Fetched: September 3rd, 2020, 5:01am GMT

Management of pigmented skin lesions during pregnancy.

Aust J Gen Pract. 2019 09;48(9):621-624

Authors: Friedman EB, Scolyer RA, Thompson JF

Abstract
BACKGROUND: As a result of the rapidly changing hormonal milieu, changing or newly discovered pigmented skin lesions during pregnancy can be diagnostically challenging. It is important for GPs to be aware of the effect of gestational changes on pigment production and features that should raise concern.
OBJECTIVE: The aim of this article is to provide an understanding of common changes that may occur in pigmented lesions during pregnancy, features that are of concern and the management of suspected melanoma in pregnant women.
DISCUSSION: In pregnant women, changing naevi should be evaluated using conventional ABCDE melanoma diagnostic criteria, and suspicious lesions should not be attributed solely to a change in the hormonal milieu. In this population, diagnosed melanoma is probably best treated at a specialist centre.

PMID: 31476830 [PubMed - indexed for MEDLINE]

Skin checks in primary care.

Fetched: September 3rd, 2020, 5:01am GMT

Skin checks in primary care.

Aust J Gen Pract. 2019 09;48(9):614-619

Authors: Sinclair R, Meah N, Arasu A

Abstract
BACKGROUND: The incidence of skin cancers in Australia continues to rise. Early detection and timely management are required.
OBJECTIVE: This article presents a framework for skin examinations in primary care and outlines the various measures available to facilitate early skin cancer detection. Common characteristics of malignant cancers are also discussed.
DISCUSSION: Skin cancer awareness campaigns encourage patients to see their general practitioners (GPs) for complete skin examination. GPs are expected to correctly identify benign and malignant skin lesions and understand their high risk patients. A systematic approach to the skin examination combined with knowledge and awareness of diagnostic tools can aid in the early detection of skin malignancies, and prompt escalation as necessary.

PMID: 31476828 [PubMed - indexed for MEDLINE]

Sentinel lymph node biopsy in patients with malignant melanoma: analysis of post-operative complications.

Fetched: September 3rd, 2020, 5:01am GMT

Sentinel lymph node biopsy in patients with malignant melanoma: analysis of post-operative complications.

ANZ J Surg. 2019 09;89(9):1041-1044

Authors: Solari N, Bertoglio S, Boscaneanu A, Minuto M, Reina S, Palombo D, Bruzzi P, Cafiero F

Abstract
BACKGROUND: This study investigates the incidence of post-operative complications and risk factors of sentinel lymph node biopsy (SLNB) in melanoma patients.
METHODS: A retrospective cohort study was conducted at a single cancer institution on 408 consecutive SLNBs.
RESULTS: Fifty-five post-operative complications occurred in 39 (9.5%) patients and included: wound infection in 24 (5.9%), seroma and lymphorrhea in 15 (3.7%), wound dehiscence in seven (1.7%), lymphocele in six (1.5%) and others in three (0.7%). Univariate analysis failed to identify possible risk factors (i.e. gender, age, lymph node region, number of excised lymph nodes, Breslow index, pT levels, comorbidities, length of surgery and hospital stay). Metastatic sentinel nodes occurred in four of 135 (3%) patients with thin melanoma (Breslow <1 mm) and in 68 of 262 (25.9%) patients with Breslow >1 mm.
CONCLUSION: For patients with thin melanoma in whom the incidence of lymph node metastasis is low, the reported post-operative morbidity of almost 10% of SLNB highlights the need for careful patient selection.

PMID: 31368164 [PubMed - indexed for MEDLINE]

New-Onset Resistant Hypertension in a Newly Diagnosed Prostate Cancer Patient.

Fetched: September 3rd, 2020, 5:01am GMT

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New-Onset Resistant Hypertension in a Newly Diagnosed Prostate Cancer Patient.

Am J Hypertens. 2019 11 15;32(12):1214-1217

Authors: Klomjit N, Rowan DJ, Kattah AG, Bancos I, Taler SJ

Abstract
BACKGROUND: New onset resistant hypertension in a previously stable patient with chronic hypertension should lead to consideration of secondary causes. Electrolyte abnormalities are useful clues for identifying some common causes, especially mineralocorticoid excess.
CASE PRESENTATION: We report the case of a 69-year-old man who developed severe resistant hypertension despite the use of 6 antihypertensive medications, including diuretics. He had metabolic alkalosis and hypokalemia with suppressed plasma renin activity and serum aldosterone. Concurrently, he was diagnosed with small cell neuroendocrine carcinoma of the prostate gland, a rare form of prostate cancer. Despite absence of typical Cushingoid features, investigation confirmed the diagnosis of ectopic adrenocorticotropic hormone (ACTH) syndrome from neuroendocrine prostate cancer. Because of the severity of his hypercortisolism, he underwent urgent bilateral adrenalectomy for hormonal and symptomatic control. Blood pressure improved significantly and he was dismissed with a single antihypertensive agent. Unfortunately, the patient died from his cancer 1 month later.
CONCLUSION: Primary and secondary hyperaldosteronism are usually diagnosed based on measurements of aldosterone and plasma renin activity. However, if plasma renin activity and aldosterone are both low, rare causes of mineralocorticoid excess such as ectopic ACTH syndrome should be entertained.

PMID: 31353410 [PubMed - indexed for MEDLINE]

Permalink for 'Immunotherapy-induced severe neutropenia with neurotoxicity: A case of a 75-year-old woman with ulcerative colitis diagnosed with melanoma.'

Immunotherapy-induced severe neutropenia with neurotoxicity: A case of a 75-year-old woman with ulcerative colitis diagnosed with melanoma.

Fetched: September 3rd, 2020, 5:01am GMT

Immunotherapy-induced severe neutropenia with neurotoxicity: A case of a 75-year-old woman with ulcerative colitis diagnosed with melanoma.

J Oncol Pharm Pract. 2020 Apr;26(3):730-734

Authors: Patel R, Pai L

Abstract
INTRODUCTION: Immune checkpoint inhibitors have transformed the field of oncology moving immuno-oncology to the forefront of cancer treatment. However, immune checkpoint inhibitors can result in serious immune-related adverse events. Hematologic toxicities are rare with incidence of neutropenia from nivolumab less than 1%.
CASE REPORT: We present a case of refractory neutropenia in a 75-year-old woman with ulcerative colitis on adjuvant nivolumab for stage III melanoma.
MANAGEMENT AND OUTCOME: The patient's neutropenia did not improve with high-dose intravenous steroids, filgrastim, mycophenolate mofetil, or intravenous immunoglobulin. She also developed significant neurological symptoms from nivolumab. She was transitioned to comfort measures given her persistent symptoms and poor functional status.
DISCUSSION: Though hematologic malignancies of immune checkpoint inhibitors are rare, they should be considered after other diagnoses are excluded. We discuss the serious immune-related adverse effects of immune checkpoint inhibitors in a patient with an underlying autoimmune disease and general treatment approaches.

PMID: 31315551 [PubMed - indexed for MEDLINE]

Capsaicin-like analogue induced selective apoptosis in A2058 melanoma cells: Design, synthesis and molecular modeling.

Fetched: September 3rd, 2020, 5:01am GMT

Capsaicin-like analogue induced selective apoptosis in A2058 melanoma cells: Design, synthesis and molecular modeling.

Bioorg Med Chem. 2019 07 01;27(13):2893-2904

Authors: Pereira GJV, Tavares MT, Azevedo RA, Martins BB, Cunha MR, Bhardwaj R, Cury Y, Zambelli VO, Barbosa EG, Hediger MA, Parise-Filho R

Abstract
The use of molecules inspired by natural scaffolds has proven to be a very promising and efficient method of drug discovery. In this work, capsaicin, a natural product from Capsicum peppers with antitumor properties, was used as a prototype to obtain urea and thiourea analogues. Among the most promising compounds, the thiourea compound 6g exhibited significant cytotoxic activity against human melanoma A2058 cells that was twice as high as that of capsaicin. Compound 6g induced significant and dose-dependent G0/G1 cell cycle arrest in A2058 cells triggering cell death by apoptosis. Our results suggest that 6g modulates the RAF/MEK/ERK pathway, inducing important morphological changes, such as formation of apoptotic bodies and increased levels of cleaved caspase-3. Compared to capsaicin, 6g had no significant TRPV1/6 agonist effect or irritant effects on mice. Molecular modeling studies corroborate the biological findings and suggest that 6g, besides being a more reactive molecule towards its target, may also present a better pharmacokinetic profile than capsaicin. Inverse virtual screening strategy found MEK1 as a possible biological target for 6g. Consistent with these findings, our observations suggested that 6g could be developed as a potential anticancer agent.

PMID: 31104785 [PubMed - indexed for MEDLINE]

Permalink for 'Pseudoprogression on treatment with immune-checkpoint inhibitors in patients with gastrointestinal malignancies: Case series and short literature review.'

Pseudoprogression on treatment with immune-checkpoint inhibitors in patients with gastrointestinal malignancies: Case series and short literature review.

Fetched: September 3rd, 2020, 5:01am GMT

Pseudoprogression on treatment with immune-checkpoint inhibitors in patients with gastrointestinal malignancies: Case series and short literature review.

Curr Probl Cancer. 2019 10;43(5):487-494

Authors: Michalarea V, Fontana E, Garces AI, Williams A, Smyth EC, Picchia S, Rao S, Chau I, Cunningham D, Bali MA

Abstract
Gastrointestinal cancers are very common cancers with colorectal being the fourth most common type, gastric the sixth, and esophageal the tenth. Although recent advances have been made in management including incorporation of antiangiogenic, anti-EGFR, and anti-HER2 directed therapies, overall their prognosis remains poor. Anti-PD-1 therapy with nivolumab and pembrolizumab are licensed for advanced chemorefractory gastroesophageal cancer and many other checkpoint inhibitor therapies are being assessed alone and in combination in these diseases. One of the challenges posed in assessing response to immunotherapy treatment is the phenomenon of pseudoprogression. This phenomenon, which is well described in patients with malignant melanoma is most frequently described as a size increase of contrast enhancing lesions or appearance of new lesions that stabilize or reduce in size with time. Most other solid tumors have a low incidence of pseudoprogression although cases have been reported for lung, head, and neck cancer and a range of gliomas. Herein we present 6 cases of patients with gastrointestinal cancers who were treated with anti-PD1 (programmed cell death) and anti-PD-L1 (programmed cell death ligand-1) antibodies, and experience pseudoprogression.

PMID: 30827742 [PubMed - indexed for MEDLINE]

Hepatic schwannoma: CT and histologic features.

Fetched: September 3rd, 2020, 5:01am GMT

Hepatic schwannoma: CT and histologic features.

Curr Probl Cancer. 2019 10;43(5):511-513

Authors: Picchia S, Terlizzo M, Bali MA

PMID: 30416007 [PubMed - indexed for MEDLINE]

Permalink for 'Overexpression of ODF1 in Gastrointestinal Tract Neuroendocrine Neoplasms: a Novel Potential Immunohistochemical Biomarker for Well-differentiated Neuroendocrine Tumors.'

Overexpression of ODF1 in Gastrointestinal Tract Neuroendocrine Neoplasms: a Novel Potential Immunohistochemical Biomarker for Well-differentiated Neuroendocrine Tumors.

Fetched: September 3rd, 2020, 5:01am GMT

Overexpression of ODF1 in Gastrointestinal Tract Neuroendocrine Neoplasms: a Novel Potential Immunohistochemical Biomarker for Well-differentiated Neuroendocrine Tumors.

Endocr Pathol. 2020 Sep 01;:

Authors: Li B, Li X, Mao R, Liu M, Fu L, Shi L, Zhao S, Fu M

Abstract
Gastrointestinal tract neuroendocrine neoplasms (NENs) are a group of rare heterogeneous tumors with different prognoses. The 2019 WHO classification of digestive system tumors defines the classification of NENs as neuroendocrine tumors (NETs G1-G3) and neuroendocrine carcinomas (NECs). We investigated outer dense fiber of sperm tails 1 (ODF1) expression in 137 gastrointestinal tract NENs including 53 NETs G1, 29 NETs G2, 3 NETs G3, and 52 NECs. Twenty adenocarcinomas and 6 squamous cell carcinomas also were included in the study. The results showed that ODF1 was positive in 83 of 85 (97.6%) primary gastrointestinal tract NETs, including 9 of 10 (90%) gastric, 19 of 19 (100%) small bowel, 10 of 11 (90.9%) colorectal, and 45 of 45 (100%) appendiceal neoplasms. There was a significantly statistical difference in the rates of ODF1 positivity in NETs (83/85, 97.6%) vs NECs (25/52, 48.1%, P < 0.001). ODF1 showed diffuse staining in NETs G1 (53/53, 100%) and NETs G2 (28/29, 96.6%), > 50% staining in NETs G3 (2/3, 66.7%), and focal staining (< 50%) in NECs (23/52, 44.2%) but 2 cases (2/52) showed > 50% staining. ODF1 showed no expression in all 20 adenocarcinomas and 6 squamous cell carcinomas. In conclusion, ODF1 was firstly identified as a novel marker for NENs, especially for NETs in the gastrointestinal tract. The expression mechanism and clinical significance of ODF1 in NENs needed further study.

PMID: 32869188 [PubMed - as supplied by publisher]

Risk factors for pancreas and lung neuroendocrine neoplasms: a case-control study.

Fetched: September 3rd, 2020, 5:01am GMT

Risk factors for pancreas and lung neuroendocrine neoplasms: a case-control study.

Endocrine. 2020 Aug 31;:

Authors: Giraldi L, Vecchioni A, Carioli G, Bilotta M, La Rosa S, Imperatori A, Volante M, Brizzi MP, Inzani F, Petrone G, Schinzari G, Bianchi A, Margaritora S, Alfieri S, La Vecchia C, Boccia S, Rindi G

Abstract
PURPOSE: Neuroendocrine neoplasia (NEN) has been displaying an incremental trend along the last two decades. This phenomenon is poorly understood, and little information is available on risk factor for neuroendocrine neoplasia development. Aim of this work is to elucidate the role of potentially modifiable risk factors for pancreatic and pulmonary NEN.
METHODS: We conducted a case-control study on 184 patients with NEN (100 pancreas and 84 lung) and 248 controls. The structured questionnaire included 84 queries on socio-demographic, behavioral, dietary and clinical information.
RESULTS: Increased risk was associated with history of cancer ("other tumor", lung OR = 7.18; 95% CI: 2.55-20.20 and pancreas OR = 5.88; 95% CI: 2.43-14.22; "family history of tumor", lung OR = 2.66; 95% CI: 1.53-4.64 and pancreas OR = 1.94; 95% CI: 1.19-3.17; "family history of lung tumor", lung OR = 2.56; 95% CI: 1.05-6.24 and pancreas OR = 2.60; 95% CI: 1.13-5.95). Type 2 diabetes mellitus associated with an increased risk of pancreatic NEN (OR = 3.01; 95% CI: 1.15-7.89).
CONCLUSIONS: Besides site-specific risk factors, there is a significant link between neuroendocrine neoplasia and cancer in general, pointing to a shared cancer predisposition.

PMID: 32869113 [PubMed - as supplied by publisher]

Recurrence Pattern and Surveillance strategy for Rectal Neuroendocrine Tumors after Endoscopic Resection.

Fetched: September 1st, 2020, 5:01am GMT

Recurrence Pattern and Surveillance strategy for Rectal Neuroendocrine Tumors after Endoscopic Resection.

J Gastroenterol Hepatol. 2020 Aug 31;:

Authors: Chung HG, Goh MJ, Kim ER, Hong SN, Kim TJ, Chang DK, Kim YH

Abstract
BACKGROUND AND AIM: Endoscopic resection is highly effective treatment option for rectal neuroendocrine tumors (NETs) as they usually present as small localized tumors. However, there are no well-established surveillance strategies following endoscopic resection. We established our own protocol for the surveillance of rectal NETs after endoscopic resection since 2013. This study aimed to assess the outcome and to optimize the surveillance strategies after endoscopic resection.
METHODS: We retrospectively analyzed the data of patients with endoscopically treated rectal NETs between January 2013 and April 2018 at Samsung Medical Center. We analyzed 337 patients with a median follow-up duration of 35.0 months (min-max: 12.0-88.3).
RESULTS: A total of 329 (97.6 %) patients had tumors ≤1 cm in size and 8 (2.4%) patients had tumors >1 cm in diameter. Synchronous rectal NETs were diagnosed in 9 (2.7%) patients. 13 (3.9%) patients were identified as having positive resection margins. Regardless of the salvage treatment, none of these patients developed recurrence. Metachronous rectal NETs were diagnosed in 9 (2.7 %) patients. Metachronous lesions were associated with the number of synchronous lesions at initial diagnosis (P < 0.001, hazard ratio = 1.75, 95% confidence interval = 1.38-2.23). Extracolonic metastasis was not detected in this study.
CONCLUSION: Although initial screening for detecting metastatic lesions using computed tomography is recommended, repeated imaging for detecting extracolonic recurrence was not necessary for small non-metastatic rectal NETs. However, regular endoscopic follow-up seems reasonable, especially in case of synchronous rectal NETs, for detecting metachronous rectal NETs.

PMID: 32864790 [PubMed - as supplied by publisher]

Pancreatic neuroendocrine tumors G3 and pancreatic neuroendocrine carcinomas: Differences in basic biology and treatment.

Fetched: September 1st, 2020, 5:01am GMT

Pancreatic neuroendocrine tumors G3 and pancreatic neuroendocrine carcinomas: Differences in basic biology and treatment.

World J Gastrointest Oncol. 2020 Jul 15;12(7):705-718

Authors: Zhang MY, He D, Zhang S

Abstract
In 2017 the World Health Organization revised the criteria for classification of pancreatic neuroendocrine neoplasms (pNENs) after a consensus conference at the International Agency for Research on Cancer. The major change in the new classification was to subclassify the original G3 group into well-differentiated pancreatic neuroendocrine tumors G3 (pNETs G3) and poorly differentiated pancreatic neuroendocrine carcinomas (pNECs), which have been gradually proven to be completely differ

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