Rare Cancer News & Clinical Trials » Endocrine/Neuroendocrine

Endocrine/Neuroendocrine (537 unread)

1 2 3 ... 15

The role of 18F-FDG PET/CT in the management of Merkel cell carcinoma: The experience of 51 studies in our institution.

Fetched: January 18th, 2021, 5:01am GMT

The role of 18F-FDG PET/CT in the management of Merkel cell carcinoma: The experience of 51 studies in our institution.

Rev Esp Med Nucl Imagen Mol. 2021 Jan 12;:

Authors: López Prior V, Llombart Cussac B

Abstract
OBJECTIVES: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine tumor with limited evidence on the role of 18F-FDG PET/CT. The aim of this study was to assess the impact of the 18F-FDG PET/CT in the management of MCC.
METHODS: Fifty-one studies of 18F-FDG PET/CT of 35 patients (19 men [54.30%]; 72.17±14.63years) with histologic diagnosis of MCC were retrospectively evaluated. The change in tumor staging and the impact on the treatment were analysed.
RESULTS: There were 23 PET/CT positive studies (45.10%) and 28 (54.90%) negative. Thirty four (66.7%) studies were performed for assessment of stage at initial presentation and 17 (33.3%) were performed during the follow up: 6 (35.29%) for suspected recurrence; 7 (41.18%) for restaging; 4 (23.53%) as a part of ongoing surveillance. On the basis of PET/CT results, there was a change in disease stage (SC) in 20 studies (39.20%) and impact in the management (MI) in 28 (54.90%): 11 (32.40%) SC and 12 (35.30%) MI in the initial staging; 5 (71.43%) SC and 7 (100%) MI in the restaging; 3 (50.00%) SC and 6 (100%) MI in suspected recurrence; 1 (25.00%) SC and 3 (75.00%) MI in the surveillance. 18F-FDG PET/CT incidentally detected one additional histologically confirmed cancer. The presence of nodal involvement in the beginning (0.0098; HR 3.82; 95%CI: 1.38-10.6), chemotherapy treatment (6e-04; HR 7.06; 95%CI: 2.30-21.60), size of primary tumor >2cm (6e-04; HR 7.06; 95%CI: 2.30-21.60) and positive resection margin (0.00069; HR 4.01; 95%CI: 1.46-11.00) were statistically significant prognostic factors for overall survival. There was a trend towards significance for worse overall survival with initial positive 18F-FDG PET/CT but the trend did not reach statistical significance.
CONCLUSION: 18F-FDG PET/CT altered the stage in 2 out of 5 studies and changed the treatment in more than half of the studies performed. The study confirms the important impact of 18F-FDG PET/CT on the management of MCC patients.

PMID: 33451922 [PubMed - as supplied by publisher]

Permalink for 'Sex Differences in Overall Survival and the Effect of Radiotherapy in Merkel Cell Carcinoma-A Retrospective Analysis of a Swedish Cohort.'

Sex Differences in Overall Survival and the Effect of Radiotherapy in Merkel Cell Carcinoma-A Retrospective Analysis of a Swedish Cohort.

Fetched: January 17th, 2021, 5:01am GMT

Sex Differences in Overall Survival and the Effect of Radiotherapy in Merkel Cell Carcinoma-A Retrospective Analysis of a Swedish Cohort.

Cancers (Basel). 2021 Jan 12;13(2):

Authors: Björn Andtback H, Björnhagen-Säfwenberg V, Shi H, Lui WO, Masucci GV, Villabona L

Abstract
Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer where Merkel cell Polyomavirus (MCPyV) contributes to the pathogenesis. In an adjuvant setting, radiotherapy (RT) is believed to give a survival benefit. The prognostic impact of sex related to MCPyV-status and adjuvant RT were analyzed in patients referred to Karolinska University Hospital. Data were collected from 113 patients' hospital records and MCPyV analyses were made in 54 patients (48%). We found a significantly better overall survival (OS) for women compared to men and a significant difference in OS in patients receiving adjuvant RT. Furthermore, we found that men with virus negative MCC have an increased risk for earlier death (HR 3.6). This indicates that MCPyV positive and negative MCC act as two different diseases, and it might be due to different mechanism in the immune response between male and female patients. This could have significance in tailoring treatment and follow-up in MCC patients in the future.

PMID: 33445741 [PubMed]

$Permalink for 'Activity of ipilimumab plus nivolumab in avelumab-refractory Merkel cell carcinoma.'$

Activity of ipilimumab plus nivolumab in avelumab-refractory Merkel cell carcinoma.

Fetched: January 15th, 2021, 5:00am GMT

Activity of ipilimumab plus nivolumab in avelumab-refractory Merkel cell carcinoma.

Cancer Immunol Immunother. 2021 Jan 13;:

Authors: Glutsch V, Kneitz H, Gesierich A, Goebeler M, Haferkamp S, Becker JC, Ugurel S, Schilling B

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine cutaneous malignancy with poor prognosis. In Europe, approved systemic therapies are limited to the PD-L1 inhibitor avelumab. For avelumab-refractory patients, efficient and safe treatment options are lacking.
METHODS: At three different sites in Germany, clinical and molecular data of patients with metastatic MCC being refractory to the PD-L1 inhibitor avelumab and who were later on treated with combined IPI/NIVO were retrospectively collected and evaluated.
RESULTS: Five patients treated at three different academic sites in Germany were enrolled. Three out of five patients investigated for this report responded to combined IPI/NIVO according to RECIST 1.1. Combined immunotherapy was well tolerated without any grade II or III immune-related adverse events. Two out of three responders to IPI/NIVO received platinum-based chemotherapy in between avelumab and combined immunotherapy.
CONCLUSION: In this small retrospective study, we observed a high response rate and durable responses to subsequent combined immunotherapy with IPI/NIVO in avelumab-refractory metastatic MCC patients. In conclusion, our data suggest a promising activity of second- or third-line PD-1- plus CTLA-4-blockade in patients with anti-PD-L1-refractory MCC.

PMID: 33439294 [PubMed - as supplied by publisher]

The Merkel Cell Polyomavirus T Antigens Function as Tumor Promoters in Murine Skin.

Fetched: January 15th, 2021, 5:00am GMT

The Merkel Cell Polyomavirus T Antigens Function as Tumor Promoters in Murine Skin.

Cancers (Basel). 2021 Jan 09;13(2):

Authors: Spurgeon ME, Liem A, Buehler D, Cheng J, DeCaprio JA, Lambert PF

Abstract
Merkel cell polyomavirus (MCPyV) causes the majority of human Merkel cell carcinomas (MCC), a rare but highly aggressive form of skin cancer. We recently reported that constitutive expression of MCC tumor-derived MCPyV tumor (T) antigens in the skin of transgenic mice leads to hyperplasia, increased proliferation, and spontaneous epithelial tumor development. We sought to evaluate how the MCPyV T antigens contribute to tumor formation in vivo using a classical, multi-stage model for squamous cell carcinoma development. In this model, two chemical carcinogens, DMBA and TPA, contribute to two distinct phases of carcinogenesis-initiation and promotion, respectively-that are required for tumors to develop. By treating the MCPyV transgenic mice with each chemical carcinogen, we determined how the viral oncogenes contributed to carcinogenesis. We observed that the MCPyV T antigens synergized with the tumor initiator DMBA, but not with the tumor promoter TPA, cause tumors. Therefore, the MCPyV tumor antigens function primarily as tumor promoters, similar to that seen with human papillomavirus (HPV) oncoproteins. These studies provide insight into the role of MCPyV T antigen expression in tumor formation in vivo and contribute to our understanding of how MCPyV may function as a human DNA tumor virus.

PMID: 33435392 [PubMed]

TTF-1 Positivity in Merkel Cell Carcinoma: The Chosen Clone Matters.

Fetched: January 13th, 2021, 5:01am GMT

TTF-1 Positivity in Merkel Cell Carcinoma: The Chosen Clone Matters.

Am J Dermatopathol. 2020 May;42(5):386-387

Authors: Creytens D

PMID: 31917690 [PubMed - indexed for MEDLINE]

Viruses in Skin Cancer (VIRUSCAN): Study Design and Baseline Characteristics of a Prospective Clinic-Based Cohort Study.

Fetched: January 13th, 2021, 5:01am GMT

Viruses in Skin Cancer (VIRUSCAN): Study Design and Baseline Characteristics of a Prospective Clinic-Based Cohort Study.

Cancer Epidemiol Biomarkers Prev. 2020 01;29(1):39-48

Authors: Amorrortu RP, Fenske NA, Cherpelis BS, Vijayan L, Zhao Y, Balliu J, Messina JL, Sondak VK, Giuliano AR, Waterboer T, Pawlita M, Gheit T, Tommasino M, Rollison DE

Abstract
BACKGROUND: Accumulating evidence suggests that cutaneous viral infections are risk factors for the development of keratinocyte carcinomas. The Viruses in Skin Cancer (VIRUSCAN) Study, a prospective cohort study, was established in 2014 to investigate the risk of keratinocyte carcinoma associated with cutaneous human papillomavirus and polyomavirus infection and the possible interaction with ultraviolet radiation exposure (UVR).
METHODS/RESULTS: VIRUSCAN incorporates repeated measures of viral infection using multiple markers of infection and quantitative measures of UVR using a spectrophotometer. Participants were recruited between July 14, 2014 and August 31, 2017 at the University of South Florida Dermatology Clinic in Tampa, FL. After excluding 124 individuals with prevalent keratinocyte carcinomas at baseline, 1,179 participants (53.2% women, 46.8% men, all ages 60 years and older) were followed for up to 4 years with routine skin exams occurring every 6 to 12 months. Here, we present the VIRUSCAN Study design, methods, and baseline characteristics, including demographics, sun exposure behavior, quantitative UVR exposure measurements, and cutaneous viral prevalence, for the full study cohort.
CONCLUSIONS: The VIRUSCAN Study will provide critical temporal evidence needed to assess the causality of the role cutaneous viral infections play in the development of keratinocyte carcinomas, as well as the potential interaction between cutaneous viral infections and UVR exposure.
IMPACT: Study findings will be valuable in future development of novel keratinocyte carcinoma prevention strategies.

PMID: 31427307 [PubMed - indexed for MEDLINE]

Disease Progression in Cutaneous Squamous Cell Carcinoma Patients With Satellitosis and In-transit Metastasis.

Fetched: January 11th, 2021, 5:01am GMT

Disease Progression in Cutaneous Squamous Cell Carcinoma Patients With Satellitosis and In-transit Metastasis.

Anticancer Res. 2021 Jan;41(1):289-295

Authors: Smile TD, Xiong DX, Varra V, Winter IW, Beal BT, Gastman BR, Geiger JL, Adelstein DJ, Bergfeld WF, Piliang MP, Billings SD, Ko JS, Knackstedt TJ, Lucas JL, Poblete-Lopez CM, Meine JG, Vij A, Vidimos AT, Koyfman SA

Abstract
BACKGROUND/AIM: Satellitosis/in-transit metastasis (S-ITM) has prognostic value in melanoma and Merkel cell carcinoma, but is not incorporated into cutaneous squamous cell carcinoma (cSCC) staging.
PATIENTS AND METHODS: From our IRB-approved registry, patients with high-risk cSCC, including patients with S-ITM, were identified. Univariate (UVA) and multivariate (MVA) analyses were performed to compare disease progression (DP) and overall survival (OS). Cumulative incidence of DP and OS analyses were performed using Fine-Gray and Kaplan-Meier methods, respectively.
RESULTS: A total of 18 S-ITM subjects were compared to 247 high risk subjects including T3N0 (n=143), N1-N3 without extranodal extension (ENE) (n=56), N1-N3 with ENE (n=26) and M1 disease (n=22). Median follow up was 16.5 months. Three-year rates of DP were 22% for T3N0, 42% for S-ITM, 48% for T4 bone invasion, 50% for N1-N3 without extranodal extension (ENE), 53% for N1-N3 with ENE, and 66% for M1. Patients with S-ITM did not experience significantly worse DP compared to those with T3N0 (HR=1.96, 95%CI=0.8-4.9; p=0.14).
CONCLUSION: Cutaneous SCC patients with S-ITM experienced outcomes similar to locally advanced non-metastatic cSCC patients. Larger studies are needed to guide incorporation into staging systems.

PMID: 33419823 [PubMed - as supplied by publisher]

Targeting the expression of T antigens with Selinexor (KPT-330) shows promise for MCPyV-positive Merkel cell carcinoma treatment.

Fetched: January 8th, 2021, 5:01am GMT

Targeting the expression of T antigens with Selinexor (KPT-330) shows promise for MCPyV-positive Merkel cell carcinoma treatment.

Br J Dermatol. 2021 Jan 05;:

Authors: Gupta R, Simonette RA, Doan HQ, Rady PL, Tyring SK

Abstract
Merkel cell carcinoma (MCC) is a rare primary neuroendocrine skin cancer. In the Northern hemisphere, the disease most commonly arises as a result of infection with Merkel cell polyomavirus (MCPyV).1 Although the incidence of MCC is only 0.7 per 100,000 individuals in the United States, this number is increasing worldwide, and the cancer is highly aggressive, often carrying a poor prognosis.2 Immunotherapies such as pembrolizumab have emerged as leading treatments for MCPyV-associated MCC; however, only a subset of patients respond to these agents, and many require other treatments to remain in remission.

PMID: 33403670 [PubMed - as supplied by publisher]

Navitoclax combined with Alpelisib effectively inhibits Merkel cell carcinoma cell growth in vitro.

Fetched: January 8th, 2021, 5:01am GMT

Navitoclax combined with Alpelisib effectively inhibits Merkel cell carcinoma cell growth in vitro.

Ther Adv Med Oncol. 2020;12:1758835920975621

Authors: Chteinberg E, Wetzels S, Gerritsen W, Temmerman L, van den Oord J, Biessen E, Kurz AK, Winnepenninckx V, Zenke M, Speel EJ, Zur Hausen A

Abstract
Background: Merkel cell carcinoma (MCC) is a highly malignant skin cancer. Despite major treatment improvements during the last decade, up to 50% of patients do not respond to therapy or develop recurrent disease. For these patients, alternative treatment options are urgently needed. Here, we assessed the efficacy of the combination of the BCL-2 inhibitor Navitoclax and the PI3K p110α inhibitor Alpelisib in MCC cell lines.
Methods: The expression of BCL-2 was assessed by immunohistochemistry in MCC and MCC cell lines. Treatment with Navitoclax and Alpelisib alone and in combination was performed on four MCC cell lines. The decrease of cell viability during treatment was assessed by XTT assay and visualized for the combinations by 3D combinatorial index plotting. The increase of apoptotic cells was determined by cleaved PARP Western blotting and Annexin V staining.
Results: Some 94% of MCCs and all three MCPyV-positive cell lines showed BCL-2 expression. Navitoclax monotreatment was shown to be highly effective when treating BCL-2-positive cell lines (IC50-values ranging from 96.0 to 323.0 nM). The combination of Alpelisib and Navitoclax resulted in even stronger synergistic and prolonged inhibitions of MCC cell viability through apoptosis up to 4 days.
Discussion: Our results show that the anti-apoptotic BCL-2 is frequently expressed in MCC and MCC cell lines. Inhibition of BCL-2 by Navitoclax in combination with Alpelisib revealed a strong synergy and prolonged inhibition of MCC cell viability and induction of apoptosis. The combination of Navitoclax and Alpelisib is a novel potential treatment option for MCC patients.

PMID: 33403016 [PubMed]

Permalink for 'Usefulness of ultrasonography in determining the surgical excision margin in non-melanocytic skin cancer: A comparative analysis of preoperative ultrasonography and postoperative histopathology.'

Usefulness of ultrasonography in determining the surgical excision margin in non-melanocytic skin cancer: A comparative analysis of preoperative ultrasonography and postoperative histopathology.

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

Usefulness of ultrasonography in determining the surgical excision margin in non-melanocytic skin cancer: A comparative analysis of preoperative ultrasonography and postoperative histopathology.

Medicine (Baltimore). 2020 Dec 18;99(51):e23789

Authors: Kim HJ, Lee SJ, Lee JH, Shin SH, Xu H, Yang I, Kim JH, Kim SH, Suh IS

Abstract
ABSTRACT: Skin cancer diagnoses are rising due to increasing ultraviolet ray exposure and an aging population. The complete surgical excision of skin cancer, including a normal tissue, has been the widely performed and determining the adequate safety margin is essential. In this study, we compared the preoperative thickness and width of skin cancer by ultrasonography with the measurements by histopathologic findings.A total of 211 patients were enrolled in this study and ultrasonography was performed on 30 patients. The width (long and short axis) and thickness of the skin cancers were measured using electronic calipers of ultrasonographic calipers preoperatively and microscope postoperatively.The skin cancers were basal cell carcinoma (n = 17), squamous cell carcinoma (n = 10), Merkel cell carcinoma (n = 1), mucinous carcinoma (n = 1), and sebaceous carcinoma (n = 1). The mean width (long and short axis) and thickness of the cancers measured by ultrasonography was 1.25 (0.76) cm, 0.96 (0.65) cm, and 0.37 (0.28) cm. The measurements by histopathology was 1.24 (0.84) cm, 0.95 (0.65) cm, and 0.27 (0.24) cm. Kendall's tau-b correlation coefficient between measurements by ultrasonography and histopathology was as follows: long axis, r = 0.733, P < .001; short axis, r = 0.671, P < .001; thickness, r = 0.740, P < .001. Spearman's rank correlation coefficient between measurements by ultrasonography and histopathology was as follows: long axis, r = 0.865, P < .001; short axis, r = 0.829, P < .001; thickness, r = 0.842, P < .001. The difference in mean thickness between the total excised tissue and the skin cancer was 0.29 (0.43) cm (range 0.05-0.40 cm) in basal cell carcinoma and 0.56 (0.58) cm (range 0.05-2.22 cm) in squamous cell carcinoma.Ultrasonography can accurately measure the width and thickness of skin cancer and predict the safety margins of the wide excision. Preoperative ultrasonography is a good diagnostic tool for surgical planning. Additional studies with larger populations are needed to quantify the range of vertical safety margins.

PMID: 33371149 [PubMed - in process]

Rare intestinal metastasis of Merkel cell carcinoma causing bowel obstruction.

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

Rare intestinal metastasis of Merkel cell carcinoma causing bowel obstruction.

ANZ J Surg. 2020 01;90(1-2):E30-E31

Authors: Nahab F, Kozman MA

PMID: 30974513 [PubMed - indexed for MEDLINE]

Neuronal intermediate filament IgGs in CSF: Autoimmune Axonopathy Biomarkers.

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

Neuronal intermediate filament IgGs in CSF: Autoimmune Axonopathy Biomarkers.

Ann Clin Transl Neurol. 2020 Dec 28;:

Authors: McKeon A, Shelly S, Zivelonghi C, Basal E, Dubey D, Flanagan E, Madhavan AA, Mariotto S, Toledano M, Tracy JA, Zekeridou A, Pittock SJ

Abstract
OBJECTIVES: To describe CSF-defined neuronal intermediate filament (NIF) autoimmunity.
METHODS: NIF-IgG CSF-positive patients (41, 0.03% of 118599 tested, 1996-2019) were included (serum was neither sensitive nor specific). Criteria-based patient NIF-IgG staining of brain and myenteric NIFs was detected by indirect immunofluorescence assay (IFA); NIF-specificity was confirmed by cell-based assays (CBAs, alpha internexin, neurofilament light [NF-L]), heavy-[NF-H] chain).
RESULTS: Sixty-one percent of 41 patients were men, median age, 61 years (range, 21-88). Syndromes were encephalopathy predominant (23), cerebellar ataxia predominant (11), or myeloradiculoneuropathies (7). MRI abnormalities (T2 hyperintensities of brain, spinal cord white matter tracts. and peripheral nerve axons) and neurophysiologic testing (EEG, EMG, evoked potentials) co-localized with clinical neurological phenotypes (multifocal in 29%). Thirty patients (73%) had ≥ 1 immunological perturbation: cancer (paraneoplastic), 22; systemic infection (parainfectious [including ehrlichosis, 3] or HIV), 7; checkpoint-inhibitor cancer immunotherapy, 4; other, 5. Cancers were as follows: neuroendocrine-lineage carcinomas, 12 (small cell, 6; Merkel cell, 5; pancreatic, 1 [11/12 had NF-L-IgG detected, versus 8/29 others, P = 0.0005]) and other, 11. Onset was predominantly subacute (92%) and accompanied by inflammatory CSF (75%), and immunotherapy response (77%). In contrast, CSF controls (15684 total) demonstrated NIF-IgG negativity (100% of test validation controls), and low frequencies of autoimmune diagnoses (20% of consecutively referred clinical specimens) and neuroendocrine-lineage carcinoma diagnosis (3.1% vs. 30% of NIF cases), P < 0.0001. Median NF-L protein concentration was higher in 8 NF-L-IgG-positive patients (median, 6718 ng/L) than 16 controls.
INTERPRETATION: Neurological autoimmunity, defined by CSF-detected NIF-IgGs, represents a continuum of treatable axonopathies, sometimes paraneoplastic or parainfectious.

PMID: 33369283 [PubMed - as supplied by publisher]

Robust Production of Merkel Cell Polyomavirus Oncogene Specific T Cells From Healthy Donors for Adoptive Transfer.

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

Robust Production of Merkel Cell Polyomavirus Oncogene Specific T Cells From Healthy Donors for Adoptive Transfer.

Front Immunol. 2020;11:592721

Authors: Davies SI, Barrett J, Wong S, Chang MJ, Muranski PJ, Brownell I

Abstract
Virus positive Merkel cell carcinoma (VP-MCC) is an aggressive but immunogenic skin malignancy driven by Merkel cell polyomavirus (MCPyV) T antigen (TAg). Since adoptive T cell transfer (ACT) can be effective against virus-driven malignancies, we set out to develop a methodology for generating MCPyV TAg specific T cells. MCPyV is a common, asymptomatic infection and virus-exposed healthy donors represent a potential source of MCPyV TAg specific T cells for ACT. Virus specific T cells were generated using monocyte-derived dendritic cells (moDCs) pulsed with MCPyV TAg peptide libraries and co-cultured with autologous T cells in supplemented with pro-inflammatory and homeostatic cytokines for 14 days. Specific reactivity was observed predominantly within the CD4+ T cell compartment in the cultures generated from 21/46 random healthy donors. Notably, responses were more often seen in donors aged 50 years and older. TAg specific CD4+ T cells specifically secreted Th1 cytokines and upregulated CD137 upon challenge with MCPyV TAg peptide libraries and autologous transduced antigen presenting cells. Expanded T cells from healthy donors recognized epitopes of both TAg splice variants found in VP-MCC tumors, and minimally expressed exhaustion markers. Our data show that MCPyV specific T cells can be expanded from healthy donors using methods appropriate for the manufacture of clinical grade ACT products.

PMID: 33362774 [PubMed - in process]

Permalink for 'Glucose-6-phosphate dehydrogenase correlates with tumor immune activity and programmed death ligand-1 expression in Merkel cell carcinoma.'

Glucose-6-phosphate dehydrogenase correlates with tumor immune activity and programmed death ligand-1 expression in Merkel cell carcinoma.

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

Glucose-6-phosphate dehydrogenase correlates with tumor immune activity and programmed death ligand-1 expression in Merkel cell carcinoma.

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

Authors: Nakamura M, Nagase K, Yoshimitsu M, Magara T, Nojiri Y, Kato H, Kobayashi T, Teramoto Y, Yasuda M, Wada H, Ozawa T, Umemori Y, Ogata D, Morita A

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) is a rare and highly malignant skin cancer. Some cases have a good prognosis and spontaneous regression can occur. Reported prognostic markers, such as Merkel cell polyoma virus infection or programmed death ligand-1 (PD-L1) expression, remain insufficient for precisely estimating the vastly different patient outcomes. We performed RNA sequencing to evaluate the immune response and comprehensively estimate prognostic values of immunogenic factors in patients with MCC.
METHODS: We collected 90 specimens from 71 patients and 53 blood serum samples from 21 patients with MCC at 10 facilities. The mRNA was extracted from formalin-fixed paraffin-embedded tissues. Next-generation sequencing, immunohistochemical staining and blood serum tests were performed.
RESULTS: Next-generation sequencing results classified MCC samples into two types: the 'immune active type' was associated with better clinical outcomes than the 'cell division type'. Expression of the glucose-6-phosphate dehydrogenase (G6PD) gene was highly significantly upregulated in the 'cell division type'. Among 395 genes, G6PD expression correlated with the presence of lymph node or distant metastases during the disease course and significantly negatively correlated with PD-L1 expression. Immunohistochemical staining of G6PD also correlated with disease-specific survival and exhibited less heterogeneity compared with PD-L1 expression. G6PD activity could be measured by a blood serum test. The detection values significantly increased as the cancer stage progressed and significantly decreased after treatment.
CONCLUSIONS: G6PD expression was an immunohistochemically and serum-detectable prognostic marker that negatively correlated with immune activity and PD-L1 levels, and could be used to predict the immunotherapy response.

PMID: 33361404 [PubMed - in process]

Merkel cell carcinoma of an unknown primary.

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

Merkel cell carcinoma of an unknown primary.

J Dtsch Dermatol Ges. 2020 Mar;18(3):253-255

Authors: Edmonston D, O'steen L, Fredenburg K, Mendenhall WM

PMID: 32077591 [PubMed - indexed for MEDLINE]

Unusual Presentation of Merkel Cell Carcinoma.

Fetched: December 23rd, 2020, 5:00am GMT

Unusual Presentation of Merkel Cell Carcinoma.

Ear Nose Throat J. 2020 03;99(3):200-202

Authors: Richa T, Ghorra C, Melkane AE

PMID: 30974990 [PubMed - indexed for MEDLINE]

Permalink for 'Immunoglobulins to mitigate paraneoplastic Lambert Eaton Myasthenic Syndrome under checkpoint inhibition in Merkel cell carcinoma.'

Immunoglobulins to mitigate paraneoplastic Lambert Eaton Myasthenic Syndrome under checkpoint inhibition in Merkel cell carcinoma.

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

Immunoglobulins to mitigate paraneoplastic Lambert Eaton Myasthenic Syndrome under checkpoint inhibition in Merkel cell carcinoma.

Neurol Res Pract. 2020;2:52

Authors: Dohrn MF, Schöne U, Küppers C, Christen D, Schulz JB, Gess B, Tauber S

Abstract
Lambert-Eaton myasthenic syndrome (LEMS) is a rare, autoimmune or paraneoplastic condition characterized by muscle weakness and fatigability. In cancer therapy, immune checkpoint inhibitors (ICI) sensitize the immune system for tumor antigens. We report a 62-year-old, female patient with paraneoplastic LEMS as first manifestation of Merkel cell carcinoma. Under avelumab, the LEMS exacerbated with worsening of limb weakness and a severely reduced vital capacity (< 1 l). To treat this immunological side effect, we added a regimen with intravenous immunoglobulins. Hereby, the LEMS improved significantly. As we were able to continue the cancer treatment, the Merkel cell carcinoma has been in remission so far. This is the first description of paraneoplastic LEMS, avelumab, and Merkel cell carcinoma. We conclude that immunoglobulins are an option to control an ICI-associated deterioration of paraneoplastic symptoms.

PMID: 33324947 [PubMed]

Merkel Cell Polyomavirus Encodes Circular RNAs (circRNAs) Enabling a Dynamic circRNA/microRNA/mRNA Regulatory Network.

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

Merkel Cell Polyomavirus Encodes Circular RNAs (circRNAs) Enabling a Dynamic circRNA/microRNA/mRNA Regulatory Network.

mBio. 2020 12 15;11(6):

Authors: Abere B, Zhou H, Li J, Cao S, Toptan T, Grundhoff A, Fischer N, Moore PS, Chang Y

Abstract
Viral noncoding RNAs have acquired increasing prominence as important regulators of infection and mediators of pathogenesis. Circular RNAs (circRNAs) generated by backsplicing events have been identified in several oncogenic human DNA viruses. Here, we show that Merkel cell polyomavirus (MCV), the etiologic cause of ∼80% of Merkel cell carcinomas (MCCs), also expresses circular RNAs. By RNase R-resistant RNA sequencing, four putative circRNA backsplice junctions (BSJs) were identified from the MCV early region (ER). The most abundantly expressed MCV circRNA, designated circMCV-T, is generated through backsplicing of all of ER exon II to form a 762-nucleotide (nt) circular RNA molecule. Curiously, circMCV-T, as well as two other less abundantly expressed putative MCV circRNAs, overlaps in a complementary fashion with the MCV microRNA (miRNA) locus that encodes MCV-miR-M1. circMCV-T is consistently detected in concert with linear T antigen transcripts throughout infection, suggesting a crucial role for this RNA molecule in the regulatory functions of the early region, known to be vital for viral replication. Knocking out the hairpin structure of MCV-miR-M1 in genomic early region expression constructs and using a new high-efficiency, recombinase-mediated, recircularized MCV molecular clone demonstrates that circMCV-T levels decrease in the presence of MCV-miR-M1, underscoring the interplay between MCV circRNA and miRNA. Furthermore, circMCV-T partially reverses the known inhibitory effect of MCV-miR-M1 on early gene expression. RNase R-resistant RNA sequencing of lytic rat polyomavirus 2 (RatPyV2) identified an analogously located circRNA, stipulating a crucial, conserved regulatory function of this class of RNA molecules in the family of polyomaviruses.IMPORTANCE Covalently closed circular RNAs were recently described in the human DNA tumor viruses Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV), and human papillomavirus (HPV). Here, we show that MCV, another DNA tumor virus, generates circRNAs from its early regulatory region in concert with T antigen linear transcripts. MCV circMCV-T interacts with another MCV noncoding RNA, miR-M1, to functionally modulate early region transcript expression important for viral replication and long-term episomal persistence. This work describes a dynamic regulatory network integrating circRNA/miRNA/mRNA biomolecules and underscores the intricate functional modulation between several classes of polyomavirus-encoded RNAs in the control of viral replication.

PMID: 33323517 [PubMed - in process]

Pan-Tumor Pathologic Scoring of Response to PD-(L)1 Blockade.

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

Pan-Tumor Pathologic Scoring of Response to PD-(L)1 Blockade.

Clin Cancer Res. 2020 02 01;26(3):545-551

Authors: Stein JE, Lipson EJ, Cottrell TR, Forde PM, Anders RA, Cimino-Mathews A, Thompson ED, Allaf ME, Yarchoan M, Feliciano J, Wang H, Jaffee EM, Pardoll DM, Topalian SL, Taube JM

Abstract
PURPOSE: Pathologic response assessment of tumor specimens from patients receiving systemic treatment provides an early indication of therapeutic efficacy and predicts long-term survival. Grading systems for pathologic response were first developed for chemotherapy in select tumor types. Immunotherapeutic agents have a mechanism of action distinct from chemotherapy and are being used across a broad array of tumor types. A standardized, universal scoring system for pathologic response that encompasses features characteristic for immunotherapy and spans tumor types is needed.
EXPERIMENTAL DESIGN: Hematoxylin and eosin-stained slides from neoadjuvant surgical resections and on-treatment biopsies were assessed for features of immune-related pathologic response (irPR). A total of 258 specimens from patients with 11 tumor types as part of ongoing clinical trials for anti-PD-(L)1 were evaluated. An additional 98 specimens from patients receiving anti-PD-(L)1 in combination with other treatments were also reviewed, including those from three additional tumor types.
RESULTS: Common irPR features (immune activation, cell death, tissue repair, and regression bed) were present in all tumor types reviewed, including melanoma, non-small cell lung, head and neck squamous cell, Merkel cell, and renal cell carcinoma, among others. Features were consistent across primary tumors, lymph nodes, and distant metastases. Specimens from patients treated with anti-PD-(L)1 in combination with another agent also exhibited irPR features.
CONCLUSIONS: irPR features are consistent across tumor types and treatment settings. Standardized, pan-tumor irPR criteria (irPRC) are defined and associated specimen-handling considerations are described. Future, prospective studies are merited to validate irPRC in larger datasets and to associate pathologic features with long-term patient outcomes.

PMID: 31672770 [PubMed - indexed for MEDLINE]

Permalink for 'Large nuclear size correlated with better overall survival, Merkel cell polyomavirus positivity, and terminal deoxynucleotidyl transferase expression in Merkel cell carcinoma.'

Large nuclear size correlated with better overall survival, Merkel cell polyomavirus positivity, and terminal deoxynucleotidyl transferase expression in Merkel cell carcinoma.

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

Large nuclear size correlated with better overall survival, Merkel cell polyomavirus positivity, and terminal deoxynucleotidyl transferase expression in Merkel cell carcinoma.

J Am Acad Dermatol. 2020 Dec 11;:

Authors: Moran JMT, Biecek P, Donizy P, Wu CL, Kopczynski J, Pieniazek M, Ryś J, Hoang MP

PMID: 33317843 [PubMed - as supplied by publisher]

Permalink for 'Droplet-digital PCR assay to detect Merkel cell polyomavirus sequences in chorionic villi from spontaneous abortion affected females.'

Droplet-digital PCR assay to detect Merkel cell polyomavirus sequences in chorionic villi from spontaneous abortion affected females.

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

Droplet-digital PCR assay to detect Merkel cell polyomavirus sequences in chorionic villi from spontaneous abortion affected females.

J Cell Physiol. 2020 03;235(3):1888-1894

Authors: Tagliapietra A, Rotondo JC, Bononi I, Mazzoni E, Magagnoli F, Gonzalez LO, Contini C, Vesce F, Tognon M, Martini F

Abstract
Droplet-digital polymerase chain reaction (ddPCR) technique was set up to detect/quantify Merkel cell polyomavirus (MCPyV) DNA in clinical specimens, including chorionic villi and peripheral blood mononuclear cells (PBMCs) from spontaneous abortion (SA)-affected females. This ddPCR assay showed high accuracy, sensitivity, and specificity in detecting MCPyV DNA cloned in a recombinant plasmid vector, the control. ddPCR was extended to MCPyV DNA to investigate/quantify its sequences in clinical samples. Overall, 400 samples were analyzed, that is, 100 chorionic villi and 100 PBMCs, from SA females (n = 100), the cases, and 100 chorionic villi and 100 PBMCs from females who underwent voluntary pregnancy interruption (VI, n = 100), the control. MCPyV DNA was detected in 4/100 (4%) and 5/100 (5%) of SA and VI chorionic villi, respectively. The mean viral DNA load was 1.99 ( ± 0.94 standard mean deviation [SD]) copy/104 cells in SA and 3.02 ( ± 1.86 [SD]) copy/104 cells in VI. In PBMCs, MCPyV DNA was revealed in 9/100 (9%) and 14/100 (14%) of SA and VI, with a mean of 2.09 ( ± 1.17 [SD]) copy/104 cells and 4.09 ( ± 4.26 [SD]) copy/104 cells in SA and VI, respectively. MCPyV gene expression analysis by quantitative PCR for the large T antigen (LT) and viral capsid protein 1 (VP1) showed their mRNAs in 2/4 (50%) SA- and 2/5 (40%) VI-MCPyV-positive samples. MCPyV DNA was detected/quantified using the ddPCR technique, in chorionic villi and PBMCs from SA and VI. In our experimental conditions, ddPCR provided a powerful tool to detect/quantify MCPyV DNA sequences in clinical samples.

PMID: 31549405 [PubMed - indexed for MEDLINE]

Predictors of immunotherapy benefit in Merkel cell carcinoma.

Fetched: December 16th, 2020, 5:01am GMT

Predictors of immunotherapy benefit in Merkel cell carcinoma.

Oncotarget. 2020 Nov 24;11(47):4401-4410

Authors: Kacew AJ, Dharaneeswaran H, Starrett GJ, Thakuria M, LeBoeuf NR, Silk AW, DeCaprio JA, Hanna GJ

Abstract
Merkel cell carcinoma is a rare cancer for which immune checkpoint blockade is standard-of-care for recurrent/metastatic disease. However, not all patients benefit from immunotherapy. A greater understanding of molecular mechanisms and predictive biomarkers are unmet needs. We retrospectively analyzed electronic health records and next-generation sequencing data of 45 patients treated at our institution from 2013 to 2020 to understand clinical and genomic correlates of benefit from immunotherapy. Our cohort predominantly included individuals with stage III disease at primary disease diagnosis and individuals with stage IV disease at recurrent/metastatic disease diagnosis. Most received immunotherapy as first-line treatment. 43% experienced objective response (median duration of response 24.2 months, 95% confidence interval 8.8-not reached). Median overall survival was 15.5 months (95% confidence interval 9.0-28.7) (median follow-up 25.2 months). Less advanced stage at primary disease diagnosis and shorter disease-free interval between completion of initial treatment and recurrence were each associated with greater odds of response (odds ratio of 0.06, p = 0.04 for stage; odds ratio 0.75, p = 0.05 for disease-free interval). Single-nucleotide variants in ARID2 and NTRK1 were associated with response (p = 0.05, without Bonferroni correction), while none of Merkel cell polyomavirus status, total mutational burden, ultraviolet mutational signatures, and copy-number alterations predicted outcomes. Patients with shorter disease-free interval may be particularly suitable immunotherapy candidates. Our molecular findings point to ARID2 and NTRK1 as potential predictive markers and/or therapeutic targets (e.g., with Trk inhibitors), although this association needs to be confirmed in a larger sample.

PMID: 33315984 [PubMed]

Merkel cell carcinoma-derived exosome-shuttle miR-375 induces fibroblast polarization by inhibition of RBPJ and p53.

Fetched: December 16th, 2020, 5:01am GMT

Merkel cell carcinoma-derived exosome-shuttle miR-375 induces fibroblast polarization by inhibition of RBPJ and p53.

Oncogene. 2020 Dec 11;:

Authors: Fan K, Spassova I, Gravemeyer J, Ritter C, Horny K, Lange A, Gambichler T, Ødum N, Schrama D, Schadendorf D, Ugurel S, Becker JC

Abstract
Merkel cell carcinoma (MCC) is a highly invasive and metastatic skin cancer. While high expression of miR-375 is a characteristic of MCC, it seems not to contribute to the malignant phenotype of MCC cells. miR-375 enrichment in MCC-derived extracellular vesicles suggests its intercellular signaling function. Here, we demonstrate that horizontally transferred miR-375 causes fibroblast polarization toward cancer-associated fibroblasts (CAFs). The polarization is evidenced by phenotypic changes and induction of α-SMA, CXCL2, and IL-1β. Fibroblast polarization is inhibited by specific antagomirs and mimicked by experimental miR-375 expression. Mechanistically, miR-375 downregulates RBPJ and p53, two key players regulating fibroblast polarization. In clinical MCC samples, in situ hybridization located miR-375 in CAFs, which correlated with high α-SMA protein and low RBPJ and TP53 expression; single-cell RNAseq revealed a disparate fibroblast polarization negatively correlating with p53 pathway-related gene expression. Thus, the functional role of miR-375 in MCC is to generate a pro-tumorigenic microenvironment by inducing fibroblast polarization.

PMID: 33311552 [PubMed - as supplied by publisher]

[Clinical and morphological features of Merkel's carcinoma in elderly patients (literature review).]

Fetched: December 16th, 2020, 5:01am GMT

[Clinical and morphological features of Merkel's carcinoma in elderly patients (literature review).]

Adv Gerontol. 2020;33(3):569-575

Authors: Ermilov VV, Barkanov VB, Mikailzade GF, Markelov VV

Abstract
Merkels cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin tumor with a high rate of recurrence and local metastasis. The average age at which MCC is diagnosed is 75 years. The identification of the role of somatic mutations and DNA repair in aging mechanisms raises the question of their direct connection with the processes of differentiation, age-related characteristics of the immune system, programmed cell death and malignant growth. In this regard, there remains a need for research aimed at improving the early diagnosis and pathogenetic treatment of elderly patients.

PMID: 33280344 [PubMed - indexed for MEDLINE]

Permalink for 'An autoimmune-based, paraneoplastic neurologic syndrome following checkpoint inhibition and concurrent radiotherapy for merkel cell carcinoma: case report.'

An autoimmune-based, paraneoplastic neurologic syndrome following checkpoint inhibition and concurrent radiotherapy for merkel cell carcinoma: case report.

Fetched: December 16th, 2020, 5:01am GMT

An autoimmune-based, paraneoplastic neurologic syndrome following checkpoint inhibition and concurrent radiotherapy for merkel cell carcinoma: case report.

Strahlenther Onkol. 2020 Jul;196(7):664-670

Authors: Sherry AD, Bezzerides M, Khattab MH, Luo G, Ancell KK, Kirschner AN

Abstract
PURPOSE: Merkel cell carcinoma is highly sensitive to both radiation and immunotherapy. Moreover, concurrent radioimmunotherapy may capitalize on anti-tumor immune activity and improve Merkel cell treatment response, although an enhanced immune system may cross-react with native tissues and lead to significant sequelae.
METHODS: Here we present a case study of a patient with metastatic Merkel cell carcinoma treated with radiotherapy concurrent with pembrolizumab.
RESULTS: After radioimmunotherapy, the patient developed sensory neuropathy, visual hallucinations, and mixed motor neuron findings. Neurologic dysfunction progressed to profound gastrointestinal dysmotility necessitating parenteral nutrition and intubation with eventual expiration.
CONCLUSION: This case represents a unique autoimmune paraneoplastic neurologic syndrome, likely specific to neuroendocrine tumors and motivated by concurrent radioimmunotherapy. Recognition of the potential role of radioimmunotherapy may provide an advantage in anticipating these severe sequelae.

PMID: 32006066 [PubMed - indexed for MEDLINE]

Large-cell variant of Merkel cell carcinoma with clear-cell change.

Fetched: December 16th, 2020, 5:01am GMT

Large-cell variant of Merkel cell carcinoma with clear-cell change.

J Cutan Pathol. 2020 Jan;47(1):1-5

Authors: Khanna U, North JP

PMID: 31840299 [PubMed - indexed for MEDLINE]

Dermatological surgery during the COVID-19 pandemic: experience of a large academic center.

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

Dermatological surgery during the COVID-19 pandemic: experience of a large academic center.

J Am Acad Dermatol. 2020 Dec 05;:

Authors: Tee MW, Stewart C, Aliessa S, Polansky M, Shah K, Petukhova T, Rossi A, Lipner SR, Minkis K

PMID: 33290801 [PubMed - as supplied by publisher]

Anterior Axillary Arch: An Anatomic Variant Every Surgeon Operating in the Axilla Should Be Aware of.

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

Anterior Axillary Arch: An Anatomic Variant Every Surgeon Operating in the Axilla Should Be Aware of.

J Surg Res. 2020 Dec 04;259:170-174

Authors: Yonkus JA, Jakub JW

Abstract
BACKGROUND: Anterior axillary arch (AAA) is a slip of latissimus dorsi muscle, of variable thickness, which crosses anterior to the axillary vessels and brachial plexus. It is the most common anatomic variant in the axilla and surgeons operating in this area should be familiar with this finding to prevent confusion and complications. The aim of this study is to enhance surgeon's awareness of AAA, report the prevalence, and to describe our experience with this anomaly.
METHODS: An institutionally maintained database was used to identify patients with AAA in a single surgeon's experience, from 2008 to 2019. Patient characteristics, including tumor type, laterality, and pathologic node counts were determined and compared with patients undergoing axillary lymph node dissection (ALND) without this anatomic anomaly.
RESULTS: Nineteen patients with AAA were identified (13 on ALND and 6 during sentinel lymph node biopsy). Indications for ALND included breast cancer (12), melanoma (5), and Merkel cell carcinoma (2). In patients with AAA undergoing an ALND, the median number of lymph nodes pathologically identified was 23 and similar to those without AAA (27, P = 0.14). The prevalence of AAA in patients who underwent ALND was 3.1% (13/422).
CONCLUSIONS: Surgeons who operate in the axilla are likely to encounter an AAA. Knowledge of this variant should improve operative efficiency and may prevent technical errors during an ALND or sentinel lymph node biopsy.

PMID: 33285431 [PubMed - as supplied by publisher]

Glioma-Associated Oncogene-1 Expression in Basal Cell Carcinoma and Its Histologic Mimics.

Fetched: December 4th, 2020, 5:00am GMT

Glioma-Associated Oncogene-1 Expression in Basal Cell Carcinoma and Its Histologic Mimics.

Am J Dermatopathol. 2020 Dec 01;:

Authors: Gradecki SE, Eid MV, Pramoonjago P, Wick MR

Abstract
Basal cell carcinoma (BCC) is the most common skin cancer, and it has numerous histologic mimics with variable prognoses and treatments. Although some immunohistochemical stains can be used for the differential diagnosis of BCC, variability and overlap in results can complicate their interpretation. Immunohistochemical staining for glioma-associated oncogene-1 (Gli-1) was performed on 26 nodular BCCs, 22 infiltrative BCCs, 9 basaloid squamous cell carcinomas, 12 desmoplastic trichoepitheliomas, 19 Merkel cell carcinomas, 11 sebaceous carcinomas, 10 cylindromas, 14 spiradenomas, 12 adenoid cystic carcinomas (AdCC), and 1 solitary trichoepithelioma. Strength of staining was scored as 0, 1+, 2+, or 3+, and distribution of staining was categorized as diffuse, multifocal, or focal. Strong, diffuse Gli-1 expression was seen in all tumors with basal epidermal-type differentiation, including BCC, trichoepithelioma, and basaloid squamous cell carcinoma. All examples of Merkel cell carcinoma were negative for cytoplasmic expression. Seven out of 11 sebaceous carcinomas were negative for Gli-1, and the remaining 4 showed 1+ expression. Cylindroma, spiradenoma, and AdCC, each an adnexal skin tumor, showed the most variable staining, but with cylindroma and spiradenoma demonstrating comparable labeling patterns. Overall, although Gli-1 may not distinguish between basal epidermal-type tumors, it may have a role in separating that group from lesions with adnexal differentiation, particularly sebaceous carcinoma, but also cylindroma, spiradenoma, and AdCC. Any cytoplasmic staining seems to exclude the diagnosis of Merkel cell carcinoma.

PMID: 33264133 [PubMed - as supplied by publisher]

Neospora caninum: a new class of biopharmaceuticals in the therapeutic arsenal against cancer.

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

Neospora caninum: a new class of biopharmaceuticals in the therapeutic arsenal against cancer.

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

Authors: Lantier L, Poupée-Beaugé A, di Tommaso A, Ducournau C, Epardaud M, Lakhrif Z, Germon S, Debierre-Grockiego F, Mévélec MN, Battistoni A, Coënon L, Deluce-Kakwata-Nkor N, Velge-Roussel F, Beauvillain C, Baranek T, Lee GS, Kervarrec T, Touzé A, Moiré N, Dimier-Poisson I

Abstract
BACKGROUND: Microorganisms that can be used for their lytic activity against tumor cells as well as inducing or reactivating antitumor immune responses are a relevant part of the available immunotherapy strategies. Viruses, bacteria and even protozoa have been largely explored with success as effective human antitumor agents. To date, only one oncolytic virus-T-VEC-has been approved by the US Food and Drug Administration for use in biological cancer therapy in clinical trials. The goal of our study is to evaluate the potential of a livestock pathogen, the protozoan Neospora caninum, non-pathogenic in humans, as an effective and safe antitumorous agent.
METHODS/RESULTS: We demonstrated that the treatment of murine thymoma EG7 by subcutaneous injection of N. caninum tachyzoites either in or remotely from the tumor strongly inhibits tumor development, and often causes their complete eradication. Analysis of immune responses showed that N. caninum had the ability to 1) lyze infected cancer cells, 2) reactivate the immunosuppressed immune cells and 3) activate the systemic immune system by generating a protective antitumor response dependent on natural killer cells, CD8-T cells and associated with a strong interferon (IFN)-γ secretion in the tumor microenvironment. Most importantly, we observed a total clearance of the injected agent in the treated animals: N. caninum exhibited strong anticancer effects without persisting in the organism of treated mice. We also established in vitro and an in vivo non-obese diabetic/severe combined immunodeficiency mouse model that N. caninum infected and induced a strong regression of human Merkel cell carcinoma. Finally, we engineered a N. caninum strain to secrete human interleukin (IL)-15, associated with the alpha-subunit of the IL-15 receptor thus strengthening the immuno-stimulatory properties of N. caninum. Indeed, this NC1-IL15hRec strain induced both proliferation of and IFN-γ secretion by human peripheral blood mononuclear cells, as well as improved efficacy in vivo in the EG7 tumor model.
CONCLUSION: These results highlight N. caninum as a potential, extremely effective and non-toxic anticancer agent, capable of being engineered to either express at its surface or to secrete biodrugs. Our work has identified the broad clinical possibilities of using N. caninum as an oncolytic protozoan in human medicine.

PMID: 33257408 [PubMed - in process]

Permalink for 'Narrow resection margins are not associated with mortality or recurrence in patients with Merkel cell carcinoma: a retrospective study.'

Narrow resection margins are not associated with mortality or recurrence in patients with Merkel cell carcinoma: a retrospective study.

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

Narrow resection margins are not associated with mortality or recurrence in patients with Merkel cell carcinoma: a retrospective study.

J Am Acad Dermatol. 2020 Nov 27;:

Authors: Jaouen F, Kervarrec T, Caille A, Le Corre Y, Dreno B, Esteve E, Wierzbicka-Hainaut E, Maillard H, Dinulescu M, Blom A, Saïag P, Samimi M

Abstract
BACKGROUND: Wide local excision constitutes the standard of care for Merkel cell carcinoma, but the optimal margin width remains controversial.
OBJECTIVES: To assess whether narrow margins (0.5 - 1 cm) were associated with outcome.
METHODS: Patients were recruited from a retrospective French multicentric cohort and included if they had had excision of primary tumor with minimum lateral margins of 0.5 cm. Factors associated with mortality and recurrence were assessed by multivariate regression.
RESULTS: Among the 214 patients included, 58 (27.1%) had undergone excision with narrow margins (0.5-1cm) versus 156 (72.9%) with wide margins (>1cm). During a median follow-up of 50.7 months, cancer-specific survival did not differ between groups [5-year specific survival rate 76.8% (95% CI 61.7-91.9) and 76.2% (95% CI 68.8-83.6)]. Overall survival, any recurrence-free survival and local recurrence-free survival did not significantly differ between groups. Cancer-specific mortality was associated with age, male sex, AJCC stage III, positive margins.
LIMITATIONS: Retrospective design, heterogenous baseline characteristics between groups.
CONCLUSION: Excision with narrow margins was not associated with outcome in this cohort, in which most patients had clear margins and post-operative radiation therapy. Residual tumor, mostly found on deep surgical margins, was independently associated with prognosis.

PMID: 33253832 [PubMed - as supplied by publisher]

Merkel Cell Carcinoma.

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

Merkel Cell Carcinoma.

Clin Exp Dermatol. 2020 Nov 30;:

Authors: Patel P, Hussain K

Abstract
Merkel cell carcinoma (MCC) of the skin is a rare, aggressive form of skin cancer which metastasises to other parts of the body. This cutaneous neuroendocrine tumour mainly affects older people with cases generally occurring over the age of 50. Merkel cell polyomavirus (MCPyV) has been shown to induce gene mutations resulting in this skin cancer, with immunosuppression and ultraviolet radiation being other key risk factors in its pathogenesis. MCC is clinically seen as a rapidly enlarging, isolated, irregular erythematous nodule typically found on sun-exposed sites. Diagnosis is through clinical examination followed by tissue biopsy which demonstrates characteristic histopathologic neuroendocrine features. Immunohistochemistry plays a crucial role with characteristic perinuclear staining with cytokeratin-20 (CK20), helping to differentiate it from other morphologically similar tumours. Sentinel lymph node biopsy and imaging is essential for staging and determining prognosis. Surgical excision is the mainstay of treatment for localised disease although adjuvant radiotherapy is often required. Metastatic disease involves a very poor prognosis and immune checkpoint inhibitors have recently shown promise in the treatment of metastatic disease. Avelumab, a monoclonal antibody which binds to the programmed death-1 (PD-1) receptor, has been approved by the National Institute for Health and Care Excellence (NICE) showing encouraging survival outcomes. It provides an option for treating metastatic carcinoma in adults after they have obtained one or more lines of chemotherapy for metastatic disease.

PMID: 33252781 [PubMed - as supplied by publisher]

Prognostic Impact of MCPyV and TIL Subtyping in Merkel Cell Carcinoma: Evidence from a Large European Cohort of 95 Patients.

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

Prognostic Impact of MCPyV and TIL Subtyping in Merkel Cell Carcinoma: Evidence from a Large European Cohort of 95 Patients.

Endocr Pathol. 2020 Mar;31(1):21-32

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

Abstract
Merkel cell carcinoma is a rare (∼ 2000 cases/year in the USA) but aggressive neuroendocrine neoplasm of the skin. In 2008, the Merkel cell polyomavirus (MCPyV) was found to be clonally integrated in approximately 80% of Merkel cell carcinomas. The remaining 20% have large numbers of UV-associated mutations. Importantly, both the UV-induced neoantigens in virus-negative Merkel cell carcinoma and the Merkel cell polyomavirus oncogenes that are required for virus-positive tumor growth are highly immunogenic. Indeed, antigen-specific T cells detected in patients are frequently "dysfunctional/exhausted," and the inhibitory ligand PD-L1 is often expressed by Merkel cell carcinoma cells. These data led to point our attention on the quantity and the quality of the immune response in Merkel cell carcinoma. Here, we found CD8+ lymphocytes are the only singly evaluated lymphocyte subclass that strongly influenced overall survival and disease-specific survival in Merkel cell carcinoma. In addition, we highlighted as Merkel cell polyomavirus is a strong prognostic factor and as it prompts a host immune response involving various lymphocyte subclasses (CD3, CD8, FoxP3, and PD-L1 positive) in MCC. For this reason, we proposed a novel eye-based "immunoscore" model, obtained by tumor infiltrating lymphocytes subtyping (CD3, CD8, FoxP3, and PD-L1) that could provide additional prognostic information in Merkel cell carcinoma.

PMID: 31808008 [PubMed - indexed for MEDLINE]

Molecular Pathogenesis of Merkel Cell Carcinoma.

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

Molecular Pathogenesis of Merkel Cell Carcinoma.

Annu Rev Pathol. 2020 Nov 23;:

Authors: DeCaprio JA

Abstract
Merkel cell carcinoma (MCC) is an aggressive neuroendocrine carcinoma of the skin with two distinct etiologies. Clonal integration of Merkel cell polyomavirus DNA into the tumor genome with persistent expression of viral T antigens causes at least 60% of all MCC. UV damage leading to highly mutated genomes causes a nonviral form of MCC. Despite these distinct etiologies, both forms of MCC are similar in presentation, prognosis, and response to therapy. At least three oncogenic transcriptional programs feature prominently in both forms of MCC driven by the virus or by mutation. Both forms of MCC have a high proliferative growth rate with increased levels of cell cycle-dependent genes due to inactivation of the tumor suppressors RB and p53, a strong MYC signature due to MYCL activation by the virus or gene amplification, and an attenuated neuroendocrine differentiation program driven by the ATOH1 transcription factor. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 16 is January 25, 2021. Please see [www.annualreviews.org] for revised estimates.

PMID: 33228463 [PubMed - as supplied by publisher]

Increased programmed death ligand-1 expression in metastatic Merkel cell carcinoma associates with better prognosis.

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

Increased programmed death ligand-1 expression in metastatic Merkel cell carcinoma associates with better prognosis.

J Dermatol Sci. 2020 Feb;97(2):165-167

Authors: Nakamura M, Magara T, Nojiri Y, Nishihara H, Kato H, Teramoto Y, Yasuda M, Wada H, Ozawa T, Umemori Y, Ogata D, Kobayashi T, Hata M, Nagase K, Morita A

PMID: 31902663 [PubMed - indexed for MEDLINE]

Expression of Connexin 43 in 32 Cases of Merkel Cell Carcinoma.

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

Expression of Connexin 43 in 32 Cases of Merkel Cell Carcinoma.

Am J Dermatopathol. 2020 Mar;42(3):178-185

Authors: Fernandez-Flores A, Varela-Vazquez A, Suárez Peñaranda JM, Mayan MD, Fonseca E

Abstract
INTRODUCTION: Connexins (Cxs) are channel proteins that allow direct connection among cells and between cells and the extracellular space. There is very little information in the literature on the expression of Cxs by Merkel cell carcinoma (MCC).
MATERIALS AND METHODS: Thirty-two cases of MCC were recovered from our archives and studied immunohistochemically for Cx43.
RESULTS: All our cases expressed several neuroendocrine markers. Most cases showed nonimmunohistochemically perceptible staining for Cx43. There was no difference between Merkel cell polyomavirus (MCPyV)-positive and MCPyV-negative cases. One case could not be evaluated. Only 2 cases showed a focal (10% of the tumor) membranous staining of Cx43. One of these cases was MCPyV-negative and, in the other, CM2B4 could not be evaluated. CM2B4 was positive in 18 cases and negative in 13 cases, and it could not be evaluated in 1 case.
CONCLUSIONS: MCC shows a low Cx43 level, with no differences between MCPyV-positive and MCPyV-negative cases. Therefore, this opens the door for Cx43 targeting in therapeutic approaches to MCC.

PMID: 31809272 [PubMed - indexed for MEDLINE]

Permalink for 'Foci of Programmed Cell Death-Ligand 1 (PD-L1)-positive Tumor Areas With Tumor-infiltrating Leukocytes (TILs) Evocative of a PD-1/PD-L1-related Adaptive Immune Resistance are Frequent in Merkel Cell Carcinoma.'

Foci of Programmed Cell Death-Ligand 1 (PD-L1)-positive Tumor Areas With Tumor-infiltrating Leukocytes (TILs) Evocative of a PD-1/PD-L1-related Adaptive Immune Resistance are Frequent in Merkel Cell Carcinoma.

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

Foci of Programmed Cell Death-Ligand 1 (PD-L1)-positive Tumor Areas With Tumor-infiltrating Leukocytes (TILs) Evocative of a PD-1/PD-L1-related Adaptive Immune Resistance are Frequent in Merkel Cell Carcinoma.

Appl Immunohistochem Mol Morphol. 2020 01;28(1):17-22

Authors: Bénigni P, Guénolé M, Bonsang B, Marcorelles P, Schick U, Uguen A

Abstract
Immune checkpoint inhibitors (ICIs) targeting the programmed cell death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) axis have revolutionized the treatment of patients with Merkel cell carcinoma (MCC). To date, no biomarker conditions access to these ICIs in MCC. We compared the tumor microenvironment of PD-L1 and PD-L1 areas in a case series of MCC searching for foci evocative of PD-1/PD-L1 adaptive immune resistance. Among 58 tumors studied on digitalized serial tissue sections, 11 (19%) were concluded as "PD-L1 tumors" [≥1% positive tumor cells (TCs) using PD-L1 immunohistochemistry in the whole tumor slide]. In addition, among the remaining 47 (81%) "PD-L1 tumors," we nevertheless also identified "PD-L1 FOV" (ie, "field of view" of about 3 mm² containing ≥1% positive TCs) in 22 (38%) additional tumors. Comparison between paired "PD-L1 field of view (FOV)" and "PD-L1 FOV" within tumors, and between "PD-L1 tumors" and "PD-L1 tumors", revealed correlations between PD-L1 positivity and the abundance of tumor-infiltrating leukocytes, arguing for areas of PD-1/PD-L1-related adaptive immune resistance at least in some foci of "PD-L1 tumors" and also in "PD-L1 tumors." Tumor heterogeneity consists in a challenge searching for biomarkers able to predict the response/nonresponse to ICIs. Progress in digital pathology and multiplex immunolabeling may permit to overcome this challenge by better analyzing the interactions between TCs and immune and nonimmune non-TCs in the same tissue section. This approach of tumor heterogeneity may contribute to elucidate and to predict why some patients respond impressively to ICIs, whereas others do not.

PMID: 31343994 [PubMed - indexed for MEDLINE]

Dermoscopy and reflectance confocal microscopy of intraepidermal Merkel cell carcinoma.

Fetched: November 22nd, 2020, 5:00am GMT

Dermoscopy and reflectance confocal microscopy of intraepidermal Merkel cell carcinoma.

Australas J Dermatol. 2020 Nov 20;:

Authors: Navarrete-Dechent C, Cordova M, Aleissa S, Battle LR, Ganly I, Pulitzer M, Rossi AM

PMID: 33216952 [PubMed - as supplied by publisher]

Role of lanreotide in an elderly patient with Merkel cell carcinoma.

Fetched: November 21st, 2020, 5:00am GMT

Role of lanreotide in an elderly patient with Merkel cell carcinoma.

Dermatol Ther. 2020 01;33(1):e13206

Authors: Ghidini A, Petrelli F, Fazio I, Santangelo D

PMID: 31886588 [PubMed - indexed for MEDLINE]

Merkel Cell Polyomavirus-Positive Panniculitic Merkel Cell Carcinoma: A Rare Neoplasm of Unknown Histogenesis.

Fetched: November 21st, 2020, 5:00am GMT

Merkel Cell Polyomavirus-Positive Panniculitic Merkel Cell Carcinoma: A Rare Neoplasm of Unknown Histogenesis.

Am J Dermatopathol. 2020 Feb;42(2):151-153

Authors: Saggini A, Lora V, Baldelli R, Orlandi A, Cota C

PMID: 30908296 [PubMed - indexed for MEDLINE]

Case of Merkel cell carcinoma in a patient with pre-existing ILD.

Fetched: November 20th, 2020, 5:00am GMT

Case of Merkel cell carcinoma in a patient with pre-existing ILD.

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

Authors: Maniar R, Anderson M, Taback B, Khan S, McDonnell D, Saqi A, Niedt GW, Carvajal R

Abstract
Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin with high rates of local recurrence and distant metastases despite treatment with traditional cytotoxic chemotherapies. The recent advances in immunotherapy, including the use of immune checkpoint blockade (ICB) has revolutionized treatment for this disease and resulted in durable responses for some patients. However, many patients, due to underlying conditions, have been insufficiently evaluated for potential use of immunotherapy. Here we present a case of ICB treatment with Programmed cell death protein 1 (PD-1) inhibition in a patient with underlying interstitial lung disease (ILD) and a new diagnosis of MCC. Through a multidisciplinary approach, we were able to maintain close monitoring with serial clinical and radiographical follow-up. The patient achieved a complete response though unrelated medical issues resulting in a treatment hold. At the last follow-up, the patient continued to experience a durable response without evidence of recurrence. This case describes the use of pembrolizumab, a PD-1 inhibitor, for the treatment of MCC in a patient with underlying ILD. The use of active surveillance with a multidisciplinary approach resulted in successful treatment of MCC without exacerbation of the underlying ILD.

PMID: 33203666 [PubMed - in process]

Chapter XX Antiviral Treatment and Cancer Control.

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

Chapter XX Antiviral Treatment and Cancer Control.

Recent Results Cancer Res. 2021;217:325-354

Authors: Shih WL, Fang CT, Chen PJ

Abstract
Hepatitis B virus (HBV), hepatitis C virus (HCV), human papilloma virus (HPV), Epstein-Barr virus (EBV), human T-cell lymphotropic virus type 1 (HTLV-1), Kaposi's sarcoma-associated herpesvirus (KSHV), and Merkel cell polyomavirus (MCV) contribute to about 10-15% global burden of human cancers. Conventional chemotherapy or molecular target therapies have been used to treat virus-associated cancers. However, a more proactive approach would be the use of antiviral treatment to suppress or eliminate viral infections to prevent the occurrence of cancer in the first place. Antiviral treatments against chronic HBV and HCV infection have achieved this goal, with significant reduction in the incidence of hepatocellular carcinoma in treated patients. Antiviral treatments for EBV, KSHV, and HTLV-1 had limited success in treating refractory EBV-associated lymphoma and post-transplant lymphoproliferative disorder, KSHV-associated Kaposi's sarcoma in AIDS patients, and HTLV-1-associated acute, chronic, and smoldering subtypes of adult T-cell lymphoma, respectively. Therapeutic HPV vaccine and RNA interference-based therapies for treating HPV-associated infection or cervical cancers also showed some encouraging results. Taken together, antiviral therapies have yielded promising results in cancer prevention and treatment. More large-scale studies in a real-world setting are necessary to confirm the efficacy of antiviral therapy. Further investigation for more effective and convenient antiviral regimens warrants more attention.

PMID: 33200371 [PubMed - in process]

Merkel Cell Polyomavirus and Human Merkel Cell Carcinoma.

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

Merkel Cell Polyomavirus and Human Merkel Cell Carcinoma.

Recent Results Cancer Res. 2021;217:303-323

Authors: Liu W, You J

Abstract
Merkel cell polyomavirus (MCPyV) is the most recently discovered human oncogenic virus. MCPyV asymptomatically infects most of the human population. In the elderly and immunocompromised, however, it can cause a highly lethal form of human skin cancer called Merkel cell carcinoma (MCC). Distinct from the productive MCPyV infection that replicates the viral genome as episomes, MCC tumors contain replication-incompetent, integrated viral genomes. Mutant MCPyV tumor antigen genes expressed from the integrated viral genomes are essential for driving the oncogenic development of MCPyV-associated MCC. In this chapter, we summarize recent discoveries on MCPyV virology, mechanisms of MCPyV-mediated oncogenesis, and the current therapeutic strategies for MCPyV-associated MCCs.

PMID: 33200370 [PubMed - in process]

An Introduction to Virus Infections and Human Cancer.

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

An Introduction to Virus Infections and Human Cancer.

Recent Results Cancer Res. 2021;217:1-11

Authors: Schiller JT, Lowy DR

Abstract
Approximately, 1.4 million virus-induced cancers occur annually, representing roughly 10% of the worldwide cancer burden, with the majority (> 85%) occurring in the lower- and middle-income countries. The viruses associated with the greatest number of cancer cases are human papillomaviruses (HPVs), which cause cervical cancer and several other epithelial malignancies, and hepatitis viruses HBV and HCV, which are responsible for the majority of hepatocellular cancer. Other oncoviruses include Epstein-Barr virus (EBV), Kaposi's sarcoma herpesvirus (KSHV), human T-cell leukemia virus (HTLV-I), and Merkel cell polyoma virus (MCPyV). These oncoviruses include various classes of DNA and RNA viruses and induce cancer by a variety of mechanisms. However, cancers develop in a minority of infected individuals and almost always after chronic infection of many year's duration. Identification of the oncoviruses has provided critical insights in human carcinogenesis and led to several interventions that may reduce the risk of developing the tumors they induce. These interventions include preventive vaccines against HBV and HPV, screening for persistent HPV and HCV infections, antivirals for the treatment of chronic HBV and HCV infection, and screening the blood supply for the presence of HBV and HCV. Further efforts to identify additional oncogenic viruses in human cancers and new insights into etiology and pathogenesis of virally induced cancers would likely lead to new approaches for prophylactic and therapeutic interventions.

PMID: 33200359 [PubMed - in process]

Diffuse and Strong TTF-1 Positivity in a Combined Merkel Cell Carcinoma.

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

Diffuse and Strong TTF-1 Positivity in a Combined Merkel Cell Carcinoma.

Am J Dermatopathol. 2020 Mar;42(3):229-231

Authors: Hughes AJ, French M, Ah-Weng A, Singh M

PMID: 31107682 [PubMed - indexed for MEDLINE]

Hematological Toxicity During Concomitant Treatment With Ruxolitinib and Avelumab for Merkel Cell Carcinoma.

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

Hematological Toxicity During Concomitant Treatment With Ruxolitinib and Avelumab for Merkel Cell Carcinoma.

Front Oncol. 2020;10:579914

Authors: Buonerba L, Di Trolio R, Grimaldi A, Tucci A, Leo E, Ingenito C, Costabile F, Ragone G, Savastano B, Uzzauto MT, Belsito Petrizzi V, Di Lorenzo G

Abstract
Background: Merkel cell carcinoma (MCC) is a rare neuroendocrine skin cancer. It frequently emerges in the presence of immunosuppression states such as myeloproliferative syndrome (MS). MS is treated with ruxolitinib, a selective JAK1 and JAK2 inhibitor. Avelumab, an anti PDL-1 inhibitor, is the standard treatment for MCC. To date it is unknown if avelumab and ruxolitinib have a synergistic or antagonistic effect when used together. Methods: We have identified all patients diagnosed with MCC, treated with avelumab, concomitant ruxolitinib, belonging to Tortora Hospital, Pagani and Santa Maria La Pietà Hospital, Nola, Italy between June 1 2019 and April 1 2020. Results: Among six MCC patients, we have found two patients in treatment with concomitant drugs. Both patients were being treated with ruxolitinib for MS as a standard regimen without suffering any hematological side effects. After starting doses of avelumab, we found thrombocytopenia, leukopenia, and anemia after cycle 1 and cycle 4, respectively, and decided to suspend both treatments. Following the suspension, the hematological values improved allowing us to restart treatment with avelumab without the need to resume ruxolitinib treatment. Conclusions: The combined treatment of ruxolitinib and avelumab demonstrated severe toxicity. Modifying the schedule or reducing the dose of both drugs needs to be studied in order to be able to treat both pathologies.

PMID: 33194706 [PubMed]

PD-1 and TIGIT coexpression identifies a circulating CD8 T cell subset predictive of response to anti-PD-1 therapy.

Fetched: November 17th, 2020, 5:00am GMT

PD-1 and TIGIT coexpression identifies a circulating CD8 T cell subset predictive of response to anti-PD-1 therapy.

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

Authors: Simon S, Voillet V, Vignard V, Wu Z, Dabrowski C, Jouand N, Beauvais T, Khammari A, Braudeau C, Josien R, Adotevi O, Laheurte C, Aubin F, Nardin C, Rulli S, Gottardo R, Ramchurren N, Cheever M, Fling SP, Church CD, Nghiem P, Dreno B, Riddell SR, Labarriere N

Abstract
BACKGROUND: Clinical benefit from programmed cell death 1 receptor (PD-1) inhibitors relies on reinvigoration of endogenous antitumor immunity. Nonetheless, robust immunological markers, based on circulating immune cell subsets associated with therapeutic efficacy are yet to be validated.
METHODS: We isolated peripheral blood mononuclear cell from three independent cohorts of melanoma and Merkel cell carcinoma patients treated with PD-1 inhibitor, at baseline and longitudinally after therapy. Using multiparameter flow cytometry and cell sorting, we isolated four subsets of CD8+ T cells, based on PD-1 and TIGIT expression profiles. We performed phenotypic characterization, T cell receptor sequencing, targeted transcriptomic analysis and antitumor reactivity assays to thoroughly characterize each of these subsets.
RESULTS: We documented that the frequency of circulating PD-1+TIGIT+ (DPOS) CD8+ T-cells after 1 month of anti-PD-1 therapy was associated with clinical response and overall survival. This DPOS T-cell population was enriched in highly activated T-cells, tumor-specific and emerging T-cell clonotypes and T lymphocytes overexpressing CXCR5, a key marker of the CD8 cytotoxic follicular T cell population. Additionally, transcriptomic profiling defined a specific gene signature for this population as well as the overexpression of specific pathways associated with the therapeutic response.
CONCLUSIONS: Our results provide a convincing rationale for monitoring this PD-1+TIGIT+ circulating population as an early cellular-based marker of therapeutic response to anti-PD-1 therapy.

PMID: 33188038 [PubMed - in process]

Viral Genomic Characterization and Replication Pattern of Human Polyomaviruses in Kidney Transplant Recipients.

Fetched: November 17th, 2020, 5:00am GMT

Viral Genomic Characterization and Replication Pattern of Human Polyomaviruses in Kidney Transplant Recipients.

Viruses. 2020 Nov 09;12(11):

Authors: Signorini L, Dolci M, Favi E, Colico C, Ferraresso M, Ticozzi R, Basile G, Ferrante P, Delbue S

Abstract
Human Polyomavirus (HPyV) infections are common, ranging from 60% to 100%. In kidney transplant (KTx) recipients, HPyVs have been associated with allograft nephropathy, progressive multifocal leukoencephalopathy, and skin cancer. Whether such complications are caused by viral reactivation or primary infection transmitted by the donor remains debated. This study aimed to investigate the replication pattern and genomic characterization of BK Polyomavirus (BKPyV), JC Polyomavirus (JCPyV), and Merkel Cell Polyomavirus (MCPyV) infections in KTx. Urine samples from 57 KTx donor/recipient pairs were collected immediately before organ retrieval/transplant and periodically up to post-operative day 540. Specimens were tested for the presence of BKPyV, JCPyV, and MCPyV genome by virus-specific Real-Time PCR and molecularly characterized. HPyVs genome was detected in 49.1% of donors and 77.2% of recipients. Sequences analysis revealed the archetypal strain for JCPyV, TU and Dunlop strains for BKPyV, and IIa-2 strain for MCPyV. VP1 genotyping showed a high frequency for JCPyV genotype 1 and BKPyV genotype I. Our experience demonstrates that after KTx, HPyVs genome remains stable over time with no emergence of quasi-species. HPyVs strains isolated in donor/recipient pairs are mostly identical, suggesting that viruses detected in the recipient may be transmitted by the allograft.

PMID: 33182443 [PubMed - in process]

Patched 1 expression in Merkel cell carcinoma.

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

Patched 1 expression in Merkel cell carcinoma.

J Dermatol. 2020 Nov 12;:

Authors: Gambichler T, Dreißigacker M, Kasakovski D, Skrygan M, Wieland U, Silling S, Gravemeyer J, Melior A, Cherouny A, Stücker M, Stockfleth E, Sand M, Becker JC

Abstract
The relevance of Hedgehog signaling in Merkel cell carcinoma has only been addressed by a few studies with conflicting results. Thus, we aimed to establish the expression of Hedgehog signaling molecules in Merkel cell carcinoma to characterize causes of aberrant expression and to correlate these findings with the clinical course of the patients. Immunohistochemistry was performed for Sonic, Indian, Patched 1 (PTCH1) and Smoothened on patients' tumor tissue. Respective mRNA expression was analyzed in 10 Merkel cell carcinoma cell lines using quantitative real-time polymerase chain reaction. PTCH1 sequencing and DNA methylation microarray analyses were carried out on tumor tissues as well as cell lines. PTCH1 immunoreactivity in Merkel cell carcinoma was similar to that of basal cell carcinomas, which both significantly differed from PTCH1 immunoreactivity in healthy skin. Most PTCH1 mutations found were synonymous or without known functional impact. However, on average, the promoter regions of both PTCH1 were hypomethylated independently from PTCH1 gene expression or Merkel cell polyomavirus status. PTCH1 and GLI1/2/3 genes were differently expressed in different cell lines; notably, there was a significant correlation between GLI2 and PTCH1 mRNA expression. Similar to PTCH1 protein expression in patient tissues, PTCH1 gene expression in Merkel cell carcinoma cell lines is highly variable, but due to the similar methylation pattern across Merkel cell carcinoma cell lines, effects other than methylation seem to be the reason for the differential expression and PTCH1 appears to be upregulated by GLI as a classical Hedgehog target gene.

PMID: 33180347 [PubMed - as supplied by publisher]

Epileptic Seizure Provoked by Bone Metastasis of Chronic Lymphoid Leukemia and Merkel Cell Carcinoma.

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

Epileptic Seizure Provoked by Bone Metastasis of Chronic Lymphoid Leukemia and Merkel Cell Carcinoma.

Case Rep Med. 2020;2020:4318638

Authors: Folyovich A, Majoros A, Jarecsny T, Pánczél G, Pápai Z, Rudas G, Kozák L, Barna G, Béres-Molnár KA, Vadasdi K, Liszkay G, Horváth E, Toldi G

Abstract
Background: Merkel cell carcinoma (MCC) is a rare primary neuroendocrine cutaneous tumor, rarely metastasizing to the brain. Chronic lymphoid leukemia (CLL) is a disease predisposing to MCC. According to previous reports, headache and focal neurological deficits suggest disease progression to the brain. We present a patient with MCC whose seizure was not elicited by a cerebral metastasis, but by bone metastases compressing the brain. Case Presentation. A 62-year-old female patient had a history of CLL. A lesion with the appearance of an atheroma was removed from the right upper arm. Histology confirmed the diagnosis of MCC. She was admitted to the neurology department with her first GM seizure. The cranial MRI/MRA showed bone metastases in the right parietal and both frontal areas, compressing the brain. Flow cytometry of CSF did not reveal metastasis of MCC.
Conclusions: The case history of the patient was unique even among the rare cases of MCC with neurological involvement. The seizure was not elicited by a cerebral metastasis, but by bone metastases compressing the brain. In addition to patient history, clinical presentation and radiological findings enabled a suspected diagnosis of skull metastasis of MCC compressing the brain, causing symptomatic epileptic seizures.

PMID: 33178284 [PubMed]

Circulating Tumor Cell Detection and Polyomavirus Status in Merkel Cell Carcinoma.

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

Circulating Tumor Cell Detection and Polyomavirus Status in Merkel Cell Carcinoma.

Sci Rep. 2020 01 31;10(1):1612

Authors: Boyer M, Cayrefourcq L, Garima F, Foulongne V, Dereure O, Alix-Panabières C

Abstract
The incidence of Merkel cell carcinoma (MCC), a rare and highly metastatic skin malignancy, has sharply increased in the last decade. Clinical biomarkers are urgently needed for MCC prognosis, treatment response monitoring, and early diagnosis of relapse. The clinical interest of circulating tumors cells (CTCs) has been validated in many solid cancers. The aim of this study was to compare CTC detection and characterization in blood samples of patients with MCC using the CellSearch System and the RosetteSep -DEPArray workflow, an innovative procedure to enrich, detect and isolate single CTCs. In preliminary experiments (using spiked MCC cell lines) both methods allowed detecting very few MCC cells. In blood samples from 19 patients with MCC at different stages, CellSearch detected MCC CTCs in 26% of patients, and the R-D workflow in 42% of patients. The detection of CTC-positive patients increased to 52% by the cumulative positivity rate of both methodologies. Moreover, Merkel cell polyomavirus DNA, involved in MCC oncogenesis, was detected in tumor biopsies, but not in all single CTCs from the same patient, reflecting the tumor heterogeneity. Our data demonstrate the possibility to detect, isolate and characterize CTCs in patients with MCC using two complementary approaches.

PMID: 32005907 [PubMed - indexed for MEDLINE]

Permalink for 'Association between Treatment Center Experience and Survival After Diagnosis of Stage I-III Merkel Cell Carcinoma Treated with Surgery with or without Postoperative Radiation Therapy.'

Association between Treatment Center Experience and Survival After Diagnosis of Stage I-III Merkel Cell Carcinoma Treated with Surgery with or without Postoperative Radiation Therapy.

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

Association between Treatment Center Experience and Survival After Diagnosis of Stage I-III Merkel Cell Carcinoma Treated with Surgery with or without Postoperative Radiation Therapy.

J Am Acad Dermatol. 2020 Nov 07;:

Authors: Chipidza FE, Thakuria M, Schoenfeld JD, Silk AW, Catalano PJ, Yoon CH, Hanna GJ, DeCaprio JA, Tishler RB, Margalit DN

PMID: 33171164 [PubMed - as supplied by publisher]

Factors Associated with Time to Treatment for Merkel Cell Carcinoma.

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

Factors Associated with Time to Treatment for Merkel Cell Carcinoma.

J Am Acad Dermatol. 2020 Nov 07;:

Authors: Tripathi R, Bordeaux JS, Nijhawan RI

PMID: 33171163 [PubMed - as supplied by publisher]

Chronic lymphocytic leukemia and second primary nonlymphoid malignancies: cytopathologic study of 17 cases.

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

Chronic lymphocytic leukemia and second primary nonlymphoid malignancies: cytopathologic study of 17 cases.

J Am Soc Cytopathol. 2020 Oct 20;:

Authors: Fitzthum AD, Wakely PE

Abstract
INTRODUCTION: Second primary nonlymphoid malignancies (SPNLM) have long been recognized as a complication of chronic lymphocytic leukemia (CLL).
MATERIALS AND METHODS: A search was made of our cytopathology database for cases of CLL that also contained a SPNLM.
RESULTS: Seventeen cases from 13 known CLL patients [M:F = 2.3:1; age range: 47-77 years, x = 67 years] met criteria for this study. SPNLMs consisted of different forms of metastatic carcinoma (10 patients) and malignant melanoma (3). Of 16 FNA biopsies and 1 pleural fluid, 82% had ancillary testing; 35% had the specimen subdivided for both flow cytometry (FCM) and immunohistochemistry (IHC). Lymph node was the most common site for FNA biopsy (12), followed by face (2), and soft tissue (2). Squamous cell carcinoma was the most common SPNLM (6), followed by melanoma (3), and there were single cases of adenocarcinoma, large cell neuroendocrine carcinoma, Merkel cell carcinoma, and papillary thyroid carcinoma. A correct specific cytologic diagnosis was made in 15 (88%) cases.
CONCLUSIONS: Cytopathology is highly proficient in recognizing SPNLM in CLL patients. Utilization of cytologic material for FCM and IHC is feasible, and extremely helpful in achieving diagnostic accuracy.

PMID: 33168473 [PubMed - as supplied by publisher]

Merkel cell carcinoma with squamous differentiation - case report.

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

Merkel cell carcinoma with squamous differentiation - case report.

Cesk Patol. 2020;56(3):177-180

Authors: Savka O, Pastrňák A

Abstract
We report a case of 81-year old female with Merkel cell carcinoma of skin with squamous differentiation and aberrant immunohistochemical profile. Primary skin tumor of left preauricular area was incompletely removed 6 months ago and diagnosed as poorly differentiated squamous cell carcinoma. After 6 months patient returns with relapse and new biopsy is made. Microscopically, mostly solid structures of poorly differentiated neoplasia with focal squamous differentiated are found. Neoplastic cells were small, polygonal, with scant cytoplasm and irregular oval dark nuclei with high mitotic activity. Immunohistochemically, tumor cells showed positivity for AE1/AE3, p63, CD56, chromogranin A, synaptophysin and in squamous parts p40. CK20 and other markers examined were negative. Merkel cell carcinoma is rare and highly aggressive skin tumor with characteristic expression of epithelial and neuroendocrine markers. In this report we want to point out that caution should be taken in excluding diagnosis of Merkel cell carcinoma from differential diagnosis based on atypical histological and immunohistochemical findings, especially the risk of confusion with less aggressive skin tumors.

PMID: 33076671 [PubMed - indexed for MEDLINE]

Malignant melanoma after treatment for Merkel cell carcinoma.

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

Malignant melanoma after treatment for Merkel cell carcinoma.

An Bras Dermatol. 2020 Sep - Oct;95(5):662-664

Authors: Ishikawa M, Yamamoto T

PMID: 32727678 [PubMed - indexed for MEDLINE]

PDQ Cancer Information Summaries

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

PDQ Cancer Information Summaries

Book. 2002

Authors:

Abstract
This PDQ cancer information summary has current information about the treatment of Merkel cell carcinoma. It is meant to inform and help patients, families, and caregivers. It does not give formal guidelines or recommendations for making decisions about health care. Editorial Boards write the PDQ cancer information summaries and keep them up to date. These Boards are made up of experts in cancer treatment and other specialties related to cancer. The summaries are reviewed regularly and changes are made when there is new information. The date on each summary ("Date Last Modified") is the date of the most recent change. The information in this patient summary was taken from the health professional version, which is reviewed regularly and updated as needed, by the PDQ Adult Treatment Editorial Board.

PMID: 26389202

Gene Regulation Using Spherical Nucleic Acids to Treat Skin Disorders.

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

Gene Regulation Using Spherical Nucleic Acids to Treat Skin Disorders.

Pharmaceuticals (Basel). 2020 Nov 02;13(11):

Authors: Holmes TR, Paller AS

Abstract
Spherical nucleic acids (SNAs) are nanostructures consisting of nucleic acids in a spherical configuration, often around a nanoparticle core. SNAs are advantageous as gene-regulating agents compared to conventional gene therapy owing to their low toxicity, enhanced stability, uptake by virtually any cell, and ability to penetrate the epidermal barrier. In this review we: (i) describe the production, structure and properties of SNAs; (ii) detail the mechanism of SNA uptake in keratinocytes, regulated by scavenger receptors; and (iii) report how SNAs have been topically applied and intralesionally injected for skin disorders. Specialized SNAs called nanoflares can be topically applied for gene-based diagnosis (scar vs. normal tissue). Topical SNAs directed against TNFα and interleukin-17A receptor reversed psoriasis-like disease in mouse models and have been tested in Phase 1 human trials. Furthermore, SNAs targeting ganglioside GM3 synthase accelerate wound healing in diabetic mouse models. Most recently, SNAs targeting toll-like receptor 9 are being used in Phase 2 human trials via intratumoral injection to induce immune responses in Merkel cell and cutaneous squamous cell carcinoma. Overall, SNAs are a valuable tool in bench-top and clinical research, and their advantageous properties, including penetration into the epidermis after topical delivery, provide new opportunities for targeted therapies.

PMID: 33147737 [PubMed]

Assessment of Age, Period, and Birth Cohort Effects and Trends in Merkel Cell Carcinoma Incidence in the United States.

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

Icon for Silverchair Information Systems

Assessment of Age, Period, and Birth Cohort Effects and Trends in Merkel Cell Carcinoma Incidence in the United States.

JAMA Dermatol. 2020 Nov 04;:

Authors: Jacobs D, Huang H, Olino K, Weiss S, Kluger H, Judson BL, Zhang Y

Abstract
Importance: Merkel cell carcinoma is an aggressive, cutaneous, neuroendocrine cancer that is increasing in incidence. Understanding why the incidence of Merkel cell carcinoma is increasing through underlying factors, such as age effects, calendar period of diagnosis effects, and birth cohort effects, can help guide resource allocation and design of screening programs.
Objectives: To evaluate the associations of patient age, calendar period of diagnosis, and birth cohort with the increasing incidence of Merkel cell carcinoma and to provide new incidence projections to 2030.
Design, Setting, and Participants: A cross-sectional retrospective study with age-period-cohort analysis and incidence projection modeling using data from the Surveillance, Epidemiology, and End Results Program database of 9 registries from 1987 to 2016 was conducted among 3720 patients with Merkel cell carcinoma. Statistical analysis was conducted from October 20, 2019, to July 29, 2020.
Exposures: Age effects (ie, physiology), period of diagnosis effects (ie, changes in diagnostics and clinical awareness), and birth cohort effects (ie, environmental risk factors) over time were assessed.
Main Outcomes and Measures: Incidence rates of Merkel cell carcinoma.
Results: Among the 3720 patients in the study (2200 male patients [59.1%]; median age, 77 years [interquartile range, 68-84 years]), during the period from 2012 to 2016, the age-adjusted Merkel cell carcinoma incidence rate was 0.66 per 100 000 (95% CI, 0.62-0.70), which represented a 3.5-times (95% CI, 3.0-4.2) increase from 1987 to 1991. The incidence of Merkel cell carcinoma increased with patient age across calendar periods and birth cohorts; the highest incidence rate was observed for those aged 85 years or older, with an age-adjusted rate from 2012 to 2016 of 14.6 per 100 000 for men and 5.5 per 100 000 for women. Although the birth cohort effect has continued to increase over time, the calendar period of diagnosis effect has started to plateau. It is projected that there will be 3023 new cases of Merkel cell carcinoma in 2020 and 5130 new cases in 2030, increased from an estimated 1933 cases in 2010.
Conclusions and Relevance: The slowing down of the period effect (ie, changes in diagnostics and awareness) found in this longitudinal cohort study suggests that part of the initial increased incidence of Merkel cell carcinoma was associated with increased detection. However, the projected increase in incidence rate is likely associated with the aging population and increasing risk factor exposure in more recent birth cohorts.

PMID: 33146688 [PubMed - as supplied by publisher]

Immunotherapy and potential predictive biomarkers in the treatment of neuroendocrine neoplasia.

Fetched: November 4th, 2020, 5:00am GMT

Immunotherapy and potential predictive biomarkers in the treatment of neuroendocrine neoplasia.

Future Oncol. 2020 Nov 02;:

Authors: Xu G, Wang Y, Zhang H, She X, Yang J

Abstract
Neuroendocrine neoplasias (NENs) are a heterogeneous group of rare tumors scattered throughout the body. Surgery, locoregional or ablative therapies as well as maintenance treatments are applied in well-differentiated, low-grade NENs, whereas cytotoxic chemotherapy is usually applied in high-grade neuroendocrine carcinomas. However, treatment options for patients with advanced or metastatic NENs are limited. Immunotherapy has provided new treatment approaches for many cancer types, including neuroendocrine tumors, but predictive biomarkers of immune checkpoint inhibitors (ICIs) in the treatment of NENs have not been fully reported. By reviewing the literature and international congress abstracts, we summarize the current knowledge of ICIs, potential predicative biomarkers in the treatment of NENs, implications and efficacy of ICIs as well as biomarkers for NENs of gastroenteropancreatic system, lung NENs and Merkel cell carcinoma in clinical practice.

PMID: 33136448 [PubMed - as supplied by publisher]

Possible Oncogenic Viruses Associated with Lung Cancer.

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

Possible Oncogenic Viruses Associated with Lung Cancer.

Onco Targets Ther. 2020;13:10651-10666

Authors: Hu Y, Ren S, He Y, Wang L, Chen C, Tang J, Liu W, Yu F

Abstract
Lung cancer is the most common cause of cancer death worldwide. Tobacco smoking is the most predominant etiology for lung cancer. However, only a small percentage of heavy smokers develop lung cancer, which suggests that other cofactors are required for lung carcinogenesis. Viruses have been central to modern cancer research and provide profound insights into cancer causes. Nevertheless, the role of virus in lung cancer is still unclear. In this article, we reviewed the possible oncogenic viruses associated with lung cancer.

PMID: 33116642 [PubMed]

Efficacy of Electrochemotherapy in the Treatment of Cutaneous Melanoma Metastases and Rare Non-melanoma Skin Cancer.

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

Efficacy of Electrochemotherapy in the Treatment of Cutaneous Melanoma Metastases and Rare Non-melanoma Skin Cancer.

Anticancer Res. 2020 Nov;40(11):6485-6492

Authors: Borgognoni L, Pescitelli L, Gerlini G, Brandani P, Gelli R, Giannotti V, Bellucci F, Sestini S

Abstract
BACKGROUND: We aimed to verify the clinical efficacy and safety of the electrochemotherapy in melanoma metastases and in cases of rare non-melanoma tumors that were difficult to treat for the specific anatomical site or for patient comorbidities.
PATIENTS AND METHODS: We treated 68 patients (699 cutaneous nodules), 44 patients with metastatic melanomas and 24 patients with non-melanoma tumors, at the Melanoma & Skin Cancer Unit, Florence, Italy.
RESULTS: We obtained an objective response of 89.7% (88.6% in melanomas and 91.7% in non-melanoma tumors), complete response 54.4% and partial response 35.3%.
CONCLUSION: This study showed that electrochemotherapy is effective in the treatment of melanoma metastases and in rare types of non-melanoma tumors. In particular, we successfully treated rare tumors as angiosarcoma, pleomorphic sarcoma, myxofibrosarcoma, sarcoma di Kaposi, porocarcinoma, sebaceous carcinoma, Merkel cell carcinoma, malignant blue nevus, undifferentiated epitheliomorphic cell neoplasia and metastases from thyroid carcinoma. No serious adverse events were observed.

PMID: 33109587 [PubMed - in process]

The landscape of host genetic factors involved in immune response to common viral infections.

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

The landscape of host genetic factors involved in immune response to common viral infections.

Genome Med. 2020 Oct 27;12(1):93

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

Abstract
BACKGROUND: 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 therapeutic opportunities.
METHODS: We conducted a comprehensive study including genome-wide and transcriptome-wide association analyses to identify genetic loci associated with immunoglobulin G antibody response to 28 antigens for 16 viruses using serological data from 7924 European ancestry participants in the UK Biobank cohort.
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. We identified specific amino acid (AA) residues that are associated with seroreactivity, the strongest associations presented in a range of AA positions within DRβ1 at positions 11, 13, 71, and 74 for Epstein-Barr virus (EBV), Varicella zoster virus (VZV), human herpesvirus 7, (HHV7), and Merkel cell polyomavirus (MCV). Genome-wide association analyses discovered 7 novel genetic loci outside the HLA associated with viral antibody response (P < 5.0 × 10-8), including FUT2 (19q13.33) for human polyomavirus BK (BKV), STING1 (5q31.2) for MCV, and CXCR5 (11q23.3) and TBKBP1 (17q21.32) for HHV7. 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 EBV nuclear antigen. We also demonstrated pleiotropy between viral response genes and complex diseases, from autoimmune disorders to cancer to neurodegenerative and psychiatric conditions.
CONCLUSIONS: Our study confirms the importance of the HLA region in host response to viral infection and elucidates novel genetic determinants beyond the HLA that contribute to host-virus interaction.

PMID: 33109261 [PubMed - in process]

Changing Body Weight-Based Dosing to a Flat Dose for Avelumab in Metastatic Merkel Cell and Advanced Urothelial Carcinoma.

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

Changing Body Weight-Based Dosing to a Flat Dose for Avelumab in Metastatic Merkel Cell and Advanced Urothelial Carcinoma.

Clin Pharmacol Ther. 2020 03;107(3):588-596

Authors: Novakovic AM, Wilkins JJ, Dai H, Wade JR, Neuteboom B, Brar S, Bello CL, Girard P, Khandelwal A

Abstract
Avelumab, an anti-programmed death-ligand 1 monoclonal antibody approved for the treatment of metastatic Merkel cell carcinoma and platinum-treated urothelial carcinoma, was initially approved with a 10 mg/kg weight-based dose. We report pharmacokinetic (PK)/pharmacodynamic analyses for avelumab comparing weight-based dosing and a flat 800 mg dose, developed using data from 1,827 patients enrolled in 3 clinical trials (NCT01772004, NCT01943461, and NCT02155647). PK metrics were simulated for weight-based and flat-dosing regimens and summarized by quartiles of weight. Derived exposure metrics were used in simulations of exposure-safety (various tumors) and exposure-efficacy (objective responses; Merkel cell or urothelial carcinoma). Flat dosing was predicted to provide similar exposure to weight-based dosing, with slightly lower variability. Exposure-safety and exposure-efficacy simulations suggested similar benefit:risk profiles for the two dosing regimens. These pharmacometric analyses provided the basis for the US Food and Drug Administration approval of a flat dose of avelumab 800 mg every 2 weeks in approved indications.

PMID: 31553054 [PubMed - indexed for MEDLINE]

Permalink for 'Merkel cell carcinoma in Latin America: a contribution from an expanded access program for avelumab to address issues from experts' recommendations.'

Merkel cell carcinoma in Latin America: a contribution from an expanded access program for avelumab to address issues from experts' recommendations.

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

Merkel cell carcinoma in Latin America: a contribution from an expanded access program for avelumab to address issues from experts' recommendations.

Cancer Immunol Immunother. 2020 Oct 26;:

Authors: Munhoz RR, Cayol F, Corrales L, Gerson R, Tilli M, Barreto EO, Sánchez Castillo JO, Schmerling RA, Cinat G

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive malignancy, associated with poor outcomes in patients with metastatic disease (mMCC). Management has been dramatically altered as a result of incorporating immune checkpoint blockade agents. MCC data from Latin America (LATAM) come from case-series or individual records. Regional registries are lacking. A need for better registries to improve current knowledge about MCC is highlighted. Our objectives were to describe a real-world experience with avelumab as a second-line (or first-line in unfit patients) treatment in a subset of LATAM participants enrolled in a global Expanded Access Program (EAP) for patients with mMCC, and to evaluate its contribution to the resolution of the concerns described in a recent regional experts review.
MATERIALS AND METHODS: We reviewed data of LATAM participants in an avelumab EAP for mMCC treatment (NCT03089658). EAP patient had unresectable or mMCC with progressive disease after one line of chemotherapy, and were ineligible for clinical trials or unfit for chemotherapy.
RESULTS: 46 patients (median age: 71.6 years; 60.9% males; median treatment duration: 7.9 months) were included in the LATAM EAP. Physician-assessed objective responses were available for 19 patients. Complete response rate was 15.8% and partial response rate reached 42.1%, summarizing an objective response rate of 57.9%. Stable disease rate was 10.5%, with a disease control response of 68.4%.
CONCLUSION: Avelumab showed robust efficacy and a safety profile consistent with global EAP data. Results are aimed to improve current knowledge about mMCC treatment and access to immunooncologic strategies for treating LATAM patients.

PMID: 33104838 [PubMed - as supplied by publisher]

Evidence and Considerations on Treatment of Small Size Merkel Cell Head and Neck Carcinoma.

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

Evidence and Considerations on Treatment of Small Size Merkel Cell Head and Neck Carcinoma.

Int Arch Otorhinolaryngol. 2020 Oct;24(4):e487-e491

Authors: Kotelnikova EF, Laus M, Croce A

Abstract
Introduction Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine malignant cancer. It is an epidermal cancer common in the head and neck. Objectives Though there is limited number of cases described in the literature for the treatment difficult to obtain. Our purpose was to present the clinical course and treatment of four patients with MCC. Methods We conducted a retrospective analysis and obtained detailed clinical information for all 4 patients treated for MCC at the ENT Department of the SS Annunziata Hospital in Chieti, Italy, from 2013 through 2015. Results In our study, two patients presented with the tumor in a rare site (lower eyelid). All of the patients underwent surgical treatment: three patients had free excision margins and negative sentinel lymph nodes (SLNs) while 1 patient had free excision margins and positive SLNs. The latter patient underwent ipsilateral neck dissection. In another patient, the fluorodeoxyglucose positron emission topography (FDG PET)/computed tomography (CT) performed 6 months after the surgery has shown high metabolic activity in the left parotid gland, and the patient underwent total parotidectomy and a neck dissection. Conclusion Sentinel lymph node biopsy is a useful technique in small size MCCs of the head and neck. However, the parotid gland should be strictly controlled in patients with lower eyelid tumors.

PMID: 33101516 [PubMed]

Permalink for 'Immune checkpoint inhibition therapy for advanced skin cancer in patients with concomitant hematological malignancy: a retrospective multicenter DeCOG study of 84 patients.'

Immune checkpoint inhibition therapy for advanced skin cancer in patients with concomitant hematological malignancy: a retrospective multicenter DeCOG study of 84 patients.

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

Immune checkpoint inhibition therapy for advanced skin cancer in patients with concomitant hematological malignancy: a retrospective multicenter DeCOG study of 84 patients.

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

Authors: Leiter U, Loquai C, Reinhardt L, Rafei-Shamsabadi D, Gutzmer R, Kaehler K, Heinzerling L, Hassel JC, Glutsch V, Sirokay J, Schlecht N, Rübben A, Gambichler T, Schatton K, Pfoehler C, Franklin C, Terheyden P, Haferkamp S, Mohr P, Bischof L, Livingstone E, Zimmer L, Weichenthal M, Schadendorf D, Meiwes A, Keim U, Garbe C, Becker JC, Ugurel S

Abstract
BACKGROUND: Skin cancers are known for their strong immunogenicity, which may contribute to a high treatment efficacy of immune checkpoint inhibition (ICI). However, a considerable proportion of patients with skin cancer is immuno-compromised by concomitant diseases. Due to their previous exclusion from clinical trials, the ICI treatment efficacy is poorly investigated in these patients. The present study analyzed the ICI treatment outcome in advanced patients with skin cancer with a concomitant hematological malignancy.
METHODS: This retrospective multicenter study included patients who were treated with ICI for locally advanced or metastatic melanoma (MM), cutaneous squamous cell carcinoma (cSCC), or Merkel cell carcinoma (MCC), and had a previous diagnosis of a hematological malignancy irrespective of disease activity or need of therapy at ICI treatment start. Comparator patient cohorts without concomitant hematological malignancy were extracted from the prospective multicenter skin cancer registry ADOREG. Treatment outcome was measured as best overall response, progression-free (PFS), and overall survival (OS).
RESULTS: 84 patients (MM, n=52; cSCC, n=15; MCC, n=17) with concomitant hematological malignancy were identified at 20 skin cancer centers. The most frequent concomitant hematological malignancies were non-Hodgkin's lymphoma (n=70), with chronic lymphocytic leukemia (n=32) being the largest entity. While 9 patients received ICI in an adjuvant setting, 75 patients were treated for advanced non-resectable disease (55 anti-PD-1; 8 anti-PD-L1; 5 anti-CTLA-4; 7 combinations). In the latter 75 patients, best objective response (complete response+partial response) was 28.0%, disease stabilization was 25.3%, and 38.6% showed progressive disease (PD). Subdivided by skin cancer entity, best objective response was 31.1% (MM), 26.7% (cSCC), and 18.8% (MCC). Median PFS was 8.4 months (MM), 4.0 months (cSCC), and 5.7 months (MCC). 1-year OS rates were 78.4% (MM), 65.8% (cSCC), and 47.4% (MCC). Comparison with respective ADOREG patient cohorts without hematological malignancy (n=392) revealed no relevant differences in ICI therapy outcome for MM and MCC, but a significantly reduced PFS for cSCC (p=0.002).
CONCLUSIONS: ICI therapy showed efficacy in advanced patients with skin cancer with a concomitant hematological malignancy. Compared with patients without hematological malignancy, the observed ICI therapy outcome was impaired in cSCC, but not in MM or MCC patients.

PMID: 33093156 [PubMed - in process]

Permalink for 'A Comprehensive Proteomics Analysis of the JC Virus (JCV) Large and Small Tumor Antigen Interacting Proteins: Large T Primarily Targets the Host Protein Complexes with V-ATPase and Ubiquitin Ligase Activities While Small t Mostly Associates with Those Ha'

A Comprehensive Proteomics Analysis of the JC Virus (JCV) Large and Small Tumor Antigen Interacting Proteins: Large T Primarily Targets the Host Protein Complexes with V-ATPase and Ubiquitin Ligase Activities While Small t Mostly Associates with Those Ha

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

A Comprehensive Proteomics Analysis of the JC Virus (JCV) Large and Small Tumor Antigen Interacting Proteins: Large T Primarily Targets the Host Protein Complexes with V-ATPase and Ubiquitin Ligase Activities While Small t Mostly Associates with Those Having Phosphatase and Chromatin-Remodeling Functions.

Viruses. 2020 Oct 20;12(10):

Authors: Saribas S, Safak M

Abstract
The oncogenic potential of both the polyomavirus large (LT-Ag) and small (Sm t-Ag) tumor antigens has been previously demonstrated in both tissue culture and animal models. Even the contribution of the MCPyV tumor antigens to the development of an aggressive human skin cancer, Merkel cell carcinoma, has been recently established. To date, the known primary targets of these tumor antigens include several tumor suppressors such as pRb, p53, and PP2A. However, a comprehensive list of the host proteins targeted by these proteins remains largely unknown. Here, we report the first interactome of JCV LT-Ag and Sm t-Ag by employing two independent "affinity purification/mass spectroscopy" (AP/MS) assays. The proteomics data identified novel targets for both tumor antigens while confirming some of the previously reported interactions. LT-Ag was found to primarily target the protein complexes with ATPase (v-ATPase and Smc5/6 complex), phosphatase (PP4 and PP1), and ligase (E3-ubiquitin) activities. In contrast, the major targets of Sm t-Ag were identified as Smarca1/6, AIFM1, SdhA/B, PP2A, and p53. The interactions between "LT-Ag and SdhB", "Sm t-Ag and Smarca5", and "Sm t-Ag and SDH" were further validated by biochemical assays. Interestingly, perturbations in some of the LT-Ag and Sm t-Ag targets identified in this study were previously shown to be associated with oncogenesis, suggesting new roles for both tumor antigens in novel oncogenic pathways. This comprehensive data establishes new foundations to further unravel the new roles for JCV tumor antigens in oncogenesis and the viral life cycle.

PMID: 33092197 [PubMed - in process]

Phosphoinositide 3'-Kinase γ Facilitates Polyomavirus Infection.

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

Phosphoinositide 3'-Kinase γ Facilitates Polyomavirus Infection.

Viruses. 2020 Oct 20;12(10):

Authors: Clark P, Gee GV, Albright BS, Assetta B, Han Y, Atwood WJ, DiMaio D

Abstract
Polyomaviruses are small, non-enveloped DNA tumor viruses that cause serious disease in immunosuppressed people, including progressive multifocal leukoencephalopathy (PML) in patients infected with JC polyomavirus, but the molecular events mediating polyomavirus entry are poorly understood. Through genetic knockdown approaches, we identified phosphoinositide 3'-kinase γ (PI3Kγ) and its regulatory subunit PIK3R5 as cellular proteins that facilitate infection of human SVG-A glial cells by JCPyV. PI3Kα appears less important for polyomavirus infection than PI3Kγ. CRISPR/Cas9-mediated knockout of PIK3R5 or PI3Kγ inhibited infection by authentic JCPyV and by JC pseudovirus. PI3Kγ knockout also inhibited infection by BK and Merkel Cell pseudoviruses, other pathogenic human polyomaviruses, and SV40, an important model polyomavirus. Reintroduction of the wild-type PI3Kγ gene into the PI3Kγ knock-out SVG-A cells rescued the JCPyV infection defect. Disruption of the PI3Kγ pathway did not block binding of JCPyV to cells or virus internalization, implying that PI3Kγ facilitates some intracellular step(s) of infection. These results imply that agents that inhibit PI3Kγ signaling may have a role in managing polyomavirus infections.

PMID: 33092168 [PubMed - in process]

Primary Treatment Selection for Clinically Node-Negative Merkel Cell Carcinoma of the Head and Neck.

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

Primary Treatment Selection for Clinically Node-Negative Merkel Cell Carcinoma of the Head and Neck.

Otolaryngol Head Neck Surg. 2020 Oct 20;:194599820967001

Authors: Jacobs D, Olino K, Park HS, Clune J, Cheraghlou S, Girardi M, Burtness B, Kluger H, Judson BL

Abstract
OBJECTIVE: Merkel cell carcinoma practice guidelines recommend sentinel lymph node biopsy after wide local excision for the initial management of clinically node-negative disease without distant metastases (cN0M0). Despite guideline publication, treatment selection remains variable. We hypothesized that receipt of guideline-recommended care would be more common in patients evaluated at academic centers and institutions with high melanoma case volumes and that such therapy would be associated with improved overall survival.
STUDY DESIGN: Retrospective cohort analysis.
SETTING: The National Cancer Database from 2004 to 2015.
METHODS: A total of 3500 patients were included. We utilized Kaplan-Meier analysis and logistic and Cox proportional hazard regressions. Survival analysis was performed on inverse probability-weighted cohorts.
RESULTS: There has been a trend toward evaluation at academic programs at a rate of 1.58% of patients per year (95% CI, 1.06%-2.11%) since 2004. However, the percentage of patients receiving guideline-compliant primary tumor excision and lymph node evaluation has plateaued at approximately 50% since 2012. Guideline-compliant surgical management was more commonly provided to patients evaluated at academic programs than nonacademic programs but only when those institutions had a high melanoma case volume (odds ratio, 2.01; 95% CI, 1.62-2.48). Receipt of guideline-compliant primary tumor excision and lymph node evaluation was associated with improved overall survival (hazard ratio, 0.70; 95% CI, 0.64-0.76).
CONCLUSION: Facility factors affect rates of receipt of guideline-compliant initial surgical management for patients with node-negative Merkel cell carcinoma. Given the survival benefit of such treatment, patients may benefit from care at hospitals with high melanoma case volumes.

PMID: 33079010 [PubMed - as supplied by publisher]

Reduced Wide Local Excision Margins are Associated with Increased Risk of Relapse and Death from Merkel Cell Carcinoma.

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

Reduced Wide Local Excision Margins are Associated with Increased Risk of Relapse and Death from Merkel Cell Carcinoma.

Ann Surg Oncol. 2020 Oct 18;:

Authors: Andruska N, Mahapatra L, Brenneman RJ, Rich JT, Baumann BC, Compton L, Thorstad WL, Daly MD

Abstract
INTRODUCTION: Current recommendations regarding the size of wide local excision (WLE) margins for Merkel cell carcinoma (MCC) are not well established.
METHODS: WLE and pathologic margins were respectively reviewed from 79 patients with stage I or II MCC, who underwent WLE at Washington University in St Louis from 2005 to 2019. Outcomes included local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant recurrence-free survival (DRFS), disease-free survival (DFS), and disease-specific survival (DSS).
RESULTS: Thirty-two percent of patients received adjuvant radiotherapy (aRT). At 1 year, DFS was 51.3%, 71.4%, and 87.8% for patients with WLE margins < 1 cm, 1-1.9 cm, and ≥ 2 cm, respectively (p = 0.02). At 3 years, the DSS was 57.7%, 82.6%, and 100% for patients with WLE margins < 1 cm, 1-1.9 cm, and ≥ 2 cm, respectively (p = 0.02). Multivariable Cox analysis demonstrated that every 1-cm increase in WLE margins was associated with improved RRFS [hazard ratio (HR) = 0.28, 95% confidence interval (CI): 0.11-0.75], DRFS (HR 0.30, CI 0.08-0.99), DFS (HR 0.42, CI 0.21-0.86), and DSS (HR 0.16, CI 0.04-0.61). WLE and pathologic margin size were moderately-to-strongly correlated (r = 0.66). Close or positive pathologic margins (< 3 mm) were associated with reduced DRFS (HR 6.83, CI 1.80-25.9), DFS (HR 2.98, CI 1.31-6.75), and DSS (HR 3.52, CI 1.14-10.9).
CONCLUSION: Reduced WLE and pathologic margins were associated with higher risk of relapse and death from MCC. Larger WLE margins are important in populations with lower rates of adjuvant radiation.

PMID: 33073342 [PubMed - as supplied by publisher]

Is Merkel Cell Carcinoma of Lymph Node Actually Metastatic Cutaneous Merkel Cell Carcinoma?

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

Is Merkel Cell Carcinoma of Lymph Node Actually Metastatic Cutaneous Merkel Cell Carcinoma?

Am J Clin Pathol. 2020 08 05;154(3):369-380

Authors: Lawrence LEB, Saleem A, Sahoo MK, Tan SK, Pinsky BA, Natkunam Y, Kunder CA, Stehr H, Zehnder JL

Abstract
OBJECTIVES: The possibility of a so-called primary lymph node neuroendocrine carcinoma has been described in the literature. Here we evaluate cases fitting such a diagnosis and find that the cases demonstrate a convincing and pervasive pattern consistent with metastatic Merkel cell carcinoma.
METHODS: Six cases of primary lymph node Merkel cell carcinoma and one case of metastatic neuroendocrine carcinoma at a bony site, all with unknown primary, were sequenced using a combination of whole-exome and targeted panel methods. Sequencing results were analyzed for the presence of an ultraviolet (UV) mutational signature or off-target detection of Merkel cell polyomavirus (MCPyV).
RESULTS: Four of six primary lymph node cases were positive for a UV mutational signature, with the remaining two cases positive for off-target alignment of MCPyV. One case of neuroendocrine carcinoma occurring at a bony site was also positive for a UV mutational signature.
CONCLUSIONS: We find no evidence to corroborate the existence of so-called primary Merkel cell carcinoma of lymph node.

PMID: 32445471 [PubMed - indexed for MEDLINE]

Permalink for 'Merkel Cell Polyomavirus Large T Antigen is Dispensable in G2 and M-Phase to Promote Proliferation of Merkel Cell Carcinoma Cells.'

Merkel Cell Polyomavirus Large T Antigen is Dispensable in G2 and M-Phase to Promote Proliferation of Merkel Cell Carcinoma Cells.

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

Merkel Cell Polyomavirus Large T Antigen is Dispensable in G2 and M-Phase to Promote Proliferation of Merkel Cell Carcinoma Cells.

Viruses. 2020 Oct 14;12(10):

Authors: Houben R, Ebert M, Hesbacher S, Kervarrec T, Schrama D

Abstract
Merkel cell carcinoma (MCC) is an aggressive skin cancer frequently caused by the Merkel cell polyomavirus (MCPyV), and proliferation of MCPyV-positive MCC tumor cells depends on the expression of a virus-encoded truncated Large T antigen (LT) oncoprotein. Here, we asked in which phases of the cell cycle LT activity is required for MCC cell proliferation. Hence, we generated fusion-proteins of MCPyV-LT and parts of geminin (GMMN) or chromatin licensing and DNA replication factor1 (CDT1). This allowed us to ectopically express an LT, which is degraded either in the G1 or G2 phase of the cell cycle, respectively, in MCC cells with inducible T antigen knockdown. We demonstrate that LT expressed only in G1 is capable of rescuing LT knockdown-induced growth suppression while LT expressed in S and G2/M phases fails to support proliferation of MCC cells. These results suggest that the crucial function of LT, which has been demonstrated to be inactivation of the cellular Retinoblastoma protein 1 (RB1) is only required to initiate S phase entry.

PMID: 33066686 [PubMed - in process]

Targeting the epigenetic addiction of Merkel cell carcinoma.

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

Targeting the epigenetic addiction of Merkel cell carcinoma.

EMBO Mol Med. 2020 Oct 16;:e13347

Authors: Mauri F, Blanpain C

Abstract
Merkel cell carcinoma (MCC) is a rare but very aggressive neuroendocrine cancer of the skin, with very limited therapeutic options. Although immunotherapy is effective in some cases, there is an unmet need for new therapeutic approaches in MCCs. In this issue of EMBO Molecular Medicine, Leiendecker et al identify a selective vulnerability of MCC for inhibitors of the lysine-specific histone demethylase 1A (LSD1). LSD1 inhibitors promote differentiation of tumor cells toward normal Merkel cell fate, impairing tumor cell growth in vivo, and opening new avenues for the treatment of patients with MCC.

PMID: 33063436 [PubMed - as supplied by publisher]

Regionally Metastatic Merkel Cell Carcinoma Associated with Paraneoplastic Anti-N-methyl-D-aspartate Receptor Encephalitis.

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

Regionally Metastatic Merkel Cell Carcinoma Associated with Paraneoplastic Anti-N-methyl-D-aspartate Receptor Encephalitis.

Case Rep Oncol Med. 2020;2020:1257587

Authors: Shalhout SZ, Emerick KS, Sadow PM, Linnoila JJ, Miller DM

Abstract
Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neuroendocrine cancer with a high risk of recurrence and metastasis. MCC is generally associated with advanced age, fair skin, sun exposure, immunosuppression, and in the majority of cases, the Merkel cell polyomavirus. Neuroendocrine malignancies are associated with a variety of paraneoplastic neurological syndromes (PNS), characterized as autoimmune responses to malignancy-associated expression of neural antigens. Our literature review underscores previous case reports of MCC-associated PNS with voltage-gated calcium channel (VGCC) and anti-Hu (or ANNA-1) autoantibodies. We present the case of a 59-year-old male with regionally metastatic Merkel cell carcinoma complicated by the paraneoplastic manifestation of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. His primary lower neck subcutaneous MCC and metastasis were initially treated with surgery. Additional recurrent lymph node metastases were successfully treated with definitive intensity-modulated radiation therapy. His PNS improved with rituximab therapy. Although rare, this case highlights that in the setting of seizures and prominent psychiatric symptoms accompanying an MCC diagnosis, evaluation for autoimmune paraneoplastic encephalitis is warranted. Awareness and detection of preexisting PNS are crucial in the era of immune checkpoint inhibitors (ICI) for advanced MCC, where treatment with ICI has the potential to exacerbate preexisting autoimmune PNS and lead to worsened or even lethal neurologic immune-related adverse events (nirAEs).

PMID: 33062358 [PubMed]

Permalink for 'Clinical, FDG-PET and molecular markers of immune checkpoint inhibitor response in patients with metastatic Merkel cell carcinoma.'

Clinical, FDG-PET and molecular markers of immune checkpoint inhibitor response in patients with metastatic Merkel cell carcinoma.

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

Clinical, FDG-PET and molecular markers of immune checkpoint inhibitor response in patients with metastatic Merkel cell carcinoma.

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

Authors: Weppler AM, Pattison A, Bhave P, De Ieso P, Raleigh J, Hatzimihalis A, Gill AJ, Balachander S, Callahan J, Chua M, Au-Yeung G, McArthur GA, Hicks RJ, Tothill RW, Sandhu S

Abstract
BACKGROUND: Metastatic Merkel cell carcinoma (mMCC) is an aggressive neuroendocrine malignancy of the skin with a poor prognosis. Immune checkpoint inhibitors (ICIs) have shown substantial efficacy and favorable safety in clinical trials.
METHODS: Medical records of patients (pts) with mMCC treated with ICIs from August 2015 to December 2018 at Peter MacCallum Cancer Centre in Australia were analyzed. Response was assessed with serial imaging, the majority with FDG-PET/CT scans. RNA sequencing and immunohistochemistry for PD-L1, CD3 and Merkel cell polyomavirus (MCPyV) on tumor samples was performed.
RESULTS: 23 pts with mMCC were treated with ICIs. A median of 8 cycles (range 1 to 47) were administered, with treatment ongoing in 6 pts. Objective responses (OR) were observed in 14 pts (61%): 10 (44%) complete responses (CR) and 4 (17%) partial responses (PR). Median time to response was 8 weeks (range 6 to 12) and 12-month progression-free survival rate was 39%. Increased OR were seen in pts aged less than 75 (OR 80% vs 46%), no prior history of chemotherapy (OR 64% vs 50%), patients with an immune-related adverse event (OR 100% vs 43%) and in MCPyV-negative tumors (OR 69% vs 43%). Pts with a CR had lower mean metabolic tumor volume on baseline FDG-PET/CT scan (CR: 35.7 mL, no CR: 187.8 mL, p=0.05). There was no correlation between PD-L1 positivity and MCPyV status (p=0.764) or OR (p=0.245). 10 pts received radiation therapy (RT) during ICI: 4 pts started RT concurrently (OR 75%, CR 50%), 3 pts had isolated ICI-resistant lesions successfully treated with RT and 3 pts with multisite progression continued to progress despite RT. Overall, 6 pts (26%) had grade 1-2 immune-related adverse events.
CONCLUSION: ICIs showed efficacy and safety in mMCC consistent with trial data. Clinical and imaging predictors of response were identified.

PMID: 33060145 [PubMed - in process]

Proteomic approach to discover human cancer viruses from formalin-fixed tissues.

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

Proteomic approach to discover human cancer viruses from formalin-fixed tissues.

JCI Insight. 2020 Oct 15;:

Authors: Toptan T, Cantrell PS, Zeng X, Liu Y, Sun M, Yates NA, Chang Y, Moore PS

Abstract
The challenge of discovering a completely new human tumor virus of unknown phylogeny or sequence depends on detecting viral molecules and differentiating them from host molecules in the virus-associated neoplasm. We developed differential peptide subtraction (DPS) using differential mass-spectrometry (dMS) followed by targeted analysis to facilitate this discovery. We validated this approach by analyzing Merkel cell carcinoma (MCC), an aggressive human neoplasm, in which ~80% of cases are caused by the human Merkel cell polyomavirus (MCV). Approximately 20% of MCC have a high mutational burden and are negative for MCV, but are microscopically indistinguishable from virus positive cases. Using 23 (12 MCV positive, 11 MCV negative) formalin-fixed MCC, DPS identified both viral and human biomarkers (MCV Large T antigen, CDKN2AIP, SERPINB5 and TRIM29) that discriminates MCV positive and negative MCC. Statistical analysis of 498,131 dMS features not matching the human proteome by DPS revealed 562 (0.11%) to be up-regulated in virus-infected samples. Remarkably, four (20%) of the top 20 candidate MS spectra originated from MCV T oncoprotein peptides and confirmed by reverse translation degenerate oligonucleotide sequencing. DPS is a robust proteomic approach to identify novel viral sequences in infectious tumors when nucleic acid-based methods are not feasible.

PMID: 33055416 [PubMed - as supplied by publisher]

Positron Emission Tomography in Merkel Cell Carcinoma.

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

Positron Emission Tomography in Merkel Cell Carcinoma.

Cancers (Basel). 2020 Oct 09;12(10):

Authors: Sachpekidis C, Sidiropoulou P, Hassel JC, Drakoulis N, Dimitrakopoulou-Strauss A

Abstract
Merkel cell carcinoma (MCC) is a rare neuroendocrine skin malignancy usually arising as a nonspecific nodule on sun-exposed areas of the head and neck. Given the poor prognosis of this aggressive tumor, assessment of disease burden in pre- and post-treatment care may ensure an optimal management with significant implications for patient surveillance and prognosis. Although imaging has established its role in locally advanced or distant metastatic MCC, a standard imaging algorithm is yet to be determined and respective recommendations are mainly based on melanoma. Positron emission tomography/computed tomography (PET/CT) is increasingly evolving as a valuable imaging tool in metastatic or unresectable MCC, mostly utilizing the glucose analogue 18F-fluorodeoxyglucose (18F-FDG) as a radiotracer. Despite being inferior in detecting the disease in its early stages compared to the "gold standard" of sentinel lymph node biopsy, recent evidence suggests an important role for 18F-FDG PET/CT in the routine workup of localized MCC. Moreover, 68Ga-labeled somatostatin analogues have been employed as PET tracers in the field of MCC with promising, yet comparable to 18F-FDG, results. This article provides a structured literature review of the most important studies investigating the role of PET or PET/CT in the clinical practice of MCC.

PMID: 33050255 [PubMed]

p40 expression in Merkel cell carcinoma.

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

p40 expression in Merkel cell carcinoma.

Hum Pathol. 2020 06;100:54-55

Authors: Kervarrec T, Guyétant S, Jullie ML

PMID: 32234323 [PubMed - indexed for MEDLINE]

An Aggressive Presentation of Merkel Cell Carcinoma: A Case Report.

Fetched: October 15th, 2020, 5:01am GMT

An Aggressive Presentation of Merkel Cell Carcinoma: A Case Report.

J Investig Med High Impact Case Rep. 2020 Jan-Dec;8:2324709620963714

Authors: Ines Z, Sabrine H, Saadallah F, Mohamed Ali A, Lamia C, Riadh C, Khaled R

Abstract
Merkel cell carcinoma (MCC) is a rare malignant neuroendocrine tumor more common in immunosuppressed old patients. It is characterized by a high frequency of local recurrence, regional nodal metastasis, distant metastasis, and low survival rate. The diagnosis of MCC is challenging due to its rarity and can be clinically mistaken for other skin cancer. We report a case of locally advanced MCC of the left groin with aggressive behavior that was finally controlled with a combined treatment and we collected data from the literature to discuss the appropriate therapeutic algorithm for the management of this uncommon skin tumor.

PMID: 33047644 [PubMed - in process]

Permalink for 'Pembrolizumab and other immune checkpoint inhibitors in locally advanced or metastatic merkel cell carcinoma: safety and efficacy.'

Pembrolizumab and other immune checkpoint inhibitors in locally advanced or metastatic merkel cell carcinoma: safety and efficacy.

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

Pembrolizumab and other immune checkpoint inhibitors in locally advanced or metastatic merkel cell carcinoma: safety and efficacy.

Expert Rev Anticancer Ther. 2020 Oct 12;:

Authors: Marchand A, Kervarrec T, Bhatia S, Samimi M

Abstract
INTRODUCTION: Merkel Cell Carcinoma (MCC) is a rare aggressive skin cancer, mostly affecting elderly patients. Until recently, patients with advanced disease were treated with cytotoxic chemotherapies despite rapid chemoresistance and high toxicity. As with other cancers, immune checkpoint inhibitors (CPI), including pembrolizumab, allow durable responses with a manageable safety profile in these patients.
AREAS COVERED: This review describes the rationale for using PD-1/PD-L1 inhibitors in MCC, as well as efficacy and safety results from the 3 open-label trials investigating pembrolizumab or other PD-1/PD-L1 inhibitors in patients with advanced MCC. Real-life experience and predictive pre-treatment biomarkers are discussed to assess which patients are likely to be candidates for such strategies. Ongoing fields of research include the use of CPI in the adjuvant or neoadjuvant setting and combined strategies in refractory patients. Expert opinion: CPI have become the standard of care for frontline treatment in patients with advanced MCC. Earlier introduction of CPI in the disease course, including neo-adjuvant and adjuvant settings, is likely to improve the outcomes further. Given the rarity of this cancer, we still need to harmonize efforts in order to conduct large scale trials and efficiently identify best optimal care.

PMID: 33044876 [PubMed - as supplied by publisher]

Safe application of extensive radiotherapy to a cardiac resynchronization device.

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

Safe application of extensive radiotherapy to a cardiac resynchronization device.

ESC Heart Fail. 2020 Oct 11;:

Authors: Schernthaner C, Kopp M, Dagn K, Rettenbacher L, Weiss L, Meyersburg D, Brandt MC, Hoppe UC, Strohmer B

Abstract
Patients with cardiac implantable electronic devices undergoing radiotherapy (RT) are prone to the risk of device failure. Guidelines and manufacturer's instructions are lacking practical recommendations for cumulative radiation doses to pacemakers or implantable cardioverter defibrillators. The present case demonstrates the effect of RT of a Merkel cell carcinoma near the location of a cardiac resynchronization therapy pacemaker. Despite guideline recommendations, surgical relocation or de novo implantation of the device on the contralateral side was avoided to prevent the dissemination of tumour cells, inflammation, and wound healing complications. A total dose of 47.25 Gy applied in very close proximity to the cardiac resynchronization therapy pacemaker was carried out safely without jeopardizing the patient and any device malfunction during and after treatment within >1.5 years of follow-up period. The present case demonstrates that high-dose RT near to a cardiac resynchronization therapy device can be carried out safely. Special precautions during RT as well as close device follow-up interrogations are mandatory. Large-scale studies are needed for the true frequency of adverse events.

PMID: 33040476 [PubMed - as supplied by publisher]

Recent Highlights: Onco Viral Exploitation of the SUMO System.

Fetched: October 11th, 2020, 5:00am GMT

Recent Highlights: Onco Viral Exploitation of the SUMO System.

Curr Issues Mol Biol. 2020;35:1-16

Authors: Mattoscio D, Medda A, Chiocca S

Abstract
Small ubiquitin-like modifier (SUMO)ylation is a crucial post-translational modification that controls functions of a wide collection of proteins and biological processes. Hence, given its pleiotropic role, viruses have developed many approaches to usurp SUMO conjugation to exploit the cellular host environment for their own benefit. Consistently, cancer cells also frequently impact on SUMO to force cellular transformation, underlining the importance of SUMO in health and diseases. Therefore, after a brief introduction to the multistep SUMOylation pathway, in this review we will focus our attention on several examples of strategies adopted by oncogenic viruses to hijack SUMOylation in order to promote infection, persistence and malignant transformation of host cells.

PMID: 31422930 [PubMed - indexed for MEDLINE]

LSD1 inhibition induces differentiation and cell death in Merkel cell carcinoma.

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

LSD1 inhibition induces differentiation and cell death in Merkel cell carcinoma.

EMBO Mol Med. 2020 Oct 07;:e12525

Authors: Leiendecker L, Jung PS, Krecioch I, Neumann T, Schleiffer A, Mechtler K, Wiesner T, Obenauf AC

Abstract
Merkel cell carcinoma (MCC) is a highly aggressive, neuroendocrine skin cancer that lacks actionable mutations, which could be utilized for targeted therapies. Epigenetic regulators governing cell identity may represent unexplored therapeutic entry points. Here, we targeted epigenetic regulators in a pharmacological screen and discovered that the lysine-specific histone demethylase 1A (LSD1/KDM1A) is required for MCC growth in vitro and in vivo. We show that LSD1 inhibition in MCC disrupts the LSD1-CoREST complex leading to displacement and degradation of HMG20B (BRAF35), a poorly characterized complex member that is essential for MCC proliferation. Inhibition of LSD1 causes derepression of transcriptional master regulators of the neuronal lineage, activates a gene expression signature resembling normal Merkel cells, and induces cell cycle arrest and cell death. Our study unveils the importance of LSD1 for maintaining cellular plasticity and proliferation in MCC. There is also growing evidence that cancer cells exploit cellular plasticity and dedifferentiation programs to evade destruction by the immune system. The combination of LSD1 inhibitors with checkpoint inhibitors may thus represent a promising treatment strategy for MCC patients.

PMID: 33026191 [PubMed - as supplied by publisher]

Safety and Efficacy of Immune Checkpoint Inhibitors in Patients on Dialysis: A Retrospective Case Series.

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

Safety and Efficacy of Immune Checkpoint Inhibitors in Patients on Dialysis: A Retrospective Case Series.

Am J Kidney Dis. 2020 08;76(2):299-302

Authors: Strohbehn IA, Lee M, Seethapathy H, Chute D, Rahma O, Guidon A, Neilan TG, Zlotoff DA, Okin D, Rengarajan M, Reynolds K, Sise ME

PMID: 32417401 [PubMed - indexed for MEDLINE]

Permalink for 'The HDAC Inhibitor Domatinostat Promotes Cell Cycle Arrest, Induces Apoptosis and Increases Immunogenicity of Merkel Cell Carcinoma Cells.'

The HDAC Inhibitor Domatinostat Promotes Cell Cycle Arrest, Induces Apoptosis and Increases Immunogenicity of Merkel Cell Carcinoma Cells.

Fetched: October 3rd, 2020, 5:00am GMT

The HDAC Inhibitor Domatinostat Promotes Cell Cycle Arrest, Induces Apoptosis and Increases Immunogenicity of Merkel Cell Carcinoma Cells.

J Invest Dermatol. 2020 Sep 28;:

Authors: Song L, Bretz AC, Gravemeyer J, Spassova I, Muminova S, Gambichler T, Sriram A, Ferrone S, Becker JC

Abstract
Merkel cell carcinoma (MCC) is a rare, highly aggressive skin cancer for which immune modulation by immune checkpoint inhibitors show remarkable response rates. However, primary or secondary resistance to immunotherapy prevents benefits in a significant proportion of patients. For MCC, one immune escape mechanism is insufficient recognition by T cells due to downregulation of major histocompatibility complex (MHC) class I surface expression. Histone deacetylase (HDAC) inhibitors have been demonstrated to epigenetically reverse low MHC class I expression caused by downregulation of the antigen processing machinery (APM). Domatinostat, an orally available small molecule inhibitor targeting HDAC class I, is currently in clinical evaluation to overcome resistance to immunotherapy. Here, we present preclinical data on its efficacy and mode of action in MCC. Single-cell RNA-sequencing revealed a distinct gene expression signature of antigen processing and presentation, cell cycle arrest and execution phase of apoptosis upon treatment. Accordingly, functional assays showed that it induced G2M arrest and apoptosis. In surviving cells, APM component gene transcription and translation were up-regulated, consequently resulting in increased MHC class I surface expression. Altogether, domatinostat not only exerts direct anti-tumoral effects, but also restores HLA class I surface expression on MCC cells. Therefore, restoring surviving MCC cells' susceptibility to recognition and elimination by cognate cytotoxic T cells.

PMID: 33002502 [PubMed - as supplied by publisher]

Pembrolizumab-induced lichen planus pemphigoides in a patient with metastatic Merkel cell carcinoma.

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

Pembrolizumab-induced lichen planus pemphigoides in a patient with metastatic Merkel cell carcinoma.

JAAD Case Rep. 2020 Oct;6(10):1045-1047

Authors: Kwon CW, Murthy RK, Kudchadkar R, Stoff BK

PMID: 32995442 [PubMed]

Permalink for 'Decreased 5-hydroxymethylcytosine immunoreactivity in primary Merkel cell carcinoma is a strong predictor for disease-specific death.'

Decreased 5-hydroxymethylcytosine immunoreactivity in primary Merkel cell carcinoma is a strong predictor for disease-specific death.

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

Decreased 5-hydroxymethylcytosine immunoreactivity in primary Merkel cell carcinoma is a strong predictor for disease-specific death.

Br J Dermatol. 2019 08;181(2):389-390

Authors: Gambichler T, Schmitt K, Rüddel I, Dreibigacker M, Stockfleth E, Becker JC

PMID: 30703276 [PubMed - indexed for MEDLINE]

Merkel cell carcinoma of the lower lip: A case report and literature review.

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

Merkel cell carcinoma of the lower lip: A case report and literature review.

Oral Oncol. 2020 Sep 25;:105019

Authors: de Arruda JAA, Mesquita RA, Canedo NHS, Agostini M, Abrahão AC, de Andrade BAB, Romañach MJ

Abstract
Merkel cell carcinoma (MCC) is an aggressive primary cutaneous neuroendocrine carcinoma that predominantly affects the sun-damaged skin of the head and neck region, extremities, and trunk of white older individuals. Microscopically, small to intermediate round blue cells show granular nuclei with a salt-and-pepper chromatin pattern, and are usually positive for epithelial and neuroendocrine markers, particularly for cytokeratin 20 in a perinuclear dot-like staining. The 5-year overall survival rate for individuals with localized MCC is 51% and the most common treatment choice is surgery with adjuvant radiotherapy. As far as we know, 23 cases of MCC of the lips have been reported to date in the English-language literature. We herein contribute by reporting a case of MCC affecting the lower lip of an 81-year-old male patient from Rio de Janeiro, Brazil, which likely represents the first reported case from Latin America. A review of the current literature is also included in an effort to familiarize providers with this rare, but potentially lethal neuroendocrine tumor.

PMID: 32988749 [PubMed - as supplied by publisher]

Regulation of Polyomavirus Transcription by Viral and Cellular Factors.

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

Regulation of Polyomavirus Transcription by Viral and Cellular Factors.

Viruses. 2020 Sep 24;12(10):

Authors: Yang JF, You J

Abstract
Polyomavirus infection is widespread in the human population. This family of viruses normally maintains latent infection within the host cell but can cause a range of human pathologies, especially in immunocompromised individuals. Among several known pathogenic human polyomaviruses, JC polyomavirus (JCPyV) has the potential to cause the demyelinating disease progressive multifocal leukoencephalopathy (PML); BK polyomavirus (BKPyV) can cause nephropathy in kidney transplant recipients, and Merkel cell polyomavirus (MCPyV) is associated with a highly aggressive form of skin cancer, Merkel cell carcinoma (MCC). While the mechanisms by which these viruses give rise to the relevant diseases are not well understood, it is clear that the control of gene expression in each polyomavirus plays an important role in determining the infectious tropism of the virus as well as their potential to promote disease progression. In this review, we discuss the mechanisms governing the transcriptional regulation of these pathogenic human polyomaviruses in addition to the best-studied simian vacuolating virus 40 (SV40). We highlight the roles of viral cis-acting DNA elements, encoded proteins and miRNAs that control the viral gene expression. We will also underline the cellular transcription factors and epigenetic modifications that regulate the gene expression of these viruses.

PMID: 32987952 [PubMed - in process]

Isolated Limb Perfusion on Nonmelanoma Skin Cancer for Limb Salvage: A Series of Four Cases.

Fetched: September 30th, 2020, 5:00am GMT

Isolated Limb Perfusion on Nonmelanoma Skin Cancer for Limb Salvage: A Series of Four Cases.

Cureus. 2020 Aug 24;12(8):e9998

Authors: Jiménez Herevia AE, Tavares de la Paz LA, Hinojosa Ugarte D, Nieves Condoy J

Abstract
Nonmelanoma skin cancer (NMSC) is more prevalent than all the other cancers combined together. The most common regions affected by skin cancer are the head and neck, but there is a large proportion of the cases located on the limbs. They could be bulky, very extensive and/or located in specialized regions like the hands or near to a joint. Most of those cases should be amputated, with several compromises of the function and a negative impact on the patients' quality of life. Isolated limb perfusion is a proven alternative to limb salvage on soft tissue sarcomas, but there are just a few reports about its application on non-melanoma skin cancer. The aim of the article is to describe the outcomes and prove the benefits and effectiveness to avoid limb amputation when using isolated limb perfusion on locally advanced non-melanoma skin cancer. We present clinical, retrospective study as a case series report. The study includes four patients with locally advanced non-melanoma skin cancer in the limb - three cases with squamous cell carcinoma (SCC), and one patient with Merkel cell carcinoma (MCC) who underwent to tumor necrosis factor-alpha (TNFα) and melphalan based isolated perfusion of the limb (TM-ILP). Toxicity, clinical response, and limb salvage were described. Patients were treated in the oncological surgical department in a referral hospital in Mexico. The limb salvage rate was achieved in 75%. All patients had a favorable response to TM-ILP. Complete response of the tumor was noted on two (50%) of the patients (one with histopathological confirmation), the other 50% had a partial response to the TM-ILP. No serious toxicity related to TM-ILP was observed. One patient (25%) developed regional lymph involvement six months after perfusion. Lymphadenectomy was performed, and the patient subsequently has a six-year disease-free survival. In conclusion, TM-ILP could be an effective, reliable, and safe therapy on limb salvage in selected patients with non-melanoma skin cancer who are not adequate surgical candidates.

PMID: 32983697 [PubMed]

State of the art of Mohs surgery for rare cutaneous tumors in the Spanish Registry of Mohs Surgery (REGESMOHS).

Fetched: September 30th, 2020, 5:00am GMT

State of the art of Mohs surgery for rare cutaneous tumors in the Spanish Registry of Mohs Surgery (REGESMOHS).

Int J Dermatol. 2020 Mar;59(3):321-325

Authors: Rodríguez-Jiménez P, Jimenez YD, Reolid A, Sanmartın-Jimenez O, Garces JR, Rodríguez-Prieto MA, Medrano RM, Vilarrasa E, de Eusebio-Murillo E, Redondo P, Ciudad-Blanco C, Morales-Gordillo V, Toll-Abelló A, Artola-Igarza JL, Pacheco MLA, Markixana IA, Fernández RS, Rubio AA, Vázquez-Veiga H, Flórez-Menéndez A, de la Cueva Dobao P, Botella-Estrada R, Garcia-Bracamonte B, Carnero-González L, Ruiz-Salas V, Sánchez-Sambucety P, López-Estebaranz JL, Gil P, Barchino L, Arenal MM, Ocerin-Guerra I, Hueso L, Seoane-Pose MJ, Gonzalez-Sixto B, Cano-Martinez N, Escutia-Muñoz B, Ortiz-Romero PL, Garcia-Doval I, Descalzo MA, REGESMOHS (Registro Español de Cirugía de Mohs)

Abstract
BACKGROUND: The use of Mohs micrographic surgery (MMS) for rare cutaneous tumors is poorly defined. We aim to describe the demographics, tumor presentation and topography, surgery characteristics and complications of MMS for rare cutaneous tumors in a national registry.
METHODS: Prospective cohort study of patients treated with MMS in Spain between July 2013 and June 2018. The inclusion criteria were patients with cutaneous tumors with final diagnosis different from basal cell carcinoma, squamous cell carcinoma, dermatofibrosarcoma protuberans, or any kind of melanoma.
RESULTS: Five thousand and ninety patients were recorded in the registry, from which only 73 tumors (1.4%) fulfilled the inclusion criteria: atypical fibroxanthoma (18), microcystic adnexal carcinoma (10), extramammary Paget's disease (7), Merkel cell carcinoma (5), dermatofibroma (4), trichilemmal carcinoma (4), desmoplastic trichoepithelioma (4), sebaceous carcinoma (3), leiomyosarcoma (2), porocarcinoma (2), angiosarcoma (2), trichoblastoma (1), superficial acral fibromyxoma (1), and others (10). No intra-surgery morbidity was registered. Postsurgery complications appeared in six patients (9%) and were considered mild. Median follow-up time was 0.9 years during which three Merkel cell carcinomas, one angiosarcoma, one microcystic adnexal carcinoma, and four others recurred (12.3%).
CONCLUSION: This national registry shows that rare cutaneous tumors represent a negligible part of the total MMS performed in our country with a low complication rate.

PMID: 31777957 [PubMed - indexed for MEDLINE]

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]

SerUM Markers in MERkel Cell Carcinoma Patients: a Longitudinal moniTorIng Study for optiMization of European Guidelines

Posted: January 12th, 2021, 3:00pm GMT

Condition: Merkel Cell Carcinoma
Intervention: Other: Samples
Sponsors: University Hospital, Tours; European Academy of Dermatology and Venerology
Not yet recruiting

Safety and Efficacy of XmAb18087 ± Pembrolizumab in Advanced Merkel Cell Carcinoma or Extensive-stage Small Cell Lung Cancer

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

Conditions: Merkel Cell Carcinoma; Small Cell Lung Cancer
Interventions: Biological: XmAb18087; Drug: XmAb18087 ± Pembrolizumab
Sponsors: Xencor, Inc.; ICON plc
Not yet recruiting

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
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
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

Intravenous TAEK-VAC-HerBy Vaccine Alone and in Combination Treatment in HER2 Cancer Patients

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

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

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

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

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

FT500 as Monotherapy and in Combination With Immune Checkpoint Inhibitors in Subjects With Advanced Solid Tumors

Posted: February 15th, 2019, 3:00pm GMT

Conditions: Advanced Solid Tumors; Lymphoma; Gastric Cancer; Colorectal Cancer; Head and Neck Cancer; Squamous Cell Carcinoma; EGFR Positive Solid Tumor; HER2-positive Breast Cancer; Hepatocellular Carcinoma; Small Cell Lung Cancer; Renal Cell Carcinoma; Pancreas Cancer; Melanoma; NSCLC; Urothelial Carcinoma; Cervical Cancer; Microsatellite Instability; Merkel Cell Carcinoma
Interventions: Drug: FT500; Drug: Nivolumab; Drug: Pembrolizumab; Drug: Atezolizumab; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: IL-2
Sponsor: Fate Therapeutics
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 Merkel Cell Carcinoma; Advanced or Metastatic Cutaneous Squamous Cell Carcinoma; Advanced or Metastatic Melanoma; Advanced or Metastatic Head and Neck Squamous Cell Carcinoma; Advanced or Metastatic Solid Tumors
Interventions: Drug: Cavrotolimod; 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

How Microbes and Metabolism May Predict Skin Cancer Immunotherapy Outcomes

Posted: December 12th, 2017, 3:00pm GMT

Conditions: Autoimmunity; Melanoma; Merkel Cell Carcinoma; Squamous Cell Carcinoma of the Skin; Basal Cell Carcinoma; Skin Cancer
Intervention: Biological: Immunotherapy
Sponsor: Washington University School of Medicine
Recruiting

Phase Ib of L-NMMA and Pembrolizumab

Posted: August 2nd, 2017, 2:00pm GMT

Conditions: Non-Small Cell Lung Cancer; Malignant Melanoma; Head and Neck Squamous Cell Carcinoma; Classical Hodgkin Lymphoma; Urothelial Carcinoma Bladder; DNA Repair-Deficiency Disorders
Interventions: Drug: L-NMMA; Drug: Pembrolizumab
Sponsor: Jorge G. Darcourt
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 Skin Carcinoma; Adnexal Carcinoma; Anaplastic Large Cell Lymphoma, ALK-Negative; Anaplastic Large Cell Lymphoma, ALK-Positive; Apocrine Carcinoma; Cylindrocarcinoma; Digital Papillary Adenocarcinoma; Endocrine Mucin-Producing Sweat Gland Carcinoma; Extramammary Paget Disease; Extraocular Cutaneous Sebaceous Carcinoma; Hidradenocarcinoma; Keratoacanthoma; Malignant Sweat Gland Neoplasm; Merkel Cell Carcinoma; Microcystic Adnexal Carcinoma; NK-Cell Lymphoma, Unclassifiable; Papillary Adenocarcinoma; Porocarcinoma; Primary Cutaneous Mucinous Carcinoma; Recurrent Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Recurrent T-Cell Non-Hodgkin Lymphoma; Refractory Anaplastic Large Cell Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Refractory Merkel Cell Carcinoma; Refractory Mycosis Fungoides; Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Skin Squamous Cell Carcinoma; Refractory T-Cell Non-Hodgkin Lymphoma; Sezary Syndrome; Signet Ring Cell Carcinoma; Skin Basal Cell Carcinoma; Skin Basosquamous Cell Carcinoma; Skin Squamous Cell Carcinoma; Spiradenocarcinoma; Squamoid Eccrine Ductal Carcinoma; Squamous Cell Carcinoma of Unknown Primary; 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

Study to Evaluate Safety and Dosimetry of Lutathera in Adolescent Patients With GEP-NETs and PPGLs

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

Conditions: Gastroenteropancreatic Neuroendocrine Tumors; Pheochromocytoma; Paraganglioma
Intervention: Drug: Lutetium [177Lu] oxodotreotide/dotatate
Sponsor: Advanced Accelerator Applications
Not yet recruiting

Use of Non-invasive Optical Analysis in Neurosurgery

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

Conditions: Brain Tumour; Glioma; Meningioma; Brain Metastases; Schwannoma
Intervention: Device: Intra-operative multispectral / hyperspectral analysis
Sponsor: Imperial College London
Not yet recruiting

Permalink for 'A Phase II, Single Arm Study of Chemoimmunotherapy for the Treatment of Men With Neuroendocrine or Aggressive Variant Metastatic Prostate Cancer'

A Phase II, Single Arm Study of Chemoimmunotherapy for the Treatment of Men With Neuroendocrine or Aggressive Variant Metastatic Prostate Cancer

Posted: January 14th, 2021, 3:00pm GMT

Conditions: Metastatic Prostate Neuroendocrine Carcinoma; Metastatic Prostate Cancer
Interventions: Drug: Nivolumab; Drug: Ipilimumab; Drug: Carboplatin; Drug: Cabazitaxel
Sponsors: Andrew J. Armstrong, MD; Bristol-Myers Squibb
Not yet recruiting

18F-DOPA II - PET Imaging Optimization

Posted: January 13th, 2021, 3:00pm GMT

Conditions: Congenital Hyperinsulinism; Neuroblastoma; Parkinson Disease; Lewy Body Disease; Neuroendocrine Tumors; Brain Tumor
Interventions: Drug: 18F-DOPA; Drug: Furosemide Injection
Sponsor: University of Alberta
Not yet recruiting

Nab-paclitaxel Combined With Bevacizumab in the Treatment of Metastatic Neuroendocrine Carcinoma

Posted: January 12th, 2021, 3:00pm GMT

Condition: Neuroendocrine Carcinoma
Intervention: Drug: Nab-paclitaxel Combined With Bevacizumab
Sponsors: Peking University; Qilu Pharmaceutical Co., Ltd.
Recruiting

A Study of AMG 757 in Participants With Neuroendocrine Prostate Cancer

Posted: January 11th, 2021, 3:00pm GMT

Condition: Neuroendocrine Prostate Cancer
Intervention: Drug: AMG 757
Sponsor: Amgen
Not yet recruiting

Sargramostim (GM-CSF) + PD-1

Posted: January 11th, 2021, 3:00pm GMT

Conditions: Unresectable Melanoma; Metastatic Melanoma; Stage III Melanoma; Stage IV Melanoma
Interventions: Drug: Sargramostim (GM-CSF); Drug: Pembrolizumab (anti-PD-1)
Sponsors: Dana-Farber Cancer Institute; Partner Therapeutics (PTx)
Not yet recruiting

Niraparib and Dostarlimab for the Treatment of Small Cell Lung Cancer and Other High-Grade Neuroendocrine Carcinomas

Posted: January 8th, 2021, 3:00pm GMT

Conditions: Lung Small Cell Carcinoma; Neuroendocrine Carcinoma; Stage III Lung Cancer AJCC v8; Stage IIIA Lung Cancer AJCC v8; Stage IIIB Lung Cancer AJCC v8; Stage IIIC Lung Cancer AJCC v8
Interventions: Biological: Dostarlimab; Drug: Niraparib
Sponsor: M.D. Anderson Cancer Center
Not yet recruiting

Asian Investigation of Lanreotide Autogel® in the Management of GEP-NETs

Posted: January 6th, 2021, 3:00pm GMT

Condition: Neuroendocrine Tumors
Intervention: Drug: Lanreotide autogel
Sponsors: Asan Medical Center; Samsung Medical Center; Seoul St. Mary's Hospital; Severance Hospital; Seoul National University Bundang Hospital
Recruiting

Intralesional Influenza Vaccine for the Treatment of Stage I, II, and IV Melanoma

Posted: January 6th, 2021, 3:00pm GMT

Research of Pathological Imaging Diagnosis of Ocular Tumors Based on New Artificial Intelligence Algorithm

Posted: January 5th, 2021, 3:00pm GMT

Conditions: Melanoma (Skin); Melanoma in Situ; Nevus Eye; Sebaceous Gland Carcinoma of the Eyelid; Basal Cell Carcinoma; Squamous Cell Carcinoma in Situ; Ocular Tumor
Intervention:
Sponsor: Peking University
Not yet recruiting

Telotristat Ethyl for Reducing Intraoperative Carcinoid Crisis in Patients With Neuroendocrine Tumors

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

Condition: Neuroendocrine Tumors
Intervention: Drug: Telotristat Ethyl Oral Tablet
Sponsor: University of Chicago
Not yet recruiting

Improving Patient and Caregiver Understanding of Risks and Benefits of Immunotherapy for Lung Cancer or Melanoma

Posted: December 16th, 2020, 3:00pm GMT

Conditions: Stage IV Melanoma; Advanced Lung Cancer; Stage IV Non-small Cell Lung Cancer; Unresectable Non-Small Cell Lung Carcinoma; Unresectable Stage III Non-small-cell Lung Cancer; Immunotherapy; Immune Checkpoint Inhibitors; Small Cell Lung Cancer Extensive Stage
Interventions: Other: Educational Video and QPL List; Other: Usual Care
Sponsors: Massachusetts General Hospital; Conquer Cancer Foundation
Not yet recruiting

Testing Lutetium Lu 177 Dotatate in Patients With Somatostatin Receptor Positive Advanced Bronchial Neuroendocrine Tumors

Posted: December 14th, 2020, 3:00pm GMT

Conditions: Functioning Lung Carcinoid Tumor; Locally Advanced Lung Neuroendocrine Neoplasm; Lung Atypical Carcinoid Tumor; Lung Neuroendocrine Neoplasm; Lung Typical Carcinoid Tumor; Metastatic Lung Neuroendocrine Neoplasm; Non-Functioning Lung Carcinoid Tumor; Recurrent Lung Neuroendocrine Neoplasm; Unresectable Lung Neuroendocrine Neoplasm
Interventions: Drug: Everolimus; Drug: Lutetium Lu 177 Dotatate
Sponsor: National Cancer Institute (NCI)
Not yet recruiting

United Kingdom (UK) Patient Preference Study of Somatuline Autogel and Treatment Administration Setting

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

Condition: Neuroendocrine Tumours (NET)
Intervention:
Sponsor: Ipsen
Not yet recruiting

Effect of Diet on the Immune System in Patients With Stage III-IV Melanoma Receiving Immunotherapy, DIET Study

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

Conditions: Clinical Stage III Cutaneous Melanoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Metastatic Melanoma; Pathologic Stage III Cutaneous Melanoma AJCC v8; Pathologic Stage IV Cutaneous Melanoma AJCC v8; Unresectable Melanoma
Interventions: Other: Dietary Intervention; Other: Quality-of-Life Assessment; Other: Questionnaire Administration
Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI)
Recruiting

Camrelizumab Combined With Chemotherapy for Recurrent or Advanced Cervical Neuroendocrine Carcinomas

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

Conditions: Chemotherapy; Anti-pd-1 Antibody; Cervical Neuroendocrine Carcinoma; Adverse Drug Event; Recurrent Cervical Carcinoma; Advanced Cervical Carcinoma; Objective Response Rate
Intervention: Drug: Drug therapy
Sponsor: Lei Li
Recruiting

Using 18F- FDG,18F-DOPA and 68Ga-DOTATATE PET/CT in Detection and Evaluation of Response in Patients With NET Undergoing PRRT

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

Condition: Neuroendocrine Tumors
Intervention:
Sponsors: Dr. Nayruz Knaana; Sheba Medical Center
Recruiting

Lenvatinib and Pembrolizumab in Resectable Mucosal Melanoma

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

Conditions: Mucosal Melanoma; Neoadjuvant Treatment
Intervention: Drug: Lenvatinib, Pembrolizumab
Sponsor: Beijing Cancer Hospital
Not yet recruiting

Low-Dose-Rate Brachytherapy Combined With Immune Checkpoint Inhibition in Cancer

Posted: November 9th, 2020, 3:00pm GMT

Condition: Cutaneous Malignant Melanoma
Interventions: Radiation: Low Dose Rate Brachytherapy (LDR); Drug: Nivolumab
Sponsor: Case Comprehensive Cancer Center
Not yet recruiting

A Clinical Trial Evaluating the Safety of Combining Lutathera(R) and Azedra(R) to Treat Mid-gut Neuroendocrine Tumors

Posted: November 4th, 2020, 3:00pm GMT

Conditions: Gastro-enteropancreatic Neuroendocrine Tumor; Neuroendocrine Tumors
Interventions: Drug: Lutathera; Drug: Azedra
Sponsors: David Bushnell; National Institutes of Health (NIH); National Cancer Institute (NCI); Progenics Pharmaceuticals, Inc.
Not yet recruiting

Permalink for 'Study of PRRT in Metastatic, World Health Organization (WHO) Grade 1 or 2, SSTR Positive, GEP-NET Who Are Candidates for Cytoreductive Surgery'

Study of PRRT in Metastatic, World Health Organization (WHO) Grade 1 or 2, SSTR Positive, GEP-NET Who Are Candidates for Cytoreductive Surgery

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

Condition: Gastroenteropancreatic Neuroendocrine Tumor
Interventions: Drug: Lutathera; Drug: Gallium 68 Dotatate; Procedure: Computed Tomography (CT); Procedure: Magnetic Resonance Imaging (MRI); Procedure: PET/CT
Sponsors: Stanford University; Advanced Accelerator Applications
Not yet recruiting

Early Drain Removal Versus Standard Drain Management After Distal Pancreatectomy (Early-Dist)

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

Conditions: Pancreas Disease; Complication,Postoperative; PROMs; Pancreatic Fistula
Interventions: Procedure: Early drain removal; Procedure: Standard drain removal
Sponsor: IRCCS San Raffaele
Recruiting

Permalink for 'Impact of Telemonitoring for the Management of Side Effects in Patients With Melanoma, Lung or Renal Cancer, Treated With Immunotherapy Combination of Nivolumab and Ipilimumab'

Impact of Telemonitoring for the Management of Side Effects in Patients With Melanoma, Lung or Renal Cancer, Treated With Immunotherapy Combination of Nivolumab and Ipilimumab

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

Conditions: Melanoma; Lung Cancer; Renal Cancer
Intervention: Behavioral: Tele-monitoring
Sponsor: Hospices Civils de Lyon
Not yet recruiting

Permalink for 'Cabazitaxel, Carboplatin, and Cetrelimab Followed by Niraparib With or Without Cetrelimab for the Treatment of Aggressive Variant Metastatic Prostate Cancer'

Cabazitaxel, Carboplatin, and Cetrelimab Followed by Niraparib With or Without Cetrelimab for the Treatment of Aggressive Variant Metastatic Prostate Cancer

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

Conditions: Aggressive Variant Prostate Carcinoma; Castration-Resistant Prostate Carcinoma; Metastatic Prostate Carcinoma; Metastatic Prostate Neuroendocrine Carcinoma; Metastatic Prostate Small Cell Carcinoma; Stage IV Prostate Cancer AJCC v8
Interventions: Drug: Cabazitaxel; Drug: Carboplatin; Biological: Cetrelimab; Drug: Niraparib
Sponsor: M.D. Anderson Cancer Center
Not yet recruiting

Permalink for 'Interactive Survivorship Program for the Improvement of Healthcare Resources in Adolescent and Young Adult Cancer Survivors, INSPIRE-AYA Study'

Interactive Survivorship Program for the Improvement of Healthcare Resources in Adolescent and Young Adult Cancer Survivors, INSPIRE-AYA Study

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

Conditions: Clinical Stage I Cutaneous Melanoma AJCC v8; Clinical Stage IA Cutaneous Melanoma AJCC v8; Clinical Stage IB Cutaneous Melanoma AJCC v8; Clinical Stage II Cutaneous Melanoma AJCC v8; Clinical Stage IIA Cutaneous Melanoma AJCC v8; Clinical Stage IIB Cutaneous Melanoma AJCC v8; Clinical Stage IIC Cutaneous Melanoma AJCC v8; Clinical Stage III Cutaneous Melanoma AJCC v8; Hematopoietic and Lymphoid Cell Neoplasm; Invasive Malignant Neoplasm; Leukemia; Lymphoma; Malignant Solid Neoplasm; Pathologic Stage I Cutaneous Melanoma AJCC v8; Pathologic Stage IA Cutaneous Melanoma AJCC v8; Pathologic Stage IB Cutaneous Melanoma AJCC v8; Pathologic Stage II Cutaneous Melanoma AJCC v8; Pathologic Stage IIA Cutaneous Melanoma AJCC v8; Pathologic Stage IIB Cutaneous Melanoma AJCC v8; Pathologic Stage IIC 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; Sarcoma; Stage I Colorectal Cancer AJCC v8; Stage II Colorectal Cancer AJCC v8; Stage IIA Colorectal Cancer AJCC v8; Stage IIB Colorectal Cancer AJCC v8; Stage IIC Colorectal Cancer AJCC v8; Stage III Colorectal Cancer AJCC v8; Stage IIIA Colorectal Cancer AJCC v8; Stage IIIB Colorectal Cancer AJCC v8; Stage IIIC Colorectal Cancer AJCC v8
Interventions: Other: Informational Intervention; Other: Internet Mobile Technology; Other: Internet-Based Intervention; Other: Questionnaire Administration; Procedure: Supportive Care
Sponsors: Fred Hutchinson Cancer Research Center; National Cancer Institute (NCI)
Not yet recruiting

Safety and Efficacy of XmAb18087 ± Pembrolizumab in Advanced Merkel Cell Carcinoma or Extensive-stage Small Cell Lung Cancer

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

Conditions: Merkel Cell Carcinoma; Small Cell Lung Cancer
Interventions: Biological: XmAb18087; Drug: XmAb18087 ± Pembrolizumab
Sponsors: Xencor, Inc.; ICON plc
Not yet recruiting

CIRcular and Non-coding RNAs as Clinically USeful Biomarkers in Pancreaticobiliary Cancers

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

Conditions: Pancreatic Cancer; Biliary Tract Cancer
Intervention:
Sponsor: Royal Surrey County Hospital NHS Foundation Trust
Not yet recruiting

Targeted Agent Evaluation in Digestive Cancers in China Based on Molecular Characteristics

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

Conditions: Biliary Tract Neoplasms; Gastric Cancer; Esophageal Squamous Cell Carcinoma; Colorectal Cancer; Gastrointestinal Stromal Tumors; Pancreatic Cancer; Neuroendocrine Tumors; Unknown Primary Cancer; Digestive Cancer
Interventions: Drug: FGFR Inhibitor, IDH1 Inhibitor, HER2 Inhibitor, PARP Inhibitor, BRAF Inhibitor, MEK Inhibitor, ICIs, EGFR-TKIs, NTRK-TKI, and et. al.; Drug: Other Therapy
Sponsors: Peking University; Hangzhou DIAN Medical Diagnostic Center Co., Ltd., China
Recruiting

Open-Label Surufatinib in European Patients With NET

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

Conditions: Neuroendocrine Tumours; Neuroendocrine Tumour of the Lung; Small Intestinal NET
Intervention: Drug: Surufatinib
Sponsor: Hutchison Medipharma Limited
Not yet recruiting

Surufatinib in Combination With Tislelizumab in Subjects With Advanced Solid Tumors

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

Conditions: Metastatic Solid Tumor; Colorectal Cancer; Neuroendocrine Tumors; Small Cell Lung Cancer; Gastric Cancer; Soft Tissue Sarcoma
Interventions: Drug: Surufatinib and Tislelizumab _ Part 1; Drug: Surufatinib and Tislelizumab _ Part 2
Sponsors: Hutchison Medipharma Limited; BeiGene
Not yet recruiting

A Storage Facility for Tissues Obtained From Patients With Malignant Melanoma

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

Condition: Melanoma
Intervention: Procedure: Biospecimen Collection
Sponsors: Ohio State University Comprehensive Cancer Center; National Cancer Institute (NCI)
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
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, Inc.
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)
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: Elimusertib; Drug: Irinotecan Sucrosofate; 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
Recruiting

Permalink for 'Oral Cryotherapy Plus Acupressure and Acupuncture Versus Oral Cryotherapy for Decreasing Chemotherapy-Induced Peripheral Neuropathy From Oxaliplatin-Based Chemotherapy in Patients With Gastrointestinal Cancer'

Oral Cryotherapy Plus Acupressure and Acupuncture Versus Oral Cryotherapy for Decreasing Chemotherapy-Induced Peripheral Neuropathy From Oxaliplatin-Based Chemotherapy in Patients With Gastrointestinal Cancer

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

Conditions: Appendix Carcinoma; Colon Carcinoma; Esophageal Carcinoma; Gastric Carcinoma; Liver and Intrahepatic Bile Duct Carcinoma; Malignant Digestive System Neoplasm; Pancreatic Carcinoma; Rectal Carcinoma; Small Intestinal Carcinoma; Anal Carcinoma; Digestive System Carcinoma; Digestive System Neuroendocrine Tumor; Pancreatic Neuroendocrine Tumor
Interventions: Procedure: Acupuncture Therapy; Procedure: Acupressure Therapy; Procedure: Oral Cryotherapy; Other: Questionnaire Administration; Other: Quality-of-Life Assessment
Sponsors: University of Washington; National Cancer Institute (NCI); The Safeway Foundation
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-LM3 and 68Ga-NODAGA-JR11 PET/CT
Sponsor: Peking Union Medical College Hospital
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
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
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
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
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
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
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)
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
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: Centre Hospitalier Universitaire Dijon; National Cancer Institute, France
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
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: 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

The Landmark Series: Management of Small Bowel Neuroendocrine Tumors.

Fetched: January 18th, 2021, 5:01am GMT

The Landmark Series: Management of Small Bowel Neuroendocrine Tumors.

Ann Surg Oncol. 2021 Jan 15;:

Authors: Tran CG, Sherman SK, Howe JR

Abstract
Surgical resection is the foundation for treatment of small bowel neuroendocrine tumors (SBNETs). Guidelines for surgical management of SBNETs rely on retrospective data, which suggest that primary tumor resection and cytoreduction improve symptoms, prevent future complications, and lengthen survival. In advanced NETs, improvement in progression-free survival has been reported in large, randomized, controlled trials of various medical treatments, including somatostatin analogues, targeted therapy, and peptide receptor radionuclide therapy. This review discusses important studies influencing the management of SBNETs and the limitations of current evidence regarding surgical interventions for SBNETs.

PMID: 33452604 [PubMed - as supplied by publisher]

Permalink for 'Pancreatic Gastrinoma, Gastrointestinal Stromal Tumor (GIST), Pheochromocytoma, and Hürthle Cell Neoplasm in a Patient with Neurofibromatosis Type 1: A Case Report and Literature Review.'

Pancreatic Gastrinoma, Gastrointestinal Stromal Tumor (GIST), Pheochromocytoma, and Hürthle Cell Neoplasm in a Patient with Neurofibromatosis Type 1: A Case Report and Literature Review.

Fetched: January 18th, 2021, 5:01am GMT

Pancreatic Gastrinoma, Gastrointestinal Stromal Tumor (GIST), Pheochromocytoma, and Hürthle Cell Neoplasm in a Patient with Neurofibromatosis Type 1: A Case Report and Literature Review.

Am J Case Rep. 2021 Jan 16;22:e927761

Authors: Arif AA, Kim PTW, Melck A, Churg A, Schwartz Z, Stuart HC

Abstract
BACKGROUND Neurofibromatosis type 1 (NF1) is a multi-tumor syndrome in which affected patients develop malignancies that are rare in the overall population, such as tumors of neural or endocrine origin. CASE REPORT A 67-year-old woman with a clinical diagnosis of NF1 presented with abdominal pain and pneumoperitoneum. She underwent small-bowel resections for a perforated jejunal lesion and a second lesion in the ileum; pathology showed a neurofibroma at the site of the perforation and a 1-cm low-grade GIST, respectively. Additional staging with cross-sectional imaging identified a 3.7-cm pancreatic head mass and a 1.7-cm left adrenal mass; biochemical studies revealed elevated serum gastrin and urinary free metanephrines and catecholamines consistent with pheochromocytoma. Initial surgical management was a left posterior retroperitoneoscopic adrenalectomy. Postoperatively, gallium-68-DOTATOC PET/CT showed uptake in the pancreatic head and a 28-mm left thyroid nodule. Months later, she had an open pancreaticoduodenectomy. Pathology showed pheochromocytoma and a low-grade (G1) gastrinoma involving 2/8 peripancreatic lymph nodes (pT3pN1M0), respectively. Fine-needle aspiration biopsy of the thyroid nodule showed features consistent with a Hürthle cell neoplasm. Genetic testing identified a pathogenic mutation in NF1 and no mutations in BRCA1/2, CDC72, MEN1, or PALB2. The patient continues surveillance, with no evidence of recurrent disease. CONCLUSIONS We report the fifth case of gastrinoma associated with NF1 and the first to arise from the pancreas. This case of a pancreatic neuroendocrine tumor was associated with multiple additional neoplasms. Neuroendocrine tumors found in NF1 should raise suspicion of other malignancies.

PMID: 33452231 [PubMed - as supplied by publisher]

The correlation between tumor markers and Ga-68 DOTA-TATE PET/CT findings in patients with advanced medullary thyroid cancer.

Fetched: January 18th, 2021, 5:01am GMT

The correlation between tumor markers and Ga-68 DOTA-TATE PET/CT findings in patients with advanced medullary thyroid cancer.

Rev Esp Med Nucl Imagen Mol. 2021 Jan 12;:

Authors: Arici S, Karyagar SS, Erdemir RU, Cekin R, Atcı MM, Güven O, Karyagar S, Cihan Ş

Abstract
BACKGROUND: Medullary thyroid cancer is a rare type of neuroendocrine tumor. Calcitonin (Ctn) and carcinoembryonic antigen (CEA) are used as markers for medullary thyroid cancer. The aim of the study was to evaluate the importance of serum Ctn and CEA levels in predicting total tumor volume.
MATERIAL AND METHODS: Ga-68 DOTA-TATE PET/CT findings such as whole-body somatostatin receptor-expressing metabolic tumor volume (SSR-E MTV) and total lesion volume (SSR-E TLV) were calculated and correlation analysis was done for tumor markers and whole-body SSR-E MTV and TLV.
RESULTS: A total of 28 patients with advanced medullary thyroid cancer were included in this retrospective study. In the correlation analysis, there was a statistically significant positive correlation between Ctn and whole-body SSR-E MTV (rho=0.503 and P=.008). Similarly, significant positive correlation was observed between Ctn and whole-body SSR-E TLV (rho=0.436 and P=.023). There was a significant positive correlation between CEA and whole-body SSR-E MTV (rho=0.584 and P=.007). Also, a positive correlation was observed between CEA and whole-body SSR-E TLV (rho=0.436 and P=.023). These correlations were most marked in patients with Ctn≥152pg/mL and/or both nodal and bone involvement.
CONCLUSION: These results could stimulate clinicians to perform Ga-68 PET for treatment decisions, especially in patients with high CEA and Ctn levels at the time of diagnosis.

PMID: 33451923 [PubMed - as supplied by publisher]

The role of 18F-FDG PET/CT in the management of Merkel cell carcinoma: The experience of 51 studies in our institution.

Fetched: January 18th, 2021, 5:01am GMT

The role of 18F-FDG PET/CT in the management of Merkel cell carcinoma: The experience of 51 studies in our institution.

Rev Esp Med Nucl Imagen Mol. 2021 Jan 12;:

Authors: López Prior V, Llombart Cussac B

PMID: 33451922 [PubMed - as supplied by publisher]

Triple threat: pancreatic cystic lesion presenting with spontaneous hemorrhage is found to harbor three distinct neoplasms.

Fetched: January 18th, 2021, 5:01am GMT

Triple threat: pancreatic cystic lesion presenting with spontaneous hemorrhage is found to harbor three distinct neoplasms.

World J Surg Oncol. 2021 Jan 15;19(1):15

Authors: Cha DE, Horn C, Passeri M

Abstract
BACKGROUND: Pancreatic serous cystadenoma (SCA) is a benign, cystic lesion with an indolent growth pattern. Complications such as spontaneous hemorrhage or malignant transformation from SCA are extremely rare. Our case report describes an unusual presentation of a patient with a previously diagnosed SCA, made unique by the presence of three separate neoplasms in the final specimen.
CASE PRESENTATION: A 74-year-old male with a previous diagnosis of SCA presented emergently with epigastric pain and non-bilious vomiting. Laboratory results were notable for a hemoglobin of 8.3 g/dl. CT scan of the abdomen demonstrated a complex, solid-cystic mass in the pancreatic head with a large hematoma and questionable focus of active hemorrhage. Surgical resection was recommended due to the risk of malignancy, possibility of re-bleeding, and symptoms of severe duodenal compression. Pancreaticoduodenectomy was performed, and final pathology demonstrated three separate neoplasms: serous cystadenoma, intraductal papillary mucinous neoplasm, and neuroendocrine tumor.
CONCLUSION: While pancreatic SCA are benign tumors that can be observed safely in the majority of cases, surgical intervention is often indicated in patients with large, symptomatic cysts or when diagnosis is unclear. When undergoing surveillance, it is crucial for both the patient and the care team to be aware of the possibility of rare, but life-threatening complications, such as hemorrhage. Likewise, the possibility of misdiagnosis or concurrent neoplasia should be considered.

PMID: 33451339 [PubMed - as supplied by publisher]

Procalcitonin expression in patients with large cell neuroendocrine carcinoma of the lung.

Fetched: January 18th, 2021, 5:01am GMT

Procalcitonin expression in patients with large cell neuroendocrine carcinoma of the lung.

BMC Res Notes. 2021 Jan 15;14(1):25

Authors: Itoga M, Tanaka H, Taima K, Ishioka Y, Sakamoto H, Takanashi S, Kurose A, Tasaka S

Abstract
OBJECTIVE: Procalcitonin (PCT) has received much attention as a serum marker for bacterial infection. Elevated serum PCT is occasionally seen in severe trauma, heatstroke, and neoplastic diseases, including lung cancer with neuroendocrine component.
RESULTS: In the present study, we evaluated PCT expression in the specimen of pulmonary neuroendocrine tumors, comparing large cell neuroendocrine carcinoma (LCNEC), carcinoid, and small cell lung carcinoma (SCLC). Pathological specimens of 10 LCNEC, 4 carcinoid, and 7 SCLC cases were evaluated with immunochemical staining of PCT. Clinical characteristics and serum levels of PCT and C-reactive protein were also evaluated. We observed positive PCT expression in 5 (50%) LCNEC and 2 (50%) carcinoid specimens that were surgically resected. Whereas serum PCT levels were not elevated in patients with PCT-positive carcinoid, two out of three LCNEC patients with high PCT expression in the tumor had elevated serum PCT levels that reflected disease progression. In patients with SCLC, PCT was not detected in the tumor or serum. This is the first immunohistochemical study of the PCT expression in the lung tumor specimens. We concluded that, in patients with LCNEC, high serum PCT levels may be indicative of disease activity and serve as a biomarker.

PMID: 33451319 [PubMed - as supplied by publisher]

Clinicopathologic and Molecular Features of Mixed Neuroendocrine Non-Neuroendocrine Neoplasms of the Gallbladder.

Fetched: January 17th, 2021, 5:01am GMT

Clinicopathologic and Molecular Features of Mixed Neuroendocrine Non-Neuroendocrine Neoplasms of the Gallbladder.

Gastroenterology Res. 2020 Dec;13(6):269-278

Authors: Alawad M, Gupta R, Haseeb MA, Brunicardi FC

Abstract
Neuroendocrine neoplasms of the gallbladder are rare, comprising 0.5% of all neuroendocrine cancers and about 2% of gallbladder cancers. These neoplasms can also be found along with other malignant neoplasms of epithelial origin, mostly adenocarcinomas. Herein, we describe an unusual finding of a three-component mixed neuroendocrine non-neuroendocrine neoplasm (MiNEN) of the gallbladder. We also review the literature on 29 similar cases and summarize key features. We report on a 62-year-old woman who presented with right upper quadrant pain with a positive Murphy's sign. A clinical diagnosis of neoplasia was entertained and she underwent cholecystectomy. Gross examination of the specimen revealed a 5-cm exophytic mass at the gallbladder fundus. Histopathologic examination of the mass showed an infiltrating squamous cell carcinoma, an adjacent neuroendocrine carcinoma (each of these two components composed more than 30% of the neoplasm), and a superficial adenocarcinoma (composing 10% of the neoplasm). Gallbladder MiNENs present with similar symptoms and in the same age group as do carcinomas; however, their prognosis is often poor. Specific management and treatment guidelines have not been established since MiNENs are very rare.

PMID: 33447306 [PubMed]

Fibrinogen/Albumin Ratio as a Promising Marker for Predicting Survival in Pancreatic Neuroendocrine Neoplasms.

Fetched: January 17th, 2021, 5:01am GMT

Fibrinogen/Albumin Ratio as a Promising Marker for Predicting Survival in Pancreatic Neuroendocrine Neoplasms.

Cancer Manag Res. 2021;13:107-115

Authors: Deng S, Fan Z, Xia H, Gong Y, Qian Y, Huang Q, Cheng H, Jin K, Xiao Z, Luo G, Yu X, Liu C

Abstract
Background: The fibrinogen/albumin ratio (FAR) has been widely reported to be a possible biomarker for predicting prognosis in several types of tumors, but the prognostic value of the FAR in pancreatic neuroendocrine neoplasms (Pan-NENs) has not been systematically studied.
Patients and Methods: In total, 324 patients with Pan-NENs were recruited. The patients were divided into 2 subgroups according to the FAR cutoff value, and clinicopathological characteristics of the 2 subgroups were compared. Overall survival (OS) was the primary endpoint, and progression-free survival (PFS) was the secondary endpoint. The prognostic value of the FAR was analyzed in univariate and multivariate analyses.
Results: The optimal cutoff value for the FAR was calculated to be 0.08 for OS. The patients with a FAR ≥0.08 had higher proportions of nonfunctioning tumors, Pan-NECs, grade 3 tumors, and stage IV tumors than those with a FAR <0.08. In the univariate analysis, a FAR ≥ 0.08 was associated with poor OS (hazard ratio (HR) = 2.37, P < 0.001) and PFS (HR = 2.37, P < 0.001). In the multivariate analysis, a FAR ≥0.08 was an independent risk factor for poor OS (HR = 4.70, P < 0.001) and PFS (HR = 1.80, P = 0.006).
Conclusion: The pretreatment FAR, which includes fibrinogen and albumin, was a feasible and predictive biomarker for prognosis in patients with Pan-NENs. An elevated FAR, based on a cutoff value of 0.08, was an independent risk factor for poor OS and PFS.

PMID: 33447083 [PubMed]

Neuroendocrine liver metastasis from the small intestine: Is surgery beneficial for survival?

Fetched: January 17th, 2021, 5:01am GMT

Neuroendocrine liver metastasis from the small intestine: Is surgery beneficial for survival?

Orphanet J Rare Dis. 2021 Jan 14;16(1):30

Authors: Selberherr A, Freermann S, Koperek O, Niederle MB, Riss P, Scheuba C, Niederle B

Abstract
BACKGROUND: Neuroendocrine neoplasia of the small intestine (siNEN) are frequently diagnosed with liver metastases. The impact of the presence of liver metastases on overall survival and the necessity of surgery for liver metastasis is discussed controversially. The aim of this study is to evaluate and compare the overall long-term survival of patients with siNENs with and without liver metastasis at initial diagnosis and the possible benefit of surgical treatment as compared to active surveillance of metastases. 123 consecutive patients with siNENs were treated between 1965 and 2016. All clinical and histological records were reevaluated including analysis of the proliferation rates in all specimens. The 1-, 5-, 10- and 20-year overall survival was estimated by Kaplan-Meier analysis for patients with and without liver metastasis and according to the type of treatment (surgical vs. surveillance) of liver metastases if present.
RESULTS: The 1-, 5-, 10- and 20-year overall survival rate was 89.0%, 68.4%, 52.8% and 31.0% in patients without and 89.5%, 69.5%, 33.2% and 3.6% in those with liver metastases. No statistically significant differences were observed comparing the two groups. Within the group of patients with liver metastases, the type of treatment (surgical vs. surveillance) was in favor of patients undergoing surgery. Multivariate analysis showed that the presence of liver metastases upon diagnosis was an individual risk factor associated with worse survival.
CONCLUSION: The presence of liver metastasis at initial diagnosis does not have a statistically significant influence on survival. Surgery for hepatic metastasis seems to show a benefit for overall survival and may be indicated especially in patients symptomatic due to high tumor burden and serotonin hypersecretion to reduce hormone activity.

PMID: 33446229 [PubMed - in process]

Clinical Challenges in the Management of Neuroendocrine Tumors.

Fetched: January 17th, 2021, 5:01am GMT

Clinical Challenges in the Management of Neuroendocrine Tumors.

J Clin Med. 2021 Jan 12;10(2):

Authors: Panzuto F

Abstract
Neuroendocrine tumors (NET) are rare and heterogeneous diseases, whose prognosis is affected by several factors including the primary tumor site, grading, somatostatin receptor expression, and disease staging [...].

PMID: 33445572 [PubMed]

[Congenital ocular melanocytosis].

Fetched: January 17th, 2021, 5:01am GMT

[Congenital ocular melanocytosis].

Rev Med Liege. 2021 Jan;76(1):2-6

Authors: Dequinze M, Borlon A, Bonnet S, Lepièce G

Abstract
Congenital oculodermal melanocytosis represents a unilateral accumulation of melanocytes in the episclera, sclera and uveal tract. Clinically, it manifests with iris heterochromia, episcleral and scleral pigmented patches, dark pigmentation of the trabecular meshwork and the fundus. This congenital disorder is a predisposing factor for uveal melanoma and chronic glaucoma. We report here the case of a Caucasian woman who presents some of these characteristics.

PMID: 33443321 [PubMed - indexed for MEDLINE]

The impact of metformin on survival in patients with melanoma-national cohort study.

Fetched: January 17th, 2021, 5:01am GMT

The impact of metformin on survival in patients with melanoma-national cohort study.

Ann Epidemiol. 2020 12;52:23-25

Authors: Urbonas V, Rutenberge J, Patasius A, Dulskas A, Burokiene N, Smailyte G

Abstract
PURPOSE: The primary study outcome was melanoma-specific mortality in patients with type 2 diabetes mellitus (T2DM) using metformin.
METHODS: Data regarding patients were provided by the Lithuanian Cancer Registry and were linked with National Health Insurance Fund in accordance with unique personal identification numbers during the period of thirteen years.
RESULTS: About 2817 patients met eligibility criteria and were included in the retrospective cohort study. About 163 patients had pre-existing T2DM and 103 of them were treated with metformin. In the multivariable analysis, there was significant risk difference in melanoma-specific survival between diabetic, metformin-using patients, and nondiabetic patients (P=0.02) in favor of metformin users.
CONCLUSION: Melanoma patients with T2DM treated with metformin had lower risk of melanoma-specific mortality; however, prospective controlled studies are mandatory to confirm this finding.

PMID: 32980534 [PubMed - indexed for MEDLINE]

Demographic Factors Associated with Toxicity in Patients Treated with Anti-Programmed Cell Death-1 Therapy.

Fetched: January 17th, 2021, 5:01am GMT

Demographic Factors Associated with Toxicity in Patients Treated with Anti-Programmed Cell Death-1 Therapy.

Cancer Immunol Res. 2020 07;8(7):851-855

Authors: Shah KP, Song H, Ye F, Moslehi JJ, Balko JM, Salem JE, Johnson DB

Abstract
Immune checkpoint inhibitors (ICI) are now routinely used in multiple cancers but may induce autoimmune-like side effects known as immune-related adverse events (irAE). Although classical autoimmune diseases have well-known risk factors, including age, gender, and seasonality, the clinical factors that lead to irAEs are not well-defined. To explore these questions, we assessed 455 patients with advanced melanoma treated with ICI at our center and a large pharmacovigilance database (VigiBase). We found that younger age was associated with a similar rate of any irAEs but more frequent severe irAEs and more hospitalizations (OR, 0.97 per year). Paradoxically, however, older patients had more deaths and increased length of stay (LOS) when hospitalized. This was partially due to a distinct toxicity profile: Colitis and hepatitis were more common in younger patients, whereas myocarditis and pneumonitis had an older age distribution both in our center and in VigiBase. This pattern was particularly apparent with combination checkpoint blockade with ipilimumab and nivolumab. We did not find a link between gender or seasonality on development of irAEs in univariate or multivariate analyses, although winter hospitalizations were associated with marginally increased LOS. This study identifies age-specific associations of irAEs.

PMID: 32350001 [PubMed - indexed for MEDLINE]

T-type calcium channel inhibition restores sensitivity to MAPK inhibitors in de-differentiated and adaptive melanoma cells.

Fetched: January 17th, 2021, 5:01am GMT

T-type calcium channel inhibition restores sensitivity to MAPK inhibitors in de-differentiated and adaptive melanoma cells.

Br J Cancer. 2020 03;122(7):1023-1036

Authors: Granados K, Hüser L, Federico A, Sachindra S, Wolff G, Hielscher T, Novak D, Madrigal-Gamboa V, Sun Q, Vierthaler M, Larribère L, Umansky V, Utikal J

Abstract
BACKGROUND: Drug resistance remains as one of the major challenges in melanoma therapy. It is well known that tumour cells undergo phenotypic switching during melanoma progression, increasing melanoma plasticity and resistance to mitogen-activated protein kinase inhibitors (MAPKi).
METHODS: We investigated the melanoma phenotype switching using a partial reprogramming model to de-differentiate murine melanoma cells and target melanoma therapy adaptation against MAPKi.
RESULTS: Here, we show that partially reprogrammed cells are a less proliferative and more de-differentiated cell population, expressing a gene signature for stemness and suppressing melanocyte-specific markers. To investigate adaptation to MAPKi, cells were exposed to B-Raf Proto-Oncogene (BRAF) and mitogen-activated protein kinase kinase (MEK) inhibitors. De-differentiated cells became less sensitive to MAPKi, showed increased cell viability and decreased apoptosis. Furthermore, T-type calcium channels expression increased in adaptive murine cells and in human adaptive melanoma cells. Treatment with the calcium channel blocker mibefradil induced cell death, differentiation and susceptibility to MAPKi in vitro and in vivo.
CONCLUSION: In summary, we show that partial reprogramming of melanoma cells induces de-differentiation and adaptation to MAPKi. Moreover, we postulated a calcium channel blocker such as mibefradil, as a potential candidate to restore sensitivity to MAPKi in adaptive melanoma cells.

PMID: 32063604 [PubMed - indexed for MEDLINE]

Detection and prognostic role of heterogeneous populations of melanoma circulating tumour cells.

Fetched: January 17th, 2021, 5:01am GMT

Detection and prognostic role of heterogeneous populations of melanoma circulating tumour cells.

Br J Cancer. 2020 03;122(7):1059-1067

Authors: Aya-Bonilla CA, Morici M, Hong X, McEvoy AC, Sullivan RJ, Freeman J, Calapre L, Khattak MA, Meniawy T, Millward M, Ziman M, Gray ES

Abstract
BACKGROUND: Circulating tumour cells (CTCs) can be assessed through a minimally invasive blood sample with potential utility as a predictive, prognostic and pharmacodynamic biomarker. The large heterogeneity of melanoma CTCs has hindered their detection and clinical application.
METHODS: Here we compared two microfluidic devices for the recovery of circulating melanoma cells. The presence of CTCs in 43 blood samples from patients with metastatic melanoma was evaluated using a combination of immunocytochemistry and transcript analyses of five genes by RT-PCR and 19 genes by droplet digital PCR (ddPCR), whereby a CTC score was calculated. Circulating tumour DNA (ctDNA) from the same patient blood sample, was assessed by ddPCR targeting tumour-specific mutations.
RESULTS: Our analysis revealed an extraordinary heterogeneity amongst melanoma CTCs, with multiple non-overlapping subpopulations. CTC detection using our multimarker approach was associated with shorter overall and progression-free survival. Finally, we found that CTC scores correlated with plasma ctDNA concentrations and had similar pharmacodynamic changes upon treatment initiation.
CONCLUSIONS: Despite the high phenotypic and molecular heterogeneity of melanoma CTCs, multimarker derived CTC scores could serve as viable tools for prognostication and treatment response monitoring in patients with metastatic melanoma.

PMID: 32037400 [PubMed - indexed for MEDLINE]

Permalink for 'Dissecting Mechanisms of Melanoma Resistance to BRAF and MEK Inhibitors Revealed Genetic and Non-Genetic Patient- and Drug-Specific Alterations and Remarkable Phenotypic Plasticity.'

Dissecting Mechanisms of Melanoma Resistance to BRAF and MEK Inhibitors Revealed Genetic and Non-Genetic Patient- and Drug-Specific Alterations and Remarkable Phenotypic Plasticity.

Fetched: January 17th, 2021, 5:01am GMT

Dissecting Mechanisms of Melanoma Resistance to BRAF and MEK Inhibitors Revealed Genetic and Non-Genetic Patient- and Drug-Specific Alterations and Remarkable Phenotypic Plasticity.

Cells. 2020 01 07;9(1):

Authors: Hartman ML, Sztiller-Sikorska M, Gajos-Michniewicz A, Czyz M

Abstract
The clinical benefit of MAPK pathway inhibition in BRAF-mutant melanoma patients is limited by the development of acquired resistance. Using drug-naïve cell lines derived from tumor specimens, we established a preclinical model of melanoma resistance to vemurafenib or trametinib to provide insight into resistance mechanisms. Dissecting the mechanisms accompanying the development of resistance, we have shown that (i) most of genetic and non-genetic alterations are triggered in a cell line- and/or drug-specific manner; (ii) several changes previously assigned to the development of resistance are induced as the immediate response to the extent measurable at the bulk levels; (iii) reprogramming observed in cross-resistance experiments and growth factor-dependence restricted by the drug presence indicate that phenotypic plasticity of melanoma cells largely contributes to the sustained resistance. Whole-exome sequencing revealed novel genetic alterations, including a frameshift variant of RBMX found exclusively in phospho-AKThigh resistant cell lines. There was no similar pattern of phenotypic alterations among eleven resistant cell lines, including expression/activity of crucial regulators, such as MITF, AXL, SOX, and NGFR, which suggests that patient-to-patient variability is richer and more nuanced than previously described. This diversity should be considered during the development of new strategies to circumvent the acquired resistance to targeted therapies.

PMID: 31936151 [PubMed - indexed for MEDLINE]

Incidental giant cystic pheochromocytoma: a case report and review of the literature.

Fetched: January 17th, 2021, 5:01am GMT

Incidental giant cystic pheochromocytoma: a case report and review of the literature.

Scott Med J. 2020 May;65(2):64-70

Authors: Clements HA, Wilson MS, Smith DM

Abstract
INTRODUCTION: Pheochromocytoma is a tumour arising from the adrenal medulla, which secretes catecholamines. Approximately 20% of pheochromocytomas are cystic and more likely to be asymptomatic. They should be surgically resected as all have a malignant potential and pose cardiovascular risk. Case presentation: We report the case of a 61-year-old female patient admitted electively for laparoscopic adrenalectomy for a large cystic pheochromocytoma detected incidentally. Diagnosis was confirmed preoperatively by elevated 24-h urinary metanephrines. The patient was treated preoperatively with alpha and beta blockade. Surgery was without complication; she had an uneventful postoperative recovery and no evidence of recurrence at one-year follow-up.
CONCLUSION: This case highlights the necessity of investigating for biochemical function in all adrenal lesions by measuring metanephrines, even when entirely cystic on imaging. Given the surgical and anaesthetic risk in resection of pheochromocytoma, attaining a preoperative diagnosis allows for careful preoperative planning and safe surgery.

PMID: 31931648 [PubMed - indexed for MEDLINE]

Dissimilar Appearances Are Deceptive-Common microRNAs and Therapeutic Strategies in Liver Cancer and Melanoma.

Fetched: January 17th, 2021, 5:01am GMT

Dissimilar Appearances Are Deceptive-Common microRNAs and Therapeutic Strategies in Liver Cancer and Melanoma.

Cells. 2020 01 02;9(1):

Authors: Linck-Paulus L, Hellerbrand C, Bosserhoff AK, Dietrich P

Abstract
: In this review, we summarize the current knowledge on miRNAs as therapeutic targets in two cancer types that were frequently described to be driven by miRNAs-melanoma and hepatocellular carcinoma (HCC). By focusing on common microRNAs and associated pathways in these-at first sight-dissimilar cancer types, we aim at revealing similar molecular mechanisms that are evolved in microRNA-biology to drive cancer progression. Thereby, we also want to outlay potential novel therapeutic strategies. After providing a brief introduction to general miRNA biology and basic information about HCC and melanoma, this review depicts prominent examples of potent oncomiRs and tumor-suppressor miRNAs, which have been proven to drive diverse cancer types including melanoma and HCC. To develop and apply miRNA-based therapeutics for cancer treatment in the future, it is essential to understand how miRNA dysregulation evolves during malignant transformation. Therefore, we highlight important aspects such as genetic alterations, miRNA editing and transcriptional regulation based on concrete examples. Furthermore, we expand our illustration by focusing on miRNA-associated proteins as well as other regulators of miRNAs which could also provide therapeutic targets. Finally, design and delivery strategies of miRNA-associated therapeutic agents as well as potential drawbacks are discussed to address the question of how miRNAs might contribute to cancer therapy in the future.

PMID: 31906510 [PubMed - indexed for MEDLINE]

Some Considerations in Treating Malignant Head and Neck Paragangliomas-Reply.

Fetched: January 17th, 2021, 5:01am GMT

Some Considerations in Treating Malignant Head and Neck Paragangliomas-Reply.

JAMA Otolaryngol Head Neck Surg. 2020 02 01;146(2):210-211

Authors: McCrary HC, Cannon RB, Buchmann LO

PMID: 31725851 [PubMed - indexed for MEDLINE]

Permalink for 'High-resolution MRI demonstrates that more than 90% of small intracranial melanoma metastases develop in close relationship to the leptomeninges.'

High-resolution MRI demonstrates that more than 90% of small intracranial melanoma metastases develop in close relationship to the leptomeninges.

Fetched: January 17th, 2021, 5:01am GMT

High-resolution MRI demonstrates that more than 90% of small intracranial melanoma metastases develop in close relationship to the leptomeninges.

Neuro Oncol. 2020 03 05;22(3):423-432

Authors: Lasocki A, Khoo C, Lau PKH, Kok DL, Mcarthur GA

Abstract
BACKGROUND: Despite classic teaching that intracranial metastases typically arise at the gray-white matter junction, small intracranial melanoma metastases (IMM) are frequently observed at the interface between the cortex and leptomeninges (ie, "corticomeningeal interface"), suggesting possible leptomeningeal origin.
METHODS: MRI brain examinations of melanoma patients treated at a specialist oncology center from July 2015 to June 2017 were retrospectively reviewed. The MRI examination on which IMM were first visible was identified, utilizing 1 mm volumetric postcontrast imaging prior to local therapy. Individual metastases (up to 10 per patient) were assessed for the presence of leptomeningeal contact, as well as their number, size, and morphology. Lesions ≥10 mm in long axis were excluded, in order to examine early metastatic disease.
RESULTS: Seventy-five patients had evidence of IMM. Fifteen patients had only lesion(s) measuring ≥10 mm at diagnosis, leaving 60 patients. One hundred ninety-two individual metastases were examined (median 2 per patient; interquartile range, 1-4), 174 (91%) demonstrating leptomeningeal contact. A nodular morphology was observed in 154 of 192 (82%), 32 (17%) were ovoid but elongated along the cortex, and 6 (3%) were linear. Only 3 patients (5%) also exhibited a "classic" linear leptomeningeal disease appearance.
CONCLUSIONS: Most IMM measuring between 2 and 9 mm in diameter are corticomeningeal nodules. These data raise the hypothesis that deeper parenchymal extension of IMM occurs secondarily. If the leptomeninges provide a preferential site for establishment of IMM, further investigation of the underlying biology of this phenomenon may provide opportunities for novel therapeutic strategies for patients with IMM.

PMID: 31498868 [PubMed - indexed for MEDLINE]

Pancreatic neuroendocrine tumours: spectrum of imaging findings.

Fetched: January 17th, 2021, 5:01am GMT

Pancreatic neuroendocrine tumours: spectrum of imaging findings.

Gland Surg. 2020 Dec;9(6):2215-2224

Authors: Bicci E, Cozzi D, Ferrari R, Grazzini G, Pradella S, Miele V

Abstract
Pancreatic neuroendocrine tumours (pNETs) are rare and heterogeneous group of neoplasms presenting with a wide variety of symptoms and biological behaviour, from indolent to aggressive ones. pNETs are stratified into functional or non-functional, because of their ability to produce metabolically active hormones. pNETs can be an isolate phenomenon or a part of a hereditary syndrome like von Hippel-Lindau syndrome or neurofibromatosis-1. The incidence has increased in the last years, also because of the improvement of cross-sectional imaging. Computed tomography (CT), magnetic resonance imaging (MRI) and functional imaging are the mainstay imaging modalities used for tumour detection and disease extension assessment, due to easy availability and better contrast/spatial resolution. Radiological imaging plays a fundamental role in detection, characterization and surveillance of pNETs and is involved in almost every stage of patients' management. Moreover, with specific indications and techniques, interventional radiology can also play a role in therapeutic management. Surgery is the treatment of choice, consisting of either partial pancreatectomy or enucleation of the primary tumour. This article reviews the radiologic features of different pNETs as well as imaging mimics, in order to help radiologists to avoid potential pitfalls, to reach the correct diagnosis and to support the multidisciplinary team in establishing the right treatment.

PMID: 33447574 [PubMed]

Correlation of genomic alterations and PD-L1 expression in thymoma.

Fetched: January 17th, 2021, 5:01am GMT

Correlation of genomic alterations and PD-L1 expression in thymoma.

J Thorac Dis. 2020 Dec;12(12):7561-7570

Authors: Jovanovic D, Markovic J, Ceriman V, Peric J, Pavlovic S, Soldatovic I

Abstract
Thymic epithelial tumors (TETs) include several anterior mediastinal malignant tumours: thymomas, thymic carcinomas and thymic neuroendocrine cancers. There is significant variety in the biologic features and clinical course of TETs and many attempts have been made to identify target genes for successful therapy of TETs. Next generation sequencing (NGS) represents a huge advancement in diagnostics and these new molecular technologies revealed that thymic neoplasms have the lowest tumor mutation burden among all adult malignant tumours with a different pattern of molecular aberrations in thymomas and thymic carcinomas. As for the PD-L1 expression in tumor cells in thymoma and thymic carcinoma, it varies a lot in published studies, with findings of PD-L1 expression from 23% to 92% in thymoma and 36% to 100% in thymic carcinoma. When correlated PD-L1 expression with disease stage some controversial results were obtained, with no association with tumor stage in most studies. This is, at least in part, explained by the fact that several diverse PD-L1 immunohistochemical tests were used in each trial, with four different antibodies (SP142, SP263, 22C3, and 28-8), different definition of PD-L1 positivity and cutoff values throughout the studies as well. There is a huge interest in using genomic features to produce predictive genomic-based immunotherapy biomarkers, particularly since recent data suggest that certain tumor-specific genomic alterations, either individually or in combination, appear to influence immune checkpoint activity and better responses as the outcome, so as such in some cancer types they may complement existing biomarkers to improve the selection criteria for immunotherapy.

PMID: 33447447 [PubMed]

Permalink for 'Pseudotumoral form of schistosomiasis mimicking neuroendocrine tumor: a case report and brief review of the differential diagnosis of retroperitoneal masses.'

Pseudotumoral form of schistosomiasis mimicking neuroendocrine tumor: a case report and brief review of the differential diagnosis of retroperitoneal masses.

Fetched: January 17th, 2021, 5:01am GMT

Pseudotumoral form of schistosomiasis mimicking neuroendocrine tumor: a case report and brief review of the differential diagnosis of retroperitoneal masses.

Pan Afr Med J. 2020;37:186

Authors: Marín-Martínez L, Kyriakos G, Sánchez-Gutiérrez D

Abstract
Differential diagnosis of retroperitoneal masses may become complex and requires careful anamnesis, physical examination and several complementary tests. We present the clinical case of a male patient aged 45 years who was diagnosed with a 4cm paraaortic lesion compatible with neuroendocrine tumor in the abdominal computed tomography (CT) exam. The workup performed with SPECT-CT, somatostatin receptors scintigraphy, MIBG scintigraphy, 24-hour urine total and fractionated catecholamines and 24-hour urine 5-OH indoleacetic did not confirm the first diagnostic impression. Finally, the lesion was biopsied and presence of micro-organisms was revealed. Further exams confirmed schistosomiasis as the cause of the paraaortic lesion. Histological diagnosis can be helpful with regard to the differential diagnosis of retroperitoneal masses.

PMID: 33447341 [PubMed - in process]

Surgery vs Observation for Patients With Small Pancreatic Neuroendocrine Tumors.

Fetched: January 15th, 2021, 5:00am GMT

Surgery vs Observation for Patients With Small Pancreatic Neuroendocrine Tumors.

JAMA Surg. 2021 Jan 13;:

Authors: Aziz H, Howe JR, Pawlik TM

PMID: 33439231 [PubMed - as supplied by publisher]

WLS-Wnt signaling promotes neuroendocrine prostate cancer.

Fetched: January 15th, 2021, 5:00am GMT

WLS-Wnt signaling promotes neuroendocrine prostate cancer.

iScience. 2021 Jan 22;24(1):101970

Authors: Bland T, Wang J, Yin L, Pu T, Li J, Gao J, Lin TP, Gao AC, Wu BJ

Abstract
Neuroendocrine prostate cancer (NEPC) is a lethal prostate cancer subtype arising as a consequence of more potent androgen receptor (AR) targeting in castration-resistant prostate cancer (CRPC). Its molecular pathogenesis remains elusive. Here, we report that the Wnt secretion mediator Wntless (WLS) is a major driver of NEPC and aggressive tumor growth in vitro and in vivo. Mechanistic studies showed that WLS is a transcriptional target suppressed by AR that activates the ROR2/PKCδ/ERK signaling pathway to support the neuroendocrine (NE) traits and proliferative capacity of NEPC cells. Analysis of clinical samples and datasets revealed that WLS was highly expressed in CRPC and NEPC tumors. Finally, treatment with the Wnt secretion inhibitor LGK974 restricted NE prostate tumor xenograft growth in mice. These findings collectively characterize the contribution of WLS to NEPC pathogenesis and suggest that WLS is a potential therapeutic target in NEPC.

PMID: 33437943 [PubMed]

Permalink for 'Prognosis analysis of patients with pancreatic neuroendocrine tumors after surgical resection and the application of enucleation.'

Prognosis analysis of patients with pancreatic neuroendocrine tumors after surgical resection and the application of enucleation.

Fetched: January 15th, 2021, 5:00am GMT

Prognosis analysis of patients with pancreatic neuroendocrine tumors after surgical resection and the application of enucleation.

World J Surg Oncol. 2021 Jan 12;19(1):11

Authors: Chen J, Yang Y, Liu Y, Kan H

Abstract
OBJECTIVE: To investigate the prognostic factors of patients with pancreatic neuroendocrine tumor (pNETs) after surgical resection, and to analyze the value of enucleation for pNETs without distant metastasis that are well-differentiated (G1) and have a diameter ≤ 4 cm.
METHODS: Data from pNET patients undergoing surgical resection between 2004 and 2017 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier analysis and log-rank testing were used for the survival comparisons. Adjusted HRs with 95% CIs were calculated using univariate and multivariate Cox regression models to estimate the prognostic factors. P < 0.05 was regarded as statistically significant.
RESULTS: This study found that female, cases diagnosed after 2010, and pancreatic body/tail tumors were protective factors for good survival, while histological grade G3, a larger tumor size, distant metastasis, AJCC 8th stage III-IV and age over 60 were independent prognostic factors for a worse OS/CSS. For the pNETs that were well-differentiated (G1) and had a tumor diameter ≤ 4 cm, the type of surgery was an independent factor for the long-term prognosis of this group. Compared with pancreaticoduodenectomy and total pancreatectomy, patients who were accepted enucleation had better OS/CSS.
CONCLUSION: For pNETs patients undergoing surgical resection, sex, year of diagnosis, tumor location, pathological grade, tumor size, distant metastasis, race, and age were independent prognostic factors associated with the OS/CSS of patients. For pNETs patients with G1 and a tumor diameter less than 4 cm, if the tumor was located over 3 mm from the pancreatic duct, enucleation may be a wise choice.

PMID: 33436017 [PubMed - in process]

Drug perturbation gene set enrichment analysis (dpGSEA): a new transcriptomic drug screening approach.

Fetched: January 15th, 2021, 5:00am GMT

Drug perturbation gene set enrichment analysis (dpGSEA): a new transcriptomic drug screening approach.

BMC Bioinformatics. 2021 Jan 12;22(1):22

Authors: Fang M, Richardson B, Cameron CM, Dazard JE, Cameron MJ

Abstract
BACKGROUND: In this study, we demonstrate that our modified Gene Set Enrichment Analysis (GSEA) method, drug perturbation GSEA (dpGSEA), can detect phenotypically relevant drug targets through a unique transcriptomic enrichment that emphasizes biological directionality of drug-derived gene sets.
RESULTS: We detail our dpGSEA method and show its effectiveness in detecting specific perturbation of drugs in independent public datasets by confirming fluvastatin, paclitaxel, and rosiglitazone perturbation in gastroenteropancreatic neuroendocrine tumor cells. In drug discovery experiments, we found that dpGSEA was able to detect phenotypically relevant drug targets in previously published differentially expressed genes of CD4+T regulatory cells from immune responders and non-responders to antiviral therapy in HIV-infected individuals, such as those involved with virion replication, cell cycle dysfunction, and mitochondrial dysfunction. dpGSEA is publicly available at [https:] .
CONCLUSIONS: dpGSEA is an approach that uniquely enriches on drug-defined gene sets while considering directionality of gene modulation. We recommend dpGSEA as an exploratory tool to screen for possible drug targeting molecules.

PMID: 33435872 [PubMed - in process]

Permalink for 'Chemotherapy-Induced Upregulation of Somatostatin Receptor-2 Increases the Uptake and Efficacy of 177Lu-DOTA-Octreotate in Neuroendocrine Tumor Cells.'

Chemotherapy-Induced Upregulation of Somatostatin Receptor-2 Increases the Uptake and Efficacy of 177Lu-DOTA-Octreotate in Neuroendocrine Tumor Cells.

Fetched: January 15th, 2021, 5:00am GMT

Chemotherapy-Induced Upregulation of Somatostatin Receptor-2 Increases the Uptake and Efficacy of 177Lu-DOTA-Octreotate in Neuroendocrine Tumor Cells.

Cancers (Basel). 2021 Jan 10;13(2):

Authors: Shah RG, Merlin MA, Adant S, Zine-Eddine F, Beauregard JM, Shah GM

Abstract
The peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTA-octreotate (LuTate) is recommended for different types of neuroendocrine tumors (NETs) which overexpress somatostatin receptors (SSTR). A combination with chemotherapy improves objective response to LuTate in NET patients and here we characterized chemotherapy-induced upregulation of SSTR2 receptors as a cause for this improved response to LuTate. The NET cell lines with low (BON-1) or relatively high (NCI-H727) SSTR2-expression levels, and non-NET cancer and normal cells were treated with chemotherapeutic drugs and assessed for upregulation of SSTR2. We report that an exposure to low or high doses of drugs, such as temozolomide for 24 h or 5 day results in upregulation of SSTR2 between 3-7 days, increased LuTate uptake and decreased rate of cell proliferation. This effect is at the level of SSTR2-mRNA and is more pronounced in low SSTR2 expressing BON-1 than in high SSTR2 expressing NCI-H727 or non-NET cancer or normal cells. Thus, a properly timed pre-treatment with low-dose chemotherapy could not only improve therapeutic efficacy of LuTate in NET patients who are presently eligible for PRRT, but also allow PRRT to be administered to patients with low SSTR-expressing NETs, who would otherwise not respond to this modality because of insufficient radiation delivery.

PMID: 33435224 [PubMed]

[Expression of sperm-specific glyceraldehyde-3-phosphate dehydrogenase in melanoma cells changes their energy metabolism].

Fetched: January 15th, 2021, 5:00am GMT

[Expression of sperm-specific glyceraldehyde-3-phosphate dehydrogenase in melanoma cells changes their energy metabolism].

Biomed Khim. 2020 Sep;66(5):372-377

Authors: Melnikova AK, Kuravsky ML, Kulikova KV, Sevostyanova IA, Muronetz VI

Abstract
The somatic isoform of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH; EC1.2.1.12) is involved in such crucial for cancer cells development pathways as induction of apoptosis and glycolytic regulation. At the same time, sperm-specific isoform (GAPDHS) does not exhibit all the same functions as somatic enzyme. The expression of sperm-specific GAPDH without N-terminal domain in some melanoma cells along with somatic isoenzyme, shown in our previous work, has led to the proposal of this unusual enzyme's possible role in regulation of cancer cells glycolysis. In the presented work we have tested production of GAPDHS in 13 additional melanoma cell lines by immunoblotting. We have also gathered data on energy metabolism in 5 selected cell lines by evaluation of glucose uptake and lactate production in differing conditions. We have demonstrated that in standard cultivation media glucose uptake by MelP cells, producing substantial amounts of GAPDHS protein was higher than in MelKor cells, producing lesser amounts of GAPDHS. All other analyzed cell lines that do not produce GAPDHS (MelMS, MelSi and Malme3M) had even a lower glucose uptake rate.

PMID: 33140730 [PubMed - indexed for MEDLINE]

Approach to skin malignancies in COVID-19 pandemic days.

Fetched: January 15th, 2021, 5:00am GMT

Approach to skin malignancies in COVID-19 pandemic days.

J Biol Regul Homeost Agents. 2020 Nov-Dec;34(6):1977-1982

Authors: Aslan Kayıran M, Karadag AS, Wollina U

Abstract
COVID-19 pandemic emerged as a condition that changed our entire life and led us to develop new perspectives on diseases. Cancers are generally additional risk factors for COVID-19, and this has implications also for skin cancer patients. Those patients require special attention, due to situations such as an increased risk of infection as a result of visiting the hospital for treatment. It is imperative that the diagnosis and treatment of patients who have a cancer that progresses rapidly, such as malignant melanoma, high-risk squamous cell carcinoma and a high risk of metastasis, are delayed. Due to the relatively long-lasting nature of basal cell carcinoma and, as almost no metastasis would be expected, its treatment may be postponed, except for those that occur in areas such as the eyes and mouth. Diagnosis and treatment of skin cancers is a process that requires many procedures. Throughout this process, physicians should take appropriate precautions that are sufficient to protect both the patient and themselves in the best way without leading to any delay in the procedures.

PMID: 33111514 [PubMed - indexed for MEDLINE]

CD147 inhibitors as a treatment for melanoma: Promising agents against SARS-CoV-2 infection.

Fetched: January 15th, 2021, 5:00am GMT

CD147 inhibitors as a treatment for melanoma: Promising agents against SARS-CoV-2 infection.

Dermatol Ther. 2020 Nov;33(6):e14449

Authors: Pourani MR, Nekooghadam SM, Youssefian L, Vahidnezhad H, Abdollahimajd F

PMID: 33098610 [PubMed - indexed for MEDLINE]

Genome-wide RNAi screen for genes regulating glycolytic response to vemurafenib in BRAFV600 melanoma cells.

Fetched: January 15th, 2021, 5:00am GMT

Genome-wide RNAi screen for genes regulating glycolytic response to vemurafenib in BRAFV600 melanoma cells.

Sci Data. 2020 10 12;7(1):339

Authors: Smith LK, Parmenter T, Gould CM, Madhamshettiwar PB, Sheppard KE, Simpson KJ, McArthur GA

Abstract
Identification of mechanisms underlying sensitivity and response to targeted therapies, such as the BRAF inhibitor vemurafenib, is critical in order to improve efficacy of these therapies in the clinic and delay onset of resistance. Glycolysis has emerged as a key feature of the BRAF inhibitor response in melanoma cells, and importantly, the metabolic response to vemurafenib in melanoma patients can predict patient outcome. Here, we present a multiparameter genome-wide siRNA screening dataset of genes that when depleted improve the viability and glycolytic response to vemurafenib in BRAFV600 mutated melanoma cells. These datasets are suitable for analysis of genes involved in cell viability and glycolysis in steady state conditions and following treatment with vemurafenib, as well as computational approaches to identify gene regulatory networks that mediate response to BRAF inhibition in melanoma.

PMID: 33046726 [PubMed - indexed for MEDLINE]

Pembrolizumab-Induced Thyroiditis and Colitis-Presentation and Resolution on Serial FDG PET/CT.

Fetched: January 15th, 2021, 5:00am GMT

Pembrolizumab-Induced Thyroiditis and Colitis-Presentation and Resolution on Serial FDG PET/CT.

Clin Nucl Med. 2021 Feb 01;46(2):e121-e122

Authors: Nawwar AA, Searle J, Lyburn ID

Abstract
ABSTRACT: A 58-year-old man with previous melanoma of the left leg underwent whole-body 18F-FDG PET/CT to stage metastatic disease prior to commencing pembrolizumab. Follow-up FDG PET/CT after 3 months of treatment showed partial metabolic response of soft tissue and nodal metastases and diffuse increased thyroid and colonic uptake, suggestive of thyroiditis and colitis. Pembrolizumab was ceased, and a repeat FDG PET/CT scan showed regression of uptake in the thyroid gland and colon, in keeping with resolution of inflammatory change. Immune-related adverse events induced by Immune checkpoint inhibitors, such as pembrolizumab, should be recognized-cessation of treatment often leads to resolution.

PMID: 32969909 [PubMed - indexed for MEDLINE]

Development and long-term evaluation of a new 68Ge/68Ga generator based on nano-SnO2 for PET imaging.

Fetched: January 15th, 2021, 5:00am GMT

Development and long-term evaluation of a new 68Ge/68Ga generator based on nano-SnO2 for PET imaging.

Sci Rep. 2020 07 29;10(1):12756

Authors: Romero E, Martínez A, Oteo M, Ibañez M, Santos M, Morcillo MÁ

Abstract
Radionuclide generator systems can routinely provide radionuclides on demand such as 68Ga produced by a 68Ge/68Ga generator without the availability of an on-site accelerator or a research reactor. Thus, in this work nano-SnO2 was used to develop a new 68Ge/68Ga generator which was evaluated over a period of 17 months and 305 elution cycles. The elution yield was 91.1 ± 1.8% in the first 7 mL (1 M HCl as eluent) when the generator was new and then it decreased with time and use to 73.8 ± 1.9%. Around 80% of the elutable 68Ga activity was obtained in 1 mL and the 68Ge content in the eluate did not exceed 1 × 10-4% over the investigation period when it was eluted regularly. The described generator provided adequate results for radiolabelling of DOTA-TOC with direct use of eluate. In addition, [68Ga]Ga-DOTA-TOC was tested satisfactorily for in vivo tumor detection by microPET/CT imaging in a lung cancer mouse model.

PMID: 32728067 [PubMed - indexed for MEDLINE]

Antitumor effect of a pyrazolone-based-complex [Cu(PMPP-SAL)(EtOH)] against murine melanoma B16 cell in vitro and in vivo.

Fetched: January 15th, 2021, 5:00am GMT

Antitumor effect of a pyrazolone-based-complex [Cu(PMPP-SAL)(EtOH)] against murine melanoma B16 cell in vitro and in vivo.

Acta Pharm. 2020 Dec 01;70(4):561-575

Authors: Abula A, Zhao J, Xu G, Li Y, Sun S

Abstract
Pyrazolone-based derivative metal complexes were reported to have cytotoxicity in some tumor cells. In this study, the antitumor effect of [Cu(PMPP-SAL)(EtOH)] (PMPP-SAL = N-(1-phenyl-3-methyl-4-propenylidene-5-pyrazolone)- salicylidene hydrazide anion) in murine melanoma B16 cells in vitro and in vivo was investigated. The results showed that [Cu(PMPP-SAL)(EtOH)] inhibited the survival of B16 cells in vitro, and the IC50 value was superior to cisplatin (DDP) (p < 0.001). B16 cell apoptosis was significantly higher in comparison to the control group (DMSO) (p < 0.01), and cell cycle arrest occurred at the G0/G1 phase. When challenged C57 BL/6J mice were treated with [Cu(PMPPSAL)(EtOH)], a smaller volume of B16 solid tumors were reported than the control group (p < 0.01), with lower positive expression indices of CD 34, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) (p < 0.01). Moreover, the tumor growth was suppressed in mice due to the induction of apoptosis, as detected by the TUNEL assay (p < 0.001). In summary, [Cu(PMPP-SAL)(EtOH)] effectively inhibited the growth of B16 cells in vitro and in vivo due to the induction of apoptosis and the inhibition of intra-tumoral angiogenesis, demonstrating its therapeutic potential in melanoma treatment.

PMID: 32412431 [PubMed - indexed for MEDLINE]

Permalink for 'Distinctive low epidermal nerve fiber density in schwannomatosis patients provides a major parameter for diagnosis and differential diagnosis.'

Distinctive low epidermal nerve fiber density in schwannomatosis patients provides a major parameter for diagnosis and differential diagnosis.

Fetched: January 15th, 2021, 5:00am GMT

Distinctive low epidermal nerve fiber density in schwannomatosis patients provides a major parameter for diagnosis and differential diagnosis.

Brain Pathol. 2020 03;30(2):386-391

Authors: Farschtschi SC, Kluwe L, Schön G, Friedrich RE, Matschke J, Glatzel M, Weis J, Hagel C, Mautner VF

Abstract
Schwannomatosis and neurofibromatosis type 2 (NF2) are two distinct neuro-genetic tumor predisposition disorders, which, however, share some clinical and genetic features. While germline mutations in the NF2 gene are only found in NF2, a majority of schwannomatosis patients have germline mutations in the SMARCB1 or LZTR1 genes. The overlapping clinical phenotypes pose a serious challenge in differential diagnosis and in risk stratification of these two entities which is further complicated by frequent mosaicism in both disorders. Chronic neuropathic pain which is a typical consequence of small fiber neuropathy, is characteristic for schwannomatosis. By contrast, NF2 patients do not have chronic pain but may have moderate to severe sensory deficits and paresis which are not characteristic for schwannomatosis. In the present study, we determined intraepidermal nerve fiber density (IEND) in skin biopsies of 34 clinically ascertained schwannomatosis and 25 NF2 patients. In the NF2 group, 11/25 (44%) presented with IEND below the age- and gender-matched bottom 5% normative reference IEND. In contrast, nearly all (33/34 = 97%) schwannomatosis patients showed IEND below or on the bottom 5% normative reference. The reduction of IEND in schwannomatosis patients was age-independent. Paired t-test revealed no difference between the NF2-IEND and the corresponding bottom 5% normative reference (P = 0.98). By contrast, IEND in the schwannomatosis patients were highly significantly lower than the corresponding 5% normative reference IEND (P < 0.0001). In addition, the difference between the IEND of our patients and the 5% lowest normative reference IEND was highly significantly larger in schwannomatosis patients than in NF2 patients (P < 0.0001). IEND of our patients did not correlate with neither the presence nor types of germline mutations in neither the NF2 nor the LZTR1 gene. In conclusion, schwannomatosis patients have marked low IEND which provides a major parameter for diagnosis and differential diagnosis.

PMID: 31424590 [PubMed - indexed for MEDLINE]

Aquaporin-1 Protein Expression of the Primary Tumor May Predict Cerebral Progression of Cutaneous Melanoma.

Fetched: January 15th, 2021, 5:00am GMT

Aquaporin-1 Protein Expression of the Primary Tumor May Predict Cerebral Progression of Cutaneous Melanoma.

Pathol Oncol Res. 2020 Jan;26(1):405-410

Authors: Imrédi E, Liszkay G, Kenessey I, Plotár V, Gödény M, Tóth B, Fedorcsák I, Tímár J

Abstract
Brain metastasis is a frequent complication of the progression of malignant melanoma. In a previous study aquaporin 1 (AQP1) protein expression was found to be associated with increased mortality and decreased progression free survival in cutaneous melanoma. To explore further the potential of this marker we studied the AQP1 protein expression in 67 metastatic melanoma patients using immunohistochemistry. Primary tumor samples were acquired from patients with brain (BR) (n = 44) and extra-cranial (EC) (n = 23) metastases, while brain metastatic samples were collected during neurosurgical resection (n = 5). Patients with brain metastases had shorter overall survival (p = 0.02) and significantly higher AQP1 expression in the primary tumors (median H-score = 250 vs. 140, p = 0.044) as compared to patients of the EC metastasis group. AQP1 expression was found to be significantly lower in the brain metastases compared to the corresponding primary tumors (median H-score = 35 vs. 300 p = 0.01). However, in brain metastases AQP1 expression was heterogenous, AQP1 protein was more abundant in the melanoma cells far away from the capillaries as compared to tumor cells adjacent to vessels indicating a hypoxia-driven expression of AQP1. We suggest that AQP1 expression could well be a prognostic marker of brain metastatic potential of human cutaneous melanoma.

PMID: 30378011 [PubMed - indexed for MEDLINE]

Biomarkers Associated with Clinical Outcome of Advanced Melanoma Patients Treated with Ipilimumab.

Fetched: January 15th, 2021, 5:00am GMT

Biomarkers Associated with Clinical Outcome of Advanced Melanoma Patients Treated with Ipilimumab.

Pathol Oncol Res. 2020 Jan;26(1):317-325

Authors: Balatoni T, Ladányi A, Fröhlich G, Czirbesz K, Kovács P, Pánczél G, Bence E, Plótár V, Liszkay G

Abstract
Ipilimumab was the first immunotherapy approved for metastatic melanoma in decades and is currently registered as a second-line treatment. However, new immunotherapies, in combination with ipilimumab, offer even better clinical outcomes for patients compared with single-agent treatments, at the expense of improved toxicity. The aim of this study was to evaluate the feasibility of ipilimumab outside the clinical trials and to identify survival predictors for treatment benefit. Data were collected on 47 advanced melanoma patients treated with ipilimumab between 2010 and 2015 at a single center. Association of clinical characteristics (including primary tumor characteristics), serum lactate dehydrogenase (LDH), erythrocyte sedimentation rate, absolute eosinophil, lymphocyte, and neutrophil count, neutrophil/lymphocyte and eosinophil/lymphocyte ratio with toxicity and clinical outcome were assessed using univariate and multivariate analysis. Median progression-free survival at a median follow-up of 10 months was 2.7 months and median overall survival was 9.8 months. Objective response was observed in 17% of patients and the disease control rate at week 24 was 40%. The 1- and 2-year survival rates documented were 40 and 28%, respectively. Significant association between high LDH level (>1.5× upper limit of normal) and decreased overall survival was demonstrated in uni- and multivariate analysis (hazard ratio [HR]: 3.554, 95% CI: 1.225-10.306, p = 0.019). Neither biomarkers nor clinical outcome were associated with toxicity. Using baseline serum LDH to identify patients most likely to benefit from ipilimumab therapy could serve as a simple and inexpensive biomarker of clinical outcome.

PMID: 30225783 [PubMed - indexed for MEDLINE]

Permalink for 'IL-2 And IL-15 Induced NKG2D, CD158a and CD158b Expression on T, NKT- like and NK Cell Lymphocyte Subsets from Regional Lymph Nodes of Melanoma Patients.'

IL-2 And IL-15 Induced NKG2D, CD158a and CD158b Expression on T, NKT- like and NK Cell Lymphocyte Subsets from Regional Lymph Nodes of Melanoma Patients.

Fetched: January 15th, 2021, 5:00am GMT

IL-2 And IL-15 Induced NKG2D, CD158a and CD158b Expression on T, NKT- like and NK Cell Lymphocyte Subsets from Regional Lymph Nodes of Melanoma Patients.

Pathol Oncol Res. 2020 Jan;26(1):223-231

Authors: Vuletić A, Jovanić I, Jurišić V, Milovanović Z, Nikolić S, Spurnić I, Konjević G

Abstract
Regional lymph nodes (LN)s represent important immunological barriers in spreading of malignant tumors. However, they are the most frequent early metastatic site in melanoma. Immunomodulatory agents including cytokines have been included in therapy of melanoma and have shown severe side effects and toxicity. In this sense, there is a growing need for bringing these agents to further in vitro testing that may enlighten aspects of their regional application. Therefore, the aim of this study was to investigate the effect of interleukin (IL)-2 and IL-15, the two cytokines with similar immune-enhancing effects, on the expression of activating NKG2D, inhibitory CD158a and CD158b receptors on CD8+ T, NKT-like and NK cell lymphocyte subsets from regional LNs of melanoma patients. In this study, we showed significant effects of IL-2 and IL-15 cytokine treatments on the expression of activating NKG2D and on inhibitory CD158a and CD158b receptors on lymphocytes, CD8+ T, NKT-like and NK cell lymphocyte subsets originating from regional LNs of melanoma patients. Furthermore, IL-2 and IL-15 by inducing the expression of NKG2D activating receptor on innate and on adaptive lymphocyte subsets and by augmenting NK cell antitumor cytotoxicity that correlated with the cytokine-induced NKG2D expression, increased antitumor potential of immune cells in regional LNs of melanoma patients irrespective of LN involvement. These findings indicate the importance of immune cell population from regional LNs of melanoma patients in the development of immune intervention strategies that may if applied locally increase antitumor potential to the level that controls tumor progressions.

PMID: 29948616 [PubMed - indexed for MEDLINE]

Delayed imaging with oral contrast improves [68Ga]Ga-DOTANOC PET/CT detection of primary duodenal neuroendocrine tumor (NET).

Fetched: January 12th, 2021, 5:01am GMT

Delayed imaging with oral contrast improves [68Ga]Ga-DOTANOC PET/CT detection of primary duodenal neuroendocrine tumor (NET).

Eur J Nucl Med Mol Imaging. 2021 Jan 09;:

Authors: Mei R, Allegri V, Calabrò D, Fanti S, Ambrosini V

PMID: 33423095 [PubMed - as supplied by publisher]

Systemic Treatment of Advanced Gastroenteropancreatic Neuroendocrine Tumors in Korea: Literature Review and Expert Opinion.

Fetched: January 12th, 2021, 5:01am GMT

Systemic Treatment of Advanced Gastroenteropancreatic Neuroendocrine Tumors in Korea: Literature Review and Expert Opinion.

Cancer Res Treat. 2020 Dec 29;:

Authors: Yoo C, Oh CR, Kim ST, Bae WK, Choi HJ, Oh DY, Lee MA, Ryoo BY

Abstract
Neuroendocrine tumors (NETs) are a group of malignancies arising from neuroendocrine cells and frequently originate in the gastrointestinal tract and pancreas. Although curative resection is the main treatment for localized disease, systemic therapy is needed for relapsed or metastatic/unresectable gastroenteropancreatic NETs (GEP-NETs). Although there are several NET treatment guidelines from various countries, the geographical discrepancies between patient clinical characteristics, the regulatory approval status for therapeutic agents, and medical practices necessitate specific guidelines for Korean patients. We here provide a consensus review of the diagnosis, staging and systemic treatment of Korean GEP-NET patients. Systemic therapy options and the current Korean expert consensus on these treatments, including somatostatin analogs, targeted therapies such as everolimus and sunitinib, peptide receptor radionuclide treatments, and cytotoxic chemotherapies are addressed.

PMID: 33421978 [PubMed - as supplied by publisher]

Usefulness of selective arterial calcium injection tests for functional pancreatic neuroendocrine tumors.

Fetched: January 11th, 2021, 5:01am GMT

Usefulness of selective arterial calcium injection tests for functional pancreatic neuroendocrine tumors.

Sci Rep. 2021 Jan 08;11(1):235

Authors: Nakano Y, Kitago M, Shinoda M, Nakatsuka S, Kurihara I, Yagi H, Abe Y, Oshima G, Hori S, Yokose T, Kitagawa Y

Abstract
The selective arterial calcium injection (SACI) test is useful for patients with functional pancreatic neuroendocrine tumors (F-PNETs). This study evaluated which patients with F-PNETs would benefit from the SACI test. We retrospectively analyzed the preoperative findings of patients on computed tomography (CT), magnetic resonance imaging (MRI), CT angiography (CTA), and the SACI test. Fourteen patients who underwent pancreatectomy between January 1997 and September 2016 for F-PNETs were evaluated. We classified these patients into groups A, B, and C; group A, one tumor detected by either CT or MRI; group B, multiple tumors detected; and group C, the tumor location was accordant on CT, MRI, and CTA, but the SACI test revealed another tumor. In group A, the tumor was also detected by CTA and the SACI test was positive on calcium injection. In group B, the focus tumor among the multiple tumors was detected by the SACI test. In group C, another tumor was identified by the SACI test, whose location was different from that detected using CT and MRI. The SACI test is more useful for multiple F-PNETs on CT or MRI. If CT or MRI detects a single tumor, the SACI test or CTA may be unnecessary.

PMID: 33420290 [PubMed - as supplied by publisher]

Permalink for 'Peptide receptor radiotherapy re-treatment in patients with progressive neuroendocrine tumors: A systematic review and meta-analysis.'

Peptide receptor radiotherapy re-treatment in patients with progressive neuroendocrine tumors: A systematic review and meta-analysis.

Fetched: January 10th, 2021, 5:01am GMT

Peptide receptor radiotherapy re-treatment in patients with progressive neuroendocrine tumors: A systematic review and meta-analysis.

Cancer Treat Rev. 2020 Dec 22;93:102141

Authors: Strosberg J, Leeuwenkamp O, Siddiqui MK

Abstract
BACKGROUND: This review and meta-analysis examined published evidence of peptide receptor radionuclide therapy (PRRT) re-treatment efficacy and safety in patients with advanced neuroendocrine tumors (NETs).
METHODS: Embase, MEDLINE, MEDLINE In-Progress, and Cochrane CENTRAL were searched (database inception-present) to identify evidence of efficacy and safety of PRRT re-treatment in adults with NETs previously treated with 177Lu- and/or 90Y-PRRT. Progression-free survival (PFS), overall survival (OS), disease control rate (DCR) from time of re-treatment were assessed. Data were pooled using medians and variance for time-to-event outcomes and inverse-variance weighted proportions (Freeman-Tukey method) for binary outcomes.
RESULTS: Of 567 studies screened, 13 reported re-treatment efficacy outcomes. In random-effects meta-analyses of 177Lu-PRRT re-treatment, median PFS (N = 7 studies [414patients]) was 12.52 months (95% CI 9.82-15.22) with moderate heterogeneity across studies (I2 = 50.5%), median OS (N = 2 [194 patients]) was 26.78 months (95% CI 18.73-34.83) with moderate-to-high heterogeneity (I2 = 57.5%), and DCR (N = 8 [347 patients]) was 71% (95% CI 66-75) with high heterogeneity (I2 = 81.5%). PFS was similar with either 177Lu-PRRT re-treatment alone or in combination with 90Y-PRRT. Grade 3/4 adverse events occurred in 5% (95% CI 2-8) of patients receiving 177Lu-PRRT re-treatment (N = 5 [271 patients]) with few grade 3/4 renal toxicities (0% [95% CI 0-1]). Pooled myelodysplastic syndrome and acute myeloid leukemia incidence was 0% (95%CI 0-2).
CONCLUSION: Re-treatment with 177Lu-PRRT provided encouraging median PFS in patients with NETs with a safety profile similar to initial PRRT.

PMID: 33418096 [PubMed - as supplied by publisher]

Pancreaticoduodenectomy with vascular divestment for locally advanced pancreatic neuroendocrine tumour.

Fetched: January 10th, 2021, 5:01am GMT

Pancreaticoduodenectomy with vascular divestment for locally advanced pancreatic neuroendocrine tumour.

ANZ J Surg. 2021 Jan 08;:

Authors: Rosso E, Petrucciani N, El Zibawi M, Iannelli A

PMID: 33417734 [PubMed - as supplied by publisher]

Permalink for 'The panel of Syntaxin 1 and Insulinoma-Associated Protein 1 outperforms classic neuroendocrine markers in pulmonary neuroendocrine neoplasms.'

The panel of Syntaxin 1 and Insulinoma-Associated Protein 1 outperforms classic neuroendocrine markers in pulmonary neuroendocrine neoplasms.

Fetched: January 10th, 2021, 5:01am GMT

The panel of Syntaxin 1 and Insulinoma-Associated Protein 1 outperforms classic neuroendocrine markers in pulmonary neuroendocrine neoplasms.

APMIS. 2021 Jan 08;:

Authors: Zombori T, Turkevi-Nagy S, Sejben A, Juhász-Nagy G, Cserni G, Furák J, Tiszlavicz L, Krenács L, Kővári B

Abstract
AIM: Syntaxin-1 (STX1) is a recently described highly sensitive and specific neuroendocrine marker. We evaluated the applicability of STX1 as an immunohistochemical marker in pulmonary neuroendocrine neoplasms (NENs). We compared STX1 with established neuroendocrine markers, including insulinoma-associated protein 1 (INSM1).
EXPERIMENTAL DESIGN: Typical carcinoids (n = 33), atypical carcinoids (n = 7), small cell lung carcinomas ([SCLCs] n = 30), and large cell neuroendocrine lung carcinomas (n = 17) were immunostained using tissue microarray for STX1, chromogranin-A, synaptophysin, CD56, and INSM1.
MAIN RESULTS: Eighty-four of eighty-seven (96.5%) NENs showed STX1 positivity. Carcinoids and LCNECs typically presented a combined strong membranous and weak cytoplasmic staining pattern; cytoplasmic expression was predominately observed in SCLCs. The sensitivity of STX1 was 90% in SCLCs and 100% in typical carcinoids, atypical carcinoids, and large cell neuroendocrine lung carcinomas. The overall sensitivity of STX1 in pulmonary NENs was 96.6%, and the sensitivity of the other markers was as follows: chromogranin-A (85.2%), synaptophysin (85.2%), CD56 (92.9%), and INSM1 (97. 7%). STX1 was found to be an excellent neuroendocrine marker of pulmonary NENs, with sensitivity and specificity surpassing that of classic markers.
MAJOR CONCLUSION: We propose a panel of STX1 and INSM1 for the routine immunohistochemical workup of pulmonary NENs.

PMID: 33417719 [PubMed - as supplied by publisher]

Prognostic Factors in Curative Resected Locoregional Small Intestine Neuroendocrine Neoplasms.

Fetched: January 10th, 2021, 5:01am GMT

Prognostic Factors in Curative Resected Locoregional Small Intestine Neuroendocrine Neoplasms.

World J Surg. 2021 Jan 08;:

Authors: Evers M, Rinke A, Rütz J, Ramaswamy A, Maurer E, Bartsch DK

Abstract
BACKGROUND: Small intestinal neuroendocrine neoplasms (SI-NEN) are rare, and only about 40% of patients are diagnosed without distant metastases. Aim of the study was to identify prognostic factors in patients with potentially curative resected locoregional SI-NEN.
METHODS: Patients with curative resected locoregional SI-NEN (ENETS stages I-III) were retrieved from a prospective data base. Demographic, surgical and pathological data of patients with and without disease recurrence were retrospectively analyzed using univariate and multivariate analysis.
RESULTS: In a 20-year period, 65 of 203 (32%) patients with SI-NEN were operated for stages I-III disease. Thirty-eight (58.5%) patients were men, and the median age at surgery was 59 (range 37-87) years. After median follow-up of 65 months, 14 patients experienced disease relapse median 28.5 (range 6-122) months after initial surgery, of which 2 died due to their disease. Multivariate analysis revealed age ≥ 60 years (HR = 6.41, 95% CI 1.38-29.67, p = 0.017), tumor size ≥ 2 cm (HR = 26.54, 95% CI 4.46-157.62, p < 0.001), lymph node ratio > 0.5 (HR 7.18, 95% CI 1.74-29.74, p = 0.007) and multifocal tumor growth (HR = 6.98, 95% CI 1.66-29.39, p = 0.008) as independent negative prognostic factors and right hemicolectomy compared to segmental small bowel resection (HR = 0.04, 95% CI 0.01-0.24, p < 0.001) as independent protector against recurrence.
CONCLUSION: Patients with locoregional SI-NEN with an age ≥ 60 years, tumor size ≥ 2 cm, lymph node ratio > 0.5 and multiple small bowel tumor foci have an increased risk for recurrence and might benefit from adjuvant treatment. In contrast, right hemicolectomy of ileal SI-NEN seems to reduce the risk of recurrence.

PMID: 33416940 [PubMed - as supplied by publisher]

Permalink for 'Metastatic small cell carcinoma of the lung with prominent spindle cell morphology and hemangiopericytoma-like vascular pattern: A sarcoma mimicker.'

Metastatic small cell carcinoma of the lung with prominent spindle cell morphology and hemangiopericytoma-like vascular pattern: A sarcoma mimicker.

Fetched: January 10th, 2021, 5:01am GMT

Metastatic small cell carcinoma of the lung with prominent spindle cell morphology and hemangiopericytoma-like vascular pattern: A sarcoma mimicker.

SAGE Open Med Case Rep. 2020;8:2050313X20981177

Authors: Nsour E, Al Khader A, Al-Tarawneh B

Abstract
Small cell carcinoma is a malignant neuroendocrine tumor with aggressive clinical behavior. Histologically, the tumor is characterized by the proliferation of small, round, blue cells. Here, we present the case of a 50-year-old man with a 1-month history of enlarging chest wall mass. Microscopic examination of the lesion revealed a highly cellular neoplasm composed of closely packed, atypical spindle cells with scant cytoplasm, inconspicuous nucleoli, and brisk mitotic activity. The hemangiopericytoma-like vascular pattern was prominent. Areas showing a fibrosarcoma-like fascicular pattern were also observed. The tumor was immunohistochemically positive for TTF1, synaptophysin, and chromogranin, confirming small cell carcinoma. Further investigations revealed a lung origin and widespread metastases. The tumor in this case closely mimicked synovial sarcoma or malignant peripheral nerve sheath tumor. Small cell carcinoma demonstrates a hemangiopericytoma-like pattern that can mimic sarcoma histologically. This is a serious pitfall that can significantly affect the speed of diagnosis and management.

PMID: 33414922 [PubMed]

Anterior mediastinal large cell neuroendocrine carcinoma with elevated AFP: A case report and review.

Fetched: January 10th, 2021, 5:01am GMT

Anterior mediastinal large cell neuroendocrine carcinoma with elevated AFP: A case report and review.

Mol Clin Oncol. 2021 Feb;14(2):34

Authors: Komisarof J, Qiu H, Velez MJ, Mulford D

Abstract
Large cell neuroendocrine carcinoma (LCNEC) is a rare and aggressive cancer that typically presents in the lung. The current case report describes a 56 year old male who presented to Strong Memorial Hospital with progressive dyspnea and was revealed to have a large anterior mediastinal tumor with metastases to axillary, hilar and mediastinal lymph nodes. Tumor marker results revealed an elevated plasma level of α-fetoprotein (AFP), which initially pointed towards a diagnosis of teratoma, but the tumor stained positive for neuroendocrine markers CD56, chromogranin, and synaptophysin on biopsy, consistent with LCNEC. AFP-positive tumor cells were identified, and no alternate cause for the elevated AFP was identified. The patient underwent genetic testing revealing the tumor to be ALK, ROS1, KRAS, BRAF and EGFR wild type. The patient received 6 cycles of chemotherapy with cisplatin (80 mg/m2) and etoposide (100 mg/m2) and then radiation with an initial minor response. The patients course was complicated by the development of superior vena cava syndrome requiring emergency stenting. The results of the current case suggest that AFP may be worthy of further exploration as a potential tumor marker in LCNEC.

PMID: 33414915 [PubMed]

Loss of EHF facilitates the development of treatment-induced neuroendocrine prostate cancer.

Fetched: January 10th, 2021, 5:01am GMT

Loss of EHF facilitates the development of treatment-induced neuroendocrine prostate cancer.

Cell Death Dis. 2021 Jan 05;12(1):46

Authors: Long Z, Deng L, Li C, He Q, He Y, Hu X, Cai Y, Gan Y

Abstract
The rising of a highly aggressive subtype of castration-resistant prostate cancer (CRPC) named treatment-induced neuroendocrine prostate cancer (t-NEPC) after androgen deprivation therapy (ADT) is well known for its features of the neuroendocrine differentiation (NED) and androgen receptor (AR) independence. However, t-NEPC is still largely unknown. Here, we found that EHF is notably depressed in t-NEPC tumors, patient-derived xenografts, transgenic mice, and cell models. Results from cell lines uncovered that ADT represses EHF expression, which is required for the ADT-induced NED. Mechanism dissection revealed that ADT decreases the EHF transcription via relieving the AR binding to different androgen-responsive elements, which then promotes the expression and enzymatic activity of enhancer of zeste homolog 2 (EZH2), consequently catalyzing tri-methylation lysine 27 of histone H3 for transcriptional repression of its downstream genes to promote the NED. Furthermore, preclinical studies from cell and mice models proved that recovery of EHF expression or using EZH2 inhibitor can attenuate aggressive properties of CRPC cells, hinder the progression of t-NEPC, and promote the response of CPRC cells to enzalutamide. Together, we elucidate that the ADT/AR/EHF/EZH2 signaling is required for the ADT-enhanced NED and plays a critical role in the progression of t-NEPC.

PMID: 33414441 [PubMed - in process]

Mutation Profile of Thymic Carcinoma and Thymic Neuroendocrine Tumor by Targeted Next-generation Sequencing.

Fetched: January 10th, 2021, 5:01am GMT

Mutation Profile of Thymic Carcinoma and Thymic Neuroendocrine Tumor by Targeted Next-generation Sequencing.

Clin Lung Cancer. 2020 Dec 02;:

Authors: Sakane T, Sakamoto Y, Masaki A, Murase T, Okuda K, Nakanishi R, Inagaki H

Abstract
BACKGROUND: Thymic carcinoma is a rare mediastinal neoplasm, and little is known about its genetic variability, which has hampered the development of targeted therapies.
PATIENTS AND METHODS: We tested a next-generation sequencing panel containing 50 common cancer-related genes in 48 cases of thymic carcinoma and 6 cases of thymic neuroendocrine tumor.
RESULTS: We detected 42 variant calls in 21 of 54 cases. There was no significant difference in mutation frequency between thymic carcinoma and thymic neuroendocrine tumors. Among these, TP53 was the most frequently mutated gene (18.5%), followed by KIT (7.4%) and PDGFRA (5.6%). According to the gene pathways and groups, the p53 pathway, including TP53 and ATM, was most frequently affected (20.4%), followed by the receptor tyrosine kinase (RTK)/RAS pathway (18.5%) and PI3K pathway (5.6%). According to the OncoKB, an expert-guided precision oncology knowledge base, 7 genes among 10 cases (18.5%) were annotated with level 1 evidence, suggesting potentially therapeutic targets. Prognostic analyses, conducted in thymic squamous cell carcinomas, revealed that tumor cases harboring gene mutations in RTKs, including KIT (7.4%), PDGFRA (5.6%) and EGFR (3.7%), were significantly associated with a worse overall survival time (P = .0481). Among clinicopathologic factors, the advanced Masaoka stage was marginally associated with a worse overall survival (P = .0757). In the subsequent multivariate analysis, neither of the factors achieved statistical significance.
CONCLUSIONS: In this preliminary next-generation sequencing study, we unexpectedly found evidence suggesting that several gene mutations might be therapeutic targets. The gene mutations in RTKs may be a valuable prognostic factor in thymic squamous cell carcinoma.

PMID: 33414055 [PubMed - as supplied by publisher]

Permalink for 'Differentiation of insulinoma from accessory spleen by 99mTc-labelled heat-denaturated red blood cell scintigraphy: case report.'

Differentiation of insulinoma from accessory spleen by 99mTc-labelled heat-denaturated red blood cell scintigraphy: case report.

Fetched: January 10th, 2021, 5:01am GMT

Differentiation of insulinoma from accessory spleen by 99mTc-labelled heat-denaturated red blood cell scintigraphy: case report.

BMC Endocr Disord. 2021 Jan 07;21(1):6

Authors: Gezer E, Çetinarslan B, Karakaya D, Cantürk Z, Selek A, Sözen M, İşgören S

Abstract
BACKGROUND: Neuroendocrine tumors (NETs) are rare tumors harboring overexpression of somatostatin receptors (SSTRs) on their cell membrane. Because some organs, such as the spleen, adrenal glands and liver, physiologically express SSTR, it might be challenging to distinguish some pancreatic NETs located in the pancreatic tail from the accessory spleen next to the splenic hilum. In this manuscript, we report a case with hypoglycemia attack and 2 different masses displayed by Gallium 68-tetraazacyclododecane tetraacetic acid-octreotate (68Ga-DOTATATE) positron emission tomography/computed tomography (PET/CT).
CASE PRESENTATION: A 63-year-old woman presented to the hospital with confusion and profuse sweating. Biochemical diagnosis of insulinoma was established. 68Ga-DOTATATE PET/CT revealed two masses with increased tracer uptake located adjacent to the splenic hilum and inferior pole of the spleen which were initially reported as two separate accessory spleens. Then, 99mTc-labelled heat-denaturated red blood cell (99mTc-HDRBC) scintigraphy-single-photon emission computed tomography (SPECT)/CT was performed to distinguish a NET in the pancreatic tail from accessory spleen at the splenic hilum. Enhanced tracer uptake remained in the inferior pole of spleen, but not in the splenic hilum. The lesions were suggestive of insulinoma in the pancreatic tail and an accessory spleen adjacent to the inferior pole of the spleen.
CONCLUSION: Approximately 10% of the population have an accessory spleen which can show similar imaging characteristics with pancreatic NETs, especially if located in the pancreatic tail. In our presented case, 99mTc-HDRBC scintigraphy-SPECT/CT is a useful nuclear medicine method to differentiate a NET in the pancreatic tail from accessory spleen at the splenic hilum which may avoid unnecessary surgeries in the presence of enhanced tracer uptake or vice versa.

PMID: 33413309 [PubMed - in process]

Recurrence of a neuroendocrine tumor of adrenal origin: a case report with more than a decade follow-up.

Fetched: January 10th, 2021, 5:01am GMT

Recurrence of a neuroendocrine tumor of adrenal origin: a case report with more than a decade follow-up.

BMC Endocr Disord. 2021 Jan 07;21(1):9

Authors: Rahmani F, Tohidi M, Dehghani M, Broumand B, Hadaegh F

Abstract
BACKGROUND: Neuroendocrine tumor (NET) with adrenocorticotropic hormone (ACTH) secretion are very rare. To our knowledge, no follow-up study is published for ACTH-secreting NET, regardless of the primary site, to show second occurrence of tumor after a long follow-up, following resection of primary tumor.
CASE PRESENTATION: Here, we describe a 49-year-old-man with cushingoid feature, drowsiness and quadriparesis came to emergency department at December 2005. Laboratory tests revealed hyperglycemia, metabolic alkalosis, severe hypokalemia, and chemical evidence of an ACTH-dependent hypercortisolism as morning serum cortisol of 57 μg /dL without suppression after 8 mg dexamethasone suppression test, serum ACTH level of 256 pg/mL, and urine free cortisol of > 1000 μg /24 h. Imaging showed only bilateral adrenal hyperplasia, without evidence of pituitary adenoma or ectopic ACTH producing tumors. Importantly, other diagnostic tests for differentiating Cushing disease (CD) from ectopic ACTH producing tumor, such as inferior petrosal sinus sampling (IPSS), corticotropin releasing hormone (CRH) stimulation test, octreotide scan or fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan were not available in our country at that time. Therefore, bilateral adrenalectomy was performed that led to clinical and biochemical remission of hypercortisolism and decreased ACTH level to < 50 pg/mL, findings suggestive of a primary focus of NET in adrenal glands. After 11 years uncomplicated follow up, the ACTH level elevated up to 341 pg/mL and re-evaluation showed a 2 cm nodule in the middle lobe of the right lung. Surgical excision of the pulmonary nodule yielded a carcinoid tumor with positive immunostaining for ACTH; leading to decrease in serum ACTH level to 98 pg/mL. Subsequently after 7 months, serum ACHT levels rose again. More investigation showed multiple lung nodules with metastatic bone lesions accompanied by high serum chromogranin level (2062 ng/mL), and the patient managed as a metastatic NET, with bisphosphonate and somatostatin receptor analogues.
CONCLUSION: This case of surgically-treated NET showing a secondary focus of carcinoid tumor after one decade of disease-free follow-up emphasizes on the importance of long-term follow-up of ACTH-secreting adrenal NET.

PMID: 33413271 [PubMed - in process]

Intraconal Retro-Orbital B-Type Antoni Neurinoma Causing Vision Loss.

Fetched: January 10th, 2021, 5:01am GMT

Intraconal Retro-Orbital B-Type Antoni Neurinoma Causing Vision Loss.

J Craniofac Surg. 2020 Sep;31(6):e597-e599

Authors: Bagaglia SA, Meduri A, Inferrera L, Gennaro P, Gabriele G, Polito E, Fruschelli M, Lorusso N, Tarantello A, Mazzotta C

Abstract
Schwannoma is a rare benign tumor, originating from Schwann cells of the peripheral nerve sheath. We describe a case of intraconal orbital schwannoma, causing compression to the optic nerve and progressive visual impairment treated with surgical resection. The diagnosis of benign orbital schwannoma was provided by histopathological examination (large spindle cell tumor with AntoniB-type cell pattern) and also with immunohistochemistry (positivity for S-100 protein). The 6 months' follow-up was performed. The patient was asymptomatic during the 6-month follow-up.

PMID: 32649535 [PubMed - indexed for MEDLINE]

Delayed Supratentorial Intracerebral Hemorrhage After Posterior Fossa Acoustic Neuroma Surgery.

Fetched: January 10th, 2021, 5:01am GMT

Delayed Supratentorial Intracerebral Hemorrhage After Posterior Fossa Acoustic Neuroma Surgery.

J Craniofac Surg. 2020 Sep;31(6):e592-e593

Authors: Abuzayed B, Alawneh K, Qawasmeh MA, Abdalla K, Al-Ali M, Raffee L

Abstract
A 72-year-old female patient was complaining from gradual loss of hearing in the left ear, left facial palsy with gait imbalance. Neuroimaging showed left cerebellopontine angle extra-axial mass and was diagnosed as acoustic neuroma. She was operated with left retromastoid suboccipital and gross total excision of the tumor was achieved. Early postoperative period was uneventful and brain computed tomographic (CT) scan in the postoperative day 1 showed gross total resection of the tumor without complications, and patient was discharged at the postoperative day 4. In the postoperative day 7, the patient showed decrease level of consciousness and brain CT scan showed a small hematoma in the anterior part of the left temporal lobe, which was evolved to large intraparanchymal hemorrhage with midline shift in postoperative day 9.

PMID: 32604307 [PubMed - indexed for MEDLINE]

Permalink for 'The prognostic landscape of adaptive immune resistance signatures and infiltrating immune cells in the tumor microenvironment of uveal melanoma.'

The prognostic landscape of adaptive immune resistance signatures and infiltrating immune cells in the tumor microenvironment of uveal melanoma.

Fetched: January 10th, 2021, 5:01am GMT

The prognostic landscape of adaptive immune resistance signatures and infiltrating immune cells in the tumor microenvironment of uveal melanoma.

Exp Eye Res. 2020 07;196:108069

Authors: Wang Y, Xu Y, Dai X, Lin X, Shan Y, Ye J

Abstract
Uveal melanoma (UM) is the most common primary intraocular malignancy in adults and has a high mortality rate. Tumor microenvironment (TME) is crucial in controlling and influencing the behavior of malignant tumors. Thus, illustrating the prognostic values of adaptive immune resistance signatures and infiltrating immune cells in the TME of UM may provide scientific rationales for immunotherapy. In this study, the gene expression data of 80 primary UM and 103 primary skin cutaneous melanoma (SKCM) samples with relevant clinical information were obtained from The Cancer Genome Atlas (TCGA) database. The TME was analyzed by the xCell, EPIC, ESTIMATE and TIMER algorithms. The relationships and prognostic values of immune infiltrates and mutated genes were further investigated. We found that primary UM and primary SKCM exhibited distinct TMEs. Higher levels of infiltrating stromal and immune cells in UM were related to more aggressive biology and poor prognosis. Increased CD8+ T cell level, as well as several adaptive immune resistance markers, was a predictive factor of poor prognosis in UM. Furthermore, some common mutations of UM were associated with its TME. This study analyzed the immune landscape of adaptive immune resistance signatures and infiltrating immune cells in the TME of UM. Identification of these immune-related biomarkers may thus enable the prediction of prognosis and the selection of optimal immunotherapy strategies in UM.

PMID: 32439398 [PubMed - indexed for MEDLINE]

Permalink for 'Wide-Field (15 × 9 mm) Swept-Source Optical Coherence Tomography Angiography Following Plaque Radiotherapy of Choroidal Melanoma: An Analysis of 105 eyes.'

Wide-Field (15 × 9 mm) Swept-Source Optical Coherence Tomography Angiography Following Plaque Radiotherapy of Choroidal Melanoma: An Analysis of 105 eyes.

Fetched: January 10th, 2021, 5:01am GMT

Wide-Field (15 × 9 mm) Swept-Source Optical Coherence Tomography Angiography Following Plaque Radiotherapy of Choroidal Melanoma: An Analysis of 105 eyes.

Asia Pac J Ophthalmol (Phila). 2020 Jul-Aug;9(4):326-334

Authors: Lim LS, Camp DA, Ancona-Lezama D, Mazloumi M, Patel SP, McLaughlin JW, Ferenczy SR, Mashayekhi A, Shields CL

Abstract
PURPOSE: The aim of this study was to evaluate retinal microvascular abnormalities following plaque radiotherapy of choroidal melanoma (CM) using wide-field swept-source optical coherence tomography angiography (OCTA).
DESIGN: Single-centre retrospective review.
METHODS: Retrospective case series of 105 CM patients treated with I-125 plaque radiotherapy and imaged with wide-field (15 × 9 mm) SS-OCTA from March 2018 to August 2018 at the Ocular Oncology Service, Wills Eye Hospital (Philadelphia, PA).
RESULTS: At mean follow-up of 49 months (range 4-297) after plaque radiotherapy, there were 52 eyes (50%) with clinically evident radiation retinopathy (CERR) and 53 eyes (50%) without CERR. Comparison (CERR vs controls) revealed foveal avascular zone enlargement (1.7 vs 0.23 mm, P = 0.03) and reduction of capillary vascular density (CVD) in the superficial and deep plexus in the total wide-field (43% vs 47%, P < 0.001, and 46% vs 48%, P = 0.001, respectively), peripapillary region (66% vs 77%, P < 0.001, and 66% vs 72%, P = 0.001, respectively), and papillomacular bundle (60% vs 68%, P < 0.001, and 61% vs 64%, P = 0.03, respectively). Comparison (no CERR vs controls) revealed nonsignificant foveal avascular zone enlargement (1.20 vs 0.23 mm, P = 0.16) and reduction of CVD in the superficial plexus (46% vs 47%, P = 0.008), and not the deep plexus (48% vs 48%, P = 0.42) of the total wide-field. Comparison of irradiated eyes (CERR vs no CERR) showed reduction of CVD in the superficial and deep plexus of the total wide-field (43% vs 46%, P < 0.006, and 46% vs 48% P < 0.02, respectively), peripapillary region (66% vs 74%, P < 0.001, and 66% vs 72% P < 0.01, respectively), and superficial plexus in the papillomacular bundle (60% vs 65%, P = 0.03).
CONCLUSIONS: Following plaque radiotherapy for choroidal melanoma, wide-field swept-source optical coherence tomography angiography demonstrates retinal microvascular abnormalities in the CVD in eyes with and without CERR. These findings are important in early detection and monitoring of radiation retinopathy.

PMID: 32371740 [PubMed - indexed for MEDLINE]

BRAFi induced demethylation of miR-152-5p regulates phenotype switching by targeting TXNIP in cutaneous melanoma.

Fetched: January 10th, 2021, 5:01am GMT

BRAFi induced demethylation of miR-152-5p regulates phenotype switching by targeting TXNIP in cutaneous melanoma.

Apoptosis. 2020 04;25(3-4):179-191

Authors: Li K, Tang M, Tong S, Wang C, Sun Q, Lv M, Sun X, Wang T, Jin S

Abstract
Treatment of advanced BRAFV600-mutant melanoma using BRAF inhibitors (BRAFi) eventually leads to drug resistance and selects for highly metastatic tumor cells. We compared the most differentially dysregulated miRNA expression profiles of vemurafenib-resistant and highly-metastatic melanoma cell lines obtained from GEO DataSets. We discovered miR-152-5p was a potential regulator mediating melanoma drug resistance and metastasis. Functionally, knockdown of miR-152-5p significantly compromised the metastatic ability of BRAFi-resistant melanoma cells and overexpression of miR-152-5p promoted the formation of slow-cycling phenotype. Furthermore, we explored the cause of how and why miR-152-5p affected metastasis in depth. Mechanistically, miR-152-5p targeted TXNIP which affected metastasis and BRAFi altered the methylation status of MIR152 promoter. Our study highlights the crucial role of miR-152-5p on melanoma metastasis after BRAFi treatment and holds significant implying that discontinuous dosing strategy may improve the benefit of advanced BRAFV600-mutant melanoma patients.

PMID: 32056038 [PubMed - indexed for MEDLINE]

Biomimetic Decoy Inhibits Tumor Growth and Lung Metastasis by Reversing the Drawbacks of Sonodynamic Therapy.

Fetched: January 10th, 2021, 5:01am GMT

Biomimetic Decoy Inhibits Tumor Growth and Lung Metastasis by Reversing the Drawbacks of Sonodynamic Therapy.

Adv Healthc Mater. 2020 01;9(1):e1901335

Authors: Zhao H, Zhao B, Li L, Ding K, Xiao H, Zheng C, Sun L, Zhang Z, Wang L

Abstract
Sonodynamic therapy (SDT) shows tremendous potential to induce immunogenic cell death (ICD) and activate antitumor immunity. However, it can aggravate hypoxia and release platelet (PLT)-associated danger-associated molecular patterns (DAMPs), which impede therapeutic efficacy and promote tumor metastasis. In order to solve these problems, a biomimetic decoy (designated as Lipo-Ce6/TPZ@MH ) is constructed to reverse the drawbacks of SDT by loading sonosensitizer chlorin e6 (Ce6) and hypoxia-activated tirapazamine (TPZ) in the red blood cells-PLTs hybrid membrane (MH )-camouflaged pH-sensitive liposome. After administration, the decoy exhibits enhanced cancer accumulation and retention abilities due to the immune escape and specific targeting behaviors by biomimetic surface coating. Upon local ultrasound, Ce6 produces toxic reactive oxygen species for SDT, and the resulting hypoxia microenvironment activates TPZ, which can realize a high-effective synergistic therapy. Meanwhile, DAMPs-mediated tumor metastasis is significantly inhibited, because the decoy retains platelet binding functions but is incapable of platelet-mediated metastasis. In addition, ICD-mediated strong antitumor immunities further prevent the growth and metastasis of the residual tumors left behind after synergistic treatment. Taken together, this study highlights the potential of using this cascade therapeutic therapy plus biomemitic decoy in one nanosystem to both eliminate melanoma in situ and suppress lung metastasis.

PMID: 31762228 [PubMed - indexed for MEDLINE]

Melanoma Incidence Among Non-Hispanic Whites in All 50 US States From 2001 Through 2015.

Fetched: January 10th, 2021, 5:01am GMT

Melanoma Incidence Among Non-Hispanic Whites in All 50 US States From 2001 Through 2015.

J Natl Cancer Inst. 2020 05 01;112(5):533-539

Authors: Thrift AP, Gudenkauf FJ

Abstract
BACKGROUND: The United States has large regional variation in primary prevention campaigns for skin cancer. We collected data from all 50 states to examine changes in melanoma incidence and performed age-period-cohort analyses to describe the simultaneous effects of age, period, and cohort on incidence rates.
METHODS: Annual melanoma incidence rates for non-Hispanic whites from 2001 to 2015 were extracted from the US Cancer Statistics registry. Secular trends were examined overall and by sex and state. We used joinpoint regression to compute annual percent change and average annual percent change and corresponding 95% confidence intervals (CIs). We also analyzed incidence trends by 5-year age group and birth cohort using incidence rate ratios and age-period-cohort modeling.
RESULTS: Melanoma incidence increased from 20.7 per 100 000 (95% CI = 20.5 to 20.9) in 2001 to 28.2 per 100 000 (95% CI = 28.0 to 28.5) in 2015, increasing by 3.90% (95% CI = 2.36% to 5.48%) annually between 2001 and 2005 and 1.68% (95% CI = 1.37% to 1.99%) annually from 2005 through 2015. The average annual percent change in melanoma incidence rates were similar for men (2.34%, 95% CI = 1.91 to 2.78) and women (2.25%, 95% CI = 1.60 to 2.91). Age-specific relative risk by birth cohort increased from circa 1921 to 1981 before decreasing. Compared with adults born circa 1956, those born circa 1991 had lower melanoma risk (incidence rate ratio = 0.85; 95% CI = 0.77 to 0.94). Geographic variation was observed; some states still have melanoma rates trending upwards in all birth cohorts.
CONCLUSIONS: The continued increase in melanoma incidence among non-Hispanic whites, particularly in states where rates continue to rise among recent and current birth cohorts, underscores the need for increased public health campaigns aimed at reducing sun exposure.

PMID: 31346623 [PubMed - indexed for MEDLINE]

Risk of lymph node metastasis after endoscopic treatment for rectal NETs 10 mm or less.

Fetched: January 5th, 2021, 5:01am GMT

Risk of lymph node metastasis after endoscopic treatment for rectal NETs 10 mm or less.

Int J Colorectal Dis. 2021 Jan 02;:

Authors: Inada Y, Yoshida N, Fukumoto K, Hirose R, Inoue K, Dohi O, Murakami T, Ogiso K, Tomie A, Kugai M, Yoriki H, Inagaki Y, Hasegawa D, Okuda K, Okuda T, Morinaga Y, Kishimoto M, Itoh Y

Abstract
PURPOSE: For rectal neuroendocrine tumors (NETs) ≤ 10 mm, endoscopic resection is a standard treatment. However, there is no consensus whether additional surgery should be performed for patients at risk of lymph node metastasis (LNM) after endoscopic resection. The purpose of this study was to analyze the results of endoscopic resection and additional surgery of rectal NETs, thereby clarify the characteristics of cases with LNM.
METHODS: This study was a multicenter retrospective cohort study conducted at 12 Japanese institutions. A total of 132 NETs ≤ 10 mm were analyzed regarding various therapeutic results. A comparative analysis was performed by dividing the cases into two groups that underwent additional surgery or not. Furthermore, the relationship between tumor size and LNM was examined.
RESULTS: The endoscopic treatments were 12 endoscopic mucosal resections (EMR), 58 endoscopic submucosal resections with ligation (ESMR-L), 29 precutting EMRs, and 33 endoscopic submucosal dissections (ESD). The R0 resection rates of EMR were 41.7%, and compared to this rate, other three treatments were 86.2% (p < 0.001), 86.2% (p = 0.005), and 97.0% (p < 0.001), respectively. There were 41 non-curative cases (31.1%), and 13 had undergone additional surgery. Then, LNM was observed in 4 of the 13 patients, with an overall rate of LNM of 3.0% (4/132). The rate of positive lymphatic invasion and the rate of LNM by tumor size ≤ 6 mm and 7-10 mm were 9.7 vs. 15.4% (p = 0.375) and 0 vs. 10.3% (p = 0.007).
CONCLUSIONS: A multicenter study revealed the priority of each endoscopic resection and the low rate of LNM for rectal NETs ≤ 6 mm.

PMID: 33388960 [PubMed - as supplied by publisher]

Adrenal ectopy and lipoma of an inguinal hernia sac: A case report & literature review.

Fetched: January 5th, 2021, 5:01am GMT

Adrenal ectopy and lipoma of an inguinal hernia sac: A case report & literature review.

Int J Surg Case Rep. 2020 Dec 28;78:356-358

Authors: Adalbert JR, Pajaro RE

Abstract
INTRODUCTION & IMPORTANCE: Ectopic adrenocortical tissue is the presence of accessory adrenal cortex tissue located outside of the adrenal glands. It is a rare, incidental finding during inguinal hernia repair. This case report aims to discuss the anatomy and important patient implications related to this finding.
CASE PRESENTATION: A 61-year-old male presented with a long-standing right direct inguinal hernia increasing in size and pain frequency. During open right anterior inguinal hernia repair, a lipoma was identified inside the hernia sac and removed. Further histopathological examination of the specimen revealed the presence of adrenocortical tissue inside the lipoma. No further interventions were performed. The postoperative and 2-year follow-up course were uneventful.
CLINICAL DISCUSSION: Adrenocortical tissue can parallel the descent of the gonads during embryogenesis, arresting at any point along this path, including the inguinal region. Ectopic adrenocortical tissue is commonly found during inguinoscrotal procedures in infants, suggesting early involution. Its incidence in hernia sacs should be recognized to prevent misdiagnosis as neuroendocrine tumors or melanomas. If adrenocortical tissue is identified during hernia reduction, further surgical exploration is not recommended. In terms of prognosis, endocrine imbalances following surgical removal cannot be ruled out, promoting careful patient monitoring. The lipoma containing the adrenal tissue in our case is a common finding during hernia repair, identified in 22% of patients at operation.
CONCLUSION: Ectopic adrenocortical tissue is a rare, incidental finding during inguinal hernia sac analysis in adults. This finding should be well-documented following removal and further studies are required to evaluate long-term outcomes.

PMID: 33388518 [PubMed - as supplied by publisher]

Clear cell neuroendocrine tumor in the gallbladder diagnosed as a benign polyp preoperatively: a case report.

Fetched: January 5th, 2021, 5:01am GMT

Clear cell neuroendocrine tumor in the gallbladder diagnosed as a benign polyp preoperatively: a case report.

World J Surg Oncol. 2021 Jan 02;19(1):3

Authors: Sumiya R, Shimizu A, Nagai T, Ono H, Kumazawa K, Endo D, Oide T, Aoyanagi N

Abstract
BACKGROUND: Gallbladder neuroendocrine neoplasm is a rare disease that is divided into neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs). Clear cell NETs of the gallbladder are extremely rare. We report the case of a patient with polypoid clear cell NET G1 of the gallbladder who underwent laparoscopic cholecystectomy.
CASE PRESENTATION: A 10-mm pedunculated polyp in the gallbladder neck was detected on a follow-up abdominal ultrasound in a 60-year-old man with chronic hepatitis and hepatitis B without medication. Six months later, an abdominal ultrasound revealed that the tumor had enlarged to 12 mm in size. He was asymptomatic and had no abnormalities in other laboratory examinations, including the tumor markers, carcinoembryonic antigen and CA19-9. Abdominal ultrasound showed a 12-mm polyp in the neck of the gallbladder with perfusion and focal thickening of the gallbladder wall. A gallbladder stone was also seen in the fundus. An enhanced computed tomography scan and magnetic resonance imaging revealed a polypoid lesion and gallbladder stone located at the neck of the gallbladder and the fundus, respectively. Malignancy could not be excluded, and hence, a laparoscopic cholecystectomy was performed. Pathologically, a pedunculated polyp (14 × 11 × 15 mm) was observed in the neck of the gallbladder, and the polypoid lesion comprised nests or trabecular growths of clear NET cells in the lamina propria (ENETS: T1N0M0; AJCC: T1aN0M0). Immunohistochemical staining with synaptophysin, chromogranin A, and CD56 was confined to the tumor. The pathological diagnosis was clear cell NET G1 of the gallbladder. Although clear cell NET is often described as a distinct manifestation of von Hippel-Lindau disease (VHL), the patient had no past medical or family history of VHL. Until his one-and-a-half-year follow-up, the patient was doing well and without any signs of recurrence.
CONCLUSION: We report an extremely rare case of gallbladder clear cell NET G1. When NET G1 is incidentally identified in a gallbladder surgical specimen, clinical information and pathological findings should be considered as references.

PMID: 33388069 [PubMed - in process]

Chromogranin A and NSE in cystic pancreatic neuroendocrine tumors.

Fetched: January 4th, 2021, 5:01am GMT

Chromogranin A and NSE in cystic pancreatic neuroendocrine tumors.

Clin Res Hepatol Gastroenterol. 2020 Dec 29;:101601

Authors: Faias S, Prazeres S, Cunha M, Pereira L, Roque R, Chaves P, Cravo M, Claro I, Silveira M, Leite V, Dias Pereira A

PMID: 33386244 [PubMed - as supplied by publisher]

Survival outcomes in sinonasal carcinoma with neuroendocrine differentiation: A NCDB analysis.

Fetched: January 3rd, 2021, 5:00am GMT

Survival outcomes in sinonasal carcinoma with neuroendocrine differentiation: A NCDB analysis.

Am J Otolaryngol. 2020 Dec 17;42(2):102851

Authors: Issa K, Ackall F, Jung SH, Li J, Jang DW, Rangarajan SV, Abi Hachem R

Abstract
BACKGROUND: Sinonasal carcinoma with neuroendocrine differentiation (SCND) is a rare group of tumors with poor prognosis. Treatment and sequence of therapies are still unclear. The goal of this study is to analyze treatment outcomes in SCND using a national database.
METHODS: The National Cancer Database was queried for SCND from 2004 to 2014. Patient demographics, tumor characteristics and treatment paradigms were tabulated. Multivariable Cox proportional hazards regression was performed for statistical analysis of treatment regimen on overall survival (OS).
RESULTS: A total of 415 patients were identified. Most patients were male (61.2%), with a median age of 58 years and the most common primary site was the nasal cavity (52.5%). T4 tumors were observed in 67.7% of cases. Unimodality (41.9%) and bimodality (43.9%) therapies were the most common treatment modalities. Radiation therapy was the only treatment administered in 30% of the patients, while 27.2% received definitive chemoradiation (CRT) and 11.6% had surgery with adjuvant CRT. In our Cox-PH model, age (HR = 1.04, p < 0.001), T4 (HR = 2.6, p = 0.004) and N2/N3 (HR = 2.18, p = 0.001) were associated with worse survival. Trimodality (HR = 0.49, p = 0.005) and bimodality (HR = 0.65, p = 0.009) therapies had a better OS compared to unimodality. Patients treated with definitive CRT or surgery with adjuvant CRT had a significant increase in OS (p = 0.01 and 0.002 respectively).
CONCLUSION: SCND appears to be best treated using a multimodality approach with definitive CRT or surgery followed by CRT. Neoadjuvant chemotherapy could be helpful in selecting the best treatment strategy.

PMID: 33385873 [PubMed - as supplied by publisher]

Clinical Epigenetics of Neuroendocrine Tumors: The Road Ahead.

Fetched: January 3rd, 2021, 5:00am GMT

Clinical Epigenetics of Neuroendocrine Tumors: The Road Ahead.

Front Endocrinol (Lausanne). 2020;11:604341

Authors: Colao A, de Nigris F, Modica R, Napoli C

Abstract
Neuroendocrine tumors, or NETs, are cancer originating in neuroendocrine cells. They are mostly found in the gastrointestinal tract or lungs. Functional NETs are characterized by signs and symptoms caused by the oversecretion of hormones and other substances, but most NETs are non-functioning and diagnosis in advanced stages is common. Thus, novel diagnostic and therapeutic strategies are warranted. Epigenetics may contribute to refining the diagnosis, as well as to identify targeted therapy interfering with epigenetic-sensitive pathways. The goal of this review was to discuss the recent advancement in the epigenetic characterization of NETs highlighting their role in clinical findings.

PMID: 33384663 [PubMed - in process]

Histopathological Chromogranin A-Positivity Is Associated with Right-Sided Colorectal Cancers and Worse Prognosis.

Fetched: January 3rd, 2021, 5:00am GMT

Histopathological Chromogranin A-Positivity Is Associated with Right-Sided Colorectal Cancers and Worse Prognosis.

Cancers (Basel). 2020 Dec 29;13(1):

Authors: Herold Z, Dank M, Herold M, Nagy P, Rosta K, Somogyi A

Abstract
BACKGROUND: Colorectal cancer (CRC) is known to be affected by paraneoplastic thrombocytosis and chromogranin A-positive neuroendocrine-cell differentiation (CgA+). Their combined effect has never been previously investigated.
METHODS: A prospective cohort pilot study of 42 CRC patients and 42 age- and sex-matched controls was carried out. Plasma interleukin-6, thrombopoietin, and serum chromogranin A and -B were measured; furthermore, tumor tissue was immunohistochemically stained for CgA+.
RESULTS: Twenty-seven and 15 patients were assigned to the chromogranin A-negative (CgA-) and CgA+ groups, respectively. Within the CgA+ group, right-sided tumors were more frequent (18.5% vs. 53.3%), no stage I cancer was found, and patients of this group were in worse general condition. Compared to control subjects, chromogranin A level was higher in the CgA+ group (p = 0.0086), thrombopoietin (p = 0.0040) and chromogranin B (p = 0.0070) in the CgA- group, while interleukin-6 was high in both tumor groups (p ≤ 0.0090). Survival was significantly worse in the CgA+ group (hazard ratio: 5.73; p = 0.0378).
CONCLUSIONS: Different thrombopoietin levels indicated distinct thrombocytosis types. Within the two CRC groups, serum levels of chromogranins changed in different directions suggesting two well-distinguishable pathophysiologies. Based on these observations we propose a new subtype of CRC, which can be characterized by chromogranin A-positive neuroendocrine-cell differentiation.

PMID: 33383764 [PubMed]

Emerging Therapies in Pheochromocytoma and Paraganglioma: Immune Checkpoint Inhibitors in the Starting Blocks.

Fetched: January 3rd, 2021, 5:00am GMT

Emerging Therapies in Pheochromocytoma and Paraganglioma: Immune Checkpoint Inhibitors in the Starting Blocks.

J Clin Med. 2020 Dec 29;10(1):

Authors: Fanciulli G, Di Molfetta S, Dotto A, Florio T, Feola T, Rubino M, de Cicco F, Colao A, Faggiano A, Nike Group

Abstract
Pheochromocytoma and paraganglioma are neuroendocrine neoplasms, originating in the adrenal medulla and in parasympathetic and sympathetic autonomic nervous system ganglia, respectively. They usually present as localized tumours curable with surgery. However, these tumours may exhibit heterogeneous clinical course, ranging from no/minimal progression to aggressive (progressive/metastatic) behavior. For this setting of patients, current therapies are unsatisfactory. Immune checkpoint inhibitors have shown outstanding results for several types of solid cancers. We therefore aimed to summarize and discuss available data on efficacy and safety of current FDA-approved immune checkpoint inhibitors in patients with pheochromocytoma and paraganglioma. After an extensive search, we found 15 useful data sources (four full-published articles, four supplements of scientific journals, seven ongoing registered clinical trials). The data we detected, even with the limit of the small number of patients treated, make a great expectation on the therapeutic use of immune checkpoint inhibitors. Besides, the newly detected predictors of response will (hopefully) be of great helps in selecting the subset of patients that might benefit the most from this class of drugs. Finally, new trials are in the starting blocks, and they are expected to shed in the next future new light on a therapy, which is considered a milestone in oncology.

PMID: 33383673 [PubMed]

Clinical features and survival outcomes of ocular melanoma in a multi-ethnic Asian cohort.

Fetched: January 3rd, 2021, 5:00am GMT

Clinical features and survival outcomes of ocular melanoma in a multi-ethnic Asian cohort.

Sci Rep. 2020 10 01;10(1):16367

Authors: Tan LLY, Hong J, Goh WL, Chang EWY, Yang VS, Poon E, Somasundaram N, Farid M, Chan ASY, Chan JY

Abstract
Ocular melanomas are uncommon cancers in Southeast Asia unlike in the West. We conducted a retrospective review of patients (n = 44) with histologically-proven ocular melanoma within a multi-ethnic Asian cohort from Singapore. Clinicopathological features and relapse patterns were examined, and survival outcomes of interest included recurrence-free survival (RFS) and overall survival (OS). Survival analysis was performed using the Kaplan-Meier method and multivariable Cox proportional regression. The study cohort included 18 male and 26 female patients, with a median age of 52 years (range 8-78). Median follow-up was 154 months. For uveal melanomas (n = 29), the 5-year RFS and OS was 56.8% and 76.6%, respectively; whilst for conjunctival melanomas (n = 15), the 5-year RFS and OS was 30.1% and 68.8%, respectively. Fifteen patients (38.5%) eventually developed metastasis, following which the median survival was only 17 months. Multivariate analysis demonstrated that higher T stage was a significant independent predictor for both OS (HR 8.69, 95% CI 1.03 to 73.09, p = 0.047) and RFS (HR 11.62, 95% CI 2.45 to 55.00, p = 0.002). Smoking history was independently predictive of better RFS (HR 0.08, 95% CI 0.01 to 0.78, p = 0.030). In conclusion, our study demonstrates the poor ocular melanoma outcomes in Southeast Asians, highlighting the necessity for urgent research in this area of unmet clinical need.

PMID: 33004998 [PubMed - indexed for MEDLINE]

Permalink for 'Challenges in diagnosis and management of neutropenia upon exposure to immune-checkpoint inhibitors: meta-analysis of a rare immune-related adverse side effect.'

Challenges in diagnosis and management of neutropenia upon exposure to immune-checkpoint inhibitors: meta-analysis of a rare immune-related adverse side effect.

Fetched: January 3rd, 2021, 5:00am GMT

Challenges in diagnosis and management of neutropenia upon exposure to immune-checkpoint inhibitors: meta-analysis of a rare immune-related adverse side effect.

BMC Cancer. 2020 Apr 14;20(1):300

Authors: Boegeholz J, Brueggen CS, Pauli C, Dimitriou F, Haralambieva E, Dummer R, Manz MG, Widmer CC

Abstract
BACKGROUND: Cancer immunotherapy via immune-checkpoint inhibition (ICI) by antibodies against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and cell death protein 1 (PD-1) have significantly improved the outcome of metastasized melanoma and of a rapidly increasing number of other cancer types. The anti-tumor effect is often accompanied by immune-related adverse events (irAE). Hematological irAE, specifically neutropenia, are rarely observed. However, neutropenia is associated with high morbidity and mortality due to infection complications. Thus, early detection and treatment is crucial.
METHODS: We present the clinical course of two patients with severe neutropenia after ICI therapy and demonstrate the difficulty of the diagnosis when a comedication of metamizole, a well-known analgesic drug used to treat cancer pain, is present. Further, we provide a comprehensive descriptive and statistical analysis of published data on diagnostics, treatment and infection complication in patients with at least grade 4 neutropenia by a systematic database search.
RESULTS: Finally, 34 patients were analyzed, including the two case reports from our cohort. The median onset of neutropenia was 10.5 weeks after first ICI administration (interquartile range: 6 weeks). In 76% (N = 26), a normalization of the neutrophil count was achieved after a median duration of neutropenia of 13 days. In a subsample of 22 patients with detailed data, the infection rate was 13%, proven by positive blood culture in 3 cases, but 68% (N = 15) presented with fever > 38 °C. Treatment regime differed relevantly, but mainly included G-CSF and intravenous corticosteroids. Death was reported in 14 patients (41%), 3 of whom (9%) were associated with hematological irAE but only two directly associated with neutropenia.
CONCLUSION: With an increasing number of cancer patients eligible to ICI therapy, the incidence of severe hematological toxicities may rise substantially over the next years. Clinicians working in the field of cancer immune therapies should be aware of neutropenia as irAE to provide immediate treatment.

PMID: 32290812 [PubMed - indexed for MEDLINE]

Permalink for 'Comprehensive routine diagnostic screening to identify predictive mutations, gene amplifications, and microsatellite instability in FFPE tumor material.'

Comprehensive routine diagnostic screening to identify predictive mutations, gene amplifications, and microsatellite instability in FFPE tumor material.

Fetched: January 3rd, 2021, 5:00am GMT

Comprehensive routine diagnostic screening to identify predictive mutations, gene amplifications, and microsatellite instability in FFPE tumor material.

BMC Cancer. 2020 Apr 07;20(1):291

Authors: Steeghs EMP, Kroeze LI, Tops BBJ, van Kempen LC, Ter Elst A, Kastner-van Raaij AWM, Hendriks-Cornelissen SJB, Hermsen MJW, Jansen EAM, Nederlof PM, Schuuring E, Ligtenberg MJL, Eijkelenboom A

Abstract
BACKGROUND: Sensitive and reliable molecular diagnostics is needed to guide therapeutic decisions for cancer patients. Although less material becomes available for testing, genetic markers are rapidly expanding. Simultaneous detection of predictive markers, including mutations, gene amplifications and MSI, will save valuable material, time and costs.
METHODS: Using a single-molecule molecular inversion probe (smMIP)-based targeted next-generation sequencing (NGS) approach, we developed an NGS panel allowing detection of predictive mutations in 33 genes, gene amplifications of 13 genes and microsatellite instability (MSI) by the evaluation of 55 microsatellite markers. The panel was designed to target all clinically relevant single and multiple nucleotide mutations in routinely available lung cancer, colorectal cancer, melanoma, and gastro-intestinal stromal tumor samples, but is useful for a broader set of tumor types.
RESULTS: The smMIP-based NGS panel was successfully validated and cut-off values were established for reliable gene amplification analysis (i.e. relative coverage ≥3) and MSI detection (≥30% unstable loci). After validation, 728 routine diagnostic tumor samples including a broad range of tumor types were sequenced with sufficient sensitivity (2.4% drop-out), including samples with low DNA input (< 10 ng; 88% successful), low tumor purity (5-10%; 77% successful), and cytological material (90% successful). 75% of these tumor samples showed ≥1 (likely) pathogenic mutation, including targetable mutations (e.g. EGFR, BRAF, MET, ERBB2, KIT, PDGFRA). Amplifications were observed in 5.5% of the samples, comprising clinically relevant amplifications (e.g. MET, ERBB2, FGFR1). 1.5% of the tumor samples were classified as MSI-high, including both MSI-prone and non-MSI-prone tumors.
CONCLUSIONS: We developed a comprehensive workflow for predictive analysis of diagnostic tumor samples. The smMIP-based NGS analysis was shown suitable for limited amounts of histological and cytological material. As smMIP technology allows easy adaptation of panels, this approach can comply with the rapidly expanding molecular markers.

PMID: 32264863 [PubMed - indexed for MEDLINE]

Hypericin photodynamic activity in DPPC liposomes - part II: stability and application in melanoma B16-F10 cancer cells.

Fetched: January 3rd, 2021, 5:00am GMT

Hypericin photodynamic activity in DPPC liposomes - part II: stability and application in melanoma B16-F10 cancer cells.

Photochem Photobiol Sci. 2020 May 01;19(5):620-630

Authors: de Morais FAP, Gonçalves RS, Vilsinski BH, Lazarin-Bidóia D, Balbinot RB, Tsubone TM, Brunaldi K, Vatatu Nakamura C, Hioka N, Caetano W

Abstract
Hypericin (Hyp) is considered a promising photosensitizer for Photodynamic Therapy (PDT), due to its high hydrophobicity, affinity for cell membranes, low toxicity and high photooxidation activity. In this study, Hyp photophysical properties and photodynamic activity against melanoma B16-F10 cells were optimized using DPPC liposomes (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) as a drug delivery system. This nanoparticle is used as a cell membrane biomimetic model and solubilizes hydrophobic drugs. Hyp oxygen singlet lifetime (τ) in DPPC was approximately two-fold larger than that in P-123 micelles (Pluronic™ surfactants), reflecting a more hydrophobic environment provided by the DPPC liposome. On the other hand, singlet oxygen quantum yield values (ΦΔ1O2) in DPPC and P-123 were similar; Hyp molecules were preserved as monomers. The Hyp/DPPC liposome aqueous dispersion was stable during fluorescence emission and the liposome diameter remained stable for at least five days at 30 °C. However, the liposomes collapsed after the lyophilization/rehydration process, which was resolved by adding the lyoprotectant Trehalose to the liposome dispersion before lyophilization. Cell viability of the Hyp/DPPC formulation was assessed against healthy HaCat cells and high-metastatic melanoma B16-F10 cells. Hyp incorporated into the DPPC carrier presented a higher selectivity index than the Hyp sample previously solubilized in ethanol under the illumination effect. Moreover, the IC50 was lower for Hyp in DPPC than for Hyp pre-solubilized in ethanol. These results indicate the potential of the formulation of Hyp/DPPC for future biomedical applications in PDT treatment.

PMID: 32248218 [PubMed - indexed for MEDLINE]

Permalink for 'Melanoma xenotransplant on the chicken chorioallantoic membrane: a complex biological model for the study of cancer cell behaviour.'

Melanoma xenotransplant on the chicken chorioallantoic membrane: a complex biological model for the study of cancer cell behaviour.

Fetched: January 3rd, 2021, 5:00am GMT

Melanoma xenotransplant on the chicken chorioallantoic membrane: a complex biological model for the study of cancer cell behaviour.

Histochem Cell Biol. 2020 Aug;154(2):177-188

Authors: Strnadová K, Španko M, Dvořánková B, Lacina L, Kodet O, Shbat A, Klepáček I, Smetana K

Abstract
The globally increasing incidence of cancer, including melanoma, requires novel therapeutic strategies. Development of successful novel drugs is based on clear identification of the target mechanisms responsible for the disease progression. The specific cancer microenvironment represents a critically important aspect of cancer biology, which cannot be properly studied in simplistic cell culture conditions. Among other traditional options, the study of melanoma cell growth on the chicken chorioallantoic membrane offers several significant advantages. This model offers increased complexity compared to usual in silico culture models and still remains financially affordable. Using this model, we studied the growth of three established human melanoma cell lines: A2058, BLM, G361. The combination of histology, immunohistochemistry with the application of human-specific antibodies, intravascular injection of contrast material such as filtered Indian ink, Mercox solution and phosphotungstic acid, and X-ray micro-CT and live-cell monitoring was employed. Melanoma cells spread well on the chicken chorioallantoic membrane. However, invasion into the stroma of the chorioallantoic membrane and the limb primordium graft was rare. The melanoma cells also significantly influenced the architecture of the blood vessel network, resulting in the orientation of the vessels to the site of the tumour cell inoculation. The system of melanoma cell culture on the chorioallantoic membrane is suitable for the study of melanoma cell growth, particularly of rearrangement of the host vascular pattern after cancer cell implantation. The system also has promising potential for further development.

PMID: 32232553 [PubMed - indexed for MEDLINE]

Carbon-Fiber Nanoelectrodes for Real-Time Discrimination of Vesicle Cargo in the Native Cellular Environment.

Fetched: January 3rd, 2021, 5:00am GMT

Carbon-Fiber Nanoelectrodes for Real-Time Discrimination of Vesicle Cargo in the Native Cellular Environment.

ACS Nano. 2020 03 24;14(3):2917-2926

Authors: Roberts JG, Mitchell EC, Dunaway LE, McCarty GS, Sombers LA

Abstract
Carbon-fiber microelectrodes have proven to be an indispensable tool for monitoring exocytosis events using amperometry. When positioned adjacent to a cell, a traditional microdisc electrode is well suited for quantification of discrete exocytotic release events. However, the size of the electrode does not allow for intracellular electrochemical measurements, and the amperometric approach cannot distinguish between the catecholamines that are released. In this work, carbon nanoelectrodes were developed to permit selective electrochemical sampling of nanoscale vesicles in the cell cytosol. Classical voltammetric techniques and electron microscopy were used to characterize the nanoelectrodes, which were ∼5 μm long and sharpened to a nanometer-scale tip that could be wholly inserted into individual neuroendocrine cells. The nanoelectrodes were coupled with fast-scan cyclic voltammetry to distinguish secretory granules containing epinephrine from other catecholamine-containing granules encountered in the native cellular environment. Both vesicle subtypes were encountered in most cells, despite prior demonstration of populations of chromaffin cells that preferentially release one of these catecholamines. There was substantial cell-to-cell variability in relative epinephrine content, and vesicles containing epinephrine generally stored more catecholamine than the other vesicles. The carbon nanoelectrode technology thus enabled analysis of picoliter-scale biological volumes, revealing key differences between chromaffin cells at the level of the dense-core granule.

PMID: 32058693 [PubMed - indexed for MEDLINE]

Increasing the Potential Interacting Area of Nanomedicine Enhances Its Homotypic Cancer Targeting Efficacy.

Fetched: January 3rd, 2021, 5:00am GMT

Increasing the Potential Interacting Area of Nanomedicine Enhances Its Homotypic Cancer Targeting Efficacy.

ACS Nano. 2020 03 24;14(3):3259-3271

Authors: Zhu J, Sevencan C, Zhang M, McCoy RSA, Ding X, Ye J, Xie J, Ariga K, Feng J, Bay BH, Leong DT

Abstract
The cancer cell membrane contains an arsenal of highly specific homotypic moieties that can be used to recognize its own kind. These cell membranes are often used to coat spherical nanoparticles to enhance nanomedicines' targeting specificities and uptakes. A sphere, however, has only a point contact with a surface at any given time. It is shown here that, by retaining a flatter morphology of the cracked cell membrane through stiffening with in situ synthesized gold nanomaterials, an increased area of interaction could be maintained and hence improve upon the in vitro and in vivo homotypic targeting capabilities between cancer cell types. This enhancement is especially important in vivo as any nanomedicine with targeting moieties probably has a single pass at interacting with the target cell before subsequent system clearance. Possible future clinical applications may involve the usage of a patient's autologous tumor biopsy tissues, which are very limited in supply, and therefore ensuring that we capitalize on the entire collective surface area of the cancer cell membrane available becomes an important consideration in the design and delivery our cell membrane-derived nanomedicines.

PMID: 32049490 [PubMed - indexed for MEDLINE]

Permalink for 'Bioactive Anti-inflammatory, Antibacterial, Antioxidative Silicon-Based Nanofibrous Dressing Enables Cutaneous Tumor Photothermo-Chemo Therapy and Infection-Induced Wound Healing.'

Bioactive Anti-inflammatory, Antibacterial, Antioxidative Silicon-Based Nanofibrous Dressing Enables Cutaneous Tumor Photothermo-Chemo Therapy and Infection-Induced Wound Healing.

Fetched: January 3rd, 2021, 5:00am GMT

Bioactive Anti-inflammatory, Antibacterial, Antioxidative Silicon-Based Nanofibrous Dressing Enables Cutaneous Tumor Photothermo-Chemo Therapy and Infection-Induced Wound Healing.

ACS Nano. 2020 03 24;14(3):2904-2916

Authors: Xi Y, Ge J, Wang M, Chen M, Niu W, Cheng W, Xue Y, Lin C, Lei B

Abstract
Traditional skin tumor surgery and chronic bacterial-infection-induced wound healing/skin regeneration is still a challenge. The ideal strategy should eliminate the tumor, enhance wound healing/skin formation, and be anti-infection. Herein, we designed a multifunctional elastomeric poly(l-lactic acid)-poly(citrate siloxane)-curcumin@polydopamine hybrid nanofibrous scaffold (denoted as PPCP matrix) for tumor-infection therapy and infection-induced wound healing. The PPCP matrix showed intrinsically multifunctional properties including antioxidative, anti-inflammatory, photothermal, antibacterial, anticancer, and angiogenesis bioactivities. The polydopamine/curcumin presented an excellent near-infrared photothermal/cancer cell toxicity capacity, respectively, which supported PPCP for synergetic skin tumor therapy and antibacterial properties in vitro/in vivo. Additionally, the PPCP nanofibrous matrix significantly promotes the adhesion and proliferation of normal skin cells and accelerates the cutaneous wound healing in normal mice and bacterial-infected mice by enhancing the early angiogenesis. The PPCP nanofibrous matrix with multifunctional bioactivities provides a competitive strategy for skin tumor and bacterial-infection-induced wound healing.

PMID: 32031782 [PubMed - indexed for MEDLINE]

Permalink for 'Why did they change that? Practical implications of the evolving classification of neuroendocrine tumours of the gastrointestinal tract.'

Why did they change that? Practical implications of the evolving classification of neuroendocrine tumours of the gastrointestinal tract.

Fetched: January 2nd, 2021, 5:01am GMT

Why did they change that? Practical implications of the evolving classification of neuroendocrine tumours of the gastrointestinal tract.

Histopathology. 2021 Jan;78(1):162-170

Authors: Gill AJ

Abstract
Neuroendocrine neoplasms (NENs) of the gastrointestinal tract (GIT) comprise neuroendocrine tumours (NETs) and neuroendocrine carcinomas (NECs). During the last decade the classification and grading of GIT NENs has undergone significant changes, culminating in the World Health Organisation (WHO) 2019 classification. These changes, some of which are attributable to an only partially successful attempt to achieve uniform nomenclature among different organs, include: slight changes to the cut-off used for the Ki-67 proliferative index to distinguish grade 1 from grade 2 NETs; an emphasis on the distinction between grade 3 NETs (low-grade NETs with a high proliferative rate) and NECs which, by definition, are all high grade; classification of tumours with mixed non-neuroendocrine and neuroendocrine differentiation as MiNENs; and replacement of the term 'goblet cell carcinoid' with 'goblet cell adenocarcinoma'. While some of these changes seem minor, even semantic, each was made for very specific reasons which reflect an improved understanding of neuroendocrine neoplasia. The changes have definite implications for pathologists in clinical practice, not all of which may be readily apparent. This review is an attempt to explain the background behind each of the recent changes to the classification of neuroendocrine neoplasms of the gastrointestinal tract and summarise their impact on surgical pathologists - including a guide on how to approach certain recurrent difficulties encountered with the WHO 2019 system in routine clinical practice.

PMID: 33382490 [PubMed - in process]

A rare tumor of the gallbladder: Small cell neuroendocrine carcinoma.

Fetched: January 2nd, 2021, 5:01am GMT

A rare tumor of the gallbladder: Small cell neuroendocrine carcinoma.

North Clin Istanb. 2020;7(6):624-627

Authors: Kepil N, Akinci O, Batur S, Zengin AK

Abstract
Small cell neuroendocrine carcinoma of the gallbladder is a rare, aggressive malignancy that does not yet have a standard treatment protocol. In this case report, we aimed to share our experience about a 74-year-old male patient presented to our clinic with the complaint of episodic abdominal pain and underwent cholecystectomy under elective conditions due to a polyp with a diameter of 4 cm visualized in the gallbladder on ultrasound and diagnosed with neuroendocrine carcinoma as a result of histopathological examination.

PMID: 33381705 [PubMed]

Rare Cancer News & Clinical Trials » Endocrine/Neuroendocrine

Feeds

Endocrine/Neuroendocrine (537 unread)

Fetched: January 18th, 2021, 5:01am GMT

Fetched: January 17th, 2021, 5:01am GMT

Fetched: January 15th, 2021, 5:00am GMT

Fetched: January 15th, 2021, 5:00am GMT

Fetched: January 13th, 2021, 5:01am GMT

Fetched: January 13th, 2021, 5:01am GMT

Fetched: January 11th, 2021, 5:01am GMT

Fetched: January 8th, 2021, 5:01am GMT

Fetched: January 8th, 2021, 5:01am GMT

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

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

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

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

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

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

Fetched: December 23rd, 2020, 5:00am GMT

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

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

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

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

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

Fetched: December 16th, 2020, 5:01am GMT

Fetched: December 16th, 2020, 5:01am GMT

Fetched: December 16th, 2020, 5:01am GMT

Fetched: December 16th, 2020, 5:01am GMT

Fetched: December 16th, 2020, 5:01am GMT

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

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

Fetched: December 4th, 2020, 5:00am GMT

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

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

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

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

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

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

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

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

Fetched: November 22nd, 2020, 5:00am GMT

Fetched: November 21st, 2020, 5:00am GMT

Fetched: November 21st, 2020, 5:00am GMT

Fetched: November 20th, 2020, 5:00am GMT

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

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

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

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

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

Fetched: November 17th, 2020, 5:00am GMT

Fetched: November 17th, 2020, 5:00am GMT

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

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

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

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

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

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

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

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

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

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

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

Fetched: November 4th, 2020, 5:00am GMT

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

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

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

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

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

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

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

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

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

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

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

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

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