Rare Cancer News & Clinical Trials » Endocrine/Neuroendocrine

Endocrine/Neuroendocrine (525 unread)

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Molecular Mechanisms of Merkel Cell Polyomavirus Transformation and Replication.

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

Molecular Mechanisms of Merkel Cell Polyomavirus Transformation and Replication.

Annu Rev Virol. 2020 Jun 30;:

Authors: Liu W, You J

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

PMID: 32603631 [PubMed - as supplied by publisher]

Periocular skin cancer: Diagnosis and management.

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

Periocular skin cancer: Diagnosis and management.

Dis Mon. 2020 Jun 26;:101046

Authors: Moran JM, Phelps PO

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

PMID: 32600650 [PubMed - as supplied by publisher]

Bone marrow involvement with Merkel cell carcinoma.

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

Bone marrow involvement with Merkel cell carcinoma.

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

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

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

PMID: 32595130 [PubMed - in process]

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

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

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

Front Med (Lausanne). 2020;7:198

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

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

PMID: 32582722 [PubMed]

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

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

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

Cancer Cytopathol. 2020 Jun 23;:

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

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

PMID: 32573984 [PubMed - as supplied by publisher]

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

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

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

Otolaryngol Head Neck Surg. 2020 Jun 23;:194599820932553

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

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

PMID: 32571145 [PubMed - as supplied by publisher]

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

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

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

J Surg Oncol. 2020 Jun 20;:

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

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

PMID: 32562583 [PubMed - as supplied by publisher]

p110δ PI3K as a therapeutic target of solid tumours.

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

p110δ PI3K as a therapeutic target of solid tumours.

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

Authors: Xenou L, Papakonstanti EA

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

PMID: 32556179 [PubMed - in process]

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

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

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

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

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

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

PMID: 32545409 [PubMed]

Merkel cell carcinoma with divergent differentiation.

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

Merkel cell carcinoma with divergent differentiation.

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

Authors: Gaitskell K, Nassar S, Ibrahim H

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

PMID: 31580510 [PubMed - indexed for MEDLINE]

Neoadjuvant Checkpoint Inhibitor Therapy for Merkel Cell Carcinoma.

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

Neoadjuvant Checkpoint Inhibitor Therapy for Merkel Cell Carcinoma.

J Clin Oncol. 2020 Jun 12;:JCO2000752

Authors: Brohl AS, Sondak VK

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

PMID: 32530767 [PubMed - as supplied by publisher]

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

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

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

Ann Surg Oncol. 2020 Jun 11;:

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

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

PMID: 32529274 [PubMed - as supplied by publisher]

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

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

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

Ann Palliat Med. 2020 Jun 02;:

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

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

PMID: 32527130 [PubMed - as supplied by publisher]

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

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

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

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

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

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

PMID: 31350728 [PubMed - indexed for MEDLINE]

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

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

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

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

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

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

PMID: 31250007 [PubMed - indexed for MEDLINE]

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

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

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

medRxiv. 2020 May 30;:

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

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

PMID: 32511533 [PubMed]

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

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

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

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

Authors: Jenkins LN, Howle JR, Veness MJ

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

PMID: 30959572 [PubMed - indexed for MEDLINE]

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

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

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

Histol Histopathol. 2020 May 04;:18231

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

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

PMID: 32495847 [PubMed - as supplied by publisher]

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

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

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

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

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

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

PMID: 32483262 [PubMed - in process]

Selective reactivation of STING signaling to target Merkel cell carcinoma.

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

Selective reactivation of STING signaling to target Merkel cell carcinoma.

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

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

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

PMID: 32482869 [PubMed - as supplied by publisher]

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

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

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

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

Authors: Bharmal M, Hunger M, Schlichting M

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

PMID: 31563260 [PubMed - indexed for MEDLINE]

The Landmark Series: Non-melanoma Skin Cancers.

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

The Landmark Series: Non-melanoma Skin Cancers.

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

Authors: Lee AY, Berman RS

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

PMID: 31549317 [PubMed - indexed for MEDLINE]

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

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

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

Cancer. 2020 Jun 01;:

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

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

PMID: 32478867 [PubMed - as supplied by publisher]

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

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

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

Epigenetics. 2020 May 30;:1-6

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

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

PMID: 32475296 [PubMed - as supplied by publisher]

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

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

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

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

Ann Surg Oncol. 2020 May 30;:

Authors: van Veenendaal LM, van Akkooi ACJ

PMID: 32474817 [PubMed - as supplied by publisher]

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

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

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

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

Patient. 2020 May 30;:

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

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

PMID: 32472503 [PubMed - as supplied by publisher]

Neoadjuvant Immunotherapy: Making Strides.

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

Neoadjuvant Immunotherapy: Making Strides.

Cancer Discov. 2020 May 28;:

Authors:

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

PMID: 32467341 [PubMed - as supplied by publisher]

Risk of rare cancers among solid organ transplant recipients.

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

Risk of rare cancers among solid organ transplant recipients.

J Natl Cancer Inst. 2020 May 27;:

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

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

PMID: 32462187 [PubMed - as supplied by publisher]

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

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

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

J Am Acad Dermatol. 2020 May 24;:

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

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

PMID: 32461079 [PubMed - as supplied by publisher]

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

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

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

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

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

PMID: 30535745 [PubMed - indexed for MEDLINE]

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

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

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

Dermatol Ther. 2020 May 23;:e13675

Authors: Wollina U, Koch A, Cardoso JC

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

PMID: 32447821 [PubMed - as supplied by publisher]

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

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

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

BioDrugs. 2020 May 23;:

Authors: Patrinely JR, Dewan AK, Johnson DB

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

PMID: 32447657 [PubMed - as supplied by publisher]

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

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

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

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

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

Authors:

PMID: 32434786 [PubMed - in process]

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

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

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

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

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

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

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

PMID: 32430019 [PubMed - in process]

Merkel Cell Carcinoma - Current Controversies and Future Directions.

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

Merkel Cell Carcinoma - Current Controversies and Future Directions.

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

Authors: Steven N, Lawton P, Poulsen M

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

PMID: 31594644 [PubMed - indexed for MEDLINE]

A case of merkel leptomeningeal evolution after complete remission upon anti-PD-1 treatment.

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

A case of merkel leptomeningeal evolution after complete remission upon anti-PD-1 treatment.

Eur J Cancer. 2019 May;113:55-57

Authors: Godeau M, Pages-Laurent C, Severino-Freire M, Guinard E, Tauber M, Larrieu-Ciron D, Lamant L, Evrard SM, Riffaud L, Sibaud V, Boulinguez S, Meyer N

PMID: 30981092 [PubMed - indexed for MEDLINE]

Reply to: Letter re: Efficacy of isolated limb perfusion (ILP) in patients with Merkel cell carcinoma: A multicenter experience.

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

Reply to: Letter re: Efficacy of isolated limb perfusion (ILP) in patients with Merkel cell carcinoma: A multicenter experience.

Eur J Surg Oncol. 2019 06;45(6):1122-1123

Authors: van Veenendaal LM, Madu MF, Tesselaar MET, Verhoef CK, Grünhagen DJ, van Akkooi ACJ

PMID: 30808525 [PubMed - indexed for MEDLINE]

Permalink for 'Surface charge of Merkel cell polyomavirus small T antigen determines cell transformation through allosteric FBW7 WD40 domain targeting.'

Surface charge of Merkel cell polyomavirus small T antigen determines cell transformation through allosteric FBW7 WD40 domain targeting.

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

Surface charge of Merkel cell polyomavirus small T antigen determines cell transformation through allosteric FBW7 WD40 domain targeting.

Oncogenesis. 2020 May 19;9(5):53

Authors: Nwogu N, Ortiz LE, Kwun HJ

Abstract
Merkel cell polyomavirus (MCV) small T (sT) is the main oncoprotein in Merkel cell carcinoma (MCC) development. A unique domain of sT, LT stabilization domain (LSD), has been reported to bind and inactivate multiple SCF (Skp1-Cullin-F-box) E3 ligases. These interactions impede the turnover of MCV large T (LT) antigen and cellular oncoproteins such as c-Myc and cyclin E, thereby promoting viral replication and cell transformation. However, it is currently unclear how this LSD region contributes to multiple transforming activities of sT. Structural docking simulation of sT and F-box and WD repeat domain-containing 7 (FBW7) revealed a novel allosteric interaction between sT and FBW7 WD40 domain. This model is supported by experimental evidence confirming that charge engineering in the LSD alters sT-WD40 binding. Specifically, loss of net positive charge in the LSD prevents sT-FBW7 binding by abrogating the electrostatic interaction, thus impeding inhibition of FBW7 by sT. Furthermore, positively charged mutations in the LSD significantly restored the sT function and its ability to transform rodent fibroblast cells. We infer that the surface charge of sT is a major determinant for targeting E3 ligases, which leads to sT-induced cell transformation, an observation that could be used to develop targeted therapeutics for MCC.

PMID: 32427880 [PubMed]

Improved survival in women versus men with merkel cell carcinoma.

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

Improved survival in women versus men with merkel cell carcinoma.

J Am Acad Dermatol. 2020 May 15;:

Authors: Tam M, Luu M, Barker CA, Gharavi NM, Hamid O, Shiao SL, Nguyen AT, Lu DJ, Ho AS, Zumsteg ZS

Abstract
BACKGROUND: Studies have observed that women have better outcomes than men in melanoma, but less is known about the influence of sex differences on outcomes for other aggressive cutaneous malignancies.
OBJECTIVE: To investigate whether women and men have disparate outcomes in Merkel cell carcinoma (MCC).
METHODS: Patients with nonmetastatic MCC undergoing surgery and lymph node evaluation were identified from the National Cancer Database (NCDB) and the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier analysis and Cox proportional hazards regression models were used for overall survival, and competing-risks analysis and Fine-Gray models were used for cause-specific and other-cause mortality.
RESULTS: The NCDB cohort (n = 4178) included 1516 (36%) women. Women had a consistent survival advantage compared with men in propensity score-matched analysis (66.0% vs 56.8% at 5 years, P < .001) and multivariable Cox regression (hazard ratio, 0.68; 95% confidence interval, 0.61-0.75; P < .001). Similarly, women had a survival advantage in the SEER validation cohort (n = 1202) with 457 (38.0%) women, which was entirely due to differences in MCC-specific mortality (5-year cumulative incidence: 16.4% vs 26.7%, P = .002), with no difference in other-cause mortality (16.8% vs 17.8%, P = .43) observed in propensity score-matched patients.
LIMITATIONS: Potential selection bias from a retrospective data set.
CONCLUSION: In MCC, women have improved survival compared with men, driven by MCC-related mortality.

PMID: 32423829 [PubMed - as supplied by publisher]

Permalink for 'Author Correction: Merkel cell polyomavirus activates LSD1-mediated blockade of non-canonical BAF to regulate transformation and tumorigenesis.'

Author Correction: Merkel cell polyomavirus activates LSD1-mediated blockade of non-canonical BAF to regulate transformation and tumorigenesis.

Fetched: May 18th, 2020, 5:00am GMT

Author Correction: Merkel cell polyomavirus activates LSD1-mediated blockade of non-canonical BAF to regulate transformation and tumorigenesis.

Nat Cell Biol. 2020 May 15;:

Authors: Park DE, Cheng J, McGrath JP, Lim MY, Cushman C, Swanson SK, Tillgren ML, Paulo JA, Gokhale PC, Florens L, Washburn MP, Trojer P, DeCaprio JA

Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper.

PMID: 32415271 [PubMed - as supplied by publisher]

Permalink for 'Avelumab in patients with previously treated metastatic Merkel cell carcinoma: long-term data and biomarker analyses from the single-arm phase 2 JAVELIN Merkel 200 trial.'

Avelumab in patients with previously treated metastatic Merkel cell carcinoma: long-term data and biomarker analyses from the single-arm phase 2 JAVELIN Merkel 200 trial.

Fetched: May 18th, 2020, 5:00am GMT

Avelumab in patients with previously treated metastatic Merkel cell carcinoma: long-term data and biomarker analyses from the single-arm phase 2 JAVELIN Merkel 200 trial.

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

Authors: D'Angelo SP, Bhatia S, Brohl AS, Hamid O, Mehnert JM, Terheyden P, Shih KC, Brownell I, Lebbé C, Lewis KD, Linette GP, Milella M, Georges S, Shah P, Ellers-Lenz B, Bajars M, Güzel G, Nghiem PT

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer associated with a high risk of metastasis. In 2017, avelumab (anti-programmed death-ligand 1 (PD-L1)) became the first approved treatment for patients with metastatic MCC (mMCC), based on the occurrence of durable responses in a subset of patients. Here, we report long-term efficacy and safety data and exploratory biomarker analyses in patients with mMCC treated with avelumab.
METHODS: In a cohort of this single-arm, phase 2 trial (JAVELIN Merkel 200), patients with mMCC and disease progression after prior chemotherapy received avelumab 10 mg/kg intravenously every 2 weeks. The primary endpoint was confirmed objective response rate (ORR) by independent review per Response Evaluation Criteria in Solid Tumors V.1.1. Other assessments included duration of response, progression-free survival, overall survival (OS), safety and biomarker analyses.
RESULTS: As of 14 September 2018, 88 patients had been followed up for a median of 40.8 months (range 36.4-49.7 months). The ORR was 33.0% (95% CI 23.3% to 43.8%), including a complete response in 11.4% (10 patients), and the median duration of response was 40.5 months (95% CI 18.0 months to not estimable). As of 2 May 2019 (≥44 months of follow-up), the median OS was 12.6 months (95% CI 7.5 to 17.1 months) and the 42-month OS rate was 31% (95% CI 22% to 41%). Of long-term survivors (OS >36 months) evaluable for PD-L1 expression status (n=22), 81.8% had PD-L1+ tumors. In exploratory biomarker analyses, high tumor mutational burden (≥2 non-synonymous somatic variants per megabase) and high major histocompatibility complex class I expression (30% of tumors with highest expression) were associated with trends for improved ORR and OS. In long-term safety assessments (≥36 months of follow-up), no new or unexpected adverse events were reported, and no treatment-related deaths occurred.
CONCLUSIONS: Avelumab showed continued durable responses and meaningful long-term survival outcomes in patients with mMCC, reinforcing avelumab as a standard-of-care treatment option for this disease.
TRIAL REGISTRATION NUMBER: NCT02155647.

PMID: 32414862 [PubMed - in process]

Merkel Cell Carcinoma Treatment in Finland in 1986-2016-A Real-World Data Study.

Fetched: May 18th, 2020, 5:00am GMT

Merkel Cell Carcinoma Treatment in Finland in 1986-2016-A Real-World Data Study.

Cancers (Basel). 2020 May 13;12(5):

Authors: Sahi H, Their J, Gissler M, Koljonen V

Abstract
Merkel cell carcinoma (MCC) is a rare cutaneous carcinoma that has gained enormous interest since the discovery of Merkel cell polyoma virus, which is a causative oncogenic agent in the majority of MCC tumours. Increased research has focused on effective treatment options with immuno-oncology. In this study, we reviewed the real-world data on different treatments given to MCC patients in Finland in 1986-2016. We used the Finnish Cancer Registry database to find MCC patients and the Hospital Discharge Register and the Cause-of-Death Register to obtain treatment data. We identified 376 MCC patients and 33 different treatment entities and/or combinations of treatment. An increase was noted in the incidence of MCC since 2005. Therefore, the cohort was divided into two groups: the "early" group with time of diagnosis between years 1986 and 2004 and the "late" group with time of diagnosis between 2005 and 2016. The multitude of different treatment combinations is a relatively new phenomenon; before the year 2005, only 11 treatments or treatment combinations were used for MCC patients. Our data show that combining radiation therapy with simple excision provided a survival advantage, which was, however, lost after adjustment for stage or age. Our registry study serves as a baseline treatment efficacy comparison as we move into the age of immunotherapy in MCC. Standardizing the treatment of MCC patients in Finland requires more work on awareness and multidisciplinary co-operation.

PMID: 32414207 [PubMed]

Patterns of Metastasis in Merkel Cell Carcinoma.

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

Patterns of Metastasis in Merkel Cell Carcinoma.

Ann Surg Oncol. 2020 May 13;:1-11

Authors: Song Y, Azari FS, Tang R, Shannon AB, Miura JT, Fraker DL, Karakousis GC

Abstract
Background: Merkel cell carcinoma (MCC) is a cutaneous neuroendocrine malignancy with a propensity for regional and distant spread. Because of the relative infrequency of this disease, the patterns of metastasis in MCC are understudied.
Methods: Patients with American Joint Committee on Cancer (8th edition) stage I-IV MCC treated at our institution were identified (1/1/2008-2/28/2018). The first site of metastasis was classified as regional [regional lymph node (LN) basin, in-transit] or distant. Distant metastasis-free (DMFS) and MCC-specific (MSS) survival were estimated.
Results: Of 133 patients, 64 (48%) had stage I, 13 (10%) stage II, 48 (36%) stage III, and 8 (6%) stage IV disease at presentation. The median follow-up time in patients who remained alive was 36 (interquartile range 20-66) months. Regional or distant metastases developed in 78 (59%) patients. The first site was regional in 87%, including 73% with isolated LN involvement, and distant in 13%. Thirty-seven (28%) patients eventually developed distant disease, which most commonly involved the abdominal viscera (51%) and distant LNs (46%) first. The lung (0%) and brain (3%) were rarely the first distant sites. Stage III MCC at presentation was significantly associated with worse DMFS (hazard ratio 4.87, P = 0.001) and stage IV disease with worse MSS (hazard ratio 6.30, P = 0.002).
Conclusions: Regional LN metastasis is the most common first metastatic event in MCC, confirming the importance of nodal evaluation. Distant disease spread appears to have a predilection for certain sites. Understanding these patterns could help to guide surveillance strategies.

PMID: 32410812 [PubMed - as supplied by publisher]

Patterns of Metastasis in Merkel Cell Carcinoma.

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

Patterns of Metastasis in Merkel Cell Carcinoma.

Ann Surg Oncol. 2020 May 13;:

Authors: Song Y, Azari FS, Tang R, Shannon AB, Miura JT, Fraker DL, Karakousis GC

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) is a cutaneous neuroendocrine malignancy with a propensity for regional and distant spread. Because of the relative infrequency of this disease, the patterns of metastasis in MCC are understudied.
METHODS: Patients with American Joint Committee on Cancer (8th edition) stage I-IV MCC treated at our institution were identified (1/1/2008-2/28/2018). The first site of metastasis was classified as regional [regional lymph node (LN) basin, in-transit] or distant. Distant metastasis-free (DMFS) and MCC-specific (MSS) survival were estimated.
RESULTS: Of 133 patients, 64 (48%) had stage I, 13 (10%) stage II, 48 (36%) stage III, and 8 (6%) stage IV disease at presentation. The median follow-up time in patients who remained alive was 36 (interquartile range 20-66) months. Regional or distant metastases developed in 78 (59%) patients. The first site was regional in 87%, including 73% with isolated LN involvement, and distant in 13%. Thirty-seven (28%) patients eventually developed distant disease, which most commonly involved the abdominal viscera (51%) and distant LNs (46%) first. The lung (0%) and brain (3%) were rarely the first distant sites. Stage III MCC at presentation was significantly associated with worse DMFS (hazard ratio 4.87, P = 0.001) and stage IV disease with worse MSS (hazard ratio 6.30, P = 0.002).
CONCLUSIONS: Regional LN metastasis is the most common first metastatic event in MCC, confirming the importance of nodal evaluation. Distant disease spread appears to have a predilection for certain sites. Understanding these patterns could help to guide surveillance strategies.

PMID: 32405979 [PubMed - as supplied by publisher]

Permalink for 'Immune status and the efficacy of radiotherapy on overall survival for patients with localized Merkel cell carcinoma: An analysis of the National Cancer Database.'

Immune status and the efficacy of radiotherapy on overall survival for patients with localized Merkel cell carcinoma: An analysis of the National Cancer Database.

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

Immune status and the efficacy of radiotherapy on overall survival for patients with localized Merkel cell carcinoma: An analysis of the National Cancer Database.

J Med Imaging Radiat Oncol. 2020 May 05;:

Authors: Yusuf MB, Gaskins J, Wall W, Tennant P, Bumpous J, Dunlap N

Abstract
BACKGROUND: Immunosuppressed (IS) patients with Merkel cell carcinoma (MCC) have worse outcomes compared to immunocompetent (IC) patients, and it is unclear if adjuvant radiotherapy (RT) is beneficial for these patients. We sought to determine the effect of immune status on adjuvant RT efficacy regarding overall survival (OS) for patients with localized MCC.
METHODS: This was an observational study of National Cancer Database (NCDB) identifying patients with stage I/II or III MCC with known immune status diagnosed from 2010 to 2014. The median follow-up time was 29 months. OS was described using Kaplan-Meier methods and compared for subgroups by immune status and adjuvant RT using log-rank tests, multivariable Cox regression and interaction effect testing.
RESULTS: A total of 2049 IC and 255 IS patients were included. Adjuvant RT was associated with decreased hazard of death for stage I/II MCC (HR 0.65, CI 0.54-0.78) adjusting for factors including immune status. Interaction effect testing did not demonstrate a significant difference in the effect of adjuvant RT on OS between IC and IS status in either stage I/II or III MCC (both P values > 0.05).
CONCLUSIONS: In this observational study, adjuvant RT was associated with decreased hazard of death for patients with stage I/II MCC regardless of immune status. Adjuvant RT should be considered for both IS and IC patients with localized MCC.

PMID: 32372566 [PubMed - as supplied by publisher]

Letter re: Efficacy of isolated limb perfusion (ILP) in patients with Merkel cell carcinoma: A multicenter experience.

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

Letter re: Efficacy of isolated limb perfusion (ILP) in patients with Merkel cell carcinoma: A multicenter experience.

Eur J Surg Oncol. 2019 06;45(6):1121

Authors: Kroon HM, Thompson JF

PMID: 30420186 [PubMed - indexed for MEDLINE]

A Therapeutic and Diagnostic Multidisciplinary Pathway for Merkel Cell Carcinoma Patients.

Fetched: May 2nd, 2020, 5:00am GMT

A Therapeutic and Diagnostic Multidisciplinary Pathway for Merkel Cell Carcinoma Patients.

Front Oncol. 2020;10:529

Authors: Rastrelli M, Del Fiore P, Buja A, Vecchiato A, Rossi CR, Chiarion Sileni V, Tropea S, Russano F, Zorzi M, Spina R, Cappellesso R, Mazzarotto R, Cavallin F, Bassetto F, Bezzon E, Ferrazzi B, Alaibac M, Mocellin S

Abstract
Merkel Cell Carcinoma (MCC) is a highly aggressive neuroendocrine neoplasm of the skin. Due to its rarity, the management of MCC is not standardized across centers. In this article, we present the experience of the Veneto region in the North-East of Italy, where a committee of skin cancer experts has proposed a clinical pathway for the diagnosis and treatment of MCC. Putting together the evidence available in the international literature, we outlined the best approach to the management of patients affected with this malignancy step- by- step for each possible clinical situation. Crucial in this pathway is the role of the multidisciplinary team to deal with the lack of robust information on each aspect of the management of this disease.

PMID: 32351898 [PubMed]

Permalink for 'Primary Parotid Merkel Type Small Cell Neuroendocrine Carcinoma with Oligometastasis to the Brain and Adrenal Gland: Case Report and Review of Literature.'

Primary Parotid Merkel Type Small Cell Neuroendocrine Carcinoma with Oligometastasis to the Brain and Adrenal Gland: Case Report and Review of Literature.

Fetched: May 2nd, 2020, 5:00am GMT

Primary Parotid Merkel Type Small Cell Neuroendocrine Carcinoma with Oligometastasis to the Brain and Adrenal Gland: Case Report and Review of Literature.

Head Neck Pathol. 2020 Apr 29;:

Authors: Young S, Oh J, Bukhari H, Ng T, Chau N, Tran E

Abstract
Oligometastatic disease is a hypothesized intermediate stage of disease between localized and widespread metastatic cancer. Localized treatment of oligometastatic lesions may offer survival advantages in addition to systemic treatment. In this case report, we describe a patient who presented with small cell neuroendocrine carcinoma "Merkel type" (SNECM) of the parotid gland which had metastasized to the brain and adrenal gland. He was treated with chemotherapy followed by stereotactic radiotherapy and volumetric modulated arc therapy for oligometastasis. He maintains good functional status with low burden of disease at 20-months after diagnosis. SNECM is a rare and aggressive parotid cancer with immunohistochemical and morphologic similarities to Merkel cell carcinoma (MCC). There are only 44 cases of parotid SNECM in the English literature. This is the first case to describe management of oligometastatic SNECM and we review literature on management of both SNECM and metastatic MCC.

PMID: 32350808 [PubMed - as supplied by publisher]

Unique Role of Histone Methyltransferase PRDM8 in the Tumorigenesis of Virus-Negative Merkel Cell Carcinoma.

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

Unique Role of Histone Methyltransferase PRDM8 in the Tumorigenesis of Virus-Negative Merkel Cell Carcinoma.

Cancers (Basel). 2020 Apr 24;12(4):

Authors: Orouji E, Peitsch WK, Orouji A, Houben R, Utikal J

Abstract
Merkel cell carcinoma (MCC) is a deadly skin cancer, and about 80% of its cases have been shown to harbor integrated Merkel polyomavirus in the tumor cell genome. Viral oncoproteins expressed in the tumor cells are considered as the oncogenic factors of these virus-positive Merkel cell carcinoma (VP-MCC). In contrast, the molecular pathogenesis of virus-negative MCC (VN-MCC) is less well understood. Using gene expression analysis of MCC cell lines, we found histone methyltransferase PRDM8 to be elevated in VN-MCC. This finding was confirmed by immunohistochemical analysis of MCC tumors, revealing that increased PRDM8 expression in VN-MCC is also associated with increased H3K9 methylation. CRISPR-mediated silencing of PRDM8 in MCC cells further supported the histone methylating role of this protein in VN-MCC. We also identified miR-20a-5p as a negative regulator of PRDM8. Taken together, our findings provide insights into the role of PRDM8 as a histone methyltransferase in VN-MCC tumorigenesis.

PMID: 32344701 [PubMed]

Permalink for 'Gracilis musculotendinous free flap for lower extremity reconstruction after surgical removal of malignant tumors: A report of five cases.'

Gracilis musculotendinous free flap for lower extremity reconstruction after surgical removal of malignant tumors: A report of five cases.

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

Gracilis musculotendinous free flap for lower extremity reconstruction after surgical removal of malignant tumors: A report of five cases.

Microsurgery. 2019 Sep;39(6):515-520

Authors: Pedreira R, Calotta NA, Deune EG

Abstract
BACKGROUND: Lower extremity reconstruction is challenging because of the need to restore form and function. Despite the many options for soft-tissue coverage, little research has addressed combined tendon and soft-tissue reconstitution. We present a series of patients undergoing lower extremity tendon reconstruction and wound coverage with a single free gracilis flap and its tendon.
METHODS: We studied five patients (age range, 51-81 years) undergoing lower limb reconstruction for defects involving soft tissue and tendon between 1998 and 2016 in the senior author's practice. Wounds (all in the foot and ankle region) were caused by sarcoma (n = 4) and Merkel cell carcinoma (n = 1) and ranged from 6.5-10 × 8-12 cm. Donor tendons, 2-18 cm long, were used to reconstruct the tibialis anterior, extensor hallucis longus, extensor digitorum longus, and extensor retinaculum. Patient characteristics and outcomes were reviewed retrospectively.
RESULTS: Reconstructions used a gracilis muscle free flap and its tendon. Flap sizes ranged 5-6.5 × 11-14 cm. Complications were one case of cellulitis and one case of reoperation for flap thinning and tenolysis. All patients had at least 7 months of follow-up (mean: 37 months; range: 7-104 months). At latest follow-up, all patients were ambulatory. On average, patients resumed assisted ambulation 27 days postoperatively and unassisted ambulation 62 days postoperatively.
CONCLUSIONS: For complex wounds with soft-tissue and tendinous defects, the gracilis muscle free flap may be a reconstructive option. We recommend it be considered as a single-donor incision option for lower extremity reconstruction.

PMID: 30810247 [PubMed - indexed for MEDLINE]

Permalink for 'Functional reconstruction of total upper eyelid defects with a composite radial forearm-palmaris longus tenocutaneous free flap: A report of two cases.'

Functional reconstruction of total upper eyelid defects with a composite radial forearm-palmaris longus tenocutaneous free flap: A report of two cases.

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

Functional reconstruction of total upper eyelid defects with a composite radial forearm-palmaris longus tenocutaneous free flap: A report of two cases.

Microsurgery. 2019 Sep;39(6):559-562

Authors: Iwanaga H, Nuri T, Okada M, Ueda K

Abstract
This report presents reconstruction of wide- and full-thickness upper eyelid defects with a composite radial forearm-splitting palmaris longus tendon flap, which maintains eyelid opening and closing functions and supporting tissue in a Meibomian gland carcinoma in the right upper eyelid (case 1) and Merkel cell carcinoma in the right upper eyelid (case 2). After tumor resection with excisional margins, the defects involved the muscle, tarsal, and mucosa, with defect sizes of 60 × 40 mm and 85 × 40 mm, respectively. A radial forearm flap with the palmaris longus tendon was transferred. The tendon was split into two strips: the upper strip was fixed to the frontal muscles for the opening function and the lower strip to the medial palpebral ligament and orbicularis oculi muscle to maintain the closing function. Flap vessels were anastomosed to the superficial temporal artery and vein through the subdermal tunnel. Postoperative courses were uneventful. At the 5-year (case 1) and 4-year (case 2) follow-up periods, there were no tumor recurrence and keratalgia, and the eyelid opening and closing functions were maintained. This approach may contribute to achievement of not only the opening function but also the closing function of the reconstructed eyelid.

PMID: 30666696 [PubMed - indexed for MEDLINE]

Expression and prognostic significance of programmed death-ligand 1 (PD-L1) in Merkel cell carcinoma.

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

Expression and prognostic significance of programmed death-ligand 1 (PD-L1) in Merkel cell carcinoma.

J BUON. 2019 Sep-Oct;24(5):2155-2160

Authors: Richter I, Dvorak TJECJBTBJ

Abstract
PURPOSE: To detect the expression of programmed death-ligand 1 (PD-L1) in Merkel cell carcinoma (MCC) and to determine the prognostic influence of the PD-L1 expression.
METHODS: A total of 13 patients with MCC were retrospectively evaluated (12 patients with primary skin lesion, one patient was diagnosed as unknown primary MCC). All patients underwent surgical resection. PD-L1 was determinated by imunohistochemistry. Immunostaining results were evaluated semiquantitatively. The prognostic influence of the expression of PD-L1 on overall survival (OS) was calculated with the Kaplan-Meier method and log-rank test.
RESULTS: PD-L1 positivity was detected in 8 patients (61.5%), in all cases the result was 1+. PD-L1 negativity was shown in the remaining 5 patients. In patients with PD-L1 positivity median OS was 42.1 months (95% CI 9.3-42.1) compared with median OS of 9.4 months (95% CI 2.1-80.9) in the group of patients without PD-L1 positivity (p=0.417).
CONCLUSIONS: PD-L1 positivity was found in 61.5% of patients with MCC. No prognostic significance of PD-L1 expression for OS was demonstrated.

PMID: 31786889 [PubMed - indexed for MEDLINE]

Caring for Patients Treated With Checkpoint Inhibitors for the Treatment of Metastatic Merkel Cell Carcinoma.

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

Caring for Patients Treated With Checkpoint Inhibitors for the Treatment of Metastatic Merkel Cell Carcinoma.

Semin Oncol Nurs. 2019 10;35(5):150924

Authors: Rubin KM, Hoffner B, Bullock AC

Abstract
OBJECTIVE: To provide an overview for oncology nurses about Merkel cell carcinoma and its management with immunotherapy.
DATA SOURCES: A literature search was conducted from 2013 to the present using search terms including "Merkel cell carcinoma," "avelumab," "pembrolizumab," "immune-mediated adverse events," and "infusion-related reactions." Clinical experience of the authors was also considered.
CONCLUSION: Oncology nurses can expect to manage an increasing number of patients with Merkel cell carcinoma because of increased incidence of the disease, as well as evolving immunotherapy treatment paradigms. Both avelumab and pembrolizumab possess favorable safety profiles but are associated with immune-mediated and infusion-related reactions.
IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses need to understand Merkel cell carcinoma and be able to recognize the signs and symptoms of immune-mediated adverse events and infusion-related reactions associated with treatment to provide early intervention.

PMID: 31514991 [PubMed - indexed for MEDLINE]

Neoadjuvant Nivolumab for Patients With Resectable Merkel Cell Carcinoma in the CheckMate 358 Trial.

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

Neoadjuvant Nivolumab for Patients With Resectable Merkel Cell Carcinoma in the CheckMate 358 Trial.

J Clin Oncol. 2020 Apr 23;:JCO2000201

Authors: Topalian SL, Bhatia S, Amin A, Kudchadkar RR, Sharfman WH, Lebbé C, Delord JP, Dunn LA, Shinohara MM, Kulikauskas R, Chung CH, Martens UM, Ferris RL, Stein JE, Engle EL, Devriese LA, Lao CD, Gu J, Li B, Chen T, Barrows A, Horvath A, Taube JM, Nghiem P

Abstract
PURPOSE: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer commonly driven by the Merkel cell polyomavirus (MCPyV). The programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) immunosuppressive pathway is often upregulated in MCC, and advanced metastatic MCC frequently responds to PD-1 blockade. We report what we believe to be the first trial of anti-PD-1 in the neoadjuvant setting for resectable MCC.
METHODS: In the phase I/II CheckMate 358 study of virus-associated cancer types, patients with resectable MCC received nivolumab 240 mg intravenously on days 1 and 15. Surgery was planned on day 29. Tumor regression was assessed radiographically and microscopically. Tumor MCPyV status, PD-L1 expression, and tumor mutational burden (TMB) were assessed in pretreatment tumor biopsies.
RESULTS: Thirty-nine patients with American Joint Committee on Cancer stage IIA-IV resectable MCC received ≥ 1 nivolumab dose. Three patients (7.7%) did not undergo surgery because of tumor progression (n = 1) or adverse events (n = 2). Any-grade treatment-related adverse events occurred in 18 patients (46.2%), and grade 3-4 events in 3 patients (7.7%), with no unexpected toxicities. Among 36 patients who underwent surgery, 17 (47.2%) achieved a pathologic complete response (pCR). Among 33 radiographically evaluable patients who underwent surgery, 18 (54.5%) had tumor reductions ≥ 30%. Responses were observed regardless of tumor MCPyV, PD-L1, or TMB status. At a median follow-up of 20.3 months, median recurrence-free survival (RFS) and overall survival were not reached. RFS significantly correlated with pCR and radiographic response at the time of surgery. No patient with a pCR had tumor relapse during observation.
CONCLUSION: Nivolumab administered approximately 4 weeks before surgery in MCC was generally tolerable and induced pCRs and radiographic tumor regressions in approximately one half of treated patients. These early markers of response significantly predicted improved RFS. Additional investigation of these promising findings is warranted.

PMID: 32324435 [PubMed - as supplied by publisher]

Permalink for 'High somatostatin receptor expression and efficacy of somatostatin analogues in patients with metastatic Merkel cell carcinoma.'

High somatostatin receptor expression and efficacy of somatostatin analogues in patients with metastatic Merkel cell carcinoma.

Fetched: April 24th, 2020, 5:00am GMT

High somatostatin receptor expression and efficacy of somatostatin analogues in patients with metastatic Merkel cell carcinoma.

Br J Dermatol. 2020 Apr 22;:

Authors: Akaike T, Qazi J, Anderson A, Behnia FS, Shinohara M, Akaike G, Hippe DS, Thomas H, Takagishi SR, Lachance K, Park SY, Tarabadkar ES, Iyer JG, Blom A, Parvathaneni U, Vesselle H, Nghiem P, Bhatia S

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive, high-grade, cutaneous neuroendocrine tumour (NET). PD-1/PD-L1 blocking agents have efficacy in metastatic MCC (mMCC), but half of patients do not derive durable benefit. Somatostatin analogues (SSA) are commonly used to treat low- and moderate-grade NETs that express somatostatin receptors (SSTR).
OBJECTIVES: To assess SSTR expression and efficacy of SSA in mMCC, a high-grade NET.
METHODS: In this retrospective study of 40 patients with mMCC, SSTR expression was assessed radiologically by somatostatin receptor scintigraphy (SRS; N=39) and/or immunohistochemically when feasible (N=9). 19 patients (18 had SRS uptake in MCC tumours) were treated with SSA. Disease control (DC) was defined as progression-free survival (PFS) of ≥ 120 days after initiation of SSA.
RESULTS: Thirty-three of 39 (85%) patients had some degree (low-52%; moderate-23%; high-10%) of SRS uptake. Of 19 patients treated with SSA, 7 patients had a response-evaluable target lesion; 3 of these 7 (43%) patients experienced DC with a median PFS of 237 days [range 152-358]. 12 of 19 patients did not have a response-evaluable lesion due to antecedent radiation; 5 of these 12 (42%) patients experienced DC (median PFS of 429 days [range 143-1757]). The degree of SSTR expression (by SRS and/or immunohistochemistry) did not correlate significantly with the efficacy endpoints.
CONCLUSIONS: In contrast to other high-grade NETs, mMCC tumours appear to frequently express SSTR. SSA can lead to clinically meaningful disease control with minimal side effects. SSTR targeting using SSA or other novel approaches should be explored further for mMCC.

PMID: 32320473 [PubMed - as supplied by publisher]

Promoter activity of Merkel cell Polyomavirus variants in human dermal fibroblasts and a Merkel cell carcinoma cell line.

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

Promoter activity of Merkel cell Polyomavirus variants in human dermal fibroblasts and a Merkel cell carcinoma cell line.

Virol J. 2020 Apr 19;17(1):54

Authors: Abdulsalam I, Rasheed K, Sveinbjørnsson B, Ehlers B, Moens U

Abstract
BACKGROUND: Merkel cell polyomavirus (MCPyV) is a human polyomavirus that establishes a life-long harmless infection in most individuals, with dermal fibroblasts believed to be the natural host cell. However, this virus is the major cause of Merkel cell carcinoma (MCC), an aggressive skin cancer. Several MCPyV variants with polymorphism in their promoter region have been isolated, but it is not known whether these differences affect the biological properties of the virus.
METHODS: Using transient transfection studies in human dermal fibroblasts and the MCC cell line MCC13, we compared the transcription activity of the early and late promoters of the most commonly described non-coding control region MCPyV variant and six other isolates containing specific mutation patterns.
RESULTS: Both the early and late promoters were significantly stronger in human dermal fibroblasts compared with MCC13 cells, and a different promoter strength between the MCPyV variants was observed. The expression of full-length large T-antigen, a viral protein that regulates early and late promoter activity, inhibited early and late promoter activities in both cell lines. Nonetheless, a truncated large T-antigen, which is expressed in virus-positive MCCs, stimulated the activity of its cognate promoter.
CONCLUSION: The promoter activities of all MCPyV variants tested was stronger in human dermal fibroblasts, a cell line that supports viral replication, than in MCC13 cells, which are not permissive for MCPyV. Truncated large T-antigen, but not full-length large T-antigen stimulated viral promoter activity. Whether, the difference in promoter strength and regulation by large T-antigen may affect the replication and tumorigenic properties of the virus remains to be determined.

PMID: 32306957 [PubMed - in process]

Permalink for 'Intratumoral G100, a TLR4 Agonist, Induces Antitumor Immune Responses and Tumor Regression in Patients with Merkel Cell Carcinoma.'

Intratumoral G100, a TLR4 Agonist, Induces Antitumor Immune Responses and Tumor Regression in Patients with Merkel Cell Carcinoma.

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

Intratumoral G100, a TLR4 Agonist, Induces Antitumor Immune Responses and Tumor Regression in Patients with Merkel Cell Carcinoma.

Clin Cancer Res. 2019 02 15;25(4):1185-1195

Authors: Bhatia S, Miller NJ, Lu H, Longino NV, Ibrani D, Shinohara MM, Byrd DR, Parvathaneni U, Kulikauskas R, Ter Meulen J, Hsu FJ, Koelle DM, Nghiem P

Abstract
PURPOSE: G100 is a toll-like receptor 4 (TLR4) agonist that triggers innate and adaptive antitumor immune responses in preclinical models. This pilot study assessed the safety, efficacy, and immunologic activity of intratumoral (IT) administration of G100 in patients with Merkel cell carcinoma (MCC).
PATIENTS AND METHODS: Patients with locoregional MCC (n = 3; cohort A) received neoadjuvant IT G100 (2 weekly doses at 5 μg/dose) followed by surgery and radiotherapy; patients with metastatic MCC (n = 7; cohort B) received 3 doses in a 6-week cycle and could receive additional cycles with/without radiotherapy.
RESULTS: IT G100 was safe and feasible in both neoadjuvant and metastatic settings. Treatment-related adverse events were mostly grade 1 or 2 injection-site reactions. IT G100 led to increased inflammation in the injected tumors with infiltration of CD8+ and CD4+ T cells and activation of immune-related genes. These proinflammatory changes were associated with local tumor regression and appeared to promote systemic immunity. All 3 cohort A patients successfully completed therapy; 2 patients remain recurrence free at 44+ and 41+ months, including 1 with a pathologic complete response after G100 alone. In cohort B, 2 patients achieved sustained partial responses, both lasting 33+ months after 2 cycles of therapy.
CONCLUSIONS: In this first-in-human study, IT G100 induced antitumor immune responses, demonstrated acceptable safety, and showed encouraging clinical activity.See related commentary by Marquez-Rodas et al., p. 1127.

PMID: 30093453 [PubMed - indexed for MEDLINE]

T CELL REPERTOIRE IN COMBINATION WITH T CELL DENSITY PREDICTS CLINICAL OUTCOMES IN PATIENTS WITH MERKEL CELL CARCINOMA.

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

T CELL REPERTOIRE IN COMBINATION WITH T CELL DENSITY PREDICTS CLINICAL OUTCOMES IN PATIENTS WITH MERKEL CELL CARCINOMA.

J Invest Dermatol. 2020 Apr 15;:

Authors: Farah M, Reuben A, Spassova I, Yang RK, Kubat L, Nagarajan P, Ning J, Li W, Aung PP, Curry JL, Torres-Cabala CA, Hudgens CW, Ugurel S, Schadendorf D, Gumbs C, Little LD, Futreal A, Wistuba II, Prieto VG, Wang L, Wong MK, Wargo JA, Becker JC, Tetzlaff MT

Abstract
The integrity of the immune system represents a pivotal risk factor and prognostic biomarker for Merkel cell carcinoma (MCC). Higher density of tumor-associated T cells correlates with improved MCC-specific survival, but the prognostic importance of the T cell infiltrate reactivity is unknown. We evaluated the T cell receptor (TCR) repertoire associated with 72 primary MCCs and correlated metrics of the TCR repertoire with clinicopathologic characteristics and patient outcomes.

PMID: 32304704 [PubMed - as supplied by publisher]

The association between facility volume and overall survival in patients with Merkel cell carcinoma.

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

The association between facility volume and overall survival in patients with Merkel cell carcinoma.

J Surg Oncol. 2020 Apr 15;:

Authors: Yoshida EJ, Luu M, Freeman M, Essner R, Gharavi NM, Shiao SL, Mallen-St Clair J, Hamid O, Ho AS, Zumsteg ZS

Abstract
BACKGROUND: Merkel cell carcinoma is an uncommon malignancy often requiring multidisciplinary management. The purpose of this study was to determine whether high-volume facilities have improved outcomes in patients with Merkel cell carcinoma relative to lower-volume facilities.
METHODS: A total of 5304 patients from the National Cancer Database with stage I-III Merkel cell carcinoma undergoing surgery were analyzed. High-volume facilities were the top 1% by case volume. Multivariable Cox regression and propensity score-matching were performed to account for imbalances between groups.
RESULTS: Treatment at high-volume facilities (hazard ratio: 0.74; 95% confidence interval: 0.65-0.84, P < .001) was independently associated with improved overall survival (OS) in multivariable analyses. In propensity score-matched cohorts, 5-year OS was 62.3% at high-volume facilities vs 56.8% at lower-volume facilities (P < .001). Median OS was 111 months at high-volume facilities vs 79 months at lower-volume facilities.
CONCLUSION: Treatment at high-volume facilities is associated with improved OS in Merkel cell carcinoma. Given the impracticality of referring all elderly patients with Merkel cell carcinoma to a small number of facilities, methods to mitigate this disparity should be explored.

PMID: 32297324 [PubMed - as supplied by publisher]

Clinical Relevance of Liquid Biopsy in Melanoma and Merkel Cell Carcinoma.

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

Clinical Relevance of Liquid Biopsy in Melanoma and Merkel Cell Carcinoma.

Cancers (Basel). 2020 Apr 13;12(4):

Authors: Boyer M, Cayrefourcq L, Dereure O, Meunier L, Becquart O, Alix-Panabières C

Abstract
Melanoma and Merkel cell carcinoma are two aggressive skin malignancies with high disease-related mortality and increasing incidence rates. Currently, invasive tumor tissue biopsy is the gold standard for their diagnosis, and no reliable easily accessible biomarker is available to monitor patients with melanoma or Merkel cell carcinoma during the disease course. In these last years, liquid biopsy has emerged as a candidate approach to overcome this limit and to identify biomarkers for early cancer diagnosis, prognosis, therapeutic response prediction, and patient follow-up. Liquid biopsy is a blood-based non-invasive procedure that allows the sequential analysis of circulating tumor cells, circulating cell-free and tumor DNA, and extracellular vesicles. These innovative biosources show similar features as the primary tumor from where they originated and represent an alternative to invasive solid tumor biopsy. In this review, the biology and technical challenges linked to the detection and analysis of the different circulating candidate biomarkers for melanoma and Merkel cell carcinoma are discussed as well as their clinical relevance.

PMID: 32295074 [PubMed]

Management of localized Merkel cell carcinoma at high-volume facilities is associated with improved survival.

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

Management of localized Merkel cell carcinoma at high-volume facilities is associated with improved survival.

J Am Acad Dermatol. 2019 12;81(6):1414-1415

Authors: Elias ML, Lambert WC, Schwartz RA

PMID: 31103565 [PubMed - indexed for MEDLINE]

Permalink for 'Endoscopic Ultrasound-Guided Fine Needle Aspiration of a PET/CT-Positive Small Hilar Lymph Node for the Diagnosis of Metastatic Merkel Cell Carcinoma.'

Endoscopic Ultrasound-Guided Fine Needle Aspiration of a PET/CT-Positive Small Hilar Lymph Node for the Diagnosis of Metastatic Merkel Cell Carcinoma.

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

Endoscopic Ultrasound-Guided Fine Needle Aspiration of a PET/CT-Positive Small Hilar Lymph Node for the Diagnosis of Metastatic Merkel Cell Carcinoma.

J Gastrointestin Liver Dis. 2019 Sep 01;28(3):261

Authors: Antonini F, Vicentini R, Giorgini S, Macarri G

Abstract
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PMID: 31517317 [PubMed - indexed for MEDLINE]

Robot-assisted inguinal lymphadenectomy: preliminary experience and perioperative outcomes from an Italian referral center.

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

Robot-assisted inguinal lymphadenectomy: preliminary experience and perioperative outcomes from an Italian referral center.

Ther Adv Urol. 2020 Jan-Dec;12:1756287220913386

Authors: Cozzi G, Musi G, Ferro M, Prestianni P, Bianchi R, Giulia G, Alessandro MF, Luzzago S, Pennacchioli E, de Cobelli O

Abstract
Background: Inguinal lymphadenectomy remains the gold standard for the treatment of inguinal lymph node metastases from penile carcinoma, melanoma, Merkel cell carcinoma, and squamous cell carcinoma (SCC). This procedure is associated with significant complications. In order to reduce morbidity, minimally invasive approaches have been described. We report our preliminary experience with robot-assisted inguinal lymphadenectomies (RAIL).
Methods: RAIL was performed according to the Sotelo technique. When indicated, a robot-assisted pelvic lymphadenectomy (RAPLND) was performed. We recorded age, sex, comorbidities, baseline oncologic diagnosis, operative time, hospital stay, lymph node yield, complications, time to drain removal, and oncologic outcomes.
Results: From December 2016 to February 2019, 13 patients underwent RAIL. Median age was 65 years (range: 31-85 years). Primary malignancy was melanoma in five patients, Merkel cell carcinoma in four, dermal duct tumor in one, penile cancer in two, and SCC in one. RAIL was monolateral in 12 cases and bilateral in 1 case. A total of 10 monolateral RAPLNDs were performed; median operative time was 279 min (range: 169-320). Median lymph nodes yield was 11 (range: 2-24) for monolateral RAIL and 9 for monolateral RAPLND (range 2-24). Median hospital stay was 4 days (range: 2-5). No procedure was converted to open. Median follow up was 16 months (range: 5-31). Five Clavien-Dindo grade I complications were recorded. Median time to drain removal was 32.5 days (range 7-65). Three recurrences and two cancer-related deaths were recorded.
Conclusions: RAIL is feasible and associated with a short hospital stay, with little incidence of perioperative complications.

PMID: 32284736 [PubMed]

Merkel cell polyomavirus activates LSD1-mediated blockade of non-canonical BAF to regulate transformation and tumorigenesis.

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

Merkel cell polyomavirus activates LSD1-mediated blockade of non-canonical BAF to regulate transformation and tumorigenesis.

Nat Cell Biol. 2020 Apr 13;:

Authors: Park DE, Cheng J, McGrath JP, Lim MY, Cushman C, Swanson SK, Tillgren ML, Paulo JA, Gokhale PC, Florens L, Washburn MP, Trojer P, DeCaprio JA

Abstract
Merkel cell carcinoma (MCC)-a neuroendocrine cancer of the skin-is caused by the integration of Merkel cell polyomavirus and persistent expression of large T antigen and small T antigen. We report that small T antigen in complex with MYCL and the EP400 complex activates the expression of LSD1 (KDM1A), RCOR2 and INSM1 to repress gene expression by the lineage transcription factor ATOH1. LSD1 inhibition reduces the growth of MCC in vitro and in vivo. Through a forward-genetics CRISPR-Cas9 screen, we identified an antagonistic relationship between LSD1 and the non-canonical BAF (ncBAF) chromatin remodelling complex. Changes in gene expression and chromatin accessibility caused by LSD1 inhibition were partially rescued by BRD9 inhibition, revealing that LSD1 and ncBAF antagonistically regulate an overlapping set of genes. Our work provides mechanistic insight into the dependence of MCC on LSD1 and a tumour suppressor role for ncBAF in cancer.

PMID: 32284543 [PubMed - as supplied by publisher]

Artesunate Affects T Antigen Expression and Survival of Virus-Positive Merkel Cell Carcinoma.

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

Artesunate Affects T Antigen Expression and Survival of Virus-Positive Merkel Cell Carcinoma.

Cancers (Basel). 2020 Apr 09;12(4):

Authors: Sarma B, Willmes C, Angerer L, Adam C, Becker JC, Kervarrec T, Schrama D, Houben R

Abstract
Merkel cell carcinoma (MCC) is a rare and highly aggressive skin cancer with frequent viral etiology. Indeed, in about 80% of cases, there is an association with Merkel cell polyomavirus (MCPyV); the expression of viral T antigens is crucial for growth of virus-positive tumor cells. Since artesunate-a drug used to treat malaria-has been reported to possess additional anti-tumor as well as anti-viral activity, we sought to evaluate pre-clinically the effect of artesunate on MCC. We found that artesunate repressed growth and survival of MCPyV-positive MCC cells in vitro. This effect was accompanied by reduced large T antigen (LT) expression. Notably, however, it was even more efficient than shRNA-mediated downregulation of LT expression. Interestingly, in one MCC cell line (WaGa), T antigen knockdown rendered cells less sensitive to artesunate, while for two other MCC cell lines, we could not substantiate such a relation. Mechanistically, artesunate predominantly induces ferroptosis in MCPyV-positive MCC cells since known ferroptosis-inhibitors like DFO, BAF-A1, Fer-1 and β-mercaptoethanol reduced artesunate-induced death. Finally, application of artesunate in xenotransplanted mice demonstrated that growth of established MCC tumors can be significantly suppressed in vivo. In conclusion, our results revealed a highly anti-proliferative effect of the approved and generally well-tolerated anti-malaria compound artesunate on MCPyV-positive MCC cells, suggesting its potential usage for MCC therapy.

PMID: 32283634 [PubMed]

Merkel cell carcinoma in situ: New insights into the cells of origin.

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

Merkel cell carcinoma in situ: New insights into the cells of origin.

Australas J Dermatol. 2019 Nov;60(4):e311-e313

Authors: Yang A, Cordoba C, Cheung K, Konya J

Abstract
We report a case of a 71-year-old male who presented with a small skin-coloured plaque on his cheek. Histopathology demonstrated an intraepidermal carcinoma with follicular involvement. No evidence of dermal invasion was seen. Immunohistochemical studies showed areas of positive staining for CK20, EMA and synaptophysin. Histopathology findings were found to be most consistent with a diagnosis of intraepidermal carcinoma with features of Merkel cell carcinoma in situ, in combination with a squamous cell carcinoma in situ, with follicular involvement. Recent advances and findings suggest Merkel cell polyomavirus MCPyV-positive Merkel cell carcinoma and MCPyV-negative Merkel cell carcinoma have different cells of origin from different germ layers.

PMID: 31025338 [PubMed - indexed for MEDLINE]

Immune checkpoint inhibitor rechallenge in patients with immune-related myositis.

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

Immune checkpoint inhibitor rechallenge in patients with immune-related myositis.

Ann Rheum Dis. 2019 11;78(11):e129

Authors: Delyon J, Brunet-Possenti F, Leonard-Louis S, Arangalage D, Baudet M, Baroudjian B, Lebbe C, Hervier B, PATIO Group

PMID: 30242031 [PubMed - indexed for MEDLINE]

FDA Accelerated Approval of Pembrolizumab for Recurrent Locally Advanced or Metastatic Merkel Cell Carcinoma.

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

FDA Accelerated Approval of Pembrolizumab for Recurrent Locally Advanced or Metastatic Merkel Cell Carcinoma.

Oncologist. 2020 Apr 09;:

Authors: Bradford D, Demko S, Jin S, Mishra-Kalyani P, Beckles AR, Goldberg KB, Lemery S, Ward A, Keegan P, Pazdur R

Abstract
On December 19, 2018, the Food and Drug Administration granted accelerated approval to pembrolizumab (KEYTRUDA, Merck & Co. Inc., Whitehouse Station, NJ) for adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). Approval was based on Cancer Immunotherapy Trials Network protocol 9, also known as KEYNOTE-017 (NCT02267603), a multicenter, nonrandomized, open-label trial that enrolled 50 patients with recurrent locally advanced or metastatic MCC who had not received prior systemic therapy for their advanced disease. The major efficacy outcome measures were overall response rate (ORR) and response duration assessed by blinded independent central review per RECIST 1.1. The ORR was 56% (95% confidence interval: 41, 70) with a complete response rate of 24%. The median response duration was not reached. Among the 28 patients with responses, 96% had response durations of greater than 6 months and 54% had response durations of greater than 12 months. The most common adverse reactions of pembrolizumab reported in at least 20% of patients who received pembrolizumab as a single agent were fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain. IMPLICATIONS FOR PRACTICE: This report presents key information on the basis for the Food and Drug Administration's accelerated approval of pembrolizumab for the treatment of recurrent locally advanced or metastatic Merkel cell carcinoma, including efficacy and safety information. This approval provides patients and physicians with an additional treatment option for this aggressive and life-threatening carcinoma.

PMID: 32272501 [PubMed - as supplied by publisher]

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

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

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

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

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

Authors: Walker JW, Lebbé C, Grignani G, Nathan P, Dirix L, Fenig E, Ascierto PA, Sandhu S, Munhoz R, Benincasa E, Flaskett S, Reed J, Engelsberg A, Hariharan S, Kasturi V

Abstract
BACKGROUND: Avelumab, a human anti-programmed death-ligand 1 immunoglobulin G1 monoclonal antibody, showed favorable efficacy and safety in patients with metastatic Merkel cell carcinoma (mMCC) in the phase II JAVELIN Merkel 200 trial, leading to approval in multiple countries. We describe real-world experience with avelumab in patients with mMCC from an expanded access program.
METHODS: Eligible patients had mMCC and progressive disease during or after chemotherapy or were ineligible for chemotherapy or clinical trial participation. Patients received an initial 3-month supply of avelumab (administered as 10 mg/kg intravenously every 2 weeks until progressive disease or unacceptable toxicity); resupply was allowed following complete response, partial response, stable disease, or clinical benefit per physician assessment.
RESULTS: Between December 15, 2015, and March 4, 2019, 558 of 620 requests from 38 countries were medically approved, and 494 patients received avelumab. Among 240 evaluable patients, the objective response rate was 46.7% (complete response in 22.9%, including 3 of 16 potentially immunocompromised patients), and the disease control rate was 71.2%. The median duration of treatment in evaluable patients with response was 7.9 months (range, 1.0-41.7) overall and 5.2 months (range, 3.0-13.9) in immunocompromised patients. No new safety signals were identified. The expanded access program closed for new requests on December 31, 2018, as required after regulatory approval; benefitting patients continued to receive avelumab.
CONCLUSIONS: The avelumab expanded access program for patients with mMCC demonstrated efficacy and safety in a real-world setting, consistent with the results from JAVELIN Merkel 200, and provided a treatment for patients with limited options.

PMID: 32269140 [PubMed - in process]

Permalink for 'Tumor Ulceration, Reduced Infiltration of CD8-Lymphocytes, High Neutrophil-to-CD8-Lymphocyte Ratio and Absence of MC Virus are Negative Prognostic Markers for Patients with Merkel Cell Carcinoma.'

Tumor Ulceration, Reduced Infiltration of CD8-Lymphocytes, High Neutrophil-to-CD8-Lymphocyte Ratio and Absence of MC Virus are Negative Prognostic Markers for Patients with Merkel Cell Carcinoma.

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

Tumor Ulceration, Reduced Infiltration of CD8-Lymphocytes, High Neutrophil-to-CD8-Lymphocyte Ratio and Absence of MC Virus are Negative Prognostic Markers for Patients with Merkel Cell Carcinoma.

Cancers (Basel). 2020 Apr 06;12(4):

Authors: Naseri S, Steiniche T, Georgsen JB, Thomsen R, Ladekarl M, Heje M, Damsgaard TE, Bønnelykke-Behrndtz ML

Abstract
(1) Background: Merkel cell carcinoma (MCC) is caused by the Merkel cell polyomavirus and UV radiation. Understanding of the underlying biology is limited, but identification of prognostic markers may lead to better prognostic stratification for the patients. (2) Methods: Ninety patients diagnosed with MCC (1996-2012) were included. Virus status was estimated by polymerase chain reaction (qPCR) and immunohistochemistry (IHC). Ulceration status, PD-L1, cd66b neutrophils, cd8 lymphocytes and biomarkers of vascularization (cd34 endothelial cells) and migration (e-cadherin) were estimated by IHC and analyzed with digital pathology. (3) Results: Virus was present in 47% of patient samples and correlated with lower E-cadherin expression (p = 0.0005), lower neutrophil-to-CD8 lymphocyte ratio (N:CD8 ratio) (p = 0.02) and increased PD-L1 expression (p = 0.03). Ulceration was associated with absence of virus (p = 0.03), increased neutrophil infiltration (p < 0.0001) and reduced CD8 lymphocyte infiltration (p = 0.04). In multivariate analysis, presence of virus (p = 0.01), ulceration (p = 0.05) and increased CD8 lymphocyte infiltration (p = 0.001) showed independent prognostic impacts on MCC-specific survival. (3) Conclusions: In this study, we found that a high N:CD8 ratio, ulceration, virus-negative status and absence of CD8 lymphocytes are negative prognostic markers. Accurate prognostic stratification of the patients may be important in the clinical setting for determination of adjuvant treatment.

PMID: 32268526 [PubMed]

Permalink for 'Expression of novel proteins by polyomaviruses and recent advances in the structural and functional features of agnoprotein of JC virus, BK virus, and simian virus 40.'

Expression of novel proteins by polyomaviruses and recent advances in the structural and functional features of agnoprotein of JC virus, BK virus, and simian virus 40.

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

Expression of novel proteins by polyomaviruses and recent advances in the structural and functional features of agnoprotein of JC virus, BK virus, and simian virus 40.

J Cell Physiol. 2019 06;234(6):8295-8315

Authors: Saribas AS, Coric P, Bouaziz S, Safak M

Abstract
Polyomavirus family consists of a highly diverse group of small DNA viruses. The founding family member (MPyV) was first discovered in the newborn mouse in the late 1950s, which induces solid tumors in a wide variety of tissue types that are the epithelial and mesenchymal origin. Later, other family members were also isolated from a number of mammalian, avian and fish species. Some of these viruses significantly contributed to our current understanding of the fundamentals of modern biology such as transcription, replication, splicing, RNA editing, and cell transformation. After the discovery of first two human polyomaviruses (JC virus [JCV] and BK virus [BKV]) in the early 1970s, there has been a rapid expansion in the number of human polyomaviruses in recent years due to the availability of the new technologies and brought the present number to 14. Some of the human polyomaviruses cause considerably serious human diseases, including progressive multifocal leukoencephalopathy, polyomavirus-associated nephropathy, Merkel cell carcinoma, and trichodysplasia spinulosa. Emerging evidence suggests that the expression of the polyomavirus genome is more complex than previously thought. In addition to encoding universally expressed regulatory and structural proteins (LT-Ag, Sm t-Ag, VP1, VP2, and VP3), some polyomaviruses express additional virus-specific regulatory proteins and microRNAs. This review summarizes the recent advances in polyomavirus genome expression with respect to the new viral proteins and microRNAs other than the universally expressed ones. In addition, a special emphasis is devoted to the recent structural and functional discoveries in the field of polyomavirus agnoprotein which is expressed only by JCV, BKV, and simian virus 40 genomes.

PMID: 30390301 [PubMed - indexed for MEDLINE]

A primary neuroendocrine tumor of the left ventricle presenting with diarrhea-an unusual experience and literature review.

Fetched: April 6th, 2020, 5:00am GMT

A primary neuroendocrine tumor of the left ventricle presenting with diarrhea-an unusual experience and literature review.

Diagn Pathol. 2020 Apr 03;15(1):32

Authors: Li C, Huang J, Yang X, Xia J, Xu G, Zheng H

Abstract
BACKGROUND: Neuroendocrine tumors (NETs) can secrete bioactive amines in the bloodstream, resulting in the carcinoid syndrome characterized by diarrhea and flushing. The frequency of occurrence of primary cardiac neuroendocrine neoplasms is lesser than that of metastases, and hence, metastases must be adequately ruled out before diagnosis. Cardiac tumors, both primary and metastatic, mainly result in heart-related symptoms, such as heart failure and acquired valvular dysfunction. Here, we report a unique case of a primary left ventricular neuroendocrine tumor presenting with diarrhea.
CASE PRESENTATION: A 51-year-old female complaining of intermittent diarrhea for 2 years was admitted to our hospital. Enhancement of total abdominal computed tomography scan, echocardiography, and magnetic resonance imaging indicated a mass in the left ventricle. The indexes of myocardial enzymes were normal. Histologically, round cells with well-differentiated neuroendocrine morphology were arranged in typical pseudo-glandular, trabecular, ribbon-like, and solid nest patterns. Immunohistochemically, the tumor cells were positive for cytokeratin, chromogranin, synaptophysin, and CD56. However, they were negative for caudal type homeobox 2, S100, paired box gene 8, thyroid transcription factor 1, and CD20, which ruled out the origin of gastrointestinal, pancreatic, lung, and Merkel cell carcinomas. The symptoms of diarrhea disappeared after the operation. The patient was asymptomatic at the 9-month follow-up.
CONCLUSION: Cardiac neuroendocrine tumors with diarrhea are considerably rare and related clinical research is limited. We presented a case and reviewed related articles to improve the identification, diagnosis, and management of patients with cardiac neuroendocrine tumors. The site of origin of a neuroendocrine tumor is clinically vital, and identification of an occult primary tumor using imaging modalities is necessary. Immunohistochemistry is well-suited to indicate the origin of the tumor. Regular follow-up is necessary for both poorly differentiated and well-differentiated cardiac neuroendocrine tumors. It is suggested to detect some neuroendocrinal markers for patients with unexplained reasons of diarrhea.

PMID: 32245475 [PubMed - as supplied by publisher]

Permalink for 'Triple Collision Tumor Comprising Merkel Cell Carcinoma with an Unusual Immunophenotype, Squamous Cell Carcinoma In-Situ, and Basal Cell Carcinoma.'

Triple Collision Tumor Comprising Merkel Cell Carcinoma with an Unusual Immunophenotype, Squamous Cell Carcinoma In-Situ, and Basal Cell Carcinoma.

Fetched: April 5th, 2020, 5:00am GMT

Triple Collision Tumor Comprising Merkel Cell Carcinoma with an Unusual Immunophenotype, Squamous Cell Carcinoma In-Situ, and Basal Cell Carcinoma.

J Cutan Pathol. 2020 Apr 03;:

Authors: Hobbs MM, Geers TE, Brown TS, Malone JC

Abstract
Merkel cell carcinoma (MCC) is a rare, aggressive primary cutaneous neuroendocrine cancer which almost always exhibits the cytokeratin (CK)20+/thyroid transcription factor (TTF)-1- immunophenotype. MCC may occur concurrently with squamous cell carcinoma (SCC), Bowen's disease, and/or basal cell carcinoma (BCC), with some evidence that MCCs which occur in conjunction with other neoplasms exhibit different immunophenotypes compared to pure MCC cases. We present a case of CK20-/TTF-1+ MCC concurrent with Bowen's disease and BCC, and discuss possible differences in the pathogenesis of pure vs combined MCC. We also review the literature for this unusual immunophenotype, noting that most cases occur in combined MCC. This article is protected by copyright. All rights reserved.

PMID: 32243639 [PubMed - as supplied by publisher]

Immune status and the efficacy of adjuvant radiotherapy for patients with localized Merkel cell carcinoma of the head and neck.

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

Immune status and the efficacy of adjuvant radiotherapy for patients with localized Merkel cell carcinoma of the head and neck.

Clin Transl Oncol. 2020 Apr 02;:

Authors: Yusuf M, Gaskins J, May ME, Mandish S, Wall W, Fisher W, Tennant P, Jorgensen J, Bumpous J, Dunlap N

Abstract
PURPOSE: Immunosuppressed (IS) patients are at increased risk for developing Merkel cell carcinoma (MCC) with worsened outcomes compared to immunocompetent (IC) patients. We sought to determine the effects of immune status on the efficacy of adjuvant RT regarding OS for patients with stage I, II or III (localized) MCC of the head and neck.
METHODS/PATIENTS: The National Cancer Database was queried for patients with resected, localized MCC of the head and neck with known immune status. Kaplan-Meier methods were used to describe OS. Log-rank tests, multivariable Cox regression models and interaction effect testing were used to compare OS by subgroup categorized by patient and treatment factors including immune status and adjuvant RT receipt.
RESULTS: A total of 892 (89.6%) IC and 104 (10.4%) IS patients with MCC of the head and neck were included. Adjuvant RT was associated with improved 3-year OS rate for both IS patients (49.4% vs. 35.5%, p = 0.0467) and stage I/II IC patients (72.4% vs. 62.9%, p = 0.0092). Adjuvant RT was associated with decreased hazard of death (HR 0.77, 95% CI 0.62-0.95). Interaction effect testing did not demonstrate a difference in the efficacy of adjuvant RT on OS between IC and IS status (p = 0.157).
CONCLUSIONS: In this NCDB analysis, adjuvant RT was associated with decreased hazard of death for patients with localized MCC of the head and neck regardless of immune status and should be considered for both IS and IC patients.

PMID: 32239428 [PubMed - as supplied by publisher]

Landscape and Future Perspectives of Immunotherapy in Neuroendocrine Neoplasia.

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

Landscape and Future Perspectives of Immunotherapy in Neuroendocrine Neoplasia.

Cancers (Basel). 2020 Mar 30;12(4):

Authors: Maggio I, Manuzzi L, Lamberti G, Ricci AD, Tober N, Campana D

Abstract
BACKGROUND: Neuroendocrine neoplasms are rare entities consisting of a heterogeneous group of tumors that can originate from neuroendocrine cells present in the whole body. Their different behavior, metastatic potential, and prognosis are highly variable, depending on site of origin, grade of differentiation, and proliferative index. The aim of our work is to summarize the current knowledge of immunotherapy in different neuroendocrine neoplasms and its implication in clinical practice.
RESULTS: Several studies evaluated the efficacy and safety of immunotherapy in neuroendocrine neoplasms, in any setting of treatment, alone or in combination. Studies led to approval in neuroendocrine neoplasia of the lung, in combination with chemotherapy as first-line treatment or as a single-agent in a third-line setting, and Merkel cell carcinoma as a single agent. Results in other settings have been disappointing so far.
CONCLUSIONS: Immunotherapy seems a valid treatment option for high grade, poorly differentiated neoplasms. Future trials should explore the combination of immunotherapy with other agents, such as anti-angiogenic or other immunotherapy agents, in order to evaluate potential efficacy in low and intermediate grades, well differentiated tumors.

PMID: 32235636 [PubMed]

Merkel Cell Carcinoma: A 28-Year Experience.

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

Merkel Cell Carcinoma: A 28-Year Experience.

Otolaryngol Head Neck Surg. 2020 Mar 31;:194599820913622

Authors: Kwan K, Ghazizadeh S, Moon AS, Rünger D, Sajed D, Elashoff D, St John M

Abstract
OBJECTIVE: To evaluate the management and recurrence outcomes of head and neck Merkel cell carcinoma (HN-MCC) at a single institution.
STUDY DESIGN: A retrospective review of outcomes in patients with HN-MCC.
SETTING: A tertiary center from May 1990 to December 2018.
SUBJECTS AND METHODS: Electronic medical records of patients with HN-MCC were reviewed.
RESULTS: Sixty cases were included, with 67% (40 of 60) males and a mean age of 73.3 years. Imaging had a moderate sensitivity and specificity for detection of occult disease when compared with histopathologic analysis. Forty-two percent (25 of 60) of patients underwent neck dissection, and 12% (7 of 60) had a sentinel lymph node biopsy (SLNB). There was a high rate of negative SLNB findings. The majority of patients were treated with surgery alone (29 of 60), followed by a cohort (21 of 60) treated with surgery plus adjuvant treatment, and 10 of 60 patients were treated with radiation therapy with or without chemotherapy. Recurrence-free survival was 50%, 45%, and 42% at 1, 2, and 5 years.
CONCLUSIONS: We report higher recurrence rates and higher negative SLNB result rates than other studies. Our results affirm that imaging may not be a substitute for SLNB and that it had an intermediate ability to identify the occult disease. Traditional predictors, including SLNB and cervical node pathology, may not identify patients at risk for recurrence in HN-MCC. We report similar recurrence rates in patients who had treatment of the cervical nodes by radiation therapy or neck dissection as compared with those who did not receive neck treatment.

PMID: 32228136 [PubMed - as supplied by publisher]

Management of regional metastatic disease in cutaneous malignancy of the head and neck. 3. Merkel cell carcinoma.

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

Management of regional metastatic disease in cutaneous malignancy of the head and neck. 3. Merkel cell carcinoma.

Br J Oral Maxillofac Surg. 2019 11;57(9):847-856

Authors: Bowe CM, Gurney B, Whitaker S, Newlands C

Abstract
This is the third of three articles that give an overview of the current evidence for management of the neck and parotid in patients with cutaneous cancers of the head and neck. In this paper we discuss Merkel cell carcinoma (MCC) and review the latest evidence for management of the regional nodes.

PMID: 31615708 [PubMed - indexed for MEDLINE]

Polyomavirus-driven Merkel cell carcinoma: Prospects for therapeutic vaccine development.

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

Polyomavirus-driven Merkel cell carcinoma: Prospects for therapeutic vaccine development.

Mol Carcinog. 2020 Mar 27;:

Authors: Tabachnick-Cherny S, Pulliam T, Church C, Koelle DM, Nghiem P

Abstract
Great strides have been made in cancer immunotherapy including the breakthrough successes of anti-PD-(L)1 checkpoint inhibitors. In Merkel cell carcinoma (MCC), a rare and aggressive skin cancer, PD-(L)1 blockade is highly effective. Yet, ~50% of patients either do not respond to therapy or develop PD-(L)1 refractory disease and, thus, do not experience long-term benefit. For these patients, additional or combination therapies are needed to augment immune responses that target and eliminate cancer cells. Therapeutic vaccines targeting tumor-associated antigens, mutated self-antigens, or immunogenic viral oncoproteins are currently being developed to augment T-cell responses. Approximately 80% of MCC cases in the United States are driven by the ongoing expression of viral T-antigen (T-Ag) oncoproteins from genomically integrated Merkel cell polyomavirus (MCPyV). Since T-Ag elicits specific B- and T-cell immune responses in most persons with virus-positive MCC (VP-MCC), and ongoing T-Ag expression is required to drive VP-MCC cell proliferation, therapeutic vaccination with T-Ag is a rational potential component of immunotherapy. Failure of the endogenous T-cell response to clear VP-MCC (allowing clinically evident tumors to arise) implies that therapeutic vaccination will need to be potent anśd synergize with other mechanisms to enhance T-cell activity against tumor cells. Here, we review the relevant underlying biology of VP-MCC, potentially applicable therapeutic vaccine platforms, and antigen delivery formats. We also describe early successes in the field of therapeutic cancer vaccines and address several clinical scenarios in which VP-MCC patients could potentially benefit from a therapeutic vaccine.

PMID: 32219902 [PubMed - as supplied by publisher]

Adjuvant radiotherapy for Merkel cell carcinoma: A systematic review and meta-analysis.

Fetched: March 29th, 2020, 5:00am GMT

Adjuvant radiotherapy for Merkel cell carcinoma: A systematic review and meta-analysis.

Radiother Oncol. 2019 05;134:211-219

Authors: Petrelli F, Ghidini A, Torchio M, Prinzi N, Trevisan F, Dallera P, De Stefani A, Russo A, Vitali E, Bruschieri L, Costanzo A, Seghezzi S, Ghidini M, Varricchio A, Cabiddu M, Barni S, de Braud F, Pusceddu S

Abstract
Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous malignancy with a high propensity for local recurrence and regional and distant metastases. The main treatment is surgery with narrow excision margins and draining nodes, plus or minus adjuvant radiotherapy (RT) on the surgical bed and/or lymph nodes. We performed a systematic review and meta-analysis of the benefits of adjuvant RT in MCC treatment. PubMed, EMBASE, and the Cochrane Library were systematically searched to identify relevant studies published before September 2018. Prospective trials and retrospective series comparing adjuvant RT vs. no RT in resected primary MCCs were included. Primary endpoint was to evaluate the outcomes of MCC patients who received adjuvant RT in term of overall survival (OS) and disease-free survival (DFS). Hazard ratios (HRs) for OS and DFS were aggregated according to a fixed or random effect model. Secondary endpoints were local, locoregional, and distant DFS. A total of 17,179 MCCs across 29 studies were analysed. There was a significant difference in OS between the RT and no RT arms (HR = 0.81, 95%CI 0.75-0.86, P < 0.001). There was also a significant difference in DFS in favour of adjuvant RT (HR = 0.45, 95%CI 0.32-0.62, P < 0.001). Adjuvant RT improved locoregional DFS and local DFS but not distant DFS (HR = 0.3, 95%CI 0.22-0.42; HR = 0.21, 95%CI 0.14-0.33, and HR = 0.79, 95%CI 0.49-1.14, respectively). Meta-regression analysis showed that high Newcastle-Ottawa scale scores, stage I-II MCCs, shorter follow-up durations, size >2 cm, and being of a younger age were associated with increased OS. This systematic review and meta-analysis suggests a survival and DFS benefit for postoperative radiation of MCCs. Intermediate stage MCCs derive the maximum benefit with local and regional relapses reduced by 80% and 70%, respectively. Conversely, distant metastases were not significantly prevented.

PMID: 31005218 [PubMed - indexed for MEDLINE]

Updates and new perspectives in nonmelanoma skin cancer therapy: highlights from 'Immunotherapy Bridge'.

Fetched: March 28th, 2020, 5:00am GMT

Updates and new perspectives in nonmelanoma skin cancer therapy: highlights from 'Immunotherapy Bridge'.

Immunotherapy. 2020 Mar 24;:

Authors: Ascierto PA, Garbe C

Abstract
Over the last few years, extensive research has improved our understanding of tumor immunology and has enabled the development of novel treatments. The state of the art of immunotherapy in various types of malignancies was exhaustively discussed in the 'Immunotherapy bridge' meeting, which was held in Naples on 4-5 December 2019. Highlights related to the immunological treatment of nonmelanoma skin cancer are the content of this article.

PMID: 32208790 [PubMed - as supplied by publisher]

Immunologic Characteristics of Nonmelanoma Skin Cancers: Implications for Immunotherapy.

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

Immunologic Characteristics of Nonmelanoma Skin Cancers: Implications for Immunotherapy.

Am Soc Clin Oncol Educ Book. 2020 Mar;40:1-10

Authors: Hall ET, Fernandez-Lopez E, Silk AW, Dummer R, Bhatia S

Abstract
In this review, we summarize the immunology of nonmelanoma skin cancers (NMSCs) and the clinical data with immunotherapy in this heterogeneous group of cancers that include basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (CSCC), and Merkel cell carcinoma (MCC). NMSCs are exceedingly common, and their treatment consumes substantial health care resources. Annual global mortality from NMSCs is comparable to that from malignant melanoma. Although the majority of NMSCs are localized at diagnosis and are treated effectively with surgery, metastases (nodal and distant) can sometimes arise and require systemic therapy. Given the success of immunotherapy in treating cutaneous melanoma, there has been an increasing interest in studying the immunology of NMSCs. Immunocompromised patients have a substantially higher risk of developing NMSCs (particularly CSCC and MCC), suggesting a role of the immune system in the pathogenesis of these cancers. Similar to cutaneous melanoma, the pathogenesis of BCC, CSCC, and virus-negative MCC is related to DNA damage from ultraviolet radiation exposure, and these cancers have a very high tumor mutational burden, which likely results in higher levels of tumor neoantigens that may be targets for the immune system. Viral antigens in virus-positive MCC are also strongly immunogenic. Emerging data from clinical trials of immune checkpoint inhibitors in NMSCs look very promising and are rapidly changing the treatment landscape of these cancers. Specifically, pembrolizumab and avelumab are U.S. Food and Drug Administration-approved for treatment of metastatic MCC and cemiplimab for metastatic CSCC. Several ongoing trials are investigating novel immunotherapies (monotherapies as well as combination) for treatment of NMSCs.

PMID: 32207669 [PubMed - in process]

The Obesity-Related Gut Bacterial and Viral Dysbiosis Can Impact the Risk of Colon Cancer Development.

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

The Obesity-Related Gut Bacterial and Viral Dysbiosis Can Impact the Risk of Colon Cancer Development.

Microorganisms. 2020 Mar 19;8(3):

Authors: Campisciano G, de Manzini N, Delbue S, Cason C, Cosola D, Basile G, Ferrante P, Comar M, Palmisano S

Abstract
An incorrect food regimen from childhood is suggested to negatively impact the gut microbiome composition leading to obesity and perhaps to colon rectal cancer (CRC) in adults. In this study, we show that the obesity and cancer gut microbiota share a characteristic microbial profile with a high colonization by mucin degraders species, such as Hafnia alvei and Akkermansia muciniphila. In addition, the species Clostridium bolteae, a bacterium associated with insulin resistance, dyslipidemia, and inflammation, has been associated with the presence of oncogenic Human Polyomaviruses (HPyVs). Merkel cell Polyomavirus (MCPyV) and BK Polyomavirus (BKPyV) were the most frequently oncogenic viruses recovered in the gut of both obese and tumor patients. Considering the high seroprevalence of HPyVs in childhood, their association with specific bacterial species deserve to be further investigated. Data from the present study highlight the presence of a similar microbiome pattern in CRC and obese subjects, suggesting that obese microbiome may represent an opportunity for tumorigenic/driver bacteria and viruses to trigger cell transformation.

PMID: 32204328 [PubMed]

Prognostic Significance of "Nonsolid" Microscopic Metastasis in Merkel Cell Carcinoma Sentinel Lymph Nodes.

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

Prognostic Significance of "Nonsolid" Microscopic Metastasis in Merkel Cell Carcinoma Sentinel Lymph Nodes.

Am J Surg Pathol. 2019 07;43(7):907-919

Authors: Erstine EM, Tetzlaff MT, Jia X, Aung PP, Prieto VG, Funchain P, Gastman BR, Billings SD, Ko JS

Abstract
Our recent work regarding Merkel cell carcinoma sentinel lymph node (SLN) metastasis found that "solid" pattern microscopic metastasis conferred worse prognosis than the "nonsolid" ones. The goals of the present study were to (1) compare the prognostic significance/outcomes of 2 diagnostic groups-patients with a nonsolid pattern of SLN metastasis and those with diagnostically negative SLN biopsies (SLNB), and (2) evaluate the durability of SLN metastasis after extensive sectioning. Five-level, step-wise sectioning at 250-μm intervals was performed in all SLN blocks with an immunohistochemical stain for CK20 on all levels. The presence and pattern of metastases were recorded and analyzed as were corresponding patient and tumor parameters. Median follow-up durations for all patients (n=38), positive SLNB (n=16) and negative SLNB (n=22) groups were 56.3, 50.4, and 66.8 months, respectively. Overall survival (OS) and disease-specific survival (DSS) did not differ between the 2 diagnostic groups (OS P=0.65, DSS P=0.37) but did differ by immune status (immunocompetent vs. immunosuppressed, OS P=0.03, DSS P=0.005) and primary tumor category (OS P<0.0001, DSS P=0.001). On deeper sectioning, all 16 diagnostically positive SLNB continued to show nonsolid microscopic metastasis, and 32% (7/22) diagnostically negative SLNB revealed nonsolid metastasis. DSS was worse for sinusoidal-pattern metastasis versus all others (P=0.02). Five of 38 patients (13%) died of disease; the only immunocompetent patient had sinusoidal-pattern metastasis discovered in a diagnostically negative SLNB. Our data suggest that outcome for nonsolid metastasis is similar to that of negative SLNB with the exception of the sinusoidal pattern, which was associated with worse outcome. Larger studies are warranted to quantify and compare microscopic metastatic tumor burden by pattern and confirm whether the sinusoidal pattern confers an intermediate prognostic risk between solid and other nonsolid microscopic metastases.

PMID: 31094923 [PubMed - indexed for MEDLINE]

Clinical and molecular characterization of virus-positive and virus-negative Merkel cell carcinoma.

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

Clinical and molecular characterization of virus-positive and virus-negative Merkel cell carcinoma.

Genome Med. 2020 Mar 18;12(1):30

Authors: Starrett GJ, Thakuria M, Chen T, Marcelus C, Cheng J, Nomburg J, Thorner AR, Slevin MK, Powers W, Burns RT, Perry C, Piris A, Kuo FC, Rabinowits G, Giobbie-Hurder A, MacConaill LE, DeCaprio JA

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine carcinoma of the skin caused by either the integration of Merkel cell polyomavirus (MCPyV) and expression of viral T antigens or by ultraviolet-induced damage to the tumor genome from excessive sunlight exposure. An increasing number of deep sequencing studies of MCC have identified significant differences between the number and types of point mutations, copy number alterations, and structural variants between virus-positive and virus-negative tumors. However, it has been challenging to reliably distinguish between virus positive and UV damaged MCC.
METHODS: In this study, we assembled a cohort of 71 MCC patients and performed deep sequencing with OncoPanel, a clinically implemented, next-generation sequencing assay targeting over 400 cancer-associated genes. To improve the accuracy and sensitivity for virus detection compared to traditional PCR and IHC methods, we developed a hybrid capture baitset against the entire MCPyV genome and software to detect integration sites and structure.
RESULTS: Sequencing from this approach revealed distinct integration junctions in the tumor genome and generated assemblies that strongly support a model of microhomology-initiated hybrid, virus-host, circular DNA intermediate that promotes focal amplification of host and viral DNA. Using the clear delineation between virus-positive and virus-negative tumors from this method, we identified recurrent somatic alterations common across MCC and alterations specific to each class of tumor, associated with differences in overall survival. Finally, comparing the molecular and clinical data from these patients revealed a surprising association of immunosuppression with virus-negative MCC and significantly shortened overall survival.
CONCLUSIONS: These results demonstrate the value of high-confidence virus detection for identifying molecular mechanisms of UV and viral oncogenesis in MCC. Furthermore, integrating these data with clinical data revealed features that could impact patient outcome and improve our understanding of MCC risk factors.

PMID: 32188490 [PubMed - in process]

miRNAs in the Diagnosis and Prognosis of Skin Cancer.

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

miRNAs in the Diagnosis and Prognosis of Skin Cancer.

Front Cell Dev Biol. 2020;8:71

Authors: Neagu M, Constantin C, Cretoiu SM, Zurac S

Abstract
Skin cancer is, at present, the most common type of malignancy in the Caucasian population. Its incidence has increased rapidly in the last decade for both melanoma and non-melanoma skin cancer. Differential expression profiles of microRNAs (miRNAs) have been reported for a variety of different cancers, including skin cancers. Since miRNAs' discovery as regulators of gene expression, their importance grew in the field of oncology. miRNAs can post-transcriptionally regulate gene expression, tumor initiation, development progression, and aggressiveness. Nowadays, these short regulatory RNAs are perceived as one of the epigenetic markers for the identification of new diagnostic and/or prognostic molecular markers. Moreover, as miRNAs can drive tumorigenesis, they might eventually represent new therapy targets. Some miRNAs are pleiotropic, such as miR-214, which was found deregulated in several other tumors besides skin cancers. Some others are specific for one or more skin cancer types, like miR-21 and miR-221 for cutaneous melanoma and cutaneous squamous carcinoma or miR-155 for melanoma and cutaneous lymphoma. The goal of this review was to summarize some of the main miRNA detection technologies that are used to evaluate miRNAs in tissues and body fluids. Furthermore, their quantification limits, conformity, and robustness are discussed. Aberrant miRNA expression is analyzed for cutaneous melanoma, cutaneous squamous cell carcinoma (CSCC), skin lymphomas, cutaneous lymphoma, and Merkel cell carcinoma (MCC). In this type of disease, miRNAs are described as potential biomarkers to diagnose early lesion and/or early metastatic disease. In the future, whether in tissue or circulating in body fluids, miRNAs will gain their place in skin cancer diagnosis, prognosis, and future therapeutic targets.

PMID: 32185171 [PubMed]

Prevalent and diverse intratumoral oncoprotein-specific CD8+ T cells within polyoma virus-driven Merkel cell carcinomas.

Fetched: March 19th, 2020, 5:00am GMT

Prevalent and diverse intratumoral oncoprotein-specific CD8+ T cells within polyoma virus-driven Merkel cell carcinomas.

Cancer Immunol Res. 2020 Mar 16;:

Authors: Jing L, Ott M, Church CD, Kulikauskas RM, Ibrani D, Iyer JG, Afanasiev OK, Colunga A, Cook MM, Xie H, Greninger AL, Paulson KG, Chapuis AG, Bhatia S, Nghiem P, Koelle DM

Abstract
Merkel cell carcinoma (MCC) is often caused by persistent expression of Merkel cell polyomavirus (MCPyV) T-antigen (T-Ag). These non-self proteins comprise about 400 amino acids (AAs). Clinical responses to immune checkpoint inhibitors, seen in about half of patients, may relate to T-Ag-specific T cells. Strategies to increase CD8+ T-cell number, breadth, or function could augment checkpoint inhibition, but vaccines to augment immunity must avoid delivery of oncogenic T-antigen domains. We probed MCC tumor-infiltrating lymphocytes (TILs) with an artificial antigen-presenting cell (aAPC) system and confirmed T-Ag recognition with synthetic peptides, HLA-peptide tetramers, and dendritic cells (DCs). TILs from 9 of 12 (75%) subjects contained CD8+ T cells recognizing 1-8 MCPyV epitopes per person. Analysis of 16 MCPyV CD8+ TIL epitopes and prior TIL data indicated that 97% of MCPyV+ MCC patients had HLA alleles with the genetic potential that restrict CD8+ T-cell responses to MCPyV T-Ag. The LT AA 70-110 region was epitope-rich, whereas the oncogenic domains of T-Ag were not commonly recognized. Specific recognition of T-Ag-expressing DCs was documented. Recovery of MCPyV oncoprotein-specific CD8+ TILs from most tumors indicated that antigen indifference was unlikely to be a major cause of checkpoint inhibition failure. The myriad of epitopes restricted by diverse HLA alleles indicate that vaccination can be a rational component of immunotherapy if tumor immune suppression can be overcome, and the oncogenic regions of T-Ag can be modified without impacting immunogenicity.

PMID: 32179557 [PubMed - as supplied by publisher]

Comprehensive metagenomic analysis of blastic plasmacytoid dendritic cell neoplasm.

Fetched: March 19th, 2020, 5:00am GMT

Comprehensive metagenomic analysis of blastic plasmacytoid dendritic cell neoplasm.

Blood Adv. 2020 Mar 24;4(6):1006-1011

Authors: Nomburg J, Bullman S, Chung SS, Togami K, Walker MA, Griffin GK, Morgan EA, LeBoeuf NR, DeCaprio JA, Meyerson M, Lane AA

Abstract
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a hematologic malignancy believed to originate from plasmacytoid dendritic cells (pDCs), the immune cells responsible for producing type 1 interferons during infection. Nearly all patients with BPDCN have prominent skin involvement, with cutaneous infiltration occupying the dermis and subcutis. One half of patients present with BPDCN cells only in the skin, with no evidence of disease elsewhere. Because normal pDCs are rare or absent in cutaneous sites, and they only traffic to the skin after activation by pathogen or inflammation, our aim was to determine if a microorganism is associated with BPDCN. We performed RNA sequencing in BPDCN skin and bone marrow, with cutaneous T-cell lymphoma (CTCL) and normal skin as controls. GATK-PathSeq was used to identify known microbial sequences. Bacterial reads in BPDCN skin were components of normal flora and did not distinguish BPDCN from controls. We then developed a new computational tool, virID (Viral Identification and Discovery; [https:] for identification of microbial-associated reads remaining unassigned after GATK-PathSeq. We found no evidence for a known or novel virus in BPDCN skin or bone marrow, despite confirming that virID could identify Merkel cell polyomavirus in Merkel cell carcinoma, human papillomavirus in head and neck squamous cell carcinoma, and Kaposi's sarcoma herpesvirus in Kaposi's sarcoma in a blinded fashion. Thus, at the level of sensitivity used here, we found no clear pathogen linked to BPDCN.

PMID: 32182365 [PubMed - in process]

Regulation of Autophagy in Cells Infected With Oncogenic Human Viruses and Its Impact on Cancer Development.

Fetched: March 19th, 2020, 5:00am GMT

Regulation of Autophagy in Cells Infected With Oncogenic Human Viruses and Its Impact on Cancer Development.

Front Cell Dev Biol. 2020;8:47

Authors: Vescovo T, Pagni B, Piacentini M, Fimia GM, Antonioli M

Abstract
About 20% of total cancer cases are associated to infections. To date, seven human viruses have been directly linked to cancer development: high-risk human papillomaviruses (hrHPVs), Merkel cell polyomavirus (MCPyV), hepatitis B virus (HBV), hepatitis C virus (HCV), Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV), and human T-lymphotropic virus 1 (HTLV-1). These viruses impact on several molecular mechanisms in the host cells, often resulting in chronic inflammation, uncontrolled proliferation, and cell death inhibition, and mechanisms, which favor viral life cycle but may indirectly promote tumorigenesis. Recently, the ability of oncogenic viruses to alter autophagy, a catabolic process activated during the innate immune response to infections, is emerging as a key event for the onset of human cancers. Here, we summarize the current understanding of the molecular mechanisms by which human oncogenic viruses regulate autophagy and how this negative regulation impacts on cancer development. Finally, we highlight novel autophagy-related candidates for the treatment of virus-related cancers.

PMID: 32181249 [PubMed]

Permalink for 'Global PD-L1 Signals and Tumor-Infiltrating Lymphocytes: Markers of Immunogenicity in Different Subsets of Merkel Cell Carcinoma and Potential Therapeutic Implications.'

Global PD-L1 Signals and Tumor-Infiltrating Lymphocytes: Markers of Immunogenicity in Different Subsets of Merkel Cell Carcinoma and Potential Therapeutic Implications.

Fetched: March 18th, 2020, 5:00am GMT

Global PD-L1 Signals and Tumor-Infiltrating Lymphocytes: Markers of Immunogenicity in Different Subsets of Merkel Cell Carcinoma and Potential Therapeutic Implications.

Am J Dermatopathol. 2019 Nov;41(11):819-825

Authors: Walsh NM, Castonguay MC, Carter MD, Pasternak S, Ly TY, Doucette S, Hanly JG, Saggini A, Cerroni L

Abstract
We previously studied the genetic and immunohistochemical profiles of subsets of Merkel cell carcinoma (MCC) stratified by morphology and Merkel cell polyomavirus (MCPyV) status. Recent advances in the immunotherapy of this disease prompted us to examine markers of immunogenicity [PD-L1 expression and tumor-infiltrating lymphocytes (TILS) in these subsets]. The observed clinical responses to checkpoint inhibition of the PD-1/PD-L1 pathway have not correlated with PD-L1 expression by MCC cells, and recent evidence suggests that functions of this pathway within the immune tumor microenvironment may be relevant. We conducted a semiquantitative (high, moderate, and minimal) immunohistochemical evaluation of the global PD-L1 signal in 52 cases of MCC, segregated in 3 subsets [pure MCPyV-positive (n = 28), pure MCPyV-negative (n = 9), and combined MCPyV-negative (n = 15)]. TILS were categorized as brisk, nonbrisk, or absent. Intersubset comparisons revealed that high global PD-L1 signals were exclusively associated with pure MCPyV-positive MCCs contrasted with virus-negative cases (P = 0.0003). Moderate signals were seen across all 3 groups. Brisk TILS were significantly associated with MCPyV-positive MCCs compared with MCPyV-negative cases (P = 0.029). Neither parameter (PD-L1 or TILS) was significantly different between the MCPyV-negative groups. Of potential clinical relevance, MCPyV seems to convey greater immunogenicity to MCCs than the high mutational burden/greater neoantigen load of MCPyV-negative cases. Interesting too is the fact that subset-related profiles of these markers mirrored those noted at genetic and immunohistochemical levels, separating pure MCPyV-positive MCCs from the virus-negative subsets.

PMID: 31634167 [PubMed - indexed for MEDLINE]

Co-occurrence of Merkel Cell Carcinoma and Chronic Inflammatory Demyelinating Polyneuropathy.

Fetched: March 13th, 2020, 5:00am GMT

Co-occurrence of Merkel Cell Carcinoma and Chronic Inflammatory Demyelinating Polyneuropathy.

JAMA Dermatol. 2020 Mar 11;:

Authors: Kuo AM, Barker CA

PMID: 32159728 [PubMed - as supplied by publisher]

Permalink for 'The Possibility of Using Genotoxicity, Oxidative Stress and Inflammation Blood Biomarkers to Predict the Occurrence of Late Cutaneous Side Effects after Radiotherapy.'

The Possibility of Using Genotoxicity, Oxidative Stress and Inflammation Blood Biomarkers to Predict the Occurrence of Late Cutaneous Side Effects after Radiotherapy.

Fetched: March 13th, 2020, 5:00am GMT

The Possibility of Using Genotoxicity, Oxidative Stress and Inflammation Blood Biomarkers to Predict the Occurrence of Late Cutaneous Side Effects after Radiotherapy.

Antioxidants (Basel). 2020 Mar 07;9(3):

Authors: Chaouni S, Lecomte DD, Stefan D, Leduc A, Barraux V, Leconte A, Grellard JM, Habrand JL, Guillamin M, Sichel F, Laurent C

Abstract
Despite the progresses performed in the field of radiotherapy, toxicity to the healthy tissues remains a major limiting factor. The aim of this work was to highlight blood biomarkers whose variations could predict the occurrence of late cutaneous side effects. Two groups of nine patients treated for Merkel Cell Carcinoma (MCC) were established according to the grade of late skin toxicity after adjuvant irradiation for MCC: grade 0, 1 or 2 and grade 3 or 4 of RTOG (Radiation Therapy Oncology Group)/EORTC (European Organization for Research and Treatment of Cancer). To try to discriminate these 2 groups, biomarkers of interest were measured on the different blood compartments after ex vivo irradiation. In lymphocytes, cell cycle, apoptosis and genotoxicity were studied. Oxidative stress was evaluated by the determination of the erythrocyte antioxidant capacity (superoxide dismutase, catalase, glutathione peroxidase, reduced and oxidized glutathione) as well as degradation products (protein carbonylation, lipid peroxidation). Inflammation was assessed in the plasma by the measurement of 14 cytokines. The most radiosensitive patients presented a decrease in apoptosis, micronucleus frequency, antioxidant enzyme activities, glutathione and carbonyls; and an increase in TNF-a (Tumor Necrosis Factor a), IL-8 (Interleukin 8) and TGF-β1 (Transforming Growth Factor β1) levels. These findings have to be confirmed on a higher number of patients and before radiotherapy and could allow to predict the occurrence of late skin side effects after radiotherapy.

PMID: 32156042 [PubMed]

Oncogenic Viral Protein Interactions with p53 Family Proteins.

Fetched: March 13th, 2020, 5:00am GMT

Oncogenic Viral Protein Interactions with p53 Family Proteins.

Klin Onkol. 2019;32(Supplementum 3):72-77

Authors: Brychtová V, Hrabal V, Vojtěšek B

Abstract
BACKGROUND: Cellular transformation induced by oncogenic viruses is a complex process including viral molecules, host cells and environmental factors. Viruses alone are unable to reproduce and thus they need a host to use their signalling, proteosynthetic and metabolic pathways. One target host molecule is the p53 tumour suppressor. Viral proteins functionally inactivate p53 and deregulate the expression of proteins active during apoptosis, cell proliferation and DNA damage response. Hepatitis virus B HbX protein and hepatitis virus C proteins NS2 and NS5A interact with p53 and prevent its localisation to the nucleus and thus reduce its transcriptional activity. Another mechanism lies in elevated p53 degradation caused by the BZLF1 protein of the Epstein-Barr virus, the LANA protein of the Kaposi sarcoma virus and human papilloma virus E6. The Merkel cell polyomavirus large T antigen does not interact directly with p53, however it acts through downregulation of p53 mediated transcription. The tax protein of human T cell lymphotropic virus type 1 modifies p53 posttranslationally and thus blocks its interaction with other factors of transcription machinery. Due to its tumour suppressor function and role in the maintenance of the genome integrity, the p53 protein is one of the best studied proteins. Following this, evolutionary homologues with important developmental functions p63 and p73 are intensively studied as well. Their roles in oncogenesis have not been clarified yet.
PURPOSE: This review describes some of their known interactions with oncogenic viral proteins.

PMID: 31627709 [PubMed - indexed for MEDLINE]

Permalink for 'A pilot study of alternative TrkAIII splicing in Merkel cell carcinoma: a potential oncogenic mechanism and novel therapeutic target.'

A pilot study of alternative TrkAIII splicing in Merkel cell carcinoma: a potential oncogenic mechanism and novel therapeutic target.

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

A pilot study of alternative TrkAIII splicing in Merkel cell carcinoma: a potential oncogenic mechanism and novel therapeutic target.

J Exp Clin Cancer Res. 2019 Oct 22;38(1):424

Authors: Cappabianca L, Guadagni S, Maccarone R, Sebastiano M, Chiominto A, Farina AR, Mackay AR

Abstract
BACKGROUND: Merkel cell carcinomas (MCCs) are rare, aggressive, therapeutically-challenging skin tumours that are increasing in incidence and have poor survival rates. The majority are caused by genomic Merkel cell polyomavirus (MCPyV) integration and MCPyV T-antigen expression. Recently, a potential oncogenic role for the tropomyosin-related tyrosine kinase A receptor (TrkA) has been proposed in MCC. Alternative TrkAIII splicing is a TrkA oncogenic activation mechanism that can be promoted by SV40 large T-antigen, an analogue of MCPyV large T-antigen. In this pilot study, therefore, we have evaluated TrkAIII splicing as a novel potential oncogenic mechanism and therapeutic target in MCPyV positive MCC.
METHODS: Formalin-fixed paraffin-embedded MCC tissues, consisting of 10 stage IV, 1 stage IIIB, 1 stage IIB, 4 stage IIA and 2 stage I tumours, from patients diagnosed and treated from September 2006 to March, 2019, at the University of L'Aquila, L'Aquila, Italy, were compared to 3 primary basal cell carcinomas (BCCs), 3 primary squamous cell carcinomas (SCCs) and 2 normal skin samples by RT-PCR for MCPyV large T-antigen, small T-antigen, VP-1 expression and alternative TrkAIII splicing and by indirect IF for evidence of intracellular TrkA isoform expression and activation.
RESULTS: 9 of 10 Recurrent stage IV MCCs were from patients (P.1-3) treated with surgery plus loco-regional Melphalan chemotherapy and remaining MMCs, including 1 stage IV tumour, were from patients treated with surgery alone (P. 4-11). All MCPyV positive MCCs exhibiting MCPyV large T-antigen expression (17 of 18MCCs, 90%) exhibited alternative TrkAIII mRNA splicing (100%), which was exclusive in a significant number and predominant (> 50%) in all stage IV MCCs and the majority of stage 1-III MCCs. MCCs with higher TrkAIII to 18S rRNA expression ratios also exhibited strong or intermediate immunoreactivity to anti-TrkA antibodies, consistent with cytoplasmic TrkAIII expression and activation. In contrast, the MCPyV negative MCC, BCCs, SCCs and normal skin tissues all exhibited exclusive fully-spliced TrkA mRNA expression, associated with variable immunoreactivity for non-phosphorylated but not phosphorylated TrkA.
CONCLUSIONS: MCPyV positive MCCs but not MCPyV negative MCC, BCCs and SCCs exhibit predominant alternative TrkAIII splicing, with evidence of intracellular TrkAIII activation. This establishes a new potential MCC subset, unveils a novel potential MCPyV oncogenic mechanism and identifies TrkAIII as a novel potential therapeutic target in MCPyV positive MCC.

PMID: 31640749 [PubMed - indexed for MEDLINE]

Permalink for 'Sentinel lymph node positivity and overall survival in immunosuppressed patients with Merkel cell carcinoma: A national cohort study.'

Sentinel lymph node positivity and overall survival in immunosuppressed patients with Merkel cell carcinoma: A national cohort study.

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

Sentinel lymph node positivity and overall survival in immunosuppressed patients with Merkel cell carcinoma: A national cohort study.

Br J Dermatol. 2020 Mar 09;:

Authors: Song Y, Zheng C, Shannon AB, Fraker DL, Miura JT, Karakousis GC

Abstract
Merkel cell carcinoma (MCC), a neuroendocrine cutaneous malignancy, may be especially aggressive in immunocompromised patients.1,2 Factors associated with sentinel lymph node (SLN) involvement and overall survival (OS) have been described for the general population with clinically-localized MCC, but prognostic factors in immunosuppressed patients have not been well characterized.3,4 The study objectives were to identify characteristics associated with SLN status and OS in this patient population.

PMID: 32147810 [PubMed - as supplied by publisher]

Prevalence of CD8+ cytotoxic lymphocytes in human neoplasms.

Fetched: March 8th, 2020, 5:00am GMT

Prevalence of CD8+ cytotoxic lymphocytes in human neoplasms.

Cell Oncol (Dordr). 2020 Mar 05;:

Authors: Blessin NC, Spriestersbach P, Li W, Mandelkow T, Dum D, Simon R, Hube-Magg C, Lutz F, Viehweger F, Lennartz M, Fraune C, Nickelsen V, Fehrle W, Göbel C, Weidemann S, Clauditz T, Lebok P, Möller K, Steurer S, Izbicki JR, Sauter G, Minner S, Jacobsen F, Luebke AM, Büscheck F, Höflmayer D, Wilczak W, Burandt E, Hinsch A

Abstract
PURPOSE: Immune checkpoint inhibitors have recently been approved by the US FDA as first and/or second line therapy in a subset of cancer types. Recent evidence suggests that the quantity of tumor infiltrating lymphocytes (TILs) influences the likelihood of response to immune checkpoint inhibitors. Here, we set out to assess the density of CD8+ lymphocytes in a wide range of different cancer types and subtypes.
METHODS: The density of CD8+ lymphocytes was compared across different cancer types using tissue microarrays (TMAs) composed of up to 50 tumor samples each from 84 different cancer types and subtypes. In total 2652 cancers and 608 normal tissues were successfully analyzed by CD8 immunohistochemistry followed by automated image analysis of digitized slides.
RESULTS: We found that the median CD8+ lymphocyte counts ranged from 6 cells/mm2 in pleomorphic adenoma up to 1573 cells/mm2 in Hodgkin's lymphoma. The CD8 counts were generally lower in normal tissues compared to cancer tissues. Blood vessels of the spleen were the only non-lymphatic tissue staining positive for CD8. Tumor types approved for checkpoint inhibitor therapy, including malignant melanoma (81), muscle invasive urothelial carcinoma (119), small cell lung cancer (120), clear cell renal cell cancer (153), squamous cell carcinoma (189) and adenocarcinoma of the lung (328) as well as Hodgkin's lymphoma (1573) were all ranking among the upper half of our list. Comparably high CD8 densities (median cells/mm2) were also found in several rare and aggressive cancer types including Merkel cell carcinoma (70), angiosarcoma (95), anaplastic thyroid cancer (156) and embryonal carcinoma of the testis (186). In 73 of the 84 analyzed cancer types, the highly variable CD8 counts occasionally exceeded the average CD8 count of tumors for which checkpoint inhibitors have been approved.
CONCLUSION: These data support the concept that among most tumor types at least some individual cancers may benefit from treatment with immune checkpoint inhibitors.

PMID: 32141029 [PubMed - as supplied by publisher]

Permalink for 'TdT Expression Is a Marker of Better Survival in Merkel Cell Carcinoma, and Expression of B-Cell Markers Is Associated With Merkel Cell Polyomavirus.'

TdT Expression Is a Marker of Better Survival in Merkel Cell Carcinoma, and Expression of B-Cell Markers Is Associated With Merkel Cell Polyomavirus.

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

TdT Expression Is a Marker of Better Survival in Merkel Cell Carcinoma, and Expression of B-Cell Markers Is Associated With Merkel Cell Polyomavirus.

Am J Clin Pathol. 2020 Mar 05;:

Authors: Hoang MP, Donizy P, Wu CL, Kopczynski J, Pieniazek M, Miller DM, Ryś J

Abstract
OBJECTIVES: Merkel cell carcinoma is a rare but very aggressive cutaneous tumor. We evaluated the prognostic potential of B-cell markers (terminal deoxynucleotidyl transferase [TdT], PAX5, CD117), follicular stem cell markers (CK15, CK19), p63, p53, RB, and Merkel cell polyomavirus (MCPyV; CM2B4) in 136 primary cutaneous Merkel cell carcinomas.
METHODS: Clinical, histopathologic, and immunohistochemical analyses were performed. The results were correlated with patient outcomes by Fisher exact test, log-rank tests, and Cox multivariate models.
RESULTS: By Fisher exact test, although TdT significantly correlated with both lack of progression (P = .0087) and alive status (P = .0056), MCPyV status correlated only with alive status (P = .031). In univariate analyses, TdT, MCPyV, and RB significantly correlated with improved overall survival, whereas p63 and CK15 correlated with worse overall survival. However, in multivariate analyses, only TdT expression remained as an independent predictor of improved overall survival, Merkel cell carcinoma-specific survival, and progression-free survival. By linear regression analyses, significant correlations between MCPyV vs TdT, PAX5, and CD117 were observed.
CONCLUSIONS: TdT expression is a potential marker of better survival in Merkel cell carcinoma. Expression of B-cell markers is associated with MCPyV, suggesting that clonal viral integration might play a role in the expression of these markers.

PMID: 32134459 [PubMed - as supplied by publisher]

Low prevalence of Merkel cell polyomavirus in human epithelial thymic tumors.

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

Low prevalence of Merkel cell polyomavirus in human epithelial thymic tumors.

Thorac Cancer. 2019 03;10(3):445-451

Authors: Chteinberg E, Klufah F, Rennspiess D, Mannheims MF, Abdul-Hamid MA, Losen M, Keijzers M, De Baets MH, Kurz AK, Zur Hausen A

Abstract
BACKGROUND: The etiology of thymic epithelial tumors is unknown. Murine polyomavirus strain PTA has been shown to induce thymomas in mice. Recently, using diverse molecular techniques, we reported the presence of human polyomavirus 7 (HPyV7) in thymic epithelial tumors. In the present study, we investigated the prevalence of Merkel cell polyomavirus (MCPyV) in thymic epithelial tumors.
METHODS: Thirty-six thymomas were screened for MCPyV by PCR and subsequently tested by DNA and RNA in situ hybridization and immunohistochemistry. Twenty-six thymomas were diagnosed with myasthenia gravis (MG).
RESULTS: MCPyV DNA was detected by PCR in 7 (19.4%) of the 36 thymic epithelial tumors and in six of these, the presence of MCPyV was confirmed by fluorescence situ hybridization. Of these, 3 (28.6%) revealed weak MCPyV LT-antigen protein expression. In addition, one of the MCPyV positive thymomas tested positive for MCPyV LT RNA with RNAscope. Of interest, two out of the three thymomas that previously tested positive for MCPyV by immunohistochemistry also tested positive for HPyV7. One of the 11 MG-negative and 2 of the 25 MG-positive were positive for MCPyV.
CONCLUSIONS: MCPyV DNA and MCPyV protein expression can be detected in human epithelial thymoma; however, to a far lesser extent than HPyV7. Our data strongly indicate that because of its infrequent detection and weak expression, MCPyV is unlikely to play an important role in the etiopathogenesis of human thymomas.

PMID: 30628176 [PubMed - indexed for MEDLINE]

Management Recommendations for Merkel Cell Carcinoma-A Danish Perspective.

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

Management Recommendations for Merkel Cell Carcinoma-A Danish Perspective.

Cancers (Basel). 2020 Feb 28;12(3):

Authors: Naseri S, Steiniche T, Ladekarl M, Bønnelykke-Behrndtz ML, Hölmich LR, Langer SW, Venzo A, Tabaksblat E, Klausen S, Skaarup Larsen M, Junker N, Chakera AH

Abstract
Merkel cell carcinoma (MCC) is a rare malignant neuroendocrine carcinoma of the skin with a poor prognosis and an apparent increase in incidence. Due to its rarity, evidence-based guidelines are limited, and there is a lack of awareness among clinicians. This review constitutes the consensus management recommendations developed by the Danish MCC expert group and is based on a systematic literature search. Patients with localized disease are recommended surgical excision and adjuvant radiotherapy to the primary site; however, this may be omitted in patients with MCC with low risk features. Patients with regional lymph node involvement are recommended complete lymph node removal and adjuvant radiotherapy in case of extracapsular disease. Metastatic disease was traditionally treated with chemotherapy, however, recent clinical trials with immune therapy have been promising. Immune checkpoint inhibitors targeting the programmed cell death protein 1(PD-1)/programmed death-ligand 1(PD-L1) axis should therefore be strongly considered as first-line treatment for fit patients. A 5-year follow-up period is recommended involving clinical exam every 3 months for 2 years and every 6 months for the following 3 years and PET-CT one to two times a year or if clinically indicated. These national recommendations are intended to offer uniform patient treatment and hopefully improve prognosis.

PMID: 32121063 [PubMed]

Systematic review of sentinel lymph node biopsy in Merkel cell carcinoma of the head and neck.

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

Systematic review of sentinel lymph node biopsy in Merkel cell carcinoma of the head and neck.

Head Neck. 2018 12;40(12):2704-2713

Authors: Karunaratne YG, Gunaratne DA, Veness MJ

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neuroendocrine tumor arising on the head and neck in 40%-50% of patients. Between 20% and 40% will harbor subclinical nodal metastasis.
METHODS: Using search terms 'Merkel AND sentinel', MEDLINE, PUMED, and EMBASE databases were systematically reviewed for publications regarding sentinel lymph node biopsy (SLNB) in classification I and II MCC of the head and neck.
RESULTS: Twenty-nine publications encompassing 136 patients were included. The SLNB finding was positive in 42 patients (30.9%). Primary MCC was located on the malar/zygomatic (34.4%), forehead/frontal (13.5%), and nasal (13.5%) regions. Recurrence in an SLNB negative nodal basin result occurred in 10 patients (false negative rate of 19.2%). Site of primary MCC was not associated with a false-negative SLNB result; however, there was a non-statistically significant trend for increased frequency among midline lesions.
CONCLUSIONS: Sentinel lymph node biopsy (SLNB) is recommended for eligible patients with classification I and II head and neck MCC.

PMID: 29934958 [PubMed - indexed for MEDLINE]

DETECTing Merkel Cell Polyomavirus in Merkel Tumors.

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

DETECTing Merkel Cell Polyomavirus in Merkel Tumors.

Front Mol Biosci. 2020;7:10

Authors: Arora R, Gupta K, Vijaykumar A, Krishna S

Abstract
Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer caused either by Merkel cell polyomavirus (MCV) T antigen expression, post-integration (~80% cases), or by UV-mediated DNA damage. Interestingly, overall survival of MCV-positive Merkel cell carcinoma patients is better, making this differential information of significant diagnostic and prognostic value. Also, MCV provides a direct target for therapy in MCC patients. Currently, the methods used for diagnosis of MCV in tumors are often discordant and unreliable. Here we used a guided molecular scissors based-DNA Endonuclease Targeted CRISPR Trans Reporter (DETECTR) technique to develop an in vitro molecular diagnostic tool for MCV-positive MCC. DETECTR couples recombinase polymerase based amplification of target MCV DNA with Cas12a mediated detection. CRISPR diagnostics couple specific detection followed by cutting of the pathogenic DNA by the Cas enzyme-gRNA complex, with non-specific cutting of ssDNA that provides a measurable visual cue. To detect MCV DNA in MCC, we designed Cas12a gRNAs targeting the MCV DNA and tested their targeting efficiency, and sensitivity using a fluorophore quencher labeled reporter assay. We show that MCV DETECTR system can detect MCV integrated in Merkel tumor rapidly, specifically and with femto-molar sensitivity. Our study is a preliminary, proof-of-principle analysis showing the use of CRISPR for MCV diagnosis. Further validation in human tumor samples is needed for its clinical use in the near future. This new system is promising and we hope it can be coupled with immunohistochemical studies to diagnose the viral status of MCC in clinics soon.

PMID: 32118036 [PubMed]

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
Not yet recruiting

Immunotherapy Merkel Adjuvant Trial

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

Conditions: Merkel Cell Carcinoma; Merkel Cell Carcinoma, Stage I; Merkel Cell Carcinoma, Stage II; Merkel Cell Carcinoma, Stage III; Neuroendocrine Tumors; Carcinoma Neuroendocrine Skin
Interventions: Drug: Avelumab; Drug: Placebo
Sponsor: Melanoma and Skin Cancer Trials Limited
Not yet recruiting

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

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

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

Targeted Therapy and Avelumab in Merkel Cell Carcinoma

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

Condition: Metastatic Merkel Cell Carcinoma
Interventions: Drug: Avelumab; Radiation: External Beam Radiation Therapy (EBRT); Radiation: Lutetium-177 (177Lu)-DOTATATE
Sponsor: Melanoma and Skin Cancer Trials Limited
Not yet recruiting

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

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

Conditions: Cancer; Neoplasms; Metastatic Cancer; Triple Negative Breast Cancer; Gastric Cancer; Cervical Cancer; Ovarian Cancer; Hepatocellular Carcinoma; Squamous Cell Carcinoma of Head and Neck; Urothelial Carcinoma; Urothelial Neoplasm; Non Small Cell Lung Cancer; Renal Cell Carcinoma; Locally Advanced Solid Tumor; Locally Advanced Malignant Neoplasm; Squamous Cell Carcinoma; Sarcoma; Merkel Cell Carcinoma; Bladder Cancer
Interventions: Drug: OC-001; Drug: OC-001 in Combination
Sponsor: Ocellaris Pharma, Inc.
Not yet 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
Not yet recruiting

LITT and Pembrolizumab in Recurrent Brain Metastasis

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

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

Immunotherapy With IFx-Hu2.0 Vaccine for Advanced MCC or cSCC

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

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

Adoptive Transfer of Tumor Infiltrating Lymphocytes for Advanced Solid Cancers

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

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

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

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

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

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

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

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

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

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

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

Lymph Node Identification in Skin Malignancy Using ICG Transcutaneously Study

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Atezolizumab and Bevacizumab in Treating Patients With Rare Solid Tumors

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Conditions: Carcinoma, Non-Small-Cell Lung; Urothelial Carcinoma; Malignant Melanoma; Head and Neck Squamous Cell Carcinoma
Interventions: Drug: CAN04; Drug: Pembrolizumab
Sponsor: Cantargia AB
Not yet 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
Not yet 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
Not yet recruiting

Cabozantinib in High Grade Neuroendocrine Neoplasms

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

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

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

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

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

Conditions: Colitis; Lung Non-Small Cell Carcinoma; Malignant Genitourinary System Neoplasm; Malignant Solid Neoplasm; Melanoma
Interventions: Biological: Infliximab; Biological: Vedolizumab
Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI)
Not yet recruiting

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

OH2 Injection in Solid Tumors

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

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

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

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

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

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

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

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

Cohort of Well-differentiated Grade 3 Neuroendocrine Digestive Tumors

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

Condition: Neuroendocrine Tumors
Intervention: Drug: platinum chemotherapy
Sponsors: Assistance Publique - Hôpitaux de Paris; Ipsen
Not yet 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)
Not yet recruiting

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

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

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

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

Portal Vein Resection in Pancreatic Neuroendocrine Tumours

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

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

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

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

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

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

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

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

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

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

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

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

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

Mobile Application to Collect PRO Data in NET Patients

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

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

Gallium-68 Labeled LM3 PET/CT in Neuroendocrine Tumors

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

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

National Cancer Institute "Cancer Moonshot Biobank"

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

Conditions: Acute Myeloid Leukemia; Castration-Resistant Prostate Carcinoma; Clinical Stage III Cutaneous Melanoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8; Hematopoietic and Lymphoid Cell Neoplasm; Lung Non-Small Cell Carcinoma; Lung Small Cell Carcinoma; Malignant Solid Neoplasm; Pathologic Stage III Cutaneous Melanoma AJCC v8; Pathologic Stage IIIA Cutaneous Melanoma AJCC v8; Pathologic Stage IIIB Cutaneous Melanoma AJCC v8; Pathologic Stage IIIC Cutaneous Melanoma AJCC v8; Pathologic Stage IIID Cutaneous Melanoma AJCC v8; Pathologic Stage IV Cutaneous Melanoma AJCC v8; Pathologic Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8; Refractory Plasma Cell Myeloma; Stage III Lung Cancer AJCC v8; Stage IIIA Lung Cancer AJCC v8; Stage IIIB Lung Cancer AJCC v8; Stage IIIC Lung Cancer AJCC v8; Stage IV Colorectal Cancer AJCC v8; Stage IV Lung Cancer AJCC v8; Stage IV Prostate Cancer AJCC v8; Stage IVA Colorectal Cancer AJCC v8; Stage IVA Lung Cancer AJCC v8; Stage IVA Prostate Cancer AJCC v8; Stage IVB Colorectal Cancer AJCC v8; Stage IVB Lung Cancer AJCC v8; Stage IVB Prostate Cancer AJCC v8; Stage IVC Colorectal Cancer AJCC v8
Interventions: Procedure: Biospecimen Collection; Other: Medical Chart Review
Sponsor: National Cancer Institute (NCI)
Not yet recruiting

Immunotherapy Merkel Adjuvant Trial

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

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

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

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

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

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

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

Conditions: Ectomesenchymoma; Recurrent Adrenal Gland Pheochromocytoma; Recurrent Ependymoma; Recurrent Ewing Sarcoma; Recurrent Hepatoblastoma; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Glioma; Recurrent Medulloblastoma; Recurrent Melanoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Rhabdoid Tumor; Recurrent Rhabdoid Tumor of the Kidney; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Recurrent Thyroid Gland Carcinoma; Recurrent WHO Grade II Glioma; Refractory Adrenal Gland Pheochromocytoma; Refractory Ependymoma; Refractory Ewing Sarcoma; Refractory Hepatoblastoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Glioma; Refractory Medulloblastoma; Refractory Melanoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Peripheral Primitive Neuroectodermal Tumor; Refractory Rhabdoid Tumor; Refractory Rhabdoid Tumor of the Kidney; Refractory Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma; Refractory Thyroid Gland Carcinoma; Refractory WHO Grade II Glioma; Wilms Tumor
Intervention: Drug: Tipifarnib
Sponsor: National Cancer Institute (NCI)
Not yet recruiting

Database ITANET - ENETS Registry

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

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

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

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

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

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

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

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

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

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

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

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

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

Conditions: Pulmonary Neuroendocrine Neoplasm; Pheochromocytoma; Paraganglioma; Thymus Carcinoid
Intervention: Drug: 177Lu-DOTATOC
Sponsor: Excel Diagnostics and Nuclear Oncology Center
Not yet recruiting

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

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

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

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

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

Effect of Dexmedetomidine on Brain Homeostasis and Neurocognitive Outcome

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

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

Targeted Therapy and Avelumab in Merkel Cell Carcinoma

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

A Study to Evaluate the Safety, Tolerability and Pharmacokinetics of HH2710 in Patient With Advanced Tumors

Posted: December 13th, 2019, 3:00pm GMT

Conditions: Advanced Tumors; Melanoma; Non-Small-Cell Lung Cancer; Erdheim-Chester Disease; Other RAS/RAF/MEK/ERK Mutated Tumors
Intervention: Drug: HH2710
Sponsor: ShangHai HaiHe Pharmaceutical
Recruiting

Study of INBRX-106 in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)

Posted: December 13th, 2019, 3:00pm GMT

Conditions: Solid Tumor; Non-Small Cell Lung Cancer; Melanoma; Head and Neck Cancer; Gastric Cancer; Renal Cell Carcinoma; Urothelial Carcinoma
Interventions: Drug: INBRX-106 - Hexavalent OX40 agonist antibody; Drug: Pembrolizumab
Sponsors: Inhibrx, Inc.; Merck Sharp & Dohme Corp.
Recruiting

Personalized CAPTEM Radiopeptide Therapy of Advanced, Non-resectable Neuroendocrine Cancer

Posted: December 11th, 2019, 3:00pm GMT

Condition: Neuroendocrine Tumors
Intervention: Drug: 177Lu-DOTATOC
Sponsors: University of Warmia and Mazury; Maria Sklodowska-Curie Institute - Oncology Center; The Medical University of Warsaw; Poland; The Diagnostic and Therapeutic Center Gammed; Poland; National Center for Research and Development, Poland
Recruiting

Granzyme B PET Imaging Drug as a Predictor of Immunotherapy Response in Melanoma or NSCLC Participants

Posted: November 19th, 2019, 3:00pm GMT

Conditions: Melanoma; Non-Small Cell Lung Cancer
Intervention: Drug: Single Arm
Sponsors: Cytosite Biopharma Inc.; Massachusetts General Hospital; University of Alabama at Birmingham
Recruiting

Adoptive Tumor-infiltrating Lymphocyte Transfer With Nivolumab for Melanoma

Posted: November 18th, 2019, 3:00pm GMT

Condition: Advanced Melanoma
Intervention: Drug: Combination of TIL Transfer with anti-PD-1 Therapy and low dose IL-2
Sponsors: University Hospital, Basel, Switzerland; GMP network of Basel
Not yet recruiting

Permalink for 'A Phase II Study on Adjuvant Vaccination With Dendritic Cells Loaded With Autologous Tumor Homogenate in Resected Stage IV Rare Cancers.'

A Phase II Study on Adjuvant Vaccination With Dendritic Cells Loaded With Autologous Tumor Homogenate in Resected Stage IV Rare Cancers.

Posted: November 18th, 2019, 3:00pm GMT

Conditions: Head Neck Tumors; Neuroendocrine Tumors; Soft Tissue Sarcoma; Rare Cancer; Vaccination
Interventions: Biological: Autologous DC vaccine; Drug: Interleukin-2
Sponsor: Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
Recruiting

Immunotherapy With IFx-Hu2.0 Vaccine for Advanced MCC or cSCC

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

A Study of ZN-c3 in Participants With Solid Tumors

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

Conditions: Solid Tumor; Epithelial Ovarian Cancer; Fallopian Tube Cancer; Peritoneal Cancer; Triple Negative Breast Cancer; Small Cell Lung Cancer; Metastatic Breast Cancer; Malignant Melanoma; Non Small Cell Lung Cancer; Urothelial Carcinoma
Interventions: Drug: ZN-c3; Drug: Talazoparib; Drug: Pembrolizumab
Sponsor: K-Group Beta
Recruiting

Testing the Combination of XL184 (Cabozantinib), Nivolumab, and Ipilimumab for Poorly Differentiated Neuroendocrine Tumors

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

Conditions: Metastatic Large Cell Neuroendocrine Carcinoma; Metastatic Neuroendocrine Carcinoma; Metastatic Neuroendocrine Neoplasm; Metastatic Small Cell Carcinoma
Interventions: Drug: Cabozantinib; Drug: Cabozantinib S-malate; Biological: Ipilimumab; Biological: Nivolumab
Sponsor: National Cancer Institute (NCI)
Recruiting

Permalink for 'Testing the Addition of a New Anti-cancer Drug, Radium-223 Dichloride, to the Usual Treatment (Cabozantinib) for Advanced Renal Cell Cancer That Has Spread to the Bone, the RadiCaL Study'

Testing the Addition of a New Anti-cancer Drug, Radium-223 Dichloride, to the Usual Treatment (Cabozantinib) for Advanced Renal Cell Cancer That Has Spread to the Bone, the RadiCaL Study

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

Conditions: Advanced Renal Cell Carcinoma; Chromophobe Renal Cell Carcinoma; Clear Cell Renal Cell Carcinoma; Collecting Duct Carcinoma; Kidney Medullary Carcinoma; Metastatic Malignant Neoplasm in the Bone; Papillary Renal Cell Carcinoma; Stage IV Renal Cell Cancer AJCC v8; Unclassified Renal Cell Carcinoma
Interventions: Drug: Cabozantinib; Drug: Cabozantinib S-malate; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Radiation: Radium Ra 223 Dichloride
Sponsor: National Cancer Institute (NCI)
Recruiting

Enterade in Carcinoid/Non-Carcinoid Syndrome Neuroendocrine Tumor Patients With Quality of Life Limiting Bowel Frequency

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

Conditions: Neuroendocrine Tumor; Carcinoid Syndrome
Interventions: Dietary Supplement: Enterade®; Other: Functional Assessment of Chronic Illness Therapy for Patients with Diarrhea (version 4.0)
Sponsors: Vanderbilt-Ingram Cancer Center; Entrinsic Health Solutions, Inc.
Recruiting

A Personalized NeoAntigen Cancer Vaccine Combined With Anti-PD-1 in Melanoma

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

Condition: Melanoma (Skin)
Interventions: Drug: Peptide; Drug: Anti-PD-1; Drug: rhGM-CSF; Drug: Imiquimod 5% Topical Cream
Sponsor: Xiangya Hospital of Central South University
Recruiting

Predicting Responsiveness in Oncology Patients Based on Host Response Evaluation During Anti Cancer Treatments

Posted: August 14th, 2019, 2:00pm GMT

Conditions: Stage IV Non-small Cell Lung Cancer; Stage IV Malignant Melanoma
Intervention: Other: Plasma sample collection
Sponsor: OncoHost Ltd.
Recruiting

An Investigational Scan (68Ga-DOTATATE PET/CT) in Diagnosing Pediatric Metastatic Neuroendocrine Tumors

Posted: July 31st, 2019, 2:00pm GMT

Conditions: Ganglioneuroblastoma; Ganglioneuroma; Metastatic Neuroblastoma
Interventions: Procedure: Computed Tomography; Drug: Gallium Ga 68-DOTATATE; Procedure: Positron Emission Tomography
Sponsors: Mayo Clinic; National Cancer Institute (NCI)
Recruiting

Open Label Study to Analyze the Effect of Telotristat Ethyl on Weight Regulation/Gain

Posted: July 26th, 2019, 2:00pm GMT

Conditions: Pancreatic Cancer; Neuroendocrine Tumors; Cachexia; Cancer
Intervention: Drug: telotristat ethyl
Sponsors: Andrew Hendifar, MD; Lexicon Pharmaceuticals
Not yet recruiting

Permalink for 'Peptide Receptor Radionuclide Therapy in the Treatment of Advanced, Non-resectable and/or Symptomatic Tumors With SSTR Overexpression'

Peptide Receptor Radionuclide Therapy in the Treatment of Advanced, Non-resectable and/or Symptomatic Tumors With SSTR Overexpression

Posted: July 23rd, 2019, 2:00pm GMT

Condition: Neuroendocrine Tumors
Interventions: Drug: 90Y-DOTATATE; Drug: (177Lu-DOTAOTyr3)Octreotate; Drug: 90Y DOTATATE and 177Lu DOTATATE (mix each of 50%)
Sponsors: University of Warmia and Mazury; Stowarzyszenie Pacjentów i Osób Wspierających Chorych na Guzy Neuroendokrynne
Recruiting

The Master Registry of Oncology Outcomes Associated With Testing and Treatment

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

Conditions: Adenocarcinoma; Adenocystic Carcinoma; Anal Cancer; Appendix Cancer; Brain Tumor; Glioblastoma; Astrocytoma; Bile Duct Cancer; Cholangiocarcinoma; Bladder Cancer; Bone Cancer; Synovial Sarcoma; Chondrosarcoma; Liposarcoma; Sarcoma, Kaposi; Sarcoma,Soft Tissue; Sarcoma; Osteosarcoma; CNS Cancer; Brain Stem Neoplasms; Breast Cancer; Cervical Cancer; Colorectal Cancer; Rectal Cancer; Colon Cancer; Esophageal Cancer; Esophagus Cancer; Cancer of Colon; Pancreatic Cancer; Cancer of Pancreas; Testis Cancer; Testicular Cancer; Ureter Cancer; Renal Cell Carcinoma; Kidney Cancer; Gestational Trophoblastic Tumor; Head and Neck Neoplasms; Parotid Tumor; Larynx Cancer; Tongue Cancer; Pharynx Cancer; Salivary Gland Cancer; Acute Myeloid Leukemia; Chronic Myeloid Leukemia; Acute Lymphoblastic Leukemia; Multiple Myeloma; Non Hodgkin Lymphoma; Carcinoid Tumor; Lung Cancer; Neuroendocrine Tumors; Mesothelioma; Thyroid Cancer; Parathyroid Neoplasms; Adrenal Cancer; Small Bowel Cancer; Stomach Cancer; Liver Cancer; Hepatic Cancer; Melanoma; Skin Cancer; Unknown Primary Tumors; Uterine Cancer; Fallopian Tube Cancer; Ovarian Cancer; Prostate Cancer; Vaginal Cancer; Penile Cancer; Vulvar Cancer; Waldenstrom Macroglobulinemia; Cancer, Advanced; Thymus Cancer; Nasopharyngeal Carcinoma; Multiple Endocrine Neoplasia; Pheochromocytoma; Small Cell Carcinoma; Pulmonary Carcinoma
Interventions: Diagnostic Test: Biomarker Testing (L); Drug: Systemic Treatment (T); Other: Patient Reported Outcomes (P)
Sponsor: Taproot Health
Not yet recruiting

Sonidegib and Pembrolizumab in Treating Patients With Advanced Solid Tumors

Posted: July 5th, 2019, 2:00pm GMT

Conditions: Clinical Stage III Cutaneous Melanoma AJCC v8; Clinical Stage III Gastric Cancer AJCC v8; Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Clinical Stage IV Gastric Cancer AJCC v8; Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IVA Gastric Cancer AJCC v8; Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IVB Gastric Cancer AJCC v8; Clinical Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8; High-Frequency Microsatellite Instability; Locally Advanced Urothelial Carcinoma; Metastatic Gastric Adenocarcinoma; Metastatic Gastroesophageal Junction Adenocarcinoma; Metastatic Head and Neck Squamous Cell Carcinoma; Metastatic Lung Non-Small Cell Carcinoma; Metastatic Malignant Solid Neoplasm; Metastatic Melanoma; Metastatic Pancreatic Adenocarcinoma; Metastatic Urothelial Carcinoma; Mismatch Repair Deficiency; Pathologic Stage III Cutaneous Melanoma AJCC v8; Pathologic Stage III Gastric Cancer AJCC v8; Pathologic Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IIIA Gastric Cancer AJCC v8; Pathologic Stage IIIA Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IIIB Gastric Cancer AJCC v8; Pathologic Stage IIIB Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IIIC Gastric Cancer AJCC v8; Pathologic Stage IV Cutaneous Melanoma AJCC v8; Pathologic Stage IV Gastric Cancer AJCC v8; Pathologic Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8; PD-L1 Positive; Progressive Disease; Recurrent Head and Neck Squamous Cell Carcinoma; Refractory Lung Non-Small Cell Carcinoma; Refractory Pancreatic Adenocarcinoma; Stage II Pancreatic Cancer AJCC v8; Stage IIA Pancreatic Cancer AJCC v8; Stage IIB Pancreatic Cancer AJCC v8; Stage III Pancreatic Cancer AJCC v8; Stage IV Cutaneous Squamous Cell Carcinoma of the Head and Neck 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 Malignant Solid Neoplasm; Unresectable Melanoma; Unresectable Pancreatic Adenocarcinoma
Interventions: Biological: Pembrolizumab; Drug: Sonidegib
Sponsors: Mayo Clinic; National Cancer Institute (NCI)
Recruiting

Permalink for 'PROCLAIM: CX-072-002: Study of PD-L1 Probody Therapeutic CX-072 in Combination With Other Anticancer Therapy in Adults With Solid Tumors'

PROCLAIM: CX-072-002: Study of PD-L1 Probody Therapeutic CX-072 in Combination With Other Anticancer Therapy in Adults With Solid Tumors

Posted: June 20th, 2019, 2:00pm GMT

Conditions: Solid Tumor; Unresectable or Metastatic Melanoma
Interventions: Drug: CX-072; Drug: Ipilimumab
Sponsor: CytomX Therapeutics
Recruiting

Permalink for 'Platinum-doublet Chemotherapy and Nivolumab for the Treatment of Subjects With Neuroendocrine Neoplasms (NENs) of the Gastroenteropancreatic (GEP) Tract or of Unknown (UK) Origin.'

Platinum-doublet Chemotherapy and Nivolumab for the Treatment of Subjects With Neuroendocrine Neoplasms (NENs) of the Gastroenteropancreatic (GEP) Tract or of Unknown (UK) Origin.

Posted: June 10th, 2019, 2:00pm GMT

Conditions: Neuroendocrine Tumors; Neuroendocrine Neoplasm; Gastroenteropancreatic Neuroendocrine Tumor
Interventions: Drug: Nivolumab; Drug: Carboplatin; Drug: Etoposide
Sponsor: Grupo Espanol de Tumores Neuroendocrinos
Recruiting

Lenvatinib and Everolimus in Treating Patients With Advanced, Unresectable Carcinoid Tumors

Posted: May 15th, 2019, 2:00pm GMT

Conditions: Advanced Carcinoid Tumor; Digestive System Neuroendocrine Neoplasm; Multiple Endocrine Neoplasia Type 1; Neuroendocrine Neoplasm; Unresectable Carcinoid Tumor
Interventions: Drug: Everolimus; Drug: Lenvatinib
Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI)
Recruiting

Study of IDE196 in Patients With Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions

Posted: May 13th, 2019, 2:00pm GMT

Conditions: Metastatic Uveal Melanoma; Cutaneous Melanoma; Colorectal Cancer; Other Solid Tumors
Intervention: Drug: IDE196
Sponsor: IDEAYA Biosciences
Recruiting

Adoptive Transfer of Tumor Infiltrating Lymphocytes for Advanced Solid Cancers

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

Neoantigen Vaccine Plus Locally Administered Ipilimumab and Systemic Nivolumab in Advanced Melanoma

Posted: April 26th, 2019, 2:00pm GMT

Condition: Melanoma
Interventions: Drug: Nivolumab; Biological: NeoVax plus Montanide; Drug: Ipilimumab
Sponsors: Dana-Farber Cancer Institute; National Cancer Institute (NCI)
Not yet recruiting

Dosimetry Guided PRRT With 177Lu-DOTATATE in Children

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

Conditions: Neuroendocrine Tumors; Neuroblastoma; Pheochromocytoma; Paraganglioma
Interventions: Drug: 177Lu-DOTA-tyr3-OCTREOTATE; Procedure: Peptide Receptor Radiotherapy (PRRT)
Sponsors: Sue O'Dorisio; Advanced Accelerator Applications
Not yet recruiting

Permalink for 'Pembrolizumab With Chemotherapy in Metastatic or Unresectable High Grade Gastroenteropancreatic or Lung Neuroendocrine Carcinoma'

Pembrolizumab With Chemotherapy in Metastatic or Unresectable High Grade Gastroenteropancreatic or Lung Neuroendocrine Carcinoma

Posted: April 3rd, 2019, 2:00pm GMT

Conditions: Neuroendocrine Carcinoma; Large Cell Neuroendocrine Carcinoma of the Lung; High Grade Neuroendocrine Carcinoma, Any Site
Intervention: Drug: Pembrolizumab
Sponsors: Ochsner Health System; Merck Sharp & Dohme Corp.
Recruiting

Survivin Long Peptide Vaccine in Treating Patients With Metastatic Neuroendocrine Tumors

Posted: March 19th, 2019, 2:00pm GMT

Conditions: Lung Atypical Carcinoid Tumor; Lung Typical Carcinoid Tumor; Metastatic Pancreatic Neuroendocrine Tumor
Interventions: Biological: Incomplete Freund's Adjuvant; Drug: Octreotide Acetate; Biological: Sargramostim; Biological: SVN53-67/M57-KLH Peptide Vaccine
Sponsors: Roswell Park Cancer Institute; NeuroEndocrine Tumor Research Foundation (NETRF); National Cancer Institute (NCI)
Recruiting

Permalink for 'Pharmacokinetic Drug-drug Interaction Study of Encorafenib and Binimetinib on Probe Drugs in Patients With BRAF V600-mutant Melanoma or Other Advanced Solid Tumors'

Pharmacokinetic Drug-drug Interaction Study of Encorafenib and Binimetinib on Probe Drugs in Patients With BRAF V600-mutant Melanoma or Other Advanced Solid Tumors

Posted: March 6th, 2019, 3:00pm GMT

Conditions: Advanced Solid Tumors; Metastatic Melanoma
Interventions: Drug: losartan; Drug: dextromethorphan; Drug: caffeine; Drug: omeprazole; Drug: midazolam; Drug: rosuvastatin; Drug: bupropion immediate release (IR); Drug: encorafenib; Drug: binimetinib; Drug: modafinil
Sponsors: Pfizer; Pierre Fabre Laboratories
Recruiting

A Study of XmAb®22841 Monotherapy & in Combination w/ Pembrolizumab in Subjects w/ Selected Advanced Solid Tumors

Posted: February 21st, 2019, 3:00pm GMT

Conditions: Melanoma; Cervical Carcinoma; Pancreatic Carcinoma; Triple Negative Breast Cancer; Hepatocellular Carcinoma; Urothelial Carcinoma; Squamous Cell Carcinoma of the Head and Neck; Nasopharyngeal Carcinoma; Renal Cell Carcinoma; Non-small Cell Lung Carcinoma; Small Cell Lung Carcinoma; Gastric or Gastroesophageal Junction Adenocarcinoma; Advanced or Metastatic Solid Tumors; Prostate Carcinoma; MSI-H; Mismatch Repair Deficiency; Epithelial Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Carcinoma; Intrahepatic Cholangiocarcinoma
Interventions: Biological: XmAb®22841; Biological: Pembrolizumab (Keytruda®)
Sponsors: Xencor, Inc.; ICON Clinical Research
Recruiting

Permalink for 'A Prospective Translational Tissue Collection Study in Early and Advanced Pancreatic Ductal Adenocarcinoma and Pancreatic Neuroendocrine Tumours to Enable Further Disease Characterisation and the Development of Potential Predictive and Prognostic Biomark'

A Prospective Translational Tissue Collection Study in Early and Advanced Pancreatic Ductal Adenocarcinoma and Pancreatic Neuroendocrine Tumours to Enable Further Disease Characterisation and the Development of Potential Predictive and Prognostic Biomark

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

Condition: Pancreatic Adenocarcinoma
Intervention:
Sponsor: Royal Marsden NHS Foundation Trust
Recruiting

Study of RP1 Monotherapy and RP1 in Combination With Nivolumab

Posted: December 6th, 2018, 3:00pm GMT

Conditions: Cancer; Melanoma (Skin); Melanoma, Uveal; Melanoma, Ocular; Bladder Cancer; Mismatch Repair Deficiency; Microsatellite Instability; Non-melanoma Skin Cancer
Interventions: Biological: RP1; Biological: nivolumab
Sponsor: Replimune Inc.
Recruiting

An Exploratory Study of Pembrolizumab Plus Entinostat in Non-Inflamed Stage III/IV Melanoma

Posted: December 5th, 2018, 3:00pm GMT

Condition: Melanoma
Interventions: Drug: Entinostat; Drug: Pembrolizumab
Sponsors: UNC Lineberger Comprehensive Cancer Center; Syndax Pharmaceuticals, Inc.
Recruiting

Biomarker Study of Pancreatic Neuroendocrine Tumours

Posted: November 15th, 2018, 3:00pm GMT

Condition: Pancreatic Neuroendocrine Tumor
Interventions: Radiation: 18F-FDG-PET; Radiation: 68Ga-DOTATOC-PET; Radiation: Computed tomography; Other: Core needle biopsy; Other: Phlebotomy
Sponsor: Uppsala University
Recruiting

CBL0137 in Treating Patients With Advanced Extremity Melanoma or Sarcoma

Posted: November 1st, 2018, 2:00pm GMT

Conditions: Advanced Cutaneous Melanoma of the Extremity; Advanced Sarcoma of the Extremity; Clinical Stage III Cutaneous Melanoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Pathologic Stage IIIB Cutaneous Melanoma AJCC v8; Pathologic Stage IIIC Cutaneous Melanoma AJCC v8; Pathologic Stage IV Cutaneous Melanoma AJCC v8; Recurrent Cutaneous Melanoma of the Extremity; Recurrent Sarcoma of the Extremity; Stage III Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8; Stage IIIA Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8; Stage IIIB Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8; Stage IV Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8
Intervention: Drug: FACT Complex-targeting Curaxin CBL0137
Sponsors: Roswell Park Cancer Institute; National Cancer Institute (NCI); Incuron
Recruiting

Evaluating an Amino Acid Based Medical Food w/ Diarrhea in Carcinoid Syndrome & Other NETs

Posted: October 29th, 2018, 2:00pm GMT

Conditions: Neuroendocrine Tumors; Carcinoid Tumor of GI System; Diarrhea; Carcinoid Syndrome
Intervention: Dietary Supplement: Amino Acid Based Medical Food/Drink
Sponsors: Lowell Anthony, MD; Entrinsic Health Solutions, Inc.
Recruiting

Precise DCE-MRI in Diagnosing Participants With Recurrent High Grade Glioma or Melanoma Brain Metastases

Posted: October 5th, 2018, 2:00pm GMT

Conditions: Brain Metastases; Glioma of Brain; Brain Tumor; Metastatic Melanoma
Interventions: Device: Dynamic Contrast-Enhanced Magnetic Resonance Imaging; Drug: Bevacizumab Injection
Sponsors: University of Southern California; National Cancer Institute (NCI)
Not yet recruiting

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

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

Permalink for 'A Study to testABI-009 in Patients With Metastatic, Unresectable, Low or Intermediate Grade Neuroendocrine Tumors of the Lung or Gastroenteropancreatic System'

A Study to testABI-009 in Patients With Metastatic, Unresectable, Low or Intermediate Grade Neuroendocrine Tumors of the Lung or Gastroenteropancreatic System

Posted: September 13th, 2018, 2:00pm GMT

Condition: Neuroendocrine Tumors
Intervention: Drug: ABI-009
Sponsors: Robert Ramirez; Aadi, LLC
Recruiting

pDNA Intralesional Cancer Vaccine for Cutaneous Melanoma

Posted: August 31st, 2018, 2:00pm GMT

Conditions: Cutaneous Melanoma, Stage III; Cutaneous Melanoma, Stage IV
Intervention: Biological: IFx-Hu2.0
Sponsors: Morphogenesis, Inc.; H. Lee Moffitt Cancer Center and Research Institute
Recruiting

[68Ga]DOTATATE-PET/MRI in Hepatocellular Carcinoma

Posted: August 27th, 2018, 2:00pm GMT

Condition: Hepatocellular Carcinoma
Intervention: Diagnostic Test: [68Ga]DOTATATE-PET/MRI
Sponsor: University of Alabama at Birmingham
Recruiting

Safety, Tolerability, Immunogenicity, and Antitumor Activity of GEN-009 Adjuvanted Vaccine

Posted: August 16th, 2018, 2:00pm GMT

Conditions: Cutaneous Melanoma; Non-small Cell Lung Cancer; Squamous Cell Carcinoma of the Head and Neck; Urothelial Carcinoma; Renal Cell Carcinoma
Interventions: Biological: GEN-009 Adjuvanted Vaccine; Drug: Nivolumab; Drug: Pembrolizumab
Sponsor: Genocea Biosciences, Inc.
Recruiting

Study of CVM-1118 for Patients With Advanced Neuroendocrine Tumors

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

Conditions: Neuroendocrine Tumors; Pancreatic Neuroendocrine Tumor; Gastro-enteropancreatic Neuroendocrine Tumor; Lung Neuroendocrine Neoplasm; Neuroendocrine Carcinoma
Intervention: Drug: CVM-1118
Sponsor: TaiRx, Inc.
Recruiting

Permalink for 'A Phase 1b Dose Escalation/Expansion Study of Abexinostat in Combination With Pembrolizumab in Patients With Advanced Solid Tumor Malignancies'

A Phase 1b Dose Escalation/Expansion Study of Abexinostat in Combination With Pembrolizumab in Patients With Advanced Solid Tumor Malignancies

Posted: July 18th, 2018, 2:00pm GMT

Conditions: Stage III Cutaneous Melanoma; Stage IV Cutaneous Melanoma; Locally Advanced Melanoma; Locally Advanced Solid Neoplasm; Metastatic Head and Neck Squamous Cell Carcinoma; Metastatic Malignant Solid Neoplasm; Metastatic Melanoma; Metastatic Urothelial Carcinoma; Non-Small Cell Lung Carcinoma; Stage IB Lung Cancer AJCC v7; Stage III Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8; Stage III Lung Cancer AJCC v8; Stage III Ureter Cancer AJCC v8; Stage IIIA Lung Cancer AJCC v8; Stage IIIB Lung Cancer AJCC v8; Stage IIIC Lung Cancer AJCC v8; Stage IV Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8; Stage IV Lung Cancer AJCC v8; Stage IV Ureter Cancer AJCC v8; Stage IVA Lung Cancer AJCC v8; Stage IVB Lung Cancer AJCC v8
Interventions: Drug: Abexinostat; Biological: Pembrolizumab
Sponsors: Rahul Aggarwal; Xynomic Pharmaceuticals, Inc.
Recruiting

Intra-arterial Lutetium-177-dotatate for Treatment of Patients With Neuro-endocrine Tumor Liver Metastases

Posted: July 18th, 2018, 2:00pm GMT

Conditions: Neuroendocrine Tumors; Liver Metastases
Intervention: Drug: Lutetium Lu 177-DOTATATE
Sponsor: Marnix Lam
Recruiting

Ixazomib, Gemcitabine, and Doxorubicin in Treating Patients With Locally Advanced or Metastatic Kidney Cancer

Posted: July 16th, 2018, 2:00pm GMT

Conditions: Metastatic Kidney Medullary Carcinoma; Metastatic Renal Cell Carcinoma; SMARCB1 Negative; Stage III Renal Cell Cancer AJCC v8; Stage IV Renal Cell Cancer AJCC v8
Interventions: Drug: Doxorubicin; Drug: Doxorubicin Hydrochloride; Drug: Gemcitabine; Drug: Gemcitabine Hydrochloride; Drug: Ixazomib; Drug: Ixazomib Citrate
Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI)
Recruiting

Permalink for '18FDG PET for Early Identification of Tumor Exhaust for Immunotherapy in Patients With Locally Advanced or Metastatic Non-Small Cell Bronchopulmonary Carcinoma or Melanoma'

18FDG PET for Early Identification of Tumor Exhaust for Immunotherapy in Patients With Locally Advanced or Metastatic Non-Small Cell Bronchopulmonary Carcinoma or Melanoma

Posted: July 12th, 2018, 2:00pm GMT

Condition: Non-Small Cell Bronchopulmonary Carcinoma or Melanoma
Intervention: Radiation: 18FDG PET
Sponsor: Centre Antoine Lacassagne
Recruiting

Olaparib Before Surgery in Treating Participants With Localized Prostate Cancer

Posted: June 27th, 2018, 2:00pm GMT

Conditions: ATM Biallelic Inactivation; ATM Gene Mutation; ATM Monoallelic Inactivation; BRCA1 Biallelic Inactivation; BRCA1 Gene Mutation; BRCA2 Biallelic Inactivation; BRCA2 Gene Mutation; FANCA Biallelic Inactivation; Homologous Recombination Deficiency; PALB2 Biallelic Inactivation; PALB2 Gene Mutation; Prostate Adenocarcinoma Without Evidence of Neuroendocrine Differentiation; Stage I Prostate Cancer AJCC v8; Stage II Prostate Cancer AJCC v8; Stage IIA Prostate Cancer AJCC v8; Stage IIB Prostate Cancer AJCC v8; Stage IIC Prostate Cancer AJCC v8
Interventions: Drug: Olaparib; Procedure: Radical Prostatectomy
Sponsors: University of Washington; National Cancer Institute (NCI); AstraZeneca
Recruiting

Perception of Information and Quality of Life in Neuroendocrine Tumour on Lanreotide Autogel

Posted: June 19th, 2018, 2:00pm GMT

Condition: Neuroendocrine Tumors
Intervention: Other: Data collection
Sponsor: Ipsen
Recruiting

Oral TrkA Inhibitor VMD-928 for Treatment of Advanced Adult Solid Tumors or Lymphoma

Posted: June 14th, 2018, 2:00pm GMT

Conditions: Solid Tumor; Lymphoma; Thymic Carcinoma and Thymoma; Mesothelioma; Head and Neck Squamous Cell Carcinoma; Ovarian Cancer; Hepatocellular Carcinoma; Squamous Cell Carcinoma of Lung; Esophageal Cancer; Adenoid Cystic Carcinoma; Prostate Cancer; Cervical Cancer; Gastric Cancer; Melanoma; Acute Myeloid Leukemia; Pancreatic Carcinoma; Non Hodgkin Lymphoma
Intervention: Drug: VMD-928 300-mg Capsules
Sponsor: VM Oncology, LLC
Recruiting

Lymph Node Identification in Skin Malignancy Using ICG Transcutaneously Study

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

Permalink for 'Clinical characteristics and prognostic factors of surgically resected combined small cell lung cancer: a retrospective study.'

Clinical characteristics and prognostic factors of surgically resected combined small cell lung cancer: a retrospective study.

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

Clinical characteristics and prognostic factors of surgically resected combined small cell lung cancer: a retrospective study.

Lung Cancer. 2020 Jun 17;146:244-251

Authors: Lei Y, Feng H, Qiang H, Shang Z, Chang Q, Qian J, Zhang Y, Zhong R, Fan X, Chu T

Abstract
OBJECTIVES: Small cell lung cancer (SCLC) is the most malignant lung cancer. Some of them are mixed with non-small cell lung cancer(NSCLC, Non SCLC),which are called combined small cell lung cancer (C-SCLC).Due to the difficulty of pathological diagnosis and the complexity of treatment, studies of C-SCLC have just been rising in recent years. This study is to evaluate the clinical and pathologic characteristics of C-SCLC.
METHODS: Stage Ⅰ-Ⅲa C-SCLC patients who received radical R0 surgery between 2009-2018 in Shanghai Chest Hospital were enrolled. Clinical characteristics and prognosis were analyzed.
RESULTS: Totally 181 patients were included, most of them were small cell combined with large cell neuroendocrine components(SCLC/LCNEC,58.0 %,N = 105),then with adenocarcinoma(SCLC/ADC:13.8 %,N = 25),and finally with squamous cell carcinoma(SCLC/SCC:13.3 %,N = 24).Median DFS and OS of C-SCLC patients underwent radical surgery were 32.5 and 49.7 months.1,3 and 5 years DFS rates of the entire cohort were 68.5 %,32.6 % and 16.0 %,respectively. Patients with SCLC/LCNEC had longer DFS (44.1 m vs. 20.4 m, p = 0.040) and longer OS trend (62.1 m vs. 33.2 m, p = 0.122).Groups of whether tumor invaded the pleura(p = 0.028 and p = 0.050),lymph node stage(p = 0.029 and p = 0.010) and the courses of adjuvant chemotherapy(p = 0.011 and p = 0.001) had statistical differences on DFS and OS.
CONCLUSIONS: SCLC/LCNEC was the most common type of C-SCLC. Patients' DFS and OS were also longer than other combined types. Adjuvant chemotherapy for SCLC is still the main treatment for surgical C-SCLC. Further studies are needed to clarify the clinical characteristics and prognosis of C-SCLC.

PMID: 32592985 [PubMed - as supplied by publisher]

Selective application of neuroendocrine markers in the diagnosis and treatment of small cell lung cancer.

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

Selective application of neuroendocrine markers in the diagnosis and treatment of small cell lung cancer.

Clin Chim Acta. 2020 Jun 24;:

Authors: Du J, Li Y, Wang L, Zhou Y, Shen Y, Xu F, Chen Y

Abstract
AIMS: Here, we explored the potential application and selection of neuroendocrine biomarkers in the diagnosis and treatment of small cell lung cancer.
METHODS: We retrospectively analyzed 118 patients with small cell lung cancer (SCLC), 166 patients with non-small cell lung cancer (NSCLC), 33 patients with benign lung disease (BLD), and 200 healthy individuals admitted to Zhejiang Provincial People's Hospital between January 1, 2015 and May 31, 2019. All the patients were newly diagnosed with either SCLC, NSCLC, or BLD and previously untreated. Peripheral blood levels of ProGRP, NSE, CEA, and CYFRA21-1 were analyzed during the follow-up treatment, and 2-fold reference intervals were defined as effective elevation. We used paired results to analyze the diagnostic efficiency of proGRP and NSE on SCLC.
RESULTS: In the 118 SCLC patients, proGRP levels were significantly higher compared with NSE levels. The diagnostic efficiencies of NSE and ProGRP for SCLC were 0.8554 and 0.9053, respectively. The combined diagnostic efficiency (0.9426) was higher relative to NSE, but there was no significant difference compared with proGRP. The effective elevation rate of proGRP was 45.3% higher than that of NSE in the limited stage of SCLC. In the extensive disease of SCLC patients, 70.7 % cases had more than 10-fold increase in proGRP value, whereas 56.9 % cases had less than 5-fold increase in NSE value. Compared with pre-treatment, the median concentrations of proGRP increased by 204.0% higher than that of NSE (71.3%) in the progressive group. Besides, the dynamic change in imaging characteristics and tumor size had a strong correlation with the levels of proGRP.
SIGNIFICANCE: ProGRP is a reliable neuroendocrine biomarker in SCLC. The effective elevation of proGRP has a potential diagnostic and efficacy value in the evaluation of SCLC. However, the combined detection of proGRP and NSE does not significantly improve the diagnosis of lung cancer.

PMID: 32592711 [PubMed - as supplied by publisher]

Permalink for 'Nivolumab exerts therapeutic effects against metastatic lesions from early gastric adenocarcinoma with a small proportion of neuroendocrine carcinoma after gastrectomy: a case report.'

Nivolumab exerts therapeutic effects against metastatic lesions from early gastric adenocarcinoma with a small proportion of neuroendocrine carcinoma after gastrectomy: a case report.

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

Nivolumab exerts therapeutic effects against metastatic lesions from early gastric adenocarcinoma with a small proportion of neuroendocrine carcinoma after gastrectomy: a case report.

Clin J Gastroenterol. 2020 Jun 26;:

Authors: Sawayama H, Komohara Y, Hirao H, Sakata K, Takata N, Yoshinaka I, Harada K, Baba H

Abstract
Gastric neuroendocrine carcinoma (NEC) is an aggressive disease with high metastatic ability. Gastric cancer has intra-tumoral and intra-patient heterogeneity and may contain NEC. We discuss the case of a 75-year-old man who underwent distal gastrectomy for early gastric cancer. Tumor pathology revealed that nearly all of the tumor (> 95%) was well-differentiated adenocarcinoma, with NEC detected in a small area (< 5%) at the invasion front. No metastasis was identified in the dissected lymph nodes (LN). Multiple liver metastases were detected 3 months after surgery. The metastatic lesion was resistant to both chemotherapy regimens; namely, SOX (S-1 combined with oxaliplatin) and ramucirumab combined with paclitaxel. However, tumor regression was detected after nivolumab treatment. The tumor regression continued for 26 cycles (13 months). Irinotecan treatment was then administered. After 18 irinotecan treatment cycles for 11 months, the para-aortic LN rapidly enlarged. Following biopsy, the swollen para-aortic LN was diagnosed as the recurrence of NEC components of the gastric cancer. Treatment with carboplatin combined with etoposide has been effective and continued. We report a case of NEC para-aorta LN metastases from early gastric cancer with a low proportion of NEC (< 5%). A partial response of the distant metastatic lesions was observed with nivolumab therapy.

PMID: 32592148 [PubMed - as supplied by publisher]

A case of small cell neuroendocrine carcinoma of the ampulla of Vater.

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

A case of small cell neuroendocrine carcinoma of the ampulla of Vater.

Surg Case Rep. 2020 Jun 26;6(1):150

Authors: Ito H, Wada Y, Takami Y, Ryu T, Ureshino H, Imamura H, Sasaki S, Ohno A, Hijioka M, Kaku T, Kawabe K, Kawauchi S, Saitsu H

Abstract
BACKGROUND: Gastroenteric neuroendocrine carcinomas (NECs) account for 6.2% of gastroenteric neuroendocrine tumors (NETs), and only 1% or less of gastroenteric NETs occur in the ampulla of Vater (AoV). Clinical features of NEC of the AoV remain obscure.
CASE PRESENTATION: A 65-year-old man visited a general practitioner because of jaundice, and an abdominal contrast-enhanced computed tomography scan revealed a tumor of 11 mm in diameter, which was enhanced in the arterial phase at the duodenal papilla, with dilation of the upstream bile duct. Gastrointestinal scope revealed an unexposed tumor of the AoV. Based on a biopsy of the site, a moderately differentiated tubular adenocarcinoma was suspected, and pancreatoduodenectomy was performed. Histopathological examination revealed dysplasia and highly proliferative small tumor cells, with solid and nodular formation at the AoV. Histological analysis showed a high mitotic count, and immunohistochemical staining revealed a Ki-67 index of 40-50% and cells positive for synaptophysin, chromogranin A, and p53. Small cell-type NEC was finally diagnosed. Four months post pancreatoduodenectomy, multiple liver metastases developed, and systemic chemotherapy was administered. Salvage liver resection for liver metastases was performed 14 months after the pancreatoduodenectomy. Unfortunately, multiple liver metastases developed 2 months after liver resection, and the patient died 18 months after the pancreatoduodenectomy.
CONCLUSIONS: Neuroendocrine carcinoma originating from the bile duct is very rare; therefore, in this article, we provide a review of the literature and a case report.

PMID: 32592083 [PubMed - as supplied by publisher]

US phase 1 first-in-human study of taletrectinib (DS-6051b/AB-106), a ROS1/TRK inhibitor, in patients with advanced solid tumors.

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

US phase 1 first-in-human study of taletrectinib (DS-6051b/AB-106), a ROS1/TRK inhibitor, in patients with advanced solid tumors.

Clin Cancer Res. 2020 Jun 26;:

Authors: Papadopoulos KP, Borazanci E, Shaw AT, Katayama R, Shimizu Y, Zhu VW, Sun TY, Wakelee HA, Madison R, Schrock AB, Senaldi G, Nakao N, Hanzawa H, Masaya T, Isoyama T, Nakamaru K, Deng C, Li M, Fran F, Zhao Q, Gao Y, Seto T, Janne PA, Ou SI

Abstract
PURPOSE: Taletrectinib (DS-6051b/AB-106) is an oral, tyrosine kinase inhibitor of ROS1 and NTRK with potent pre-clinical activity against ROS1 G2032R solvent-front mutation among others. We report the first-in-human US-phase 1 results of taletrectinib.
PATIENTS AND METHODS: Patients ≥18 years old with neuroendocrine tumors, with tumor-induced pain, or tumors harboring ROS1/NTRK rearrangements were eligible. Accelerated titration followed by modified continuous reassessment method and escalation with overdose control was used (50-1200 mg once daily [QD] or 400 mg twice daily). Primary objectives were safety/tolerability, and maximum tolerated dose (MTD) determination. Secondary objectives were food-effect pharmacokinetics and antitumor activity.
RESULTS: A total of 46 patients were enrolled. Steady-state peak concentration (Cmax) and exposure (AUC0-8) increased dose dependently from 50 mg to 800 mg QD doses. The ratio of the geometric mean of AUC0-24 between low-fat-diet-fed/fasted state was 123% (90% confidence interval: 104% - 149%). Dose-limiting toxicities (grade 3 transaminases increase) occurred in 2 patients (1200 mg QD dose). MTD was 800 mg QD. Most common treatment-related adverse events (TRAEs) were nausea (47.8%), diarrhea (43.5%), and vomiting (32.6%). Pain score reductions were observed in the 800 mg QD-dose cohort. Confirmed ORR was 33.3% among the 6 RECIST-evaluable crizotinib-refractory ROS1+ NSCLC patients. One TPM3-NTRK1 differentiated thyroid cancer patient achieving a confirmed partial response (PR) of 27 months at data cutoff. We identified a cabozantinib-sensitive ROS1 L2086F as an acquired taletrectinib-resistance mutation.
CONCLUSIONS: Taletrectinib has manageable toxicities at the MTD of 800 mg daily. Preliminary efficacy was observed in crizotinib-refractory ROS1+ NSCLC patients.

PMID: 32591465 [PubMed - as supplied by publisher]

Rb and p53 execute distinct roles in the development of pancreatic neuroendocrine tumors.

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

Rb and p53 execute distinct roles in the development of pancreatic neuroendocrine tumors.

Cancer Res. 2020 Jun 26;:

Authors: Yamauchi Y, Kodama Y, Shiokawa M, Kakiuchi N, Marui S, Kuwada T, Sogabe Y, Tomono T, Mima A, Morita T, Matsumori T, Ueda T, Tsuda M, Nishikawa Y, Kuriyama K, Sakuma Y, Ota Y, Maruno T, Uza N, Masuda A, Tatsuoka H, Yabe D, Minamiguchi S, Masui T, Inagaki N, Uemoto S, Chiba T, Seno H

Abstract
Pancreatic neuroendocrine tumors (PanNET) were classified into grades (G) 1-3 by the World Health Organization in 2017, but the precise mechanisms of PanNET initiation and progression have remained unclear. In this study, we used a genetically engineered mouse model to investigate the mechanisms of PanNET formation. Although pancreas-specific deletion of the Rb gene (Pdx1-Cre;Rbf/f) in mice did not affect pancreatic exocrine cells, the α-cell/β-cell ratio of islet cells was decreased at 8 months of age. During long-term observation (18-20 months), mice formed well-differentiated PanNET with a Ki67-labeling index of 2.7%. In contrast, pancreas-specific induction of a p53 mutation (Pdx1-Cre;Trp53R172H) had no effect on pancreatic exocrine and endocrine tissues, but simultaneous induction of a p53 mutation with Rb gene deletion (Pdx1-Cre;Trp53R172H;Rb f/f) resulted in the formation of aggressive PanNET with a Ki67-labeling index of 24.7% over the short-term (4 months). In Pdx1-Cre;Trp53R172H;Rb f/f mice, mRNA expression of Pten and Tsc2, negative regulators of the mTOR pathway, significantly decreased in the islet cells, and activation of the mTOR pathway was confirmed in subsequently formed PanNET. Thus, by manipulating Rb and p53 genes, we established a multistep progression model from dysplastic islets to indolent PanNET and aggressive metastatic PanNET in mice. These observations suggest that Rb and p53 have distinct roles in the development of PanNET.

PMID: 32591410 [PubMed - as supplied by publisher]

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

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

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

Cancer Cytopathol. 2020 Jun 23;:

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

PMID: 32573984 [PubMed - as supplied by publisher]

Clinicopathologic Features of Gastroenteropancreatic Neuroendocrine Tumors (GEP-NET) s: A Single-Center Experience.

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

Clinicopathologic Features of Gastroenteropancreatic Neuroendocrine Tumors (GEP-NET) s: A Single-Center Experience.

Balkan Med J. 2020 Jun 23;:

Authors: Akın Telli T, Esin E, Yalçın Ş

Abstract
Background: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a heterogenous group of neoplasms originating from the neuroendocrine system of the gastrointestinal tract and pancreas. There aren't many large well-designed studies investigating NETs in Turkey.
Aims: To define the clinicopathologic, demographic and survival features of patients with GEPNETs.
Study Design: Retrospective observational cohort study.
Methods: In this study, we reviewed hospital records of patients. The data was analyzed retrospectively and we investigated clinical, pathological and survival features and prognosis of patients with GEP-NETs (n=128) admitted to medical oncology department between 2003 and 2014. Survival curve estimation was performed using the Kaplan-Meier method. Univariate and multivariate Cox regression models were utilized to assess prognostic factors for survival.
Result: Among 128 patients with GEP-NETs, 61 (47.7%) were female and 67 (52.3%) were male. The most common site of tumor was stomach (36.7%). The most common stage at diagnosis was stage 4 (40.9%). The median follow-up period was 37 months. Three-years overall survival (OS) rate was 78% and 5-years OS rate was 69%. The factors that can significantly affect OS rate were clinical stage, grade, presence of metastasis at diagnosis and Ki-67 proliferation index; these factors were associated with 3 and 5-years OS rate. Moreover, grade (Hazard ratio (HR)=8.34, 95% CI: 2.16-32.22, p=0.01) and presence of metastasis at diagnosis (HR=3.18, 95% CI: 1.30-7.77, p=0.01) predicted OS independently in multivariate model, when adjusted for age and gender.
Conclusion: Higher grade and presence of metastasis at diagnosis were found to be negative independent prognostic indicators of survival in patients with GEP-NETs.

PMID: 32573179 [PubMed - as supplied by publisher]

Permalink for 'ASO Author Reflections: Assessing the Value of Primary Tumor Resection in Midgut Neuroendocrine Tumors with Liver-Only Metastases.'

ASO Author Reflections: Assessing the Value of Primary Tumor Resection in Midgut Neuroendocrine Tumors with Liver-Only Metastases.

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

ASO Author Reflections: Assessing the Value of Primary Tumor Resection in Midgut Neuroendocrine Tumors with Liver-Only Metastases.

Ann Surg Oncol. 2020 Jun 22;:

Authors: Manguso N, Gangi A

PMID: 32572852 [PubMed - as supplied by publisher]

Gastroenteropancreatic Neuroendocrine Tumors.

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

Gastroenteropancreatic Neuroendocrine Tumors.

Semin Pediatr Surg. 2020 Jun;29(3):150928

Authors: Kotagal M, von Allmen D

PMID: 32571513 [PubMed - in process]

Permalink for 'Dual Targeting of Norepinephrine Transporter (NET) Function and Thyrointegrin αvβ3 Receptors in the Treatment of Neuroblastoma.'

Dual Targeting of Norepinephrine Transporter (NET) Function and Thyrointegrin αvβ3 Receptors in the Treatment of Neuroblastoma.

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

Dual Targeting of Norepinephrine Transporter (NET) Function and Thyrointegrin αvβ3 Receptors in the Treatment of Neuroblastoma.

J Med Chem. 2020 Jun 23;:

Authors: Karakus OO, Godugu K, Rajabi M, Mousa SA

Abstract
Therapeutic targeting of the norepinephrine transporter (NET) function with benzylguanidine, (BG), conjugated with the high affinity thyrointegrin αvβ3 antagonist TriAzole Tetraiodothyroacetic acid, TAT, via non-cleavable bonding to polyethylene glycol (PEG400) (P) might allow for effective treatment options in neuroblastoma. BG-P-TAT is a dual targeting agent, targeting the NET function and the thyrointegrin αvβ3 receptors that are over-expressed in neuroblastoma and other neuroendocrine tumors. Various cancer cells and actively dividing tumor-endothelial cells express the thyrointegrin αvβ3 receptors. In this work, the novel compound BG-P-TAT was synthesized and evaluated in neuroblastoma SKNF 1 cell line for improved targeting and to offer a new strategy for patients with neuroblastoma. BG-P-TAT demonstrated significant suppression of neuroblastoma tumor progression, growth and viability in a dose-dependent manner. In conclusion, BG-P-TAT represent a potential lead candidate for the treatment of neuroblastoma and other neuroendocrine tumors.

PMID: 32571015 [PubMed - as supplied by publisher]

Permalink for 'Atezolizumab, vemurafenib, and cobimetinib as first-line treatment for unresectable advanced BRAFV600 mutation-positive melanoma (IMspire150): primary analysis of the randomised, double-blind, placebo-controlled, phase 3 trial.'

Atezolizumab, vemurafenib, and cobimetinib as first-line treatment for unresectable advanced BRAFV600 mutation-positive melanoma (IMspire150): primary analysis of the randomised, double-blind, placebo-controlled, phase 3 trial.

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

Atezolizumab, vemurafenib, and cobimetinib as first-line treatment for unresectable advanced BRAFV600 mutation-positive melanoma (IMspire150): primary analysis of the randomised, double-blind, placebo-controlled, phase 3 trial.

Lancet. 2020 06 13;395(10240):1835-1844

Authors: Gutzmer R, Stroyakovskiy D, Gogas H, Robert C, Lewis K, Protsenko S, Pereira RP, Eigentler T, Rutkowski P, Demidov L, Manikhas GM, Yan Y, Huang KC, Uyei A, McNally V, McArthur GA, Ascierto PA

Abstract
BACKGROUND: IMspire150 aimed to evaluate first-line combination treatment with BRAF plus MEK inhibitors and immune checkpoint therapy in BRAFV600 mutation-positive advanced or metastatic melanoma.
METHODS: IMspire150 was a randomised, double-blind, placebo-controlled phase 3 study done at 112 institutes in 20 countries. Patients with unresectable stage IIIc-IV, BRAFV600 mutation-positive melanoma were randomly assigned 1:1 to 28-day cycles of atezolizumab, vemurafenib, and cobimetinib (atezolizumab group) or atezolizumab placebo, vemurafenib, and cobimetinib (control group). In cycle 1, all patients received vemurafenib and cobimetinib only; atezolizumab placebo was added from cycle 2 onward. Randomisation was stratified by lactate dehydrogenase concentration and geographical region. Blinding for atezolizumab was achieved by means of an identical intravenous placebo, and blinding for vemurafenib was achieved by means of a placebo tablet. The primary outcome was investigator-assessed progression-free survival. This trial (ClinicalTrials.gov, NCT02908672) is ongoing but no longer recruiting patients.
FINDINGS: Between Jan 13, 2017, and April 26, 2018, 777 patients were screened and 514 were enrolled and randomly assigned to the atezolizumab group (n=256) or control group (n=258). At a median follow-up of 18·9 months (IQR 10·4-23·8), progression-free survival as assessed by the study investigator was significantly prolonged with atezolizumab versus control (15·1 vs 10·6 months; hazard ratio [HR] 0·78; 95% CI 0·63-0·97; p=0·025). Common treatment-related adverse events (>30%) in the atezolizumab and control groups were blood creatinine phosphokinase increased (51·3% vs 44·8%), diarrhoea (42·2% vs 46·6%), rash (40·9%, both groups), arthralgia (39·1% vs 28·1%), pyrexia (38·7% vs 26·0%), alanine aminotransferase increased (33·9% vs 22·8%), and lipase increased (32·2% vs 27·4%); 13% of patients in the atezolizumab group and 16% in the control group stopped all treatment because of adverse events.
INTERPRETATION: The addition of atezolizumab to targeted therapy with vemurafenib and cobimetinib was safe and tolerable and significantly increased progression-free survival in patients with BRAFV600 mutation-positive advanced melanoma.
FUNDING: F Hoffmann-La Roche and Genentech.

PMID: 32534646 [PubMed - indexed for MEDLINE]

Permalink for 'Assessment of clinical outcomes with immune checkpoint inhibitor therapy in melanoma patients with CDKN2A and TP53 pathogenic mutations.'

Assessment of clinical outcomes with immune checkpoint inhibitor therapy in melanoma patients with CDKN2A and TP53 pathogenic mutations.

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

Assessment of clinical outcomes with immune checkpoint inhibitor therapy in melanoma patients with CDKN2A and TP53 pathogenic mutations.

PLoS One. 2020;15(3):e0230306

Authors: DeLeon TT, Almquist DR, Kipp BR, Langlais BT, Mangold A, Winters JL, Kosiorek HE, Joseph RW, Dronca RS, Block MS, McWilliams RR, Kottschade LA, Rumilla KM, Voss JS, Seetharam M, Sekulic A, Markovic SN, Bryce AH

Abstract
BACKGROUND: CDKN2A and TP53 mutations are recurrent events in melanoma, occurring in 13.3% and 15.1% of cases respectively and are associated with poorer outcomes. It is unclear what effect CDKN2A and TP53 mutations have on the clinical outcomes of patients treated with checkpoint inhibitors.
METHODS: All patients with cutaneous melanoma or melanoma of unknown primary who received checkpoint inhibitor therapy and underwent genomic profiling with the 50-gene Mayo Clinic solid tumor targeted cancer gene panel were included. Patients were stratified according to the presence or absence of mutations in BRAF, NRAS, CDKN2A, and TP53. Patients without mutations in any of these genes were termed quadruple wild type (QuadWT). Clinical outcomes including median time to progression (TTP), median overall survival (OS), 6-month and 12-month OS, 6-month and 12-month without progression, ORR and disease control rate (DCR) were analyzed according to the mutational status of CDKN2A, TP53 and QuadWT.
RESULTS: A total of 102 patients were included in this study of which 14 had mutations of CDKN2A (CDKN2Amut), 21 had TP53 mutations (TP53mut), and 12 were QuadWT. TP53mut, CDKN2Amut and QuadWT mutational status did not impact clinical outcomes including median TTP, median OS, 6-month and 12-month OS, 6-month and 12-month without progression, ORR and DCR. There was a trend towards improved median TTP and DCR in CDKN2Amut cohort and a trend towards worsened median TTP in the QuadWT cohort.
CONCLUSION: Cell cycle regulators such as TP53 and CDKN2A do not appear to significantly alter clinical outcomes when immune checkpoint inhibitors are used.

PMID: 32196516 [PubMed - indexed for MEDLINE]

Durability of Hearing Preservation Following Microsurgical Resection of Vestibular Schwannoma.

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

Durability of Hearing Preservation Following Microsurgical Resection of Vestibular Schwannoma.

Otol Neurotol. 2019 12;40(10):1363-1372

Authors: Dowling EM, Patel NS, Lohse CM, Driscoll CLW, Neff BA, Van Gompel JJ, Link MJ, Carlson ML

Abstract
OBJECTIVE: To ascertain long-term hearing outcomes in patients with serviceable hearing following microsurgical resection of sporadic vestibular schwannoma (VS).
STUDY DESIGN: Retrospective cohort.
SETTING: Tertiary academic referral center.
PATIENTS: Forty-three adult subjects with unilateral sporadic VS who had serviceable hearing (American Academy of Otolaryngology-Head and Neck Surgery [AAO-HNS] class A or B) on initial postoperative audiogram following microsurgical resection between 2003 and 2016 with a minimum of two postoperative audiograms available for review.
INTERVENTION: Surgical treatment with a retrosigmoid or middle cranial fossa approach.
MAIN OUTCOME MEASURE: Rate of maintaining serviceable hearing, as estimated using the Kaplan-Meier method, in accordance with the 1995 and 2012 AAO-HNS guidelines on reporting hearing outcomes.
RESULTS: The median immediate postoperative pure-tone average (PTA) and word recognition score (WRS) were 31 dB and 95%, respectively. At last follow-up, the median PTA was 38 dB with a median change of 5 dB from initial postoperative audiogram, and the median WRS was 90% with a median change of 0% from initial postoperative audiogram. Eight patients developed non-serviceable hearing at a median of 4.1 years following microsurgical resection (interquartile range, 2.9-7.0). The median duration of hearing follow-up for the 35 patients who maintained serviceable hearing was 3.1 years (interquartile range, 2.2-7.5). Tumor control was achieved in 41 (95%) patients. The rate of maintaining serviceable hearing at 5 years was 81%.
CONCLUSION: Microsurgical resection provides excellent tumor control and durable long-term hearing in those with AAO-HNS class A or B hearing postoperatively. The paradigm of proactive microsurgical resection-when the tumor is small and hearing is good-hinges on the surgeon's ability to preserve residual hearing in a very high percentage of cases at or near preoperative hearing levels to maintain an advantage over conservative observation with regard to long-term hearing preservation.

PMID: 31725593 [PubMed - indexed for MEDLINE]

Permalink for 'Obesity Is Not Associated With Postoperative Complications After Vestibular Schwannoma Surgery in a Large Single Institution Series.'

Obesity Is Not Associated With Postoperative Complications After Vestibular Schwannoma Surgery in a Large Single Institution Series.

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

Obesity Is Not Associated With Postoperative Complications After Vestibular Schwannoma Surgery in a Large Single Institution Series.

Otol Neurotol. 2019 12;40(10):1373-1377

Authors: Lipschitz N, Kohlberg GD, Walters ZA, Tawfik KO, Samy RN, Pensak ML, Zuccarello M, Andaluz N, Dinapoli VA, Breen JT

Abstract
OBJECTIVE: Determine whether elevated body mass index (BMI) is associated with postoperative complications after vestibular schwannoma (VS) surgery.
STUDY DESIGN: Retrospective case series.
SETTING: Tertiary referral center.
PATIENTS: Two hundred six patients undergoing surgery for VS between 2010 and 2017, grouped into obese and nonobese patients.
INTERVENTION: Surgery for VS resection.
MAIN OUTCOME MEASURES: Postoperative facial nerve outcomes, length of hospital stay, presence of postoperative cerebrospinal fluid leak, 30-day readmission, return to the operating room, wound complications, cardiovascular and thromboembolic complications.
RESULTS: After excluding 1 patient for missing BMI, our cohort included 205 patients. Seventy-nine patients (38.5%) were obese (mean BMI 36.2 kg/m, range 30-55.1) and the remaining 126 (61.5%) were nonobese (mean BMI 25.0, range 18.8-29.8 kg/m). Compared with nonobese patients, obesity was not associated with postoperative cerebrospinal fluid leak (OR 1.1, 95% CI 0.93-1.1), length of hospital stay (OR 0.98, 95% CI 0.65-1.47), 30-day readmission rates (1.04, 95% CI 0.95-1.14), return to operating room (OR 1.05, 95% CI 0.98-1.11), or other wound-related complications (OR 0.99, 95% CI 0.94-1.04).
CONCLUSION: In this cohort, elevated BMI was not associated with an increased risk for postoperative complications after VS surgery. Our findings may mitigate concerns associated with surgical management of VS in obese patients.

PMID: 31634280 [PubMed - indexed for MEDLINE]

Long telomeres and cancer risk: the price of cellular immortality.

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

Icon for American Society for Clinical Investigation

Long telomeres and cancer risk: the price of cellular immortality.

J Clin Invest. 2019 08 05;129(9):3474-3481

Authors: McNally EJ, Luncsford PJ, Armanios M

Abstract
The distribution of telomere length in humans is broad, but it has finite upper and lower boundaries. Growing evidence shows that there are disease processes that are caused by both short and long telomere length extremes. The genetic basis of these short and long telomere syndromes may be linked to mutations in the same genes, such as the telomerase reverse transcriptase (TERT), but through differential effects on telomere length. Short telomere syndromes have a predominant degenerative phenotype marked by organ failure that most commonly manifests as pulmonary fibrosis and are associated with a relatively low cancer incidence. In contrast, insights from studies of cancer-prone families as well as genome-wide association studies (GWAS) have identified both rare and common variants that lengthen telomeres as being strongly associated with cancer risk. We have hypothesized that these cancers represent a long telomere syndrome that is associated with a high penetrance of cutaneous melanoma and chronic lymphocytic leukemia. In this Review, we will synthesize the clinical and human genetic observations with data from mouse models to define the role of telomeres in cancer etiology and biology.

PMID: 31380804 [PubMed - indexed for MEDLINE]

Complete responses to two different anti-PD1 agents in a metastatic melanoma patient.

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

Complete responses to two different anti-PD1 agents in a metastatic melanoma patient.

J Oncol Pharm Pract. 2020 Mar;26(2):496-499

Authors: Kilickap S, Guven DC, Aktepe OH, Aktas BY, Dizdar O

Abstract
In the last decade, immune checkpoint inhibitors changed the landscape of metastatic melanoma. However, the optimal duration of treatment and treatment cessation in responders is largely unknown. Herein, we represent a heavily pretreated metastatic melanoma case who had a complete response to pembrolizumab and also a complete response with nivolumab after progression during drug-free follow-up. We think that reinduction with a different anti-PD1 antibody may be used in patients with metastatic melanoma responders. Clinical trials with prespecified sequential treatment protocols and large real-life data can further delineate this subject.

PMID: 31256744 [PubMed - indexed for MEDLINE]

Permalink for 'Discontinuation of anti-PD-1 antibody therapy in the absence of disease progression or treatment limiting toxicity: clinical outcomes in advanced melanoma.'

Discontinuation of anti-PD-1 antibody therapy in the absence of disease progression or treatment limiting toxicity: clinical outcomes in advanced melanoma.

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

Discontinuation of anti-PD-1 antibody therapy in the absence of disease progression or treatment limiting toxicity: clinical outcomes in advanced melanoma.

Ann Oncol. 2019 07 01;30(7):1154-1161

Authors: Jansen YJL, Rozeman EA, Mason R, Goldinger SM, Geukes Foppen MH, Hoejberg L, Schmidt H, van Thienen JV, Haanen JBAG, Tiainen L, Svane IM, Mäkelä S, Seremet T, Arance A, Dummer R, Bastholt L, Nyakas M, Straume O, Menzies AM, Long GV, Atkinson V, Blank CU, Neyns B

Abstract
BACKGROUND: Programmed cell death protein 1 (PD-1) blocking monoclonal antibodies improve the overall survival of patients with advanced melanoma but the optimal duration of treatment has not been established.
PATIENTS AND METHODS: This academic real-world cohort study investigated the outcome of 185 advanced melanoma patients who electively discontinued anti-PD-1 therapy with pembrolizumab (N = 167) or nivolumab (N = 18) in the absence of disease progression (PD) or treatment limiting toxicity (TLT) at 14 medical centres across Europe and Australia.
RESULTS: Median time on treatment was 12 months (range 0.7-43). The best objective tumour response at the time of treatment discontinuation was complete response (CR) in 117 (63%) patients, partial response (PR) in 44 (24%) patients and stable disease (SD) in 16 (9%) patients; 8 (4%) patients had no evaluable disease (NE). After a median follow-up of 18 months (range 0.7-48) after treatment discontinuation, 78% of patients remained free of progression. Median time to progression was 12 months (range 2-23). PD was less frequent in patients with CR (14%) compared with patients with PR (32%) and SD (50%). Six out of 19 (32%) patients who were retreated with an anti-PD-1 at the time of PD obtained a new antitumour response.
CONCLUSIONS: In this real-world cohort of advanced melanoma patients discontinuing anti-PD-1 therapy in the absence of TLT or PD, the duration of anti-PD-1 therapy was shorter when compared with clinical trials. In patients obtaining a CR, and being treated for >6 months, the risk of relapse after treatment discontinuation was low. Patients achieving a PR or SD as best tumour response were at higher risk for progression after discontinuing therapy, and defining optimal treatment duration in such patients deserves further study. Retreatment with an anti-PD-1 at the time of progression may lead to renewed antitumour activity in some patients.
CLINICAL TRIAL REGISTRATION: NCT02673970 [https:]

PMID: 30923820 [PubMed - indexed for MEDLINE]

Patient-Focused Online Resources for Melanoma: Highly Variable Content and Quality.

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

Patient-Focused Online Resources for Melanoma: Highly Variable Content and Quality.

J Cancer Educ. 2019 Aug;34(4):775-781

Authors: Alshaikh EA, Almedimigh AF, Alruwaili AM, Almajnoni AH, Alhajiahmed A, Almalki TS, Alfaraj SZ, Pines JM

Abstract
When patients are diagnosed or concerned with the diagnosis of melanoma, they commonly use the Internet for information. We assessed the content of patient-focused websites about melanoma. We searched for "melanoma" in four search engines then assessed the first 30 websites in each search. Among included sites, we describe potentially useful content about melanoma: website quality, readability, popularity, and social media sharing. In 31 included websites, > 80% mentioned the definition and risk factors for melanoma, when to seek medical help, how to diagnose, and treatment options, and > 70% described preventive measures. However, website quality was variable: 61% of websites had disclosures, 54% were dated, 41% had a clear author, and 41% had references. Average readability ranged from 8th to 12th grade, which is above recommended reading levels for patient websites. Despite this variation and high reading levels, we identified many high-quality melanoma websites for patients.

PMID: 29732480 [PubMed - indexed for MEDLINE]

A metastatic tumor is no different to a viral pandemic: lessons learnt from COVID-19 may teach us to change the PRRT paradigm.

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

A metastatic tumor is no different to a viral pandemic: lessons learnt from COVID-19 may teach us to change the PRRT paradigm.

Eur J Nucl Med Mol Imaging. 2020 Jun 20;:

Authors: Paganelli G, Bodei L, Modlin I

PMID: 32564170 [PubMed - as supplied by publisher]

Development and Validation of Prognostic Nomograms for Patients with Duodenal Neuroendocrine Neoplasms.

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

Development and Validation of Prognostic Nomograms for Patients with Duodenal Neuroendocrine Neoplasms.

Med Sci Monit. 2020 Jun 21;26:e922613

Authors: Sun S, Wang W, He C

Abstract
BACKGROUND This study was designed to predict prognosis of patients with primary duodenal neuroendocrine neoplasms (D-NENs) by developing nomograms. MATERIAL AND METHODS Patients diagnosed with D-NENs between 1988 and 2015 were queried from the SEER database and a total of 965 appropriate cases were randomly separated into the training and validation sets. Kaplan-Meier analysis was used to generated survival curves, and the difference among the groups was assessed by the log-rank test. Independent prognostic indicators were acquired by Cox regression analysis, and were used to develop predictive overall survival (OS) and cancer-specific survival (CSS) nomograms. Harrell's concordance index (C-index), area under the curve (AUC), calibration curves, and decision curve analysis (DCA) were used to assess the efficacy of nomograms. Tumor stage was regarded as a benchmark in predicting prognostic compared with the nomograms built in this study. RESULTS The C-index was 0.739 (0.690-0.788) and 0.859 (0.802-0.916) for OS and CSS nomograms, respectively. Calibration curves exhibited obvious consistency between the nomograms and the actual observations. In addition, C-index, AUC, and DCA were better than tumor stage in the evaluative performance of nomograms. CONCLUSIONS The nomograms were able to predict the 1-, 5-, and 10-year OS and CSS for D-NENs patients. The good performance of these nomograms suggest that they can be used for evaluating the prognosis of patients with D-NENs and can facilitate individualized treatment in clinical practice.

PMID: 32564052 [PubMed - in process]

Colorectal neuroendocrine tumors: A case series.

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

Colorectal neuroendocrine tumors: A case series.

Int J Surg Case Rep. 2020 Jun 12;72:411-417

Authors: Warsinggih, Liliyanto, Prihantono, Ariani GDW, Faruk M

Abstract
INTRODUCTION: Neuroendocrine tumors (NET) of the colon and sigmoid colon are uncommon compared to colorectal adenocarcinoma. Few reports have been made of NET of the colon and sigmoid colon that presents with peritonitis and large bowel obstruction.
CASE PRESENTATION: Here, we report two cases of NET of the colon and sigmoid colon, which were diagnosed and treated at our institution. In our first case, a 66-year-old man with a history of abdominal distension was diagnosed with NET via histopathology of the sigmoid colon. The second case involved a 45-year-old woman with the chief complaints of abdominal distention and inability to defecate; specimen histopathology of the descending colon showed neuroendocrine carcinoma features. Clinical outcome was very poor in our patients: eight months after the resection, the second patient demonstrated a sign of metastasis on the liver.
CONCLUSION: An uncommon case of colon and sigmoid colon carcinoma with neuroendocrine and diagnostic difficulties precludes an exact description of the initial diagnostic criteria and management. Thus, our case series offers an overview of initial symptoms, radiological and histopathological features for early diagnosis, and proper management of NET.

PMID: 32563832 [PubMed - as supplied by publisher]

The Risk of Second Primary Malignancies in Patients With Lung Neuroendocrine Tumors: A Population-Based Study on SEER Database.

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

The Risk of Second Primary Malignancies in Patients With Lung Neuroendocrine Tumors: A Population-Based Study on SEER Database.

Curr Probl Cancer. 2020 Jun 12;:100613

Authors: Bu X, Wang X, Wei L, Liu J, Chen M

Abstract
PURPOSE: We investigated the at-risk sites of second primary malignancies (SPMs) and evaluate the risk factors of SPMs among lung neuroendocrine tumors (LNETs) survivors by using the surveillance, epidemiology, and end results (SEER) database.
METHODS: Propensity-score matching was performed to conduct a case-control study from the surveillance, epidemiology, and end results (SEER) database. Cox regression analysis and multiple primary standardized incidence ratios were performed to investigate the risk factors of occurrence of SPMs among patients with LNETs.
RESULTS: Of 3,206 patients with LNETs after matching, 539 developed SPMs. The risk of developing SPMs was higher in older patients (55-74 vs ≦54: hazard ratios [HR] 1.875; age ≧75 vs ≦54: HR 2.713), higher-stage of LNETs (regional vs localized: HR 1.387; distant vs localized: HR 2.732) and recent periods of diagnosis (2004-2014 vs 1984-1993: HR 1.735). Patients with SCLC, TC and LENEC had a higher risk for SPMs compared to general population. Lung and bronchus, larynx and some digestive organs had higher risk for SPMs while some sex hormone related organs like prostate, breast, and female reproductive system had a lower incidence of SPMs.
CONCLUSIONS: Patients with LNETs had overall higher risks of SPMs than general population. Different types of second primary malignancies occurred in different periods after LNETs were diagnosed. Further investigations are required to screen different second primary malignancies for those with primary LNETs.

PMID: 32563531 [PubMed - as supplied by publisher]

Targeting Pheochromocytoma/Paraganglioma with polyamine inhibitors.

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

Targeting Pheochromocytoma/Paraganglioma with polyamine inhibitors.

Metabolism. 2020 Jun 17;:154297

Authors: Rai SK, Bril F, Hatch HM, Xu Y, Shelton L, Kalavalapalli S, Click A, Lee D, Beecher C, Kirby A, Kong K, Trevino J, Jha A, Jatav S, Kriti K, Luthra S, Garrett TJ, Guingab-Cagmat J, Plant D, Bose P, Cusi K, Hromas RA, Tischler AS, Powers JF, Gupta P, Bibb J, Beuschlein F, Robledo M, Calsina B, Timmers H, Taieb D, Kroiss M, Richter S, Langton K, Eisenhofer G, Bergeron R, Pacak K, Tevosianc SG, Ghayee HK

Abstract
BACKGROUND: Pheochromocytomas (PCCs) and paragangliomas (PGLs) are neuroendocrine tumors that are mostly benign. Metastatic disease does occur in about 10% of cases, and for these patients no effective therapies are available. Patients with mutations in the succinate dehydrogenase subunit B (SDHB) gene tend to have metastatic disease. We hypothesized that a down-regulation in the active succinate dehydrogenase B subunit should result in notable changes in cellular metabolic profile and could present a vulnerability point for successful pharmacological targeting.
METHODS: Metabolomic analysis was performed on human hPheo1 cells and shRNA SDHB knockdown hPheo1 (hPheo1 SDHB KD) cells. Additional analysis of 115 human fresh frozen samples was conducted. In vitro studies using N1,N11-diethylnorspermine (DENSPM) and N1,N12- diethylspermine (DESPM) treatments were carried out. DENSPM efficacy was assessed in human cell line derived mouse xenografts.
RESULTS: Components of the polyamine pathway were elevated in hPheo1 SDHB KD cells compared to wild-type cells. A similar observation was noted in SDHx PCC/PGLs tissues compared to their non-mutated counterparts. Specifically, spermidine, and spermine were significantly elevated in SDHx-mutated PCC/PGLs, with a similar trend in hPheo1 SDHB KD cells. Polyamine pathway inhibitors DENSPM and DESPM effectively inhibited growth of hPheo1 cells in vitro as well in mouse xenografts.
CONCLUSIONS: This study demonstrates overactive polyamine pathway in PCC/PGL with SDHB mutations. Treatment with polyamine pathway inhibitors significantly inhibited hPheo1 cell growth and led to growth suppression in xenograft mice treated with DENSPM. These studies strongly implicate the polyamine pathway in PCC/PGL pathophysiology and provide new foundation for exploring the role for polyamine analogue inhibitors in treating metastatic PCC/PGL. Précis. Cell line metabolomics on hPheo1 cells and PCC/PGL tumor tissue indicate that the polyamine pathway is activated. Polyamine inhibitors in vitro and in vivo demonstrate that polyamine inhibitors are promising for PCC/PGL treatment.

PMID: 32562798 [PubMed - as supplied by publisher]

Invasive solid papillary carcinoma with neuroendocrine differentiation of the breast: a case report and literature review.

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

Invasive solid papillary carcinoma with neuroendocrine differentiation of the breast: a case report and literature review.

Surg Case Rep. 2020 Jun 19;6(1):143

Authors: Lin X, Matsumoto Y, Nakakimura T, Ono K, Umeoka S, Torii M, Yoshibayashi H, Toi M

Abstract
BACKGROUND: Solid papillary carcinoma (SPC) of the breast is a rare breast cancer that accounts for less than 1% of all breast cancers. The optimal clinical management of SPC remains controversial. Here, we report a case of invasive SPC with neuroendocrine differentiation in addition to review of the current literature.
CASE PRESENTATION: A premenopausal 46-year-old female presented with a mass in her left breast that tended to increase in size over a 10-month period. Mammography and ultrasonography revealed a mass in the left upper-inner quadrant. The resulting images suggested a category 3 breast tumor according to the Breast Imaging Reporting and Data System (BI-RADS). A core needle biopsy (CNB) was performed, and the pathological findings showed a solid papillary pattern and atypical cells suggestive of noninvasive SPC. After a left partial mastectomy and sentinel lymph node biopsy (SLNB), the specimens were sent for histopathological analysis for further investigation. Postoperative pathological findings suggested invasive SPC. Whole-breast radiation therapy and adjuvant hormonal therapy were performed as postoperative treatments. Three years after surgery, multiple lung metastases were detected, and the patient was treated with a gonadotropin-releasing hormone agonist and an aromatase inhibitor. Five months later, multiple liver metastases and bone metastases appeared, and oral 5-fluorouracil was chosen for the subsequent treatment. The patient has been treated for 5 years to date, and she is continuing to take oral 5-fluorouracil and is alive without any further disease progression.
CONCLUSIONS: We report a rare case of premenopausal invasive SPC with multiple metastases. Further study is needed to clarify the molecular characteristics and clinical behaviors of SPC and to explore the optimal treatment strategy.

PMID: 32562013 [PubMed - as supplied by publisher]

Transanal Minimally Invasive Surgery (TAMIS) in Qatar: initial experience.

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

Transanal Minimally Invasive Surgery (TAMIS) in Qatar: initial experience.

BMC Surg. 2020 Jun 19;20(1):138

Authors: Abutaka A, Ahmed A, Abunada M, Kurer M

Abstract
BACKGROUND: Transanal Minimally Invasive Surgery (TAMIS) has revolutionized local excision of mid and high rectal lesions; benign or malignant. It is a technique that is developed as a hybrid between Transanal Endoscopic Microsurgery (TEM) and laparoscopic surgery for resection of rectal lesions.
METHODS: We retrospectively reviewed prospectively collected data on patients who underwent TAMIS for benign and early malignant rectal lesions between Jan 2015 and Sept 2019, at Hamad General Hospital, Doha, Qatar. We assessed the following outcomes: feasibility, fragmentation of specimen, operative time, length of stay (LOS) post-operative complications, and margin negativity.
RESULTS: Seventeen consecutive patients underwent TAMIS for benign and malignant rectal lesions. The average length of stay (LOS) is 1.5 days (1-6 days). Seven patients had different types of benign adenomas, five patients had proven adenocarcinoma, three patients had well-differentiated neuroendocrine tumors, one patient with hyperplastic polyp, and one patient had inflammatory polyp. No fragmentation occurred or detected by histopathologic examination, except in a patient who had inflammatory polyp, where the lesion removed in two fragments.
CONCLUSION: TAMIS procedure is feasible and safe even in a relatively low-volume colorectal unit. Using this tool, many patients can avoid unnecessary radical surgery. Therefore, we believe that TAMIS should form part of every specialized colorectal service repertoire. To our knowledge, this is the largest series in the gulf region.

PMID: 32560638 [PubMed - as supplied by publisher]

Permalink for 'Are volume-dependent parameters in positron emission tomography predictive of postoperative recurrence after resection in patients with thymic carcinoma?'

Are volume-dependent parameters in positron emission tomography predictive of postoperative recurrence after resection in patients with thymic carcinoma?

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

Are volume-dependent parameters in positron emission tomography predictive of postoperative recurrence after resection in patients with thymic carcinoma?

Surg Today. 2020 Jun 13;:

Authors: Hamaji M, Koyasu S, Omasa M, Nakakura A, Morita S, Nakagawa T, Miyahara S, Miyata R, Yokoyama Y, Kawakami K, Suga M, Takahashi M, Terada Y, Muranishi Y, Miyahara R, Sumitomo R, Huang CL, Aoyama A, Takahashi Y, Date H

Abstract
This study aimed to investigate the association between the volume-dependent parameters in 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG PET/CT) and a recurrence of thymic carcinoma. A retrospective chart review was performed based on our multi-institutional database to identify patients undergoing PET prior to resection of thymic carcinoma or neuroendocrine carcinoma between 1991 and 2018. The PET parameters (metabolic tumor volume and total lesion glycolysis) were evaluated retrospectively. The relevant factors were extracted and a survival analysis was performed using the Kaplan-Meier method. Sixteen patients were thus deemed to be eligible for analysis. The median follow-up period following resection was 2.65 years (range: 0.96-0.68 years). The recurrence-free survival was significantly longer in patients with a metabolic tumor volume < = 22.755 cm3 and with total lesion glycolysis < = 105.4006 g/mL (p = 0.001 and 0.001, respectively, by a log-rank test). The metabolic tumor volume and total lesion glycolysis may, therefore, be predictive of the postoperative recurrence of thymic carcinoma.

PMID: 32535710 [PubMed - as supplied by publisher]

Changing Insulinoma Management Due to Incidentally Discovered Metastasis: A Case Report.

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

Changing Insulinoma Management Due to Incidentally Discovered Metastasis: A Case Report.

Am J Case Rep. 2020 Jun 14;21:e923356

Authors: Madan R, Mettler T, Froelich J, Chow LS

Abstract
BACKGROUND Hypoglycemia is rare in individuals without drug-treated diabetes mellitus. In a seemingly well individual, the differential diagnosis of hypoglycemia narrows to 2 major categories: 1) accidental, surreptitious, or intentional hypoglycemia, or 2) endogenous hyperinsulinism (EHH). Insulinomas are the most common cause of EHH. Localization of insulinomas can be challenging, as most tumors are less than 2 cm in size and may be present in any part of the pancreas. In fact, almost 30% of neuroendocrine tumors (NET) cannot be located preoperatively by traditional imaging techniques such as computerized tomography (CT) or magnetic resonance imaging (MRI). CASE REPORT This report describes a case of metastatic insulinoma in a patient with a complex medical history. CT with contrast of the abdomen identified 1 lesion located in the pancreas body. Endoscopic ultrasound (EUS) identified an additional 3 to 4 hypoechoic lesions in the pancreatic neck and body. 68-Gallium Dotatate scanning identified 3 distinct lesions within the pancreas and a right posterior rib sclerotic lesion. CONCLUSIONS Reliance upon traditional imaging techniques (CT/MRI) for tumor localization would not have identified the multifocal pancreatic lesions and the metastatic bone lesion. Accurate identification of multifocal, metastatic insulinomas requires multiple imaging modalities, including first-line non-invasive imaging (CT or MRI) followed by second-line imaging (EUS or nuclear imaging).

PMID: 32535614 [PubMed - as supplied by publisher]

Super-late pulmonary recurrence after radical esophagectomy for esophageal squamous cell carcinoma.

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

Super-late pulmonary recurrence after radical esophagectomy for esophageal squamous cell carcinoma.

Int J Surg Case Rep. 2020 Jun 06;72:166-171

Authors: Umemura A, Akiyama Y, Iwaya T, Koeda K, Sugimoto R, Sugai T, Endo F, Baba S, Nikai H, Nitta H, Takahara T, Otuska K, Kimura T, Saito H, Deguchi H, Tomoyasu M, Sasaki A

Abstract
INTRODUCTION: Pulmonary metastases from esophageal squamous cell carcinoma (ESCC) are often detected bilateral and multiple lesions and are often accompanied by metastases to other sites. The concept of oligometastasis has been developed, and limited distant metastases have been considered as indications for surgical resection for the purpose of extending overall survival. We herein present a long-surviving case of super-late pulmonary recurrence of ESCC, seven years after radical esophagectomy.
PRESENTATION OF CASE: A 71-year-old woman who underwent radical subtotal esophagectomy with three-field lymph node dissection with a diagnosis of an advanced poorly differentiated ESCC with cT3N1M0 seven years ago visited our hospital. Chest X-ray and computed tomography at the 7-year follow-up revealed a solitary pulmonary tumor, 1.5 cm in diameter, at the right middle lobe without any extrapulmonary metastases; however, we could not diagnose whether primary lung cancer or pulmonary metastasis of ESCC was present. Therefore, we performed thoracoscopic partial resection of the right middle lobe. A histopathological examination including immunohistochemical staining revealed that the tumor was not derived from both alveolar epithelium and neuroendocrine cells and was diagnosed as pulmonary oligometastasis of ESCC. She has been followed for four years without re-recurrence.
CONCLUSION: Pulmonary oligometastases of ESCC should be considered as surgical indications if the tumor is detected after a long disease-free interval without any extrapulmonary recurrences.

PMID: 32535535 [PubMed - as supplied by publisher]

Permalink for 'Phase II study of pembrolizumab efficacy and safety in women with recurrent small cell neuroendocrine carcinoma of the lower genital tract.'

Phase II study of pembrolizumab efficacy and safety in women with recurrent small cell neuroendocrine carcinoma of the lower genital tract.

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

Phase II study of pembrolizumab efficacy and safety in women with recurrent small cell neuroendocrine carcinoma of the lower genital tract.

Gynecol Oncol. 2020 Jun 11;:

Authors: Frumovitz M, Westin SN, Salvo G, Zarifa A, Xu M, Yap TA, Rodon AJ, Karp DD, Abonofal A, Jazaeri AA, Naing A

Abstract
OBJECTIVE: To investigate the efficacy and safety of pembrolizumab in women with recurrent small cell neuroendocrine tumors of the lower genital tract.
METHODS: We conducted an open-label, investigator-initiated phase II basket trial of pembrolizumab 200 mg intravenously every 3 weeks in patients with rare tumors (ClinicalTrials.gov: NCT02721732). The trial had prespecified cohorts, including small cell malignancies of extrapulmonary origin. Eligibility criteria included disease progression during standard treatment in the 6 months before study enrollment. Patients were enrolled from February 2017 to February 2019. The primary endpoint was the proportion of patients alive without progression at 27 weeks. Response to pembrolizumab was evaluated every 9 weeks (3 cycles) with radiographic imaging.
RESULTS: Seven women with gynecologic extrapulmonary small cell carcinoma were enrolled, 6 with cervical and 1 with vulvar carcinoma. No patient was progression free at 27 weeks. At first radiologic assessment, 1 patient had stable disease, while 6 had progression. The single patient with stable disease at 6 weeks had disease progression at 14 weeks. The median progression-free interval was 2.1 months (range 0.8-3.3 months). Severe treatment-related adverse events (≥grade 3) were seen in 2 of 7 patients (29%); 1 patient had grade 3 asymptomatic elevation of serum alkaline phosphatase, and 1 had grade 3 asymptomatic elevation of serum alanine aminotransferase.
CONCLUSIONS: Pembrolizumab alone showed minimal activity in women with recurrent small cell neuroendocrine tumors of the lower genital tract. Treatment was well tolerated in the majority of study participants, and the rate of severe adverse events was low.

PMID: 32534809 [PubMed - as supplied by publisher]

Review of Nonmammary Metastases to the Breast: Imaging and Clinical Presentation.

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

Review of Nonmammary Metastases to the Breast: Imaging and Clinical Presentation.

Curr Probl Diagn Radiol. 2020 May 17;:

Authors: Choudhery S, Xiao L, Zingula S

Abstract
OBJECTIVES: The purpose of our study is to review the imaging findings of breast metastases from nonmammary sources at our institution and to explore the mode of initial detection of these breast metastases.
METHODS: In this study, we reviewed our electronic medical record and our breast imaging database for all patients who presented with nonmammary metastases to breasts between 5/1/2009 and 12/1/2019. We reviewed all available imaging data, clinical notes, and pathology reports.
RESULTS: Sixteen cases of nonmammary metastases to the breast were included in this study, of which there were 4 (25%) metastases from melanoma, 3 (19%) from carcinoid tumor, 2 (13%) from lung cancer, 2 (13%) from leiomyosarcoma, 1 (6%) each from lipsarcoma, renal cell carcinoma, colon cancer, neuroendocrine tumor, and adenoid cystic carcinoma. 6/8 (75%) lesions that had breast imaging were oval in shape with circumscribed or microlobulated margins on mammography and/or ultrasound. 13/16 (81%) breast metastases were asymptomatic and diagnosed on systemic staging exams. Three out of 16 (19%) nonmammary breast metastases were palpable and were diagnosed on subsequent breast imaging.
CONCLUSIONS: Most (25%) nonmammary breast metastases in our patient population occur from melanoma and most breast metastases (75%) are oval in shape with circumscribed or microlobulated margins. Majority (81%) of these lesions are asymptomatic and initially diagnosed on systemic staging tests, and the remaining are discovered as palpable lesions.

PMID: 32534793 [PubMed - as supplied by publisher]

Synchronous detection of SDHA-related gallbladder paraganglioma and pancreatic neuroendocrine tumor.

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

Synchronous detection of SDHA-related gallbladder paraganglioma and pancreatic neuroendocrine tumor.

Pathol Res Pract. 2020 Jul;216(7):153006

Authors: Aaquist T, Medhus JB, Thomassen A, Detlefsen S

Abstract
Primary gallbladder paragangliomas (PGLs) are exceedingly rare. PGLs are extraadrenal neuroendocrine tumors that are morphologically inseparable from intraadrenal pheochromocytomas. PGLs and pheochromocytomas are some of the most heritable tumor types in the body and are often associated with other tumors or part of a genetic syndrome. We report a case of gallbladder PGL presenting synchronously with pancreatic neuroendocrine tumor (NET) and pulmonary IgG4-related disease in a 74-year old male patient with disseminated prostate adenocarcinoma. Due to the high rate of germline mutations and the possible syndromal manifestation of PGLs as well as pancreatic NETs, this patient was offered genetic testing, and a pathogenic SDHA germline mutation was found. Immunohistochemically, there was loss of SDHA and SDHB in the PGL but neither in the NET nor in the prostate adenocarcinoma. To our knowledge, this case is the first report of gallbladder PGL associated with pancreatic NET. It is likely that the identified SDHA germline mutation played a role in the development of gallbladder PGL in this patient.

PMID: 32534711 [PubMed - as supplied by publisher]

Mixed adenoneuroendocrine carcinoma of the gallbladder, amphicrine type: Case report and review of literature.

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

Mixed adenoneuroendocrine carcinoma of the gallbladder, amphicrine type: Case report and review of literature.

Pathol Res Pract. 2020 Jul;216(7):152997

Authors: Zhang D, Li P, Szankasi P, Liao X

Abstract
Amphicrine type mixed adenoneuroendocrine carcinoma (MANEC), also known as amphicrine carcinoma, is an exceedingly rare neoplasm comprising of tumor cells simultaneously demonstrating both neuroendocrine and exocrine differentiation. Majority of reported cases were found in tubular gastrointestinal tracts such as colon. Herein, we report the first case of amphicrine carcinoma in gallbladder in a 57-year-old female who presented with abdominal pain, vomiting, and gallbladder mass on imaging followed by radical cholecystectomy. Macroscopically, the tumor was a polypoid solid mass with a firm and tan-white cut surface located at the gallbladder fundus. Histologically, the tumor cells were composed of monotonous-appearing signet-ring cells with fine chromatin, variably conspicuous nucleoli, brisk mitotic figures, and spotty necrosis. They were loosely clustered, forming nests and cords but no glandular formation. Immunohistochemically, the entire tumor showed strong and diffuse immunoreactivity for CDX2, p53, and synaptophysin, with patchy positivity for CD56, chromogranin, and INSM1. Kreyberg stain highlighted both intracytoplasmic and extracellular mucin. Ki-67 proliferation index was approximately 70%. Next-generation sequencing performed on a 724 cancer-related gene panel identified TP53 mutation at c.844C>T (p.R282W). To our knowledge, this is the first case of amphicrine carcinoma in gallbladder. It highlights the complex dynamism and controversial pathogenesis of this unique entity, the exact mechanism and clinicopathologic behavior of which are not yet understood.

PMID: 32534704 [PubMed - as supplied by publisher]

ASCL1 promotes tumor progression through cell-autonomous signaling and immune modulation in a subset of lung adenocarcinoma.

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

ASCL1 promotes tumor progression through cell-autonomous signaling and immune modulation in a subset of lung adenocarcinoma.

Cancer Lett. 2020 Jun 10;:

Authors: Miyashita N, Horie M, Mikami Y, Urushiyama H, Fukuda K, Miyakawa K, Matsuzaki H, Makita K, Morishita Y, Harada H, Backman M, Lindskog C, Brunnström H, Micke P, Nagase T, Saito A

Abstract
The master regulator of neuroendocrine differentiation, achaete-scute complex homolog 1 (ASCL1) defines a subgroup of lung adenocarcinoma. However, the mechanistic role of ASCL1 in lung tumorigenesis and its relation to the immune microenvironment is principally unknown. Here, the immune landscape of ASCL1-positive lung adenocarcinomas was characterized by immunohistochemistry. Furthermore, ASCL1 was transduced in mouse lung adenocarcinoma cell lines and comparative RNA-sequencing and secretome analyses were performed. The effects of ASCL1 on tumorigenesis were explored in an orthotopic syngeneic transplantation model. ASCL1-positive lung adenocarcinomas revealed lower infiltration of CD8+, CD4+, CD20+, and FoxP3+ lymphocytes and CD163+ macrophages indicating an immune desert phenotype. Ectopic ASCL1 upregulated cyclin transcript levels, stimulated cell proliferation, and enhanced tumor growth in mice. ASCL1 suppressed secretion of chemokines, including CCL20, CXCL2, CXCL10, and CXCL16, indicating effects on immune cell trafficking. In accordance with lower lymphocytes infiltration, ASCL1-positive lung adenocarcinomas demonstrated lower abundance of CXCR3-and CCR6-expressing cells. In conclusion, ASCL1 mediates its tumor-promoting effect not only through cell-autonomous signaling but also by modulating chemokine production and immune responses. These findings suggest that ASCL1-positive tumors present a clinically relevant lung cancer entity.

PMID: 32534174 [PubMed - as supplied by publisher]

Grade 3 well-differentiated neuroendocrine tumor of the rectum: a case report.

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

Grade 3 well-differentiated neuroendocrine tumor of the rectum: a case report.

Surg Case Rep. 2020 Jun 12;6(1):130

Authors: Ito M, Hirano Y, Isii T, Kondo H, Wang L, Asari M, Obara N, Yamaguchi S

Abstract
BACKGROUND: The 2019 revised World Health Organization (WHO) classification of tumors of endocrine organs classifies grade 3 gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN G3) into well-differentiated tumors (NET G3) and poorly differentiated carcinomas (NEC G3). There are few reported cases of NET G3 occurring in the rectum.
CASE PRESENTATION: A 71-year-old man complained of bright red blood in his stool. Total colonoscopy revealed a mass in the lower rectum. Pathologic examination yielded a diagnosis of group 1. Computed tomography revealed swollen paraintestinal lymph nodes and multiple liver metastases. We performed laparoscopic abdominoperineal resection not only to avoid the unbearable symptoms caused by tumor growth but to make a pathological diagnosis. The tumor measured 3.5 × 2.8 cm, and the pathological diagnosis was stage IV neuroendocrine carcinoma. He underwent chemotherapy with irinotecan plus cisplatin, followed by carboplatin plus etopside, but his disease did not respond to either regimen. Twenty-seven months after surgery, he died of his disease. Upon re-examination of the surgical specimen, the tumor was consistent with the 2019 WHO classification of NET G3.6 CONCLUSION: A definite diagnosis of NET G3 or NEC G3 must be made to determine the appropriate treatment strategy for patients with GEP-NEN G3. Further case reports and case series are needed to establish the optimal therapy.

PMID: 32533349 [PubMed - as supplied by publisher]

Permalink for 'Immunotherapy of Ipilimumab and Nivolumab in patients with advanced neuroendocrine tumours: a subgroup analysis of the CA209-538 clinical trial for rare cancers.'

Immunotherapy of Ipilimumab and Nivolumab in patients with advanced neuroendocrine tumours: a subgroup analysis of the CA209-538 clinical trial for rare cancers.

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

Immunotherapy of Ipilimumab and Nivolumab in patients with advanced neuroendocrine tumours: a subgroup analysis of the CA209-538 clinical trial for rare cancers.

Clin Cancer Res. 2020 Jun 12;:

Authors: Klein O, Kee D, Markman B, Michael M, Underhill CR, Carlino MS, Jackett L, Lum C, Scott CL, Nagrial A, Behren A, So JY, Palmer J, Cebon JS

Abstract
PURPOSE: Combination immunotherapy with anti-CTLA-4 and anti-PD-1 blockade has demonstrated significant clinical activity across several tumour types. Neuroendocrine tumors (NETs) are a heterogeneous group of rare tumors with limited treatment options. CA209-538 is a clinical trial of combination immunotherapy with ipilimumab and nivolumab in rare cancers, including advanced NETs.
EXPERIMENTAL DESIGN: CA209-538 is a prospective multicentre clinical trial in patients with advanced rare cancers. Patients received treatment with nivolumab at a dose of 3mg/kg and ipilimumab at 1mg/kg every three weeks for four doses, followed by nivolumab 3mg/kg every two weeks and continued for up to 96 weeks, until disease progression or the development of unacceptable toxicity. Response was assessed every 12 weeks by RECIST 1.1. The primary endpoint was clinical benefit rate.
RESULTS: Twenty-nine patients with advanced NETs received treatment. Three patients (10%) had low, 13 (45%) intermediate and 13 (45%) high grade tumors; lung was the most common primary site (39%). The objective response rate was 24% with a CBR of 72%; 43% of patients with pancreatic neuroendocrine neoplasms (NENs) and 33% of patients with atypical bronchial carcinoid achieved an objective response. The median progression free survival was 4.8 months (95% CI: 2.7, 10.5) and overall survival 14.8 months (95% CI: 4.1,21.3). Immune-related toxicity was reported in 66% of patients with 34% experiencing grade 3/4 events.
CONCLUSIONS: Combination immunotherapy with ipilimumab and nivolumab demonstrated significant clinical activity in subgroups of patients with advanced NETs including patients with atypical bronchial carcinoid and high grade pancreatic NENs.

PMID: 32532787 [PubMed - as supplied by publisher]

Androgen Deprivation Induces Reprogramming of Prostate Cancer Cells to Stem-Like Cells.

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

Androgen Deprivation Induces Reprogramming of Prostate Cancer Cells to Stem-Like Cells.

Cells. 2020 Jun 10;9(6):

Authors: Sánchez BG, Bort A, Vara-Ciruelos D, Díaz-Laviada I

Abstract
In the past few years, cell plasticity has emerged as a mode of targeted therapy evasion in prostate adenocarcinoma. When exposed to anticancer therapies, tumor cells may switch into a different histological subtype, such as the neuroendocrine phenotype which is associated with treatment failure and a poor prognosis. In this study, we demonstrated that long-term androgen signal depletion of prostate LNCaP cells induced a neuroendocrine phenotype followed by re-differentiation towards a "stem-like" state. LNCaP cells incubated for 30 days in charcoal-stripped medium or with the androgen receptor antagonist 2-hydroxyflutamide developed neuroendocrine morphology and increased the expression of the neuroendocrine markers βIII-tubulin and neuron specific enolase (NSE). When cells were incubated for 90 days in androgen-depleted medium, they grew as floating spheres and had enhanced expression of the stem cell markers CD133, ALDH1A1, and the transporter ABCB1A. Additionally, the pluripotent transcription factors Nanog and Oct4 and the angiogenic factor VEGF were up-regulated while the expression of E-cadherin was inhibited. Cell viability revealed that those cells were resistant to docetaxel and 2-hidroxyflutamide. Mechanistically, androgen depletion induced the decrease in AMP-activated kinase (AMPK) expression and activation and stabilization of the hypoxia-inducible factor HIF-1α. Overexpression of AMPK in the stem-like cells decreased the expression of stem markers as well as that of HIF-1α and VEGF while it restored the levels of E-cadherin and PGC-1α. Most importantly, docetaxel sensitivity was restored in stem-like AMPK-transfected cells. Our model provides a new regulatory mechanism of prostate cancer plasticity through AMPK that is worth exploring.

PMID: 32531951 [PubMed - as supplied by publisher]

COVID-19 and Cushing's syndrome: recommendations for a special population with endogenous glucocorticoid excess.

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

COVID-19 and Cushing's syndrome: recommendations for a special population with endogenous glucocorticoid excess.

Lancet Diabetes Endocrinol. 2020 Jun 09;:

Authors: Pivonello R, Ferrigno R, Isidori AM, Biller BMK, Grossman AB, Colao A

PMID: 32531251 [PubMed - as supplied by publisher]

Neoadjuvant Checkpoint Inhibitor Therapy for Merkel Cell Carcinoma.

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

Neoadjuvant Checkpoint Inhibitor Therapy for Merkel Cell Carcinoma.

J Clin Oncol. 2020 Jun 12;:JCO2000752

Authors: Brohl AS, Sondak VK

PMID: 32530767 [PubMed - as supplied by publisher]

Permalink for 'A case of pancreatic mixed acinar-neuroendocrine carcinoma successfully diagnosed with endoscopic ultrasound-guided fine needle aspiration.'

A case of pancreatic mixed acinar-neuroendocrine carcinoma successfully diagnosed with endoscopic ultrasound-guided fine needle aspiration.

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

A case of pancreatic mixed acinar-neuroendocrine carcinoma successfully diagnosed with endoscopic ultrasound-guided fine needle aspiration.

Clin J Gastroenterol. 2020 Jun 11;:

Authors: Niiya F, Takano Y, Azami T, Kobayashi T, Maruoka N, Wakabayashi T, Matsuo K, Tanaka K, Norose T, Ohike N, Nagahama M

Abstract
Mixed acinar-neuroendocrine carcinoma (MAEC) of the pancreas is a rare entity, and obtaining a preoperative diagnosis is difficult. We report a case of pancreatic MAEC successfully diagnosed with EUS-FNA. The case was a 72-year-old male with upper abdominal pain. Abdominal CT showed an irregular, hypovascular tumor of pancreatic tail. EUS-FNA was performed using a 22G needle. Immunostaining revealed positive results for the acinar marker trypsin and the neuroendocrine markers chromogranin A and synaptophysin. The possibility for MAEC was considered. He underwent distal pancreatectomy and splenectomy. Immunohistochemical examination of the tumor cells showed a wide range of positivity for bcl-10 and trypsin as well as for chromogranin A and synaptophysin, but negative results for CA19-9 and AFP. Considering that ≥ 30% tumors were positive for both acinar and neuroendocrine markers, the patient was diagnosed with MAEC.

PMID: 32529486 [PubMed - as supplied by publisher]

miR375-3p Distinguishes Low-Grade Neuroendocrine From Non-neuroendocrine Lung Tumors in FFPE Samples.

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

miR375-3p Distinguishes Low-Grade Neuroendocrine From Non-neuroendocrine Lung Tumors in FFPE Samples.

Front Mol Biosci. 2020;7:86

Authors: Detassis S, Del Vescovo V, Grasso M, Masella S, Cantaloni C, Cima L, Cavazza A, Graziano P, Rossi G, Barbareschi M, Ricci L, Denti MA

Abstract
Lung cancer is still one of the leading cause of death worldwide. The clinical variability of lung cancer is high and drives treatment decision. In this context, correct discrimination of pulmonary neuroendocrine tumors is still of critical relevance. The spectrum of neuroendocrine tumors is various, and each type has molecular and phenotypical differences. In order to advance in the discrimination of neuroendocrine from non-neuroendocrine lung tumors, we tested a series of 95 surgically resected and formalin-fixed paraffin embedded lung cancer tissues, and we analyzed the expression of miR205-5p and miR375-3p via TaqMan RT-qPCR. Via a robust mathematical approach, we excluded technical outliers increasing the data reproducibility. We found that miR375-3p levels are higher in low-grade neuroendocrine lung tumor samples compared to non-neuroendocrine lung tumors. However, miR375-3p is not able to distinguish among different types of neuroendocrine lung tumors. In this work, we provide a new molecular marker for distinguishing non-neuroendocrine from low-grade neuroendocrine lung tumors samples establishing an easy miRNA score to be used in clinical settings, enabling the pathologist to classify more accurately lung tumors biopsies, which may be ambiguously cataloged in routine examination.

PMID: 32528971 [PubMed]

Medullary Thyroid Carcinoma Presenting as Metastatic Disease to the Breast.

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

Medullary Thyroid Carcinoma Presenting as Metastatic Disease to the Breast.

Case Rep Pathol. 2020;2020:6138409

Authors: Kanteti AP, Atiya S, Hein A, Cox JL, Martinez Duarte E

Abstract
Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor that is derived from C cells of the thyroid gland. It is a rare aggressive tumor, known to metastasize to lymph nodes, liver, bones, and lungs. A 41-year-old female, who presented with a breast mass, was initially diagnosed with invasive ductal carcinoma. She was also found to have a thyroid mass which was later diagnosed as MTC. On a rereview of the breast pathology, the morphologic features were strikingly similar to the MTC. Further investigation revealed that this was in fact a very rare case of MTC that had metastasized to the breast. We have identified 20 cases of MTC metastasizing to the breast in the literature that supports its occurrence as a real possibility. Albeit rare, medullary thyroid carcinoma should be considered in the differential diagnosis of a breast mass.

PMID: 32528739 [PubMed]

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

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

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

Ann Palliat Med. 2020 Jun 02;:

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

PMID: 32527130 [PubMed - as supplied by publisher]

Siglec1-expressing subcapsular sinus macrophages provide soil for melanoma lymph node metastasis.

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

Icon for eLife Sciences Publications, Ltd

Siglec1-expressing subcapsular sinus macrophages provide soil for melanoma lymph node metastasis.

Elife. 2019 12 24;8:

Authors: Singh R, Choi BK

Abstract
Lymph nodes (LNs) are a common site of metastasis in solid cancers, and cutaneous melanomas show inherent properties of LN colonization. However, interactions between LN stroma and pioneer metastatic cells during metastatic colonization remain largely uncharacterized. Here we studied mice implanted with GFP-expressing melanoma cells to decipher early LN colonization events. We show that Siglec1-expressing subcapsular sinus (SCS) macrophages provide anchorage to pioneer metastatic cells. We performed in vitro co-culture to demonstrate that interactions between hypersialylated cancer cells and Siglec1 drive the proliferation of cancer cells. When comparing the transcriptome profile of Siglec1-interacting cancer cells against non-Siglec1-interacting cancer cells, we detected enrichment in positive regulators of cell cycle progression. Further, knockout of St3gal3 sialyltransferase compromised the metastatic efficiency of tumor cells by reducing α-2,3-linked sialylation. Thus, the interaction between Siglec1-expressing SCS macrophages and pioneer metastatic cells drives cell cycle progression and enables efficient metastatic colonization.

PMID: 31872800 [PubMed - indexed for MEDLINE]

SPION decorated exosome delivery of TNF-α to cancer cell membranes through magnetism.

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

SPION decorated exosome delivery of TNF-α to cancer cell membranes through magnetism.

Nanoscale. 2020 Jan 07;12(1):173-188

Authors: Zhuang M, Chen X, Du D, Shi J, Deng M, Long Q, Yin X, Wang Y, Rao L

Abstract
Tumor necrosis factor (TNF-α) is capable of inducing apoptosis and is a promising candidate for genetic engineering drugs in cancer therapy; however, the serious side-effects of TNF-α hinder their clinical application. In the present study, a method for preparing fusion proteins of cell-penetrating peptides (CPP) and TNF-α (CTNF-α)-anchored exosomes coupled with superparamagnetic iron oxide nanoparticles (CTNF-α-exosome-SPIONs) with membrane targeting anticancer activity has been demonstrated. To acquire exosomes with TNF-α anchored in its membrane, a CTNF-α expression vector was constructed and a stable mesenchymal stem cell cell line that expressed CTNF-α was established. Conjugating transferrin-modified SPIONs (Tf-SPIONs) onto CTNF-α-exosomes through transferrin-transferrin receptor (Tf-TfR) interaction yields CTNF-α-exosome-SPIONs with good water dispersibility. The incorporation of TNF-α into exosomes and the conjugation of SPIONs significantly enhanced the binding capacity of TNF-α to its membrane-bound receptor TNFR I, thus increasing the therapeutic effects. CTNF-α-exosome-SPIONs significantly enhanced tumor cell growth inhibition via induction of the TNFR I-mediated apoptotic pathway. In vivo studies using murine melanoma subcutaneous cancer models showed that TNF-α-loaded exosome-based vehicle delivery enhanced cancer targeting under an external magnetic field and suppressed tumor growth with mitigating toxicity. Taken together, our results suggest that CTNF-α-exosome-SPIONs showed great potential in membrane targeting therapy.

PMID: 31803890 [PubMed - indexed for MEDLINE]

Intravitreous Cutaneous Metastatic Melanoma in the Era of Checkpoint Inhibition: Unmasking and Masquerading.

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

Intravitreous Cutaneous Metastatic Melanoma in the Era of Checkpoint Inhibition: Unmasking and Masquerading.

Ophthalmology. 2020 02;127(2):240-248

Authors: Francis JH, Berry D, Abramson DH, Barker CA, Bergstrom C, Demirci H, Engelbert M, Grossniklaus H, Hubbard B, Iacob CE, Jaben K, Kurli M, Postow MA, Wolchok JD, Kim IK, Wells JR

Abstract
PURPOSE: Cutaneous melanoma metastatic to the vitreous is very rare. This study investigated the clinical findings, treatment, and outcome of patients with metastatic cutaneous melanoma to the vitreous. Most patients received checkpoint inhibition for the treatment of systemic disease, and the significance of this was explored.
DESIGN: Multicenter, retrospective cohort study.
PARTICIPANTS: Fourteen eyes of 11 patients with metastatic cutaneous melanoma to the vitreous.
METHODS: Clinical records, including fundus photography and ultrasound results, were reviewed retrospectively, and relevant data were recorded for each patient eye.
MAIN OUTCOME MEASURES: Clinical features at presentation, ophthalmic and systemic treatments, and outcomes.
RESULTS: The median age at presentation of ophthalmic disease was 66 years (range, 23-88 years), and the median follow-up from diagnosis of ophthalmic disease was 23 months. Ten of 11 patients were treated with immune checkpoint inhibition at some point in the treatment course. The median time from starting immunotherapy to ocular symptoms was 17 months (range, 4.5-38 months). Half of eyes demonstrated amelanotic vitreous debris. Five eyes demonstrated elevated intraocular pressure, and 4 eyes demonstrated a retinal detachment. Six patients showed metastatic disease in the central nervous system. Ophthalmic treatment included external beam radiation (30-40 Gy) in 6 eyes, intravitreous melphalan (10-20 μg) in 4 eyes, enucleation of 1 eye, and local observation while receiving systemic treatment in 2 eyes. Three eyes received intravitreous bevacizumab for neovascularization. The final Snellen visual acuity ranged from 20/20 to no light perception.
CONCLUSIONS: The differential diagnosis of vitreous debris in the context of metastatic cutaneous melanoma includes intravitreal metastasis, and this seems to be particularly apparent during this era of treatment with checkpoint inhibition. External beam radiation, intravitreous melphalan, and systemic checkpoint inhibition can be used in the treatment of ophthalmic disease. Neovascular glaucoma and retinal detachments may occur, and most eyes show poor visual potential. Approximately one quarter of patients demonstrated ocular disease that preceded central nervous system metastasis. Patients with visual symptoms or vitreous debris in the context of metastatic cutaneous melanoma would benefit from evaluation by an ophthalmic oncologist.

PMID: 31708274 [PubMed - indexed for MEDLINE]

Permalink for 'Elucidating value: the role of cost-effectiveness analysis in the decision-making process for the management of BRAF V600E/K mutation-positive melanoma.'

Elucidating value: the role of cost-effectiveness analysis in the decision-making process for the management of BRAF V600E/K mutation-positive melanoma.

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

Elucidating value: the role of cost-effectiveness analysis in the decision-making process for the management of BRAF V600E/K mutation-positive melanoma.

J Med Econ. 2019 12;22(12):1241-1242

Authors: Petrou P

PMID: 31560259 [PubMed - indexed for MEDLINE]

Twelve-year results of LINAC-based radiosurgery for vestibular schwannomas.

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

Twelve-year results of LINAC-based radiosurgery for vestibular schwannomas.

Strahlenther Onkol. 2020 Jan;196(1):40-47

Authors: Anselmo P, Casale M, Arcidiacono F, Trippa F, Rispoli R, Draghini L, Terenzi S, Di Marzo A, Maranzano E

Abstract
PURPOSE: To report long-term outcomes of 53 patients with vestibular schwannomas (VS) submitted to a single high-dose LINAC-based radiosurgery (SRS) in our institution.
METHODS: 48 (92%) patients were evaluable for clinical and MRI response as well as late toxicity. At a median follow-up of 12 years (range 2-16 years), local control (LC), hearing capacity, trigeminal and facial nerve function, and toxicity were assessed. Hearing capacity was classified according to the Gardner-Robertson scale, where class I-II patients had "serviceable hearing."
RESULTS: Median dose of SRS was 16.5 Gy (range 13-20 Gy) and median tumor volume 1.7 cm3 (range 0.09-7.4 cm3). 35 (73%) patients were treated with SRS alone, in the remaining 13 (27%) patients, SRS was performed as salvage therapy for recurrent or progressive tumors after previous microsurgery. Before SRS, 44 patients (92%) had hearing loss and 25 (52%) had "non-serviceable" hearing. Tumor extension, classified with Koos categories, was grade I-II in 27 (56%) and grade III-IV in 21 (44%) cases. LC was 100% and hearing preservation in "serviceable hearing" patients was 91%. 4 (11%) patients developed incomplete and intermittent ipsilateral facial nerve palsy which regressed in a median time of 6 months. Trigeminal toxicity was registered in 11 (23%) patients, reversible in 6 (13%) and permanent in 5 (10%). Only Koos tumor grade III-IV significantly influenced late toxicity (p = 0.01).
CONCLUSION: LC and hearing preservation after SRS were excellent. Toxicity proved acceptable. Although the median administered dose (16.5 Gy) was rather high, the only factor which significantly influenced late toxicity was Koos tumor grade III-IV.

PMID: 31384957 [PubMed - indexed for MEDLINE]

Permalink for 'Journey of the Patient With Melanoma: Understanding Resource Use and Bridging the Gap Between Dermatologist, Surgeon, and Oncologist in Different Health Care Systems.'

Journey of the Patient With Melanoma: Understanding Resource Use and Bridging the Gap Between Dermatologist, Surgeon, and Oncologist in Different Health Care Systems.

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

Journey of the Patient With Melanoma: Understanding Resource Use and Bridging the Gap Between Dermatologist, Surgeon, and Oncologist in Different Health Care Systems.

J Glob Oncol. 2019 07;5:1-8

Authors: Pereira da Veiga CR, Pereira da Veiga C, Drummond-Lage AP, Alves Wainstein AJ, Cristina de Melo A

Abstract
PURPOSE: New scientific evidence has led to modifications in the clinical practice of handling melanoma. In health care systems, there is currently a wide variety of clinical procedures to treat cancer, and the various routes have different effects on the survival of patients with cancer. Thus, this article aimed to evaluate the journey of patients with melanoma in the public and private health care systems in Brazil from the viewpoint of different medical professionals involved in the diagnosis and treatment of the disease. The study also considers the resources used for the complete delivery cycle of health care at different stages of the evolution of melanoma.
METHODS: We conducted a behavioral study by applying a questionnaire to a group of medical professionals. A nonprobabilistic sampling method for convenience was used, justified by the heterogeneous national incidence and the limited availability of medical professionals who diagnose and treat melanoma.
RESULTS: The questionnaire was answered by 138 doctors, including doctors from the Brazilian states with the highest concentration of medical specialists and regions with a higher melanoma incidence. The results of this study have the potential to enrich our understanding of the reality of Brazilian health care systems and, at the same time, allow us to discuss the multiple ways in which professionals from diverse specialist fields understand and explain decision making in health care.
CONCLUSION: Health care decision making is complex and, among other factors, depends on the diversity of available health resources and the knowledge of which treatments provide the greatest benefit to patients and greatest value to the system as a whole. This work can inform debates and reflection that are applicable not only in Brazil, but also in various other countries with similar realities.

PMID: 31283414 [PubMed - indexed for MEDLINE]

Characterization of Malignant Head and Neck Paragangliomas at a Single Institution Across Multiple Decades.

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

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Characterization of Malignant Head and Neck Paragangliomas at a Single Institution Across Multiple Decades.

JAMA Otolaryngol Head Neck Surg. 2019 07 01;145(7):641-646

Authors: McCrary HC, Babajanian E, Calquin M, Carpenter P, Casazza G, Naumer A, Greenberg S, Kohlmann W, Cannon R, Monroe MM, Hunt JP, Buchmann L

Abstract
Importance: Malignant head and neck paragangliomas (HNPGLs) are rare entities, and there are limited data regarding optimal treatment recommendations to improve clinical outcomes.
Objective: To classify succinate dehydrogenase (SDH) germline mutations associated with malignant HNPGLs, evaluate time from diagnosis to identification of malignant tumor, describe locations of metastases and the functional status of malignant HNPGLs, and determine the role of selective neck dissection at the time of initial surgical resection.
Design, Setting, and Participants: A retrospective cohort study was completed of patients diagnosed with paragangliomas on various sites on the body at an academic tertiary cancer hospital between the years 1963 and 2018. A subanalysis of HNPGLs was also completed. Data regarding diagnosis, gene and mutation, tumor characteristics and location, and treatments used were reviewed between February 2017 and March 2018.
Main Outcomes and Measures: Mutations of SDH genes associated with benign and malignant HNPGLs, treatments used, time to the discovery of malignancy, and location of metastasis.
Results: Of the 70 patients included in the study, 40 (57%) were male, and the mean (SD) age was 47 (21.1) years. Of patients with tumors isolated to the head and neck, 38 (54%) had benign HNPGLs, which were associated with mutations in the genes SDH subunit B (SDHB) (n = 18; 47%), SDH subunit C (n = 2; 5%), and SDH subunit D (n = 18; 47%). Among those with malignant HNPGLs, all but 1 patient had mutations in SDHB (n = 5; 83%); 1 patient had no mutation associated with their disease. The average age at diagnosis for malignant HNPGLs was 35 years, while benign tumors were diagnosed at an average age at 36 years. All patients with malignant disease underwent surgery. Four patients were found to have metastasis at the time of selective neck dissection. Among patients with malignant HNPGLs, 5 (83%) were treated with adjuvant radiation, and 1 (17%) was treated with adjuvant chemotherapy.
Conclusions and Relevance: Malignant HNPGLs are rare entities that are difficult to diagnose and are typically identified by the presence of regional or distant metastasis. The results of this study found the prevalence of malignant HNPGLs to be 9%. These data suggest that it is beneficial to perform a selective neck dissection at the time of tumor excision. All patients with malignant HNPGLs but 1 had SDHB mutations.

PMID: 31194233 [PubMed - indexed for MEDLINE]

Permalink for 'Propofol suppresses proliferation, invasion, and migration of human melanoma cells via regulating microRNA-137 and fibroblast growth factor 9.'

Propofol suppresses proliferation, invasion, and migration of human melanoma cells via regulating microRNA-137 and fibroblast growth factor 9.

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

Propofol suppresses proliferation, invasion, and migration of human melanoma cells via regulating microRNA-137 and fibroblast growth factor 9.

J Cell Physiol. 2019 12;234(12):23279-23288

Authors: Yu H, Ma M, Wang X, Zhou Z, Li R, Guo Q

Abstract
Propofol is an intravenous anesthetic widely used in clinical surgeries, such as tumor resection. Propofol affects the growth of many cancers, though its effect on melanoma is unknown. Our study aimed to explore how propofol affects melanoma cells. Melanoma cells A2058 and WM793B were cultured with propofol for 24 hr. Propofol significantly suppressed proliferation, migration, and invasion of A2058 and WM793B cells. Lower miR-137 level was observed in A2058 and WM793B cells, compared with normal human epidermal melanocyte HEMa-LP cells. Propofol-induced miR-137 upregulation and decreased proliferation, invasive ability, and migrated ability of A2058 and WM793B cells. Transfection with the miR-137 inhibitor reversed these effects. Additionally, miR-137 was verified to target and negatively regulate fibroblast growth factor 9 (FGF9) expression. Propofol efficiently downregulated FGF9 protein expression by upregulating miR-137. Furthermore, FGF9 overexpression abrogated propofol's repressive effects on the malignant potential of A2058 and WM793B cells. These findings indicate that propofol suppressed melanoma cell proliferation, invasion, and migration by regulating miR-137 and FGF9.

PMID: 31134615 [PubMed - indexed for MEDLINE]

Pre-operative ctDNA predicts survival in high-risk stage III cutaneous melanoma patients.

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

Pre-operative ctDNA predicts survival in high-risk stage III cutaneous melanoma patients.

Ann Oncol. 2019 05 01;30(5):815-822

Authors: Lee JH, Saw RP, Thompson JF, Lo S, Spillane AJ, Shannon KF, Stretch JR, Howle J, Menzies AM, Carlino MS, Kefford RF, Long GV, Scolyer RA, Rizos H

Abstract
BACKGROUND: The outcomes of patients with stage III cutaneous melanoma who undergo complete surgical resection can be highly variable, and estimation of individual risk of disease recurrence and mortality remains imprecise. With recent demonstrations of effective adjuvant targeted and immune checkpoint inhibitor therapy, more precise stratification of patients for costly and potentially toxic adjuvant therapy is needed. We report the utility of pre-operative circulating tumour DNA (ctDNA) in patients with high-risk stage III melanoma.
PATIENTS AND METHODS: ctDNA was analysed in blood specimens that were collected pre-operatively from 174 patients with stage III melanoma undergoing complete lymph node (LN) dissection. Cox regression analyses were used to evaluate the prognostic significance of ctDNA for distant metastasis recurrence-free survival and melanoma-specific survival (MSS).
RESULTS: The detection of ctDNA in the discovery and validation cohort was 34% and 33%, respectively, and was associated with larger nodal melanoma deposit, higher number of melanoma involved LNs, more advanced stage and high lactate dehydrogenase (LDH) levels. Detectable ctDNA was significantly associated with worse MSS in the discovery [hazard ratio (HR) 2.11 P < 0.01] and validation cohort (HR 2.29, P = 0.04) and remained significant in a multivariable analysis (HR 1.85, P = 0.04). ctDNA further sub-stratified patients with AJCC stage III substage, with increasing significance observed in more advanced stage melanoma.
CONCLUSION: Pre-operative ctDNA predicts MSS in high-risk stage III melanoma patients undergoing complete LN dissection, independent of stage III substage. This biomarker may have an important role in determining prognosis and stratifying patients for adjuvant treatment.

PMID: 30860590 [PubMed - indexed for MEDLINE]

Neuronal autoantibodies associated with cognitive impairment in melanoma patients.

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

Neuronal autoantibodies associated with cognitive impairment in melanoma patients.

Ann Oncol. 2019 05 01;30(5):823-829

Authors: Bartels F, Strönisch T, Farmer K, Rentzsch K, Kiecker F, Finke C

Abstract
BACKGROUND: Cancer-related cognitive impairment is an important complication in cancer patients, yet the underlying mechanisms remain unknown. Over the last decade, the field of paraneoplastic neurological syndromes has been dramatically changed by the discovery of new neuronal autoantibodies, some of them associated with cognitive impairment. We aimed to assess the prevalence of neuronal autoantibodies in melanoma patients and their association with neurological and cognitive dysfunction.
PATIENTS AND METHODS: A total of 157 consecutive melanoma patients with a median age of 63 years were recruited at the Department of Dermatology, Charité-Universitätsmedizin Berlin and tested for neuronal autoantibodies. A comprehensive neuropsychological assessment was carried out in a selected subgroup of 84 patients after exclusion of patients with confounding factors for a cognitive dysfunction, including brain metastases, relevant medication, and neurological disorders.
RESULTS: Neuronal autoantibodies were found in 22.3% of melanoma patients. The most frequent antibodies were IgA/IgM anti-NMDAR antibodies. Applying the International Cognition and Cancer Task Force criteria, 36.9% had cognitive impairment, however, with a threefold higher odds in antibody-positive compared with antibody-negative patients (57.1% versus 30.2%, OR = 3.1, 95% CI: 1.1 to 8.6; P = 0.037). In patients with anti-NMDAR antibodies, this impairment increased with higher antibody titers (P = 0.007). Antibody-positive patients had a significantly impaired overall cognitive performance (z-value: -0.38 ± 0.69 versus 0.00 ± 0.56; P = 0.014) as well as significant impairments in tests of memory, attention, and executive function. In a multiple linear regression analysis, autoantibodies were an independent risk factor for cognitive impairment (B = -0.282; 95% CI: -0.492 to -0.071; P = 0.009). Autoantibody seropositivity was associated with immune checkpoint inhibitor treatment and a history of autoimmune diseases.
CONCLUSIONS: A large number of melanoma patients harbor neuronal autoantibodies that are associated with significant cognitive impairment affecting memory, attention, and executive function. Neuronal autoantibodies might represent a pathophysiological factor and possible biomarker in the development of cancer-related cognitive impairment.

PMID: 30840061 [PubMed - indexed for MEDLINE]

Prediction and monitoring of relapse in stage III melanoma using circulating tumor DNA.

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

Prediction and monitoring of relapse in stage III melanoma using circulating tumor DNA.

Ann Oncol. 2019 05 01;30(5):804-814

Authors: Tan L, Sandhu S, Lee RJ, Li J, Callahan J, Ftouni S, Dhomen N, Middlehurst P, Wallace A, Raleigh J, Hatzimihalis A, Henderson MA, Shackleton M, Haydon A, Mar V, Gyorki DE, Oudit D, Dawson MA, Hicks RJ, Lorigan P, McArthur GA, Marais R, Wong SQ, Dawson SJ

Abstract
BACKGROUND: The advent of effective adjuvant therapies for patients with resected melanoma has highlighted the need to stratify patients based on risk of relapse given the cost and toxicities associated with treatment. Here we assessed circulating tumor DNA (ctDNA) to predict and monitor relapse in resected stage III melanoma.
PATIENTS AND METHODS: Somatic mutations were identified in 99/133 (74%) patients through tumor tissue sequencing. Personalized droplet digital PCR (ddPCR) assays were used to detect known mutations in 315 prospectively collected plasma samples from mutation-positive patients. External validation was performed in a prospective independent cohort (n = 29).
RESULTS: ctDNA was detected in 37 of 99 (37%) individuals. In 81 patients who did not receive adjuvant therapy, 90% of patients with ctDNA detected at baseline and 100% of patients with ctDNA detected at the postoperative timepoint relapsed at a median follow up of 20 months. ctDNA detection predicted patients at high risk of relapse at baseline [relapse-free survival (RFS) hazard ratio (HR) 2.9; 95% confidence interval (CI) 1.5-5.6; P = 0.002] and postoperatively (HR 10; 95% CI 4.3-24; P < 0.001). ctDNA detection at baseline [HR 2.9; 95% CI 1.3-5.7; P = 0.003 and postoperatively (HR 11; 95% CI 4.3-27; P < 0.001] was also associated with inferior distant metastasis-free survival (DMFS). These findings were validated in the independent cohort. ctDNA detection remained an independent predictor of RFS and DMFS in multivariate analyses after adjustment for disease stage and BRAF mutation status.
CONCLUSION: Baseline and postoperative ctDNA detection in two independent prospective cohorts identified stage III melanoma patients at highest risk of relapse and has potential to inform adjuvant therapy decisions.

PMID: 30838379 [PubMed - indexed for MEDLINE]

Ocular Tilt Reaction in Compensated Vestibular Schwannoma.

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

Ocular Tilt Reaction in Compensated Vestibular Schwannoma.

J Neuroophthalmol. 2019 06;39(2):244-246

Authors: Komiyama A, Kobayashi M, Nakamura H, Araki Y

PMID: 30640312 [PubMed - indexed for MEDLINE]

Permalink for 'High Expression of NEK2 and PIM1, but Not PIM3, Is Linked to an Aggressive Phenotype of Bronchopulmonary Neuroendocrine Neoplasms.'

High Expression of NEK2 and PIM1, but Not PIM3, Is Linked to an Aggressive Phenotype of Bronchopulmonary Neuroendocrine Neoplasms.

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

High Expression of NEK2 and PIM1, but Not PIM3, Is Linked to an Aggressive Phenotype of Bronchopulmonary Neuroendocrine Neoplasms.

Endocr Pathol. 2020 Jun 05;:

Authors: Motylewska E, Braun M, Stępień H

Abstract
Dysregulations of the NEK2 and PIM1-3 kinase signaling axes have been implicated in the pathogenesis of several cancers, including those with a neuroendocrine phenotype. However, their impact on bronchopulmonary neuroendocrine neoplasms (BP-NENs) has not been investigated. The aim of this pilot study was to determine mRNA and protein levels of NEK2, PIM1, and PIM3 in a group of 49 patients with BP-NENs: 11 typical carcinoids, 5 atypical carcinoids, 11 large cell neuroendocrine carcinomas, 22 small cell lung carcinomas (SCLC). The expression was measured using TaqMan-based RT-PCR and immunohistochemistry. NEK2 and PIM1 mRNA levels were higher in the SCLC patients than in the other BP-NEN groups (p < 0.001). There was an association between NEK2 mRNA and protein expression (p = 0.023) and elevated NEK2 mRNA levels were related to reduced survival in BP-NEN patients (p = 0.015). Patients with higher PIM1 protein expression had also diminished survival comparing with those with weak or no PIM1 expression (p = 0.037). Elevated NEK2 and PIM1 expression were related to aggressive tumor phenotype and indirectly affected the overall survival of BP-NEN patients. Our pilot study supports the need for future investigation of the biological function of NEK2 and PIM1 in BP-NEN transformation to verify the clinical value of our findings.

PMID: 32504181 [PubMed - as supplied by publisher]

Regulation of natural killer cell activity by glucocorticoids, serotonin, dopamine, and epinephrine.

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

Regulation of natural killer cell activity by glucocorticoids, serotonin, dopamine, and epinephrine.

Cell Mol Immunol. 2020 Jun 05;:

Authors: Capellino S, Claus M, Watzl C

Abstract
The immune system and the nervous system are highly complex organs composed of various different cells that must interact with each other for proper function of the system. This communication can be mediated by soluble factors. The factors released by the nervous system (neurotransmitters) differ from those released by the immune system (cytokines). Nevertheless, the nervous and immune systems can influence each other's activity because immune cells express neurotransmitter receptors, and neurons express cytokine receptors. Moreover, immune cells can synthesize and release neurotransmitters themselves, thus using neurotransmitter-mediated pathways via autocrine and paracrine mechanisms. Natural killer (NK) cells are innate lymphocytes that are important for early and effective immune reactions against infections and cancer. Many studies have shown the strong influence of stress and the nervous system on NK cell activity. This phenomenon may be one reason why chronic stress leads to a higher incidence of infections and cancer. Here, we review the effects of neuroendocrine factors on the different activities of NK cells. Understanding the effects of neuroendocrine factors on NK cell activities during physiological and pathophysiological conditions may result in novel therapeutic strategies to enhance NK cell functions against tumors.

PMID: 32503998 [PubMed - as supplied by publisher]

The patient-level effect of the cost of Cancer care - financial burden in German Cancer patients.

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

The patient-level effect of the cost of Cancer care - financial burden in German Cancer patients.

BMC Cancer. 2020 Jun 05;20(1):529

Authors: Mehlis K, Witte J, Surmann B, Kudlich M, Apostolidis L, Walther J, Jäger D, Greiner W, Winkler EC

Abstract
BACKGROUND: Financial toxicity of cancer has so far been discussed primarily in the US health care system and is associated with higher morbidity and mortality. In European health care systems, the socio-economic impact of cancer is poorly understood. This study investigates the financial burden and patient-reported outcomes of neuroendocrine (NET) or colorectal (CRC) cancer patients at a German Comprehensive Cancer Center.
METHODS: This prospective cross-sectional study surveyed 247 advanced stage patients (n = 122 NET/n = 125 CRC) at the National Center for Tumor Diseases, in Germany about cancer-related out-of-pocket costs, income loss, distress, and quality of life. Multiple linear regression analysis was performed to demonstrate the effects of economic deterioration on patients' quality of life and distress.
RESULTS: 81% (n = 199) of the patients reported out-of-pocket costs, and 37% (n = 92) income loss as a consequence of their disease. While monthly out-of-pocket costs did not exceed 200€ in 77% of affected patients, 24% of those with income losses reported losing more than 1.200€ per month. High financial loss relative to income was significantly associated with patients' reporting a worse quality of life (p < .05) and more distress (p < .05).
CONCLUSIONS: Financial toxicity in third-party payer health care systems like Germany is caused rather by income loss than by co-payments. Distress and reduced quality of life due to financial problems seem to amplify the burden that already results from a cancer diagnosis and treatment. If confirmed at a broader scale, there is a need for targeted support measures at the individual and system level.

PMID: 32503459 [PubMed - as supplied by publisher]

Permalink for 'Dose-Dependent Acute Effects of Everolimus Administration on Immunological, Neuroendocrine and Psychological Parameters in Healthy Men.'

Dose-Dependent Acute Effects of Everolimus Administration on Immunological, Neuroendocrine and Psychological Parameters in Healthy Men.

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

Dose-Dependent Acute Effects of Everolimus Administration on Immunological, Neuroendocrine and Psychological Parameters in Healthy Men.

Clin Transl Sci. 2020 May 31;:

Authors: Hörbelt T, Kahl AL, Kolbe F, Hetze S, Wilde B, Witzke O, Schedlowski M

Abstract
The rapamycin analogue everolimus (EVR) is a potent inhibitor of the mammalian target of rapamycin (mTOR) and clinically used to prevent allograft rejections as well as tumor growth. The pharmacokinetic and immunosuppressive efficacy of EVR have been extensively reported in patient populations and in vitro studies. However, dose-dependent ex vivo effects upon acute EVR administration in healthy volunteers are rare. Moreover, immunosuppressive drugs are associated with neuroendocrine changes and psychological disturbances. It is largely unknown so far whether and to what extend EVR affects neuroendocrine functions, mood, and anxiety in healthy individuals. Thus, in the present study, we analyzed the effects of three different clinically applied EVR doses (1.5, 2.25, and 3 mg) orally administered 4 times in a 12-hour cycle to healthy male volunteers on immunological, neuroendocrine, and psychological parameters. We observed that oral intake of medium (2.25 mg) and high doses (3 mg) of EVR efficiently suppressed T cell proliferation as well as IL-10 cytokine production in ex vivo mitogen-stimulated peripheral blood mononuclear cell. Further, acute low (1.5 mg) and medium (2.25 mg) EVR administration increased state anxiety levels accompanied by significantly elevated noradrenaline (NA) concentrations. In contrast, high-dose EVR significantly reduced plasma and saliva cortisol as well as NA levels and perceived state anxiety. Hence, these data confirm the acute immunosuppressive effects of the mTOR inhibitor EVR and provide evidence for EVR-induced alterations in neuroendocrine parameters and behavior under physiological conditions in healthy volunteers.

PMID: 32475067 [PubMed - as supplied by publisher]

Permalink for 'Outcomes of cytoreductive operations for peritoneal carcinomatosis with or without liver cytoreduction in patients with small bowel neuroendocrine tumors.'

Outcomes of cytoreductive operations for peritoneal carcinomatosis with or without liver cytoreduction in patients with small bowel neuroendocrine tumors.

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

Outcomes of cytoreductive operations for peritoneal carcinomatosis with or without liver cytoreduction in patients with small bowel neuroendocrine tumors.

Surgery. 2020 May 27;:

Authors: Wonn SM, Limbach KE, Pommier SJ, Ratzlaff AN, Leon EJ, McCully BH, Pommier RF

Abstract
BACKGROUND: This study determines how much cytoreduction for small bowel neuroendocrine tumors with peritoneal carcinomatosis and liver metastases can be achieved and the corresponding survival benefits of different levels of clearance.
METHODS: Records of patients with small bowel neuroendocrine tumors with peritoneal carcinomatosis were reviewed and scored using the Lyon Stage system. Kaplan-Meier survival was calculated and compared by log-rank analysis.
RESULTS: Among 323 patients with small bowel neuroendocrine tumors identified, 98 (30%) had peritoneal carcinomatosis. At laparotomy, 82% had Lyon Stage ≥3 compared with 78% who had Lyon Stage ≤2 after debulking (P < .00001). Median overall survival for Lyon Stage = 0 was 132 months and 51 months for Lyon Stage ≥1 (P = .026). For incomplete clearance, overall survival was 76 months for Lyon Stage ≤1 compared with 32 months for Lyon Stage ≥3 (P = .037). Seventy-nine (81%) patients had liver metastases, and 57 underwent >70% liver metastases cytoreduction. Overall survival was 76 months for Lyon Stage ≤1 and >70% liver metastases cytoreduction, 38.5 months for Lyon Stage ≥3 and >70% liver metastases cytoreduction, 22 months for Lyon Stage ≤1 and liver metastases not cytoreduced, and 20 months for Lyon Stage ≥3 and liver metastases not cytoreduced (P = .018).
CONCLUSION: A majority of patients with peritoneal carcinomatosis from small bowel neuroendocrine tumors can be cytoreduced. Best survival times are seen with complete clearance; however, there are improved survival times for Lyon Stage ≤1. In patients with liver metastases, best survival after cytoreduction is seen when both Lyon Stage ≤1 and liver metastases >70% are achieved.

PMID: 32473829 [PubMed - as supplied by publisher]

MYC Drives Temporal Evolution of Small Cell Lung Cancer Subtypes by Reprogramming Neuroendocrine Fate.

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

MYC Drives Temporal Evolution of Small Cell Lung Cancer Subtypes by Reprogramming Neuroendocrine Fate.

Cancer Cell. 2020 May 30;:

Authors: Ireland AS, Micinski AM, Kastner DW, Guo B, Wait SJ, Spainhower KB, Conley CC, Chen OS, Guthrie MR, Soltero D, Qiao Y, Huang X, Tarapcsák S, Devarakonda S, Chalishazar MD, Gertz J, Moser JC, Marth G, Puri S, Witt BL, Spike BT, Oliver TG

Abstract
Small cell lung cancer (SCLC) is a neuroendocrine tumor treated clinically as a single disease with poor outcomes. Distinct SCLC molecular subtypes have been defined based on expression of ASCL1, NEUROD1, POU2F3, or YAP1. Here, we use mouse and human models with a time-series single-cell transcriptome analysis to reveal that MYC drives dynamic evolution of SCLC subtypes. In neuroendocrine cells, MYC activates Notch to dedifferentiate tumor cells, promoting a temporal shift in SCLC from ASCL1+ to NEUROD1+ to YAP1+ states. MYC alternatively promotes POU2F3+ tumors from a distinct cell type. Human SCLC exhibits intratumoral subtype heterogeneity, suggesting that this dynamic evolution occurs in patient tumors. These findings suggest that genetics, cell of origin, and tumor cell plasticity determine SCLC subtype.

PMID: 32473656 [PubMed - as supplied by publisher]

Jumping the gun: traumatic splenosis mimicking 68-gallium-dotatate avid neuroendocrine tumour.

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

Jumping the gun: traumatic splenosis mimicking 68-gallium-dotatate avid neuroendocrine tumour.

ANZ J Surg. 2020 May 30;:

Authors: Sachawars E, Lin M, Sidhom GE

PMID: 32473071 [PubMed - as supplied by publisher]

The Clinical Significance of Neuroendocrine Features in Invasive Breast Carcinomas.

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

The Clinical Significance of Neuroendocrine Features in Invasive Breast Carcinomas.

Oncologist. 2020 May 30;:

Authors: Lai BW, Tsang JY, Poon IK, Shao Y, Chan SK, Tam FK, Cheung SY, Shea KH, Tse GM

Abstract
The latest World Health Organization (WHO) classification categorized invasive breast carcinomas (IBCs) with neuroendocrine (NE) differentiations into neuroendocrine neoplasms (including well-differentiated neuroendocrine tumor [NET] and poorly differentiated neuroendocrine carcinoma [NEC]) and IBC no special type with NE features (IBC-NST-NE). However, little is documented of the clinical significance of this classification; also the precise thresholds and choices of NE markers were variable. In the current study, a large cohort of patients with IBC with NE differentiation were morphologically classified based on the WHO criteria and the clinical relevance of expression of different NE markers (synaptophysin [SYN], chromogranin [CG], and CD56) was evaluated. Among 1,372 IBCs, 52 NET (3.8%) and 172 IBC-NST-NE (12.5%) were identified. Compared with the IBC-no NE cases, NET and IBC-NST-NE were similarly associated with positive estrogen receptor (ER) expression and lower grade (p < .001). For patient outcome, IBC-NST-NE, but not NET, demonstrated significantly worse survival than the IBC-no NE cases. Based on high (≥50%) and low (<50%) expression for each NE marker, independent poor disease-free survival for SYNlo CGlo and SYNhi CGlo cancers (IBC-no NE cases as references, hazard ratio [HR], ≤1.429; p ≤ .026) was found. Interestingly, SYN and CG expression correlated with each other and they shared similar clinicopathologic characteristics; but not with with CD56. In addition, CD56-only positive cases were associated with hormone receptors negativity and basal markers positivity (p ≤ .019), and patients' outcome was similar to IBC-no NE cancers. Our findings suggested that NE markers expression may provide information to fine tune treatment strategy. The relevance of CD56 as NE marker requires further studies. IMPLICATIONS FOR PRACTICE: Invasive breast carcinomas (IBCs) with neuroendocrine (NE) differentiation are heterogeneous in clinicopathologic parameters, biomarker expression, and prognosis. However, there are no specific therapies targeting NE differentiation, and all carcinomas with any NE differentiation are treated similarly as other IBCs. Our findings suggested stratification basing on NE marker expression levels may provide added prognostically pertinent information, aiding better treatment strategy. In addition, CD56-only positive carcinomas showed a different clinicopathologic and biomarker expression profile compared with those with chromogranin and synaptophysin expression. Relevance of CD56 as an NE marker requires further studies.

PMID: 32472950 [PubMed - as supplied by publisher]

177Lu-PRRT in advanced gastrointestinal neuroendocrine tumors: 10-year follow-up of the IRST phase II prospective study.

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

177Lu-PRRT in advanced gastrointestinal neuroendocrine tumors: 10-year follow-up of the IRST phase II prospective study.

Eur J Nucl Med Mol Imaging. 2020 May 29;:

Authors: Paganelli G, Sansovini M, Nicolini S, Grassi I, Ibrahim T, Amadori E, Di Iorio V, Monti M, Scarpi E, Bongiovanni A, Altini M, Urso L, Cittanti C, Matteucci F, Severi S

Abstract
PURPOSE: In March 2014, we reported the activity and safety of 177Lu-DOTA-octreotate peptide receptor radionuclide therapy (Lu-PRRT) at two different dosages (18.5 GBq and 27.5 GBq in 5 cycles) in patients with progressive metastatic gastrointestinal neuroendocrine tumors (GI-NETs). Disease control rate (DCR) and toxicity were addressed. Herein, we report the late toxicity, progression-free survival (PFS), and overall survival (OS) in the same cohort after a 10-year follow-up.
METHODS: We conducted an open-label, disease-oriented prospective phase II trial. From March 2008 to June 2011, 43 patients received 3.7 GBq or 5.5 GBq of Lu-PRRT every 6 to 8 weeks, each cycle repeated 5 times. All patients showed 68Gallium-DOTA-peptide PET/Octreoscan® positivity (score 3-4 Rotterdam scale) in known lesions. Tumor burden was estimated radiologically. Time-to-event data (PFS and OS) were described using Kaplan-Meier curves and compared with the log-rank test.
RESULTS: Forty-three patients (28 males and 15 females) were evaluable and were monitored for a median period of 118 months (range 12.6-139.6). Median PFS in patients receiving 18.5 GBq was 59.8 months (95% confidence interval [95% CI] 14.3-79.6), identical to that of patients treated with 27.5 GBq (59.8 months, 95% CI 23.4-82.0). Median OS was 71.0 months (95% CI 46.1-107.3) in the group who received 18.5 GBq and 97.6 months (95% CI 64.3-not reached) in the group treated with 27.5 GBq (P = 0.22). Patients with progression limited to lymph nodes showed significantly longer median PFS and OS than those with hepatic lesions (P = 0.02 for PFS and P = 0.04 for OS). Age over 65 years at the time of PRRT was also significant for OS. Of note, no late hematological or renal toxicity was observed in either group.
CONCLUSIONS: The long-term follow-up of the IRST phase II study shows that Lu-PRRT is a safe and effective therapy for patients with advanced GI-NET, the most important prognostic factor being tumor burden, hepatic lesions, and age. We believe that Lu-PRRT should be offered to patients with early-stage disease.

PMID: 32472437 [PubMed - as supplied by publisher]

Permalink for 'Metabolomics, machine learning and immunohistochemistry to predict succinate dehydrogenase mutational status in phaeochromocytomas and paragangliomas.'

Metabolomics, machine learning and immunohistochemistry to predict succinate dehydrogenase mutational status in phaeochromocytomas and paragangliomas.

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

Metabolomics, machine learning and immunohistochemistry to predict succinate dehydrogenase mutational status in phaeochromocytomas and paragangliomas.

J Pathol. 2020 May 27;:

Authors: Wallace PW, Conrad C, Brückmann S, Pang Y, Caleiras E, Murakami M, Korpershoek E, Zhuang Z, Rapizzi E, Kroiss M, Gudziol V, J L M Timmers H, Mannelli M, Pietzsch J, Beuschlein F, Pacak K, Robledo M, Klink B, Peitzsch M, Gill AJ, Tischler AS, de Krijger RR, Papathomas T, Aust D, Eisenhofer G, Richter S

Abstract
Phaeochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumours with a hereditary background in over one third of patients. Mutations in succinate dehydrogenase (SDH) genes increase the risk for PPGLs and several other tumours. Mutations in subunit B (SDHB) in particular are a risk factor for metastatic disease, further highlighting the importance of identifying SDH mutations for patient management. Genetic variants of unknown significance, where implications for the patient and family members are unclear, are a problem for interpretation. For such cases, reliable methods for evaluating protein functionality are required. Immunohistochemistry for SDHB (SDHB-IHC) is the method of choice but does not assess functionality at the enzymatic level. Liquid chromatography mass spectrometry-based measurements of metabolite precursors and products of enzymatic reactions provides an alternative method. Here, we compare SDHB-IHC with metabolite profiling in 189 tumours from 187 PPGL patients. Besides evaluating succinate:fumarate ratios (SFR), machine learning algorithms were developed to establish predictive models for interpreting metabolite data. Metabolite profiling showed higher diagnostic specificity compared to SDHB-IHC (99.2% versus 92.5%, p = 0.021), whereas sensitivity was comparable. Application of machine learning algorithms to metabolite profiles improved predictive ability over that of the SFR, in particular for hard-to-interpret cases of head and neck paragangliomas (AUC 0.9821 versus 0.9613, p = 0.044). Importantly, the combination of metabolite profiling with SDHB-IHC has complementary utility, as SDHB-IHC correctly classified all but one of the false-negatives from metabolite profiling strategies while metabolite profiling correctly classified all but one of the false-negatives/positives from SDHB-IHC. From 186 tumours with confirmed status of SDHx variant pathogenicity, the combination of the two methods resulted in 185 correct predictions, highlighting the benefits of both strategies for patient management. This article is protected by copyright. All rights reserved.

PMID: 32462735 [PubMed - as supplied by publisher]

EUS Ablation in a Patient with Multiple Metastatic Pancreatic Tumors from ACTH-producing Thymic Neuroendocrine Neoplasm.

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

EUS Ablation in a Patient with Multiple Metastatic Pancreatic Tumors from ACTH-producing Thymic Neuroendocrine Neoplasm.

Dig Endosc. 2020 May 27;:

Authors: Chang LK, Chen KC, Cheng MF, Lin CC, Wang HP, Sung CT, Chen JH, Yen RF, Hsu CL, Shih SR

Abstract
Adrenocorticotropic hormone (ACTH)-producing neuroendocrine neoplasm (NEN) of the thymus is rare. Lymph nodes and bones are the most common metastatic sites. Most cases present with florid Cushing's syndrome (CS). Here, we reported a 58-year-old woman, who presented with intermittent flush and weight loss. Imaging studies revealed tumors in the mediastinum, pancreas, and bones. Contrast-enhanced harmonic endoscopic ultrasound (EUS) of the pancreatic tumors showed heterogeneous and hyperenhancing characteristics. EUS elastography revealed a heterogeneous stiff pattern. EUS-fine needle biopsy to the pancreatic lesion confirmed the NEN nature. Serum ACTH and cortisol levels were abnormally high. Immunohistochemical staining of the thymic and pancreatic specimens was positive for ACTH. However, the patient did not have obvious CS appearance. The patient underwent surgery, radiation, EUS-guided ethanol injection, and anti-cancer medications, but the disease still progressed. The patient died from infection 16 months after NEN diagnosed. In conclusion, pancreas can be a metastatic site for ACTH-producing thymic NEN. EUS-associated procedures can help in the diagnosis and treatment of pancreatic metastatic NEN.

PMID: 32462727 [PubMed - as supplied by publisher]

$Permalink for 'A Rare Cause of Refractory Chronic Diarrhea and Cachexia: A Case Report.'$

A Rare Cause of Refractory Chronic Diarrhea and Cachexia: A Case Report.

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

A Rare Cause of Refractory Chronic Diarrhea and Cachexia: A Case Report.

Iran J Public Health. 2020 Feb;49(2):386-388

Authors: Hadj Kacem F, Chebbi D, Chakroun A, Charfi N, Ghorbel D, Mnif F, Mnif M, Rekik N, Abid M

Abstract
VIPoma is an unusual neuroendocrine neoplasm that autonomously secretes VIP. It is associated with secretory diarrhea and electrolyte disturbances. Herein we report a case of a male patient, who was hospitalized in the Department of Endocrinology in Hedi Chaker Hospital, Sfax, Tunisia. He presented VIPoma syndrome, with hepatic metastases at diagnosis. He had a history of chronic, watery diarrhea. He was dehydrated with many electrolytic disorders as hypokalemia, hyponatremia and metabolic acidosis. Abdominal CT scan showed a heterogeneous mass in the pancreatic head with multiple hepatic lesions. A high VIP hormone level was found. Histological study of a liver biopsy revealed hepatic metastases of neuroendocrine carcinoma. The patient received analogues of somatostatin and systemic chemotherapy, with a transient symptomatic relief. Sadly the patient was lost to follow-up.

PMID: 32461947 [PubMed]

Primary skull base neuroendocrine carcinoma-a case report and review of literature.

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

Primary skull base neuroendocrine carcinoma-a case report and review of literature.

Radiol Case Rep. 2020 Jul;15(7):1071-1077

Authors: Joshi VV, Thombare P, Verma M, Kamat N, Patkar D

Abstract
Skull-based neuroendocrine carcinomas are rare tumors with only a few case reports in literature. Here we present an unusual case of primary neuroendocrine carcinoma of the skull in 60-year-old male which was proven on surgical biopsy. The imaging features of this rare tumor along with differential diagnosis are discussed with brief review of the literature.

PMID: 32461779 [PubMed]

Permalink for 'Chromosomal and molecular pathway alterations in the neuroendocrine carcinoma and adenocarcinoma components of gastric mixed neuroendocrine-nonneuroendocrine neoplasm.'

Chromosomal and molecular pathway alterations in the neuroendocrine carcinoma and adenocarcinoma components of gastric mixed neuroendocrine-nonneuroendocrine neoplasm.

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

Chromosomal and molecular pathway alterations in the neuroendocrine carcinoma and adenocarcinoma components of gastric mixed neuroendocrine-nonneuroendocrine neoplasm.

Mod Pathol. 2020 May 27;:

Authors: Sun L, Zhang J, Wang C, Zhao S, Shao B, Guo Y, Liu Y, Sun Y

Abstract
Gastric mixed adenoneuroendocrine carcinoma (MANEC) is a clinically aggressive subtype of mixed neuroendocrine-nonneuroendocrine neoplasm (MiNEN) with unclear clonal origin. In this study, we analyzed high-resolution copy number (CN) profiling data using the OncoScan CNV Assay in the neuroendocrine carcinoma (NEC) and adenocarcinoma components of eight MANECs. Some common CNVs, including the gain of CCNE1 (19q12) and the loss of FAT1 (4q35.2), were frequently detected in both components; these CNVs were verified by FISH, qPCR and immunohistochemistry staining assays in samples with sufficient material. The identification of common CNVs in both components supports the likelihood of single clonal origin of morphologically heterogeneous tumor cells and suggests several novel genetic events potentially involved in the development of gastric MANEC. We also detected and validated some CNVs and alterations specific for the NEC component, such as MAPK1 loss and MAPK signaling pathway alterations, which could contribute to the neuroendocrine differentiation of gastric MANEC. In addition, we found that the NEC component presented more CNVs and greater CN loss than the adenocarcinoma component (P = 0.007 and P = 0.004, respectively); the NEC components from different cases were not clustered in the hierarchical clustering analysis, indicating the marked genetic heterogenicity of the NEC component in gastric MANEC. In summary, this study describes the cytogenetic characteristics of each component of gastric MANEC, providing some clues for further studies on the development and progression of gastric MANEC as well as providing some potential therapeutic targets.

PMID: 32461621 [PubMed - as supplied by publisher]

A case of MODY5-like manifestations without mutations or deletions in coding and minimal promoter regions of the HNF1B gene.

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

A case of MODY5-like manifestations without mutations or deletions in coding and minimal promoter regions of the HNF1B gene.

Endocr J. 2020 May 27;:

Authors: Kuwabara-Ohmura Y, Iizuka K, Liu Y, Takao K, Nonomura K, Kato T, Mizuno M, Hosomichi K, Tajima A, Miyazaki T, Horikawa Y, Yabe D

Abstract
Pancreatic tail hypoplasia is a common manifestation of maturity onset diabetes of the young (MODY) 5 that can cause reno-genito-urinary malformations such as renal cysts and bicornuate uterus. A 69-year-old female was admitted to our hospital for consultation on her relatively high HbA1c value. At age 20, she was diagnosed with uterus bicornis. At age 68, she was diagnosed with pancreas tail hypoplasia, renal cysts and non-functioning pancreatic neuroendocrine tumor (NET) in addition to right hydronephrosis due to multiple ureteral bladder carcinomas. She received total right nephrectomy, ureterectomy and partial cystectomy for multiple ureteral bladder carcinomas [non-invasive papillary urothelial carcinoma, low grade (G1), pTa, LV10, u-rtx, RM0, and pN0 (0/8)]. She also received distal pancreatomy for pancreatic NET [NET G1]. She then was referred to our department at age 69 due to increase in her HbA1c value from 6.2 to 7.2%; 75 g oral glucose tolerance test revealed impaired glucose tolerance. Her clinical characteristics (uterus bicornis, pancreas hypoplasia, and renal cysts) closely resembled the phenotype of MODY5, in which mutations in the HNF1B gene have been reported. Our genetic testing failed to detect any mutation or microdeletion in the coding or minimal promoter regions of the HNF1B gene. Although there remains a possibility that genetic mutations in introns and regulatory regions of the HNF1B gene might cause the MODY5-like manifestations in this patient, these results might suggest involvement of genes other than HNF1B in the pathogenesis of our patient's disease.

PMID: 32461507 [PubMed - as supplied by publisher]

Targeting RET Kinase in Neuroendocrine Prostate Cancer.

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

Targeting RET Kinase in Neuroendocrine Prostate Cancer.

Mol Cancer Res. 2020 May 27;:

Authors: VanDeusen HR, Ramroop JR, Morel KL, Bae S, Sheahan AV, Sychev Z, Lau NA, Cheng LC, Tan VM, Li Z, Petersen A, Lee JK, Park JW, Yang R, Hwang JH, Coleman I, Witte ON, Morrissey C, Corey E, Nelson PS, Ellis L, Drake JM

Abstract
The increased treatment of metastatic castration resistant prostate cancer (mCRPC) with second-generation anti-androgen therapies (ADT) has coincided with a greater incidence of lethal, aggressive variant prostate cancer (AVPC) tumors that have lost dependence on androgen receptor (AR) signaling. These AR independent tumors may also transdifferentiate to express neuroendocrine lineage markers and are termed neuroendocrine prostate cancer (NEPC). Recent evidence suggests kinase signaling may be an important driver of NEPC. To identify targetable kinases in NEPC, we performed global phosphoproteomics comparing several AR independent to AR dependent prostate cancer cell lines and identified multiple altered signaling pathways, including enrichment of RET kinase activity in the AR independent cell lines. Clinical NEPC patient samples and NEPC patient derived xenografts displayed upregulated RET transcript and RET pathway activity. Genetic knockdown or pharmacological inhibition of RET kinase in multiple mouse and human models of NEPC dramatically reduced tumor growth and decreased cell viability. Our results suggest that targeting RET in NEPC tumors with high RET expression could be an effective treatment option. Currently, there are limited treatment options for patients with aggressive neuroendocrine prostate cancer and none are curative. Implications: Identification of aberrantly expressed RET kinase as a driver of tumor growth in multiple models of NEPC provides a significant rationale for testing the clinical application of RET inhibitors in AVPC patients.

PMID: 32461304 [PubMed - as supplied by publisher]

A rare case report of pituicytoma with biphasic pattern and admixed with scattered Herring bodies.

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

A rare case report of pituicytoma with biphasic pattern and admixed with scattered Herring bodies.

World J Surg Oncol. 2020 May 27;18(1):108

Authors: Cao Y, Zeng Y, Qin X, Tan Y, Zeng M, Wang L, Cao X, Zou L, Wang C

Abstract
BACKGROUND: Pituicytoma is a rare pituitary non-neuroendocrine tumour. The awareness of pituitary non-neuroendocrine tumours has gradually increased over the past several decades, but the knowledge of some histological variants of the tumours is limited, particularly in clinicopathological significance. Here, we report a rare case of pituicytoma variant.
CASE PRESENTATION: A 71-year-old man presented with sudden symptoms of stroke including urinary incontinence, weakness in right lower limb, and trouble speaking. Physical examinations showed a right facial paralysis. The radiological examinations eventually found a 1.7 × 1.4 × 1.3 cm sellar occupied lesion. After symptomatic treatment improved the symptoms, the patient underwent transsphenoidal resection of the pituitary mass. Histologically, the tumour contained hypocellular area and hypercellular area. The hypocellular area showed elongated spindle cells arranged in a fascicular pattern around small vessels and scattered Herring bodies; the hypercellular area showed a large number of pseudorosettes. Immunohistochemistrically, the tumour cells were positive for thyroid transcription factor-1, S100, and neuron-specific enolase. Neurofilament only showed a little positive in the hypocellular area, and silver impregnation was only noted in a perivascular distribution. The patient had no recurrence 4 months after the surgery.
CONCLUSIONS: The rare variant of pituicytoma has a favourable prognosis. Moreover, it needs to be distinguished pituicytomas with pseudorosettes from ependymomas because of different prognosis. Lastly, Herring bodies may occasionally be seen in the pituicytoma, which could be a potential diagnostic pitfall.

PMID: 32460843 [PubMed - in process]

Permalink for 'Identification of a novel SDHB c.563 T > C mutation responsible for Paraganglioma syndrome and genetic analysis of the SDHB gene in China: a case report.'

Identification of a novel SDHB c.563 T > C mutation responsible for Paraganglioma syndrome and genetic analysis of the SDHB gene in China: a case report.

Rare Cancer News & Clinical Trials » Endocrine/Neuroendocrine

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Endocrine/Neuroendocrine (525 unread)

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