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Endocrine/Neuroendocrine (536 unread)

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Identification of Therapeutic Vulnerabilities in Small Cell Neuroendocrine Prostate Cancer.

Fetched: December 8th, 2019, 5:01am GMT

Identification of Therapeutic Vulnerabilities in Small Cell Neuroendocrine Prostate Cancer.

Clin Cancer Res. 2019 Dec 05;:

Authors: Corella AN, Cabiliza Ordonio MVA, Coleman I, Lucas JM, Kaipainen A, Nguyen HM, Sondheim D, Brown L, True LD, Lee JK, MacPherson D, Nghiem P, Gulati R, Morrissey C, Corey E, Nelson PS

Abstract
PURPOSE: Small-cell neuroendocrine prostate cancer (SCNPC) exhibits an aggressive clinical course and incidence rates appear to be increasing following resistance to potent androgen receptor (AR) antagonists. Currently, treatment options are limited and few model systems are available to identify new approaches for treatment. We sought to evaluate commonalities between SCNPC and other aggressive neuroendocrine carcinomas to identify therapeutic targets.
EXPERIMENTAL DESIGN: We generated whole transcriptome RNAseq data from AR-active prostate cancers (ARPC) and SCNPCs from tumors collected at rapid autopsy, and two other NE carcinomas, Merkel Cell Carcinoma (MCC) and small-cell lung cancer (SCLC). We performed cross-tumor comparisons to identify conserved patterns of expression of druggable targets. We tested inhibitors to highly upregulated drug targets in a panel of PC cell lines and in vivo patient-derived xenograft (PDX) models.
RESULTS: We identified BCL2 as highly upregulated in SCNPC compared to ARPC. Inhibitors targeting BCL2 induced apoptotic cell death in SCNPC cell lines at nanomolar concentrations while ARPC cell lines were resistant. Treatment with the BCL2 inhibitor Navitoclax lead to a reduction of growth of SCNPC PDX tumors in vivo, while ARPC PDX models were more resistant. We identified Wee1 as a second druggable target upregulated in SCNPC. Treatment with the combination of Navitoclax and the Wee1 inhibitor AZD-1775 repressed the growth of SCNPC PDX resistant to single agent BCL2 inhibitors.
CONCLUSIONS: The combination of BCL2 and Wee1 inhibition presents a novel therapeutic strategy for the treatment of SCNPC.

PMID: 31806643 [PubMed - as supplied by publisher]

Permalink for 'The Ubiquitin specific Protease Usp7, a novel Merkel cell polyomavirus Large T-Antigen interaction partner, modulates viral DNA replication.'

The Ubiquitin specific Protease Usp7, a novel Merkel cell polyomavirus Large T-Antigen interaction partner, modulates viral DNA replication.

Fetched: December 7th, 2019, 5:01am GMT

The Ubiquitin specific Protease Usp7, a novel Merkel cell polyomavirus Large T-Antigen interaction partner, modulates viral DNA replication.

J Virol. 2019 Dec 04;:

Authors: Czech-Sioli M, Siebels S, Radau S, Zahedi RP, Schmidt C, Dobner T, Grundhoff A, Fischer N

Abstract
Merkel Cell Polyomavirus (MCPyV) is the major cause for Merkel Cell Carcinoma (MCC), a rare but highly aggressive skin cancer predominantly found in elderly and immunosuppressed patients. The early viral gene products large T-Antigen (LT) and small T-Antigen (sT) are important for efficient viral DNA replication and both contribute to transformation processes. Mainly, these functions are executed through interactions with host factors. We here identify the cellular Ubiquitin-specific-processing protease 7 (Usp7) as a new interaction partner of the MCPyV LT.Using GST pulldown experiments, we show that MCPyV LT directly binds to Usp7, and that N- as well as the C-terminal regions of LT bind to the TRAF (tumor necrosis factor receptor-associated) domain of Usp7. We demonstrate that endogenous Usp7 co-precipitates with MCPyV T-antigens and re-localizes to viral DNA replication centers in cells actively replicating MCPyV genomes. We show that Usp7 does not alter ubiquitination levels of the T-antigens; however, Usp7 binding increases the binding affinity of LT to the origin of replication thereby negatively regulating viral DNA replication. Together, these data identify Usp7 as a restriction factor of MCPyV replication. In contrast to other DNA viruses, Usp7 does not affect MCPyV gene expression via its ubiquitination activity, but solely influences MCPyV DNA replication via novel mechanism that modulates binding of LT to viral DNA.Importance MCPyV is the only human polyomavirus that is associated with cancer; the majority of Merkel cell cancers have a viral etiology. While much emphasis was investigated to understand the transformation process by MCPyV oncoproteins and cellular factors, we have only limited knowledge on cellular factors participating in the MCPyV life cycle. We here describe Usp7, a cellular deubiquitination enzyme, as a new factor involved in MCPyV replication. Usp7 is known in the context of large DNA tumor viruses, EBV and KSHV, to restrict viral replication. Similar to EBV, where Usp7 binding to EBNA1 increases EBNA1 binding affinity to viral DNA, we find MCPyV LT binding to the origin of replication to be increased in the presence of Usp7 resulting in restriction of viral DNA replication. However, Usp7 induced restriction of MCPyV replication is independent of its enzymatic activity thereby constituting a novel mechanism of Usp7 induced restriction of viral replication.

PMID: 31801860 [PubMed - as supplied by publisher]

Merkel cell carcinoma mimicking transformed chronic lymphocytic leukemia/small lymphocytic lymphoma.

Fetched: December 5th, 2019, 5:01am GMT

Merkel cell carcinoma mimicking transformed chronic lymphocytic leukemia/small lymphocytic lymphoma.

Clin Case Rep. 2019 Nov;7(11):2256-2257

Authors: Bah I, Li S, Yin CC, Tang G, Xu J

Abstract
Although MCC has been reported in patients with CLL/SLL, it is extremely rare to observe these two within the same tumor. MCC's positivity for PAX5 and TdT may pose a diagnostic challenge by mimicking transformed CLL/SLL. A thorough workup is critical in reaching the correct diagnosis.

PMID: 31788294 [PubMed]

Concurrent Metastatic Merkel Cell Carcinoma and Cutaneous Squamous Cell Carcinoma in the Same Lymph Node.

Fetched: December 5th, 2019, 5:01am GMT

Concurrent Metastatic Merkel Cell Carcinoma and Cutaneous Squamous Cell Carcinoma in the Same Lymph Node.

Am J Dermatopathol. 2019 Jun;41(6):e61-e63

Authors: Suaiti L, Onajin O, Sangueza O

Abstract
The coexistence of Merkel cell carcinoma (MCC) and squamous cell carcinoma (SCC) in the same cutaneous lesion is well known. The pathogenesis is believed to be distinct from conventional polyomavirus-related MCC, and it has a more aggressive course. Metastasis of MCC and SCC to the same lymph node is exceedingly rare with only one previously reported case in the English literature. To the best of our knowledge, this is the second case of MCC and SCC with metastasis to the same lymph node. Our case demonstrates the aggressive nature of the combined MCC and SCC in the setting of immunosuppression.

PMID: 30461423 [PubMed - indexed for MEDLINE]

Male Sex is an Inherent Risk Factor for Basal Cell Carcinoma.

Fetched: November 29th, 2019, 5:01am GMT

Male Sex is an Inherent Risk Factor for Basal Cell Carcinoma.

J Skin Cancer. 2019;2019:8304271

Authors: Bassukas ID, Tatsioni A

Abstract
Basal cell carcinoma (BCC) is more frequent among females <40 years old; however, it affects preferentially older males (>60 years old). In order to contribute to the study of the still largely unknown mechanisms that underlie this peculiar sex-dependent shift, we compared the kinetics of the increase of the age-specific BCC incidence rates (R) as a function of age in males and females. Studies reporting sex-stratified R were found using a PubMed search and male to female age-specific incidence rate ratios (RR) were calculated for each age-class as reported in each study and assigned to the mean of the corresponding age periods. Trends in age were assessed with Kendall's τ test and relationships between two variables by inverse variance method-weighed Loess and linear regression analysis. Sixteen data sets were eligible and confirmed a significant shift in the male to female ratio (Kendall's τ = 0.530; P < 0.001). Moreover, the slope parameter b = 1.205 (SE = 0.014) of the best fit (r 2 = 0.980) regression line resulting by plotting male vs. female age-specific incidence rates predicts a statistically significant (P = 0.001), constant, about 20% faster increase of R in males of all ages. Similar relationship are also evident for cutaneous squamous cell and Merkel cell carcinoma and, even more intriguing, for sums of all cancers (excluding BCC and SCC) in many different registries. In conclusion, females are probably born with an inherently higher risk to develop BCC; however, also with a much slower increase rate of this risk as a function of age. Notably this observation seems to be not a BCC peculiarity. Because of its high incidence coupled with moderate morbidity and extremely low mortality rates, BCC may serve as a valuable, single-tumor paradigm to reproach the complex mechanisms that underline the interaction of age and sex in the pathogenesis of human malignancies.

PMID: 31772775 [PubMed]

Permalink for 'Anti-PD1 in Merkel cell carcinoma and cutaneous squamous cell carcinoma, description of five cases and recent data from the literature.'

Anti-PD1 in Merkel cell carcinoma and cutaneous squamous cell carcinoma, description of five cases and recent data from the literature.

Fetched: November 29th, 2019, 5:01am GMT

Anti-PD1 in Merkel cell carcinoma and cutaneous squamous cell carcinoma, description of five cases and recent data from the literature.

J Eur Acad Dermatol Venereol. 2019 Apr;33(4):e159-e161

Authors: Sellah D, Saint-Jean M, Peuvrel L, Khammari A, Quéreux G, Dréno B

PMID: 30451326 [PubMed - indexed for MEDLINE]

Permalink for 'Human oncoviruses: Mucocutaneous manifestations, pathogenesis, therapeutics, and prevention: Hepatitis viruses, human T-cell leukemia viruses, herpesviruses, and Epstein-Barr virus.'

Human oncoviruses: Mucocutaneous manifestations, pathogenesis, therapeutics, and prevention: Hepatitis viruses, human T-cell leukemia viruses, herpesviruses, and Epstein-Barr virus.

Fetched: November 27th, 2019, 5:01am GMT

Human oncoviruses: Mucocutaneous manifestations, pathogenesis, therapeutics, and prevention: Hepatitis viruses, human T-cell leukemia viruses, herpesviruses, and Epstein-Barr virus.

J Am Acad Dermatol. 2019 Jul;81(1):23-41

Authors: Mui UN, Haley CT, Vangipuram R, Tyring SK

Abstract
In 1964, the first human oncovirus, Epstein-Barr virus, was identified in Burkitt lymphoma cells. Since then, 6 other human oncoviruses have been identified: human papillomavirus, Merkel cell polyomavirus, hepatitis B and C viruses, human T-cell lymphotropic virus-1, and human herpesvirus-8. These viruses are causally linked to 12% of all cancers, many of which have mucocutaneous manifestations. In addition, oncoviruses are associated with multiple benign mucocutaneous diseases. Research regarding the pathogenic mechanisms of oncoviruses and virus-specific treatment and prevention is rapidly evolving. Preventative vaccines for human papillomavirus and hepatitis B virus are already available. This review discusses the mucocutaneous manifestations, pathogenesis, diagnosis, treatment, and prevention of oncovirus-related diseases. The first article in this continuing medical education series focuses on diseases associated with human papillomavirus and Merkel cell polyomavirus, while the second article in the series focuses on diseases associated with hepatitis B and C viruses, human T-cell lymphotropic virus-1, human herpesvirus-8, and Epstein-Barr virus.

PMID: 30502415 [PubMed - indexed for MEDLINE]

Permalink for 'Polyomavirus-positive Merkel cell carcinoma derived from a trichoblastoma suggests an epithelial origin of this Merkel cell carcinoma.'

Polyomavirus-positive Merkel cell carcinoma derived from a trichoblastoma suggests an epithelial origin of this Merkel cell carcinoma.

Fetched: November 26th, 2019, 5:01am GMT

Polyomavirus-positive Merkel cell carcinoma derived from a trichoblastoma suggests an epithelial origin of this Merkel cell carcinoma.

J Invest Dermatol. 2019 Nov 21;:

Authors: Kervarrec T, Aljundi M, Appenzeller S, Samimi M, Maubec E, Cribier B, Deschamps L, Sarma B, Sarosi EM, Berthon P, Levy A, Bousquet G, Tallet A, Touzé A, Guyétant S, Schrama D, Houben R

Abstract
Merkel cell carcinoma (MCC), an aggressive neuroendocrine carcinoma of the skin, is to date the only human cancer known to be frequently caused by a polyomavirus. However, it is a matter of debate which cells are targeted by the Merkel cell polyomavirus (MCPyV) to give rise to the phenotypically multifaceted MCC cells. To assess the lineage of origin of MCPyV-positive MCC, genetic analysis of a very rare tumor combining benign trichoblastoma and MCPyV-positive MCC was conducted by massive parallel sequencing. Although MCPyV was found to be integrated only in the MCC part, six somatic mutations were shared by both tumor components. The mutational overlap between trichoblastoma and MCPyV-positive MCC part of the combined tumor implies that MCPyV integration occurred in an epithelial tumor cell prior to MCC development. Therefore, our report demonstrates that MCPyV-positive MCC can derive from the epithelial lineage.

PMID: 31759946 [PubMed - as supplied by publisher]

p63 Is a Promising Marker in the Diagnosis of Unusual Skin Cancer.

Fetched: November 22nd, 2019, 5:01am GMT

p63 Is a Promising Marker in the Diagnosis of Unusual Skin Cancer.

Int J Mol Sci. 2019 Nov 17;20(22):

Authors: Smirnov A, Anemona L, Novelli F, Piro CM, Annicchiarico-Petruzzelli M, Melino G, Candi E

Abstract
Skin cancer is the most common type of cancer worldwide. Ozone depletion and climate changes might cause a further increase in the incidence rate in the future. Although the early detection of skin cancer enables it to be treated successfully, some tumours can evolve and become more aggressive, especially in the case of melanoma. Therefore, good diagnostic and prognostic markers are needed to ensure correct detection and treatment. Transcription factor p63, a member of the p53 family of proteins, plays an essential role in the development of stratified epithelia such as skin. In this paper, we conduct a comprehensive review of p63 expression in different types of skin cancer and discuss its possible use in the diagnosis and prognosis of cutaneous tumours.

PMID: 31744230 [PubMed - in process]

Recent updates in the management of Merkel Cell Carcinoma.

Fetched: November 21st, 2019, 5:01am GMT

Recent updates in the management of Merkel Cell Carcinoma.

J Pak Med Assoc. 2019 Nov;69(11):1693-1699

Authors: Abbasi AN, Ahmed SM, Qureshi BM

Abstract
Merkel cell carcinoma is an aggressive non-melanomatous cutaneous tumour of neuroendocrine origin with an increasing incidence in the recent years. It is a tumour of the elderly and immunosuppressed, which most often appears on sun-exposed areas of the body. The clinical features of the cutaneous or subcutaneous lesions hardly contribute to the diagnosis, and, hence, histopathology and immunohistochemistry play a vital role in diagnosis. The latest staging system by the American Joint Committee on Cancer includes non-nodal invasion to adjacent structures i.e. bone, muscle, fascia, or cartilage into the criteria, in additionto size and depth of invasion. The management reliesheavily on a multidisciplinary approach due to rarity of incidence of this disease. According to the international guidelines, surgical management is still the preferred choice. The beneficial role of adjuvant radiotherapy has now been more clearly documented. Data is insufficient to assess whether chemotherapy improves disease-free or overall survival.

PMID: 31740881 [PubMed - in process]

Contemporary Topics in Radiation Medicine: Skin Cancer.

Fetched: November 21st, 2019, 5:01am GMT

Contemporary Topics in Radiation Medicine: Skin Cancer.

Hematol Oncol Clin North Am. 2020 Feb;34(1):189-203

Authors: Gao SJ, Decker RH

Abstract
Radiation plays an important role in the management of a variety of skin cancers. This article discusses the role of radiation in the treatment of cutaneous squamous cell carcinoma, basal cell carcinoma, Merkel cell carcinoma, cutaneous T-cell lymphoma, and B-cell lymphomas.

PMID: 31739944 [PubMed - in process]

For Whom the Cell Tolls? Intratumoral Treatment Links Innate and Adaptive Immunity.

Fetched: November 21st, 2019, 5:01am GMT

For Whom the Cell Tolls? Intratumoral Treatment Links Innate and Adaptive Immunity.

Clin Cancer Res. 2019 02 15;25(4):1127-1129

Authors: Marquez-Rodas I, Aznar MA, Calles A, Melero I

Abstract
Intratumoral immunotherapy can potentially modulate the tumor microenvironment (TME) and potentiate the effects of concomitant or sequential systemic immunotherapies. Intratumoral administration of different Toll-like receptor agonists, including TLR4, can potentiate these effects through innate and adaptive immunity connection.See related article by Bhatia et al., p. 1185.

PMID: 30262506 [PubMed - indexed for MEDLINE]

Permalink for 'Concurrent Neuroendocrine Carcinoma of the Skin (Merkel Cell Carcinoma) and Squamous Cell Carcinoma of the Skin on the Right Ear Helix.'

Concurrent Neuroendocrine Carcinoma of the Skin (Merkel Cell Carcinoma) and Squamous Cell Carcinoma of the Skin on the Right Ear Helix.

Fetched: November 20th, 2019, 5:01am GMT

Concurrent Neuroendocrine Carcinoma of the Skin (Merkel Cell Carcinoma) and Squamous Cell Carcinoma of the Skin on the Right Ear Helix.

Int J Surg Pathol. 2019 Feb;27(1):64-66

Authors: Fischer S, Federspil PA, Kriegsmann K, Longerich T, Kriegsmann M

PMID: 29607680 [PubMed - indexed for MEDLINE]

Can dermoscopy open a new way to diagnosing Merkel cell carcinoma?

Fetched: November 17th, 2019, 5:01am GMT

Can dermoscopy open a new way to diagnosing Merkel cell carcinoma?

Int J Dermatol. 2019 Mar;58(3):e68-e71

Authors: Sadeghinia A, Ghanadan A, Ehsani A, Noormohammadpour P, Ansari MS

PMID: 30675720 [PubMed - indexed for MEDLINE]

Permalink for 'Non-specific labeling of macrophages with anti-cytokeratin 20 (SP33) in the evaluation of nodal micrometastasis from Merkel cell carcinoma: A pitfall for metastasis.'

Non-specific labeling of macrophages with anti-cytokeratin 20 (SP33) in the evaluation of nodal micrometastasis from Merkel cell carcinoma: A pitfall for metastasis.

Fetched: November 17th, 2019, 5:01am GMT

Non-specific labeling of macrophages with anti-cytokeratin 20 (SP33) in the evaluation of nodal micrometastasis from Merkel cell carcinoma: A pitfall for metastasis.

J Cutan Pathol. 2019 Jan;46(1):88-90

Authors: Venturi M, Pilloni L

PMID: 30288773 [PubMed - indexed for MEDLINE]

Incidental Finding of Benign Trichilemmal Cysts on 99mTc-Octreotide Scan.

Fetched: November 15th, 2019, 5:01am GMT

Incidental Finding of Benign Trichilemmal Cysts on 99mTc-Octreotide Scan.

Clin Nucl Med. 2019 Oct;44(10):834-835

Authors: Neshandar Asli I, Norouzi G

Abstract
A 63-year-old woman with neuroendocrine carcinoma of the colon was referred to our department for staging with Tc-octreotide scan. Two focal, highly intense, superficial lesions were detected in patient's scalp and paralumbar region, medial to the right kidney. Pathology correlation was recommended, revealing them both to be benign trichilemmal cysts. This unexpected finding strengthens the hypothesis of Merkel cell carcinoma and trichilemmal cysts originating from pluripotent stem cells of adnexal epithelium, making a neuroendocrine differentiation for the latter plausible.

PMID: 31306209 [PubMed - indexed for MEDLINE]

Merkel cell polyomavirus is uncommon in New Zealand Merkel cell carcinomas.

Fetched: November 15th, 2019, 5:01am GMT

Merkel cell polyomavirus is uncommon in New Zealand Merkel cell carcinomas.

Br J Dermatol. 2018 11;179(5):1197-1198

Authors: Woodhouse B, Robb TJ, Hearn JI, Houseman PS, Hayward G, Miller R, Restall AP, Findlay M, Lawrence B, Print CG, Parker K, Blenkiron C

PMID: 29928756 [PubMed - indexed for MEDLINE]

Merkel Cell Carcinoma of the Wrist: A Case Report.

Fetched: November 15th, 2019, 5:01am GMT

Merkel Cell Carcinoma of the Wrist: A Case Report.

Ann Plast Surg. 2018 08;81(2):244-247

Authors: Min HJ, Kim JH, Kim YW, Cheon YW

Abstract
PURPOSE: Merkel cell carcinomas are a rare type of neuroendocrine tumors of the head, neck, and extremities commonly found in older patients. Merkel cell carcinomas present as red-to-purple and nontender nodules with or without surface ulceration, usually measuring 2 cm in diameter.
CASE PRESENTATIONS: An 83-year-old woman with a skin-colored nodule on the dorsal aspect of her right wrist was referred to our department for treatment. The regional lymph nodes were not palpable, and the positron emission tomography/computed tomography scan did not reveal any distant metastases. We conducted wide excision of the lesion and sentinel lymph node biopsy. The defect caused by the excision and partial bone resection was reconstructed using a radical forearm rotational flap and a split-thickness skin graft. Postoperatively, the patient received adjuvant radiation therapy. We observed wound healing and an absence of complications such as recurrence at 1-year follow-up.
CONCLUSIONS: Merkel cell carcinomas are rare but aggressive neuroendocrine skin cancers, which rarely occur in the upper extremity. Our treatment of nonamputative wide excision and sentinel lymph node dissection, followed by postoperative radiation therapy, showed no local or distant recurrence. Here, we review the current literature on Merkel cell carcinomas and describe our approach of treatment.

PMID: 29794506 [PubMed - indexed for MEDLINE]

Permalink for 'Lymph node identification in skin malignancy using indocyanine green transcutaneously study: Study protocol for a diagnostic accuracy study.'

Lymph node identification in skin malignancy using indocyanine green transcutaneously study: Study protocol for a diagnostic accuracy study.

Fetched: November 15th, 2019, 5:01am GMT

Lymph node identification in skin malignancy using indocyanine green transcutaneously study: Study protocol for a diagnostic accuracy study.

Medicine (Baltimore). 2019 Nov;98(44):e17839

Authors: Lese I, Leckenby JI, Taddeo A, Constantinescu M, Olariu R

Abstract
INTRODUCTION: The incidence of malignant melanoma has been rising steadily over the past decades and Merkel cell carcinoma is a highly aggressive neuroendocrine skin tumor with a high mortality rate. Sentinel lymph node (SLN) biopsy is a recommended prognostic tool in primary cutaneous malignant melanomas of intermediate thickness and in all clinically node-negative Merkel cell carcinomas. The gold standard method for identification of SLNs is lymphoscintigraphy, which involves radioactive tracers. Indocyanine green-based near-infrared fluorescence imaging (NIRFI) has been also used for intraoperative SLN identification. We aim to evaluate the diagnostic sensitivity of the VisionSense VS3 NIRFI device for SNL identification. This device uses stereoscopic 3D high definition for both fluorescence and visible light imaging. Our hypothesis is that SLNs may be identified transcutaneously using fluorescent dye injections and NIRFI; therefore, obviating the need for lymphoscintigraphy in the future. METHODS AND ANALYSIS:: lymph node identification in skin malignancy using indocyanine green transcutaneously is a prospective diagnostic sensitivity study conducted at the Department of Plastic and Hand Surgery at the University Hospital Berne, Inselspital, Switzerland. The study aims at recruiting 93 patients (start date September 2017) to compare the accuracy of VisionSense VS3 camera at identifying SLNs transcutaneously with the current gold standard, lymphoscintigraphy. Moreover, a secondary objective is to determine if anatomical location of the SLN and patient factors (eg, body mass index, age) have an impact on the ability of VisionSense to detect SLNs when compared with the same gold standard.
TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT03545334.

PMID: 31689874 [PubMed - indexed for MEDLINE]

Permalink for 'Antibody response to polyomavirus primary infection: high seroprevalence of Merkel cell polyomavirus and lymphoid tissue involvement.'

Antibody response to polyomavirus primary infection: high seroprevalence of Merkel cell polyomavirus and lymphoid tissue involvement.

Fetched: November 10th, 2019, 5:01am GMT

Antibody response to polyomavirus primary infection: high seroprevalence of Merkel cell polyomavirus and lymphoid tissue involvement.

J Neurovirol. 2018 06;24(3):314-322

Authors: Cason C, Monasta L, Zanotta N, Campisciano G, Maestri I, Tommasino M, Pawlita M, Villani S, Comar M, Delbue S

Abstract
Human polyomaviruses (HPyVs) asymptomatically infect the human population establishing latency in the host, and their seroprevalence can reach 90% in healthy adults. Few studies have focused on the pediatric population, and there are no reports regarding the seroprevalence of all the newly isolated HPyVs among Italian children. Therefore, we investigated the frequency of serum antibodies against 12 PyVs in 182 immunocompetent children from Northeast Italy, by means of a multiplex antibody detection system. Additionally, secondary lymphoid tissues were collected to analyze the presence of HPyV DNA sequences using a specific real-time PCRs or PCRs. Almost 100% of subjects were seropositive for at least one PyV. Seropositivity ranged from 3% for antibodies against simian virus 40 (SV40) in children from 0 to 3 years, to 91% for antibodies against WU polyomavirus (WUPyV) and HPyV10 in children from 8 to 17 years. The mean number of PyV for which children were seropositive increased with the increasing of age: 4 standard deviations (SD) 1.8 in the 0-3-year group, 5 (SD 1.9) in the 4-7-year group, and 6 (SD 2.2) in the 8-17-year group. JC polyomavirus (JCPyV) DNA was detected in 1% of the adenoids, WUPyV in 12% of the tonsils, and 28% of the adenoids, and Merkel cell polyomavirus (MCPyV) was present in 6 and 2% of the tonsils and adenoids, respectively. Our study gives new insights on the serological evidence of exposure to PyVs during childhood, and on their possible respiratory route of transmission.

PMID: 29330826 [PubMed - indexed for MEDLINE]

Optimal adjuvant radiotherapy dose for stage I, II or III Merkel cell carcinoma: an analysis of the National Cancer Database.

Fetched: November 9th, 2019, 5:01am GMT

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Optimal adjuvant radiotherapy dose for stage I, II or III Merkel cell carcinoma: an analysis of the National Cancer Database.

Jpn J Clin Oncol. 2019 Nov 07;:

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

Abstract
BACKGROUND: We performed an analysis of the National Cancer Database to determine optimal doses of conventionally-fractionated adjuvant radiotherapy for patients with stage I/II or III Merkel cell carcinoma.
METHODS: The cohort included 2735 patients with resected Merkel cell carcinoma of the head and neck, trunk or extremities receiving radiotherapy. Exclusion criteria included doses of radiotherapy <30 or >80 Gy, or dose per fraction >200 or <180 cGy. Recursive partitioning analysis and spline models were used to select dose thresholds. Multivariable Cox regression was performed to validate thresholds with respect to overall survival.
RESULTS: Recursive partitioning analysis models defined a threshold of 57 Gy for stage I/II Merkel cell carcinoma, above which 3-year overall survival rate was decreased (P < 0.0001). The 3-year overall survival rate for patients receiving 50.0-57.0 Gy (81.2%) was greater compared to doses of 30.0-49.9 Gy (75.3%) or >57.0 Gy (70%, P < 0.0001). Doses > 57.0 Gy were associated with an increased hazard of death (1.31, confidence interval 1.07-1.60) with respect to doses of 50.0-57.0 Gy. Doses < 50.0 Gy for stage III Merkel cell carcinoma were associated with worsened 3-year overall survival (P < 0.0001) and increased hazard of death (2.01, confidence interval 1.43-2.82) with respect to doses between 50.0 and 57.0 Gy.
CONCLUSIONS: Our results support doses of 50-57 Gy for most patients with stage I/II Merkel cell carcinoma receiving conventionally-fractionated adjuvant radiotherapy. In contrast to a prior National Cancer Database analysis, our results suggest doses ≥ 50 Gy should be strongly considered for patients with stage III Merkel cell carcinoma regardless of anatomic subsite.

PMID: 31697368 [PubMed - as supplied by publisher]

Permalink for 'Merkel Cell Polyomavirus downregulates N-myc downstream regulated gene-1 (NDRG1) leading to cellular proliferation and migration.'

Merkel Cell Polyomavirus downregulates N-myc downstream regulated gene-1 (NDRG1) leading to cellular proliferation and migration.

Fetched: November 8th, 2019, 5:01am GMT

Merkel Cell Polyomavirus downregulates N-myc downstream regulated gene-1 (NDRG1) leading to cellular proliferation and migration.

J Virol. 2019 Nov 06;:

Authors: Gupta P, Shahzad N, Harold A, Shuda M, Venuti A, Romero-Medina MC, Pacini L, Brault L, Robitaille A, Taverniti V, Hernandez-Vargas H, Durand G, Le Calvez-Kelm F, Gheit T, Accardi R, Tommasino M

Abstract
Merkel cell polyomavirus (MCPyV) is the first human polyomavirus etiologically associated with Merkel cell carcinoma (MCC), a rare and aggressive form of skin cancer. Similar to other polyomaviruses, MCPyV encodes early T antigen genes, a viral oncogene required for MCC tumor growth. To identify the unique oncogenic properties of MCPyV, we analysed the gene expression profiles in human spontaneously immortalized keratinocytes (NIKs) expressing the early genes from six distinct human polyomaviruses (PyVs), including MCPyV. A comparison of the gene expression profiles revealed 28 genes specifically deregulated by MCPyV. In particular, the MCPyV early gene downregulated the expression of the tumor suppressor gene N-myc downstream regulated gene-1 (NDRG1) in NIKs-MCPyV and hTERT-MCPyV human keratinocytes (HK) as compared to their controls. In MCPyV-positive MCC cells, the expression of NDRG1 was downregulated by the MCPyV early gene, as T antigen knockdown rescued the level of NDRG1. In addition, NDRG1 overexpression in hTERT-MCPyV HK or MCC cells resulted in decrease of cells in S phase and cell proliferation inhibition. Moreover, a decrease in wound healing capacity in hTERT-MCPyV HK was observed. Further analysis revealed that NDRG1 exerts its biological effect in Merkel cell lines by regulating the expression of CDK2 and cyclinD1 proteins. Overall NDRG1 plays an important role in MCPyV induced cellular proliferation.Importance Merkel Cell Carcinoma was first described in 1972 as a neuroendocrine tumor of skin most of which in 2008, was reported to be caused by a PyV named Merkel Cell Polyomavirus (MCPyV), the first PyV linked to human cancer. Thereafter, numerous studies have been conducted to understand the etiology of this virus induced carcinogenesis. However, it is still a new field and much work is needed to understand the molecular pathogenesis of MCC. In the current work, we sought to identify the host genes specifically deregulated by MCPyV as opposed to other PyVs in order to better understand the relevance of the genes analyzed on the biological impact and progression of the disease. These findings open newer avenues for targeted drug therapies thereby providing hope for management of patients suffering from this highly aggressive cancer.

PMID: 31694959 [PubMed - as supplied by publisher]

Merkel cell carcinoma in Taiwan: A series of 24 cases and literature review.

Fetched: November 8th, 2019, 5:01am GMT

Merkel cell carcinoma in Taiwan: A series of 24 cases and literature review.

Medicine (Baltimore). 2019 Oct;98(42):e17538

Authors: Chang JW, Chang YY, Huang YL, Lo YF, Ho TY, Huang YT, Chen HW, Yeh CN, Wu CE

Abstract
Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine carcinoma of the skin. The available reports of MCC in Asia are limited; in this study, we report the largest series of MCC in Taiwan to date.The series is composed by 24 pathologically proven MCC cases, which were retrospectively reviewed in Chang Gung Memorial Hospital in Taiwan between 2000 and 2018.The tumor occurred predominantly in men (80%) and in the elderly (median 74.8 years). Twenty-one patients had locoregional MCC and 3 had metastatic MCC at the time of diagnosis. Patients with pathologically proven negative nodes by sentinel lymph node biopsy (SLNB) showed better survival time than those without SLNB in 16 clinically node-negative MCC cases undergoing primary surgery. Salvage surgery for loco-regional recurrence lengthened the survival time and possibly cured recurrent MCC. Palliative chemotherapy with cisplatin and etoposide showed a response rate of 25%, progression-free survival of 3.6 months, and overall survival of 14.8 months in 4 metastatic/recurrent MCC. Avelumab treatment was effective in 1 patient, who achieved a durable disease control.This observational cohort of MCC patients in Taiwan suggests aggressive surgical intervention including wide excision and lymph node management, salvage operation is critical for early MCC patients, and palliative chemotherapy and immunotherapy showed their efficacy for advanced MCC patients.

PMID: 31626116 [PubMed - indexed for MEDLINE]

Permalink for 'Danger is only skin deep: aggressive epidermal carcinomas. An overview of the diagnosis, demographics, molecular-genetics, staging, prognostic biomarkers, and therapeutic advances in Merkel cell carcinoma.'

Danger is only skin deep: aggressive epidermal carcinomas. An overview of the diagnosis, demographics, molecular-genetics, staging, prognostic biomarkers, and therapeutic advances in Merkel cell carcinoma.

Fetched: November 5th, 2019, 5:01am GMT

Danger is only skin deep: aggressive epidermal carcinomas. An overview of the diagnosis, demographics, molecular-genetics, staging, prognostic biomarkers, and therapeutic advances in Merkel cell carcinoma.

Mod Pathol. 2019 Nov 01;:

Authors: Tetzlaff MT, Harms PW

Abstract
Merkel cell carcinoma (MCC) is a high grade primary cutaneous neuroendocrine carcinoma and is among the most aggressive cutaneous malignancies. The rising incidence of MCC, together with its often rapidly aggressive course, underscore a critical need to recognize the histopathologic and the immunohistochemical features that inform its accurate diagnosis. In the current review, we summarize the current state of knowledge regarding the accurate diagnosis of MCC and the exclusion of other entities in the differential diagnosis. We provide a comprehensive review of genomic studies that identified the molecular-genetic drivers of MCC as well as a summary of studies identifying prognostic biomarkers that can facilitate risk stratification. Importantly, Merkel cell polyomavirus (MCPyV) appears to be causative in most cases of MCC and represents both a diagnostic and prognostic marker. Finally, as staging of MCC has undergone critical refinements with the introduction of the 8th Edition of the American Joint Committee on Cancer staging system, we provide an update on MCC staging. In particular, the prognostic significance of the sentinel lymph node (SLN) in MCC necessitates a systematic approach to its evaluation and diagnosis to ensure accurate and consistent risk stratification for patients, and we therefore provide a comprehensive overview of SLN evaluation in MCC. Finally, the intimate relationship between MCC and the integrity of the host immune system has led to paradigm-shifting therapeutic advances with the successful application of immune checkpoint blockade to treat patients with advanced disease, and we therefore summarize those studies and the correlative studies in which predictive biomarkers have been identified.

PMID: 31676786 [PubMed - as supplied by publisher]

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

Fetched: November 2nd, 2019, 5:01am GMT

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

Clin Cancer Res. 2019 Oct 31;:

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

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

PMID: 31672770 [PubMed - as supplied by publisher]

Effectiveness of Multi-Prognostic Index in older patients with advanced malignancies treated with immunotherapy.

Fetched: November 2nd, 2019, 5:01am GMT

Effectiveness of Multi-Prognostic Index in older patients with advanced malignancies treated with immunotherapy.

J Geriatr Oncol. 2019 Oct 28;:

Authors: Sbrana A, Antognoli R, Pasqualetti G, Linsalata G, Okoye C, Calsolaro V, Paolieri F, Bloise F, Ricci S, Antonuzzo A, Monzani F

Abstract
BACKGROUND: Older adults with cancer are less likely to be offered treatment for cost-benefit concern. The Multi-Prognostic Index (MPI) has been validated in various clinical settings for survival estimation. We aimed to evaluate MPI as a screening tool for older adults with cancer eligible to receive immunotherapy.
PATIENTS AND METHODS: Older adults with advanced or metastatic cancer, admitted to the Oncology Day Hospital of the University Hospital of Pisa from January 2017 to May 2018, eligible to receive immunotherapy were prospectively enrolled. In addition to routine oncological evaluation, each patient received a comprehensive geriatric assessment with MPI calculation. Overall survival (Cox-adjusted curve) was stratified by tertiles of MPI score. Drug toxicity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (Version 4.03: June 14, 2010).
RESULTS: Seventy-nine patients [26.6% women, mean age (±SD) 74.0 ± 6.1 years] were enrolled with the following diagnosis: melanoma (51.9%), non-small cell lung cancer (25.3%), renal cell cancer (12.7%), urothelial cancer (8.9%) and Merkel cell carcinoma (1.2%). Median follow-up was 7 months (range 1-35). The patients' survival rate resulted progressively longer proceeding from the first to the third MPI tertile [HR 1.76 (0.49-6.31) Vs 2nd tertile, p < 0.05; HR 5.33 (1.68-16.89) Vs 3rd tertile, p < 0.01].
CONCLUSIONS: MPI score is an effective tool for the stratification of older patients with cancer eligible for immunotherapy with checkpoint inhibitors. Further studies are required to achieve conclusive remarks on MPI usefulness in different underlying tumor types.

PMID: 31672558 [PubMed - as supplied by publisher]

Pembrolizumab-associated mucous membrane pemphigoid in a patient with Merkel cell carcinoma.

Fetched: November 1st, 2019, 5:01am GMT

Pembrolizumab-associated mucous membrane pemphigoid in a patient with Merkel cell carcinoma.

Br J Dermatol. 2018 10;179(4):993-994

Authors: Haug V, Behle V, Benoit S, Kneitz H, Schilling B, Goebeler M, Gesierich A

PMID: 29758087 [PubMed - indexed for MEDLINE]

[Human Oncogenic Viruses: Old Facts and New Hypotheses].

Fetched: October 31st, 2019, 5:01am GMT

[Human Oncogenic Viruses: Old Facts and New Hypotheses].

Mol Biol (Mosk). 2019 Sep-Oct;53(5):871-880

Authors: Bogolyubova AV

Abstract
Numerous studies on the nature of neoplastic growth have demonstrated that oncogenic viruses maybe one of the factors causing cancer. According to various estimates, 10-20% of all human cancers are caused by viruses. For example, the Epstein-Barr virus (EBV), hepatitis B and C viruses, human papillomavirus (HPV), human T-lymphotropic virus type 1 (HTLV-1), human herpesvirus type 8 (HHV-8), and Merkel cell polyomavirus were implicated in initiating tumors. At the same time, the long period between viral infection and the manifestation of cancer significantly complicates the search for a causal relationship between the presence of a virus in the human organism and the malignant transformation. For this reason, the role of certain viruses in the initiation of neoplastic processes in humans remains an unresolved issue.

PMID: 31661485 [PubMed - in process]

Letter to the Editor in reference to: Expression of 15-lipoxygenase-1 in Merkel cell carcinoma is linked to advanced disease.

Fetched: October 31st, 2019, 5:01am GMT

Letter to the Editor in reference to: Expression of 15-lipoxygenase-1 in Merkel cell carcinoma is linked to advanced disease.

Clin Otolaryngol. 2019 03;44(2):205-206

Authors: Narayanan D, Doan H, Simonette R, Rady PL, Tyring SK

PMID: 30367539 [PubMed - indexed for MEDLINE]

Permalink for 'One in a hundred million: Merkel cell carcinoma in pediatric and young adult patients is rare but more likely to present at advanced stages based on US registry data.'

One in a hundred million: Merkel cell carcinoma in pediatric and young adult patients is rare but more likely to present at advanced stages based on US registry data.

Fetched: October 30th, 2019, 5:01am GMT

One in a hundred million: Merkel cell carcinoma in pediatric and young adult patients is rare but more likely to present at advanced stages based on US registry data.

J Am Acad Dermatol. 2019 06;80(6):1758-1760

Authors: Paulson KG, Nghiem P

PMID: 30165170 [PubMed - indexed for MEDLINE]

Nivolumab combined with ruxolitinib: antagonism or synergy?

Fetched: October 30th, 2019, 5:01am GMT

Nivolumab combined with ruxolitinib: antagonism or synergy?

Ann Oncol. 2018 05 01;29(5):1334-1335

Authors: Debureaux PE, Arrondeau J, Bouscary D, Goldwasser F

PMID: 29788168 [PubMed - indexed for MEDLINE]

Permalink for 'Multidimensional, quantitative assessment of PD-1/PD-L1 expression in patients with Merkel cell carcinoma and association with response to pembrolizumab.'

Multidimensional, quantitative assessment of PD-1/PD-L1 expression in patients with Merkel cell carcinoma and association with response to pembrolizumab.

Fetched: October 29th, 2019, 5:01am GMT

Multidimensional, quantitative assessment of PD-1/PD-L1 expression in patients with Merkel cell carcinoma and association with response to pembrolizumab.

J Immunother Cancer. 2018 10 01;6(1):99

Authors: Giraldo NA, Nguyen P, Engle EL, Kaunitz GJ, Cottrell TR, Berry S, Green B, Soni A, Cuda JD, Stein JE, Sunshine JC, Succaria F, Xu H, Ogurtsova A, Danilova L, Church CD, Miller NJ, Fling S, Lundgren L, Ramchurren N, Yearley JH, Lipson EJ, Cheever M, Anders RA, Nghiem PT, Topalian SL, Taube JM

Abstract
BACKGROUND: We recently reported a 56% objective response rate in patients with advanced Merkel cell carcinoma (MCC) receiving pembrolizumab. However, a biomarker predicting clinical response was not identified.
METHODS: Pretreatment FFPE tumor specimens (n = 26) were stained for CD8, PD-L1, and PD-1 by immunohistochemistry/immunofluorescence (IHC/IF), and the density and distribution of positive cells was quantified to determine the associations with anti-PD-1 response. Multiplex IF was used to test a separate cohort of MCC archival specimens (n = 16), to identify cell types expressing PD-1.
RESULTS: Tumors from patients who responded to anti-PD-1 showed higher densities of PD-1+ and PD-L1+ cells when compared to non-responders (median cells/mm2, 70.7 vs. 6.7, p = 0.03; and 855.4 vs. 245.0, p = 0.02, respectively). There was no significant association of CD8+ cell density with clinical response. Quantification of PD-1+ cells located within 20 μm of a PD-L1+ cell showed that PD-1/PD-L1 proximity was associated with clinical response (p = 0.03), but CD8/PD-L1 proximity was not. CD4+ and CD8+ cells in the TME expressed similar amounts of PD-1.
CONCLUSIONS: While the binomial presence or absence of PD-L1 expression in the TME was not sufficient to predict response to anti-PD-1 in patients with MCC, we show that quantitative assessments of PD-1+ and PD-L1+ cell densities as well as the geographic interactions between these two cell populations correlate with clinical response. Cell types expressing PD-1 in the TME include CD8+ T-cells, CD4+ T-cells, Tregs, and CD20+ B-cells, supporting the notion that multiple cell types may potentiate tumor regression following PD-1 blockade.

PMID: 30285852 [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: October 25th, 2019, 5:01am 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 - in process]

Immunohistochemical profiles of different subsets of Merkel cell carcinoma.

Fetched: October 24th, 2019, 5:01am GMT

Immunohistochemical profiles of different subsets of Merkel cell carcinoma.

Hum Pathol. 2018 12;82:232-238

Authors: Pasternak S, Carter MD, Ly TY, Doucette S, Walsh NM

Abstract
The literature records many examples of Merkel cell carcinoma (MCC) exhibiting aberrant immunohistochemical profiles. These can lead to diagnostic difficulty. The objectives of the current study were (1) to examine the immunohistochemical profile of different subsets of MCC to determine whether predictable subset-specific patterns exist and (2) to establish whether shared immunophenotypic patterns might reveal links between individual subsets, as demonstrated previously at a genetic level. In 52 cases of MCC, stratified by viral status and morphology, we studied 5 markers commonly used in the diagnostic evaluation of these tumors (CK20, CK7, chromogranin, neurofilament and TTF-1). Expression of these proteins was recorded as quantitative (H-scores) and absolute (positive vs negative) variables. In general, our data indicate that the "classical" or expected panel (CK20+, NF+, Chromo+, TTF-1, CK7-) is observed significantly more often in pure Merkel cell polyomavirus (MCPyV)-positive than in MCPyV-negative cases (78% vs 25%; P = .002). Neurofilament was less frequently encountered in MCPyV-negative than in MCPyV-positive tumors (66.7% vs 100%; P = .001) and expression of TTF-1 (37.5% vs 3.6%; P = .003) and CK7 (45.8 vs 14.3; P = .02) was more frequent. No significant immonophenotypic differences were observed between pure and combined MCPyV-negative tumors. Recognition of the more aberrant immunohistochemical profile of MCPyV-negative MCC should inform the diagnostic approach to this tumor. Moreover, the shared aberrant immunophenotype in pure and combined MCPyV-negative tumors supports a link between these entities and serves to separate them from MCPyV-positive tumors.

PMID: 30067951 [PubMed - indexed for MEDLINE]

Radiotherapy in the Multidisciplinary Management of Merkel Cell Carcinoma.

Fetched: October 24th, 2019, 5:01am GMT

Radiotherapy in the Multidisciplinary Management of Merkel Cell Carcinoma.

J Natl Compr Canc Netw. 2018 06;16(6):776-781

Authors: Green MD, Hayman JA

Abstract
The management of Merkel cell carcinoma (MCC) requires multidisciplinary care for optimal patient outcomes. Radiotherapy (RT) is most commonly used as adjuvant therapy to improve locoregional control in patients with MCC who undergo surgery. Additionally, it can sometimes be used as definitive monotherapy for patients who decline or are not candidates for surgery and as palliative treatment in those with metastatic MCC. This article discusses the indications, treatment considerations, and recommended dose prescriptions for RT in the management of early- and advanced-stage disease. Considerable hope exists that immunotherapy advances will synergize with RT to further enhance clinical outcomes.

PMID: 29891527 [PubMed - indexed for MEDLINE]

Merkel Cell Carcinoma, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology.

Fetched: October 24th, 2019, 5:01am GMT

Merkel Cell Carcinoma, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology.

J Natl Compr Canc Netw. 2018 06;16(6):742-774

Authors: Bichakjian CK, Olencki T, Aasi SZ, Alam M, Andersen JS, Blitzblau R, Bowen GM, Contreras CM, Daniels GA, Decker R, Farma JM, Fisher K, Gastman B, Ghosh K, Grekin RC, Grossman K, Ho AL, Lewis KD, Loss M, Lydiatt DD, Messina J, Nehal KS, Nghiem P, Puzanov I, Schmults CD, Shaha AR, Thomas V, Xu YG, Zic JA, Hoffmann KG, Engh AM

Abstract
This selection from the NCCN Guidelines for Merkel Cell Carcinoma (MCC) focuses on areas impacted by recently emerging data, including sections describing MCC risk factors, diagnosis, workup, follow-up, and management of advanced disease with radiation and systemic therapy. Included in these sections are discussion of the new recommendations for use of Merkel cell polyomavirus as a biomarker and new recommendations for use of checkpoint immunotherapies to treat metastatic or unresectable disease. The next update of the complete version of the NCCN Guidelines for MCC will include more detailed information about elements of pathology and addresses additional aspects of management of MCC, including surgical management of the primary tumor and draining nodal basin, radiation therapy as primary treatment, and management of recurrence.

PMID: 29891526 [PubMed - indexed for MEDLINE]

Prevalence of DNA of fourteen human polyomaviruses determined in blood donors.

Fetched: October 23rd, 2019, 5:01am GMT

Prevalence of DNA of fourteen human polyomaviruses determined in blood donors.

Transfusion. 2019 Oct 21;:

Authors: Kamminga S, van der Meijden E, de Brouwer C, Feltkamp M, Zaaijer H

Abstract
BACKGROUND: Human polyomaviruses (HPyVs), like herpesviruses, cause persistent infection in a large part of the population. In immunocompromised and elderly patients, PyVs cause severe diseases such as nephropathy (BK polyomavirus [BKPyV]), progressive multifocal leukoencephalopathy (JC polyomavirus [JCPyV]), and skin cancer (Merkel cell polyomavirus [MCPyV]). Like cytomegalovirus, donor-derived PyV can cause disease in kidney transplant recipients. Possibly blood components transmit PyVs as well. To study this possibility, as a first step we determined the presence of PyV DNA in Dutch blood donations.
STUDY DESIGN AND METHODS: Blood donor serum samples (n = 1016) were analyzed for the presence of DNA of 14 HPyVs using HPyV species-specific quantitative polymerase chain reaction (PCR) procedures. PCR-positive samples were subjected to confirmation by sequencing. Individual PCR findings were compared with the previously reported PyV serostatus.
RESULTS: MC polyomavirus DNA was detected in 39 donors (3.8%), JCPyV and TS polyomavirus (TSPyV) DNA in five donors (both 0.5%), and HPyV9 DNA in four donors (0.4%). BKPyV, WU polyomavirus (WUPyV), HPyV6, MW polyomavirus (MWPyV), and LI polyomavirus (LIPyV) DNA was detected in one or two donors. Amplicon sequencing confirmed the expected product for BKPyV, JCPyV, WUPyV, MCPyV, HPyV6, TSPyV, MWPyV, HPyV9, and LIPyV. For JCPyV a significant association was observed between detection of viral DNA and the level of specific IgG antibodies.
CONCLUSION: In 5.4% of Dutch blood donors PyV DNA was detected, including DNA from pathogenic PyVs such as JCPyV. As a next step, the infectivity of PyV in donor blood and transmission via blood components to immunocompromised recipients should be investigated.

PMID: 31633816 [PubMed - as supplied by publisher]

Burden of Disease, Early Diagnosis, and Treatment of Merkel Cell Carcinoma in Latin America.

Fetched: October 19th, 2019, 5:01am GMT

Burden of Disease, Early Diagnosis, and Treatment of Merkel Cell Carcinoma in Latin America.

J Glob Oncol. 2018 07;4:1-11

Authors: Schmerling RA, Casas JG, Cinat G, Ospina FEG, Kassuga LEBP, Tlahuel JLM, Mazzuoccolo LD

PMID: 30085832 [PubMed - indexed for MEDLINE]

Mercurial Metastatic Merkel Cell Carcinoma: A Case of Colonic Involvement.

Fetched: October 18th, 2019, 5:01am GMT

Mercurial Metastatic Merkel Cell Carcinoma: A Case of Colonic Involvement.

ACG Case Rep J. 2019 Jun;6(6):e00102

Authors: Liu MC, Ahmed S, Mehta S

Abstract
Merkel cell carcinoma (MCC) is a neuroendocrine skin cancer that typically presents as a painless erythematous nodule on body surfaces visible to the sun. Metastatic disease is typical to the lymph nodes, liver, and lungs. There are previous case reports of patients with metastases to the gastrointestinal tract including the stomach, small intestine, and pancreas. To our knowledge, there are only rare occurrences of metastases to the colon. We report a patient with a history of MCC treated with chemotherapy who presented with hematochezia and underwent a colonoscopy that showed a partially obstructing, edematous, friable 7-cm circumferential mass in the transverse colon. Biopsy confirmed the diagnosis of MCC that metastasized to the transverse colon.

PMID: 31616771 [PubMed]

Principles of prophylactic and therapeutic management of skin toxicity during treatment with checkpoint inhibitors.

Fetched: October 18th, 2019, 5:01am GMT

Principles of prophylactic and therapeutic management of skin toxicity during treatment with checkpoint inhibitors.

Postepy Dermatol Alergol. 2019 Aug;36(4):382-391

Authors: Kamińska-Winciorek G, Cybulska-Stopa B, Lugowska I, Ziobro M, Rutkowski P

Abstract
The introduction of immunotherapy into the treatment of cancer patients has revolutionised the oncological approach and significantly improved patient survival. The key drugs are immune checkpoint inhibitors (CPIs), whose mechanism of action is to elicit immune response against cancer cell antigens. Three types of CPIs are currently used and approved: an anti-CTLA-4 antibody, ipilimumab; anti-PD-1 antibodies, nivolumab and pembrolizumab; and anti-PD-L1 antibodies: atezolizumab, avelumab and durvalumab. CPIs have been widely used in metastatic and adjuvant melanoma settings, metastatic lung cancer, Hodgkin's lymphoma, renal cancer, bladder cancer, head and neck tumours, and Merkel cell carcinoma. However, side effects of CPIs differ from toxicities of other oncological drugs. According to literature data, in 10-30% of patients CPIs are responsible for immune-related adverse events (irAE) associated with excessive activation of the immune system. Systemic irAEs include enterocolitis, pneumonitis, hepatitis, nephritis, hypophysitis, and autoimmune thyroid disease. However, the most common irAEs of checkpoint inhibitors are dermatologic toxicities ranging from pruritus and mild dermatoses to severe reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis. Each irAE can become serious if not early diagnosed and appropriately treated. In the article we present different types of skin irAEs related to CPIs together with the recommended therapies.

PMID: 31616210 [PubMed]

Fatal enteric plexus neuropathy after one dose of ipilimumab plus nivolumab: a case report.

Fetched: October 18th, 2019, 5:01am GMT

Fatal enteric plexus neuropathy after one dose of ipilimumab plus nivolumab: a case report.

J Immunother Cancer. 2018 08 31;6(1):82

Authors: Appelbaum J, Wells D, Hiatt JB, Steinbach G, Stewart FM, Thomas H, Nghiem P, Kapur RP, Thompson JA, Bhatia S

Abstract
BACKGROUND: Immune checkpoint inhibitors (ICIs) are the treatment of choice for several cancers and can be associated with remarkable clinical benefit, but can also cause serious immune-related adverse events (irAEs). Management of rare and severe irAEs is challenged by an incomplete knowledge of their natural history and pathogenetic mechanisms. We report a case of fatal acute-onset gastro-intestinal (GI) hypomotility from myenteric plexus neuropathy following a single dose of ipilimumab plus nivolumab given for treatment of Merkel cell carcinoma (MCC).
CASE PRESENTATION: A 66-year-old man with recurrent metastatic MCC involving several organs (liver, bones and disseminated retroperitoneal lymphadenopathy) developed profound pharyngeal dysphagia and ileus that started 7 days after receiving a single administration of combination immune checkpoint blockade consisting of nivolumab (3 mg/kg) and low-dose ipilimumab (1 mg/kg). A swallowing study showed oropharyngeal dysfunction and aspiration. Imaging studies were consistent with diffuse intestinal paresis. An extensive work-up did not reveal obvious causes of these symptoms, and enteric plexopathy was suspected. Empiric immune suppressive therapy was initiated urgently. Despite an escalating immunosuppressive regimen that included high dose steroids, tacrolimus and therapeutic plasma exchange, no improvement in GI motility was seen and the patient suffered repeated episodes of aspiration. Seven weeks after the onset of GI hypomotility, the patient succumbed to sepsis from intestinal perforations. At autopsy, histologic specimens obtained from the entire GI tract (pharynx to rectum) showed near complete loss of ganglion cells within the myenteric and submucosal plexuses. An associated inflammatory infiltrate was not seen, suggesting a 'burned out' phase of illness. C4d complement deposition was found at the ganglionic sites, suggesting antibody-mediated pathogenesis. Remarkably, at sites of previously suspected Merkel cell metastases, no residual viable Merkel cell carcinoma was identified.
CONCLUSIONS: GI-tract paresis due to myenteric neuritis is a rarely reported toxicity of ICIs. Because the window of reversibility is likely to be very brief, quick and decisive interventions are warranted. Subtle functional and anatomic perturbations of the myenteric nervous system from the use of ICIs may be more prevalent than realized and should be suspected and addressed in both clinical and investigational settings.

PMID: 30170630 [PubMed - indexed for MEDLINE]

Angiosarcoma in Collision With a Merkel Cell Carcinoma: Case Report and Literature Review.

Fetched: October 13th, 2019, 5:01am GMT

Angiosarcoma in Collision With a Merkel Cell Carcinoma: Case Report and Literature Review.

Int J Surg Pathol. 2019 Oct 10;:1066896919880260

Authors: Hacking S, Chavaria H, Khan L, Das K

Abstract
Merkel cell carcinoma (MCC) is a rare entity that most commonly arises from the skin. Angiosarcoma (AS) is a rare malignancy with a predilection for elderly males, has endothelial differentiation and a notoriously poor prognosis despite aggressive therapy. Herein, we report an angiosarcoma colliding with a MCC, in a patient with a past medical history of squamous cell carcinoma, status-post radiation therapy. More specifically, our case represents a collision tumor, a rare entity composed of two histologically distinct neoplasms which coincide together at the same location. This case represents the first documented report of such a presentation. With that being said, its clinical course, prognosis, pathogenesis, and molecular profile, currently remains unclear. Importantly, neoplasms are increasingly being found to be associated with radiation therapy, of which our patient had received. Ultimately, however, with the lack of c-MYC immunohistochemical staining, and a short duration between radiation exposure and presentation, the AS in our case was likely coincidental.

PMID: 31601140 [PubMed - as supplied by publisher]

Rapidly Growing Eyelid Mass in an Elderly Man.

Fetched: October 13th, 2019, 5:01am GMT

Rapidly Growing Eyelid Mass in an Elderly Man.

JAMA Ophthalmol. 2018 06 01;136(6):710-711

Authors: Messenger WB, Liu CY, Aakalu VK

PMID: 29543951 [PubMed - indexed for MEDLINE]

Merkel cell polyomavirus is implicated in a subset of Merkel cell carcinomas, in the Indian subcontinent.

Fetched: October 12th, 2019, 5:01am GMT

Merkel cell polyomavirus is implicated in a subset of Merkel cell carcinomas, in the Indian subcontinent.

Microb Pathog. 2019 Oct 07;:103778

Authors: Arora R, Rekhi B, Chandrani P, Krishna S, Dutt A

Abstract
Merkel cell carcinoma is a rare, lethal cancer histopathologically composed of cells showing similarity with mechanoreceptor Merkel cells. Merkel cell tumors manifest in two distinct forms. While a virus called Merkel cell polyomavirus is involved in the pathogenesis of one form of Merkel tumor, the other is driven by ultraviolet (UV)-linked mutations. In this study we investigated 18 cases, from the Indian population, of Merkel cell carcinoma for immunohistochemical (IHC) expression of Merkel cell polyomavirus (MCV) T antigen, including 12 cases tested by PCR, to identify viral etiopathology. We tested the tumors with two sensitive antibodies (CM2B4 and Ab3), targeting the viral large T antigen protein and with PCR primers targeting the N terminus of T antigen. Overall, we observed 38.8% (7/18) tumors displaying positive IHC expression of Merkel cell polyomavirus T antigen and 25% (3/12) tumors showing positive results, by both, immunohistochemistry and PCR. This constitutes the first report from India showing implication of MCV in Merkel cell carcinomas. Moreover, this is one of the larger series of Merkel cell carcinomas, tested for MCV, by both immunohistochemistry and PCR, in this part of the world. These results further indicate that a slightly more number of such cases in India are likely to be caused by UV-linked damage, as opposed to Merkel cell polyomavirus mediated tumorigenesis, which is definitely implicated in a subset of cases.

PMID: 31600537 [PubMed - as supplied by publisher]

[Head & Neck Merkel Cell Carcinoma].

Fetched: October 12th, 2019, 5:01am GMT

[Head & Neck Merkel Cell Carcinoma].

Laryngorhinootologie. 2019 Jan;98(1):48-59

Authors: Steinbichler TB, Hauser U, Schartinger VH, Dudás J, Riechelmann H

Abstract
Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine tumor of the skin. Even if it is quite rare, the incidence has increased about two fold during the last twenty years. Mortality is higher than in malignant melanoma. Risk factors are chronic UV exposition and immunosuppression. MCC are most common in patients over 70 years and half of them manifest in the head and neck region. They early metastasize to regional lymph nodes. Surgical therapy should include wide resection of the primary tumor and diagnostic lymph node excision. In the head and neck region this means usually ipsilateral selective neck dissection. Adjuvant radiotherapy of the primary tumor bed and associated lymph nodes of the head and neck region decreases recurrence and should be performed in every patient regardless of the T- and N-stage. In the head and neck region adjuvant radiotherapy can only be spared in selected patients with low-risk profile (wide excisional margins > 2 cm, primary tumor size > 1 cm, absent lymphovascular infiltration, no immunosuppression and pathologic negative cervical lymph nodes). Isolated radiotherapy or systemic therapies are usually applied in patients with metastasized MCC. Disease recurrence is most common in the first two years after initial diagnosis. Patients should be examined at short intervals during this time.

PMID: 30005427 [PubMed - indexed for MEDLINE]

[Tonsil metastatic Merkel cell carcinoma from skin: report of a case].

Fetched: October 9th, 2019, 5:01am GMT

[Tonsil metastatic Merkel cell carcinoma from skin: report of a case].

Zhonghua Bing Li Xue Za Zhi. 2019 09 08;48(9):728-729

Authors: Guo L, Zhou YH, Teng YL, Bi LR

PMID: 31495098 [PubMed - indexed for MEDLINE]

Primary Ovarian High-grade Neuroendocrine Carcinoma With Merkel Cell-like Immunophenotype Arising in a Teratoma.

Fetched: October 6th, 2019, 5:01am GMT

Primary Ovarian High-grade Neuroendocrine Carcinoma With Merkel Cell-like Immunophenotype Arising in a Teratoma.

Int J Gynecol Pathol. 2019 Oct 03;:

Authors: Harkness R, Kelly PJ, McCluggage WG

Abstract
Ovarian high-grade neuroendocrine carcinomas (NECs) (small cell and large cell NEC) are rare neoplasms. They may arise in association with other ovarian tumors, most commonly epithelial neoplasms and rarely teratomas. We report a case of an 19-yr-old female with bilateral ovarian teratomas with a high-grade NEC (immunohistochemically positive with chromogranin, synaptophysin, and CD56 and MIB1 proliferation index in excess of 90%) arising within one of these. Although CK20 was negative, the NEC exhibited an immunophenotype suggestive of a Merkel cell carcinoma with diffuse positive staining with FLI-1, SATB2 and neurofilament, markers which are preferentially expressed in Merkel cell carcinoma compared with other NECs. There was also diffuse staining for SALL4. Immunohistochemistry and molecular studies for Merkel cell polyomavirus were negative. Immunohistochemical staining for CK20, FLI-1, SATB2, neurofilament, and SALL4 was performed in 6 additional primary ovarian high-grade NECs; One, 5, 5, 1, and 0 cases were positive for CK20, FLI-1, SATB2, neurofilament, and SALL4, respectively, usually with very focal immunoreactivity. Pathologists should be aware of these potential unexpected staining patterns in ovarian NECs as positivity may result in consideration of other neoplasms.

PMID: 31584482 [PubMed - as supplied by publisher]

Nodal Merkel Cell Carcinoma in Head and Neck Lesions with an Unknown Primary: A Case Report in Light of the Literature.

Fetched: October 6th, 2019, 5:01am GMT

Nodal Merkel Cell Carcinoma in Head and Neck Lesions with an Unknown Primary: A Case Report in Light of the Literature.

Yonago Acta Med. 2019 Sep;62(3):258-262

Authors: Ikeda R, Ohta N, Fukaya S, Shoji F, Suzuki T, Noguchi N, Kakuta R, Hayashi K, Kiba T, Murakami K, Nakamura Y

Abstract
Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine skin cancer. To diagnose nodal MCC with an unknown primary disease is challenging, and it has to be separated from other nodal metastatic neoplasms. We report a unique case of nodal MCC in head and neck lesions with an unknown primary. A 70-year-old woman was admitted to our department with a right submandibular mass. Fine needle aspiration biopsy was performed and indicated malignancy. F-18-fluorodeoxyglucose positron emission tomography (PET) demonstrated abnormal accumulation in the right submandibular lymph node, right palatine tonsil, and right thyroid gland. For diagnostics and treatment, bilateral selective neck lymph node dissection, right tonsillectomy, and right thyroidectomy were performed. Histopathological examination revealed that most parts of the submandibular lymph node were occupied by diffuse sheets of tumor cells. Contrary to our expectation, malignant cells were not detected in the right palatine tonsil and right thyroid. Immunohistochemistry demonstrated a marked positive reaction for AE1/AE3, chromogranin A, synaptophysin, cytokeratin 20 (CK20) and CD56 and a negative reaction for vimentin, leucocyte common antigen (LCA), thyroid transcription factor-1 (TTF1) and cytokeratin 7 (CK7) in the tumor cells. Immunostaining of Merkel cell polyomavirus-large T antigen (MCPyV-LT) showed a positive reaction and MCPyV-positive MCCs were assessed by PCR analysis, demonstrating that viral copy number was 12.8 copies per cell. These histological findings confirmed the diagnosis of Merkel cell carcinoma of the lymph node. In cases of tumors in the lymph node with a neuroendocrine appearance in head and neck lesions, it is necessary to eliminate the possibility of metastasis from MCC.

PMID: 31582892 [PubMed]

Permalink for 'Intratumoral delivery of plasmid interleukin-12 via electroporation leads to regression of injected and non-injected tumors in Merkel cell carcinoma.'

Intratumoral delivery of plasmid interleukin-12 via electroporation leads to regression of injected and non-injected tumors in Merkel cell carcinoma.

Fetched: October 6th, 2019, 5:01am GMT

Intratumoral delivery of plasmid interleukin-12 via electroporation leads to regression of injected and non-injected tumors in Merkel cell carcinoma.

Clin Cancer Res. 2019 Oct 03;:

Authors: Bhatia S, Longino NV, Miller NJ, Kulikauskas RM, Iyer JG, Ibrani D, Blom A, Byrd DR, Parvathaneni U, Twitty CG, Campbell JS, Le MH, Gargosky S, Pierce RH, Heller R, Daud AI, Nghiem P

Abstract
PURPOSE: Interleukin-12 (IL-12) promotes adaptive type-1 immunity and has demonstrated anti-tumor efficacy, but systemic administration leads to severe adverse events (AEs), including death. This pilot trial investigated safety, efficacy, and immunologic activity of intratumoral delivery of IL-12 plasmid DNA (tavo) via in vivo electroporation (i.t.-tavo-EP) in patients with Merkel cell carcinoma (MCC), an aggressive virus-associated skin cancer.
EXPERIMENTAL DESIGN: Fifteen MCC patients with superficial injectable tumor(s) received i.t.-tavo-EP on days 1, 5, and 8 of each cycle. Patients with locoregional MCC (Cohort A, N=3) received one cycle before definitive surgery in week 4. Patients with metastatic MCC (Cohort B, N=12) received up to 4 cycles total, administered at least six weeks apart. Serial tumor and blood samples were collected.
RESULTS: All patients successfully completed at least one cycle with transient, mild (Grade 1, 2) AEs and without significant systemic toxicity. Sustained (day 22) intratumoral expression of IL-12 protein was observed along with local inflammation and increased tumor-specific CD8+ T cell infiltration, which led to systemic immunologic and clinical responses. The overall response rate was 25% (3/12) in Cohort B, with two patients experiencing durable clinical benefit (16 and 55+ months respectively). Two Cohort A patients (one with pathologic complete remission) were recurrence-free at 44+ and 75+ months.
CONCLUSIONS: I.t.-tavo-EP was safe and feasible without systemic toxicity. Sustained local expression of IL-12 protein and local inflammation led to systemic immune responses and clinically meaningful benefit in some patients. Gene electrotransfer, specifically i.t.-tavo-EP, warrants further investigation for immunotherapy of cancer.

PMID: 31582519 [PubMed - as supplied by publisher]

Permalink for 'Decreased H3K27me3 Expression Is Associated With Merkel Cell Polyomavirus-negative Merkel Cell Carcinoma, Especially Combined With Cutaneous Squamous Cell Carcinoma.'

Decreased H3K27me3 Expression Is Associated With Merkel Cell Polyomavirus-negative Merkel Cell Carcinoma, Especially Combined With Cutaneous Squamous Cell Carcinoma.

Fetched: October 3rd, 2019, 5:01am GMT

Decreased H3K27me3 Expression Is Associated With Merkel Cell Polyomavirus-negative Merkel Cell Carcinoma, Especially Combined With Cutaneous Squamous Cell Carcinoma.

Anticancer Res. 2019 Oct;39(10):5573-5579

Authors: Matsushita M, Iwasaki T, Wardhani LO, Kuwamoto S, Nonaka D, Nagata K, Kato M, Kitamura Y, Hayashi K

Abstract
BACKGROUND/AIM: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer, frequently infected with Merkel cell polyomavirus (MCPyV). H3K27me3 acts as a repressive histone modification that epigenetically controls gene transcription. The aim of this study was to examine H3K27me3 expression in MCC.
MATERIALS AND METHODS: H3K27me3 expression levels were immunohistochemically analyzed in 20 MCPyV-positive MCCs, 15 MCPyV-negative MCCs with squamous cell carcinoma (SCC) (combined MCCs), and six MCPyV-negative pure MCCs.
RESULTS: Reduced H3K27me3 expression was variously observed in MCCs. H3K27me3 H-score was significantly lower in MCPyV-negative MCCs than in MCPyV-positive MCCs (p=0.002). H3K27me3 expression was significantly lower in MCPyV-negative combined MCC component than in MCPyV-positive MCCs (p<0.001), MCPyV-negative pure MCCs (p=0.036), or pure MCC histology (p<0.001). Kaplan-Meier analysis showed no association of H3K27me3 with outcome.
CONCLUSION: Differential reduction in H3K27me3 expression was observed based on MCPyV status and morphological type. These results implicate H3K27me3-mediated epigenetic changes in tumorigenesis of MCC, especially in MCPyV-negative MCC combined with SCC.

PMID: 31570452 [PubMed - in process]

Merkel Cell Carcinoma: A Case Series

Fetched: September 27th, 2019, 5:01am GMT

Merkel Cell Carcinoma: A Case Series

Ir Med J. 2018 10 11;111(9):826

Authors: Zafar SA, Ahmed OM, Boland MR, Aucharaz N, Lal A

Abstract
Introduction Merkel cell carcinoma (MCC) is a rare cutaneous tumour that is clinically aggressive with a high local, regional, and distant metastatic potential. Cases Three male patients presented to University Hospital Limerick (UHL) in 2015 with cutaneous lesions of the thorax, buttock and forearm. Once MCC was confirmed, management included surgical wide local excision (WLE) with regional lymph node dissection followed by adjuvant radiotherapy. One patient is in remission. The second has residual locoregional lymph node disease and is undergoing annual CT surveillance. The third had distant metastatic disease and is deceased from an unrelated condition. Discussion This case series highlights the presentation and management of MCC. We also discus relevant guidelines. The management of MCC is complex and there is a need to establish local or national databases to identify and monitor patients with MCC.

PMID: 30556674 [PubMed - indexed for MEDLINE]

Avelumab: A Review of Its Application in Metastatic Merkel Cell Carcinoma.

Fetched: September 27th, 2019, 5:01am GMT

Avelumab: A Review of Its Application in Metastatic Merkel Cell Carcinoma.

Ann Pharmacother. 2018 09;52(9):928-935

Authors: Joseph J, Zobniw C, Davis J, Anderson J, Trinh VA

Abstract
OBJECTIVE: To summarize the clinical development of avelumab and its clinical relevance in metastatic Merkel cell carcinoma (MCC).
DATA SOURCES: An English-language literature search using PubMed was performed using the terms avelumab, anti-PD-1, anti-PD-L1, and MCC from January of 1950 to March 2018. Data were also obtained from package inserts, meeting abstracts, and clinical registries.
STUDY SELECTION/DATA EXTRACTION: All relevant published articles of avelumab were reviewed. Clinical trial registries and meeting abstracts were used for information about ongoing trials.
DATA SYNTHESIS: Avelumab is a fully human monoclonal antibody that inhibits programmed death ligand-1, which reverses T-cell exhaustion and induces antitumor responses. Avelumab is safe and effective in previously treated metastatic MCC based on a phase II trial of previously treated patients with objective response rates in 28 of 88 patients, including 10 complete responses and 19 partial responses. Median overall survival (OS) was 12.9 months, and 1-year progression-free survival and OS were 30% and 52%, respectively. Grade 3 treatment-related side effects included lymphopenia (2 patients), serum creatine phosphokinase increase (1 patient), aminotransferase elevation (1 patient), and serum cholesterol increase (1 patient). Relevance to Patient Care and Clinical Practice: This review outlines the pharmacology and clinical trial data for avelumab in metastatic MCC and guides clinicians on avelumab's place in therapy.
CONCLUSIONS: Avelumab is the first Food and Drug Administration-approved medication for metastatic MCC and provides an advantage of durable responses and possibly improved tolerability compared with traditional platinum-based chemotherapy. Clinical trials are under way to expand its utility into the adjuvant and frontline settings.

PMID: 29616562 [PubMed - indexed for MEDLINE]

Mohs Surgery for the Treatment of Skin Cancer: A Review of Guidelines

Fetched: September 27th, 2019, 5:01am GMT

Mohs Surgery for the Treatment of Skin Cancer: A Review of Guidelines

Book. 2019 03 20

Authors: Ho C, Argáez C

Abstract
Skin cancer is an abnormal growth of skin cells – usually caused by exposure to ultraviolet radiation. The two most common types of skin cancers basal cell carcinoma and squamous cell carcinoma (usually grouped under non-melanoma skin cancers - NMSC).1,2 Melanoma, a less common but the most deadly form of skin cancer lead to 1,250 Canadian deaths in 2017.1,2 Other less common types of skin cancer include Merkel cell carcinoma, dermatofibrosarcoma protuberans, atypical fibroxanthoma and sebaceous carcinoma.3 Skin cancers can be invasive (invading through the basement membrane) or in situ (confined to the epidermis), and tumour characteristics such as size, location, and pathology influence the risk for deep tumour invasion and recurrence after treatment. Treatment for non-melanoma skin cancer usually includes surgical removal of the tumour, while treatment for melanoma may include surgery, radiation therapy, chemotherapy, and immunotherapy.4 Surgery for small skin cancer lesions can include simple excision, electrodesiccation and curettage, or cryosurgery; surgery for larger or recurrent lesions may include conventional wide excision of the tumour, or Mohs surgery.4 Mohs surgery, also known as Mohs micrographic surgery (MMS) is a surgical procedure in which thin layers of the tumour are progressively removed and examined until only cancer-free tissue remains, and can be done in a single visit at an outpatient clinic.5,6 The increased precision of MMS can also decrease scarring and reduces the likelihood for needing additional treatment or surgeries.7 Clinical evidence up to date showed that, compared with conventional surgical excision, MMS led to a significant higher cure rate for treatment of recurrent NMSC, and may have a role in the treatment of melanoma in situ and some other unusual skin cancers such as Merkel cell carcinoma and dermatofibrosarcoma protuberans.8,9 With a noticeable increase in use of MMS and associated expenditures in Canada, this Rapid Response report aims to review the evidence-based guidelines associated with the use of Mohs surgery for the treatment of skin cancer.

PMID: 31553552

Merkel cell carcinoma: A series of seven cases.

Fetched: September 26th, 2019, 5:01am GMT

Merkel cell carcinoma: A series of seven cases.

Arch Plast Surg. 2019 Sep;46(5):441-448

Authors: Lee YW, Bae YC, Nam SB, Bae SH, Kim HS

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) is a rare neuroendocrine malignancy affecting the skin, for which timely diagnosis and aggressive treatment are essential. MCC has most often been reported in Caucasians, and case reports in Asians are rare. This study presents our experiences with the surgical treatment and radiotherapy of MCC in Asian patients.
METHODS: We retrospectively reviewed the records of seven MCC patients between 2000 and 2018 from a single institution, and analyzed patient characteristics, tumor characteristics, surgical treatment, sentinel lymph node evaluation, reconstruction, adjuvant radiation therapy, and prognosis.
RESULTS: Eight MCC lesions occurred in seven patients, most commonly in the head and neck region. All patients underwent surgical excision with reconstruction. The final surgical margin was 1.0 cm in most cases, and reconstruction was most commonly performed with a splitthickness skin graft. Five patients received adjuvant radiotherapy, and two patients received sentinel lymph node biopsy. During the follow-up period, three patients remained well, two died from other causes, one experienced recurrence, and one was lost to follow-up.
CONCLUSIONS: We treated seven Asian MCC patients and our series confirmed that MCC is a very dangerous cancer in Asians as well. Based on our experiences, thorough surgical excision of MCC with histopathological clearance should be considered, with sentinel lymph node evaluation if necessary, followed by appropriate reconstruction and careful postoperative observation. Adjuvant radiation therapy is also recommended for all Asian MCC patients. The results of this case series may provide guidance for the treatment of Asian MCC patients in the future.

PMID: 31550749 [PubMed]

Hypercalcaemia due to Sarcoidosis during Treatment with Avelumab for Metastatic Merkel Cell Carcinoma.

Fetched: September 25th, 2019, 5:01am GMT

Hypercalcaemia due to Sarcoidosis during Treatment with Avelumab for Metastatic Merkel Cell Carcinoma.

Case Rep Oncol. 2019 May-Aug;12(2):639-643

Authors: Tun Min S, Nordman IIC, Tran HA

Abstract
Merkel cell carcinoma is a rare but aggressive skin cancer. Response to chemotherapy is not durable but avelumab, an anti-PD-L1 inhibitor, showed promising ongoing response in a phase II trial. Checkpoint inhibitors including avelumab are known to cause overactivation of the immune system, leading to immune-related adverse events (irAE). We describe the first reported case of hypercalcaemia secondary to reactivation of sarcoidosis in a patient with metastatic Merkel cell carcinoma on avelumab. Hypercalcaemia was managed with corticosteroids to full resolution and avelumab therapy was safely continued.

PMID: 31543781 [PubMed]

Possible immunotherapies of skin cancers

Fetched: September 22nd, 2019, 5:01am GMT

Possible immunotherapies of skin cancers

Magy Onkol. 2019 Sep 18;63(3):239-245

Authors: Lengyel LZS, Gyulai GYR

Abstract
Skin cancers represent the most common type of malignancy. The incidence rate of melanoma and non-melanoma skin cancer depicts a continuous rise worldwide, which is attributed mainly (but not exclusively) to the growing incidence of non-melanoma skin cancer in the elderly population. Most skin cancer types are sensitive to immunotherapy. Melanoma, Merkel cell carcinoma, cutaneous squamous cell carcinoma showed response rates of at least 40% for PD-1 inhibitor therapy as reported in recent articles. In this article we review the current and future immunotherapy agents and procedures for skin cancers.

PMID: 31538441 [PubMed - in process]

Cabozantinib in Patients with Advanced Merkel Cell Carcinoma.

Fetched: September 22nd, 2019, 5:01am GMT

Cabozantinib in Patients with Advanced Merkel Cell Carcinoma.

Oncologist. 2018 07;23(7):814-821

Authors: Rabinowits G, Lezcano C, Catalano PJ, McHugh P, Becker H, Reilly MM, Huang J, Tyagi A, Thakuria M, Bresler SC, Sholl LM, Shapiro GI, Haddad R, DeCaprio JA

Abstract
BACKGROUND: This study sought to determine the efficacy and safety profile of cabozantinib in patients with advanced Merkel cell carcinoma (MCC).
EXPERIMENTAL DESIGN: This prospective, phase II, single-institution trial enrolled patients with platinum-failure, recurrent/metastatic MCC to receive cabozantinib 60 mg orally daily until disease progression, withdrawal from study, or severe toxicity. The primary endpoint was disease control rate. Secondary endpoints included overall survival (OS), progression-free survival (PFS), and toxicity. Immunohistochemistry for VEGFR-2, MET, and HGF expression and next-generation sequencing of tumor tissue were performed and correlated with outcome.
RESULTS: Eight patients were accrued from January 24, 2014, to June 8, 2016. The study was closed prematurely because of toxicity and lack of responses. The most frequent adverse events were grades 1 and 2 and included anorexia, fatigue, nausea, hypothyroidism, and dysgeusia. Two patients developed nonhealing, painful ulcers and tumor-skin fistula. One patient had stable disease for 8 months. One patient withdrew from the study after 2 weeks of therapy because of adverse events. Three patients required dose reduction because of toxicity. Median PFS and OS were 2.1 and 11.2 months, respectively. No expression of MET, HGF, or VEGFR-2 was identified in tumor cells by immunohistochemistry of patients' tissue samples.
CONCLUSION: Cabozantinib was poorly tolerated and did not demonstrate activity in patients with recurrent/metastatic, platinum-failure MCC. It is unclear whether preselection of patients with the specific upregulation or genetic alteration in the targets for cabozantinib would have changed the results of this study. (Clinical trial identification number: NCT02036476) IMPLICATIONS FOR PRACTICE: This phase II study demonstrated poor tolerability and lack of activity of cabozantinib in an unselected group of patients with advanced Merkel cell carcinoma. Although it is unclear whether preselection of patients with the specific upregulation and genetic alterations in targets for cabozantinib would have changed the results of this study, this would have likely led to an extremely rare patient population that would take many years to accrue.

PMID: 29445030 [PubMed - indexed for MEDLINE]

Treatment of Advanced Merkel Cell Carcinoma: Current Therapeutic Options and Novel Immunotherapy Approaches.

Fetched: September 21st, 2019, 5:01am GMT

Treatment of Advanced Merkel Cell Carcinoma: Current Therapeutic Options and Novel Immunotherapy Approaches.

Target Oncol. 2018 10;13(5):567-582

Authors: Femia D, Prinzi N, Anichini A, Mortarini R, Nichetti F, Corti F, Torchio M, Peverelli G, Pagani F, Maurichi A, Mattavelli I, Milione M, Bedini N, Corti A, Di Bartolomeo M, de Braud F, Pusceddu S

Abstract
Advanced Merkel cell carcinoma (MCC) is a very aggressive, rare neuroendocrine tumor of the skin with a high frequency of locoregional recurrence and metastasis, and a high mortality rate. Surgical resection, sentinel lymph node biopsy, and radiotherapy represent the gold standard of treatment in patients with localized disease, while chemotherapy has a significant role in the treatment of advanced disease. However, no definitive evidence on the survival impact of radiotherapy in the advanced stages has been provided to date, and response to chemotherapy remains brief in the majority of cases, indicating an urgent need for alternative approaches. Biological and genome sequencing studies have implicated multiple molecular pathways in MCC, thus leading to the development of new agents that target angiogenic factors, anti-apoptosis molecules, poly-ADP ribose polymerase, intracellular signal proteins such as the PI3K/AKT/mTOR pathway, and peptide receptors such as somatostatin receptors. More recently, immunotherapy agents such as avelumab, pembrolizumab, and nivolumab, which act by blocking the programmed cell-death (PD)-1/PD-L1 immune checkpoint, have shown promising results, especially in the advanced setting, and should now be considered standard of care for metastatic MCC. Current research is focusing on developing new immunotherapeutic strategies, identifying predictive biomarker to aid in the selection of patients responsive to immunotherapy, and defining combination approaches to increase efficacy in refractory patients.

PMID: 30073632 [PubMed - indexed for MEDLINE]

Conversion of Sox2-dependent Merkel cell carcinoma to a differentiated neuron-like phenotype by T antigen inhibition.

Fetched: September 20th, 2019, 5:01am GMT

Conversion of Sox2-dependent Merkel cell carcinoma to a differentiated neuron-like phenotype by T antigen inhibition.

Proc Natl Acad Sci U S A. 2019 Sep 16;:

Authors: Harold A, Amako Y, Hachisuka J, Bai Y, Li MY, Kubat L, Gravemeyer J, Franks J, Gibbs JR, Park HJ, Ezhkova E, Becker JC, Shuda M

Abstract
Viral cancers show oncogene addiction to viral oncoproteins, which are required for survival and proliferation of the dedifferentiated cancer cell. Human Merkel cell carcinomas (MCCs) that harbor a clonally integrated Merkel cell polyomavirus (MCV) genome have low mutation burden and require viral T antigen expression for tumor growth. Here, we showed that MCV+ MCC cells cocultured with keratinocytes undergo neuron-like differentiation with neurite outgrowth, secretory vesicle accumulation, and the generation of sodium-dependent action potentials, hallmarks of a neuronal cell lineage. Cocultured keratinocytes are essential for induction of the neuronal phenotype. Keratinocyte-conditioned medium was insufficient to induce this phenotype. Single-cell RNA sequencing revealed that T antigen knockdown inhibited cell cycle gene expression and reduced expression of key Merkel cell lineage/MCC marker genes, including HES6, SOX2, ATOH1, and KRT20 Of these, T antigen knockdown directly inhibited Sox2 and Atoh1 expression. MCV large T up-regulated Sox2 through its retinoblastoma protein-inhibition domain, which in turn activated Atoh1 expression. The knockdown of Sox2 in MCV+ MCCs mimicked T antigen knockdown by inducing MCC cell growth arrest and neuron-like differentiation. These results show Sox2-dependent conversion of an undifferentiated, aggressive cancer cell to a differentiated neuron-like phenotype and suggest that the ontology of MCC arises from a neuronal cell precursor.

PMID: 31527246 [PubMed - as supplied by publisher]

Evolving Role of Systemic Therapies in Non-melanoma Skin Cancer.

Fetched: September 18th, 2019, 5:01am GMT

Evolving Role of Systemic Therapies in Non-melanoma Skin Cancer.

Clin Oncol (R Coll Radiol). 2019 Sep 12;:

Authors: Conforti C, Corneli P, Harwood C, Zalaudek I

Abstract
Keratinocyte cancers - basal and cutaneous squamous cell carcinoma (BCC, cSCC) - are the most common forms of non-melanoma skin cancer (NMSC) and there has been a significant increase in their incidence globally in recent decades. Although the majority of BCC and cSCC are cured with conventional surgery or radiotherapy, certain tumour or patient-determined factors may result in these modalities being inadequate or inappropriate, for example, locally advanced or metastatic disease, high tumour multiplicity, patient comorbidities and patient preferences. In these clinical circumstances, systemic treatment may be indicated, and over the past 10 years a number of new systemic agents have been approved. Nonetheless, effective systemic therapy for keratinocyte cancers remains an area of significant unmet clinical need. Improved understanding of the molecular and immune pathogenesis underlying tumour growth and development is critical for driving future advances and is a research priority. The aim of this review is to provide clinicians with an overview of systemic treatments for BCC and cSCC and will focus on current evidence for conventional chemotherapy, targeted therapies, immunotherapy, adjuvant and neoadjuvant therapy, chemoprevention and future prospects for novel systemic treatment approaches.

PMID: 31522944 [PubMed - as supplied by publisher]

Permalink for 'Long-Term Follow-Up of 90Y-Ibritumomab Tiuxetan, Fludarabine, and Total Body Irradiation-Based Nonmyeloablative Allogeneic Transplant Conditioning for Persistent High-Risk B Cell Lymphoma.'

Long-Term Follow-Up of 90Y-Ibritumomab Tiuxetan, Fludarabine, and Total Body Irradiation-Based Nonmyeloablative Allogeneic Transplant Conditioning for Persistent High-Risk B Cell Lymphoma.

Fetched: September 18th, 2019, 5:01am GMT

Long-Term Follow-Up of 90Y-Ibritumomab Tiuxetan, Fludarabine, and Total Body Irradiation-Based Nonmyeloablative Allogeneic Transplant Conditioning for Persistent High-Risk B Cell Lymphoma.

Biol Blood Marrow Transplant. 2018 11;24(11):2211-2215

Authors: Puronen CE, Cassaday RD, Stevenson PA, Sandmaier BM, Flowers ME, Green DJ, Maloney DG, Storb RF, Press OW, Gopal AK

Abstract
Nonmyeloablative allogeneic hematopoietic cell transplantation (HCT) can provide prolonged remissions in patients with advanced B cell lymphoma (B-NHL) via the graft-versus-lymphoma effect, although inferior results are seen in patients with chemoresistant, bulky, or aggressive disease. Radioimmunotherapy can safely induce responses in B-NHL with minimal nonhematologic toxicity. Initial results of 90Y-ibritumomab tiuxetan-based allografting demonstrated early safety and disease control in nonremission patients but with short follow-up. Here we report the long-term outcomes of patients treated on this study with specific emphasis on patients achieving early remissions. Eleven of 40 patients were alive at a median follow-up of 9 years (range, 5.3 to 10.2). Fourteen (35%) deaths were due to disease progression and 14 (35%) deaths to complications from HCT. One patient died of a Merkel cell carcinoma. The 5-year overall and progression-free survival for patients with indolent B-NHL was 40% and 27.5%, respectively. None of the patients with diffuse large B cell lymphoma was a long-term disease-free survivor regardless of early remission status. 90Y-ibritumomab tiuxetan-based allografting represents a viable option in patients with indolent histologies. Improved strategies are needed for aggressive B-NHL. The original trial was registered at www.clinicaltrials.gov as NCT00119392.

PMID: 30454872 [PubMed - indexed for MEDLINE]

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

Fetched: September 15th, 2019, 5:01am GMT

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

Semin Oncol Nurs. 2019 Sep 09;: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 - as supplied by publisher]

MCV-miR-M1 Targets the Host-Cell Immune Response Resulting in the Attenuation of Neutrophil Chemotaxis.

Fetched: September 15th, 2019, 5:01am GMT

MCV-miR-M1 Targets the Host-Cell Immune Response Resulting in the Attenuation of Neutrophil Chemotaxis.

J Invest Dermatol. 2018 11;138(11):2343-2354

Authors: Akhbari P, Tobin D, Poterlowicz K, Roberts W, Boyne JR

Abstract
Virus-encoded microRNAs are emerging as key regulators of persistent infection and host-cell immune evasion. Merkel cell polyomavirus, the predominant etiological agent of Merkel cell carcinoma, encodes a single microRNA, MCV-miR-M1, which targets the oncogenic Merkel cell polyomavirus large T antigen. MCV-miR-M1 has previously been shown to play an important role in the establishment of long-term infection, however, the underlying mechanism is not fully understood. A key unanswered question is whether, in addition to autoregulating large T antigen, MCV-miR-M1 also targets cellular transcripts to orchestrate an environment conducive to persistent infection. To address this, we adopted an RNA sequencing-based approach to identify cellular targets of MCV-miR-M1. Intriguingly, bioinformatics analysis of transcripts that are differentially expressed in cells expressing MCV-miR-M1 revealed several genes implicated in immune evasion. Subsequent target validation led to the identification of the innate immunity protein, SP100, as a direct target of MCV-miR-M1. Moreover, MCV-miR-M1-mediated modulation of SP100 was associated with a significant decrease in CXCL8 secretion, resulting in the attenuation of neutrophil chemotaxis toward Merkel cells harboring synthetic Merkel cell polyomavirus. Based on these observations, we propose that MCV-miR-M1 targets key immune response regulators to help facilitate persistent infection, which is a prerequisite for cellular transformation in Merkel cell carcinoma.

PMID: 29777657 [PubMed - indexed for MEDLINE]

ASO Author Reflections: Resection Margins in Merkel Cell Carcinoma: Is a 1 cm Margin Wide Enough?

Fetched: September 11th, 2019, 5:01am GMT

ASO Author Reflections: Resection Margins in Merkel Cell Carcinoma: Is a 1 cm Margin Wide Enough?

Ann Surg Oncol. 2018 12;25(Suppl 3):901

Authors: Perez MC, Zager JS

Abstract

PMID: 30151562 [PubMed - indexed for MEDLINE]

Immune checkpoint inhibitors of PD-L1 as cancer therapeutics.

Fetched: September 8th, 2019, 5:01am GMT

Immune checkpoint inhibitors of PD-L1 as cancer therapeutics.

J Hematol Oncol. 2019 Sep 05;12(1):92

Authors: Akinleye A, Rasool Z

Abstract
Since the discovery of immune checkpoint proteins, there has been a special interest in developing antibodies that block programmed cell death 1 receptor (PD-1) and programmed cell death receptor ligand 1 (PD-L1) for a subset of cancer patients. PD-1 signaling negatively regulates T cell-mediated immune responses and serves as a mechanism for tumors to evade an antigen-specific T cell immunologic response. It plays a role in promoting cancer development and progression by enhancing tumor cell survival. With this background, PD-1 signaling represents a valuable therapeutic target for novel and effective cancer immunotherapy. Clinical data shows that blockade of this PD-1 signaling significantly enhance antitumor immunity, produce durable clinical responses, and prolong survival. Currently, there are three FDA-approved PD-L1 inhibitors for various malignancies ranging from non-small cell lung cancer to Merkel cell carcinoma. This review is to summarize many ongoing phase II/III trials of atezolizumab, durvalumab, avelumab, and new PD-L1 inhibitors in clinical developments. In particular, we focus on key trials that paved the pathway to FDA-approved indications for atezolizumab, durvalumab, and avelumab. Despite the popularity and accelerated FDA approval of PD-L1 inhibitors, further considerations into predictive biomarkers, mechanisms of resistance, treatment duration, immune-related toxicities, and PD-L1 expression threshold are needed to optimize anticancer potential in this class of immunotherapy.

PMID: 31488176 [PubMed - in process]

Permalink for 'Genetic Variability of the Noncoding Control Region of Cutaneous Merkel Cell Polyomavirus: Identification of Geographically Related Genotypes.'

Genetic Variability of the Noncoding Control Region of Cutaneous Merkel Cell Polyomavirus: Identification of Geographically Related Genotypes.

Fetched: September 8th, 2019, 5:01am GMT

Genetic Variability of the Noncoding Control Region of Cutaneous Merkel Cell Polyomavirus: Identification of Geographically Related Genotypes.

J Infect Dis. 2018 04 23;217(10):1601-1611

Authors: Hashida Y, Higuchi T, Matsui K, Shibata Y, Nakajima K, Sano S, Daibata M

Abstract
Background: Merkel cell polyomavirus (MCPyV) is a ubiquitous cutaneous virus that causes Merkel cell carcinoma, which develops preferentially in white populations from Europe and North America. However, the genomic variations of MCPyV among ethnic groups have not been well delineated, and even less is known regarding alterations in the noncoding control region (NCCR) in the general population.
Methods: MCPyV strains recovered from skin swab specimens from 250 healthy participants with distinct ethnicities and geographic origins were subjected to sequencing analysis of the NCCR.
Results: A 25-base pair tandem repeat caused by a 25-base pair insertion within the NCCR was found predominantly in Japanese and East Asian individuals. Based on the presence of 2 other insertions and a deletion, the NCCR could be classified further into 5 genotypes. This tandem repeat was also found exclusively in the NCCR from Japanese patients with Merkel cell carcinoma, while other genotypes were detected in white patients from Europe and North America.
Conclusions: Our results suggest that the MCPyV NCCR varies according to ethnicity and that assessing the short NCCR sequence provides a rapid and simple means for identification of the Japanese and East Asian variant genotype. It remains to be established whether these NCCR variations are associated differentially with the pathogenesis of MCPyV-driven Merkel cell carcinoma between regions with varying endemicity.

PMID: 29409030 [PubMed - indexed for MEDLINE]

Permalink for 'Favorable Response After Only One Cycle of Peptide Receptor Radionuclide Therapy With 177Lu-DOTATATE in a Patient With Metastatic Merkel Cell Carcinoma.'

Favorable Response After Only One Cycle of Peptide Receptor Radionuclide Therapy With 177Lu-DOTATATE in a Patient With Metastatic Merkel Cell Carcinoma.

Fetched: September 7th, 2019, 5:01am GMT

Favorable Response After Only One Cycle of Peptide Receptor Radionuclide Therapy With 177Lu-DOTATATE in a Patient With Metastatic Merkel Cell Carcinoma.

Clin Nucl Med. 2019 Aug;44(8):650-652

Authors: Moghadam SZ, Divband G, Shakeri S, Aryana K

Abstract
A 77-year-old man with a history of metastatic Merkel cell carcinoma and debilitating painful cutaneous lesions was referred to our nuclear medicine department for peptide receptor radionuclide therapy with Lu-DOTATATE as ultimate therapeutic option. Post-treatment whole body scan showed multiple zones of Lu-DOTATATE uptake in the metastatic regions, which revealed significant improvement within the next 10 days of therapy. Peptide receptor radionuclide therapy in metastatic Merkel cell carcinoma is an effective therapeutic option that should be considered in earlier stages of the disease.

PMID: 31274613 [PubMed - indexed for MEDLINE]

Prevalence and risk factors of human polyomavirus infections in non-malignant tonsils and gargles: the SPLIT study.

Fetched: September 7th, 2019, 5:01am GMT

Prevalence and risk factors of human polyomavirus infections in non-malignant tonsils and gargles: the SPLIT study.

J Gen Virol. 2018 12;99(12):1686-1698

Authors: Kourieh A, Combes JD, Tommasino M, Dalstein V, Clifford GM, Lacau St Guily J, Clavel C, Franceschi S, Gheit T, For The Split Study Group

Abstract
The prevalence of 13 polyomaviruses (PyVs) in the tonsil brushings and gargles of immunocompetent children and adults was assessed. Patients undergoing tonsillectomy for benign indications were recruited in 19 centres in France. After resection, the entire outer surface of the right and left halves of the tonsils was brushed extensively. Gargles were also collected prior to surgery in selected adults. A species-specific multiplex assay was used to detect the DNA of 13 PyVs. In tonsil brushings (n=689), human PyV 6 (HPyV6) and Merkel cell PyV (MCPyV) were the most prevalent (≈15 %), followed by trichodysplasia spinulosa-associated PyV (TSPyV), BKPyV, Washington University PyV (WUPyV) and human PyV 9 (HPyV9) (1 to 5 %), and human PyV 7 (HPyV7), John Cunningham PyV (JCPyV) and Simian virus 40 (SV40) (<1 %), while no Karolinska Institute PyV (KIPyV), Malawi PyV (MWPyV), human PyV 12 (HPyV12) or Lyon IARC PyV (LIPyV) were detected. The prevalence of TSPyV and BKPyV was significantly higher in children versus adults, whereas for HPyV6 the opposite was found. HPyV6 and WUPyV were significantly more prevalent in men versus women. In gargles (n=139), MCPyV was the most prevalent (≈40 %), followed by HPyV6, HPyV9 and LIPyV (2 to 4 %), and then BKPyV (≈1 %), while other PyVs were not detected. MCPyV and LIPyV were significantly more prevalent in gargles compared to tonsil brushings, in contrast to HPyV6. We described differing patterns of individual PyV infections in tonsils and gargles in a large age-stratified population. Comparison of the spectrum of PyVs in paired tonsil samples and gargles adds to the current knowledge on PyV epidemiology, contributing towards a better understanding of PyV acquisition and transmission and its potential role in head and neck diseases.

PMID: 30407150 [PubMed - indexed for MEDLINE]

Permalink for 'Re: Prospective analysis of the utility of 18-FDG PET in Merkel cell carcinoma of the skin: A Trans Tasman Radiation Oncology Group Study, TROG 09:03 (Journal of Medical Imaging and Radiation Oncology 62 (2018) 412-419).'

Re: Prospective analysis of the utility of 18-FDG PET in Merkel cell carcinoma of the skin: A Trans Tasman Radiation Oncology Group Study, TROG 09:03 (Journal of Medical Imaging and Radiation Oncology 62 (2018) 412-419).

Fetched: September 4th, 2019, 5:01am GMT

Re: Prospective analysis of the utility of 18-FDG PET in Merkel cell carcinoma of the skin: A Trans Tasman Radiation Oncology Group Study, TROG 09:03 (Journal of Medical Imaging and Radiation Oncology 62 (2018) 412-419).

J Med Imaging Radiat Oncol. 2018 10;62(5):671

Authors: Pincus J

PMID: 30152112 [PubMed - indexed for MEDLINE]

The impact of facility characteristics on Merkel cell carcinoma outcomes: a retrospective cohort study.

Fetched: September 3rd, 2019, 5:01am GMT

The impact of facility characteristics on Merkel cell carcinoma outcomes: a retrospective cohort study.

J Am Acad Dermatol. 2019 Aug 29;:

Authors: Cheraghlou S, Agogo GO, Girardi M

Abstract
BACKGROUND: Previous work has suggested that facility-level characteristics such as case volume and academic affiliation are associated with patient survival for rare malignancies. Merkel cell carcinoma (MCC) is a rare neuroendocrine skin cancer with high mortality and rising incidence. The impact of facility characteristics on MCC outcomes is not yet established.
OBJECTIVE: We aimed to investigate the association of facility academic affiliation and case volume with MCC patient survival.
METHODS: We conducted a retrospective cohort analysis of US adult MCC cases diagnosed from 2004-2014 in the NCDB.
RESULTS: Both facility academic affiliation (p<0.001) and case volume (p<0.001) were significantly associated with patient survival. For propensity score-matched cohorts of patients treated at academic versus non-academic facilities, five-year survival was 63.0% (SE: 1.7) and 53.4% (SE: 1.9) respectively. Five-year survival for propensity score-matched cohorts of patients treated at high versus low/intermediate case volume facilities was 67.4% (SE: 2.1) and 58.6% (SE: 2.0) respectively.
LIMITATIONS: Disease-specific survival and local recurrence data were not available.
CONCLUSIONS: Treatment of MCC at academic and high-volume centers is associated with significantly improved patient survival. Further study, taking into account comorbidities and evaluating disease-specific survival, is needed to establish whether experienced centers have improved outcomes in MCC treatment.

PMID: 31473294 [PubMed - as supplied by publisher]

Viral and tumor antigen-specific CD8 T-cell responses in Merkel cell carcinoma.

Fetched: September 3rd, 2019, 5:01am GMT

Viral and tumor antigen-specific CD8 T-cell responses in Merkel cell carcinoma.

Cell Immunol. 2019 Aug 01;:103961

Authors: Samimi M, Benlalam H, Aumond P, Gaboriaud P, Fradin D, Kervarrec T, Florenceau L, Vignard V, Blom A, Touzé A, Gervois N, Labarriere N

Abstract
Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous cancer, which is immunogenic, regardless of the presence of MCPyV (80% of cases). The identification of MCC-specific epitopes recognized by CD8 T cells is crucial to expand the arsenal of immunotherapeutic treatments. Until now, most efforts focused on the identification of virus-specific epitopes, whereas immune responses directed against shared cellular tumor-specific antigens have not been evidenced. In this study, we measured T-cell responses against viral (n = 3) and tumor antigens (n = 47) from TILs derived from 21 MCC tumors. Virus-specific CD8 T-cell responses dominated MCC-specific immune responses, and we identified two new HLA-peptide complexes derived from the LT antigen, located in a region encompassing 3 previously identified epitopes. Finally, we show that MAGE-A3 antigen, frequently expressed by MCC tumors, was recognized by CD8 TILs from a virus-negative MCC tumor and thus could be a target for immunotherapy in this setting.

PMID: 31472938 [PubMed - as supplied by publisher]

Aggressive Merkel Cell Carcinoma After Janus Kinase Inhibitor Ruxolitinib for Polycythemia Vera.

Fetched: September 2nd, 2019, 5:01am GMT

Aggressive Merkel Cell Carcinoma After Janus Kinase Inhibitor Ruxolitinib for Polycythemia Vera.

In Vivo. 2019 Sep-Oct;33(5):1667-1669

Authors: Rastrelli M, Ferrazzi B, Tropea S, Costa A, Finotto S, Marino D, Campana L, Del Fiore P, Rossi CR, Alaibac M

Abstract
Merkel cell carcinoma (MCC) is a rare neuroendocrine carcinoma of the skin. It is highly aggressive and represents the second most common cause of skin cancer-related death. Ruxolitinib is an orally administered selective inhibitor of Janus associated kinases1 and 2, which is used in the management of patients with symptomatic myelofibrosis and polycythemia vera who are non-responders or intolerant to hydroxyurea. Herein, we report the case of a 47-year-old woman with a 14-year history of chronic myeloproliferative syndrome initially treated with hydroxyurea for 4 years. She was then enrolled in the Response trial and treated for 7 years with ruxolitinib subsequently developing an MCC. This report shows the possibility of development of MCC in patients treated with ruxolitinib. Periodic skin examination is indicated in patients who undergo ruxolitinib therapy, especially if they have a history of skin cancer; dermatologists and oncohematologists should be aware of this possibility in order to introduce appropriate preventive strategies.

PMID: 31471421 [PubMed - in process]

[Immune checkpoint inhibition in Merkel cell carcinoma].

Fetched: September 1st, 2019, 5:01am GMT

[Immune checkpoint inhibition in Merkel cell carcinoma].

Hautarzt. 2019 Aug 29;:

Authors: Terheyden P, Mohr A, Langan EA

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) is a rare but aggressive form of skin cancer in which Merkel cell polyomavirus infection and chronic exposure to ultraviolet radiation are key risk factors. Immune checkpoint inhibition has revolutionized the treatment of locally advanced, inoperable and metastatic MCC.
AIM: To outline the modern management of MCC based on advances in our understanding of MCC tumour biology and the development of immune checkpoint inhibitors, namely inhibitors of programmed cell death protein (PD)-1- and PD‑1 ligand 1 (PD-L1).
METHODS: A review of the scientific literature listed in PubMed.
RESULTS: First line therapy with the PD-L1 blocking antibody avelumab is associated with a response rate of 62%. In the second line setting, for example after chemotherapy, the response rate only reaches 33%. However, in patients who responded in the second line setting, 69% remained relapse free after 2 years. Treatment responses occurred on average after 6.1 weeks of therapy. First line treatment with pembrolizumab (anti-PD‑1 antibody) is associated with a 2-year survival rate of 69% and the median survival rate has not been reached. Whilst the various chemotherapy regimens are associated with similar response rates, these are typically short lived.
DISCUSSION: Checkpoint inhibition offers an effective treatment option for patients with MCC. Avelumab is currently licensed as a treatment for metastatic disease. Chemotherapy remains an option to reduce tumor load, or in the context of resistance and/or contraindications to immune checkpoint therapy. Adjuvant and neoadjuvant use of checkpoint inhibition in MCC may represent a future treatment strategy pending the results of on-going clinical trials.

PMID: 31468071 [PubMed - as supplied by publisher]

Updates on Merkel Cell Carcinoma.

Fetched: September 1st, 2019, 5:01am GMT

Updates on Merkel Cell Carcinoma.

Dermatol Clin. 2019 Oct;37(4):489-503

Authors: Emge DA, Cardones AR

Abstract
Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer associated with the Merkel cell Polyomavirus. Its incidence and mortality are increasing. There have been many advances in the last several decades in the etiology, detection, and management of MCC, but much about its natural history and most effective treatment remains unknown. Surgical excision with margins of 1 to 2 cm remains first-line therapy for early-stage MCC, but robust evidence supporting immunotherapy for patients with advanced disease has led to recent approval of immune checkpoint inhibitors in the treatment of advanced MCC.

PMID: 31466589 [PubMed - in process]

CRISPR/Cas9 Editing of the Polyomavirus Tumor Antigens Inhibits Merkel Cell Carcinoma Growth In Vitro.

Fetched: September 1st, 2019, 5:01am GMT

CRISPR/Cas9 Editing of the Polyomavirus Tumor Antigens Inhibits Merkel Cell Carcinoma Growth In Vitro.

Cancers (Basel). 2019 Aug 28;11(9):

Authors: Temblador A, Topalis D, Andrei G, Snoeck R

Abstract
Merkel cell carcinoma (MCC) is an aggressive type of skin cancer whose main causative agent is Merkel cell polyomavirus (MCPyV). MCPyV is integrated into the genome of the tumor cells in most MCCs. Virus-positive tumor cells constitutively express two viral oncoproteins that promote cell growth: the small (sT) and the large (LT) tumor antigens (TAs). Despite the success of immunotherapies in patients with MCC, not all individuals respond to these treatments. Therefore, new therapeutic options continue to be investigated. Herein, we used CRISPR/Cas9 to target the viral oncogenes in two virus-positive MCC cell lines: MS-1 and WAGA. Frameshift mutations introduced in the target sequence upon repair of the Cas9-induced DNA break resulted in decreased LT protein levels, which subsequently impaired cell proliferation, caused cell cycle arrest, and led to increased apoptosis. Importantly, a virus-negative non-MCC cell line (HEK293T) remained unaffected, as well as those cells expressing a non-targeting single-guide RNA (sgRNA). Thus, we presumed that the noted effects were not due to the off-target activity of the TAs-targeting sgRNAs. Additionally, WAGA cells had altered levels of cellular proteins involved in cell cycle regulation, supporting the observed cell cycle. Taken together, our findings provide evidence for the development of a CRISPR/Cas9-based therapeutic option for virus-positive MCC.

PMID: 31466237 [PubMed]

Somatostatin receptor type 2 expression in Merkel cell carcinoma as a prognostic factor.

Fetched: September 1st, 2019, 5:01am GMT

Somatostatin receptor type 2 expression in Merkel cell carcinoma as a prognostic factor.

J Eur Acad Dermatol Venereol. 2018 Jun;32(6):e236-e237

Authors: Orlova KV, Delektorskaya VV, Vishnevskaya YV, Kondratieva TT, Orel NF, Markovich AA, Demidov LV, Subramanian S

PMID: 29265481 [PubMed - indexed for MEDLINE]

Indocyanine Green Sentinel Node in Merkel Cell Carcinoma of the Cheek.

Fetched: August 31st, 2019, 5:01am GMT

Indocyanine Green Sentinel Node in Merkel Cell Carcinoma of the Cheek.

J Craniofac Surg. 2019 Jun;30(4):e376-e377

Authors: Gabriele G, Aboh IV, Cascino F, Zerini F, Amadi JU, Del Frate R, Xu J, Gennaro P

Abstract
Merkel cell carcinoma (MCC) is a rare malignant tumor with a neuroendocrine phenotype. The authors report a case of MCC of the left cheek region in an 85-year-old Caucasian woman who also received sentinel node biopsy using both Technectium-99m-labeled (99mTc) lymphoscintigraphy and indocyanine green lymphography.

PMID: 30865131 [PubMed - indexed for MEDLINE]

Permalink for 'Retrospective study on the correlation between 18-fluorodeoxyglucose uptake in positron emission tomography-computer tomography and tumour volume, cytological activity as assessed with Ki-67 and GLUT-1 staining in 10 cases of Merkel cell carcinoma.'

Retrospective study on the correlation between 18-fluorodeoxyglucose uptake in positron emission tomography-computer tomography and tumour volume, cytological activity as assessed with Ki-67 and GLUT-1 staining in 10 cases of Merkel cell carcinoma.

Fetched: August 31st, 2019, 5:01am GMT

Retrospective study on the correlation between 18-fluorodeoxyglucose uptake in positron emission tomography-computer tomography and tumour volume, cytological activity as assessed with Ki-67 and GLUT-1 staining in 10 cases of Merkel cell carcinoma.

J Eur Acad Dermatol Venereol. 2018 Jul;32(7):e285-e287

Authors: Kitamura S, Yanagi T, Inamura-Takashima Y, Imafuku K, Hata H, Uehara J, Ishida Y, Otsuka A, Hirata K, Shimizu H

PMID: 29377285 [PubMed - indexed for MEDLINE]

Permalink for 'In-transit recurrence of Merkel cell carcinoma associated with Bowen's disease: The first reported case successfully treated by avelumab.'

In-transit recurrence of Merkel cell carcinoma associated with Bowen's disease: The first reported case successfully treated by avelumab.

Fetched: August 28th, 2019, 5:01am GMT

In-transit recurrence of Merkel cell carcinoma associated with Bowen's disease: The first reported case successfully treated by avelumab.

J Dermatol. 2019 May;46(5):440-443

Authors: Kiyohara T, Shijimaya T, Miyamoto M, Nagano N, Nakamaru S, Makimura K, Tanimura H

Abstract
A 65-year-old Japanese man presented with a dome-shaped nodule, the base of which was contiguous with a dull brown plaque, on the left leg. After local excision of the cutaneous lesion and left inguinal lymph node dissection, several dermal and subcutaneous nodules developed successively on the left lower extremity. Hematoxylin-eosin staining of the primary cutaneous lesion demonstrated uniform neoplastic cells arranged in a trabecular pattern extending from the dermis to subcutis. Mitotic figures were abundant. Although the overlying epidermis was substantially intact, the Merkel cells had invaded the epidermis, resulting in Pautrier-like microabscesses. The hyperplastic epidermis adjacent to the nodule consisted of abnormally growing atypical keratinocytes. The enlarged left inguinal lymph node and successive secondary nodules contained Merkel cells similar to those in the primary nodule. Immunohistochemically, most tumor cells were positive for CAM5.2, synaptophysin, chromogranin A, CD56 and vimentin. The tumor cells in the left inguinal lymph node were positive for CAM5.2, synaptophysin and cytokeratin 20 but negative for CM2B4, and less than 1% of the cells expressed programmed cell death ligand 1. The patient was treated with avelumab, which showed significant efficacy against the in-transit recurrence. Two months later, all nodules had disappeared completely. We describe a case of in-transit recurrence of Merkel cell carcinoma that was associated histologically with Bowen's disease and was successfully treated with avelumab. Although accumulation of additional cases is needed, avelumab therapy may be a useful treatment for in-transit recurrence of Merkel cell carcinoma.

PMID: 30809835 [PubMed - indexed for MEDLINE]

Distant recurrence of Merkel cell carcinoma after spontaneous regression.

Fetched: August 28th, 2019, 5:01am GMT

Distant recurrence of Merkel cell carcinoma after spontaneous regression.

J Dermatol. 2019 Apr;46(4):e133-e134

Authors: Kobayashi Y, Nakamura M, Kato H, Morita A

PMID: 30230579 [PubMed - indexed for MEDLINE]

Human Polyomavirus JCPyV and Its Role in Progressive Multifocal Leukoencephalopathy and Oncogenesis.

Fetched: August 25th, 2019, 5:01am GMT

Human Polyomavirus JCPyV and Its Role in Progressive Multifocal Leukoencephalopathy and Oncogenesis.

Front Oncol. 2019;9:711

Authors: Del Valle L, Piña-Oviedo S

Abstract
The human neurotropic virus JCPyV, a member of the Polyomaviridiae family, is the opportunistic infectious agent of Progressive Multifocal Leukoencephalopathy (PML), a fatal disease seen in severe immunosuppressive conditions and, during the last decade, in patients undergoing immunotherapy. JCPyV is a ubiquitous pathogen with up to 85% of the adult population word-wide exhibiting antibodies against it. Early experiments demonstrated that direct inoculation of JCPyV into the brain of different species resulted in the development of brain tumors and other neuroectodermal-derived neoplasias. Later, several reports showed the detection of viral sequences in medulloblastomas and glial tumors, as well as expression of the viral protein T-Antigen. Few oncogenic viruses, however, have caused so much controversy regarding their role in the pathogenesis of brain tumors, but the discovery of new Polyomaviruses that cause Merkel cell carcinomas in humans and brain tumors in racoons, in addition to the role of JCPyV in colon cancer and multiple mechanistic studies have shed much needed light on the role of JCPyV in cancer. The pathways affected by the viral protein T-Antigen include cell cycle regulators, like p53 and pRb, and transcription factors that activate pro-proliferative genes, like c-Myc. In addition, infection with JCPyV causes chromosomal damage and T-Antigen inhibits homologous recombination, and activates anti-apoptotic proteins, such as Survivin. Here we review the different aspects of the biology and physiopathology of JCPyV.

PMID: 31440465 [PubMed]

Combined radio-immunotherapy leads to complete clinical regression of stage IV Merkel cell carcinoma.

Fetched: August 25th, 2019, 5:01am GMT

Combined radio-immunotherapy leads to complete clinical regression of stage IV Merkel cell carcinoma.

BMJ Case Rep. 2019 Aug 21;12(8):

Authors: Principe DR, Clark JI, Emami B, Borowicz S

Abstract
Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine tumour of the skin. While localised disease carries an overall favourable prognosis, metastatic disease is associated with poor clincal outcomes. Most cases of metastatic MCC are managed with systemic chemotherapy or immunotherapy, though 5-year survival for these patients remains a dismal 17%. Here, we present the case of a 79-year-old man with MCC of the right ear with metastases to regional lymph nodes, ipsilateral parotid gland and thoracic spine. He was treated with a combination of first-line radiotherapy and concurrent immune checkpoint inhibition (avelumab), which led to complete clinical regression of disease with minimal adverse effects. This observation suggests that combined radio-immunotherapy warrants larger-scale investigation for use in patients with unresectable MCC.

PMID: 31439556 [PubMed - in process]

ALK and EGFR expression by immunohistochemistry are associated with Merkel cell polyomavirus status in Merkel cell carcinoma.

Fetched: August 23rd, 2019, 5:01am GMT

ALK and EGFR expression by immunohistochemistry are associated with Merkel cell polyomavirus status in Merkel cell carcinoma.

Histopathology. 2019 May;74(6):829-835

Authors: Veija T, Kero M, Koljonen V, Böhling T

Abstract
AIMS: Merkel cell carcinoma, a rare cutaneous neuroendocrine tumour of the skin, can be categorised into two groups according to Merkel cell polyomavirus (MCV) presence. MCV-negative tumours are more aggressive and frequently associated with gene mutations. Some of the genes are potential therapeutic targets. We have previously reported EGFR mutations in six of 27 MCC tumours and overexpression of ALK and EZH2 at mRNA level in MCC tumours. In this study, we sought to determine expression of ALK, EGFR and EZH2 in MCC samples and assess their correlation to MCV status and clinical parameters.
METHODS AND RESULTS: Tissue microarrays were utilised and stained with primary antibodies. Staining data were statistically compared to patient sex, tumour location and development of metastasis and MCC-specific death; 112 tumours and their corresponding patient data were included. We found strong expression of ALK in 51% and strong expression of EZH2 in 76% of the tumours. There was evident correlation of ALK expression with MCV-positivity. Expression of EGFR was infrequent, presenting only in seven MCV-negative tumours. None of the proteins associated with development of metastasis or MCC specific death.
CONCLUSIONS: ALK and EZH2 expression are frequent in MCC and ALK expression correlates to MCV positivity. EGFR positive tumours might respond to EGFR inhibiting treatment.

PMID: 30588655 [PubMed - indexed for MEDLINE]

Permalink for 'Human CD4+ T cells specific for Merkel cell polyomavirus localize to Merkel cell carcinomas and target a required oncogenic domain.'

Human CD4+ T cells specific for Merkel cell polyomavirus localize to Merkel cell carcinomas and target a required oncogenic domain.

Fetched: August 15th, 2019, 5:01am GMT

Human CD4+ T cells specific for Merkel cell polyomavirus localize to Merkel cell carcinomas and target a required oncogenic domain.

Cancer Immunol Res. 2019 Aug 12;:

Authors: Longino NV, Yang J, Iyer JG, Ibrani D, Chow IT, Laing KJ, Campbell VL, Paulson KG, Kulikauskas RM, Church CD, James EA, Nghiem P, Kwok WW, Koelle DM

Abstract
Although CD4+ T cells likely play key roles in antitumor immune responses, most immuno-oncology studies have been limited to CD8+ T-cell responses due to multiple technical barriers and a lack of shared antigens across patients. Merkel cell carcinoma (MCC) is an aggressive skin cancer caused by Merkel cell polyomavirus (MCPyV) oncoproteins in 80% of cases. Because MCPyV oncoproteins are shared across most patients with MCC, it is unusually feasible to identify, characterize, and potentially augment tumor-specific CD4+ T cells. Here, we report the identification of CD4+ T-cell responses against six MCPyV epitopes, one of which included a conserved, essential viral oncogenic domain that binds/disables the cellular retinoblastoma (Rb) tumor suppressor. We found that this epitope (WEDLT209-228) could be presented by three population-prevalent HLA class II alleles, making it a relevant target in 64% of virus-positive MCC patients. Cellular staining with a WEDLT209-228-HLA-DRB1*0401 tetramer indicated that specific CD4+ T cells were detectable in 78% (14 of 18) of evaluable MCC patients, were 250-fold enriched within MCC tumors relative to peripheral blood, and had diverse T-cell receptor sequences. We also identified a modification of this domain that still allowed recognition by these CD4+ T cells, but disabled binding to the Rb tumor suppressor, a key step in the detoxification of a possible therapeutic vaccine. The use of these new tools for deeper study of MCPyV-specific CD4+ T cells may provide a broader insight into cancer-specific CD4+ T-cell responses.

PMID: 31405946 [PubMed - as supplied by publisher]

Permalink for 'Under-recognized immunoexpression of "neuroendocrine markers" and "myoepithelial markers" in basal cell carcinomas: Does it indicate true neuroendocrine and myoepithelial differentiation?'

Under-recognized immunoexpression of "neuroendocrine markers" and "myoepithelial markers" in basal cell carcinomas: Does it indicate true neuroendocrine and myoepithelial differentiation?

Fetched: August 15th, 2019, 5:01am GMT

Under-recognized immunoexpression of "neuroendocrine markers" and "myoepithelial markers" in basal cell carcinomas: Does it indicate true neuroendocrine and myoepithelial differentiation?

J Cutan Pathol. 2017 11;44(11):991-993

Authors: Goto K

PMID: 28841242 [PubMed - indexed for MEDLINE]

Ipilimumab has efficacy in metastatic Merkel cell carcinoma: a case series of five patients.

Fetched: August 15th, 2019, 5:01am GMT

Ipilimumab has efficacy in metastatic Merkel cell carcinoma: a case series of five patients.

J Eur Acad Dermatol Venereol. 2017 Sep;31(9):e389-e391

Authors: Winkler JK, Dimitrakopoulou-Strauss A, Sachpekidis C, Enk A, Hassel JC

PMID: 28256019 [PubMed - indexed for MEDLINE]

Merkel Cell Polyomavirus Small T Antigen Induces DNA Damage Response.

Fetched: August 13th, 2019, 5:01am GMT

Merkel Cell Polyomavirus Small T Antigen Induces DNA Damage Response.

Intervirology. 2019 Aug 09;:1-5

Authors: Wu JH, Narayanan D, Limmer AL, Simonette RA, Rady PL, Tyring SK

Abstract
Merkel cell carcinoma (MCC) is an aggressive neuroendocrine cancer of the skin with high rates of metastasis and mortality. Besides well-established factors including genetic mutations and UV-induced DNA damage in Merkel cell carcinogenesis, the recent discovery of the Merkel cell polyomavirus (MCPyV) has shed light on the viral etiology of MCC. In the current study, we provide novel evidence that MCPyV small T (sT) antigen induces the DNA damage response (DDR) pathway. Our data show that in human MCC cells, the presence of MCPyV is associated with hyperphosphorylation of histone H2AX, a marker for DNA damage. We observed that overexpression of MCPyV sT antigen induced the phosphorylation of histone H2AX as well as the activation of ataxia telangiectasia mutant (ATM), an upstream kinase important for H2AX phosphorylation. Moreover, we observed that MCPyV sT expression also induced the hyperphosphorylation of other ATM downstream molecules (including 53BP1 and CHK2) as well as the hypermethylation of histone 3 and histone 4. These findings disclose a novel link between MCPyV sT and the DDR pathway in MCC. Given that measurement of DDR is clinically useful for evaluating treatment response to radio- and chemotherapy, our findings warrant further investigation to evaluate the potential implications of this pathway for MCC management.

PMID: 31401636 [PubMed - as supplied by publisher]

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

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

Fetched: August 12th, 2019, 5:01am GMT

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

Clin Cancer Res. 2019 Aug 09;:

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

Abstract
PURPOSE: Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy which has demonstrated sensitivity to immune checkpoint inhibitor therapy. Here, we perform the largest genomics study in MCC to date to characterize the molecular landscape and evaluate for clinical and molecular correlates to immune checkpoint inhibitor response.
EXPERIMENTAL DESIGN: Comprehensive molecular profiling was performed on 317 tumors from patients with MCC including the evaluation of oncogenic mutations, tumor mutational burden (TMB), mutational signatures, and the Merkel Cell Polyomavirus (MCPyV). For a subset of 57 patients, a retrospective analysis was conducted to evaluate for clinical and molecular correlates to immune checkpoint inhibitor response and disease survival.
RESULTS: Genomic analyses revealed a bimodal distribution in TMB, with two molecularly distinct subgroups. 94% (n=110) of TMB-high specimens exhibited an ultraviolet light (UV) mutational signature. MCPyV genomic DNA sequences were not identified in any TMB-high cases (0/117), but were in 63% (110/175) of TMB-low cases. For 36 evaluable patients treated with checkpoint inhibitors, the overall response rate was 44% and response correlated with survival at time of review (100% vs. 20%, p<0.001). Response rate was 50% in TMB-high/UV-driven and 41% in TMB-low/MCPyV-positive tumors (p=0.63). Response rate was significantly correlated with line of therapy: 75% in first-line, 39% in second-line, and 18% in third-line or beyond (p=0.0066). PD-1, but not PD-L1, expression was associated with immunotherapy response (77% vs. 21%, p=0.00598, for PD-1 positive and negative, respectively).
CONCLUSIONS: We provide a comprehensive genomic landscape of MCC and demonstrate clinicogenomic associates of immunotherapy response.

PMID: 31399473 [PubMed - as supplied by publisher]

Permalink for 'Role and Therapeutic Targeting of the PI3K/Akt/mTOR Signaling Pathway in Skin Cancer: A Review of Current Status and Future Trends on Natural and Synthetic Agents Therapy.'

Role and Therapeutic Targeting of the PI3K/Akt/mTOR Signaling Pathway in Skin Cancer: A Review of Current Status and Future Trends on Natural and Synthetic Agents Therapy.

Fetched: August 4th, 2019, 5:01am GMT

Role and Therapeutic Targeting of the PI3K/Akt/mTOR Signaling Pathway in Skin Cancer: A Review of Current Status and Future Trends on Natural and Synthetic Agents Therapy.

Cells. 2019 Jul 31;8(8):

Authors: Chamcheu JC, Roy T, Uddin MB, Banang-Mbeumi S, Chamcheu RN, Walker AL, Liu YY, Huang S

Abstract
The mammalian or mechanistic target of rapamycin (mTOR) and associated phosphatidyl-inositiol 3-kinase (PI3K)/protein kinase B (Akt) pathways regulate cell growth, differentiation, migration, and survival, as well as angiogenesis and metabolism. Dysregulation of these pathways is frequently associated with genetic/epigenetic alterations and predicts poor treatment outcomes in a variety of human cancers including cutaneous malignancies like melanoma and non-melanoma skin cancers. Recently, the enhanced understanding of the molecular and genetic basis of skin dysfunction in patients with skin cancers has provided a strong basis for the development of novel therapeutic strategies for these obdurate groups of skin cancers. This review summarizes recent advances in the roles of PI3K/Akt/mTOR and their targets in the development and progression of a broad spectrum of cutaneous cancers and discusses the current progress in preclinical and clinical studies for the development of PI3K/Akt/mTOR targeted therapies with nutraceuticals and synthetic small molecule inhibitors.

PMID: 31370278 [PubMed - in process]

Updates on the Systemic Treatment of Advanced Non-melanoma Skin Cancer.

Fetched: July 31st, 2019, 5:01am GMT

Updates on the Systemic Treatment of Advanced Non-melanoma Skin Cancer.

Front Med (Lausanne). 2019;6:160

Authors: Tanese K, Nakamura Y, Hirai I, Funakoshi T

Abstract
Non-melanoma skin cancers (NMSCs), which represent a diverse group of cutaneous malignancies, are the most common forms of human neoplasia. The incidence of these diseases is increasing due to a number of factors, including that of increasing human lifespans. The majority of NMSCs are basal cell carcinomas (BCC) and cutaneous squamous cell carcinomas (cSCC), with the remainder being various rare skin cancers, including extramammary Paget's disease (EMPD), Merkel cell carcinoma (MCC), and several skin adnexal carcinomas. Of these, MCC usually shows aggressive behavior with a high mortality rate. On the other hand, BCC, cSCC, EMPD, and skin adnexal tumors usually show an indolent clinical course and metastasize only rarely. Nevertheless, the metastatic forms of these tumors commonly lead to poor patient outcome. A definitive management strategy for the treatment of advanced NMSC has not been established, mainly due to their rarity and lack of reliable information based on well-controlled randomized trials. Chemotherapeutic regimens for treatment of these diseases have been mainly based on the observations of isolated, small case series or clinical trials with a limited numbers of patients. However, accumulating evidence regarding their pathobiological backgrounds as well as recent advances in molecular biotechnology have facilitated the development of novel drugs for treatment of these diseases. Over the past decade, the U.S. Food and Drug Administration has approved several molecular targeting therapies, including Hedgehog inhibitors for BCC, monoclonal antibodies targeting anti-programmed death ligand-1 and anti- programmed cell death 1 (PD-1) for MCC, and anti-PD-1 for cSCC. Here, we review their clinical utility and discuss updated systemic treatment strategies for advanced NMSC.

PMID: 31355203 [PubMed]

The ALPPS procedure: hepatocellular carcinoma as a main indication. An Italian single-center experience.

Fetched: July 31st, 2019, 5:01am GMT

The ALPPS procedure: hepatocellular carcinoma as a main indication. An Italian single-center experience.

Updates Surg. 2019 Mar;71(1):67-75

Authors: Vennarecci G, Ferraro D, Tudisco A, Levi Sandri GB, Guglielmo N, Berardi G, Sperduti I, Ettorre GM

Abstract
The ALPPS is a technique that allows achieving hepatic resection by a rapid future liver remnant hypertrophy. The aim of this study was to report the experience of an Italian center with ALPPS in patients with liver tumors. A retrospective analysis of patients undergoing ALPPS between 2012 and 2017 was performed. Patients' characteristics and disease presentation, increase in future liver remnant (FLR) as well as intraoperative and postoperative short- and long-term outcomes were evaluated. A total of 24 patients underwent the ALPPS procedure: 17 procedures for hepatocarcinoma (HCC), 5 for colorectal liver metastases (CRLM), 1 for cholangiocarcinoma (CC) and 1 for Merkel Cell Carcinoma liver metastasis (MCCLM). Macrovascular invasion (MVI) was recorded in 10 (41.6%) patients: 8 (33.3%) patients with HCC had invasion of portal vein (5), middle hepatic vein (2) and inferior vena cava (1). One patient with CRLM had involvement of middle hepatic vein and one patient with CC had involvement of right portal vein and middle hepatic vein. A p-ALPPS in 14 cases (58.3%), 10 t-ALPPS (41.6%) and hanging maneuver in 19 patients (80%) were performed. Median postoperative stay was 26 days (range 16-68 days). 90-day mortality was 8.3% (two patients, one with CC and one with HCC), 90-day mortality for HCC was 5.8%. After stage 1, we counted 15 complications all of grade I; after stage 2 the number of complications was increased to 37:33 were of grade I and 4 were of grade IV. R0 resection was achieved in all patients with 100% oncology feasibility. After a median follow-up of 10 months (range 2-54), disease recurrence has been recorded in 6 patients with HCC and in 2 with CRLM. Eleven patients died, nine affected by HCC, one by CRLM, and one by CC. 2-years OS and disease-free survival (DFS) for the entire group were 47.3% and 47.5%, respectively. Concerning patients operated on for HCC, the 2-years OS and DFS were 38.5% and 60%, respectively. The ALPPS procedure is an interesting approach for large primary or secondary liver tumor with small FLR above all for large HCC associated with MVI, with acceptable OS and DFS.

PMID: 30255436 [PubMed - indexed for MEDLINE]

Absence of immunoglobulin heavy chain rearrangement in primary Merkel cell carcinomas.

Fetched: July 29th, 2019, 5:01am GMT

Absence of immunoglobulin heavy chain rearrangement in primary Merkel cell carcinomas.

Clin Exp Dermatol. 2018 12;43(8):947

Authors: Gambichler T, Segert MH, Höxtermann S, Stockfleth E, Doerler M

PMID: 29797735 [PubMed - indexed for MEDLINE]

Merkel cell carcinoma of the forehead area: a literature review and case report.

Fetched: July 27th, 2019, 5:01am GMT

Merkel cell carcinoma of the forehead area: a literature review and case report.

Oral Maxillofac Surg. 2019 Jul 24;:

Authors: Caldarelli C, Autorino U, Iaquinta C, De Marchi A

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) is an uncommon, aggressive malignancy of the skin, mostly affecting head and neck area in elderly white patients. Between head/neck sites, face accounts for 61% and forehead accounts for 17% of all face MCCs.
PURPOSE: We here present a literature review MCC cases arising in the forehead area, published in the English literature in the period 1987-2018, and report a personal observation with a late diagnosis and a treatment out of the current recommendations. The aims of this paper are to provide an up-to-date on MCC arising in the forehead area and to raise awareness about misdiagnosis of this type of lesion mimicking arteriovenous malformations (AVM).
MATERIAL AND METHOD: Literature review was performed on PubMed and Medline database and "Merkel cell carcinoma (MCC)," "forehead" and "MCC forehead location" were the terms the authors searched for. Patients' data have been drawn from descriptions of single cases and of short case series reports. For each case, data were collected about clinical characteristics, treatment modalities and outcomes. The study has been limited to the clinical features of the disease, excluding etiologic/pathogenic aspects.
RESULTS: Twenty-five patients with forehead MCC have been identified, coming from 20 sources. Nineteen presented a locoregional disease and 6 had an advanced pathology. TNM classification was reported in only two cases lacking for the other available data. Patients presented at mean age of 66 years with solitary or multiple nodules or dome-shaped/hemispherical mass, rarely ulcerated. Mean size of tumors was 1.13 cm of max diameter. Previous or concurrent malignancies or immune-hematologic disorders (AIDS) were often associated. At first investigation, lesion was often mistaken for other malignant or benign processes and, then, diagnosis was generally late. Some type of preoperative biopsy was performed in 3 patients, while the others had only a postoperative microscopic study of specimen. Initial treatment consisted in 6 cases (24%) in a not further specified about extent and width of margins local excision of the primary lesion, while a wide resection was reported in only 3 cases (12%). Surgical treatment of involved lymph-nodes was performed in 3 cases (12%). Six patients underwent radiotherapy for locoregional or distant recurrences. Mortality and overall survival rate at five years were 28% and 24%, respectively. Spontaneous regression was observed in 3 patients (12%).
CASE REPORT: Personal observation concerned an 82-year-old woman presenting with a forehead periorbital 5 × 5 cm red-bluish mass. The erythematous lesion was erroneously diagnosed as hemangioma on the base of color, the absence of any signs of malignancy, an angio CT indicating a hypervascular tissue and a FNA cytology (FNAC) lacking of malignant cells. The mass was excised as a benign lesion with about 1 cm margins extent without searching larger edges. Postoperative radiotherapy was offered to the patient after histology report, but she refused. After 4 months from surgery, she had a parotid metastasis and died from the illness in spite of platinum-based chemotherapy.
CONCLUSIONS: This study confirms the aggressiveness of forehead MCC, comparable with that of other face similar tumors. Personal case suggests that the deceitful benign feature of lesion may mimic an AVM and that FNAC may be misleading and diagnostic failure worsen prognosis. Our experience suggests that in the face smaller than 2-3 cm margins resection may increase the risk of locoregional recurrence. Therefore, postoperative wide-field irradiation should be ever delivered, after forehead MCC surgery, not only when clear margins are unattainable or involved with tumor, but also when negative microscopic edges are documented and residual cancer is thought not persist in the tumor bed. Orbit irradiation seems to be not dangerous for the eye.

PMID: 31342210 [PubMed - as supplied by publisher]

Utilization Patterns of Fellowship-Trained Mohs Surgeons in the Treatment of Merkel Cell Carcinoma.

Fetched: July 26th, 2019, 5:01am GMT

Utilization Patterns of Fellowship-Trained Mohs Surgeons in the Treatment of Merkel Cell Carcinoma.

Dermatol Surg. 2019 04;45(4):610-611

Authors: Mirhossaini RB, Cameron MC, Fathi R, Brown M

PMID: 30148734 [PubMed - indexed for MEDLINE]

Incidental Merkel Cell Carcinoma Encountered During Mohs Surgery.

Fetched: July 26th, 2019, 5:01am GMT

Incidental Merkel Cell Carcinoma Encountered During Mohs Surgery.

Dermatol Surg. 2019 04;45(4):604-606

Authors: Mafee M, Bennett DD, Swanson AM

PMID: 29933296 [PubMed - indexed for MEDLINE]

BK polyomavirus is a cause of bladder cancer.

Fetched: July 25th, 2019, 5:01am GMT

BK polyomavirus is a cause of bladder cancer.

Curr Opin Virol. 2019 Jul 20;39:8-15

Authors: Starrett GJ, Buck CB

Abstract
In 2014, the International Agency for Research on Cancer judged Merkel cell polyomavirus (MCPyV) to be a probable human carcinogen. BK polyomavirus (BKPyV, a distant cousin of MCPyV) was ruled a possible carcinogen. In this review, we argue that it has recently become reasonable to view both of these viruses as known human carcinogens. In particular, several complementary lines of evidence support a causal role for BKPyV in the development of bladder carcinomas affecting organ transplant patients. The expansion of inexpensive deep sequencing has opened new approaches to investigating the important question of whether BKPyV causes urinary tract cancers in the general population.

PMID: 31336246 [PubMed - as supplied by publisher]

Iatrogenic solid tumors following immunosuppressive therapy.

Fetched: July 24th, 2019, 5:01am GMT

Iatrogenic solid tumors following immunosuppressive therapy.

Semin Diagn Pathol. 2018 Jul;35(4):272-278

Authors: Dantey K, Pantanowitz L

Abstract
Immunosuppression induced by chronic medication, such as occurs post-transplantation, may increase a patient's risk of developing solid tumors. These are often rare tumors characterized by odd presentations. This review focuses on commonly encountered iatrogenic, non-hematopoietic solid tumors following immunotherapy and provides a practical approach to their diagnosis. All of the malignancies covered in this review are viral-induced. They include human papillomavirus (HPV)-associated carcinomas, Epstein-Barr virus (EBV)-associated tumors, Merkel cell polyomavirus (MCPyV)-related Merkel cell carcinoma, and Human Herpesvirus 8 (HHV8)-related Kaposi sarcoma. The complementary diagnostic role of ancillary studies, such as immunohistochemistry and in-situ hybridization that target these oncogenic viruses, is addressed.

PMID: 29066044 [PubMed - indexed for MEDLINE]

Skin ultrasound features of Merkel cell carcinoma.

Fetched: July 24th, 2019, 5:01am GMT

Skin ultrasound features of Merkel cell carcinoma.

J Eur Acad Dermatol Venereol. 2017 Jul;31(7):e315-e318

Authors: Hernández-Aragüés I, Vázquez-Osorio I, Alfageme F, Ciudad-Blanco C, Casas-Férnandez L, Rodríguez-Blanco MI, Suárez-Fernández R

PMID: 28045198 [PubMed - indexed for MEDLINE]

Endoscopic ultrasound diagnosis of Merkel cell carcinoma metastasising to pancreas.

Fetched: July 18th, 2019, 5:01am GMT

Endoscopic ultrasound diagnosis of Merkel cell carcinoma metastasising to pancreas.

Cytopathology. 2018 10;29(5):478-481

Authors: Pinho J, Montezuma D, Monteiro P, Dinis-Ribeiro M, Bastos P

PMID: 29665210 [PubMed - indexed for MEDLINE]

Merkel cell carcinoma: morphologic aspects on reflectance confocal microscopy.

Fetched: July 18th, 2019, 5:01am GMT

Merkel cell carcinoma: morphologic aspects on reflectance confocal microscopy.

J Eur Acad Dermatol Venereol. 2017 Nov;31(11):e480-e481

Authors: Longo C, Benati E, Borsari S, Bombonato C, Pampena R, Moscarella E, Piana S, Pellacani G

PMID: 28502121 [PubMed - indexed for MEDLINE]

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

Posted: November 11th, 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
Recruiting

Phase II Trial of Avelumab (Bavencio (R)) With IL-15 in Subjects With Clear-Cell Renal Carcinoma

Posted: November 4th, 2019, 3:00pm GMT

Condition: Clear-Cell Renal Carcinoma
Interventions: Drug: rhIL-15; Biological: Avelumab
Sponsor: National Cancer Institute (NCI)
Not yet recruiting

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

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

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

Long-term, Non-interventional, Observational Study Following Treatment With Fate Therapeutics FT500 Cellular Immunotherapy

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

Conditions: Advanced Solid Tumor; Lymphoma; Gastric Cancer; Colorectal Cancer; Head and Neck Cancer; Squamous Cell Carcinoma; EGFR Positive Solid Tumor; HER2-positive Breast Cancer; Hepatocellular Carcinoma; Small-cell Lung Cancer; Renal Cell Carcinoma; Pancreas Cancer; Melanoma; NSCLC; Urothelial Carcinoma; Cervical Cancer; Microsatellite Instability; Merkel Cell Carcinoma
Intervention: Genetic: Allogeneic natural killer (NK) cell
Sponsor: Fate Therapeutics
Recruiting

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

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

Condition: Kaposi Sarcoma
Intervention: Drug: Talimogene laherparepvec
Sponsor: Assistance Publique - Hôpitaux de Paris
Not yet recruiting

Phase II Palliative RT & Anti-PD-1/PD-L1 Checkpoint Blockade in Metastatic Merkel Cell Carcinoma

Posted: June 17th, 2019, 2:00pm GMT

Condition: Merkel Cell Carcinoma
Interventions: Drug: Pembrolizumab; Radiation: Radiation Therapy
Sponsor: Stanford University
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

High-Risk Skin Cancers With Atezolizumab Plus NT-I7

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

Conditions: Melanoma; Merkel Cell Carcinoma; Cutaneous Squamous Cell Carcinoma
Interventions: Drug: NT-I7; Drug: atezolizumab
Sponsors: NeoImmuneTech; Immune Oncology Network
Not yet recruiting

AMPLIFYing NEOepitope-specific VACcine Responses in Progressive Diffuse Glioma

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

Condition: Malignant Glioma
Interventions: Drug: IDH1R132H peptide vaccine; Drug: Avelumab
Sponsor: German Cancer Research Center
Recruiting

Evaluate Efficacy of Avelumab, haNK and N-803 in Subjects With Progressed MCC on or After Checkpoint Inhibitor 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.
Not yet recruiting

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

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

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

Permalink for 'Tacrolimus, Nivolumab, and Ipilimumab in Treating Kidney Transplant Recipients With Selected Unresectable or Metastatic Cancers'

Tacrolimus, Nivolumab, and Ipilimumab in Treating Kidney Transplant Recipients With Selected Unresectable or Metastatic Cancers

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

Conditions: Clinical Stage III Cutaneous Melanoma AJCC v8; Clinical Stage III Merkel Cell Carcinoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Clinical Stage IV Merkel Cell Carcinoma AJCC v8; High-Frequency Microsatellite Instability; Metastatic Basal Cell Carcinoma; Metastatic Melanoma; Metastatic Merkel Cell Carcinoma; Metastatic Skin Squamous Cell Carcinoma; Pathologic Stage III Cutaneous Melanoma AJCC v8; Pathologic Stage III Merkel Cell Carcinoma AJCC v8; Pathologic Stage IIIA Cutaneous Melanoma AJCC v8; Pathologic Stage IIIA Merkel Cell Carcinoma AJCC v8; Pathologic Stage IIIB Cutaneous Melanoma AJCC v8; Pathologic Stage IIIB Merkel Cell Carcinoma AJCC v8; Pathologic Stage IIIC Cutaneous Melanoma AJCC v8; Pathologic Stage IIID Cutaneous Melanoma AJCC v8; Pathologic Stage IV Cutaneous Melanoma AJCC v8; Pathologic Stage IV Merkel Cell Carcinoma AJCC v8; Unresectable Basal Cell Carcinoma; Unresectable Melanoma; Unresectable Merkel Cell Carcinoma
Interventions: Biological: Ipilimumab; Biological: Nivolumab; Drug: Prednisone; Drug: Tacrolimus
Sponsor: National Cancer Institute (NCI)
Recruiting

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

Posted: January 10th, 2019, 3:00pm GMT

Conditions: Merkel Cell Carcinoma; Pathologic Stage IIIA Merkel Cell Carcinoma AJCC v8; Pathologic Stage IIIB Merkel Cell Carcinoma AJCC v8
Interventions: Biological: Ipilimumab; Biological: Nivolumab; Radiation: Radiation Therapy
Sponsors: Joanne Jeter; National Cancer Institute (NCI)
Recruiting

A Safety and Tolerability Study of INCAGN02390 in Select Advanced Malignancies

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

Conditions: Cervical Cancer; Gastric Cancer; Stomach Cancer; Gastroesophageal Junction Cancer; Esophageal Cancer; Hepatocellular Carcinoma; Melanoma; Uveal Melanoma; Merkel Cell Carcinoma; Mesothelioma; MSI; Non-small Cell Lung Cancer; NSCLC; Ovarian Cancer; Squamous Cell Carcinoma of the Head and Neck; Small Cell Lung Cancer; Renal Cell Carcinoma; RCC; Triple-negative Breast Cancer; Urothelial Carcinoma; Mismatch Repair Deficiency
Intervention: Drug: INCAGN02390
Sponsor: Incyte Corporation
Recruiting

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

Posted: August 14th, 2018, 2:00pm GMT

Conditions: Non-small Cell Lung Cancer; Squamous Cell Carcinoma of the Head and Neck; Breast Cancer; Colorectal Cancer; Melanoma; Bladder Cancer; Ovarian Cancer; Endometrial Cancer; Merkel Cell Carcinoma; GastroEsophageal Cancer; Renal Cell Carcinoma; Castration-resistant Prostate Cancer
Interventions: Drug: AB928; Drug: AB122
Sponsor: Arcus Biosciences, Inc.
Recruiting

A Study to Evaluate the Safety and Tolerability of AB154 in Participants With Advanced Malignancies

Posted: August 14th, 2018, 2:00pm GMT

Conditions: Non-small Cell Lung Cancer; Squamous Cell Carcinoma of the Head and Neck; Renal Cell Carcinoma; Breast Cancer; Colorectal Cancer; Melanoma; Bladder Cancer; Ovarian Cancer; Endometrial Cancer; Merkel Cell Carcinoma; GastroEsophageal Cancer
Interventions: Drug: AB154; Drug: AB122
Sponsor: Arcus Biosciences, Inc.
Recruiting

A Study of INCMGA00012 in Metastatic Merkel Cell Carcinoma

Posted: July 25th, 2018, 2:00pm GMT

Condition: Metastatic Merkel Cell Carcinoma
Intervention: Drug: INCMGA00012
Sponsor: Incyte Corporation
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

A Safety and Tolerability Study of INCAGN02385 in Select Advanced Malignancies

Posted: May 25th, 2018, 2:00pm GMT

Conditions: Cervical Cancer; Microsatellite Instability (MSI)-High Endometrial Cancer; Gastric Cancer (Including Stomach and Gastroesophageal Junction [GEJ]); Esophageal Cancer; Hepatocellular Carcinoma; Melanoma (Uveal Melanoma Excluded); Merkel Cell Carcinoma; Mesothelioma; MSI-high Colorectal Cancer; Non-small Cell Lung Cancer (NSCLC); Ovarian Cancer; Squamous Cell Carcinoma of the Head and Neck (SCCHN); Small Cell Lung Cancer (SCLC); Renal Cell Carcinoma (RCC); Triple-negative Breast Cancer; Urothelial Carcinoma; Diffuse Large B-cell Lymphoma
Intervention: Biological: INCAGN02385
Sponsor: Incyte Biosciences International Sàrl
Recruiting

Pfizer Immunotherapy Combinations for Acute Myeloid Leukemia (AML) Multi-Arm Study 1

Posted: January 4th, 2018, 3:00pm GMT

Conditions: Recurrent Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia
Interventions: Biological: Anti-OX40 Antibody PF-04518600; Drug: Avelumab; Drug: Azacitidine; Drug: Gemtuzumab Ozogamicin; Drug: Glasdegib; Drug: Venetoclax
Sponsors: M.D. Anderson Cancer Center; Pfizer; National Cancer Institute (NCI)
Recruiting

How Microbes and Metabolism May Predict Skin Cancer Immunotherapy Outcomes

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

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

UCDCC#271: Phase I/II Trial of Epacadostat, Intralesional SD101, Radiotherapy in Patients With Lymphoma

Posted: October 26th, 2017, 2:00pm GMT

Conditions: Advanced Solid Tumors; Lymphoma
Interventions: Drug: epacadostat; Drug: SD-101; Radiation: Radiotherapy
Sponsor: University of California, Davis
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

French National Database of Rare Dermatological Cancers

Posted: July 7th, 2017, 2:00pm GMT

Conditions: Adnexal Tumor of Skin; Merkel Cell Carcinoma; Advanced Basal Cell Carcinoma Requiring Systemic Treatment
Intervention:
Sponsor: University Hospital, Lille
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

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 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

$Permalink for 'Trial of Intratumoral Injections of TTI-621 in Subjects With Relapsed and Refractory Solid Tumors and Mycosis Fungoides'$

Trial of Intratumoral Injections of TTI-621 in Subjects With Relapsed and Refractory Solid Tumors and Mycosis Fungoides

Posted: September 7th, 2016, 2:00pm GMT

Conditions: Solid Tumors; Mycosis Fungoides; Melanoma; Merkel-cell Carcinoma; Squamous Cell Carcinoma; Breast Carcinoma; Human Papillomavirus-Related Malignant Neoplasm; Soft Tissue Sarcoma
Interventions: Drug: TTI-621 Monotherapy; Drug: TTI-621 + PD-1/PD-L1 Inhibitor; Drug: TTI-621 + pegylated interferon-α2a; Other: TTI-621 + T-Vec; Other: TTI-621 + radiation
Sponsor: Trillium Therapeutics Inc.
Recruiting

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Studies of Dermatologic Diseases Biospecimen Acquisition Protocol

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

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

Adjuvant Therapy of Completely Resected Merkel Cell Carcinoma With Immune Checkpoint Blocking Antibodies vs Observation

Posted: July 22nd, 2014, 2:00pm GMT

Condition: Merkel Cell Carcinoma
Intervention: Drug: Nivolumab
Sponsors: Prof. Dr. med. Dirk Schadendorf; Bristol-Myers Squibb
Recruiting

Isolated Limb Perfusion of Melphalan for Melanoma and Sarcoma Treatment

Posted: August 12th, 2013, 2:00pm GMT

Condition: Metastatic Melanoma
Intervention: Drug: Melphalan
Sponsor: International Group of Endovascular Oncology
Recruiting

Clinical Evaluation of 68Ga-NOTA-MAL-Cys39-exendin-4 Positron Emission Tomography in the Detection of Insulinoma

Posted: December 4th, 2019, 3:00pm GMT

Condition: Insulinoma
Intervention: Drug: 68Ga-NOTA-MAL-Cys39-exendin-4
Sponsor: Nanjing First Hospital, Nanjing Medical University
Recruiting

Safety and Efficacy of AK104, a PD-1/CTLA-4 Bispecific Antibody, in Selected Advanced Solid Tumors

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

Conditions: Advaced Solid Tumors; Melanoma
Intervention: Biological: AK104
Sponsors: Akeso; Akeso Pharmaceuticals, Inc.
Not yet 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
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
Not yet 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

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

Posted: November 11th, 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
Sponsors: K-Group Beta; IQVIA Biotech
Recruiting

Developing a Method Using PET-MR to Improve Staging and Monitoring of Neuroendocrine Tumor

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

Condition: Neuroendocrine Tumors
Intervention: Diagnostic Test: PET/MR scan
Sponsor: Tel-Aviv Sourasky Medical Center
Not yet recruiting

Applying PET/MR in Neuroendocrine Tumors - Imaging Dynamic Processes in Both Modalities

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

Condition: Neuroendocrine Tumors
Intervention: Diagnostic Test: PET/MR scan
Sponsor: Tel-Aviv Sourasky Medical Center
Not yet recruiting

Appropriate Dosing to Optimise Personalised Cancer Treatments

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

Conditions: Melanoma Stage III; Melanoma Stage IV; Ovarian Cancer; Renal Cancer Stage III; Renal Cancer Stage IV; Lung Cancer, Non-small Cell
Interventions: Diagnostic Test: Dried blood Spot (DBS); Diagnostic Test: Venous blood sampling
Sponsor: University of Dundee
Not yet recruiting

Study of Pancreatic Neuroendocrine Tumors and Carcinomas in Alsace Region

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

Condition: Pancreatic Neuroendocrine Tumor
Intervention:
Sponsor: University Hospital, Strasbourg, France
Recruiting

Tamoxifen for Well Differentiated Neurodendocrine Tumors and Hormone Receptor Positive Expression

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

Conditions: Neuroendocrine Tumors; Progesterone Receptor Positive Tumor; Estrogen Receptor Positive Tumor
Intervention: Drug: Tamoxifen 20 mg
Sponsor: H. Lee Moffitt Cancer Center and Research Institute
Recruiting

Gene Modified Immune Cells (IL13Ralpha2 CAR T Cells) After Conditioning Regimen for the Treatment of Stage IIIC or IV Melanoma

Posted: October 8th, 2019, 2:00pm GMT

Conditions: Clinical Stage IV Cutaneous Melanoma AJCC v8; IL13RA2 Positive; Metastatic Melanoma; Cutaneous Melanoma, Stage III; Cutaneous Melanoma, Stage IV
Interventions: Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Biological: IL13Ralpha2-specific Hinge-optimized 4-1BB-co-stimulatory CAR/Truncated CD19-expressing Autologous TN/MEM Cells; Drug: Recombinant Interleukin-2
Sponsors: Jonsson Comprehensive Cancer Center; National Cancer Institute (NCI)
Recruiting

Thoracic Epidural Analgesia vs Surgical Site Infiltration With Liposomal Bupivacaine Following Open Gynecologic Surgery

Posted: October 7th, 2019, 2:00pm GMT

Conditions: Surgery; Analgesia
Interventions: Drug: Liposomal bupivacaine; Other: Thoracic epidural analgesia (bupivacaine)
Sponsors: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Pacira Pharmaceuticals, Inc
Not yet recruiting

Communicating With Patients on Cancer Resistance to Treatment: the Development of a Communication Tool. (HECTOR)

Posted: October 7th, 2019, 2:00pm GMT

Conditions: Metastatic Uveal Melanoma; Triple Negative Breast Cancer; Luminal B Breast Cancer; Pediatric Cancer
Interventions: Behavioral: Questionnaires; Behavioral: Semi-structured individual interviews; Other: Focus Group; Other: DELPHI Consensus Method
Sponsor: Institut Curie
Not yet recruiting

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

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

Radioactive Drug (177Lu-DOTATATE) for the Treatment of Locally Advanced, Metastatic, or Unresectable Rare Endocrine Cancers

Posted: September 27th, 2019, 2:00pm GMT

Conditions: Locally Advanced Adrenal Gland Pheochromocytoma; Locally Advanced Paraganglioma; Metastatic Adrenal Gland Pheochromocytoma; Metastatic Paraganglioma; Metastatic Parathyroid Gland Carcinoma; Pituitary Gland Carcinoma; Somatostatin Receptor Positive; Stage III Thyroid Gland Medullary Carcinoma AJCC v8; Stage IV Thyroid Gland Medullary Carcinoma AJCC v8; Stage IVA Thyroid Gland Medullary Carcinoma AJCC v8; Stage IVB Thyroid Gland Medullary Carcinoma AJCC v8; Stage IVC Thyroid Gland Medullary Carcinoma AJCC v8; Unresectable Adrenal Gland Pheochromocytoma; Unresectable Paraganglioma
Intervention: Drug: Lutetium Lu 177 Dotatate
Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI)
Not yet recruiting

Clinico-biological Database in Patients Treated With Metabolic Radiotherapy in the Nuclear Medicine Department

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

Conditions: Thyroid Cancer; Prostate Cancer; Neuroendocrine Tumors
Intervention: Other: Biological collection
Sponsor: Institut du Cancer de Montpellier - Val d'Aurelle
Not yet recruiting

A Non-Interventional Pilot Study to Explore the Skin Microbes in Skin Cancer

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

Conditions: Skin Cancer; Melanoma (Skin); Squamous Cell Carcinoma; Basal Cell Carcinoma; Microbiome
Intervention: Other: Non-interventional
Sponsor: ProgenaBiome
Not yet recruiting

Registry of Subjects at Risk of Pancreatic Cancer

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

Conditions: Familial Pancreatic Cancer; BRCA1 Mutation; BRCA2 Mutation; Lynch Syndrome; FAMMM - Familial Atypical Mole Malignant Melanoma Syndrome; Hereditary Pancreatitis; Peutz-Jeghers Syndrome
Interventions: Radiation: MRCP; Procedure: Endoultrasonography
Sponsor: Associazione Italiana per lo Studio del Pancreas
Recruiting

$Permalink for 'Polarized Dendritic Cell (aDC1) Vaccine, Interferon Alpha-2, Rintalolimid, and Celecoxib for the Treatment of HLA-A2+ Refractory Melanoma'$

Polarized Dendritic Cell (aDC1) Vaccine, Interferon Alpha-2, Rintalolimid, and Celecoxib for the Treatment of HLA-A2+ Refractory Melanoma

Posted: September 18th, 2019, 2:00pm GMT

Conditions: HLA-A2 Positive Cells Present; Refractory Melanoma
Interventions: Biological: Alpha-type-1 Polarized Dendritic Cells; Drug: Celecoxib; Drug: PD-1 Ligand Inhibitor; Drug: PD1 Inhibitor; Biological: Recombinant Interferon Alfa-2b; Drug: Rintatolimod
Sponsors: Roswell Park Cancer Institute; National Cancer Institute (NCI)
Not yet recruiting

Lu-177-DOTATATE (Lutathera) in Combination With Olaparib in Inoperable Gastroenteropancreatico Neuroendocrine Tumors (GEP-NET)

Posted: September 11th, 2019, 2:00pm GMT

Conditions: Gastroenteropancreatico Tumors; Neuroendocrine Tumors; Neuroendocrine Neoplasms
Interventions: Drug: Lu-177-DOTATATE; Drug: Olaparib; Diagnostic Test: Ga dotatate scanning; Diagnostic Test: FDG-PET scanning
Sponsor: National Cancer Institute (NCI)
Not yet recruiting

Image-Enhanced Endoscopy in the Gastrointestinal Tract

Posted: September 11th, 2019, 2:00pm GMT

Conditions: Gastro-Intestinal Disorder; Inflammatory Bowel Diseases; Gastro Esophageal Reflux; Atrophic Gastritis; Neuroendocrine Tumors
Intervention:
Sponsor: King's College Hospital NHS Trust
Recruiting

Immunotherapy Based on Antigen-specific Immune Effector Cells Targeting Neurofibromatosis Type II or Schwannomatosis

Posted: September 11th, 2019, 2:00pm GMT

Condition: Cancer
Intervention: Biological: Antigen-specific T cells CART/CTL and DCvac
Sponsor: Shenzhen Geno-Immune Medical Institute
Recruiting

Physical Activity Intervention Before and After Surgery in Older Adults With Lung Cancer and Their Family Caregivers

Posted: September 11th, 2019, 2:00pm GMT

Conditions: Caregiver; Lobectomy Patient; Lung Carcinoid Tumor; Lung Non-Small Cell Carcinoma
Interventions: Other: E-mail; Behavioral: Exercise Intervention; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Behavioral: Telephone-Based Intervention; Other: Text Message
Sponsors: City of Hope Medical Center; National Cancer Institute (NCI)
Not yet recruiting

68-Ga DOTATATE PET/MRI in the Diagnosis and Management of Somatostatin Receptor Positive CNS Tumors.

Posted: September 9th, 2019, 2:00pm GMT

Conditions: CNS Tumors; Meningioma; Esthesioneuroblastoma; Hemangioblastoma; Medulloblastoma; Paraganglioma; Pituitary Adenoma
Intervention: Diagnostic Test: Ga68-DOTATATE-PET/MRI
Sponsors: Weill Medical College of Cornell University; Novartis Pharmaceuticals
Recruiting

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

Posted: September 5th, 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)
Not yet recruiting

Assessment of a Serious Illness Conversation Guide (SICG) in Advanced Gastro-Intestinal Cancers

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

Conditions: Gastrointestinal Cancer; Colorectal Cancer; Pancreatic Adenocarcinoma; Gastric Cancer; Esophageal Cancer; Cholangiocarcinoma; Hepatocellular Carcinoma; Neuroendocrine Tumors; GIST, Malignant
Interventions: Behavioral: Serious Illness Conversation Guide (SICG); Behavioral: Quality of Life (QOL) survey
Sponsor: Stanford University
Recruiting

Study of ARRY-614 Plus Either Nivolumab or Ipilimumab

Posted: August 30th, 2019, 2:00pm GMT

Conditions: Renal Cell Carcinoma; Melanoma; Solid Tumor
Interventions: Drug: Phase Ib ARRY-614 + nivolumab; Drug: Phase Ib ARRY-614 + ipilimumab; Drug: Phase II ARRY-614 + ipilimumab; Drug: Phase II ARRY-614 + nivolumab (melanoma); Drug: Phase II ARRY-614 + nivolumab (RCC)
Sponsors: Jason J. Luke, MD; Array BioPharma
Not yet recruiting

Natural History and Management of Von Hippel-Lindau (VHL) Associated Pancreatic Neuroendocrine Tumors

Posted: August 29th, 2019, 2:00pm GMT

Conditions: VHL Pancreatic Neuroendocrine Tumors; Von Hippel-Lindau Disease; Neuroendocrine Tumors
Intervention:
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
Not yet 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'

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

Posted: August 27th, 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)
Not yet recruiting

Use of 68Ga-dotatate PET Scan in Neuroendocrine Carcinoma of the GI Tract

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

Condition: Neuroendocrine Carcinoma
Interventions: Drug: 68Ga-DOTATATE; Diagnostic Test: Positron Emission Tomography (PET) Scan
Sponsors: H. Lee Moffitt Cancer Center and Research Institute; Advanced Accelerator Applications
Recruiting

Pharmacogenomics Testing in Directing the Optimal Use of Supportive Care Medications in Patients With Stage III-IV Cancer

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

Conditions: Anatomic Stage III Breast Cancer AJCC v8; Anatomic Stage IIIA Breast Cancer AJCC v8; Anatomic Stage IIIB Breast Cancer AJCC v8; Anatomic Stage IIIC Breast Cancer AJCC v8; Anatomic Stage IV Breast Cancer AJCC v8; Clinical Stage III Cutaneous Melanoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Health Care Provider; Malignant Brain Neoplasm; Malignant Genitourinary System 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 IV Cutaneous Melanoma AJCC v8; Prognostic Stage III Breast Cancer AJCC v8; Prognostic Stage IIIA Breast Cancer AJCC v8; Prognostic Stage IIIB Breast Cancer AJCC v8; Prognostic Stage IIIC Breast Cancer AJCC v8; Prognostic Stage IV Breast Cancer AJCC v8; Stage III Colorectal Cancer AJCC v8; Stage III Ovarian Cancer AJCC v8; Stage III Pancreatic Cancer AJCC v8; Stage III Prostate Cancer AJCC v8; Stage IIIA Colorectal Cancer AJCC v8; Stage IIIA Ovarian Cancer AJCC v8; Stage IIIA Prostate Cancer AJCC v8; Stage IIIB Colorectal Cancer AJCC v8; Stage IIIB Ovarian Cancer AJCC v8; Stage IIIB Prostate Cancer AJCC v8; Stage IIIC Colorectal Cancer AJCC v8; Stage IIIC Ovarian Cancer AJCC v8; Stage IIIC Prostate Cancer AJCC v8; Stage IV Colorectal Cancer AJCC v8; Stage IV Ovarian Cancer AJCC v8; Stage IV Pancreatic Cancer AJCC v8; Stage IV Prostate Cancer AJCC v8; Stage IVA Colorectal Cancer AJCC v8; Stage IVA Ovarian Cancer AJCC v8; Stage IVA Pancreatic Cancer; Stage IVA Prostate Cancer AJCC v8; Stage IVB Colorectal Cancer AJCC v8; Stage IVB Ovarian Cancer AJCC v8; Stage IVB Pancreatic Cancer; Stage IVB Prostate Cancer AJCC v8; Stage IVC Colorectal Cancer AJCC v8
Interventions: Procedure: Biospecimen Collection; Other: Genetic Testing; Other: Quality-of-Life Assessment; Other: Questionnaire Administration
Sponsors: Mayo Clinic; National Cancer Institute (NCI)
Recruiting

Resection of Metastatic Pancreatic Neuroendocrine Tumors After Induction System Treatment

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

Conditions: Neuroendocrine Tumors; Metastases; Surgery
Interventions: Procedure: system treatment and surgery; Other: system treatment
Sponsor: Fudan University
Recruiting

Permalink for 'Lanreotide Combined With Telotristat Ethyl or Placebo for the First-line Treatment in Patients With Advanced Well Differentiated Small Intestinal Neuroendocrine Tumours (siNET) With Highly-functioning Carcinoid Syndrome'

Lanreotide Combined With Telotristat Ethyl or Placebo for the First-line Treatment in Patients With Advanced Well Differentiated Small Intestinal Neuroendocrine Tumours (siNET) With Highly-functioning Carcinoid Syndrome

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

Conditions: Small Intestinal NET; Carcinoid Heart Disease
Interventions: Drug: Telotristat Ethyl; Drug: Lanreotide
Sponsors: European Organisation for Research and Treatment of Cancer - EORTC; Ipsen
Not yet recruiting

Intra-Peritoneal Local Anaesthetics in Ovarian Cancer

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

Condition: Ovarian Cancer
Interventions: Drug: Ropivacaine; Drug: Saline Solution
Sponsors: Karolinska Institutet; Karolinska University Hospital
Not yet 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

Study of the Diagnostic Value of Hybrid PET/MR and PET/CT in Neuroendocrine Diseases and Tumor Induced Osteomalacia

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

Conditions: PET / CT; PET / MR; Neuroendocrine Tumors; Osteomalacia
Intervention: Device: 68Ga-DOTA-TATE PET/MR and PET/CT imaging
Sponsor: Wuhan Union Hospital, China
Recruiting

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

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

Condition: Advanced Solid Tumors
Intervention: Drug: FF-10850 Topotecan Liposome Injection
Sponsor: Fujifilm Pharmaceuticals U.S.A., Inc.
Not yet recruiting

ADP-A2M4CD8 in HLA-A2+ Subjects With MAGE-A4 Positive Tumors

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

Conditions: Synovial Sarcoma; Myxoid/Round Cell Liposarcoma (MRCLS); Melanoma; Urothelial Carcinoma; Head and Neck; Ovarian; Gastric Cancer; Esophagogastric Junction Disorder; Nonsmall Cell Lung Cancer; Esophageal Cancer
Intervention: Genetic: Autologous genetically modified ADP-A2M4CD8 cells
Sponsor: Adaptimmune
Recruiting

TAS-102 in Extrapulmonary Neuroendocrine Carcinoma

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

Condition: High-grade Extra Pulmonary Neuroendocrine Cancer
Intervention: Drug: All patients- TAS-102
Sponsors: Baylor Research Institute; Taiho Oncology, Inc.
Not yet recruiting

68Ga-DOTATATE PET-CTA Imaging for the Early Detection of Progressing Coronary Atherosclerosis

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

Condition: Coronary Arteriosclerosis
Intervention: Drug: injection of 68Ga-DOTATATE
Sponsor: Assistance Publique - Hôpitaux de Paris
Not yet recruiting

A Study of SGN-CD228A in Advanced Solid Tumors

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

Conditions: Cutaneous Melanoma; Pleural Mesothelioma; Breast Cancer; Non-small Cell Lung Cancer; Colorectal Cancer; Pancreatic Ductal Adenocarcinoma
Intervention: Drug: SGN-CD228A
Sponsor: Seattle Genetics, Inc.
Not yet recruiting

68Ga-DOTATATE PET/CT in Neuroendocrine Tumor

Posted: August 1st, 2019, 2:00pm GMT

Condition: Neuroendocrine Tumors
Intervention: Drug: 68Ga-DOTATATE
Sponsor: Peking Union Medical College Hospital
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)
Not yet recruiting

Improving Skin Cancer Management With Artificial Intelligence (04.17 SMARTI)

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

Conditions: Skin Cancer; Melanoma (Skin)
Intervention: Device: Molemap Skin Cancer Triage Artificial Intelligence Device
Sponsors: Melanoma and Skin Cancer Trials Limited; Molemap Australia Pty Ltd; Monash University, Melbourne
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: Testing: Genome; Diagnostic Test: Testing: Transcriptome; Diagnostic Test: Testing: Proteome; Drug: Treatment: CAR-T
Sponsor: Taproot Health
Not yet recruiting

Genetic Predictors of Efficiency and Safety of ICIs in Patients With Different Malignancies (ICIPRESIST-0519)

Posted: July 18th, 2019, 2:00pm GMT

Conditions: Melanoma; Squamous Cell Lung Cancer; Uveal Melanoma; Hodgkin Lymphoma
Intervention: Genetic: Genetic tests of the available tumor and plasma samples
Sponsor: Russian Academy of Medical Sciences
Recruiting

Dynamic Whole Body Positron Emission Tomography/Computed Tomography Imaging

Posted: July 12th, 2019, 2:00pm GMT

Conditions: Neuroendocrine Tumors; Prostate Cancer; Prostatic Neoplasms; Carcinoid Tumor; Paraganglioma; Neuroblastoma
Interventions: Diagnostic Test: 18F-FDG PET/CT; Diagnostic Test: 68Ga-DOTATOC PET/CT; Diagnostic Test: 18F-DCFPyL PET/CT
Sponsor: British Columbia Cancer Agency
Not yet recruiting

Sonidegib and Pembrolizumab in Treating Patients With Advanced Solid Tumors

Posted: July 3rd, 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)
Not yet recruiting

Permalink for 'A Phase II Trial of Neoadjuvant Treatment With PD-1 Inhibition (Nivolumab) With or Without IDO Inhibition (BMS-986205) and With or Without CTLA-4 Inhibition (Ipilimumab) in Resectable Stage III or IV Melanoma'

A Phase II Trial of Neoadjuvant Treatment With PD-1 Inhibition (Nivolumab) With or Without IDO Inhibition (BMS-986205) and With or Without CTLA-4 Inhibition (Ipilimumab) in Resectable Stage III or IV Melanoma

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

Conditions: Melanoma Stage III; Melanoma Stage IV
Interventions: Drug: Nivolumab; Drug: BMS-986205; Drug: Ipilimumab
Sponsors: Dana-Farber Cancer Institute; Bristol-Myers Squibb
Recruiting

Efficacy of metfOrmin in PrevenTIng Glucocorticoid-induced Diabetes in Patients With Brain Metastases

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

Conditions: Brain Metastases; Melanoma; Lung Cancer; Breast Cancer
Interventions: Drug: Dexamethasone; Drug: Metformin
Sponsors: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano; University of Milan
Recruiting

3TMPO (Triple-Tracer Strategy Against Metastatic Prostate Cancer

Posted: June 27th, 2019, 2:00pm GMT

Condition: Metastatic Castration-resistant Prostate Cancer
Interventions: Diagnostic Test: FDG Positron emission tomography (PET) scan; Diagnostic Test: PSMA Positron emission tomography (PET) scan; Diagnostic Test: OCTREOTATE Positron emission tomography (PET) scan; Other: Optional Bone or soft-tissue biopsies
Sponsors: Université de Sherbrooke; Fonds de la Recherche en Santé du Québec; Oncopole; Canadian Cancer Society Research Institute (CCSRI); Merck Canada Inc.
Not yet recruiting

Safety and Efficacy of FOLFSIM Plus Toripalimab in the Treatment of Advanced or Metastatic Neuroendocrine Carcinoma

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

Condition: Neuroendocrine Carcinoma of the Bladder
Interventions: Drug: Simmtecan, 5-FU and l-LV; Drug: Toripalimab; Drug: Etoposide, Cisplatin; Drug: Etoposide, Carboplatin
Sponsor: Peking University
Recruiting

Adoptive Cell Transfer of Autologous Tumor Infiltrating Lymphocytes and High-Dose Interleukin 2 in Select Solid Tumors

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

Conditions: Metastatic Melanoma; Locally Advanced Refractory/Recurrent Melanoma; Metastatic Head and Neck Cancer; Locally Advanced Refractory/Recurrent Head and Neck Cancer
Interventions: Biological: Autologous Tumor Infiltrating Lymphocytes; Biological: High-Dose Interleukin 2
Sponsors: Gregory Daniels; Immunotherapy Foundation
Not yet recruiting

A Study of Infusion of Autologous Melanoma Lysate Pulsed Dendritic Cells With Dengue Virus-1 #45AZ5 in Advanced Melanoma

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

Condition: Stage III and IV Melanoma
Interventions: Biological: Dengue-1 #45AZ5 virus; Biological: Autologous melanoma lysate pulsed dendritic cells
Sponsors: PrimeVax Immuno-Oncology Inc.; Advocate Lutheran General Hospital; Walter Reed Army Institute of Research (WRAIR)
Not yet recruiting

Cryoablation of Bone Metastases From Endocrine Tumors

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

Conditions: Neoplasm Metastasis; Thyroid Neoplasm; Pheochromocytoma; Adrenal Neoplasm; Neuroendocrine Tumors; Bone Metastases
Intervention: Device: cryoablation
Sponsors: Instituto do Cancer do Estado de São Paulo; University of Sao Paulo General Hospital
Recruiting

Endoscopic Treatment of Rectal Neuroendocrine Tumor(NET) Less Than 10mm

Posted: June 11th, 2019, 2:00pm GMT

Condition: Rectal Neuroendocrine Tumor
Interventions: Procedure: ESD procedure; Procedure: EMR-C procedure
Sponsor: Nanfang Hospital of Southern Medical University
Not yet recruiting

Permalink for 'Binimetinib and Palbociclib or TAS-102 in Treating Patients With KRAS and NRAS Mutant Metastatic or Unresectable Colorectal Cancer'

Binimetinib and Palbociclib or TAS-102 in Treating Patients With KRAS and NRAS Mutant Metastatic or Unresectable Colorectal Cancer

Posted: June 11th, 2019, 2:00pm GMT

Conditions: KRAS Gene Mutation; Metastatic Colorectal Carcinoma; NRAS Gene Mutation; Stage III Colorectal Cancer AJCC v8; Stage IIIA Colorectal Neuroendocrine Tumor AJCC v8; Stage IIIB Colorectal Cancer AJCC v8; Stage IIIC Colorectal Cancer AJCC v8; Stage IV Colorectal Cancer AJCC v8; Stage IVA Colorectal Cancer AJCC v8; Stage IVB Colorectal Cancer AJCC v8; Stage IVC Colorectal Cancer AJCC v8; Unresectable Carcinoma
Interventions: Drug: Binimetinib; Drug: Palbociclib; Drug: Trifluridine and Tipiracil Hydrochloride
Sponsors: Academic and Community Cancer Research United; National Cancer Institute (NCI)
Recruiting

PDR001 + Panobinostat for Melanoma and NSCLC

Posted: June 11th, 2019, 2:00pm GMT

Conditions: Melanoma; Non Small Cell Lung Cancer
Interventions: Drug: PDR001; Drug: Panobinostat
Sponsors: Muhammad Furqan; Novartis Pharmaceuticals
Not yet 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
Not yet recruiting

Study to Evaluate the Efficacy and Safety of Lutathera in Patients With Grade 2 and Grade 3 Advanced GEP-NET

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

Condition: Gastro-enteropancreatic Neuroendocrine Tumor
Interventions: Drug: Lutathera; Drug: long-acting octreotide; Drug: high dose long-acting octreotide
Sponsor: Advanced Accelerator Applications
Not yet recruiting

CT Radiomic Features of Pancreatic Neuroendocrine Neoplasms

Posted: May 30th, 2019, 2:00pm GMT

Condition: Pancreatic Neuroendocrine Tumor
Intervention: Other: CT radiomic feature evaluation
Sponsor: Francesco De Cobelli
Recruiting

Etoposide/Cisplatin Compared With Irinotecan/Cisplatin for Advanced Gastrointestinal Neuroendocrine Tumor G3 Type

Posted: May 24th, 2019, 2:00pm GMT

Condition: Gastrointestinal Neuroendocrine Tumor
Interventions: Drug: Etoposide; Drug: Irinotecan
Sponsor: Henan Cancer Hospital
Not yet recruiting

IT-hu14.18-IL2 With Radiation, Nivolumab and Ipilimumab for Melanoma

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

Condition: Melanoma
Interventions: Biological: hu14.18-IL2; Radiation: Radiation Therapy; Biological: Nivolumab; Biological: Ipilimumab
Sponsors: University of Wisconsin, Madison; National Cancer Institute (NCI); Bristol-Myers Squibb; Apeiron Biologics; Provenance Biopharmaceuticals
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

Lanreotide 120mg Effectiveness in Subjects With Pancreatic Neuroendocrine Tumours (PanNET) in Routine Clinical Practice.

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

Condition: Pancreatic Neuroendocrine Tumor
Intervention:
Sponsor: Ipsen
Recruiting

A Phase 1/2 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

Phase III Trial to Evaluate the Efficacy and Safety of JS001 Combined With Axitinib for Advanced Mucosal Melanoma

Posted: May 8th, 2019, 2:00pm GMT

Condition: Advanced Mucosal Melanoma
Interventions: Biological: JS001(Toripalimab Injection); Drug: Axitinib 1 MG [Inlyta]; Other: JS001 and Axitinib
Sponsor: Beijing Cancer Hospital
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

Diagnostic Accuracy of Preoperative Diagnostic Procedure in the Assessment of Lymph Node Metastases by NF-PanNENs

Posted: April 18th, 2019, 2:00pm GMT

Condition: Non Functioning Pancreatic Endocrine Tumor
Intervention:
Sponsor: IRCCS San Raffaele
Recruiting

Nab-PCE vs PC for MM After Failure of Anti-PD-1

Posted: April 16th, 2019, 2:00pm GMT

Condition: Advanced Melanoma
Interventions: Drug: Chemotherapeutic Combinations; Drug: chemotherapy
Sponsor: Beijing Cancer Hospital
Recruiting

A Trial of BXCL701 and Pembrolizumab in Patients With Small Cell Neuroendocrine Prostate Cancer

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

Conditions: Prostate Cancer; Neuroendocrine Tumors; Small Cell Carcinoma
Intervention: Drug: Talabostat Mesylate plus Pembrolizumab
Sponsor: BioXcel Therapeutics Inc
Recruiting

Expanded Access for the Treatment of Cancers With Rearranged During Transfection (RET) Activation

Posted: April 8th, 2019, 2:00pm GMT

Conditions: Non Small Cell Lung Cancer; Medullary Thyroid Cancer; Colon Cancer; Breast Cancer; Pancreatic Cancer; Papillary Thyroid Cancer; Other Solid Tumors With Evidence of Activating RET Alteration
Intervention: Drug: LOXO-292
Sponsors: Loxo Oncology, Inc.; Eli Lilly and Company
Available

Antiandrogen Therapy and SBRT in Treating Patients With Recurrent, Metastatic Prostate Cancer

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

Conditions: Metastatic Prostate Adenocarcinoma; Prostate Adenocarcinoma With Focal Neuroendocrine Differentiation; Recurrent Prostate Carcinoma; Stage IVB Prostate Cancer AJCC v8
Interventions: Drug: Abiraterone Acetate; Drug: Apalutamide; Drug: Leuprolide Acetate; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Radiation: Stereotactic Body Radiation Therapy
Sponsors: Jonsson Comprehensive Cancer Center; National Cancer Institute (NCI)
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

High-Risk Skin Cancers With Atezolizumab Plus NT-I7

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

A Study of Oral LOXO-292 in Pediatric Patients With Advanced Solid or Primary Central Nervous System Tumors

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

Conditions: Medullary Thyroid Cancer; Infantile Myofibromatosis; Infantile Fibrosarcoma; Papillary Thyroid Cancer; Soft Tissue Sarcoma
Intervention: Drug: LOXO-292
Sponsor: Loxo Oncology, Inc.
Recruiting

Permalink for 'The PIONEER Initiative: Precision Insights On N-of-1 Ex Vivo Effectiveness Research Based on Individual Tumor Ownership (Precision Oncology)'

The PIONEER Initiative: Precision Insights On N-of-1 Ex Vivo Effectiveness Research Based on Individual Tumor Ownership (Precision Oncology)

Posted: April 1st, 2019, 2:00pm GMT

Conditions: Cancer, All Types; Cancer of Liver; Cancer of Stomach; Cancer of Head and Neck; Cancer of Rectum; Cancer of Kidney; Cancer of Esophagus; Cancer of Colon; Cancer Skin; Cancer of Cervix; Cancer, Metastatic; Cancer of Larynx; Cancer of Neck; Cancer of Lung; Cancer of Brain and Nervous System; Cancer of Vulva, Disseminated; Cancer of Pancreas; Sarcoma; GIST; Small-cell Lung Cancer; Adenocarcinoma Lung; Cancer of Prostate; Cancer, Advanced; Adrenal Cancer; Testicular Cancer; Uterine Cancer; Bronchoalveolar Cell Lung Cancer; Cancer Unknown Primary; Glioblastoma Multiforme; Oligodendroglioma; Breast Cancer; Renal Cell Carcinoma; Hepatocellular Carcinoma; Cholangiocarcinoma; Squamous Cell Carcinoma; Transitional Cell Carcinoma; Cancer, Other; Cancer, Anal; Melanoma; Cancer, Bile Duct; Cancer, Bladder; Cancer Cords Vocal; Cancers Cell Neuroendocrine; Cancer Differentiated Poorly; Cancer, Anaplastic Thyroid
Intervention:
Sponsors: SpeciCare; Dana-Farber Cancer Institute; Kalispell Regional Medical Center; Georgia Institute of Technology; Ontario Institute for Cancer Research; SEngine Precision Medicine; Helomics
Recruiting

Permalink for 'An Efficacy Study of Adjuvant Treatment With the Personalized Cancer Vaccine mRNA-4157 and Pembrolizumab in Patients With High-Risk Melanoma (KEYNOTE-942)'

An Efficacy Study of Adjuvant Treatment With the Personalized Cancer Vaccine mRNA-4157 and Pembrolizumab in Patients With High-Risk Melanoma (KEYNOTE-942)

Posted: April 1st, 2019, 2:00pm GMT

Condition: Melanoma
Interventions: Biological: mRNA-4157; Biological: Pembrolizumab
Sponsors: ModernaTX, Inc.; Merck Sharp & Dohme Corp.
Recruiting

Permalink for 'Prospective Noninterventional Study to Assess the Use of Lanreotide Autogel® 120 mg in Patients With Locally Advanced or Metastatic Gastroenteropancreatic Neuroendocrine Tumours (GEP-NETs) in Routine Clinical Practice'

Prospective Noninterventional Study to Assess the Use of Lanreotide Autogel® 120 mg in Patients With Locally Advanced or Metastatic Gastroenteropancreatic Neuroendocrine Tumours (GEP-NETs) in Routine Clinical Practice

Posted: March 29th, 2019, 2:00pm GMT

Condition: Neuroendocrine Tumors
Intervention:
Sponsor: Ipsen
Not yet recruiting

$Permalink for 'Abemaciclib in Treating Patients With Advanced, Refractory, and Unresectable Digestive System Neuroendocrine Tumors'$

Abemaciclib in Treating Patients With Advanced, Refractory, and Unresectable Digestive System Neuroendocrine Tumors

Posted: March 27th, 2019, 2:00pm GMT

Conditions: Advanced Digestive System Neuroendocrine Neoplasm; Digestive System Neuroendocrine Tumor; Foregut Carcinoid Tumor; Hindgut Carcinoid Tumor; Locally Advanced Unresectable Digestive System Neuroendocrine Neoplasm; Metastatic Digestive System Neuroendocrine Neoplasm; Midgut Carcinoid Tumor; Pancreatic Neuroendocrine Tumor; Refractory Digestive System Neuroendocrine Neoplasm
Intervention: Drug: Abemaciclib
Sponsors: University of Washington; National Cancer Institute (NCI)
Recruiting

Permalink for 'Patient Decision Aid in Supporting Decision-Making About When to Start or Stop New Drugs, Join Clinical Trials, or Continue Active Surveillance in Patients With Medullary Thyroid Cancer and Their Caregivers'

Patient Decision Aid in Supporting Decision-Making About When to Start or Stop New Drugs, Join Clinical Trials, or Continue Active Surveillance in Patients With Medullary Thyroid Cancer and Their Caregivers

Posted: March 27th, 2019, 2:00pm GMT

Conditions: Cancer Survivor; Caregiver; Family Member; Health Care Provider; Thyroid Gland Medullary Carcinoma
Interventions: Other: Decision Aid; Other: Questionnaire Administration
Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI)
Recruiting

Study of Safety and Efficacy of DKY709 Alone or in Combination With PDR001 in Patients With Advanced Solid Tumors.

Posted: March 27th, 2019, 2:00pm GMT

Conditions: Carcinoma, Non-Small-Cell Lung; Melanoma; Nasopharyngeal Carcinoma; Microsatellite Stable Colorectal Cancer; Triple Negative Breast Cancer
Interventions: Drug: DKY709; Drug: PDR001
Sponsor: Novartis Pharmaceuticals
Recruiting

Al18F-NOTA-octreotide PET Imaging of the Somatostatin Receptor in Neuroendocrine Tumors

Posted: March 21st, 2019, 2:00pm GMT

Condition: Neuroendocrine Tumors
Interventions: Drug: Al18F-NOTA-octreotide; Device: PET/CT; Other: Venous blood samples
Sponsor: Universitaire Ziekenhuizen Leuven
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

DEBOXA for Inoperable NET Liver Metastases

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

Conditions: Neuroendocrine Tumors; Neoplasm Metastasis; Liver
Intervention: Procedure: D-TACE using CalliSpheres and Oxaliplatin
Sponsor: Xiangya Hospital of Central South University
Recruiting

68Ga-DOTATATE PET for Management of Neuroendocrine Tumors

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

Condition: Neuroendocrine Tumors
Intervention: Diagnostic Test: 68Ga -DOTATATE PET scans
Sponsor: University Health Network, Toronto
Recruiting

Low Dose Ipilimumab With Pembrolizumab in Treating Patients With Melanoma That Has Spread to the Brain

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

Conditions: Clinical Stage IV Cutaneous Melanoma AJCC v8; Metastatic Malignant Neoplasm in the Brain; Metastatic Melanoma; Pathologic Stage IV Cutaneous Melanoma AJCC v8
Interventions: Biological: Ipilimumab; Biological: Pembrolizumab
Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI)
Recruiting

Study of Tamoxifen in Well Differentiated Neuroendocrine Tumors and Hormone Receptor Positive Expression

Posted: March 12th, 2019, 2:00pm GMT

Conditions: Neuroendocrine Tumors; Progesterone Receptor Positive Tumor; Estrogen Receptor Positive Tumor
Intervention: Drug: Tamoxifen
Sponsor: AC Camargo Cancer Center
Recruiting

Cabozantinib S-Malate, Nivolumab, and Ipilimumab in Treating Patients With Metastatic Genitourinary Tumors

Posted: March 7th, 2019, 3:00pm GMT

Conditions: Bladder Adenocarcinoma; Bladder Mixed Adenocarcinoma; Bladder Small Cell Carcinoma; Bladder Squamous Cell Carcinoma; Chromophobe Renal Cell Carcinoma; Infiltrating Bladder Lymphoepithelioma-Like Carcinoma; Infiltrating Bladder Urothelial Carcinoma; Infiltrating Bladder Urothelial Carcinoma With Giant Cells; Infiltrating Bladder Urothelial Carcinoma, Nested Variant; Infiltrating Bladder Urothelial Carcinoma, Plasmacytoid Variant; Infiltrating Bladder Urothelial Carcinoma, Sarcomatoid Variant; Kidney Medullary Carcinoma; Large Cell Neuroendocrine Carcinoma; Metastatic Bladder Carcinoma; Metastatic Bladder Large Cell Neuroendocrine Carcinoma; Metastatic Bladder Small Cell Carcinoma; Metastatic Bladder Squamous Cell Carcinoma; Metastatic Infiltrating Bladder Urothelial Carcinoma, Clear Cell Variant; Metastatic Infiltrating Bladder Urothelial Carcinoma, Lipid-Rich Variant; Metastatic Infiltrating Bladder Urothelial Carcinoma, Micropapillary Variant; Metastatic Infiltrating Bladder Urothelial Carcinoma, Plasmacytoid Variant; Metastatic Infiltrating Bladder Urothelial Carcinoma, Sarcomatoid Variant; Metastatic Kidney Medullary Carcinoma; Metastatic Malignant Genitourinary System Neoplasm; Metastatic Penile Carcinoma; Metastatic Prostate Small Cell Carcinoma; Metastatic Sarcomatoid Renal Cell Carcinoma; Papillary Renal Cell Carcinoma; Sarcomatoid Renal Cell Carcinoma; Stage IV Bladder Cancer AJCC v8; Stage IV Penile Cancer AJCC v8; Stage IV Prostate Cancer AJCC v8; Stage IV Renal Cell Cancer AJCC v8; Stage IVA Bladder Cancer AJCC v8; Stage IVA Prostate Cancer AJCC v8; Stage IVB Bladder Cancer AJCC v8; Stage IVB Prostate Cancer AJCC v8; Testicular Leydig Cell Tumor; Testicular Sertoli Cell Tumor
Interventions: Drug: Cabozantinib; Drug: Cabozantinib S-malate; Biological: Ipilimumab; Biological: Nivolumab
Sponsor: 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: Array BioPharma; Pierre Fabre Laboratories
Recruiting

The Lyon Real World Evidence in Metastatic NeuroEndocrine Tumours

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

Conditions: Gastro-enteropancreatic Neuroendocrine Tumor; Health Care Costs; Metastatic Cancer
Intervention: Other: Metastatic gastroenteropancreatic and lung neuroendocrine tumors
Sponsor: Hospices Civils de Lyon
Recruiting

Inhaled Essential Oil Effect on Common QOL Concerns During Cancer Treatment

Posted: March 1st, 2019, 3:00pm GMT

Conditions: Gastrointestinal Cancer; Neuroendocrine Carcinoma; Melanoma
Interventions: Procedure: Aromatherapy and Essential Oils; Other: Subject Diary
Sponsors: Ohio State University Comprehensive Cancer Center; National Cancer Institute (NCI)
Recruiting

TTF1-positive Papillary Epithelial Tumor of Pituitary: An Epithelial Variant of Pituicytoma?

Fetched: December 8th, 2019, 5:01am GMT

TTF1-positive Papillary Epithelial Tumor of Pituitary: An Epithelial Variant of Pituicytoma?

Appl Immunohistochem Mol Morphol. 2020 Jan;28(1):e1-e5

Authors: Chatterjee D, Lath K, Radotra BD, Gupta AK, Singh P

Abstract
Low-grade epithelial tumor of pituitary region with dominant papillary architecture is extremely rare. We describe a case of 20-year female who had a recurrent nonfunctioning pituitary tumor. Histologic examination revealed a low-grade epithelial tumor with predominant papillary architecture, lined by cuboidal to columnar epithelial cells. The tumor cells were immunpositive for cytokeratin (CK), CK7, epithelial membrane antigen, carcinoembryonic antigen and showed diffuse and strong nuclear positivity for thyroid transcription factor 1. They were negative for neuroendocrine markers and pituitary hormones. Ki-67 proliferation index was low (1%). Ultrastructural examination revealed presence of microvilli, intercellular tight junctions, and keratin filaments within the tumor cells and lack of neurosecretory granules. No lesion was identified in thyroid or lung on systemic evaluation. On the basis of the morphology, immunophenotype, ultrastructural findings, and diffuse thyroid transcription factor 1 positivity, this tumor may represent an epithelial variant of pituicytoma with dominant papillary architecture. This type of differentiation is extremely rare, and to the best of our knowledge, has not been described previously in the literature.

PMID: 31809313 [PubMed - in process]

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

Fetched: December 8th, 2019, 5:01am GMT

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

Am J Dermatopathol. 2019 Dec 03;:

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

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

PMID: 31809272 [PubMed - as supplied by publisher]

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

Fetched: December 8th, 2019, 5:01am GMT

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

Endocr Pathol. 2019 Dec 05;:

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

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

PMID: 31808008 [PubMed - as supplied by publisher]

Permalink for 'Value of computed tomography evaluation in pathologic classification and prognosis prediction of gastric neuroendocrine tumors.'

Value of computed tomography evaluation in pathologic classification and prognosis prediction of gastric neuroendocrine tumors.

Fetched: December 8th, 2019, 5:01am GMT

Value of computed tomography evaluation in pathologic classification and prognosis prediction of gastric neuroendocrine tumors.

Ann Transl Med. 2019 Oct;7(20):545

Authors: Yan S, Liu T, Li Y, Zhu Y, Jiang J, Jiang L, Zhao H

Abstract
Background: The study aims to investigate the correlation of CT characteristics with pathological classifications and the prognostic value of CT features in patients with gastric neuroendocrine neoplasms (g-NENs).
Methods: Ninety-one cases of pathologically diagnosed g-NENs, including 15 cases of well-differentiated neuroendocrine tumors (NETs) (G1 and G2) and 76 cases of poor-differentiated neuroendocrine carcinomas (NECs) (G3 and MANEC) were retrospectively studied. All cases were included in correlation analysis of CT characteristics with pathologic grades. Among them, 76 patients who had fulfilled follow-up data were included for overall survival (OS) and disease-free survival (DFS) analysis.
Results: CT characteristics that favor poor differentiation include tumor location (fundus and cardia), larger tumor size (>3.0 cm), infiltrative growth, unclear tumor margin, serosa involvement, ulceration and lymph node metastasis (P<0.05). Most variables had sensitivities >80% and specificities >60% to distinguish NECs from NETs. Through log-rank analysis, it was revealed that serosa involvement, cystic degeneration, necrosis, heterogeneous enhancement and lymph node metastasis led to worse DFS and OS for patients with g-NENs (P<0.05). COX regression analysis showed that serosa involvement and lymph node metastasis were independent risk factor for DFS and OS, respectively, despite of grading, staging and therapeutic choices (P<0.05). Moreover, high Ki-67 index (>55%) in G3 g-NENs is in correlation with serosa involvement and lymph node metastasis; accordingly, patients with higher Ki-67 index had worse 1-year DFS (61.7% vs. 92.3%; P<0.05).
Conclusions: CT characteristics can be useful discriminators and prognostic factors for g-NENs and may help identify G3 g-NEC from G3 g-NEN by revealing its poor differentiation and high invasive potential.

PMID: 31807527 [PubMed]

Diarrhea: a missed D in the 4D glucagonoma syndrome.

Fetched: December 8th, 2019, 5:01am GMT

Diarrhea: a missed D in the 4D glucagonoma syndrome.

Autops Case Rep. 2019 Oct-Dec;9(4):e2019129

Authors: Cunha-Silva M, da Costa JG, Faria GAS, Massuda JY, Cintra ML, da Costa LBE, Assad VM, de Ataíde EC, Mazo DFC, Sevá-Pereira T

Abstract
Glucagonoma is a rare and slow-growing pancreatic tumor that usually manifests as glucagonoma syndrome. It is mainly characterized by a typical Dermatosis named necrolytic migratory erythema (NME), Diabetes and glucagon oversecretion. Deep vein thrombosis and Depression complete this set. We report the case of an advanced glucagonoma with liver spread, where all these 4D symptoms occurred but a chronic secretory Diarrhea was the most relevant feature. A 65-year-old man was referred to our center to investigate multiple hepatic nodules evidenced by abdominal tomography. He had a recent diagnosis of diabetes and complained of significant weight loss (25 kg), crusted skin lesions and episodes of a large amount of liquid diarrhea during the past 6 months. On admission, there were erythematous plaques and crusted erosions on his face, back and limbs, plus angular cheilitis and atrophic glossitis. The typical skin manifestation promptly led dermatologists to suspect glucagonoma as the source of our patient's symptoms. A contrast-enhanced abdominal computed tomography showed a hypervascularized pancreatic lesion and multiple hepatic nodules also hypervascularized in the arterial phase. Despite initial improvement of diarrhea after subcutaneous octreotide, the patient's impaired nutritional status limited other therapeutic approaches and he died of respiratory failure due to sepsis. His high levels of serum glucagon were not yet available so we performed an autopsy, confirming the diagnosis of metastatic glucagonoma with NME on histology. Chronic diarrhea is not a common feature in glucagonoma syndrome; however, its severity can lead to serious nutritional impairment and set a poor outcome.

PMID: 31807436 [PubMed]

Diagnostic imaging of gastrointestinal neuroendocrine neoplasms with a focus on ultrasound.

Fetched: December 8th, 2019, 5:01am GMT

Diagnostic imaging of gastrointestinal neuroendocrine neoplasms with a focus on ultrasound.

J Ultrason. 2019 Nov;19(78):228-235

Authors: Walczyk J, Sowa-Staszczak A

Abstract
The diagnosis of gastrointestinal neuroendocrine neoplasms represents a significant diagnostic challenge since these tumours have a various, often non-specific clinical presentation. Currently, more than half of gastroenteropancreatic neuroendocrine neoplasms are detected incidentally, usually during surgery, diagnostic imaging studies or endoscopic procedures performed for other indications. Sometimes the first symptom of the disease is the presence of metastatic lesions in the liver. A neuroendocrine tumour is diagnosed based on the clinical presentation, assessment of specific and non-specific biochemical markers, imaging studies and histopathological examination. Focal lesions, both primary and metastatic may be small and often have an atypical location. Diagnostic imaging of neuroendocrine tumours is of fundamental importance for determining the location of the primary lesion, staging of the disease, selection of treatment and monitoring of its effects. In addition, diagnostic imaging make it possible not only to detect tumours, but also to perform therapeutic procedures based on the result. Transabdominal ultrasound is one of the first diagnostic imaging method for neuroendocrine neoplasms. New ultrasound techniques such as ultrasound elastography, contrast-enhanced ultrasound, endoscopic ultrasound, intraductal and intraoperative ultrasound improve the efficacy of ultrasound examination. Endoscopic ultrasound is a fundamental diagnostic tool for the detection of neuroendocrine tumours of the pancreas and the distal part of the colon. Due to the large variety of neuroendocrine tumours and differences in tumour biology, clinical stage and expression of somatostatin receptors, no single imaging method is sufficient; therefore, in order to determine the right diagnosis and select the best treatment, it is recommended that a combined morphological and functional assessment be used.

PMID: 31807329 [PubMed]

Permalink for 'Inflammation-based index and 68Ga-DOTATOC PET-derived uptake and volumetric parameters predict outcome in neuroendocrine tumor patients treated with 90Y-DOTATOC.'

Inflammation-based index and 68Ga-DOTATOC PET-derived uptake and volumetric parameters predict outcome in neuroendocrine tumor patients treated with 90Y-DOTATOC.

Fetched: December 8th, 2019, 5:01am GMT

Inflammation-based index and 68Ga-DOTATOC PET-derived uptake and volumetric parameters predict outcome in neuroendocrine tumor patients treated with 90Y-DOTATOC.

J Nucl Med. 2019 Dec 05;:

Authors: Pauwels E, Van Binnebeek S, Vandecaveye V, Baete K, Vanbilloen H, Koole M, Mottaghy FM, Haustermans K, Clement PM, Nackaerts K, Van Cutsem E, Verslype C, Deroose CM

Abstract
We performed post-hoc analyses on the utility of pre-therapeutic and early interim 68Ga-DOTA-Tyr3-octreotide (68Ga-DOTATOC) positron emission tomography (PET) tumor uptake and volumetric parameters and a recently proposed biomarker, the inflammation-based index (IBI), for peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumor (NET) patients treated with 90Y-DOTATOC in the setting of a prospective phase II trial. Methods: Forty-three NET patients received up to four cycles of 1.85 GBq/m²/cycle 90Y-DOTATOC with a maximal kidney biologic effective dose of 37 Gy. All patients underwent a 68Ga-DOTATOC PET/computed tomography (CT) at baseline and seven weeks after the first PRRT cycle. 68Ga-DOTATOC-avid tumor lesions were semi-automatically delineated using a customized standardized uptake value (SUV) threshold-based approach. PRRT response was assessed on CT using RECIST 1.1. Results: Median progression-free survival (PFS) and overall survival (OS) were 13.9 and 22.3 months, respectively. An SUVmean higher than 13.7 (75th percentile (P75)) was associated with better survival (hazard ratio (HR) 0.45; P = 0.024), whereas a 68Ga-DOTATOC-avid tumor volume higher than 578 ml (P75) was associated with worse OS (HR 2.18; P = 0.037). Elevated baseline IBI was associated with worse OS (HR 3.90; P = 0.001). Multivariate analysis corroborated independent associations between OS and SUVmean (P = 0.016) and IBI (P = 0.015). No significant correlations with PFS were found. A composite score based on SUVmean and IBI allowed to further stratify patients in three categories with significantly different survival. On early interim PET, a decrease in SUVmean of more than 17% (P75) was associated with worse survival (HR 2.29; P = 0.024). Conclusion: Normal baseline IBI and high 68Ga-DOTATOC tumor uptake predict better outcome in NET patients treated with 90Y-DOTATOC. This can be used for treatment personalization. Interim 68Ga-DOTATOC PET does not provide information for treatment personalization.

PMID: 31806775 [PubMed - as supplied by publisher]

Permalink for 'Differential expression of glucose transporters and hexokinases in prostate cancer with a neuroendocrine gene signature: a mechanistic perspective for FDG imaging of PSMA-suppressed tumors.'

Differential expression of glucose transporters and hexokinases in prostate cancer with a neuroendocrine gene signature: a mechanistic perspective for FDG imaging of PSMA-suppressed tumors.

Fetched: December 8th, 2019, 5:01am GMT

Differential expression of glucose transporters and hexokinases in prostate cancer with a neuroendocrine gene signature: a mechanistic perspective for FDG imaging of PSMA-suppressed tumors.

J Nucl Med. 2019 Dec 05;:

Authors: Bakht MK, Lovnicki JM, Tubman J, Stringer KF, Chiaramonte J, Reynolds MR, Derecichei I, Ferraiuolo RM, Fifield BA, Lubanska D, Oh SW, Cheon GJ, Kwak C, Jeong CW, Kang KW, Trant JF, Morrissey C, Coleman I, Wang Y, Ahmadzadehfar H, Dong X, Porter LA

Abstract
Purpose: Although the incidence of de novo neuroendocrine prostate cancer (NEPC) is rare, recent data suggests that low expression of prostate-specific membrane antigen (PSMA) is associated with a spectrum of neuroendocrine (NE) hallmarks and androgen receptor (AR)-suppression in prostate cancer (PC). Previous clinical reports indicate that PCs with a phenotype similar to NE tumors can be more amenable to imaging by 18F-Fluorodeoxyglucose (FDG) rather than PSMA-targeting radioligands. In this study, we evaluated the association between NE gene signature and FDG uptake-associated genes including glucose transporters (GLUTs) and hexokinases, with the goal of providing a genomic signature to explain the reported FDG-avidity of PSMA-suppressed tumors. Methods: Data mining approaches, cell lines and patient-derived xenograft (PDX) models were used to study the levels of 14 members of the SLC2A family (encoding GLUT proteins), 4 members of the hexokinase family (genes: HK1 to 3 and GCK) and PSMA (FOLH1 gene) following AR-inhibition and in correlation with NE hallmarks. Also, we characterize a NE-like PC (NELPC) subset among a cohort of primary and metastatic PC samples with no NE histopathology. We measured glucose uptake in a NE-induced in vitro model and a zebrafish model by non-radioactive imaging of glucose uptake using fluorescent glucose bioprobe, GB2-Cy3. Results: This work demonstrates that a NE gene signature associates with differential expression of genes encoding GLUT and hexokinase proteins. In NELPC, elevated expression of GCK (encoding glucokinase protein) and decreased expression of SLC2A12 correlated with earlier biochemical recurrence. In tumors treated with AR-inhibitors, high expression of GCK and low expression of SLC2A12 correlated with NE histopathology and PSMA gene suppression. GLUT12-suppression and amplification of glucokinase was observed in NE-induced PC cell lines and PDX models. A higher glucose uptake was confirmed in low-PSMA tumors using a GB2-Cy3 probe in a zebrafish model. Conclusion: NE gene signature in NEPC and NELPC associates with a distinct transcriptional profile of GLUTs and HKs. PSMA-suppression correlates with GLUT12-suppression and glucokinase-amplification. Alteration of FDG uptake-associated genes correlated positively with higher glucose uptake in AR and PSMA-suppressed tumors. Zebrafish xenograft tumor models are an accurate and efficient pre-clinical method for monitoring non-radioactive glucose uptake.

PMID: 31806771 [PubMed - as supplied by publisher]

Identification of Therapeutic Vulnerabilities in Small Cell Neuroendocrine Prostate Cancer.

Fetched: December 8th, 2019, 5:01am GMT

Identification of Therapeutic Vulnerabilities in Small Cell Neuroendocrine Prostate Cancer.

Clin Cancer Res. 2019 Dec 05;:

Authors: Corella AN, Cabiliza Ordonio MVA, Coleman I, Lucas JM, Kaipainen A, Nguyen HM, Sondheim D, Brown L, True LD, Lee JK, MacPherson D, Nghiem P, Gulati R, Morrissey C, Corey E, Nelson PS

PMID: 31806643 [PubMed - as supplied by publisher]

Permalink for 'Impact of perioperative blood transfusion on survival in pancreatic neuroendocrine tumor patients: analysis from the US Neuroendocrine Study Group.'

Impact of perioperative blood transfusion on survival in pancreatic neuroendocrine tumor patients: analysis from the US Neuroendocrine Study Group.

Fetched: December 8th, 2019, 5:01am GMT

Impact of perioperative blood transfusion on survival in pancreatic neuroendocrine tumor patients: analysis from the US Neuroendocrine Study Group.

HPB (Oxford). 2019 Dec 02;:

Authors: Marincola Smith P, Baechle J, Solórzano CC, Tan M, Lopez-Aguiar AG, Dillhoff M, Beal E, Poultsides G, Cannon JGD, Rocha FG, Crown A, Cho C, Beems M, Winslow ER, Rendell VR, Krasnick BA, Fields RC, Maithel SK, Bailey CE, Idrees K

Abstract
BACKGROUND: Packed red blood cell (PRBC) transfusion has been associated with worse survival in multiple malignancies but its impact on pancreatic neuroendocrine tumors (PNETs) is unknown. The aim of this study was to determine the impact of PRBC transfusion on survival following PNET resection.
METHODS: A retrospective cohort study of PNET patients was performed using the US Neuroendocrine Tumor Study Group database. Demographic and clinical factors were compared. Kaplan-Meier and log-rank analyses were performed. Factors associated with transfusion, overall (OS), recurrence-free (RFS) and progression-free survival (PFS) were assessed by logistic regression.
RESULTS: Of 1129 patients with surgically resected PNETs, 156 (13.8%) received perioperative PRBC transfusion. Transfused patients had higher ASA Class, lower preoperative hemoglobin, larger tumors, more nodal involvement, and increased major complications (all p < 0.010). Transfused patients had worse median OS (116 vs 150 months, p < 0.001), worse RFS (83 vs 128 months, p < 0.01) in curatively resected (n = 1047), and worse PFS (11 vs 24 months, p = 0.110) in non-curatively resected (n = 82) patients. On multivariable analysis, transfusion was associated with worse OS (HR 1.80, p = 0.011) when controlling for TNM stage, tumor grade, final resection status, and pre-operative anemia.
CONCLUSION: PRBC transfusion is associated with worse survival for patients undergoing PNET resection.

PMID: 31806388 [PubMed - as supplied by publisher]

The Role of PET/CT in the Imaging of Pancreatic Neoplasms.

Fetched: December 8th, 2019, 5:01am GMT

The Role of PET/CT in the Imaging of Pancreatic Neoplasms.

Semin Ultrasound CT MR. 2019 Dec;40(6):500-508

Authors: Duan H, Baratto L, Iagaru A

Abstract
Pancreas cancer is a complex disease and its prognosis is related to the origin of the tumor cell as well as the stage of disease at the time of diagnosis. Pancreatic adenocarcinomas derive from the exocrine pancreas and are the fourth leading cause of cancer-related deaths in the United States, while well-differentiated pancreatic neuroendocrine tumors (pNETs) derived from the endocrine part of the pancreas are rare and characterized by a slow growth and good life expectancy. Surgery is the only curative treatment approach, and an accurate assessment of resectability is of paramount importance in order to avoid futile procedures. The role of molecular imaging with positron emission tomography and computed tomography ranges from indispensable for pNETs to controversial for certain scenarios in pancreatic adenocarcinomas. This review article aims to overview molecular pancreatic imaging.

PMID: 31806148 [PubMed - in process]

Rare Solid Tumor of the Exocrine Pancreas: A Pictorial Review.

Fetched: December 8th, 2019, 5:01am GMT

Rare Solid Tumor of the Exocrine Pancreas: A Pictorial Review.

Semin Ultrasound CT MR. 2019 Dec;40(6):483-499

Authors: Dioguardi Burgio M, Ronot M, Vilgrain V

Abstract
Numerous other solid primary neoplasms may arise from the pancreas besides primary ductal adenocarcinomas and neuroendocrine tumors. Although diagnosis can be difficult because of the very low incidence of these tumors, knowledge of several, typical, epidemiologic, biological, and imaging features can help obtain a correct diagnosis. This pictorial review describes the features of solid rare primary pancreatic neoplasms on computed tomography and magnetic resonance imaging focusing on characteristics that can help radiologists differentiate them from classical forms of ductal pancreatic adenocarcinoma and neuroendocrine tumors. Cystic pancreatic neoplasms are beyond the scope of the current review.

PMID: 31806147 [PubMed - in process]

Multimodality Imaging of the Pancreatic Neuroendocrine Tumors.

Fetched: December 8th, 2019, 5:01am GMT

Multimodality Imaging of the Pancreatic Neuroendocrine Tumors.

Semin Ultrasound CT MR. 2019 Dec;40(6):469-482

Authors: Singh A, Hines JJ, Friedman B

Abstract
Pancreatic neuroendocrine tumors (PNETs) are uncommon pancreatic masses which arise from amine precursor and uptake decarboxylation cells. They are classified as functional or nonfunctional based on the associated clinical symptoms. Insulinomas and gastrinomas are the most common functional tumors. PNETs are also classified based on their biologic behavior as benign or malignant. While most PNETs are sporadic, a small percentage are associated with syndromes such as multiple endocrine neoplasia type 1, von Hippel-Lindau syndrome, and are usually multiple in those cases. On imaging, most PNETs are circumscribed and hypervascular masses; however, larger tumors are often heterogeneous. The presence of calcification, cystic degeneration, and necrosis increases the likelihood of malignancy and carries a poor prognosis. Metastases have similar imaging appearance to the primary lesion and are most commonly seen in the liver, locoregional lymph nodes, and bone. This article reviews the pathologic and radiologic features of pancreatic neuroendocrine tumors as well as imaging mimics and their distinguishing features.

PMID: 31806146 [PubMed - in process]

Use of late-night salivary cortisol to monitor response to medical treatment in Cushing's disease.

Fetched: December 7th, 2019, 5:01am GMT

Use of late-night salivary cortisol to monitor response to medical treatment in Cushing's disease.

Eur J Endocrinol. 2019 Dec 01;:

Authors: Newell-Price J, Pivonello R, Tabarin A, Fleseriu M, Witek P, Gadelha MR, Petersenn S, Tauchmanova L, Ravichandran S, Gupta P, Lacroix A, Biller B

Abstract
OBJECTIVE: Monitoring of patients with Cushing's disease on cortisol-lowering drugs is usually performed with urinary free cortisol (UFC). Late-night salivary cortisol (LNSC) has an established role in screening for hypercortisolism and can help to detect loss of cortisol circadian rhythm. Less evidence exists regarding the usefulness of LNSC in monitoring pharmacological response in Cushing's disease.
DESIGN: Exploratory analysis evaluating LNSC during a Phase III study of long-acting pasireotide in Cushing's disease (clinicaltrials.gov: NCT01374906).
METHODS: Mean LNSC (mLNSC) was calculated from two samples, collected on the same days as the first two of three 24-h urine samples (used to calculate mean UFC [mUFC]). Clinical signs of hypercortisolism were evaluated over time.
RESULTS: At baseline, 137 patients had evaluable mLNSC measurements; 91.2% had mLNSC exceeding the upper limit of normal (ULN; 3.2 nmol/L). Of patients with evaluable assessments at month 12 (n=92), 17.4% had both mLNSC ≤ULN and mUFC ≤ULN; 22.8% had mLNSC ≤ULN, and 45.7% had mUFC ≤ULN. There was high variability in LNSC (intra-patient coefficient of variation [CV]: 49.4%) and UFC (intra-patient CV: 39.2%). mLNSC levels decreased over 12 months of treatment and paralleled changes in mUFC. Moderate correlation was seen between mLNSC and mUFC (Spearman's correlation: ρ=0.50 [all time points pooled]). Greater improvements in systolic/diastolic blood pressure and weight were seen in patients with both mLNSC ≤ULN and mUFC ≤ULN.
CONCLUSIONS: mUFC and mLNSC are complementary measurements for monitoring treatment response in Cushing's disease, with better clinical outcomes seen for patients in whom both mUFC and mLNSC are controlled.

PMID: 31804965 [PubMed - as supplied by publisher]

Permalink for 'A typical carcinoid of the lung - a case report with pathological correlation and propagation of the cancer stem cell line BKZ1 with synaptophysin expression.'

A typical carcinoid of the lung - a case report with pathological correlation and propagation of the cancer stem cell line BKZ1 with synaptophysin expression.

Fetched: December 7th, 2019, 5:01am GMT

A typical carcinoid of the lung - a case report with pathological correlation and propagation of the cancer stem cell line BKZ1 with synaptophysin expression.

Medicine (Baltimore). 2019 Dec;98(49):e18174

Authors: Windmöller BA, Greiner JFW, Förster C, Wilkens L, Mertzlufft F, Esch JSA, Kaltschmidt B, Kaltschmidt C, Beshay M

Abstract
RATIONALE: Neuroendocrine tumors (NETs) of the lung account for 5% of all cases of lung cancer, which itself is the leading cause of cancer-related death worldwide. In accordance to its rarity, only few cell lines of NETs exist, which even often lack key characteristics of the primary tumor, making it difficult to study underlying molecular mechanisms.
PATIENT CONCERNS: The patient reported in this case is a 71-year old woman, which never smoked but suffered under dry cough.
DIAGNOSES: Chest CT-scan showed a paracardiac nodule of the lingula with 2 × 1.8 cm in diameter.
INTERVENTIONS: The detected paracardiac nodule of the lingula was anatomically resected using video assisted thoracic surgery.
OUTCOMES: Histopathological diagnostic of the removed tissue identified the tumor as a well-differentiated typical carcinoid (TC), which represents one of the four subgroups of pulmonary NETs. Next to the successful treatment of the patient, we were able to propagate cancer stem cells (CSCs) out of the resected tumor tissue. To the best of our knowledge, we firstly isolated CSCs of a typical carcinoid, which were positive for the prominent CSC markers CD44, CD133 and nestin, confirming their stem cell properties. Additionally, CSCs, further referred as BKZ1, expressed the neuroendocrine marker synaptophysin, verifying their neuroendocrine origin. However, nuclear synaptophysin protein was also present in other stem cell populations, suggesting a role as general stem cell marker.
LESSON: In line with the importance of CSCs in cancer treatment and the lack of CSC-models for neuroendocrine neoplasms, the here described BKZ1 cancer stem cell line of a typical carcinoid represents a promising new model to study pulmonary carcinoids and particular NETs.

PMID: 31804333 [PubMed - in process]

Cancer Stem Cells and Neuroblastoma: Characteristics and Therapeutic Targeting Options.

Fetched: December 7th, 2019, 5:01am GMT

Cancer Stem Cells and Neuroblastoma: Characteristics and Therapeutic Targeting Options.

Front Endocrinol (Lausanne). 2019;10:782

Authors: Veschi V, Verona F, Thiele CJ

Abstract
The majority of embryonal tumors or childhood blastomas derive from pluripotent progenitors or fetal stem cells that acquire cancer stem cell (CSC) properties: multipotency, self-renewal ability, metastatic potential, chemoresistance, more pronounced levels of drug transporters, enhanced DNA-damage repair mechanisms, and a quiescent state. Neuroblastoma (NB) is considered a neuroendocrine tumor and is the most common extracranial neoplasm in children. NB pathogenesis has frequently been associated with epigenetic dysregulation and a failure to implement a differentiation program. The origin, characteristics, and isolation of the CSC subpopulation in NB are still incompletely understood, despite the evidence that this cell subset contributes to disease recurrence and acquired resistance to standard therapies. Here, we summarize the literature regarding the isolation and characterization of CSCs in NB over the past decades, from the early recognition of the expression of stem cell factor (SCF) or its receptor c-KIT to more recent studies identifying the ability of G-CSF and STAT3 to support stem cell-like properties in NB cells. Additionally, we review the morphological variants of NB tumors whose recent epigenetic analyses have shed light on the tumor heterogeneity so common in NB. NB-derived mesenchymal stem cells have recently been isolated from primary tumors of NB patients and associated with a pro-tumorigenic role in the tumor microenvironment, enabling immune escape by tumors, and contributing to their invasive and metastatic capabilities. In particular, we will focus on epigenetic reprogramming in the CSC subpopulation in NB and strategies to target CSCs in NB.

PMID: 31803140 [PubMed]

A prognostic nomogram in patients with distant metastasis of pancreatic neuroendocrine tumors: a population-based study.

Fetched: December 7th, 2019, 5:01am GMT

A prognostic nomogram in patients with distant metastasis of pancreatic neuroendocrine tumors: a population-based study.

Future Oncol. 2019 Dec 05;:

Authors: Cai JS, Chen HY, Lu YF, Yu RS

Abstract
Aim: Prognostic factors in patients with distant metastatic pancreatic neuroendocrine tumors (PNETs) remain uncertain. The purpose of our study is to establish a nomogram to predict survival outcomes in patients with metastatic PNETs. Methods: A total of 878 patients diagnosed with PNETs in the Surveillance, Epidemiology and End Results database between 2004 and 2016 were retrospectively identified. The Kaplan-Meier survival analysis with log-rank test was used to analyze survival outcomes. The nomogram was established after a univariate and multivariate Cox analysis. Results: The independent prognostic variables, including age, tumor grade and primary site surgery were applied to develop a nomogram. The original concordance index was 0.773 (95% CI: 0.751-0.795), and the bias-corrected concordance index was 0.769 (95% CI: 0.748-0.791). The internal calibration curves showed well consistency and veracity in predicting cancer-specific survival probabilities. Conclusion: A nomogram was constructed and verified to predict survival outcomes in patients with distant-stage PNETs.

PMID: 31802701 [PubMed - as supplied by publisher]

Permalink for 'Multimodality management, recurrence patterns, and long-term outcome of gastroenteropancreatic neuroendocrine neoplasms: Progress over 17 years.'

Multimodality management, recurrence patterns, and long-term outcome of gastroenteropancreatic neuroendocrine neoplasms: Progress over 17 years.

Fetched: December 7th, 2019, 5:01am GMT

Multimodality management, recurrence patterns, and long-term outcome of gastroenteropancreatic neuroendocrine neoplasms: Progress over 17 years.

Indian J Gastroenterol. 2019 Dec 04;:

Authors: Desai GS, Pande P, Chhabra V, Shah RC, Jagannath P

Abstract
BACKGROUND: Many advances in the management of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) happened in the last two decades. This study highlights the progress in its management over 17 years, outcomes, recurrence patterns, and follow up protocols.
METHODS: This retrospective analysis of prospectively maintained database at a single tertiary center included GEP-NEN patients from January 2001 to August 2017. Management protocols were based on European Neuroendocrine Tumor Society guidelines. Recurrences were categorized as follows: localized nodal, regional, distant hepatic, or combined. Patients were divided into cohorts: cohort 1 (2001-2006), cohort 2 (2007-2011), and cohort 3 (2012-2017). Survival patterns were analyzed.
RESULTS: One hundred and ninety-two patients were included with 98 (51.04%) grade (G) 1, 64 (33.34%) G2, and 30 (15.63%) G3. One hundred and four (54.16%) underwent curative surgery (58 G1, 27 G2, and 19 G3). Overall follow up ranged from 3 to 276 months; 39 were lost to follow up. Ninety-six patients had recurrences: 44 regional + distant and 40 liver-limited recurrences. One-, 3-, and 5-year survivals show significant differences among different treatment groups (p < 0.05). Significant increase in curative resections, chemotherapy utilization, and reduced recurrences were noted in cohort 3. Curative (R0) resection offered 1- and 3-year overall survival of 93.3% and 66.7% in cohort 1; 95.8% and 83.1% in cohort 2; and 100% and 92.9% in cohort 3.
CONCLUSION: Curative resection is the most significant factor for improved survival. Debulking surgerical procedure have a role whereas upfront peptide receptor radionuclide therapy is questionable. Chemotherapy improves overall survival in inoperable/metastatic setting. Recurrence patterns indicate that a long-term follow up greater than 10 years is necessary.

PMID: 31802438 [PubMed - as supplied by publisher]

Targeting cellular heterogeneity with CXCR2 blockade for the treatment of therapy-resistant prostate cancer.

Fetched: December 7th, 2019, 5:01am GMT

Targeting cellular heterogeneity with CXCR2 blockade for the treatment of therapy-resistant prostate cancer.

Sci Transl Med. 2019 Dec 04;11(521):

Authors: Li Y, He Y, Butler W, Xu L, Chang Y, Lei K, Zhang H, Zhou Y, Gao AC, Zhang Q, Taylor DG, Cheng D, Farber-Katz S, Karam R, Landrith T, Li B, Wu S, Hsuan V, Yang Q, Hu H, Chen X, Flowers M, McCall SJ, Lee JK, Smith BA, Park JW, Goldstein AS, Witte ON, Wang Q, Rettig MB, Armstrong AJ, Cheng Q, Huang J

Abstract
Hormonal therapy targeting androgen receptor (AR) is initially effective to treat prostate cancer (PCa), but it eventually fails. It has been hypothesized that cellular heterogeneity of PCa, consisting of AR+ luminal tumor cells and AR- neuroendocrine (NE) tumor cells, may contribute to therapy failure. Here, we describe the successful purification of NE cells from primary fresh human prostate adenocarcinoma based on the cell surface receptor C-X-C motif chemokine receptor 2 (CXCR2). Functional studies revealed CXCR2 to be a driver of the NE phenotype, including loss of AR expression, lineage plasticity, and resistance to hormonal therapy. CXCR2-driven NE cells were critical for the tumor microenvironment by providing a survival niche for the AR+ luminal cells. We demonstrate that the combination of CXCR2 inhibition and AR targeting is an effective treatment strategy in mouse xenograft models. Such a strategy has the potential to overcome therapy resistance caused by tumor cell heterogeneity.

PMID: 31801883 [PubMed - in process]

An Intrapancreatic accessory spleen presenting as a neuroendocrine tumor.

Fetched: December 6th, 2019, 5:01am GMT

An Intrapancreatic accessory spleen presenting as a neuroendocrine tumor.

Ann Ital Chir. 2019 Jul 08;8:

Authors: Cartanese C, Minardi M, Crocco A, Barile G, De Luca R, Lomonaco R, Ruggieri E, Simone M

Abstract
Although the second most common site of the accessory spleen is the tail of the pancreas, intrapancreatic accessory spleens (IPAS) are rarely recognized radiologically. When an accessory spleen is located in the pancreas, it may mimic a hypervascular pancreatic tumor. We report a case of intrapancreatic accessory spleen which radiologically (on TC) mimicked a neuroendocrine pancreatic tumor (PNET). It was not possible to be sure that the pancreatic nodule had no malignant potential; because of the close proximity to splenic vessel we performed en bloc resection of the spleen and distal pancreas. Postoperative course was uneventful. IPAS must be considered in the differential diagnosis of pancreatic tail tumors, particulary an asymptomatic small PNET; new and adequate diagnostic studies have demonstrated utility in defining these lesions. We review pertinent literature. KEY WORD: Intrapancreatic accessory spleen, Pancreatic neuroendocrine tumor.

PMID: 31799943 [PubMed - in process]

Medulloblastoma in a 6 Year Old Mixed Breed Dog: Surgical Debulking and Chemotherapy.

Fetched: December 6th, 2019, 5:01am GMT

Medulloblastoma in a 6 Year Old Mixed Breed Dog: Surgical Debulking and Chemotherapy.

Front Vet Sci. 2019;6:401

Authors: Lampe R, Vieson MD, Hague D, Connell D, Foss K, Selting KA

Abstract
A medulloblastoma was surgically debulked from a 6 year old American Staffordshire Terrier, who then received a modified lomustine (CCNU), vincristine, procarbazine, and prednisolone (LOPP) protocol. The dog improved significantly and continued to do well until deterioration and euthanasia 5 months following surgery. This is the first known published case report of surgical cytoreductive surgery of a medulloblastoma in a dog with documented response to surgery and chemotherapy. Medulloblastoma is a primitive neuroectodermal tumor that is the most common malignant central nervous system (CNS) tumor in children, though it is less common in adults. This case illustrates the value of considering human literature when creating treatment plans for uncommon brain tumors in veterinary patients. Medulloblastoma should be a differential for cerebellar tumors in young to middle aged dogs, and surgery and chemotherapy should be considered.

PMID: 31799282 [PubMed]

Permalink for 'Diagnosis of Pancreatic Cystic Lesions by Virtual Slicing: Comparison of Diagnostic Potential of Needle-Based Confocal Laser Endomicroscopy versus Endoscopic Ultrasound-Guided Fine-Needle Aspiration.'

Diagnosis of Pancreatic Cystic Lesions by Virtual Slicing: Comparison of Diagnostic Potential of Needle-Based Confocal Laser Endomicroscopy versus Endoscopic Ultrasound-Guided Fine-Needle Aspiration.

Fetched: December 6th, 2019, 5:01am GMT

Diagnosis of Pancreatic Cystic Lesions by Virtual Slicing: Comparison of Diagnostic Potential of Needle-Based Confocal Laser Endomicroscopy versus Endoscopic Ultrasound-Guided Fine-Needle Aspiration.

J Pathol Inform. 2019;10:34

Authors: Haghighi M, Sethi A, Tavassoly I, Gonda TA, Poneros JM, McBride RB

Abstract
Background: Pancreatic cystic lesions are often challenging entities for diagnosis and management. EUS-FNA diagnostic accuracy is limited by paucicellularity of cytology specimens and sampling errors. Needle-based confocal laser endomicroscopy (nCLE) provides real-time imaging of the microscopic structure of the cystic lesion and could result in a more accurate diagnosis.
Aims and Objectives: To determine the diagnostic utility of in vivo nCLE and EUS-FNA in the diagnosis and histologic characterization of pancreatic cystic lesions (PCL).
Materials and Methods: All patients diagnosed with PCL who had undergone nCLE and FNA over a 10-year period within a major urban teaching hospital were included in this study. All gastroenterology reports of the nCLE images and corresponding pathologist findings from the EUS-FNA were collected and compared with, a final diagnosis prospectively collected from clinicopathological and imaging data.
Results: A total of n=32 patients were included in this study, which consisted of n=13 serous cystadenoma (SCA), n=7 intraductal papillary mucinous neoplasms (IPMN), n=2 mucinous cystic neoplasms (MCN), n=3 well-differentiated neuroendocrine tumors, n=2 cysts, n=2 benign pancreatic lesions, n=1 adenocarcinoma, n=1 gastrointestinal stromal tumor (GIST) and n=1 lymphangioma. The overall diagnostic rate was higher in nCLE (87.5%) vs. EUS-FNA (71.9%) While the diagnostic accuracy of nCLE and EUS-FNA were comparable in characterization of benign vs. malignant lesions, the nCLE diagnosis demonstrated higher accuracy rate in identifying mucinous cystic neoplasms compared to EUS-FNA.
Conclusion: nCLE is a useful companion diagnostic tool for pancreatic cystic lesions and could assist the cytopathologist to better triage the sample for required ancillary testing and treatment planning. The combination of nCLE and EUS-FNA may be especially helpful in reducing the proportion of cases categorized as non-diagnostic.

PMID: 31799020 [PubMed]

Few Comments on "Resection Versus Observation of Small Asymptomatic Nonfunctioning Pancreatic Neuroendocrine Tumors".

Fetched: December 6th, 2019, 5:01am GMT

Few Comments on "Resection Versus Observation of Small Asymptomatic Nonfunctioning Pancreatic Neuroendocrine Tumors".

J Gastrointest Surg. 2019 Dec 03;:

Authors: Ren H, Liu X

PMID: 31797256 [PubMed - as supplied by publisher]

Clinicopathologic characteristics and survival outcomes in neuroendocrine carcinoma of the ovary.

Fetched: December 6th, 2019, 5:01am GMT

Clinicopathologic characteristics and survival outcomes in neuroendocrine carcinoma of the ovary.

Int J Gynecol Cancer. 2019 Dec 02;:

Authors: Zhu Y, Meng F, Fang H, Zhang Z, Wang L, Zheng W

Abstract
OBJECTIVE: Neuroendocrine tumors are rare in the ovary. Definitive epidemiologic and prognostic information for neuroendocrine carcinoma of the ovary is lacking. This retrospective population-based study aimed to elucidate the demographic and clinicopathologic characteristics of neuroendocrine carcinoma of the ovary.
METHODS: Patients with neuroendocrine carcinoma of the ovary diagnosed between January 1994 and December 2014were identified from the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute. Cancer-specific survival was calculated by Kaplan-Meier plots and comparisons were performed using the log-rank test. A Cox hazard regression analysis was performed to identify independent predictors of cancer-specific survival in patients with neuroendocrine carcinoma of the ovary.
RESULTS: A total of 166 patients were included, and 21.1% were younger than 50 years old. The majority of patients (59.6%) presented with unilateral tumors. Patients with neuroendocrine carcinoma of the ovary had significantly worse survival compared with most subtypes of epithelial ovarian cancer (including serous, endometrioid, mucinous, and clear cell), and similar to ovarian carcinosarcoma. The rate of cancer-specific survival was significantly different under the SEER histologic stages. Patients with low-grade neuroendocrine carcinoma of the ovary had longer average survival times than those with high-grade neuroendocrine carcinoma of the ovary (HR 3.43, 95% CI 1.56 to 7.54, p=0.002). Patients with neuroendocrine carcinoma of the ovary who underwent surgery had significantly better survival than those who did not undergo surgery (HR 2.23; 95% CI 1.45 to 3.43, p=<0.05).
CONCLUSIONS: Early clinical stage and low tumor grade independently predict better survival in patients with neuroendocrine carcinoma of the ovary. Surgery may be a useful therapy for neuroendocrine carcinoma of the ovary.

PMID: 31796530 [PubMed - as supplied by publisher]

PAK4-NAMPT Dual Inhibition as a Novel Strategy for Therapy Resistant Pancreatic Neuroendocrine Tumors.

Fetched: December 6th, 2019, 5:01am GMT

PAK4-NAMPT Dual Inhibition as a Novel Strategy for Therapy Resistant Pancreatic Neuroendocrine Tumors.

Cancers (Basel). 2019 Nov 29;11(12):

Authors: Mpilla G, Aboukameel A, Muqbil I, Kim S, Beydoun R, Philip PA, Mohammad RM, Kamgar M, Shidham V, Senapedis W, Baloglu E, Li J, Dyson G, Xue Y, El-Rayes B, Azmi AS

Abstract
Pancreatic neuroendocrine tumors (PNET) remain an unmet clinical need. In this study, we show that targeting both nicotinamide phosphoribosyltransferase (NAMPT) and p21-activated kinase 4 (PAK4) could become a synthetic lethal strategy for PNET. The expression of PAK4 and NAMPT was found to be higher in PNET tissue compared to normal cells. PAK4-NAMPT dual RNAi suppressed proliferation of PNET cell lines. Treatment with KPT-9274 (currently in a Phase I trial or analogs, PF3758309 (the PAK4 selective inhibitor) or FK866 (the NAMPT inhibitor)) suppressed the growth of PNET cell lines and synergized with the mammalian target of rapamycin (mTOR) inhibitors everolimus and INK-128. Molecular analysis of the combination treatment showed down-regulation of known everolimus resistance drivers. KPT-9274 suppressed NAD pool and ATP levels in PNET cell lines. Metabolomic profiling showed a statistically significant alteration in cellular energetic pathways. KPT-9274 given orally at 150 mg/kg 5 days/week for 4 weeks dramatically reduced PNET sub-cutaneous tumor growth. Residual tumor analysis demonstrated target engagement in vivo and recapitulated in vitro results. Our investigations demonstrate that PAK4 and NAMPT are two viable therapeutic targets in the difficult to treat PNET that warrant further clinical investigation.

PMID: 31795447 [PubMed]

Permalink for 'American registry of pathology expert opinions: Evaluation of poorly differentiated malignant neoplasms on limited samples - Gastrointestinal mucosal biopsies.'

American registry of pathology expert opinions: Evaluation of poorly differentiated malignant neoplasms on limited samples - Gastrointestinal mucosal biopsies.

Fetched: December 3rd, 2019, 5:01am GMT

American registry of pathology expert opinions: Evaluation of poorly differentiated malignant neoplasms on limited samples - Gastrointestinal mucosal biopsies.

Ann Diagn Pathol. 2019 Nov 15;44:151419

Authors: Bellizzi AM, Montgomery EA, Hornick JL

Abstract
This review reflects a collaboration between the American Registry of Pathology (the publisher of the Armed Forces Institute of Pathology Fascicles) and Annals of Diagnostic Pathology. It is part of a series of expert recommendations on topics encountered in daily practice. The authors, three pathologists with expertise in gastrointestinal tract pathology and immunohistochemistry, met on 30 July 2019 tasked with developing expert recommendations for evaluating poorly differentiated and undifferentiated malignant neoplasms encountered on mucosal biopsies of the gastrointestinal tract. We focused on esophageal, gastric, small intestinal, colorectal, and anal (i.e., tubal gut) samples. When faced with diagnostic uncertainty on the initial H&E, it is best to begin by trying to assign the broad tumor class with screening markers such as pankeratin, S100 protein or SOX10, and CD20 or CD45. Once a broad tumor class is established, more specific differentiation markers can be pursued (e.g., lineage-restricted transcription factors for adenocarcinoma; p40 for squamous cell carcinoma; chromogranin A and synaptophysin or INSM1 for neuroendocrine neoplasms). Every small biopsy containing tumor should be considered a potential molecular pathology sample; cutting extra unstained slides with this testing in mind is strongly encouraged.

PMID: 31786484 [PubMed - as supplied by publisher]

Permalink for 'Development and Validation of a Prognostic Nomogram to Guide Decision-Making for High-Grade Digestive Neuroendocrine Neoplasms.'

Development and Validation of a Prognostic Nomogram to Guide Decision-Making for High-Grade Digestive Neuroendocrine Neoplasms.

Fetched: December 2nd, 2019, 5:01am GMT

Development and Validation of a Prognostic Nomogram to Guide Decision-Making for High-Grade Digestive Neuroendocrine Neoplasms.

Oncologist. 2019 Nov 29;:

Authors: Lin Z, Wang H, Zhang Y, Li G, Pi G, Yu X, Chen Y, Jin K, Chen L, Yang S, Zhu Y, Wu G, Chen J, Zhang T

Abstract
BACKGROUND: The objective of this study was to develop and validate a nomogram to predict 1-year overall survival (OS) and 2-year OS in patients with high-grade digestive neuroendocrine neoplasms (NENs) as well as to guide selection of subgroups that could benefit from systemic chemotherapy.
SUBJECTS, MATERIALS, AND METHODS: We performed a retrospective analysis of 223 patients with NENs of the gut and hepato-biliary-pancreatic system from four centers included in the development cohort. The nomogram was externally validated in a cohort of 90 patients from another one.
RESULTS: The final model included lactate dehydrogenase, performance status, stage, Ki67, and site of primary tumor, all of which had a significant effect on OS. The uncorrected C-index was 0.761 for OS, and the bias-corrected C-index was 0.744. Predictions correlated well with observed 1-year and 2-year outcomes (judged by eye). The area under the time-dependent receiver operating characteristic curve at 12 months and 24 months was 0.876 and 0.838, respectively. The nomogram performed well in terms of both discrimination and calibration when applied to the validation cohort, and OS was significantly different between the two groups classified by nomogram score (log-rank p < .001).
CONCLUSION: The validated nomogram provided useful prediction of OS, which can be offered for clinicians to improve their abilities to assess patient prognosis, to create clinical risk groups for informing treatment or for patient stratification by disease severity in clinical trials.
IMPLICATIONS FOR PRACTICE: The high-grade neuroendocrine neoplasms of the digestive system are rare malignancies with great heterogeneity. An overall survival nomogram was developed and externally validated in this study. Two subgroups were classified by the nomogram score, and platinum-based chemotherapy may not bring clinical benefit for the low-risk patients.

PMID: 31784489 [PubMed - as supplied by publisher]

Permalink for 'A new high-performance liquid chromatography-tandem mass spectrometry method for the determination of sunitinib and N-desethyl sunitinib in human plasma: Light-induced isomerism overtaking towards therapeutic drug monitoring in clinical routine.'

A new high-performance liquid chromatography-tandem mass spectrometry method for the determination of sunitinib and N-desethyl sunitinib in human plasma: Light-induced isomerism overtaking towards therapeutic drug monitoring in clinical routine.

Fetched: December 2nd, 2019, 5:01am GMT

A new high-performance liquid chromatography-tandem mass spectrometry method for the determination of sunitinib and N-desethyl sunitinib in human plasma: Light-induced isomerism overtaking towards therapeutic drug monitoring in clinical routine.

J Pharm Biomed Anal. 2019 Oct 25;:112949

Authors: Marangon E, Buzzo M, Posocco B, Gagno S, Zanchetta M, Iacuzzi V, Poetto AS, Guardascione M, Giodini L, Toffoli G

Abstract
Sunitinib is approved for advanced renal cell cancer, imatinib-resistant or -intolerant gastrointestinal stromal tumors and pancreatic neuroendocrine cancers. It is prescribed at a fixed dose but its plasma exposure shows large inter-individual variations. Taking into account the narrow therapeutic window and the positive exposure-efficacy relationship, there is a robust rationale for its therapeutic drug monitoring. In fact, a target plasma concentration of sunitinib plus its active metabolite, N-desethyl sunitinib, ≥50 ng/mL was suggested. In order to quantify sunitinib and N-desethyl sunitinib in patients' plasma, we developed and validated a new LC-MS/MS method applicable to clinical routine. In solution, sunitinib and N-desethyl sunitinib undergo to photo-isomerization and many published methods overcome this problem by conducting the entire procedures of samples collection and handling under strictly light-protection. Our method is based on a simple and fast procedure that quantitatively reconverts the E-isomer of both analytes, obtained during sample draw and processing without light-protection, into their Z-forms. Moreover, our method uses a small plasma volume (30 μL) and the analytes are extracted by a rapid protein precipitation. It was validated according to EMA-FDA guidelines. The calibration curves resulted linear (R2 always >0.993) over the concentration ranges (0.1-500 ng/mL for sunitinib, 0.1-250 ng/mL for N-desethyl sunitinib) with a good precision (within 7.7 % for sunitinib and 10.8% for N- desethyl sunitinib) and accuracy (range 95.8-102.9% for sunitinib and 92.3-106.2% for N-desethyl sunitinib). This method was applied to a pharmacokinetic study in one patient treated with sunitinib. Moreover, as incurred samples reanalysis is an established part of the bioanalytical process to support clinical studies, its assessment was performed early in order to assure that any reproducibility issues was detected as soon as possible. The percentage difference between the two runs resulted within ±20% in all the re-analysed samples for both sunitinib and N- desethyl sunitinib.

PMID: 31784210 [PubMed - as supplied by publisher]

A paraneoplastic limbic encephalitis from an anorectal small cell neuroendocrine carcinoma: a case report.

Fetched: December 2nd, 2019, 5:01am GMT

A paraneoplastic limbic encephalitis from an anorectal small cell neuroendocrine carcinoma: a case report.

BMC Neurol. 2019 Nov 29;19(1):304

Authors: Longo R, Wagner M, Savenkoff B, de Castaing MC, Desiro G, Tubail Z, Hennequin L, Mahmoud SB, Marcon N, Quetin P, Campitiello M, Plastino F

Abstract
BACKGROUND: Paraneoplastic limbic encephalitis (PLE) is a rare autoimmune neurological syndrome observed in cancer patients. PLE is difficult to diagnose and presents a variable response to treatment, depending on the characteristics of the tumor and neuronal autoantibodies.
CASE PRESENTATION: A 64-year-old, Caucasian, non-smoker man presented with a rapidly developing cognitive impairment, personality change, spatial disorientation, and short-term memory loss associated with anorexia and cervical and inguinal lymph nodes. The 18F-FDG PET scan documented intensely hypermetabolic lymph nodes, which histologically corresponded to a metastasis from a small cell neuroendocrine carcinoma. The brain MRI revealed a high T2-weighted FLAIR signal of the hippocamps, consisted with a PLE. The presence of anti-neuronal Hu antibodies confirmed the diagnosis. The patient underwent plasmapheresis, associated to a systemic chemotherapy resulting in a partial and temporary improvement of the neurological symptoms. Four cycles of intravenous immunoglobulins were also necessary. After six cures of chemotherapy, the lymph node metastases regressed. However, a new anorectal lesion was detected and was histologically confirmed as a primary small cell neuroendocrine carcinoma, which was treated with concomitant chemoradiotherapy. At the end of this treatment, the patient showed a rapid tumor progression leading to his death.
CONCLUSIONS: This case highlights the rare entity, PLE, which is difficult to diagnose and manage. In addition, this is the first published case of PLE associated with an anorectal small cell neuroendocrine carcinoma, which appeared after completion of systemic chemotherapy.

PMID: 31783737 [PubMed - in process]

NEUROENDOCRINE TUMOR IN A CHILD WITH COMMON VARIABLE IMMUNODEFICIENCY.

Fetched: November 30th, 2019, 5:01am GMT

NEUROENDOCRINE TUMOR IN A CHILD WITH COMMON VARIABLE IMMUNODEFICIENCY.

Rev Paul Pediatr. 2019;38:e2018146

Authors: Antunes PSL, Tersariol HG, Veiga MMB, Menezes MCS, Bernardi FDC, Forte WCN

Abstract
OBJECTIVE: To report a case of a child with primary immunodeficiency who at eight years developed digestive symptoms, culminating with the diagnosis of a neuroendocrine tumor at ten years of age.
CASE DESCRIPTION: One-year-old boy began to present recurrent pneumonias in different pulmonary lobes. At four years of age, an immunological investigation showed a decrease in IgG and IgA serum levels. After the exclusion of other causes of hypogammaglobinemia, he was diagnosed with a Common Variable Immunodeficiency and started to receive monthly replacement of human immunoglobulin. The patient evolved well, but at 8 years of age began with epigastrium pain and, at 10 years, chronic persistent diarrhea and weight loss. After investigation, a neuroendocrine tumor was diagnosed, which had a rapid progressive evolution to death.
COMMENTS: Medical literature has highlighted the presence of gastric tumors in adults with Common Variable Immunodeficiency, emphasizing the importance of early diagnosis and the investigation of digestive neoplasms. Up to now there is no description of neuroendocrine tumor in pediatric patients with Common Variable Immunodeficiency. We believe that the hypothesis of digestive neoplasm is important in children with Common Variable Immunodeficiency and with clinical manifestations similar to the case described here in the attempt to improve the prognosis for pediatric patients.

PMID: 31778409 [PubMed - in process]

Role of Staging Laparoscopy in Patients Undergoing Pancreaticoduodenectomy.

Fetched: November 30th, 2019, 5:01am GMT

Role of Staging Laparoscopy in Patients Undergoing Pancreaticoduodenectomy.

Cureus. 2019 Oct 14;11(10):e5906

Authors: Ashraf MI

Abstract
Background Pancreatic cancer patients undergoing curative resection need staging laparoscopy for detecting metastatic disease not picked up on standard radiological scans. Identifying these patients can help to prevent unnecessary laparotomies and early induction of palliative therapies. The aim of our study was to determine the effect of staging laparoscopy on resectable pancreatic or periampullary tumors at our hospital. Methods Patients recommended pancreaticoduodenectomy between September 2014 and June 2018 were included in this study. Any significant finding and its impact on management was recorded. Results A total of 120 patients underwent staging laparoscopy. Fifteen patients had suspicious lesions and one patient had cirrhotic liver on staging laparoscopy. Out of these 15 patients nine patients had liver lesions, three patients with peritoneal nodules and three patients having both liver and peritoneal lesions. Among patients with liver lesions, four patients were found to have metastatic deposits. All of the remaining lesions were benign. Plan of curative resection was changed in five patients. Three patients who were planned for pancreaticoduodenectomy cancelled because of hepatic metastasis. One patient with hepatic metastasis showing neuroendocrine tumor considered for resection. One patient with resectable disease had cirrhotic liver on laparoscopy, so not medically fit for this major surgery. Conclusion In patients planned for pancreaticoduodenectomy, staging laparoscopy is an important step to detect metastatic disease involving peritoneum or viscera. It is very helpful in determining the stage of disease and further management plan.

PMID: 31777693 [PubMed]

Permalink for 'Comments on "Impact of tumor size and nodal status on recurrence of nonfunctional pancreatic neuroendocrine tumors ≤2 cm after curative resection: a multi-institutional study of 392 cases".'

Comments on "Impact of tumor size and nodal status on recurrence of nonfunctional pancreatic neuroendocrine tumors ≤2 cm after curative resection: a multi-institutional study of 392 cases".

Fetched: November 30th, 2019, 5:01am GMT

Comments on "Impact of tumor size and nodal status on recurrence of nonfunctional pancreatic neuroendocrine tumors ≤2 cm after curative resection: a multi-institutional study of 392 cases".

J Surg Oncol. 2019 Nov 27;:

Authors: Tan QQ, Liu XB

PMID: 31777075 [PubMed - as supplied by publisher]

Permalink for 'Response to comments on "Impact of tumor size and nodal status on the recurrence of nonfunctional pancreatic neuroendocrine tumors ≤2 cm after curative resection: a multi-institutional study of 392 cases".'

Response to comments on "Impact of tumor size and nodal status on the recurrence of nonfunctional pancreatic neuroendocrine tumors ≤2 cm after curative resection: a multi-institutional study of 392 cases".

Fetched: November 30th, 2019, 5:01am GMT

Response to comments on "Impact of tumor size and nodal status on the recurrence of nonfunctional pancreatic neuroendocrine tumors ≤2 cm after curative resection: a multi-institutional study of 392 cases".

J Surg Oncol. 2019 Nov 27;:

Authors: Zhang XF, Pawlik TM

PMID: 31777073 [PubMed - as supplied by publisher]

Systemic Therapies for Metastatic Pancreatic Neuroendocrine Tumors.

Fetched: November 30th, 2019, 5:01am GMT

Systemic Therapies for Metastatic Pancreatic Neuroendocrine Tumors.

Curr Treat Options Oncol. 2019 Nov 27;20(12):87

Authors: Hauser H, Gerson DS, Reidy-Lagunes D, Raj N

Abstract
OPINION STATEMENT: Over the years, there have been significant advances in systemic treatments for metastatic pancreatic neuroendocrine tumors (panNETs). Despite these advancements, uncertainty remains regarding how to best sequence available therapies. For well-differentiated and metastatic panNETs that are somatostatin receptor (SSTR) avid on functional imaging, first-line therapy typically consists of somatostatin analogs (SSAs), given their favorable toxicity profile and overall low burden for patients. When progression of disease is observed on an SSA, multiple treatment options are available, including the targeted agents everolimus and sunitinib, peptide receptor radionuclide therapy (PRRT), as well as chemotherapy, with the latter often preferred for those panNETs of heavy tumor burden, higher grade, and/or more aggressive behavior clinically and/or radiographically. Here, we review panNET classification, currently available systemic treatments, therapy sequencing, and areas of active investigation to further our treatments for the disease.

PMID: 31776785 [PubMed - in process]

Paradoxical roles of mutational load as a determinant of anticancer immunity.

Fetched: November 30th, 2019, 5:01am GMT

Paradoxical roles of mutational load as a determinant of anticancer immunity.

Nat Rev Clin Oncol. 2019 11;16(11):659

Authors: Killock D

PMID: 31562491 [PubMed - indexed for MEDLINE]

Permalink for 'Integrative and comparative genomic analyses identify clinically relevant pulmonary carcinoid groups and unveil the supra-carcinoids.'

Integrative and comparative genomic analyses identify clinically relevant pulmonary carcinoid groups and unveil the supra-carcinoids.

Fetched: November 30th, 2019, 5:01am GMT

Integrative and comparative genomic analyses identify clinically relevant pulmonary carcinoid groups and unveil the supra-carcinoids.

Nat Commun. 2019 08 20;10(1):3407

Authors: Alcala N, Leblay N, Gabriel AAG, Mangiante L, Hervas D, Giffon T, Sertier AS, Ferrari A, Derks J, Ghantous A, Delhomme TM, Chabrier A, Cuenin C, Abedi-Ardekani B, Boland A, Olaso R, Meyer V, Altmuller J, Le Calvez-Kelm F, Durand G, Voegele C, Boyault S, Moonen L, Lemaitre N, Lorimier P, Toffart AC, Soltermann A, Clement JH, Saenger J, Field JK, Brevet M, Blanc-Fournier C, Galateau-Salle F, Le Stang N, Russell PA, Wright G, Sozzi G, Pastorino U, Lacomme S, Vignaud JM, Hofman V, Hofman P, Brustugun OT, Lund-Iversen M, Thomas de Montpreville V, Muscarella LA, Graziano P, Popper H, Stojsic J, Deleuze JF, Herceg Z, Viari A, Nuernberg P, Pelosi G, Dingemans AMC, Milione M, Roz L, Brcic L, Volante M, Papotti MG, Caux C, Sandoval J, Hernandez-Vargas H, Brambilla E, Speel EJM, Girard N, Lantuejoul S, McKay JD, Foll M, Fernandez-Cuesta L

Abstract
The worldwide incidence of pulmonary carcinoids is increasing, but little is known about their molecular characteristics. Through machine learning and multi-omics factor analysis, we compare and contrast the genomic profiles of 116 pulmonary carcinoids (including 35 atypical), 75 large-cell neuroendocrine carcinomas (LCNEC), and 66 small-cell lung cancers. Here we report that the integrative analyses on 257 lung neuroendocrine neoplasms stratify atypical carcinoids into two prognostic groups with a 10-year overall survival of 88% and 27%, respectively. We identify therapeutically relevant molecular groups of pulmonary carcinoids, suggesting DLL3 and the immune system as candidate therapeutic targets; we confirm the value of OTP expression levels for the prognosis and diagnosis of these diseases, and we unveil the group of supra-carcinoids. This group comprises samples with carcinoid-like morphology yet the molecular and clinical features of the deadly LCNEC, further supporting the previously proposed molecular link between the low- and high-grade lung neuroendocrine neoplasms.

PMID: 31431620 [PubMed - indexed for MEDLINE]

BRAF+MEKi and ICI triplets show promise in melanoma.

Fetched: November 30th, 2019, 5:01am GMT

BRAF+MEKi and ICI triplets show promise in melanoma.

Nat Rev Clin Oncol. 2019 09;16(9):525

Authors: Killock D

PMID: 31239555 [PubMed - indexed for MEDLINE]

A Caudate Conundrum.

Fetched: November 30th, 2019, 5:01am GMT

A Caudate Conundrum.

Int J Radiat Oncol Biol Phys. 2019 07 01;104(3):481-482

Authors: Menzel P, Theodosopoulos P

PMID: 31162051 [PubMed - indexed for MEDLINE]

Permalink for '"Blood letting" technique with externalized microvascular anastomotic coupler: A salvage option to release intraoperative venous congestion of propeller flap.'

"Blood letting" technique with externalized microvascular anastomotic coupler: A salvage option to release intraoperative venous congestion of propeller flap.

Fetched: November 30th, 2019, 5:01am GMT

"Blood letting" technique with externalized microvascular anastomotic coupler: A salvage option to release intraoperative venous congestion of propeller flap.

Microsurgery. 2019 Mar;39(3):276-277

Authors: Tsapralis N, Pham H, Vlachogiorgos A, Kosutic D

PMID: 30566749 [PubMed - indexed for MEDLINE]

Crystal-induced oligoarthritis triggered by pembrolizumab, an immune checkpoint inhibitor.

Fetched: November 30th, 2019, 5:01am GMT

Crystal-induced oligoarthritis triggered by pembrolizumab, an immune checkpoint inhibitor.

Joint Bone Spine. 2018 10;85(5):647-648

Authors: Corominas H, Badlissi F, Shmerling RH

PMID: 29414722 [PubMed - indexed for MEDLINE]

A Novel Combination Immunotherapy Approach for Neuroendocrine Tumors.

Fetched: November 28th, 2019, 5:01am GMT

A Novel Combination Immunotherapy Approach for Neuroendocrine Tumors.

Oncology (Williston Park). 2019 Nov 14;33(11):

Authors: Patel S

PMID: 31769863 [PubMed - in process]

Variation in Hospital Utilization of Minimally Invasive Distal Pancreatectomy for Localized Pancreatic Neoplasms.

Fetched: November 28th, 2019, 5:01am GMT

Variation in Hospital Utilization of Minimally Invasive Distal Pancreatectomy for Localized Pancreatic Neoplasms.

J Gastrointest Surg. 2019 Nov 25;:

Authors: Ellis RJ, Zhang LM, Ko CY, Cohen ME, Bentrem DJ, Bilimoria KY, Yang AD, Talamonti MS, Merkow RP

Abstract
BACKGROUND: Minimally invasive distal pancreatectomy (MIDP) for localized neoplasms has been demonstrated to be feasible and safe. However, national adoption of the technique is poorly understood. Objectives of this study were to identify factors associated with use of minimally invasive distal pancreatectomy for localized neoplasms and assess hospital variation in MIDP utilization.
METHODS: Retrospective cohort study of patients with pancreatic cysts, stage I pancreatic ductal adenocarcinoma, and stage I pancreatic neuroendocrine tumors undergoing distal pancreatectomy from the ACS NSQIP Pancreas Targeted Dataset. Factors associated with use of MIDP were identified using multivariable logistic regression and hospital-level variation was assessed.
RESULTS: Analysis included 3,059 patients at 139 hospitals. Overall, 64.5% of patients underwent minimally invasive distal pancreatectomy. Patients were more likely to undergo MIDP if they had lower ASA classification (P = 0.004) or BMI ≥ 30 (P < 0.001) and less likely if they had pancreatic adenocarcinoma (P < 0.001). There was notable hospital variability in utilization (range 0 to 100% of cases). Hospital-level utilization of minimally invasive distal pancreatectomy did not appear to be driven by patient selection, as hierarchical analysis demonstrated that only 1.8% of observed hospital variation was attributable to measured patient selection factors.
CONCLUSION: Utilization of MIDP for localized pancreatic neoplasms is highly variable. While some patient-level factors are associated with MIDP use, hospital adoption of MIDP appears to be the primary driver of utilization. Monitoring hospital-level use of MIDP may be a useful quality measure to monitor uptake of emerging techniques in pancreatic surgery.

PMID: 31768832 [PubMed - as supplied by publisher]

Proinsulin-Secreting Neuroendocrine Tumors of the Pancreas: A Single-Centre Experience.

Fetched: November 28th, 2019, 5:01am GMT

Proinsulin-Secreting Neuroendocrine Tumors of the Pancreas: A Single-Centre Experience.

Gastrointest Tumors. 2019 Oct;6(3-4):64-70

Authors: Kriger AG, Berelavichus SV, Kaldarov AR, Panteleev VI, Gorin DS, Dugarova RS, Yukina MY

Abstract
Background: Proinsulinoma is a neuroendocrine tumor (NET) of the pancreas that produces prohormone proinsulin. These tumors are very rare. In the literature, they are most often presented in the form of case reports.
Materials and Methods: We studied 177 patients with NET of the pancreas who underwent surgical treatment in the A.V. Vishnevsky National Medical Research Centre of Surgery from January 2007 to December 2018.
Results: Of 81 patients with organic hyperinsulinism caused by functioning NETs of the pancreas during the study period, 3 (3.7%) had a proinsulinoma; 2 were female; and 1 was male. None of them admitted to weight gain during this period, and their BMI was normal. All patients presented with Whipple's triad during the 72-h fast. Tumor-enucleating surgery was performed: one robot assisted, two laparotomies. A normal glucose level after treatment was achieved in all cases.
Conclusion: In cases where clinical hypoglycemia is present, but the serum insulin level is within the normal range or even decreased, proinsulinoma should be suspected. For now, surgical resection remains the only effective method of treatment. Further investigation of pro-insulinomas is needed.

PMID: 31768350 [PubMed]

Merkel cell carcinoma: a case report and literature review.

Fetched: November 28th, 2019, 5:01am GMT

Merkel cell carcinoma: a case report and literature review.

J Surg Case Rep. 2019 Nov;2019(11):rjz322

Authors: Mulchan N, Cayton A, Asarian A, Xiao P

Abstract
Merkel cell carcinoma (MCC) is an aggressive cutaneous malignancy of neuroendocrine origin presenting as a painless, rapidly growing nodule. MCC often presents in elderly, fair-skinned individuals in sun-exposed areas. Diagnosis is often overlooked at time of presentation due to its rarity, but MCC is twice as deadly as malignant melanoma. There has been bigger interest in the disease due to increasing incidence and an association with the prevalent virus Merkel cell polyomavirus. This study describes an uncommon presentation of MCC as a right gluteal lesion in an Afro-Panamanian patient. The tumor was suspected to be fibrolipoma, but Immunohistochemistry revealed the diagnosis of MCC, as stains for CD56 and CK20 were positive. In addition to surgical excision, the patient was referred for adjuvant radiotherapy. This case report and literature review elucidates the clinical, histopathologic and management aspects of MCC, which will help in recognizing and treating these tumors.

PMID: 31768244 [PubMed]

Permalink for 'Cancer cell-type tropism is one of crucial determinants for the efficient systemic delivery of cancer cell-derived exosomes to tumor tissues.'

Cancer cell-type tropism is one of crucial determinants for the efficient systemic delivery of cancer cell-derived exosomes to tumor tissues.

Fetched: November 28th, 2019, 5:01am GMT

Cancer cell-type tropism is one of crucial determinants for the efficient systemic delivery of cancer cell-derived exosomes to tumor tissues.

Eur J Pharm Biopharm. 2019 Dec;145:27-34

Authors: Emam SE, Abu Lila AS, Elsadek NE, Ando H, Shimizu T, Okuhira K, Ishima Y, Mahdy MA, Ghazy FS, Ishida T

Abstract
Exosomes are gaining increasing attention as drug delivery vehicles due to their low toxicity and ability to functionally transfer biological cargos between cells. However, the therapeutic applicability of exosomes is partially hampered by a lack of cell-type specificity. In this study, therefore, we investigated the impact of cell-type tropism on the in vivo systemic delivery of exosomes to tumor tissues. Exosomes derived from murine colorectal cancer cells (C26) (C26-Exos) and murine melanoma cells (B16BL6) (B16BL6-Exos) were collected. In vitro cellular uptake of either autologous (C26) or allogeneic (B16BL6) exosomes by C26 tumor cells was determined. In vivo tumor accumulation of each type of exosomes in mice bearing C26 tumors was monitored with an in vivo imaging system (IVIS). In in vitro studies, autologous C26-Exos were more efficiently taken up by C26 cancer cells, compared to allogeneic B16BL6-Exos. For in vivo studies, exosomes were modified with surface polyethylene glycol (PEG) to improve their circulation lifetimes. Although both types of PEGylated exosomes accumulated in C26-tumor tissue, autologous exosomes were preferentially accumulated within C26-tumor tissue compared to allogeneic exosomes. The increased tumor accumulation of autologous PEGylated exosomes was accompanied by the preferential uptake of exosomes by not only C26-tumor cells but also tumor-associated immune cells. This study implies that cancer cell-type tropism is an important factor in the achievement of tumor cell targeting with cancer cell-derived exosomes.

PMID: 31629787 [PubMed - indexed for MEDLINE]

Permalink for 'Characterization of myeloid-derived suppressor cells and cytokines GM-CSF, IL-10 and MCP-1 in dogs with malignant melanoma receiving a GD3-based immunotherapy.'

Characterization of myeloid-derived suppressor cells and cytokines GM-CSF, IL-10 and MCP-1 in dogs with malignant melanoma receiving a GD3-based immunotherapy.

Fetched: November 28th, 2019, 5:01am GMT

Characterization of myeloid-derived suppressor cells and cytokines GM-CSF, IL-10 and MCP-1 in dogs with malignant melanoma receiving a GD3-based immunotherapy.

Vet Immunol Immunopathol. 2019 Oct;216:109912

Authors: Hutchison S, Sahay B, de Mello SC, Sayour EJ, Lejeune A, Szivek A, Livaccari AM, Fox-Alvarez S, Salute M, Powers L, Milner RJ

Abstract
Melanoma in humans and canines is an aggressive and highly metastatic cancer. The mucosal forms in both species share genetic and histopathologic features, making dogs a valuable spontaneous disease animal model. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells of myeloid origin with immunosuppressive capabilities, which are increased in many human cancers and contribute to tumor immune evasion. They are a possible target to improve immunotherapy outcomes. Current information regarding MDSCs in canines is minimal, limiting their use as translational model for the study of MDSCs. The objective of this study was to characterize major MDSCs subsets (monocytic and polymorphonuclear) and the cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 10 (IL-10) and monocyte chemoattractant protein-1 (MCP-1) in canines with malignant melanoma and to evaluate changes in MDSCs and the cytokines over time in response to a GD3-based active immunotherapy. Whole blood and serum collected from 30 healthy controls and 33 patients enrolled in the University of Florida melanoma vaccine trial were analyzed by flow cytometry with canine specific CD11b, MHCII and anti-human CD14 antibodies to assess ostensibly polymorphonuclear-MDSC (CD11b+ MHCII- CD14-) and monocytic-MDSC (CD11b+ MHCII- CD14+) subsets. IL-10, MCP-1 and both MDSCs subsets were significantly elevated in melanoma dogs versus controls. Both MDSCs subsets decreased significantly following GD3-based immunotherapy administration but no significant changes in cytokines were seen over time. To our knowledge, this is the first report documenting increased monocytic-MDSCs in canine melanoma. This is consistent with human malignant melanoma data, supporting dogs as a valuable model for therapeutic intervention studies.

PMID: 31446208 [PubMed - indexed for MEDLINE]

Merkel cell carcinoma of the forehead area: a literature review and case report.

Fetched: November 28th, 2019, 5:01am GMT

Merkel cell carcinoma of the forehead area: a literature review and case report.

Oral Maxillofac Surg. 2019 Sep;23(3):365-373

Authors: Caldarelli C, Autorino U, Iaquinta C, De Marchi A

PMID: 31342210 [PubMed - indexed for MEDLINE]

Nanosecond pulsed electric field inhibits malignant melanoma growth by inducing the change of systemic immunity.

Fetched: November 28th, 2019, 5:01am GMT

Nanosecond pulsed electric field inhibits malignant melanoma growth by inducing the change of systemic immunity.

Med Oral Patol Oral Cir Bucal. 2019 Jul 01;24(4):e555-e561

Authors: Zhang X, Zhang Y, Chen J, Wu Y, Zhang J, Wang J

Abstract
BACKGROUND: Nanosecond pulsed electric fields (nsPEFs) showed an inhibitory effect on proliferation of malignant melanoma. In this study, the growth of melanoma were inhibited by changing the systemic immunity .
MATERIAL AND METHODS: C57BL/6 mice with B16 malignant were exposed to 200 pulses of 100 ns duration, 30kV/cm. The mice were executed four days later. T lymphocyte has been extracted from spleen. Cell viability was evaluated by CCK-8 assay. CD3+CD4+ T cells, CD3+CD8+ T cells, regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC) were analyzed by flow cytometry . TNF-α, IL-2, IL-10, TGF-β, IFN- γ levels in supernatants were assessed by ELISA.
RESULTS: C57 malignant melanoma model were established successfully. After the treatment of nsPEFs(30 kV/cm 100 ns 200p), the numbers of T lymphocytes were increased.CD3+ CD4+ T cells changed from 48% to 51.2%;CD3+CD8+T lymphocytes increased from 39.6% to 40.4%.Treg cells reduced from 4.3% to 2.4%,MDSC decreased by 39.0% to 19.7% . In addition, the level of TNF-α, IL-2 were increased (P < 0.05) and the level of IL-10 were decreased (P < 0.05) and the level of TGF-β and IFN-γ remained stable (P > 0.05).
CONCLUSIONS: Tumor growth can be effectively inhibited by nsPEFs in vivo, which activate targets of immune respones, accumulation of inflammatory cells and immune cytokines.

PMID: 31256187 [PubMed - indexed for MEDLINE]

Permalink for 'The expression of melanoma-associated antigen A (MAGE-A) in oral squamous cell carcinoma: an evaluation of the significance for tumor prognosis.'

The expression of melanoma-associated antigen A (MAGE-A) in oral squamous cell carcinoma: an evaluation of the significance for tumor prognosis.

Fetched: November 28th, 2019, 5:01am GMT

The expression of melanoma-associated antigen A (MAGE-A) in oral squamous cell carcinoma: an evaluation of the significance for tumor prognosis.

Oral Maxillofac Surg. 2019 Sep;23(3):343-352

Authors: Trippel A, Halling F, Heymann P, Ayna M, Al-Nawas B, Ziebart T

Abstract
OBJECTIVES: Melanoma-associated antigens A had been detected repeatedly in oral squamous cell carcinoma, but not in healthy mucosa. Additionally, patients with MAGE-A expressing cancers are regarded to have a worse survival prognosis, so that MAGE-A are supposed to be part of carcinogenesis. Which role these antigens fulfill within OSCC is still, up today, largely unknown. This study examines the hypothesis that MAGE-A is being produced in OSCC but not in mucosa tissue and if MAGE-A has any correlation to clinical patient's parameters like tumor size, lymph node metastasis, distant metastasis, overall survival, and recurrence.
MATERIALS AND METHODS: For this purpose, 50 tumor samples and 39 mucosa samples were analyzed by means of PCR and immunohistochemical staining with the antibody 6C1.
RESULTS: Forty of 41 stained tumor samples showed a positive antibody reaction with a maximum staining rate of 53%. Sixteen mucosa samples showed a mild positive reaction. The PCR revealed a linear expression pattern of MAGE-A in which the genes are proportionally expressed in OSCC. We did not find any relationship between MAGE-A and tumor size, overall survival, or recurrence. There was also no connection between MAGE-A and tumor parameters Hif-1 and LDH. Their expression was detected tendentially in tumors with higher staging, advanced lymph node metastasis, and rising age of the patients. The genes MAGE-A3+6 and MAGE-A4 had a statistically significant correlation with lymph node metastasis (p = 0.007 and p = 0.004). Patients got distant metastasis and influence of MAGE-A on metastatic behavior could not be verified. The genes MAGE-A3 and -A4 are consequently qualified as tumor markers in the field of diagnosis and follow-up of OSCC.
CONCLUSIONS AND CLINICAL RELEVANCE: Two genes have great potential as target proteins in immunotherapy. The genes MAGE-A3+6 and MAGE-A4 had a statistically significant correlation with lymph node metastasis.

PMID: 31093793 [PubMed - indexed for MEDLINE]

Sharing Is Caring.

Fetched: November 28th, 2019, 5:01am GMT

Sharing Is Caring.

Dev Cell. 2019 05 06;49(3):306-307

Authors: Xue Q, Roh-Johnson M

Abstract
It is well known that melanoma lipid metabolism is regulated by intrinsic genetic and epigenetic changes in the cancer cells. However, recent work reveals that lipid metabolism is also controlled by the tumor microenvironment through the direct transfer of lipids from adipocytes to melanoma cells.

PMID: 31063747 [PubMed - indexed for MEDLINE]

Permalink for 'Gene expression profiles between cystic and solid vestibular schwannoma indicate susceptible molecules and pathways in the cystic formation of vestibular schwannoma.'

Gene expression profiles between cystic and solid vestibular schwannoma indicate susceptible molecules and pathways in the cystic formation of vestibular schwannoma.

Fetched: November 28th, 2019, 5:01am GMT

Gene expression profiles between cystic and solid vestibular schwannoma indicate susceptible molecules and pathways in the cystic formation of vestibular schwannoma.

Funct Integr Genomics. 2019 Jul;19(4):673-684

Authors: Yan S, Wang Q, Huo Z, Yang T, Yin X, Wang Z, Zhang Z, Wu H

Abstract
Previous research has shown that although NF2 gene mutation is the major cause of vestibular schwannoma (VS), it may not directly participate in cystic VS (CVS). To elucidate the underlying potential genetic mechanisms in the cystic formation of VS, we compared differences in gene expression between solid VS (SVS) and CVS via a bioinformatics analysis. The cDNA microarray method and miRNA sequencing were performed on 29 representative VSs (17 CVSs and 12 SVSs). A differential expression analysis was used to identify differentially expressed mRNAs (DEmRNAs) and miRNAs (DEmiRNAs). Then, miRNA-mRNA regulatory networks were constructed. Gene ontology (GO), a KEGG pathway enrichment analysis, and the protein-protein interaction (PPI) were used to analyze the co-differentially expressed DEmRNAs at the functional level. From the differential expression analyses, 1304 DEmRNAs, 55 DEmiRNAs, and hub genes including PTEN, FOXO1, FOXO3, VEGFA, and SIRT1 were identified. Histological evidence is presented to confirm the makeup of the hubs, which corresponded with the cDNA microarray. Our analysis revealed that the maps of apoptosis, cellular response to hypoxia, and the PI3K-Akt, AMPK, FOXO, and chemokine signaling pathways were significantly enriched. In addition, the TUNEL assay, immunoblotting analysis, and transmission electron microscope revealed increased degenerative changes in CVS. These findings could be the foundation for understanding the potential role of differential genes in the cystic formation of VS and be helpful in exploring the potential biomarkers for the differential diagnosis, prognosis, and development of drug targets for CVS.

PMID: 30953268 [PubMed - indexed for MEDLINE]

Toripalimab: First Global Approval.

Fetched: November 28th, 2019, 5:01am GMT

Toripalimab: First Global Approval.

Drugs. 2019 Apr;79(5):573-578

Authors: Keam SJ

Abstract
Toripalimab, a recombinant, humanized programmed death receptor-1 (PD-1) monoclonal antibody that binds to PD-1 and prevents binding of PD-1 with programmed death ligands 1 (PD-L1) and 2 (PD-L2), is being developed by Shanghai Junshi Bioscience Co., Ltd in China for the treatment of various cancers. In December 2018, based on positive efficacy results of a phase 2 trial and safety data from several clinical studies, toripalimab received conditional approval in China for the treatment of unresectable or metastatic melanoma that has failed previous systemic therapy. This article summarizes the milestones in the development of toripalimab leading to this first global approval for the treatment of unresectable or metastatic melanoma.

PMID: 30805896 [PubMed - indexed for MEDLINE]

The value of novel immuno-oncology treatments.

Fetched: November 28th, 2019, 5:01am GMT

Icon for Managed Care & Healthcare Communications, LLC

The value of novel immuno-oncology treatments.

Am J Manag Care. 2018 12 01;24(12):e380-e385

Authors: Romley JA, Delgado A, Shim J, Batt K

Abstract
OBJECTIVES: To assess the value to society of improved survival from novel immuno-oncology (I-O) treatments.
STUDY DESIGN: Case studies of ipilimumab for the treatment of advanced unresectable melanoma and nivolumab for advanced previously treated squamous non-small cell lung cancer (NSCLC).
METHODS: Published data and survival analysis were used to estimate survival gains. We valued the gains using an economic model developed for application to discrete changes in life expectancy. We estimated aggregate utilization and value to society using cancer registry data and literature. We assessed the share of social value that flowed to the pharmaceutical manufacturer as sales revenue based on publicly available prices.
RESULTS: For advanced melanoma, our analysis estimated an average real-world life expectancy (discounted at a 3% rate) of 32.4 months with ipilimumab versus 14.2 months with an existing standard of care. Treatment of advanced NSCLC with nivolumab generated a life expectancy of 28.1 months versus 14.3 months with an existing standard of care. Depending on model assumptions, the value of these survival gains ranged from $232,000 to $697,000 for a patient with melanoma and from $180,000 to $586,000 for one with NSCLC. Using a midpoint value to aggregate across treated patients over a 5-year window, the total value to society was estimated at $1.9 billion for ipilimumab in advanced melanoma and $1.7 billion for nivolumab in NSCLC. Less than 30% of the total value flowed to the pharmaceutical manufacturer in the form of profit.
CONCLUSIONS: The novel I-O treatments studied here generate substantial survival gains and, thus, social value. Less than half of this value accrued to the pharmaceutical manufacturer as sales revenue.

PMID: 30586486 [PubMed - indexed for MEDLINE]

Permalink for 'Phase 1 study of the combination of vemurafenib, carboplatin, and paclitaxel in patients with BRAF-mutated melanoma and other advanced malignancies.'

Phase 1 study of the combination of vemurafenib, carboplatin, and paclitaxel in patients with BRAF-mutated melanoma and other advanced malignancies.

Fetched: November 28th, 2019, 5:01am GMT

Phase 1 study of the combination of vemurafenib, carboplatin, and paclitaxel in patients with BRAF-mutated melanoma and other advanced malignancies.

Cancer. 2019 02 01;125(3):463-472

Authors: Bhatty M, Kato S, Piha-Paul SA, Naing A, Subbiah V, Huang HJ, Karp DD, Tsimberidou AM, Zinner RG, Hwu WJ, Javle M, Patel SP, Hu MI, Varadhachary GR, Conley AP, Ramzanali NM, Holley VR, Kurzrock R, Meric-Bernstam F, Kwang Chae Y, Kim KB, Falchook GS, Janku F

Abstract
BACKGROUND: BRAF inhibitors are effective against selected BRAFV600 -mutated tumors. Preclinical data suggest that BRAF inhibition in conjunction with chemotherapy has increased therapeutic activity.
METHODS: Patients with advanced cancers and BRAF mutations were enrolled into a dose-escalation study (3+3 design) to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs).
RESULTS: Nineteen patients with advanced cancers and BRAF mutations were enrolled and received vemurafenib (480-720 mg orally twice a day), carboplatin (area under the curve [AUC] 5-6 intravenously every 3 weeks), and paclitaxel (100-135 mg/m2 intravenously every 3 weeks). The MTD was not reached, and vemurafenib at 720 mg twice a day, carboplatin at AUC 5, and paclitaxel at 135 mg/m2 were the last safe dose levels. DLTs included a persistent grade 2 creatinine elevation (n = 1), grade 3 transaminitis (n = 1), and grade 4 thrombocytopenia (n = 1). Non-dose-limiting toxicities that were grade 3 or higher and occurred in more than 2 patients included grade 3/4 neutropenia (n = 5), grade 3/4 thrombocytopenia (n = 5), grade 3 fatigue (n = 4), and grade 3 anemia (n = 3). Of the 19 patients, 5 (26%; all with melanoma) had a partial response (PR; n = 4) or complete response (CR; n = 1); these responses were mostly durable and lasted 3.1 to 54.1 months. Of the 13 patients previously treated with BRAF and/or mitogen-activated protein kinase kinase (MEK) inhibitors, 4 (31%) had a CR (n = 1) or PR (n = 3). Patients not treated with prior platinum therapy had a higher response rate than those who did (45% vs 0%; P = .045).
CONCLUSIONS: The combination of vemurafenib, carboplatin, and paclitaxel is well tolerated and demonstrates encouraging activity, predominantly in patients with advanced melanoma and BRAFV600 mutations, regardless of prior treatment with BRAF and/or MEK inhibitors.

PMID: 30383888 [PubMed - indexed for MEDLINE]

Recognition of Alkaptonuria During Mohs Micrographic Surgery.

Fetched: November 28th, 2019, 5:01am GMT

Recognition of Alkaptonuria During Mohs Micrographic Surgery.

Dermatol Surg. 2019 09;45(9):1194-1195

Authors: Nemeth K, Tolkachjov SN

PMID: 30204737 [PubMed - indexed for MEDLINE]

Cold atmospheric plasma causes a calcium influx in melanoma cells triggering CAP-induced senescence.

Fetched: November 28th, 2019, 5:01am GMT

Cold atmospheric plasma causes a calcium influx in melanoma cells triggering CAP-induced senescence.

Sci Rep. 2018 07 03;8(1):10048

Authors: Schneider C, Gebhardt L, Arndt S, Karrer S, Zimmermann JL, Fischer MJM, Bosserhoff AK

Abstract
Cold atmospheric plasma (CAP) is a promising approach in anti-cancer therapy, eliminating cancer cells with high selectivity. However, the molecular mechanisms of CAP action are poorly understood. In this study, we investigated CAP effects on calcium homeostasis in melanoma cells. We observed increased cytoplasmic calcium after CAP treatment, which also occurred in the absence of extracellular calcium, indicating the majority of the calcium increase originates from intracellular stores. Application of previously CAP-exposed extracellular solutions also induced cytoplasmic calcium elevations. A substantial fraction of this effect remained when the application was delayed for one hour, indicating the chemical stability of the activating agent(s). Addition of ryanodine and cyclosporin A indicate the involvement of the endoplasmatic reticulum and the mitochondria. Inhibition of the cytoplasmic calcium elevation by the intracellular chelator BAPTA blocked CAP-induced senescence. This finding helps to understand the molecular influence and the mode of action of CAP on tumor cells.

PMID: 29968804 [PubMed - indexed for MEDLINE]

Polyomavirus-positive Merkel cell carcinoma derived from a trichoblastoma suggests an epithelial origin of this Merkel cell carcinoma.

Fetched: November 26th, 2019, 5:01am GMT

Polyomavirus-positive Merkel cell carcinoma derived from a trichoblastoma suggests an epithelial origin of this Merkel cell carcinoma.

J Invest Dermatol. 2019 Nov 21;:

Authors: Kervarrec T, Aljundi M, Appenzeller S, Samimi M, Maubec E, Cribier B, Deschamps L, Sarma B, Sarosi EM, Berthon P, Levy A, Bousquet G, Tallet A, Touzé A, Guyétant S, Schrama D, Houben R

PMID: 31759946 [PubMed - as supplied by publisher]

Defining the role of adjuvant therapy for early-stage large cell neuroendocrine carcinoma.

Fetched: November 26th, 2019, 5:01am GMT

Defining the role of adjuvant therapy for early-stage large cell neuroendocrine carcinoma.

J Thorac Cardiovasc Surg. 2019 Sep 30;:

Authors: Wakeam E, Adibfar A, Stokes S, Leighl NB, Giuliani ME, Varghese TK, Darling GE

Abstract
INTRODUCTION: Large cell neuroendocrine carcinoma is a rare, high-grade neuroendocrine tumor. The mainstay of treatment for early, node-negative disease is surgical resection, and optimal adjuvant treatment strategies are not well defined.
METHODS: Patients with early, node-negative large cell neuroendocrine carcinoma were identified in the National Cancer Database from 2004 to 2014. Patient, tumor, treatment, and hospital characteristics were examined. Survival differences in patients receiving adjuvant chemotherapy (AC) were evaluated using Kaplan-Meier curves, and adjusted multivariate Cox models were constructed. A conditional landmark analysis was used to address immortal time bias. T-stage-specific propensity score matching was used to address covariate imbalances between groups.
RESULTS: One thousand seven hundred seventy patients were identified, of whom 463 (26.2%) received AC. Patients receiving AC were younger, less comorbid, and more likely to have T2 tumors. AC was associated with significantly longer survival, which persisted after adjustment in Cox models, for patients overall (5-year overall survival, 59.2% vs 45.3%; hazard ratio, 0.69; 95% confidence interval, 0.58-0.82; P < .0001), T2 tumors (overall survival, 59.8% vs 42.1%; hazard ratio, 0.63; 95% confidence interval, 0.50-0.81; P < .0001), and tumors 2 to 3 cm (overall survival, 60.0% vs 42.6%; hazard ratio, 0.64; 95% confidence interval, 0.46-0.8; P = .002), but not tumors smaller than 2 cm. Adjuvant chest radiotherapy was not associated with longer survival. Sublobar resection was associated with worse overall survival compared with lobectomy (hazard ratio, 1.40; 95% confidence interval, 1.20-1.64; P < .0001). Propensity score matching confirmed these findings, but the association with survival for tumors 2 to 3 cm in size was not significant.
CONCLUSIONS: In this national study of early-stage large cell neuroendocrine carcinoma, AC was associated with significantly longer survival for tumors larger than 3 cm, and possibly for tumors 2 to 3 cm. Adjuvant radiation was not associated with prolonged survival.

PMID: 31759623 [PubMed - as supplied by publisher]

Imaging DNA Damage Repair in vivo Following 177Lu-DOTATATE Therapy.

Fetched: November 25th, 2019, 5:01am GMT

Imaging DNA Damage Repair in vivo Following 177Lu-DOTATATE Therapy.

J Nucl Med. 2019 Nov 22;:

Authors: O'Neill E, Kersemans V, Allen PD, Terry SYA, Baguña Torres J, Mosley M, Smart SC, Lee BQ, Falzone N, Vallis KA, Konijnenberg MW, de Jong M, Nonnekens J, Cornelissen B

Abstract
Purpose: Molecular Radiotherapy (MRT) using 177Lu-DOTATATE is a most effective therapy for the treatment of somatostatin receptor expressing neuroendocrine tumors (NETs). Despite its frequent and successful use in the clinic, little or no radiobiological considerations are taken into account at the time of treatment planning or delivery, and upon positive uptake of octreotide-based PET/SPECT imaging, treatment is usually administered as a standard dose and number of cycles without adjustment for peptide uptake, dosimetry, or radiobiological and DNA damage effects in the tumor. Here, we visualize and quantify the extent of DNA damage response following 177Lu-DOTATATE therapy using SPECT imaging with 111In-anti-γH2AX-TAT. This work is a proof-of-principle study of this in vivo non-invasive biodosimeter with beta-emitting therapeutic radiopharmaceuticals. Methods: Six cell lines were exposed to external beam radiotherapy (EBRT) or 177Lu-DOTATATE, after which the number of γH2AX foci and clonogenic survival were measured. Mice bearing CA20948 somatostatin receptor positive tumor xenografts were treated with 177Lu-DOTATATE or sham-treated, and co-injected with 111In-anti-γH2AX-TAT, 111In-IgG-TAT control, or vehicle. Results: Clonogenic survival following EBRT was cell line specific, indicating varying levels of intrinsic radiosensitivity. In vitro, cell lines treated with 177Lu-DOTATATE, clonogenic survival decreased and γH2AX foci increased in cells expressing high levels of somatostatin receptor subtype 2 (SST2). Ex vivo measurements revealed a partial correlation between 177Lu-DOTATATE uptake and γH2AX foci induction between different regions of CA20948 xenograft tumors, suggesting different parts of the tumor may react differentially to 177Lu-DOTATATE irradiation. Conclusion: 111In-anti-γH2AX-TAT allows monitoring of DNA damage following 177Lu-DOTATATE therapy, and reveals heterogeneous damage responses.

PMID: 31757844 [PubMed - as supplied by publisher]

Neuroendocrine tumour of the gallbladder.

Fetched: November 25th, 2019, 5:01am GMT

Neuroendocrine tumour of the gallbladder.

Gastroenterol Hepatol. 2019 Nov 19;:

Authors: López Marcano JA, Ramia Ángel JM, de la Plaza Llamas R, Manuel Vázquez A, Latorre Fragua R

PMID: 31757444 [PubMed - as supplied by publisher]

Permalink for 'Continuous regional arterial infusion versus intravenous administration of the protease inhibitor nafamostat mesilate for predicted severe acute pancreatitis: a multicenter, randomized, open-label, phase 2 trial.'

Continuous regional arterial infusion versus intravenous administration of the protease inhibitor nafamostat mesilate for predicted severe acute pancreatitis: a multicenter, randomized, open-label, phase 2 trial.

Fetched: November 25th, 2019, 5:01am GMT

Continuous regional arterial infusion versus intravenous administration of the protease inhibitor nafamostat mesilate for predicted severe acute pancreatitis: a multicenter, randomized, open-label, phase 2 trial.

J Gastroenterol. 2019 Nov 22;:

Authors: Hirota M, Shimosegawa T, Kitamura K, Takeda K, Takeyama Y, Mayumi T, Ito T, Takenaka M, Iwasaki E, Sawano H, Ishida E, Miura S, Masamune A, Nakai Y, Mitoro A, Maguchi H, Kimura K, Sanuki T, Ito T, Haradome H, Kozaka K, Gabata T, Kataoka K, Hirota M, Isaji S, Nakamura R, Yamagiwa K, Kayaba C, Ikeda K

Abstract
BACKGROUND: Continuous regional arterial infusion (CRAI) of protease inhibitor nafamostat mesilate (NM) is used in the context of predicted severe acute pancreatitis (SAP) to prevent the development of pancreatic necrosis. Although this therapy is well known in Japan, its efficacy and safety remain unclear.
METHODS: This investigator-initiated and -driven, multicenter, open-label, randomized, controlled trial (UMIN000020868) enrolled 39 patients with predicted SAP and low enhancement of the pancreatic parenchyma on computed tomography (CT). Twenty patients were assigned to the CRAI group, while 19 served as controls and were administered NM at the same dose intravenously (IV group). The primary endpoint was the development of pancreatic necrosis as determined by CT on Day 14, judged by blinded central review.
RESULTS: There was no difference between the CRAI and IV groups regarding the percentages of participants who developed pancreatic necrosis (more than 1/3 of the pancreas: 25.0%, range 8.7-49.1% vs. 15.8%, range 3.4-39.6%, respectively, P = 0.694; more than 2/3 of the pancreas: 20%, range 5.7-43.7% vs. 5.3%, range 0.1-26.0%, respectively, P = 0.341). The early analgesic effect was evaluated based on 24-h cumulative fentanyl consumption and additional administration by intravenous patient-controlled analgesia. The results showed that the CRAI group used significantly less analgesic. There were two adverse events related to CRAI, namely bleeding and splenic infarction.
CONCLUSIONS: CRAI with NM did not inhibit the development of pancreatic necrosis although early analgesic effect of CRAI was superior to that of IV. Less-invasive IV therapy can be considered a viable alternative to CRAI therapy.

PMID: 31758329 [PubMed - as supplied by publisher]

Permalink for 'A Survival Analysis of Patients with Localized, Asymptomatic Pancreatic Neuroendocrine Tumors: No Surgical Survival Benefit when Examining Appropriately Selected Outcomes.'

A Survival Analysis of Patients with Localized, Asymptomatic Pancreatic Neuroendocrine Tumors: No Surgical Survival Benefit when Examining Appropriately Selected Outcomes.

Fetched: November 24th, 2019, 5:01am GMT

A Survival Analysis of Patients with Localized, Asymptomatic Pancreatic Neuroendocrine Tumors: No Surgical Survival Benefit when Examining Appropriately Selected Outcomes.

J Gastrointest Surg. 2019 Nov 21;:

Authors: Powers BD, Rothermel LD, Fleming JB, Strosberg JR, Anaya DA

Abstract
BACKGROUND: Surgical resection for asymptomatic, localized, well-differentiated pancreatic neuroendocrine tumors (PNETs) is common yet controversial. Studies using overall survival as an endpoint have shown a benefit for resection; however, these results may be due to treatment selection bias. We assessed the impact of surgery on both overall (OS) and cancer-specific survival (CSS) for asymptomatic patients with stage I PNETs (AJCC 8th edition).
METHODS: Using SEER data, we identified 709 patients from 2007 to 2015 with well- and moderately differentiated stage I PNETs. We performed Kaplan-Meier survival estimates and adjusted Cox regression for OS and CSS.
RESULTS: Among 709 patients, 628 (88.6%) underwent surgery. There were 37 overall deaths and 11 cancer-specific deaths. All cancer-specific deaths occurred within 3 years of diagnosis. Five-year OS and CSS rates were 89% and 98%, respectively, for the population. Five-year OS rates were 56% in the non-surgical cohort versus 92% in the surgical cohort (log rank, p < 0.001). However, the 5-year CSS rates were similar; 94% in the non-surgical group and 98% in the surgical group (log rank, p = 0.207). On multivariable analysis, surgery predicted improved OS but not CSS.
CONCLUSION: Although OS is superior in surgically treated stage I PNETs, CSS is not improved, implying treatment selection bias towards surgery being performed in healthier patients. These data suggest that overall survival is a problematic endpoint for the study of asymptomatic, stage I PNETs. Surgery should be individualized for this cohort of patients as the primary cause of death is non-cancer related.

PMID: 31754990 [PubMed - as supplied by publisher]

Permalink for 'A Patient-Reported Outcomes Analysis Of Lanreotide In The Treatment Of NETs Patients With Carcinoid Syndrome: Evidence From The ELECT Trial.'

A Patient-Reported Outcomes Analysis Of Lanreotide In The Treatment Of NETs Patients With Carcinoid Syndrome: Evidence From The ELECT Trial.

Fetched: November 24th, 2019, 5:01am GMT

A Patient-Reported Outcomes Analysis Of Lanreotide In The Treatment Of NETs Patients With Carcinoid Syndrome: Evidence From The ELECT Trial.

Patient Relat Outcome Meas. 2019;10:335-343

Authors: Blot K, Duchateau L, Lescrauwaet B, Liyanage N, Ray D, Mirakhur B, Vinik AI

Abstract
Purpose: The purpose of this analysis of patient-reported outcomes from the ELECT (Evaluation of Lanreotide Depot/Autogel Efficacy and Safety as a Carcinoid Syndrome Treatment) trial (NCT00774930) was to explore the effect of lanreotide on symptoms of carcinoid syndrome. Specifically, this post hoc analysis was designed to identify the most important patient-reported outcomes for patients in ELECT.
Methods: The post hoc analysis of ELECT, a placebo-controlled study of lanreotide in patients with neuroendocrine tumors, evaluated patient-reported outcomes during the double-blind phase of the trial, specifically daily diarrhea and flushing symptoms, octreotide rescue use, and the EORTC QLQ-C30 and QLQ-GINET21 questionnaires at baseline and week 12. Principal component (PC) analysis was applied on baseline data to identify independent variable clusters and clinically meaningful summary measures that highly correlated to these PCs. From those, the minimum clinical important differences were derived so to perform a responder analysis.
Results: The three largest PCs captured 42.9% of the variation among baseline variables. The C30 summary score (C30-SS), diarrhea burden, and flushing burden were highly correlated with PC1, PC2, and PC3, respectively. Lanreotide patients were more likely to experience an improvement on the C30-SS (risk ratio [RR] 2.42; P=0.023), diarrhea burden (RR 2.85; P=0.005), and flushing burden (RR 1.39; P=0.31) compared to placebo patients. Lanreotide-treated patients have a higher probability of being a responder on at least one of the three domains of C30-SS, diarrhea burden, or flushing burden compared to placebo patients (RR 1.48; P=0.06).
Conclusion: The higher response rates in the diarrhea burden are consistent with the previously reported effects of lanreotide on octreotide rescue medication use, while the findings of a greater efficacy of lanreotide vs placebo in the quality-of-life domains represent a novel aspect in the benefits of lanreotide.
Trial registration: ClinicalTrials.gov identifier: NCT00774930.

PMID: 31754316 [PubMed]

Successful Treatment of Hypokalemic Rhabdomyolysis Caused by a Pancreatic VIPoma: A Case Report.

Fetched: November 24th, 2019, 5:01am GMT

Successful Treatment of Hypokalemic Rhabdomyolysis Caused by a Pancreatic VIPoma: A Case Report.

Am J Case Rep. 2019 Nov 22;20:1723-1727

Authors: Ramirez S, Lytle M, Togores E, Parellada J, Carlan SJ, Madruga M, Murillo-Alvarez RM

Abstract
BACKGROUND VIPomas are rare neuroendocrine tumors typically located in the pancreas. The majority of cases autonomously secret vasoactive intestinal polypeptide (VIP), which can result in profuse, refractory, watery diarrhea. The fluid and electrolyte imbalance can progress to dehydration and profound hypokalemia, resulting in the watery diarrhea, hypokalemia, achlorhydria (WDHA) syndrome. One previous case of a pancreatic VIPoma progressing to hypokalemic rhabdomyolysis has been described. CASE REPORT A 33-year-old woman presented with 3 months of progressive, refractory diarrhea and weakness. Her serum VIP level was elevated and imaging discovered a mass in the region of the pancreatic tail. Laparoscopic partial pancreatic resection was performed and a 3.7-cm diameter, solitary stage T2 N0 M0, well-differentiated carcinoma was removed. CONCLUSIONS A high index of suspicion is important when diagnosing chronic diarrhea. Minimally invasive surgery is an option in the surgical treatment of pancreatic VIPoma.

PMID: 31754090 [PubMed - in process]

A Bleeding Toe.

Fetched: November 24th, 2019, 5:01am GMT

A Bleeding Toe.

N Engl J Med. 2019 Nov 07;381(19):1853

Authors: Luo Z, Zhao S

PMID: 31693808 [PubMed - indexed for MEDLINE]

Permalink for 'Differential expression of p52 and RelB proteins in the metastatic and non-metastatic groups of uveal melanoma with patient outcome.'

Differential expression of p52 and RelB proteins in the metastatic and non-metastatic groups of uveal melanoma with patient outcome.

Fetched: November 24th, 2019, 5:01am GMT

Differential expression of p52 and RelB proteins in the metastatic and non-metastatic groups of uveal melanoma with patient outcome.

J Cancer Res Clin Oncol. 2019 Dec;145(12):2969-2982

Authors: Singh MK, Singh L, Chosdol K, Pushker N, Saini N, Meel R, Bakhshi S, Sen S, Kashyap S

Abstract
PURPOSE: Non-canonical NFκB (NC-NFκB) pathway plays an influential role in metastasis, which promotes cancer proliferation and progression. The aim of the study was to examine the expression of NC-NFκB proteins and their correlation with clinicopathological factors associated with metastatic cases of uveal melanoma (UM) and with the patient outcome.
METHOD: Expression of NC-NFκB proteins (p52, RelB, and co-expression of p52/RelB) was evaluated in 75 formalin-fixed cases of uveal melanoma by immunohistochemistry. Validation of nuclear immunoreactivity was done by western blotting. Transcriptional status of NC-NFκB genes was assessed in 60 fresh tumor tissues by quantitative real-time PCR. Co-immunoprecipitation was performed to determine the presence of native p52/RelB heterodimer in UM. Prognostic relevance was determined using Cox proportional hazard and Kaplan-Meier methods.
RESULTS: Immunohistochemical expression of p52, RelB, and their co-expression was observed in 81%, 68.7%, 56.2% of metastatic cases, respectively, while their expression was seen only in 38%, 33% and 30% of non-metastatic cases. Loss of BAP-1 was correlated with expression of p52 and RelB proteins. Co-immunoprecipitation assay confirmed the putative interaction of p52 with RelB protein in metastatic cases of uveal melanoma. Co-expression of p52/RelB and expression of p52 protein was significantly correlated with decreased metastasis-free survival (MFS) (p = 0.004; p = 0.002) and overall survival (OS) (p = 0.004; p = 0.032), while the RelB expression only correlated with reduced MFS (p = 0.003).
CONCLUSION: Our data showed that non-canonical NFκB proteins were significantly higher in metastatic cases and associated with poor outcome of the patients. Furthermore, the p52 protein could be used as a potential therapeutic biomarker for metastatic cases in uveal melanoma.

PMID: 31612319 [PubMed - indexed for MEDLINE]

A comparison of posttraumatic growth changes in breast cancer and melanoma.

Fetched: November 24th, 2019, 5:01am GMT

Icon for American Psychological Association

A comparison of posttraumatic growth changes in breast cancer and melanoma.

Health Psychol. 2019 Oct;38(10):878-887

Authors: Bourdon M, Blanchin M, Campone M, Quéreux G, Dravet F, Sébille V, Bonnaud Antignac A

Abstract
OBJECTIVE: This article presents a comparison of the changes of Posttraumatic Growth (PTG) in breast cancer and melanoma patients over a 2-year follow-up period and investigates the associations between coping strategies, anxiety, depression, emotional functioning, and PTG over time.
METHOD: Seventy-eight early stage melanoma patients from Nantes University Hospital and 215 breast cancer patients from Nantes Cancerology Institute completed self-administered questionnaires collecting sociodemographic and medical information and assessing health-related quality of life, coping strategies, anxiety and depression within 1 month of diagnosis and 6, 12, and 24 months after the diagnosis. PTG was assessed at 6, 12, and 24 months postdiagnosis.
RESULTS: We found that PTG increased over time for both cancers, but that breast cancer and melanoma patients did not experience the same magnitude of changes in PTG depending on time and on depression. While we did not find any relationship between anxiety, emotional functioning, negative coping and PTG; positive and emotional coping were positively associated with PTG changes for both cancers. Substance use was negatively related to PTG at 2 years postdiagnosis for melanoma and breast cancer.
CONCLUSIONS: Our findings reveal that PTG increases over time for both cancers. In addition, it provides relevant information about the coping strategies that are associated with the experience of positive changes. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

PMID: 31343219 [PubMed - indexed for MEDLINE]

NIR triggered glycosylated gold nanoshell as a photothermal agent on melanoma cancer cells.

Fetched: November 24th, 2019, 5:01am GMT

NIR triggered glycosylated gold nanoshell as a photothermal agent on melanoma cancer cells.

Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):2316-2324

Authors: Nouri S, Mohammadi E, Mehravi B, Majidi F, Ashtari K, Neshasteh-Riz A, Einali S

Abstract
Nowadays, gold nanoshells are used in targeted nano photothermal cancer therapy. This study surveyed the application of gold nanoshell (GNs) to thermal ablative therapy for melanoma cancer cells and it takes advantage of the near infrared absorption of gold nanoshells. The synthesis and characterization of glycosylated gold nanoshells (GGNs) were done. The cytotoxicity and photothermal effects of GNs on melanoma cells were evaluated using MTT assay and flow cytometry. The characterization data showed that GGNs are spherical, with a hydrodynamic size of 46.7 nm. Results suggest that the cellular uptake of GGNs was about 78%. Viability assays showed no significant toxicity at low concentrations of GNs. The higher heating rate and toxicity of cancer cells were obtained for the cells exposed to 808 nm NIR laser after incubation with GGNs rather than the GNs. The viability of these cells has dramatically decreased by 29%. Furthermore, 61% more cell lethality was achieved for A375 cells using combined photothermal therapy and treatment with GGNs in comparison to NIR radiation alone. In conclusion, our findings suggest that the synthesized gold/silica core-shell nanoparticles conjugated with glucosamine have high potentials to be considered as an efficient metal-nanoshell in the process of targeted cancer photothermal therapy.

PMID: 31184218 [PubMed - indexed for MEDLINE]

Deep Learning Based Skin Lesion Segmentation and Classification of Melanoma Using Support Vector Machine (SVM)

Fetched: November 24th, 2019, 5:01am GMT

Deep Learning Based Skin Lesion Segmentation and Classification of Melanoma Using Support Vector Machine (SVM)

Asian Pac J Cancer Prev. 2019 May 25;20(5):1555-1561

Authors: R D S, A S

Abstract
Objective: The main objective of this study is to improve the classification performance of melanoma using deep learning based automatic skin lesion segmentation. It can be assist medical experts on early diagnosis of melanoma on dermoscopy images. Methods: First A Convolutional Neural Network (CNN) based U-net algorithm is used for segmentation process. Then extract color, texture and shape features from the segmented image using Local Binary Pattern ( LBP), Edge Histogram (EH), Histogram of Oriented Gradients (HOG) and Gabor method. Finally all the features extracted from these methods were fed into the Support Vector Machine (SVM), Random Forest (RF), K-Nearest Neighbor (KNN) and Naïve Bayes (NB) classifiers to diagnose the skin image which is either melanoma or benign lesions. Results: Experimental results show the effectiveness of the proposed method. The Dice co-efficiency value of 77.5% is achieved for image segmentation and SVM classifier produced 85.19% of accuracy. Conclusion: In deep learning environment, U-Net segmentation algorithm is found to be the best method for segmentation and it helps to improve the classification performance.

PMID: 31128062 [PubMed - indexed for MEDLINE]

Sentinel Lymph Node Biopsy in Patients With Acral Melanoma: Analysis of 201 Cases From the Brazilian National Cancer Institute.

Fetched: November 24th, 2019, 5:01am GMT

Sentinel Lymph Node Biopsy in Patients With Acral Melanoma: Analysis of 201 Cases From the Brazilian National Cancer Institute.

Dermatol Surg. 2019 08;45(8):1026-1034

Authors: Nunes LF, Mendes GLQ, Koifman RJ

Abstract
BACKGROUND: Sentinel lymph node biopsy (SLNB) is the most powerful predictor of relapse-free survival (RFS) and overall survival (OS). No studies have evaluated survival of acral melanoma (AM) undergoing SLNB in Brazil.
OBJECTIVE: The objective of this study was to investigate the factors associated with the survival of patients with AM undergoing SLNB.
MATERIALS AND METHODS: Patients diagnosed with AM and submitted to SLNB were included in this study. We evaluated the epidemiologic, clinical, and histopathological data. Overall survival and RFS curves were estimated using the Kaplan-Meier method. Multivariable analyses were conducted using the Cox regression model.
RESULTS: Among the 201 patients, 117 (58.2%) were female. The median age was 64 years old. Median tumor depth was 5.0 mm. Lesions were ulcerated in 134 (66.7%). Five-year OS and RFS rates were 44.6% and 38.6%, respectively. Median follow-up time was 39 months. The factors associated with OS were Breslow thickness, ulceration, and SLNB status, and for RFS, they were Breslow thickness and SLNB status.
CONCLUSION: This is the largest series of AM submitted to SLNB. The 5-year OS and RFS rates were low (44.6% and 38.6%, respectively), and the main prognostic factors for OS were Breslow thickness, ulceration, and the status of SLNB.

PMID: 30908362 [PubMed - indexed for MEDLINE]

Clinical Features, Metastasis, and Survival in Patients Younger Than 21 Years With Posterior Uveal Melanoma.

Fetched: November 24th, 2019, 5:01am GMT

Clinical Features, Metastasis, and Survival in Patients Younger Than 21 Years With Posterior Uveal Melanoma.

JAMA Ophthalmol. 2019 01 01;137(1):75-81

Authors: Fry MV, Augsburger JJ, Corrêa ZM

Abstract
Importance: Given the rarity of posterior uveal melanoma in patients younger than 21 years, reporting clinical experience in this area has relevance.
Objective: To describe the baseline clinical features, treatment, and clinical course of a group of patients younger than 21 years who have primary posterior uveal melanoma.
Design, Setting, and Participants: This retrospective descriptive case series of patients younger than 21 years who have a primary choroidal or ciliochoroidal melanoma was conducted at a single-center subspecialty referral practice. Patients in the relevant age group who were treated in a single practice between July 1980 and December 2013 were included; clinical data collected through December 2017 were captured to permit adequate follow-up time in all cases.
Main Outcomes and Measures: Conventional descriptive statistics of relevant clinical variables (eg, demographic, tumor, treatment, and outcome variables) of each patient were recorded. Actuarial metastasis-free and overall survival curves were computed and plotted, as was a postdetection survival curve of patients who developed metastasis during available follow-up.
Results: Of 2265 patients with posterior uveal melanoma encountered by the authors during the study interval, 18 (0.8%) were younger than 21 years when diagnosed and treated. Ten were female and 8 male, and the mean (SD) age was 16.6 (4.2) years. Through available follow-up, 8 of these patients had developed metastatic uveal melanoma (44%). All 8 died of metastasis. Actuarial survival analysis showed that the cumulative probability of metastatic death in this group exceeded 50%. The median overall survival time after treatment of the primary intraocular tumor was 11.9 (95% CI, 7.3-16.5) years. The median survival time after detection of metastasis in the 8 patients who developed metastasis was 2.3 months (95% CI, 0.0-5.2) months.
Conclusions and Relevance: Posterior uveal melanoma in patients younger than 21 years appears to have a similar if not worse prognosis than patients with PUM in the population overall. Owing to the later onset of metastasis observed, patients younger than 21 years should continue to have surveillance tests for more than 10 years after treatment.

PMID: 30422230 [PubMed - indexed for MEDLINE]

Protease-activated receptor-1 impedes prostate and intestinal tumor progression in mice.

Fetched: November 24th, 2019, 5:01am GMT

Protease-activated receptor-1 impedes prostate and intestinal tumor progression in mice.

J Thromb Haemost. 2018 11;16(11):2258-2269

Authors: Adams GN, Sharma BK, Rosenfeldt L, Frederick M, Flick MJ, Witte DP, Mosnier LO, Harmel-Laws E, Steinbrecher KA, Palumbo JS

Abstract
Essentials Protease activated receptor-1 (PAR-1) has been proposed to drive cancer progression. Surprisingly, PAR-1 deletion accelerated tumor progression in two distinct experimental settings. PAR-1 deletion was shown to limit the apoptosis of transformed epithelial cells. Thrombin- and activated protein C-mediated PAR-1 activation have unique effects on tumor cell biology. SUMMARY: Background Multiple studies have implicated protease-activated receptor-1 (PAR-1), a G-protein-coupled receptor activated by proteolytic cleavage of its N-terminus, as one target coupling thrombin-mediated proteolysis to tumor progression. Objective To analyze the role of PAR-1 in the setting of two distinct spontaneously developing tumor models in mice. Methods We interbred PAR-1-deficient mice with Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mice, which spontaneously develop prostate tumors, and adenomatous polyposis coli Min (APCM in/+ ) mice, which spontaneously develop intestinal adenomas. Results Analyses of TRAMP mice with advanced disease (30 weeks) revealed that PAR-1 deficiency resulted in significantly larger and more aggressive prostate tumors. Prostates collected at an earlier time point (12 weeks of age) revealed that PAR-1 promotes apoptosis in transformed epithelia. In vitro analyses of TRAMP-derived cells revealed that activated protein C-mediated PAR-1 cleavage can induce tumor cell apoptosis, suggesting that tumor cell-intrinsic PAR-1 functions can limit tumor progression. Paralleling results in TRAMP mice, PAR-1-deficient APCM in/+ mice developed three-fold more adenomas than PAR-1-expressing mice, and the adenomas that formed were significantly larger. Moreover, loss of PAR-1 expression was shown to limit apoptosis in transformed intestinal epithelial cells. Conclusions Together, these results demonstrate a previously unrecognized role for PAR-1 in impeding tumor progression in vivo. These results also offer a cautionary note suggesting that long-term PAR-1 inhibition could increase malignancy risk in some contexts.

PMID: 30152921 [PubMed - indexed for MEDLINE]

Polη, a Y-family translesion synthesis polymerase, promotes cellular tolerance of Myc-induced replication stress.

Fetched: November 24th, 2019, 5:01am GMT

Polη, a Y-family translesion synthesis polymerase, promotes cellular tolerance of Myc-induced replication stress.

J Cell Sci. 2018 06 25;131(12):

Authors: Kurashima K, Sekimoto T, Oda T, Kawabata T, Hanaoka F, Yamashita T

Abstract
Growth of precancerous and cancer cells relies on their tolerance of oncogene-induced replication stress (RS). Translesion synthesis (TLS) plays an essential role in the cellular tolerance of various types of RS and bypasses replication barriers by employing specialized polymerases. However, limited information is available about the role of TLS polymerases in oncogene-induced RS. Here, we report that Polη, a Y-family TLS polymerase, promotes cellular tolerance of Myc-induced RS. Polη was recruited to Myc-induced RS sites, and Polη depletion enhanced the Myc-induced slowing and stalling of replication forks and the subsequent generation of double-strand breaks (DSBs). Overexpression of a catalytically dead Polη also promoted Myc-induced DSB formation. In the absence of Polη, Myc-induced DSB formation depended on MUS81-EME2 (the S-phase-specific endonuclease complex), and concomitant depletion of MUS81-EME2 and Polη enhanced RS and cell death in a synergistic manner. Collectively, these results indicate that Polη facilitates fork progression during Myc-induced RS, thereby helping cells tolerate the resultant deleterious effects. Additionally, the present study highlights the possibility of a synthetic sickness or lethality between Polη and MUS81-EME2 in cells experiencing Myc-induced RS.

PMID: 29777036 [PubMed - indexed for MEDLINE]

NEN: Advancement in Diagnosis and Minimally Invasive Therapy.

Fetched: November 22nd, 2019, 5:01am GMT

NEN: Advancement in Diagnosis and Minimally Invasive Therapy.

Rofo. 2019 Nov 20;:

Authors: Putzer D, Schullian P, Jaschke W, Bale R

Abstract
Neuroendocrine neoplasms (NEN) are a heterogeneous type of malignant disease and frequently present with symptoms caused by the secretion of metabolically active substances or the manifestation of distant metastases, with the liver being the most frequent site of spreading. Early diagnosis of metastatic disease is recognized as the major prognostic factor in NEN patients. Complete surgical resection is feasible in only selected cases. For patients with unresectable liver metastases, various locoregional treatment approaches are available. Over the last decade, therapeutic procedures including locoregional and systemic treatments have been investigated for gastroenteropancreatic NEN (GEP-NEN), especially for metastatic disease to the liver. Only a few prospective clinical trials have compared these approaches, and the management of individual patients remains subject to clinical expertise and judgement. Locoregional treatments are applicable in patients with limited metastatic involvement of the liver, and may be used for tumor debulking and symptom control in patients with diffuse liver involvement. KEY POINTS:: · Neuroendocrine Neoplasms (NENs) represent a heterogeneous class of rare malignancies.. · Surgery is the treatment of choice for primary non-metastatic NEN.. · The liver is the most frequently affected site by neuroendocrine metastases.. · In limited metastastic liver disease local curative treatment may be accomplished by surgical resection or percutaneous thermal ablation.. · Multi-probe stereotactic thermal ablation with image fusion for intraoperative evaluation of a sufficient safety margin allows for safe and effective treatment of large liver metastases.. CITATION FORMAT: · Putzer D, Schullian P, Jaschke W et al. NET: Neue Entwicklungen in Diagnostik und minimalinvasiver Therapie. Fortschr Röntgenstr 2019; DOI: 10.1055/a-1030-4631.

PMID: 31747704 [PubMed - as supplied by publisher]

Permalink for 'Clinical Profiles and Survival Outcomes of Patients With Well-Differentiated Neuroendocrine Tumors at a Health Network in New South Wales, Australia: Retrospective Study.'

Clinical Profiles and Survival Outcomes of Patients With Well-Differentiated Neuroendocrine Tumors at a Health Network in New South Wales, Australia: Retrospective Study.

Fetched: November 22nd, 2019, 5:01am GMT

Clinical Profiles and Survival Outcomes of Patients With Well-Differentiated Neuroendocrine Tumors at a Health Network in New South Wales, Australia: Retrospective Study.

JMIR Cancer. 2019 Nov 20;5(2):e12849

Authors: Reeders J, Ashoka Menon V, Mani A, George M

Abstract
BACKGROUND: Neuroendocrine tumors (NETs) are a heterogeneous group of malignancies with varying and often indolent clinicobiological characteristics according to their primary location. NETs can affect any organ and hence present with nonspecific symptoms that can lead to a delay in diagnosis. The incidence of NETs is increasing in Australia; data regarding characteristics of NETs were collected from the cancer registry of Hunter New England, Australia.
OBJECTIVE: This study aimed to explore the clinical profiles and treatment and survival outcomes of patients with well-differentiated NETs in an Australian population.
METHODS: We reviewed the data of all adult patients who received the diagnosis of NET between 2008 and 2013. The clinicopathological, treatment, and follow-up data were extracted from the local Cancer Clinical Registry. We also recorded the level of remoteness for each patient by matching the patient's residential postcode to the corresponding Australian Bureau of Statistics 2011 remoteness area category. Univariate analysis was used to find the factors associated with NET-related mortality. Survival analysis was computed.
RESULTS: Data from 96 patients were included in the study (men: 37/96, 38.5%, and women: 59/96, 61.5%). The median age at diagnosis was approximately 63 years. A higher proportion of patients lived in remote/rural areas (50/96, 52.1%) compared with those living in city/metropolitan regions (46/96, 47.9%). The most common primary tumor site was the gastroenteropancreatic tract, followed by the lung. The factors significantly associated with NET-related mortality were age, primary tumor site, surgical resection status, tumor grade, and clinical stage of the patient. At 5 years, the overall survival rate was found to be 62%, and the disease-free survival rate was 56.5%.
CONCLUSIONS: Older age, advanced unresectable tumors, evidence of metastasis, and higher-grade tumors were associated with poorer outcomes. Lung tumors had a higher risk of NET-related mortality compared with other sites.

PMID: 31746768 [PubMed]

DNA methylation of GHSR, GNG4, HOXD9 and SALL3 is a common epigenetic alteration in thymic carcinoma.

Fetched: November 22nd, 2019, 5:01am GMT

DNA methylation of GHSR, GNG4, HOXD9 and SALL3 is a common epigenetic alteration in thymic carcinoma.

Int J Oncol. 2019 Nov 18;:

Authors: Kishibuchi R, Kondo K, Soejima S, Tsuboi M, Kajiura K, Kawakami Y, Kawakita N, Sawada T, Toba H, Yoshida M, Takizawa H, Tangoku A

Abstract
Thymic epithelial tumors comprise thymoma, thymic carcinoma and neuroendocrine tumors of the thymus. Recent studies have revealed that the incidence of somatic non‑synonymous mutations is significantly higher in thymic carcinoma than in thymoma. However, limited information is currently available on epigenetic alterations in these types of cancer. In this study, we thus performed genome‑wide screening of aberrantly methylated CpG islands in thymoma and thymic carcinoma using Illumina HumanMethylation450 K BeadChip. We identified 92 CpG islands significantly hypermethylated in thymic carcinoma in relation to thymoma and selected G protein subunit gamma 4 (GNG4), growth hormone secretagogue receptor (GHSR), homeobox D9 (HOXD9) and spalt like transcription factor 3 (SALL3), which are related to cancer. We examined the promoter methylation of 4 genes in 46 thymic epithelial tumors and 20 paired thymus tissues using bisulfite pyrosequencing. Promoter methylation was significantly higher in thymic carcinoma than in thymoma and revealed a high discrimination between thymic carcinoma and thymoma in all 4 genes. Promoter methylation was higher in thymic carcinoma than in the thymus. No significant differences were observed in the promoter methylation of GNG4, HOXD9, or SALL3 between thymoma and the thymus. The promoter methylation of the 4 genes was not significantly higher in advanced‑stage tumors than in early‑stage tumors in all thymic epithelial tumors. Among the 4 genes, relapse‑free survival was significantly worse in tumors with a higher DNA methylation than in those with a lower DNA methylation in all thymic epithelial tumors. Moreover, relapse‑free survival was significantly worse in thymomas with a higher DNA methylation of HOXD9 and SALL3 than in those with a lower DNA methylation. On the whole, the findings of this study indicated that the promoter methylation of cancer‑related genes was significantly higher in thymic carcinoma than in thymoma and the thymus. This is a common epigenetic alteration of high diagnostic value in thymic carcinoma and may be involved in the carcinogenesis of thymic carcinoma. However, epigenetic alterations in the 3 genes, apart from GHSR, are not involved in the tumorigenesis of thymoma.

PMID: 31746370 [PubMed - as supplied by publisher]

Carcinoid Heart Disease: a Comprehensive Review.

Fetched: November 22nd, 2019, 5:01am GMT

Carcinoid Heart Disease: a Comprehensive Review.

Curr Cardiol Rep. 2019 Nov 19;21(11):140

Authors: Hassan SA, Palaskas NL, Agha AM, Iliescu C, Lopez-Mattei J, Chen C, Zheng H, Yusuf SW

Abstract
PURPOSE OF REVIEW: Carcinoid heart disease is a rare disorder that is associated with significant morbidity and mortality. In this review of the literature, we will present current concepts in diagnosis and management of carcinoid heart disease.
RECENT FINDINGS: Recent expert consensus guidelines highlight the role of echocardiography and screening with NT-proBNP for the evaluation of carcinoid heart disease. Advances in medical therapy along with better surgical outcomes highlight the experience and expertise that has been gained in the treatment of carcinoid heart disease. Carcinoid heart disease occurs in patients with neuroendocrine tumors who have carcinoid syndrome. Serotonin appears to play a central role in the development of carcinoid heart disease. Cardiac biomarkers and multimodality imaging can be used to aid in screening and diagnosis. The mainstay of treatment of carcinoid heart disease is surgery.

PMID: 31745664 [PubMed - in process]

[Spinal schwannomas: case series].

Fetched: November 22nd, 2019, 5:01am GMT

[Spinal schwannomas: case series].

Pan Afr Med J. 2019;33:199

Authors: Himmiche M, Joulali Y, Benabdallah IS, Benzagmout M, Chakour K, Chaoui MF

Abstract
Spinal schwannomas are benign tumors accounting for 30% of all spinal tumors. They originate from the shwann cells of the spinal roots. We report our experience in managing patients with spinal shwannomas, from diagnosis to treatment modalities, in the Department of Neurosurgery at the University Hospital Hassan II in Fez over a period of 13 years. The patients with spinal shwannomas accounted for 19.5% of those with spinal cord compression treated surgically over the same period. The average age of patients was 45 years, with a discreet female predominance. Spinal schwannomas had an insidious onset, then the median of consultation time was 18 months. The main symptoms were spinal and radicular pain. Half of our patients had neurological deficits. Medullary MRI was performed in all of our patients. Spinal schwannomas occurred predominantly in the chest (40%); 62% of shwannomas were intradural lesions, rarely extradural lesions (8%) and mixed lesions(4%). Complete Surgical resection was performed in 96% of cases with osteosynthesis in two cases and arthrodesis in a single case. Histological examination confirmed the diagnosis of benign neurinoma in 23 cases, malignant shwannoma in one case and neurofibroma in one case. Outcome was favorable in the majority of cases, two patients had complications, an infection of the wall and neurological worsening. The interest in the subject of our study is to highlight the features of these lesions and to compare the results of our case series with the data in the literature.

PMID: 31692754 [PubMed - indexed for MEDLINE]

Primary jejunal melanoma as a cause of adult intussusception: a case report and review of literature.

Fetched: November 22nd, 2019, 5:01am GMT

Primary jejunal melanoma as a cause of adult intussusception: a case report and review of literature.

Pan Afr Med J. 2019;33:214

Authors: Olatoke SA, Agodirin SO, Adenuga AT, Lawal BO, Ibrahim KO, Folaranmi OO

Abstract
Primary melanoma of the small bowel is a rare clinical entity with a paucity of published reports in literature. Most cases of gastrointestinal melanomas are metastatic lesions arising from skin or ocular origins. This is a case report of a 63 year old female with adult intussusception with jejunal melanoma as the lead point. The index patient had a long history of abdominal pain associated with significant weight loss and presented with features of intestinal obstruction. The possibility of a regressed or unidentified extra-intestinal site cannot be absolutely excluded as the patient did not have a PET scan. Due to the vague nature of clinical symptoms and signs, the diagnosis of small bowel melanoma is difficult, especially in patients with no obvious cutaneous pathology. A high index of suspicion for melanoma as a malignant lead point for adult intussusception should always be entertained.

PMID: 31692747 [PubMed - indexed for MEDLINE]

Paroxysmal Hypertension Associated With Urination.

Fetched: November 22nd, 2019, 5:01am GMT

Paroxysmal Hypertension Associated With Urination.

Hypertension. 2019 11;74(5):1068-1074

Authors: Lou Y, Fan L, Hou X, Dominiczak AF, Wang JG, Staessen JA, Almustafa B, Ching S, Persu A, Bursztyn M, Cai J, Zhang H

PMID: 31564165 [PubMed - indexed for MEDLINE]

PRIMARY MALIGNANT MELANOMA OF THE URINARY BLADDER: CASE REPORT.

Fetched: November 22nd, 2019, 5:01am GMT

PRIMARY MALIGNANT MELANOMA OF THE URINARY BLADDER: CASE REPORT.

Acta Clin Croat. 2019 Mar;58(1):180-182

Authors: Kirigin M, Lež C, Šarčević B, Šoipi Š, Jaić G, Ulamec M, Krušlin B

Abstract
Primary malignant melanoma of the urinary bladder is rare, with only 20 cases reported to date. We present a case of an 87-year-old woman with multiple comorbidities who presented with advanced urinary bladder neoplasm. Histopathologic analysis suggested melanoma of the urinary bladder. No previous or concurrent diagnosis of cutaneous melanoma was documented. The patient underwent transurethral resection of the tumor before and during hospitalization at our hospital but died shortly after due to widespread disease. Autopsy was not performed.

PMID: 31363341 [PubMed - indexed for MEDLINE]

Nivolumab-Induced Pneumonitis in Patient With Metastatic Melanoma Showing Complete Remission on 18F-FDG PET/CT.

Fetched: November 22nd, 2019, 5:01am GMT

Nivolumab-Induced Pneumonitis in Patient With Metastatic Melanoma Showing Complete Remission on 18F-FDG PET/CT.

Clin Nucl Med. 2019 Oct;44(10):806-807

Authors: Razzouk-Cadet M, Picard A, Grangeon-Chapon C, Lacour JP, Montaudié H

Abstract
A 49-year-old patient with metastatic melanoma was treated with nivolumab (Opdivo). An early F-FDG PET/CT after 2 cycles showed a progressive metabolic disease. A 4-month optimal follow-up F-FDG PET/CT showed a complete metabolic response. The treatment was stopped after 22 cycles because of immunotherapy-related pneumonitis. After discontinuation of treatment, PET/CT examinations demonstrated a metabolic complete remission during 2 years. The metabolic pattern on early PET was suggestive of pseudoprogression, which is a rare phenomenon reflecting an activation of inflammatory cells within the tumor microenvironment causing lesions to increase in size and to accumulate FDG until a sufficient immune response is developed.

PMID: 31306191 [PubMed - indexed for MEDLINE]

Gynostemma pentaphyllum saponins induce melanogenesis and activate cAMP/PKA and Wnt/β-catenin signaling pathways.

Fetched: November 22nd, 2019, 5:01am GMT

Gynostemma pentaphyllum saponins induce melanogenesis and activate cAMP/PKA and Wnt/β-catenin signaling pathways.

Phytomedicine. 2019 Jul;60:153008

Authors: Tsang TF, Chan B, Tai WC, Huang G, Wang J, Li X, Jiang ZH, Hsiao WLW

Abstract
BACKGROUND: Melanogenesis is a physiological process of melanin production in response to UV exposure, which is modulated through multi-signaling pathways including cAMP/PKA, Wnt/β-catenin and MAPK signaling cascades.
HYPOTHESIS/PURPOSE: The present study aims to investigate the molecular mechanism of hyperpigmentation induced by Gynostemma pentaphyllum saponins.
STUDY DESIGN/METHODS: In this study, we investigated the melanogenic effects of triterpenoid saponins of Gynostemma pentaphyllum (GpS), a medicinal plant. Two mouse melanogenic cell lines B16 and B16F10 were employed for the current study.
RESULTS: The results showed that non-toxic doses of GpS markedly increased melanin formation in both B16 and B16F10 cells. Western blot analysis showed that GpS treatment significantly up-regulated the expression levels of the key melanogenic proteins, including tyrosinase (TYR), microphthalmia-associated transcription factor (MITF), TRP-1 and TRP-2 in a dose-dependent manner. The phospho-CREB, which is the downstream target of PKA is also elevated upon GpS treatment. We further observed that H89, a PKA inhibitor, attenuated the GpS induced tyrosinase activity, melanin content, the expression of phospho-CREB. In addition to the cAMP/PKA signaling pathway, GpS treatment also up-regulated the β-catenin of the Wnt signaling pathway which is involved in the transcriptional activation of MITF in melanogensis. We further demonstrated that treatment with GpS markedly enhance mRNA expression of MITF, along with the downstream target molecules, TYR, TRP-1 and TRP-2. Knock-down MITF with siMITF inhibited the expression of MITF mRNA by 63%, and the melanin content was reduced 70% in the siMITF-transfected cells compared to untransfected or scramble siRNA control cells.
CONCLUSION: These findings demonstrated strong melanogenic activities of GpS, and the MITF is essential for the melanogenesis stimulated by GpS.

PMID: 31288940 [PubMed - indexed for MEDLINE]

Permalink for 'Intracranial antitumor responses of nivolumab and ipilimumab: a pharmacodynamic and pharmacokinetic perspective, a scoping systematic review.'

Rare Cancer News & Clinical Trials » Endocrine/Neuroendocrine

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Endocrine/Neuroendocrine (536 unread)

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