Rare Cancer News & Clinical Trials » Endocrine/Neuroendocrine

Endocrine/Neuroendocrine (507 unread)

Permalink for 'UV Signature Mutations Reclassify Salivary High-grade Neuroendocrine Carcinomas as Occult Metastatic Cutaneous Merkel Cell Carcinomas.'

UV Signature Mutations Reclassify Salivary High-grade Neuroendocrine Carcinomas as Occult Metastatic Cutaneous Merkel Cell Carcinomas.

Fetched: April 17th, 2019, 5:00am GMT

UV Signature Mutations Reclassify Salivary High-grade Neuroendocrine Carcinomas as Occult Metastatic Cutaneous Merkel Cell Carcinomas.

Am J Surg Pathol. 2019 May;43(5):682-687

Authors: Sun L, Cliften PF, Duncavage EJ, Lewis JS, Chernock RD

Abstract
Salivary high-grade neuroendocrine carcinomas (NECs) are rare, occur predominantly in the parotid gland, and are difficult to differentiate from metastatic cutaneous Merkel cell carcinomas (MCCs), which have overlapping morphologic, immunophenotypic, and molecular profiles. Oncogenic Merkel cell polyomavirus (MCPyV), found in 70% to 80% of MCCs, has also been reported in a few salivary NECs, but this is controversial. A promising biomarker to distinguish the 2 tumor types are UV signature mutations. UV signature mutations indicate a sun damage-induced mechanism of pathogenesis and recently have been found to be highly prevalent in MCPyV-negative MCCs but would be inconsistent with salivary origin. Here, we examine UV signature mutations as a molecular marker to distinguish primary salivary high-grade NEC from MCC. Whole exome DNA sequencing was performed on matched tumor-normal tissue from 4 MCPyV-negative high-grade salivary NECs with no other primary source identified, as well as 3 melanomas and 3 lung NECs as positive and negative controls, respectively. UV signature mutations were found in all salivary NECs, when defined as ≥60% of total mutations being C-to-T transitions at dipyrimidine sites, and when compared with known human cancer-related mutational signatures. The presence of UV signature mutations in salivary high-grade NECs strongly favors these to be occult metastatic MCCs. True salivary primary NECs are likely exceedingly rare. When a high-grade NEC is encountered in the salivary gland, the presence of UV signature mutations or MCPyV may be useful to exclude occult unknown primary MCC.

PMID: 30986802 [PubMed - in process]

Predictors of survival in neurometastatic Merkel cell carcinoma.

Fetched: April 17th, 2019, 5:00am GMT

Predictors of survival in neurometastatic Merkel cell carcinoma.

Eur J Cancer. 2018 09;101:152-159

Authors: Harary M, Kavouridis VK, Thakuria M, Smith TR

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) is a rare cutaneous malignancy of neuroendocrine origin, with about 30 cases of brain metastasis (BM) reported in the literature. Historically, the treatment of neurometastatic MCC has largely included chemotherapy and radiotherapy. The aim was to investigate predictors of overall survival (OS) in neurometastatic MCC.
METHODS: In this retrospective study, we surveyed institutional databases and conducted a systematic review of the literature to identify cases reporting on management of distant MCC BM. A pooled survival analysis was performed on the institutional and literature cases to assess predictors of OS.
RESULTS: Forty cases were included for analysis, describing operative [14] and non-operative [26] management. Median time to central nervous system involvement was 17.0-mos (interquartile range 10.5-26.5), and most patients had a single BM (62.5%). Management of intracranial disease included radiotherapy (82.5%), systemic therapy (59.5%) and surgical resection (35%). Operative management was associated with a lower intracranial burden of disease (BoD), but similar systemic BoD. Both neurosurgery (hazard ratio [HR] 0.18, 95% confidence interval [CI]: 0.06-0.54, p = 0.002), having RT (HR 0.37, 95% CI: 0.14:0.93, p = 0.04) and having a single BM (extensive intracranial BoD: HR 2.51, 95% CI: 1.12-5.6, p = 0.03) conferred an OS benefit on risk-unadjusted analysis. Only, neurosurgical resection was an independent predictor of OS (HR 0.12, 95% CI: 0.03-0.49, p = 0.003), controlling for age, BoD and radiotherapy.
CONCLUSIONS: Resection of MCC BM may confer a survival benefit given appropriate patient selection. Prospective investigation of multimodal management of neurometastatic MCC is warranted, especially given the promise of new immunotherapy agents in treating MCC.

PMID: 30071443 [PubMed - indexed for MEDLINE]

Merkel cell carcinoma in a patient with relapsing-remitting multiple sclerosis treated with fingolimod.

Fetched: April 13th, 2019, 5:00am GMT

Merkel cell carcinoma in a patient with relapsing-remitting multiple sclerosis treated with fingolimod.

J Neurol Sci. 2017 10 15;381:296-297

Authors: Calvi A, De Riz M, Lecchi E, Pietroboni A, Ghezzi L, Scarioni M, Carandini T, Pellegrinelli A, Maurichi A, Galimberti D, Scarpini E

PMID: 28991701 [PubMed - indexed for MEDLINE]

Recent Therapeutic Advances and Change in Treatment Paradigm of Patients with Merkel Cell Carcinoma.

Fetched: April 11th, 2019, 5:00am GMT

Recent Therapeutic Advances and Change in Treatment Paradigm of Patients with Merkel Cell Carcinoma.

Oncologist. 2019 Apr 08;:

Authors: Garcia-Carbonero R, Marquez-Rodas I, de la Cruz-Merino L, Martinez-Trufero J, Cabrera MA, Piulats JM, Capdevila J, Grande E, Martin-Algarra S, Berrocal A

Abstract
Merkel cell carcinoma (MCC) is a rare, aggressive, primary cutaneous neuroendocrine tumor that typically presents as an indurated nodule on sun-exposed areas of the head and neck in the white population. Major risk factors include immunosuppression, UV light exposure, and advanced age. Up to 80% of MCC are associated with Merkel cell polyomavirus. About 50% of patients present with localized disease, and surgical resection with or without adjuvant radiotherapy is generally indicated in this context. However, recurrence rates are high and overall prognosis rather poor, with mortality rates of 33%-46%. MCC is a chemosensitive disease, but responses in the advanced setting are seldom durable and not clearly associated with improved survival. Several recent trials with checkpoint inhibitors (pembrolizumab, avelumab, nivolumab) have shown very promising results with a favorable safety profile, in both chemonaïve and pretreated patients. In 2017, avelumab was approved by several regulatory agencies for the treatment of metastatic MCC, the first drug to be approved for this orphan disease. More recently, pembrolizumab has also been approved by the U.S. Food and Drug Administration in this setting. Immunotherapy has therefore become the new standard of care in advanced MCC. This article reviews current evidence and recommendations for the diagnosis and treatment of MCC and discusses recent therapeutic advances and their implications for care in patients with advanced disease. This consensus statement is the result of a collaboration between the Spanish Cooperative Group for Neuroendocrine Tumors, the Spanish Group of Treatment on Head and Neck Tumors, and the Spanish Melanoma Group. IMPLICATIONS FOR PRACTICE: Merkel cell carcinoma (MCC) is an uncommon aggressive skin cancer associated with advanced age, UV light exposure, and immunosuppression. Up to 80% are associated with Merkel cell polyomavirus. MCC is a chemosensitive disease, but tumor responses in the advanced setting are short-lived with no long-term survivors. Recent clinical trials with immune checkpoint inhibitors (i.e., pembrolizumab, avelumab, nivolumab) have shown promising results, with avelumab becoming the first drug to receive regulatory approval for this orphan indication. Further follow-up is needed, however, to define more adequately the long-term benefits of these drugs, and continued research is warranted to optimize immunotherapeutic strategies in this setting.

PMID: 30962295 [PubMed - as supplied by publisher]

Permalink for 'Diagnosis and Treatment of Merkel Cell Carcinoma in Specialized Dermatology Units: A Clinical Practice Guideline of the Spanish Academy of Dermatology and Venereology.'

Diagnosis and Treatment of Merkel Cell Carcinoma in Specialized Dermatology Units: A Clinical Practice Guideline of the Spanish Academy of Dermatology and Venereology.

Fetched: April 11th, 2019, 5:00am GMT

Diagnosis and Treatment of Merkel Cell Carcinoma in Specialized Dermatology Units: A Clinical Practice Guideline of the Spanish Academy of Dermatology and Venereology.

Actas Dermosifiliogr. 2019 Apr 05;:

Authors: Vázquez Doval J, Llombart Cussac B, Pérez Bustillo A, Paradela de la Morena S, Fuente González MJ, Fernández Figueras MT, Villanueva MJ, Rodríguez Salas N, Descalzo-Gallego MÁ, García-Doval I, Ríos-Buceta L

Abstract
BACKGROUND AND OBJECTIVE: Merkel cell carcinoma is a rare, aggressive skin cancer that is managed in a great variety of ways. However, international clinical practice guidelines give only partial coverage to issues considered major problems.The recommendations presented here aim to provide Spanish dermatologists with a guide to improving disputed aspects of diagnosis, staging, and treatment of localized Merkel cell carcinomas.
MATERIAL AND METHODS: The ADAPTE process was used. Members of the Spanish Group of Oncologic Dermatology and Surgery (GEDOC) with experience in treating Merkel cell carcinoma and interest in drafting these guidelines were selected. The group described the care process and listed the most important clinical questions. They then searched for guidelines and assessed them with the AGREE II (Appraisal of Guidelines for Research and Evaluation) tool. After consulting the guidelines for answers to their clinical questions, the group drafted the present statementand sent it for external review.
RESULTS: The guidelines that scored highest in the AGREE II assessment step were the consensus-based interdisciplinary guideline of the European Association of Dermato-Oncology and the European Organization of Research and Treatment of Cancer, and those of the Comprehensive Cancer Network, the Alberta Health Services in Canada, the American Cancer Society, and the Cutaneous Oncology Group of the French Society of Dermatology. A total of 9 clinical questions were answered based on these guidelines.
CONCLUSIONS: The guidelines presented here answer clinical questions that arise in routine practice. They can provide dermatologists with a starting point for decision-making, although available resources and patient preferences must always be borne in mind.

PMID: 30961887 [PubMed - as supplied by publisher]

Permalink for 'Treatment patterns, comorbidities, healthcare resource use, and associated costs by line of chemotherapy and level of comorbidity in patients with newly-diagnosed Merkel cell carcinoma in the United States.'

Treatment patterns, comorbidities, healthcare resource use, and associated costs by line of chemotherapy and level of comorbidity in patients with newly-diagnosed Merkel cell carcinoma in the United States.

Fetched: April 11th, 2019, 5:00am GMT

Treatment patterns, comorbidities, healthcare resource use, and associated costs by line of chemotherapy and level of comorbidity in patients with newly-diagnosed Merkel cell carcinoma in the United States.

J Med Econ. 2018 Dec;21(12):1159-1171

Authors: Kearney M, Thokagevistk K, Boutmy E, Bharmal M

Abstract
AIMS: To examine the characteristics of patients with newly-diagnosed Merkel cell carcinoma (MCC), analyze their treatment patterns and comorbidities after diagnosis, and evaluate the economic burden on the MCC patient population in the US.
MATERIALS AND METHODS: This observational, non-interventional cohort study identified patients with MCC that were newly-diagnosed between January 1, 2010 through December 31, 2014, and whose data were either in the MarketScan Commercial Claims and Encounters (CCAE) or Medicare Supplemental and Coordination of Benefits databases. Standard descriptive statistics were used to describe patient demographics, clinical characteristics, treatment regimens, and healthcare resource use (HRU) and cost.
RESULTS: Following MCC diagnosis, most patients in the study population (n = 2,177) received only surgery (34.5%) or surgery and radiotherapy without chemotherapy (22.0%), while 14.5% of patients received none of these treatments; 27.5% of patients received at least one line of chemotherapy as part of their treatment. Mean total healthcare costs per patient per year (PPPY), as well as mean inpatient, outpatient, and pharmacy costs, were significantly greater for patients who received chemotherapy compared with those who received other or no treatments. Higher HRU and mean costs were associated with increasing patient comorbidity burden, ranging from $62,401 PPPY in Deyo Charlson Comorbidity Index level 1 to $109,690 in level ≥3.
LIMITATIONS: The study used claims databases that were limited to patients who are covered by large employer-sponsored insurance and/or Medicare and did not provide information regarding the rationale for treatment choice or resource use.
CONCLUSIONS: The choice of treatment is a major factor in determining healthcare costs associated with MCC, with the highest costs in patients receiving chemotherapy. Patients with MCC often exhibit comorbidities, and both HRU and healthcare costs increase significantly with each comorbidity level.

PMID: 30149739 [PubMed - indexed for MEDLINE]

Permalink for 'Intratumoral and peritumoral lymphovascular invasion detected by D2-40 immunohistochemistry correlates with metastasis in primary cutaneous Merkel cell carcinoma.'

Intratumoral and peritumoral lymphovascular invasion detected by D2-40 immunohistochemistry correlates with metastasis in primary cutaneous Merkel cell carcinoma.

Fetched: April 11th, 2019, 5:00am GMT

Intratumoral and peritumoral lymphovascular invasion detected by D2-40 immunohistochemistry correlates with metastasis in primary cutaneous Merkel cell carcinoma.

Hum Pathol. 2018 07;77:98-107

Authors: Al-Rohil RN, Milton DR, Nagarajan P, Curry JL, Feldmeyer L, Torres-Cabala CA, Ivan D, Prieto VG, Tetzlaff MT, Aung PP

Abstract
Primary cutaneous Merkel cell carcinoma (MCC) is an aggressive neuroendocrine malignancy in which lymphovascular invasion (LVI) correlates with more aggressive phenotype. The prognostic significance of LVI detected by D2-40 immunohistochemistry (IHC) in MCC remains controversial. We aimed to determine how LVI detected by D2-40 IHC compares with LVI detected by hematoxylin and eosin (H&E) staining in predicting MCC metastasis. Clinical and histopathologic features of MCCs diagnosed and treated in 2002 to 2015 were assembled and included 58 MCC tumors from 58 patients. H&E-stained tissue sections and D2-40 IHC studies were reviewed. When LVI was present, the location (peritumoral or intratumoral) and the size of the largest invaded vessel were recorded. LVI findings by H&E staining and D2-40 IHC were compared with each other and with histologic features and clinical outcomes. H&E staining showed LVI in 37 of 58 cases; D2-40 IHC confirmed LVI in 30 of these cases but failed to confirm LVI in 7. D2-40 IHC also detected 14 cases of LVI not identified on H&E staining. Histologically, D2-40-detected LVI was associated with infiltrative growth pattern and nonbrisk lymphoid infiltrate (P = .005 and P = .055, respectively). There was a statistically significant difference between the frequency of detection of peritumoral LVI by H&E in comparison to D2-40 IHC (P = .0009). MCCs in which D2-40 IHC-detected both intratumoral and peritumoral LVI were typically larger than MCCs without (mean, 24.5 mm versus 17.3 mm; P = .03) and more frequently metastasized (87% versus 51%; P = .03). D2-40 IHC detection of both intratumoral and peritumoral LVI is associated with metastasis.

PMID: 29601841 [PubMed - indexed for MEDLINE]

Intra-patient viral evolution in polyomavirus-related diseases.

Fetched: April 10th, 2019, 5:00am GMT

Intra-patient viral evolution in polyomavirus-related diseases.

Philos Trans R Soc Lond B Biol Sci. 2019 May 27;374(1773):20180301

Authors: McIlroy D, Halary F, Bressollette-Bodin C

Abstract
Human polyomaviruses show relatively little genetic polymorphism between isolates, indicating that these viruses are genetically stable between hosts. However, it has become increasingly clear that intra-host molecular evolution is a feature of some polyomavirus (PyV) infections in humans. Mutations inducing premature stop codons in the early region of the integrated Merkel cell PyV genome lead to the expression of a truncated form of the large tumour (LT) antigen that is critical for the transformation of Merkel cell carcinoma (MCC) cells. Non-coding control region (NCCR) rearrangements and point mutations in virion protein (VP) 1 have been described in both JCPyV and BKPyV infections. In the context of JCPyV infection, molecular evolution at both these loci allows the virus to replicate effectively in the central nervous system, thereby leading to the development of progressive multifocal leukoencephalopathy (PML). In BKPyV infection, NCCR rearrangements have been linked to higher rates of virus replication in the kidney, and are proposed to play a direct causal role in the development of PyV-associated nephropathy. In all three of these infections, therefore, intra-host viral evolution appears to be an essential component of the disease process. This article is part of the theme issue 'Silent cancer agents: multi-disciplinary modelling of human DNA oncoviruses'.

PMID: 30955497 [PubMed - in process]

Travel burden associated with rare cancers: The example of Merkel cell carcinoma.

Fetched: April 7th, 2019, 5:00am GMT

Travel burden associated with rare cancers: The example of Merkel cell carcinoma.

Cancer Med. 2019 Apr 05;:

Authors: Jain R, Menzin J, Lachance K, McBee P, Phatak H, Nghiem PT

Abstract
BACKGROUND: There are limited data on the travel burden for cancer patients with rare tumor types, such as Merkel cell carcinoma (MCC).
OBJECTIVE: The objective of this study was to understand the travel burden of MCC patients.
METHODS: This study used data from an MCC registry at the Seattle Cancer Care Alliance (SCCA). All MCC patients enrolled at SCCA with a valid 3-digit ZIP code were included. Patients were followed up from January 1, 2012 until their last follow-up, death, or end of data (January 1, 2017). Travel burden was measured by one-way travel distance to SCCA from each patient's 3-digit ZIP code. Patient demographics, tumor characteristics, and follow-up visit were evaluated and stratified by one-way driving distance of ≤300 and >300 miles.
RESULTS: A total of 391 MCC patients were included (68% men, mean age = 67 years [±SD = ±11 years], 67% residing in the West, and 70% white). At diagnosis, 53% of the patients had Stage III or IV MCC. Mean one-way distance traveled by patients was 1,137 (median: 813) miles, and 57% of patients traveled >300 miles. Compared to patients who traveled ≤300 miles, those who traveled >300 miles were more likely to be <70 years old (46% vs 65%; P < 0.001), were diagnosed with advanced stage (III or IV) MCC (46% vs 59%; P = 0.01), had shorter follow-up in the cancer registry (mean: 509 vs 212 days; P < 0.001), and had fewer visits during follow-up (mean: 5.2 vs 2.5; P < 0.001).
CONCLUSIONS: In this single cancer center study, the majority of MCC patients trav-eled long distances to receive expert care. Longer travel distances appeared to be associated with younger age, a more advanced stage of cancer at study entry and fewer in-clinic visits, suggesting that travel burden may impact timely and adequate patient care for this rare cancer.

PMID: 30950224 [PubMed - as supplied by publisher]

An Unusual Presentation of Merkel Cell Carcinoma in a HIV Patient: A Case Report and Literature Review.

Fetched: April 4th, 2019, 5:00am GMT

An Unusual Presentation of Merkel Cell Carcinoma in a HIV Patient: A Case Report and Literature Review.

J Investig Med High Impact Case Rep. 2019 Jan-Dec;7:2324709619836695

Authors: Ramachandran P, Erdinc B, Gotlieb V

Abstract
Merkel cell carcinoma (MCC) is a rare, rapidly growing, aggressive neuroendocrine skin cancer that generally arises on sun-exposed areas of body such as head, neck, upper limbs, and shoulders of people with light complexity. Typically, MCC presents as shiny, flesh-colored or bluish-red, intracutaneous nodule, possibly with ulceration or crusting. In most of the cases, there is an association with Merkel cell polyomavirus. Even though these are very aggressive tumors, early detection and treatment has always given favorable outcome. There seems to be no consensus in definite prognostic markers, and advanced stages have the worst outcome even with treatment. There has been a recent trend in using PD-I/PD-L1 target therapy rather than chemotherapy in these cancers and have shown to improve survival by many months. In this article, we report a very unusual presentation of MCC first found on left frontoparietal skull as an 8-cm diameter fixed, subcutaneous mass without any typical features of MCC and was found to have metastatic spread to lung and liver. The patient was treated with palliative radiotherapy to brain and chemotherapy with cisplatin/etoposide with addition of immunotherapy later.

PMID: 30938171 [PubMed - in process]

PDQ Cancer Information Summaries

Fetched: April 4th, 2019, 5:00am GMT

PDQ Cancer Information Summaries

Book. 2002

Authors:

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

PMID: 26389202

PDQ Cancer Information Summaries

Fetched: April 4th, 2019, 5:00am GMT

PDQ Cancer Information Summaries

Book. 2002

Authors:

PMID: 26389158

The role of radiotherapy in the management of non-melanoma skin cancer.

Fetched: April 3rd, 2019, 5:00am GMT

The role of radiotherapy in the management of non-melanoma skin cancer.

Australas J Dermatol. 2019 Mar 31;:

Authors: Garbutcheon-Singh KB, Veness MJ

Abstract
The global incidence of non-melanoma skin cancer continues to increase as the global population ages with the highest incidence in the world occurring in Australian and New Zealand patients. There are numerous treatment options available for non-melanoma skin cancer patients of which radiotherapy is an efficacious and versatile tissue preserving non-surgical (or medical) option. In patients where excision may not be an option (medically/technically inoperable) or considered less ideal (e.g. cosmetic outcome), radiotherapy offers an excellent option. Following surgery, adjuvant radiotherapy in patients with unfavourable pathology can decrease the risk of recurrence and associated morbidity. Elderly and co-morbid patients with poor performance status can benefit from short-course hypofractionated radiotherapy in the setting where surgery is not an option. As with any modality, radiotherapy has advantages and disadvantages and it is therefore important for clinicians to appreciate these. We aim to present an update for clinicians that manage patients with non-melanoma skin cancer on the role of radiotherapy.

PMID: 30931531 [PubMed - as supplied by publisher]

[Lymph node metastasis of Merkel cell carcinoma without known cutaneous primary - case report].

Fetched: April 3rd, 2019, 5:00am GMT

[Lymph node metastasis of Merkel cell carcinoma without known cutaneous primary - case report].

Cesk Patol. Fall 2017;53(3):135-138

Authors: Szabó A, Richter I, Frydrychová D, Saláková M, Jirásek T

Abstract
Merkel cell carcinoma is a rare cutaneous tumor with an aggressive clinical course. In most cases it is associated with Merkel cell polyomavirus infection. Exceptionally, the tumor can present as a lymph node metastasis without a discernible cutaneous primary. In this report we present the case of a 42 year-old man with inguinal lymphadenopathy, histologically consistent with Merkel cell carcinoma. Tumor cells expressed immunohistochemically chromogranin-A, synaptophysin and displayed dot-like positivity for cytokeratin 20. The genome of MCPyV in neoplastic cells was detected using real-time PCR. A cutaneous primary has not been identified neither during the dermatologic examination, nor with PET CT scan.

PMID: 28937781 [PubMed - indexed for MEDLINE]

Permalink for 'Survival Impact of Time to Initiation of Adjuvant Radiation for Merkel Cell Carcinoma: an analysis of the National Cancer Database.'

Survival Impact of Time to Initiation of Adjuvant Radiation for Merkel Cell Carcinoma: an analysis of the National Cancer Database.

Fetched: April 1st, 2019, 5:00am GMT

Survival Impact of Time to Initiation of Adjuvant Radiation for Merkel Cell Carcinoma: an analysis of the National Cancer Database.

Pract Radiat Oncol. 2019 Mar 26;:

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

Abstract
OBJECTIVE(S): To determine the impact of time to initiation (TTI) of adjuvant radiation therapy (RT) on overall survival (OS) for patients with stage I or II Merkel cell carcinoma (MCC).
METHODS: The NCDB was queried for patients with MCC of the head and neck, trunk or extremities diagnosed from 2006 to 2014. Patients who did not undergo resection or who did not receive adjuvant RT within 180 days of surgery were excluded. TTI was defined as time from resection to first RT fraction. Linear regression was used to define factors associated with TTI. RPA modeling was performed to determine an optimal threshold for TTI. Cox proportional hazards modeling was performed to define covariates associated with OS.
RESULTS: A total of 2293 patients were included in this study. The median TTI for the cohort was 62 days (IQR 43-86 days). TTI was not associated with OS for the overall cohort by multivariable Cox modeling (p = 0.19). Age, treatment facility type, lymph node examination, anatomic subsite and surgical margin were associated with TTI (p values <0.05). Age, sex, insurance status, Charlson/Deyo comorbidity score, lymph node examination status, tumor size and surgical margin were associated with OS (all p values <0.05).
DISCUSSION: Increased TTI of adjuvant RT was not associated with OS for patients with early stage MCC in this analysis of the NCDB. The median TTI of 62 days from resection to adjuvant RT initiation for our study cohort contextualizes TTI on a national level and may offer reassurance for patients with prolonged postoperative wound healing or intercurrent illness delaying immediate RT initiation. Despite lack of a clear detriment to survival with increased TTI up to 180 days from surgery, unnecessary delays to initiating adjuvant therapy should continue to be minimized while ensuring optimal recovery from resection.

PMID: 30926480 [PubMed - as supplied by publisher]

Permalink for 'The frequency of Merkel cell polyomavirus in whole blood from immunocompetent and immunosuppressed patients with kidney disease and healthy donors.'

The frequency of Merkel cell polyomavirus in whole blood from immunocompetent and immunosuppressed patients with kidney disease and healthy donors.

Fetched: March 28th, 2019, 5:00am GMT

The frequency of Merkel cell polyomavirus in whole blood from immunocompetent and immunosuppressed patients with kidney disease and healthy donors.

Microb Pathog. 2019 Mar 22;:

Authors: Jin HT, Park SJ, Choi EK, Kim YS

Abstract
Merkel cell polyomavirus (MCPyV) is a rare, aggressive and related to human diseases in immunocompromised patients. MCPyV has been detected in skin neoplasms, various cancers, immunosuppressed patients and immunocompetent individuals. Several studies have confirmed the presence of MCPyV in patients with kidney dysfunction, such as kidney transplant (KTx) and long-term dialysis patients. The aims of this study were to quantify and compare the frequency of MCPyV in whole blood samples from immunocompetent and immunosuppressed patients and healthy blood donors and to compare MCPyV genotypes in a Korean population. DNA from Groups 1, 2, and 3 was screened for MCPyV using polymerase chain reaction (PCR) and quantitative real-time PCR (qPCR) with primer pairs targeting two regions of the large T-antigen. Thirteen of 122 whole-blood samples (12.7%) were positive for MCPyV. The virus was detected in the three groups of patients and healthy donors; specifically, in 5 of 30 (16.7%) KTx patients (Group 1), 6 of 52 (11.5%) dialysis patients (Group 2), and 4 of 40 (10%) healthy donors (Group 3). Low viral DNA loads 4.4-18 copies/μl were observed using qPCR DNA sequences from the two MCPyV-LT regions, which showed high homology with MCPyV sequences belonging to the TKS strain from Japan rather than the Chinese/European/North American strains. The MCPyV DNA was similarly amplified in whole blood from immunocompetent and immunosuppressed patients and healthy donors. This virus may be involved in establishing the persistence of infected peripheral leukocytes in the host, based on the incidence of detection of MCPyV DNA in blood samples from immunocompromised and immunocompetent subjects. This study is the first to identify a Korean MCPyV strain in whole-blood samples from Korean patients with kidney disease and healthy individuals.

PMID: 30910721 [PubMed - as supplied by publisher]

Permalink for 'A Spontaneous Regression of an Isolated Lymph Node Metastasis from a Primary Unknown Merkel Cell Carcinoma in a Patient with an Idiopathic Hyper-Eosinophilic Syndrome.'

A Spontaneous Regression of an Isolated Lymph Node Metastasis from a Primary Unknown Merkel Cell Carcinoma in a Patient with an Idiopathic Hyper-Eosinophilic Syndrome.

Fetched: March 28th, 2019, 5:00am GMT

A Spontaneous Regression of an Isolated Lymph Node Metastasis from a Primary Unknown Merkel Cell Carcinoma in a Patient with an Idiopathic Hyper-Eosinophilic Syndrome.

Am J Case Rep. 2018 Dec 04;19:1437-1440

Authors: Longo R, Balasanu O, Chastenet de Castaing M, Chatelain E, Yacoubi M, Campitiello M, Marcon N, Plastino F

Abstract
BACKGROUND Merkel cell carcinoma (MCC) is a rare, aggressive primary cutaneous neuroendocrine tumor frequently associated with Merkel cell polyomavirus infection. Despite its aggressiveness, a few reports of spontaneous MCC regression have been described in the literature, most of them following incisional biopsy supporting a hypothetical role of surgery-induced inflammation in the process of regression. CASE REPORT We report a case of 69-year-old Caucasian male who was followed for an idiopathic hyper-eosinophilic syndrome. A positron emission tomography (PET) scan documented a hyper-metabolic, left, inguinal adenopathy, histologically corresponding to a metastasis of a poorly differentiated neuroendocrine carcinoma. This lesion spontaneously regressed at clinical examination and radiological imaging. After its excisional dissection, histology was negative. Five months later, a nearby adenopathy reappeared. The patient underwent another excisional biopsy. Histology and immunohistochemistry were compatible with a lymph node metastasis of a MCC. As the patient refused radical surgery, a regional radiotherapy was performed. As of a follow-up at 10 months, he was alive and free of tumor recurrence. The hyper-eosinophilic syndrome was stable; however, the serum levels of chromogranin-A were inexplicably elevated in the absence of any tumor evidence at the PET scan. CONCLUSIONS The particularity of this case relies on the rarity of MCC complete spontaneous regression in a patient without a primary tumor and with a synchronous, idiopathic hyper-eosinophilic syndrome.

PMID: 30510152 [PubMed - indexed for MEDLINE]

Permalink for 'Sentinel lymph node biopsy in Merkel cell carcinoma: Predictors of sentinel lymph node positivity and association with overall survival.'

Sentinel lymph node biopsy in Merkel cell carcinoma: Predictors of sentinel lymph node positivity and association with overall survival.

Fetched: March 26th, 2019, 5:00am GMT

Sentinel lymph node biopsy in Merkel cell carcinoma: Predictors of sentinel lymph node positivity and association with overall survival.

J Am Acad Dermatol. 2019 Mar 19;:

Authors: Conic RR, Ko J, Saridakis S, Damiani G, Funchain P, Vidimos A, Gastman BR

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive malignancy, with high rates of recurrence and metastasis.
OBJECTIVE: To evaluate predictors of sentinel lymph node (SLN) positivity in Merkel cell carcinoma using the National Cancer Database (NCDB).
METHODS: The NCDB, from 2012-2014, was used to identify 3,048 patients with MCC of which 1,174 received a SLN biopsy (SLNB). Predictors of SLN positivity were evaluated using logistic regression, overall survival (OS) was evaluated using a Cox proportional hazards model.
RESULTS: Of patients who underwent SLNB, those with primary lesions on the trunk (OR 1.98, 95%CI 1.23-3.17, p=0.004), tumor infiltrating lymphocytes (OR 1.58, 95%CI 1.01-2.46, p=0.04), or lymphovascular invasion (OR 3.45, 95%CI 2.51-4.76, p<0.001) were more likely to have positive SLN on multivariate analysis. OS was negatively affected by age ≥75 (HR 2.55, 95%CI 1.36-4.77, p=0.003), male gender (HR 1.78, 95%CI 1.09-2.91, p=0.022), immunosuppression (3.51, 95%CI 1.72-7.13, p=0.001), and SLN positivity (3.15, 95%CI 1.98-5.04, p<0.001).
LIMITATIONS: Lack of disease specific survival, potential selection bias from a retrospective dataset.
CONCLUSIONS: Truncal MCC, tumor infiltrating lymphocytes and presence of lymphovascular invasion were independent predictors of positive SLN. OS was negatively affected by advancing age, male gender, immunosuppression, and SLN positivity.

PMID: 30902726 [PubMed - as supplied by publisher]

Permalink for 'Epidemiology and survival of Merkel cell carcinoma in New Zealand: A population-based study between 2000 and 2015 with international comparison.'

Epidemiology and survival of Merkel cell carcinoma in New Zealand: A population-based study between 2000 and 2015 with international comparison.

Fetched: March 24th, 2019, 5:00am GMT

Epidemiology and survival of Merkel cell carcinoma in New Zealand: A population-based study between 2000 and 2015 with international comparison.

Australas J Dermatol. 2019 Mar 21;:

Authors: Lee Y, Chao P, Coomarasamy C, Mathy JA

Abstract
BACKGROUND/OBJECTIVES: Merkel cell carcinoma is an aggressive neuroendocrine skin cancer. Australian studies report high incidence and poor survival rates compared internationally. While New Zealand has a comparable UV index and racial composition to Australia, survival outcomes are currently unknown. The role of Merkel cell polyoma virus in oncogenesis of Merkel cell carcinoma is an active area of research. We describe the incidence and survival of Merkel cell carcinoma in New Zealand with correlation to demographic and clinical factors including regional polyoma virus prevalence.
METHODS: Retrospective study of population-based data from the New Zealand Cancer Registry. Incidence rates were directly standardised to the US standard 2000 population. Survival was investigated using Kaplan-Meier and multivariable Cox regression models.
RESULTS: Six hundred and one cases were diagnosed in New Zealand between 2000 and 2015. The overall incidence rate was 0.96/100 000 population. Merkel cell carcinoma is more common in males, elderly and on sun-exposed areas. Eighteen percent of patients were diagnosed with distant metastasis at time of presentation. The overall 5-year survival rate and relative 5-year survival rate were 31% and 45%, respectively. Mortality was 1.9 and 2.5 times higher for stage III and IV disease, respectively, relative to stage I/II disease. Patients over age 80 had twice the mortality compared to those aged 60-69.
CONCLUSIONS: New Zealand has a high incidence of Merkel cell carcinoma and poor survival outcomes when compared internationally. We have the highest proportion of distant metastatic disease at time of diagnosis. Further research into the role of nonpolyoma-related Merkel cell carcinoma is warranted to improve Merkel cell carcinoma outcomes in New Zealand and abroad.

PMID: 30900248 [PubMed - as supplied by publisher]

Co-expression of NGF and PD-L1 on tumor-associated immune cells in the microenvironment of Merkel cell carcinoma.

Fetched: March 24th, 2019, 5:00am GMT

Co-expression of NGF and PD-L1 on tumor-associated immune cells in the microenvironment of Merkel cell carcinoma.

J Cancer Res Clin Oncol. 2018 Jul;144(7):1301-1308

Authors: Wehkamp U, Stern S, Krüger S, Weichenthal M, Hauschild A, Röcken C, Egberts F

Abstract
PURPOSE: Merkel cell carcinoma (MCC) is a malignant neuroendocrine skin tumor with known viral association. The microenvironment and its interaction with the tumor via the programmed cell death protein 1 (PD-1) pathway are crucial for response to anti-PD-1/anti-PD-L1 treatments. However, not all patients respond, which is suggestive of additional mechanisms for tumor growth and/or persistence. We previously detected tropomyosin receptor kinase A (TrkA) expression on MCC tumor cells and, therefore, gained interest in the expression of its ligand nerve growth factor (NGF).
METHODS: Thirty-nine patients from our department were studied for immunohistochemical NGF, PD-1, and PD-L1 expression and clinico-pathological correlation.
RESULTS: PD-L1 was expressed on the tumor cells in 42%. In 95%, PD-L1 expression was also found on CD68+ spindle cells at the tumor border, which co-expressed NGF in 71%. 66% contained PD-1+ tumor infiltrating lymphocytes. PD-1, PD-L1, and NGF expression seems to correlate with a worse outcome.
CONCLUSIONS: The present study shows that PD-L1 and NGF are co-expressed on spindle cells in the microenvironment. The expression of NGF might be a link of the microenvironment to the TrkA-positive tumor cells. Whether this mechanism is critical for tumor growth and lack of response to anti-PD-1/L1 treatment has to be investigated in further studies.

PMID: 29744662 [PubMed - indexed for MEDLINE]

Rapid Drug Desensitization with Chemotherapeutics (Platins, Taxanes, and Others): A Single-Center Retrospective Study.

Fetched: March 22nd, 2019, 5:00am GMT

Icon for S. Karger AG, Basel, Switzerland

Rapid Drug Desensitization with Chemotherapeutics (Platins, Taxanes, and Others): A Single-Center Retrospective Study.

Int Arch Allergy Immunol. 2019 Mar 20;:1-9

Authors: Kendirlinan R, Gümüşburun R, Çerçi P, Özbek E, Altıner S, Çelebi Sözener Z, Soyyiğit Ş, Aydın Ö, Bavbek S

Abstract
BACKGROUND: Rapid drug desensitization (RDD) induces a temporary tolerance to chemotherapeutics that induce hypersensitivity reactions (HSRs).
PURPOSE: Our objective is to report our experience with RDD to platins, taxanes, etoposide, doxorubicin, and irinotecan.
METHODS: The study was conducted as a retrospective chart review of patients with symptoms of HSRs to chemotherapeutics. HSRs were classified as grade I, II, or III, based on their severity. Skin prick/intradermal tests were performed with implicated chemotherapeutics. A 12-step RDD protocol was used.
RESULTS: The study consisted of 38 women and 3 men (mean age 53.3 ± 11.6 years). Patients had ovarian (n = 13, 31.8%), breast (n = 10, 24.4%), colon (n = 7, 17%), lung (n = 4, 9.8%), and other cancers (n = 7; endometrial sarcoma, testicular cancer, uterine cancer, ampulla of Vater tumor, choledochal tumor, peritonitis carcinomatosa, and Merkel cell carcinoma, n = 1, respectively). Twenty-two patients experienced HSRs to platins, 15 to taxanes, and 4 to other chemotherapeutics (doxorubicin, irinotecan, and etoposide). A total of 122 RDDs (47 to platins, 52 to taxanes, 23 to other chemotherapeutics) were performed. In 25 (61%) patients no reactions occurred during RDD, but breakthrough reactions developed in 16 patients (39%) with platins (n = 11), taxanes (n = 3), doxorubicin (n = 1), and irinotecan (n = 1). RDD procedures could not be completed in only 2 patients with grade II breakthrough reactions to carboplatin and oxaliplatin.
CONCLUSION: In our experience, 98.3% of 122 RDDs were completed. We found that RDD was safe and effective in this the largest series of RDD with chemotherapeutics in our country.

PMID: 30893688 [PubMed - as supplied by publisher]

Seed and soil? - Pharyngeal Merkel cell carcinoma after radiotherapy for laryngeal squamous cell carcinoma.

Fetched: March 21st, 2019, 5:00am GMT

Seed and soil? - Pharyngeal Merkel cell carcinoma after radiotherapy for laryngeal squamous cell carcinoma.

Am J Otolaryngol. 2019 Mar 09;:

Authors: Rossi MK, Kanagasabapathy DAR, Hoffman HT

Abstract
Merkel cell carcinoma (MCC) is a neuroendocrine cutaneous malignancy that may present as metastatic disease without a known primary site but, most commonly originates in the sun-exposed skin of the head, neck, and extremities. We present a 66-year-old male treated with chemo-radiation for T3N2cM0 laryngeal squamous cell carcinoma (SCCa) six years before he was diagnosed with MCC isolated to the radiated laryngopharynx. Mucosal MCC is rare and radiation-induced MCC has been hypothesized to occur in previously radiated tissue but, never before to the laryngopharynx. Implications regarding cancer biology and management is focused with discussion on relevant advances in pathologic assessment and immunotherapy.

PMID: 30885449 [PubMed - as supplied by publisher]

Merkel cell carcinoma in a patient treated with infliximab: Beware of the subcutaneous nodule.

Fetched: March 21st, 2019, 5:00am GMT

Merkel cell carcinoma in a patient treated with infliximab: Beware of the subcutaneous nodule.

Australas J Dermatol. 2018 Nov;59(4):e288-e290

Authors: Davenport R, Brennand S, Goh MS, Prakash S, Chong AH

PMID: 29658988 [PubMed - indexed for MEDLINE]

Merkel cell carcinoma incidence, trends, and survival rates among adults aged ≥50 years from United States Cancer Statistics.

Fetched: March 18th, 2019, 5:00am GMT

Merkel cell carcinoma incidence, trends, and survival rates among adults aged ≥50 years from United States Cancer Statistics.

J Am Acad Dermatol. 2019 Apr;80(4):1154-1156

Authors: Freeman MB, Holman DM, Qin J, Lunsford NB

PMID: 30876535 [PubMed - in process]

Permalink for 'Characterization of six Merkel cell polyomavirus-positive Merkel cell carcinoma cell lines: integration pattern suggest that Large T antigen truncating events occur before or during integration.'

Characterization of six Merkel cell polyomavirus-positive Merkel cell carcinoma cell lines: integration pattern suggest that Large T antigen truncating events occur before or during integration.

Fetched: March 17th, 2019, 5:00am GMT

Characterization of six Merkel cell polyomavirus-positive Merkel cell carcinoma cell lines: integration pattern suggest that Large T antigen truncating events occur before or during integration.

Int J Cancer. 2019 Mar 15;:

Authors: Schrama D, Sarosi EM, Adam C, Ritter C, Kaemmerer U, Klopocki E, König EM, Utikal J, Becker JC, Houben R

Abstract
Merkel cell carcinoma (MCC), an aggressive neuroendocrine skin tumor, is a polyomavirus-induced human cancer. To study the causal relationship of MCC carcinogenesis with the integrated Merkel cell polyomavirus (MCPyV) in detail, well-characterized MCC cell lines are needed. Consequently, in the current study we established and characterized six MCPyV-positive MCC cell lines. Microarray-based comparative genomic hybridization revealed a stable genome carrying only a limited number of chromosomal gains and deletions. All cell lines expressed MCC markers Keratin-20 and neuron-specific enolase as well as truncated MCPyV-encoded large T antigen (LT). For five cell lines, we were able to identify the MCPyV-integration sites in introns of different genes. The LT-truncating stop codon mutations and integration sites were affirmed in the respective clinical patient samples. Inverse PCR suggested that three of the cell lines contained MCPyV genomes as concatemers. This notion was confirmed for the two cell lines with known integration sites. Importantly, our observation of distinct stop codon mutations in cell lines with concatemeric MCPyV integration indicates that these LT-truncating mutations occur before integration. In summary, we provide the detailed characterization of six MCPyV-positive MCC cell lines, which are likely to serve as valuable tools in future MCC research. This article is protected by copyright. All rights reserved.

PMID: 30873613 [PubMed - as supplied by publisher]

Tumors of the Ischiorectal Fossa: A Single-Institution Experience.

Fetched: March 16th, 2019, 5:00am GMT

Tumors of the Ischiorectal Fossa: A Single-Institution Experience.

Dis Colon Rectum. 2019 02;62(2):196-202

Authors: Zhu KJ, Lee PJ, Austin KKS, Solomon MJ

Abstract
BACKGROUND: Ischiorectal fossa tumors are rare.
OBJECTIVE: This study reviews a single institution's series of ischiorectal tumors with comparison against presacral tumors and assesses the utility of preoperative biopsy and angioembolization.
DESIGN: This is a retrospective study.
SETTINGS: This study was conducted at a quaternary referral center.
PATIENTS: All patients with ischiorectal tumor treated between February 1995 and April 2017 were retrospectively reviewed. Tumors extending secondarily into the ischiorectal fossa and inflammatory pathologies were excluded.
INTERVENTIONS: Preoperative biopsy, neoadjuvant therapy, angioembolization, and surgical excision of these tumors were reviewed.
MAIN OUTCOME MEASURES: Demographic, perioperative, pathological, and oncologic outcomes were evaluated.
RESULTS: Twenty-four patients (15 female; median age 54) were identified. Two-thirds were symptomatic. Forty-six percent had a palpable mass. All patients had CT and/or MRI. Fifty percent had a preoperative biopsy, of which 83% were diagnostic, and management was altered in 50%. All patients underwent surgical excision. Fifty-five percent had local excision, 38% had radical pelvic excision, and 8% had total mesorectal excision. Two patients had preoperative angioembolization. Both had successful R0 local excision. Morbidity occurred in 25%, with 1 major complication. There was no 30-day mortality. Histopathology demonstrated 17 soft tissue tumors (3 malignant), 2 GI stromal tumors, 1 neuroendocrine tumor, 1 Merkel cell carcinoma, 1 basaloid carcinoma, 1 epidermal cyst, and 1 lipoma. R0 resection was achieved in 75%. All patients were alive after a median follow-up of 33 months. Four patients developed recurrence at a median 10 months postoperatively. All recurrences were malignant, and 75% had had a R1 resection.
LIMITATIONS: This study is limited by its small numbers. The quaternary institution source may introduce bias.
CONCLUSIONS: Ischiorectal fossa tumors are heterogeneous and more likely to be malignant than presacral tumors. Biopsy can be useful if a malignant diagnosis is suspected and changes management in 50% of cases. Preoperative embolization may be useful for large vascular tumors. R0 resection is important to minimize recurrence. See Video Abstract at [links.lww.com]

PMID: 30640835 [PubMed - indexed for MEDLINE]

Merkel cell carcinoma: Do Australians have a more aggressive variant and a worse outcome?

Fetched: March 16th, 2019, 5:00am GMT

Merkel cell carcinoma: Do Australians have a more aggressive variant and a worse outcome?

Australas J Dermatol. 2018 Aug;59(3):239-240

Authors: Veness M

PMID: 28804895 [PubMed - indexed for MEDLINE]

Merkel cell carcinoma: long-term follow-up of a single institution series and clinical outcomes by immunological status.

Fetched: March 15th, 2019, 5:00am GMT

Merkel cell carcinoma: long-term follow-up of a single institution series and clinical outcomes by immunological status.

Dermatol Online J. 2018 Feb 15;25(2):

Authors: Dasanu CA, Del Rosario M, Codreanu I, Lu Y, Farrell S, Hyams DM, Plaxe SC

Abstract
Merkel cell carcinoma (MCC) usually arises in sun-exposed areas of older patients and might be more aggressive in the immunocompromised. We performed a retrospective chart review of 40 consecutive MCC patients treated at our institution between the years 2006-2017. Clinical and epidemiologic data were utilized and therapy and survival were analyzed. Compared to Surveillance, Epidemiology, and End Results (SEER) data, our population was entirely Caucasian (100% versus 95%; P=0.11) and male predominant (75% versus 63%; P=0.11). The median age was 76. The patients more often had Tumor-Node-Metastasis (TNM) stage I disease (50% versus 39%; P=0.00003) and a primary tumor size<2cm (57.5% versus 34%; P<0.01). They received more frequently lymph node dissection (70% versus 63%, P=0.002) compared with the SEER findings. We identified a subset of immunocompromised patients (n=10) who presented with more stage III disease (40% versus 33%; P=0.021). Time to death averaged 290.1 days in this subset versus 618.2 days (P<0.001) in immunocompetent patients and their likelihood of death was 5 times higher. As clinical outcomes in MCC patients vary by immunological status, a multidisciplinary tumor-board approach may better optimize individual patient management.

PMID: 30865403 [PubMed - in process]

A case of locally-advanced Merkel cell carcinoma progressing with disseminated bone marrow metastases.

Fetched: March 15th, 2019, 5:00am GMT

A case of locally-advanced Merkel cell carcinoma progressing with disseminated bone marrow metastases.

Eur J Dermatol. 2018 Aug 01;28(4):550-551

Authors: Kobrinski DA, Choudhury AM, Shah RP

Abstract

PMID: 30325324 [PubMed - indexed for MEDLINE]

Primary Visceral Merkel Cell Carcinoma: A Case Report and Review of the Literature.

Fetched: March 15th, 2019, 5:00am GMT

Primary Visceral Merkel Cell Carcinoma: A Case Report and Review of the Literature.

Am J Dermatopathol. 2018 Dec;40(12):927-929

Authors: Siref A, Hendifar A, Balzer B

Abstract
A 63-year-old white man with no significant previous medical or surgical history presented with painless jaundice after 3 weeks of dark urine, yellow stools, and a 9-pound weight loss. Bilirubin, aspartate transaminase, alanine transaminase, and alkaline phosphatase were elevated, and a computed tomography scan detected a 10-cm, ill-defined mass at the porta hepatis compressing the common bile duct. He underwent endoscopic retrograde cholangiopancreatography with stenting and ultrasound-guided biopsies. Histologic sections showed a neoplastic population of small ovoid cells with a high N:C ratio, nuclear hyperchromasia, "smoky" chromatin and abundant mitotic figures, and characteristic of high-grade neuroendocrine carcinoma (HGNECA). Immunohistochemistry showed synaptophysin, chromogranin, Golgi pattern CK20 reactivity, and strong diffuse expression of Merkel cell polyomavirus, supporting a diagnosis of Merkel cell carcinoma (MCC). A metastatic workup, including complete skin examination and positron emission tomography scan, revealed no other site of disease. Although this patient fits the classic demographic pattern for MCC, he lacks cutaneous involvement and significant risk factors for MCC including immunosuppression and concurrent or previous malignancy. Histologically, the differential diagnosis in this anatomical site is primary or occult metastatic organ-based small-cell HGNECA. Although pure nodal MCC accounts for a minute subset of MCC, it is almost exclusively described in superficial and extremity-draining nodal basins (eg, axillary or inguinal regions). Primary visceral nodal MCC accounts for fewer than 5 cases ever reported. This case illustrates the importance of recognizing the morphologic features characteristic of MCC, regardless of anatomical location, and the value of immunohistochemistry in diagnosis, which aid in differentiating it from non-MCC mimics. Development of targeted therapy has made distinction between MCC and non-MCC HGNECA increasingly important. This patient initially responded to PD-L1 inhibitor therapy but ultimately died with disease 10 months after diagnosis.

PMID: 29894357 [PubMed - indexed for MEDLINE]

Dual inhibition of MDM2 and MDM4 in virus-positive Merkel cell carcinoma enhances the p53 response.

Fetched: March 14th, 2019, 5:00am GMT

Dual inhibition of MDM2 and MDM4 in virus-positive Merkel cell carcinoma enhances the p53 response.

Proc Natl Acad Sci U S A. 2019 01 15;116(3):1027-1032

Authors: Park DE, Cheng J, Berrios C, Montero J, Cortés-Cros M, Ferretti S, Arora R, Tillgren ML, Gokhale PC, DeCaprio JA

Abstract
Merkel cell polyomavirus (MCV) contributes to approximately 80% of all Merkel cell carcinomas (MCCs), a highly aggressive neuroendocrine carcinoma of the skin. MCV-positive MCC expresses small T antigen (ST) and a truncated form of large T antigen (LT) and usually contains wild-type p53 (TP53) and RB (RB1). In contrast, virus-negative MCC contains inactivating mutations in TP53 and RB1. While the MCV-truncated LT can bind and inhibit RB, it does not bind p53. We report here that MCV LT binds to RB, leading to increased levels of ARF, an inhibitor of MDM2, and activation of p53. However, coexpression of ST reduced p53 activation. MCV ST recruits the MYC homologue MYCL (L-Myc) to the EP400 chromatin remodeler complex and transactivates specific target genes. We observed that depletion of EP400 in MCV-positive MCC cell lines led to increased p53 target gene expression. We suspected that the MCV ST-MYCL-EP400 complex could functionally inactivate p53, but the underlying mechanism was not known. Integrated ChIP and RNA-sequencing analysis following EP400 depletion identified MDM2 as well as CK1α, an activator of MDM4, as target genes of the ST-MYCL-EP400 complex. In addition, MCV-positive MCC cells expressed high levels of MDM4. Combining MDM2 inhibitors with lenalidomide targeting CK1α or an MDM4 inhibitor caused synergistic activation of p53, leading to an apoptotic response in MCV-positive MCC cells and MCC-derived xenografts in mice. These results support dual targeting of MDM2 and MDM4 in virus-positive MCC and other p53 wild-type tumors.

PMID: 30598450 [PubMed - indexed for MEDLINE]

Permalink for 'The expression of terminal deoxynucleotidyl transferase and paired box gene 5 in Merkel cell carcinomas and its relation to the presence of Merkel cell polyomavirus DNA.'

The expression of terminal deoxynucleotidyl transferase and paired box gene 5 in Merkel cell carcinomas and its relation to the presence of Merkel cell polyomavirus DNA.

Fetched: March 14th, 2019, 5:00am GMT

The expression of terminal deoxynucleotidyl transferase and paired box gene 5 in Merkel cell carcinomas and its relation to the presence of Merkel cell polyomavirus DNA.

J Cutan Pathol. 2019 Jan;46(1):26-32

Authors: Johansson B, Sahi H, Koljonen V, Böhling T

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) tumor samples frequently express B-lymphoid lineage markers. However, the reasons for expression of specific B-lymphoid lineage markers are still unclear. We studied the expression of TdT and PAX5 (two B-cell lymphoid lineage markers) in a large pool of MCC tissue microarray samples.
METHODS: Immunoexpression and staining intensities of TdT and Pax-5 were statistically correlated with patient, tumor, Merkel cell polyomavirus (MCV), and disease-specific parameters.
RESULTS: In a cohort of 117 MCC patients and their corresponding tumor samples, TdT was expressed in 37 (31.6%) samples and PAX5 in 26 (22.2%). Simultaneous immunostaining for TdT and PAX5 was observed in 13 (11.1%) samples. A statistically significant relationship was observed between MCV virus copy number and positive TdT expression (P = 0.0056). Similarly, a significant relationship was also observed between positive TdT and tumor MCV virus positivity (P = 0.000495).
CONCLUSION: We observed frequent TdT and PAX5 immunoexpression in MCC tumor samples. However, simultaneous immunoexpression of these markers was scarce. TdT expression was statistically significantly associated with MCV positivity. The absence of a statistically significant association between tumor parameters and disease progression markers undermines the systemic use of these markers in clinical practice.

PMID: 30315594 [PubMed - indexed for MEDLINE]

Primary parotid Merkel cell carcinoma: a first imagery and treatment response assessment by 18F-FDG PET.

Fetched: March 13th, 2019, 5:00am GMT

Primary parotid Merkel cell carcinoma: a first imagery and treatment response assessment by 18F-FDG PET.

BMJ Case Rep. 2019 Mar 09;12(3):

Authors: Giroulet F, Tabotta F, Pomoni A, Prior J

PMID: 30852509 [PubMed - in process]

Adenomatoid tumour of the uterus is frequently associated with iatrogenic immunosuppression.

Fetched: March 9th, 2019, 5:00am GMT

Adenomatoid tumour of the uterus is frequently associated with iatrogenic immunosuppression.

Histopathology. 2018 Dec;73(6):1013-1022

Authors: Tamura D, Maeda D, Halimi SA, Okimura M, Kudo-Asabe Y, Ito S, Sato N, Shibahara J, Nanjo H, Terada Y, Goto A

Abstract
AIMS: Uterine adenomatoid tumour (AT) is a benign proliferation of cells showing mesothelial differentiation within the myometrium that usually presents as a single nodule. Rare diffuse uterine ATs have been reported, often in patients undergoing immunosuppressive therapy. Herein, we aimed to elucidate the general association between the incidence of uterine AT and iatrogenic immunosuppression by cohort analysis.
METHODS AND RESULTS: We analysed 611 consecutive hysterectomy specimens to determine the incidence of AT and its correlation with the immunosuppressive status. Mesothelial lineage, p16 expression, mismatch repair (MMR) protein alterations, and the possible integration of tumorigenic viruses were examined by in situ hybridizasion and immunohistochemistry. ATs were detected in 14 of 611 hysterectomy cases (2.3%). The incidence of AT was significantly higher in the immunosuppressed (IS) group (5/20, 25.0%) than in the non-IS group (9/591, 1.52%), with a relative risk of 16.4. Of the five ATs in the IS group, three were multifocal or diffuse. Latent uterine AT was detected, by in toto sectioning, in one of four immunosuppressed autopsy cases. The tumor cells of ATs commonly expressed calretinin and podoplanin. Characteristic block-type (≥90%) positivity for p16 was observed in most ATs. None of the ATs were positive for human herpes virus type 8, Merkel cell polyomavirus, SV40 large T antigen, Epstein-Barr virus, and human papilloma virus, and the MMR proteins were retained. A TRAF7 mutation was identified from macrodissected tissue in one of 12 ATs by Sanger sequencing.
CONCLUSION: Uterine AT is an immunosuppression-associated mesothelial lesion characterised by p16 overexpression.

PMID: 30099776 [PubMed - indexed for MEDLINE]

Integrating the Management of Nodal Metastasis Into the Treatment of Nonmelanoma Skin Cancer.

Fetched: March 6th, 2019, 5:00am GMT

Integrating the Management of Nodal Metastasis Into the Treatment of Nonmelanoma Skin Cancer.

Semin Radiat Oncol. 2019 Apr;29(2):171-179

Authors: Yom SS

Abstract
The two types of nonmelanoma skin cancer most apt to metastasize to lymph nodes are cutaneous squamous cell carcinoma and Merkel cell carcinoma. The clinical impact of nodal metastases of these cancers is substantial, resulting in intensification of treatment and morbidity and worsened cancer outcomes. Exact best practices are challenging to define as many specific clinical scenarios remain incompletely catalogued, characterized, or studied. In general, the role of radiation therapy is indisputably established as part of the treatment of both of these diseases although its success depends on the best available assessment of extent of disease and appropriate integration into the multimodality care plan.

PMID: 30827456 [PubMed - in process]

Permalink for 'Evaluation of Lymph Node Ratio Association With Long-term Patient Survival After Surgery for Node-Positive Merkel Cell Carcinoma.'

Evaluation of Lymph Node Ratio Association With Long-term Patient Survival After Surgery for Node-Positive Merkel Cell Carcinoma.

Fetched: March 4th, 2019, 5:00am GMT

Icon for Silverchair Information Systems

Evaluation of Lymph Node Ratio Association With Long-term Patient Survival After Surgery for Node-Positive Merkel Cell Carcinoma.

JAMA Dermatol. 2019 Mar 02;:

Authors: Cheraghlou S, Agogo GO, Girardi M

Abstract
Importance: Merkel cell carcinoma (MCC) carries the highest mortality rate among cutaneous cancers and is rapidly rising in incidence. Identification of prognostic indicators may help guide patient counseling and treatment planning. Lymph node ratio (LNR), the ratio of positive lymph nodes to the total number of examined lymph nodes, is an established prognostic indicator in other cancers.
Objectives: The primary objective was to evaluate the association between LNR and patient survival after surgery for node-positive MCC. The secondary objective was to evaluate whether the survival rates associated with adjuvant therapies vary by patient LNR status.
Design, Setting, and Participants: Retrospective cohort study of patients with node-positive MCC treated with surgery and lymphadenectomy. We queried the National Cancer Database (NCDB) and the Surveillance, Epidemiology, and End Results (SEER) registry for patient records. Data originated from 2004 through 2017 for the NCDB and from 1973 through 2016 for the SEER registry. The SEER registry comprises a population-based US cohort while cases from the NCDB include all reportable cases from Commission on Cancer-accredited facilities and represents approximately 70% of all newly diagnosed cancers in the United States. All data analysis took place between August 1, 2018, and February 11, 2019.
Exposures: The ratio of positive lymph nodes to the total number of examined lymph nodes, LNR, was stratified into quartiles.
Main Outcomes and Measures: Overall survival (NCDB) and disease-specific survival (SEER).
Results: We identified 736 eligible cases in the NCDB and 538 eligible cases in the SEER registry. Among these 1274 patients, the mean (SD) age was 71.1 (11.5) years, and 401 (31.5%) were women. After controlling for clinical and tumor factors including AJCC N staging, patient LNR of 0.07 to 0.31 (hazard ratio [HR], 1.37; 95% CI, 1.03-1.81) and greater than 0.31 (HR, 2.84; 95% CI, 2.10-3.86) was associated with significantly worse survival than an LNR less than 0.07. Univariate supplementary analysis performed in the SEER data set revealed a similar association of LNR with disease-specific survival. For patients with an LNR greater than 0.31, treatment with surgery and adjuvant chemoradiation therapy was associated with improved survival compared with surgery and adjuvant radiation therapy alone (HR, 0.61; 95% CI, 0.38-0.97), while this was not found for patients with an LNR of 0.31 or lower (HR, 0.93; 95% CI, 0.65-1.33).
Conclusions and Relevance: For lymph node-positive MCC, LNR offers a potentially prognostic metric alongside traditional TNM staging that may be useful for both patient counseling and treatment planning after surgery.

PMID: 30825411 [PubMed - as supplied by publisher]

Merkel Cell Carcinoma: Therapeutic Update and Emerging Therapies.

Fetched: March 3rd, 2019, 5:00am GMT

Merkel Cell Carcinoma: Therapeutic Update and Emerging Therapies.

Dermatol Ther (Heidelb). 2019 Feb 28;:

Authors: Villani A, Fabbrocini G, Costa C, Carmela Annunziata M, Scalvenzi M

Abstract
Merkel cell carcinoma (MCC) is a rare but highly aggressive neuroendocrine skin cancer whose incidence has almost doubled in recent decades. Risk factors for MCC include age > 65 years, immunosuppression, sun exposure and infection by Merkel cell polyomavirus. MCC usually presents as rapidly growing, firm, red to violaceous nodule localized on the sun-exposed skin. Surgery followed by radiation therapy is considered to be the first-line treatment for primary or loco-regional MCC in order to prevent recurrences and lymph node metastasis, while chemotherapy has always been used to treat advanced forms. However, responses to chemotherapy are mostly of short duration, and the associated clinical benefit on overall survival is still unclear. The use of checkpoint inhibitors (CPIs) has shown good results in the treatment of advanced MCC and, consequently, CPIs are considered emerging immunotherapeutic options for these patients, although there are still no standardized treatments for patients with metastatic disease. Here we present a complete overview of the different possibilities for the treatment of MCC according to the stage of the disease, focusing on the emerging immunotherapies used for treating advanced MCC.

PMID: 30820877 [PubMed - as supplied by publisher]

Permalink for 'B7-H3 expression in Merkel cell carcinoma-associated endothelial cells correlates with locally aggressive primary tumor features and increased vascular density.'

B7-H3 expression in Merkel cell carcinoma-associated endothelial cells correlates with locally aggressive primary tumor features and increased vascular density.

Fetched: March 1st, 2019, 5:00am GMT

B7-H3 expression in Merkel cell carcinoma-associated endothelial cells correlates with locally aggressive primary tumor features and increased vascular density.

Clin Cancer Res. 2019 Feb 26;:

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

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

PMID: 30808776 [PubMed - as supplied by publisher]

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

Fetched: March 1st, 2019, 5:00am GMT

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

Eur J Surg Oncol. 2019 Feb 16;:

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

PMID: 30808525 [PubMed - as supplied by publisher]

Permalink for 'Merkel cell carcinoma and cellular cytotoxicity: sensitivity to cellular lysis and screening for potential target antigens suitable for antibody-dependent cellular cytotoxicity.'

Merkel cell carcinoma and cellular cytotoxicity: sensitivity to cellular lysis and screening for potential target antigens suitable for antibody-dependent cellular cytotoxicity.

Fetched: March 1st, 2019, 5:00am GMT

Merkel cell carcinoma and cellular cytotoxicity: sensitivity to cellular lysis and screening for potential target antigens suitable for antibody-dependent cellular cytotoxicity.

Cancer Immunol Immunother. 2018 Aug;67(8):1209-1219

Authors: Ollier J, Kervarrec T, Samimi M, Benlalam H, Aumont P, Vivien R, Touzé A, Labarrière N, Vié H, Clémenceau B

Abstract
The recent success of checkpoint inhibitors in the treatment of Merkel cell carcinoma (MCC) confirms that MCC tumors can be immunogenic. However, no treatment directly targeting the tumor is available for use in combination with these checkpoint inhibitors to enhance their efficacity. This study was carried out to characterize MCC line sensitivity to cellular lysis and to identify cell surface antigens that could be used for direct targeting of this tumor. For five representative MCC lines, the absence or low expression of MICA, MICB, HLA-I, and ICAM-1 was associated with low level of recognition by NK cells and T lymphocytes. However, expression of HLA-I and ICAM-1 and sensitivity to cellular lysis could be restored or increased after exposure to INFγ. We tested 41 antibodies specific for 41 different antigens using a novel antibody-dependent cellular cytotoxicity (ADCC) screening system for target antigens. Anti-CD326 (EpCAM) was the only antibody capable of inducing ADCC on the five MCC lines tested. Because MCC tumors are often directly accessible, local pharmacologic manipulation to restore HLA class-I and ICAM-1 cell surface expression (and thus sensitivity to cell lysis) can potentially benefit immune therapeutic intervention. In line with this, our observation that ADCC against EpCAM can induce lysis of MCC lines and suggests that therapeutic targeting of this antigen deserves to be explored further.

PMID: 29808366 [PubMed - indexed for MEDLINE]

Merkel Cell Polyomavirus Infection and Detection.

Fetched: February 27th, 2019, 5:00am GMT

Merkel Cell Polyomavirus Infection and Detection.

J Vis Exp. 2019 Feb 07;(144):

Authors: Liu W, Krump NA, Buck CB, You J

Abstract
Merkel cell polyomavirus (MCPyV) infection can lead to Merkel cell carcinoma (MCC), a highly aggressive form of skin cancer. Mechanistic studies to fully investigate MCPyV molecular biology and oncogenic mechanisms have been hampered by a lack of adequate cell culture models. Here, we describe a set of protocols for performing and detecting MCPyV infection of primary human skin cells. The protocols describe the isolation of human dermal fibroblasts, preparation of recombinant MCPyV virions, and detection of virus infection by both immunofluorescent (IF) staining and in situ DNA-hybridization chain reaction (HCR), which is a highly sensitive fluorescence in situ hybridization (FISH) approach. The protocols herein can be adapted by interested researchers to identify other cell types or cell lines that support MCPyV infection. The described FISH approach could also be adapted for detecting low levels of viral DNAs present in the infected human skin.

PMID: 30799855 [PubMed - in process]

Characterizing the Therapeutic Potential of a Potent BET Degrader in Merkel Cell Carcinoma.

Fetched: February 25th, 2019, 5:00am GMT

Characterizing the Therapeutic Potential of a Potent BET Degrader in Merkel Cell Carcinoma.

Neoplasia. 2019 Feb 20;21(3):322-330

Authors: Choi JE, Verhaegen ME, Yazdani S, Malik R, Harms PW, Mangelberger D, Tien J, Cao X, Wang Y, Cieślik M, Gurkan J, Yazdani M, Jing X, Juckette K, Su F, Wang R, Zhou B, Apel IJ, Wang S, Dlugosz AA, Chinnaiyan AM

Abstract
Studies on the efficacy of small molecule inhibitors in Merkel cell carcinoma (MCC) have been limited and largely inconclusive. In this study, we investigated the therapeutic potential of a potent BET degrader, BETd-246, in the treatment of MCC. We found that MCC cell lines were significantly more sensitive to BETd-246 than to BET inhibitor treatment. Therapeutic targeting of BET proteins resulted in a loss of "MCC signature" genes but not MYC expression as previously described irrespective of Merkel cell polyomavirus (MCPyV) status. In MCPyV+ MCC cells, BETd-246 alone suppressed downstream targets in the MCPyV-LT Ag axis. We also found enrichment of HOX and cell cycle genes in MCPyV- MCC cell lines that were intrinsically resistant to BETd-246. Our findings uncover a requirement for BET proteins in maintaining MCC lineage identity and point to the potential utility of BET degraders for treating MCC.

PMID: 30797188 [PubMed - as supplied by publisher]

Unknown primary Merkel cell carcinoma with cutaneous spread.

Fetched: February 25th, 2019, 5:00am GMT

Unknown primary Merkel cell carcinoma with cutaneous spread.

BMJ Case Rep. 2019 Feb 21;12(2):

Authors: Barreira JV, Valejo Coelho MM, Ribeiro C, Semedo M

Abstract
The authors present the case of a woman in the seventh decade of life with medical history of: left nephrectomy for renal tuberculosis and non-Hodgkin's lymphoma treated with chemotherapy (QT) and radiotherapy. She presented with a 2-month history of non-tender, left inguinal lymph node enlargement. Positron Emission Tomography (PET)-CT -scanshowed hypermetabolic inguinal and retroperitoneal lymphadenopathies, no primary tumour. On the second dermatological examination a pink, 2 cm plaque on the anterior left knee was noted. The histopathological analysis revealed Merkel cell carcinoma. The patient underwent two lines of systemic QT, with life-threatening toxicities limiting treatment. Followed overwhelming disease progression with lymphoedema and numerous skin metastases in the left lower limb. The patient received palliative care until death. The rare incidence of such neoplasia and its uncommon clinical presentation justifies reporting this case and highlights the importance of multidisciplinary teams in the management of cancer patients.

PMID: 30796073 [PubMed - in process]

The cellular basis of mechanosensory Merkel-cell innervation during development.

Fetched: February 24th, 2019, 5:00am GMT

The cellular basis of mechanosensory Merkel-cell innervation during development.

Elife. 2019 Feb 22;8:

Authors: Jenkins BA, Fontecilla NM, Lu CP, Fuchs E, Lumpkin EA

Abstract
Touch sensation is initiated by mechanosensory neurons that innervate distinct skin structures; however, little is known about how these neurons are patterned during mammalian skin development. We explored the cellular basis of touch-receptor patterning in mouse touch domes, which contain mechanosensory Merkel cell-neurite complexes and abut primary hair follicles. At embryonic stage 16.5 (E16.5), touch domes emerge as patches of Merkel cells and keratinocytes clustered with a previously unsuspected population of Bmp4-expressing dermal cells. Epidermal Noggin overexpression at E14.5 disrupted touch-dome formation but not hair-follicle specification, demonstrating a temporally distinct requirement for BMP signaling in placode-derived structures. Surprisingly, two neuronal populations preferentially targeted touch domes during development but only one persisted in mature touch domes. Finally, Keratin-17-expressing keratinocytes but not Merkel cells were necessary to establish innervation patterns during development. These findings identify key cell types and signaling pathways required for targeting Merkel-cell afferents to discrete mechanosensory compartments.

PMID: 30794158 [PubMed - in process]

Permalink for 'Investigation of three oncogenic epitheliotropic viruses shows human papillomavirus in association with non-melanoma skin cancer.'

Investigation of three oncogenic epitheliotropic viruses shows human papillomavirus in association with non-melanoma skin cancer.

Fetched: February 24th, 2019, 5:00am GMT

Investigation of three oncogenic epitheliotropic viruses shows human papillomavirus in association with non-melanoma skin cancer.

Eur J Clin Microbiol Infect Dis. 2019 Feb 21;:

Authors: Baez CF, Gonçalves MTV, da Rocha WM, Magalhães de Souza L, Savassi-Ribas F, de Oliveira Almeida NK, Delbue S, Guimarães MAAM, Cavalcanti SMB, Luz FB, Varella RB

Abstract
Non-melanoma skin cancers (NMSC) share similar risk factors with other virus-related cancers, despite the lack of proved causal association between viral infection and NMSC development. We investigated the presence of Merkel cell polyomavirus (MCPyV), Epstein-Barr virus (EBV), and human papillomavirus (HPV) DNA in 83 NMSC fresh-frozen and 16 non-cancerous skin biopsies and evaluated viral infection according to demographical data, histopathological diagnosis, and ultraviolet exposure. Our results showed that 75% of NMSC biopsies were positive for at least one out of three viruses, whereas only 38% of non-cancerous skin biopsies were positive (p = 0.02). Notably, HPV detection was frequent in NMSC (43%) and nearly absent (one sample, 6.7%) in non-cancerous biopsies (p = 0.007). MCPyV was associated with sites of higher exposure to ultraviolet radiation (p = 0.010), while EBV was associated with a compromised immune system (p = 0.032). Our study showed that HPV was strongly associated with NMSC while EBV and MCPyV with other risk factors. Though further studies are required to elucidate the role of viral infection in NMSC development and management, this study supports the possible role of oncogenic viruses in skin cancers, especially HPV.

PMID: 30788731 [PubMed - as supplied by publisher]

Immune Checkpoint Inhibitors and Beyond: An Overview of Immune-Based Therapies in Merkel Cell Carcinoma.

Fetched: February 22nd, 2019, 5:00am GMT

Immune Checkpoint Inhibitors and Beyond: An Overview of Immune-Based Therapies in Merkel Cell Carcinoma.

Am J Clin Dermatol. 2019 Feb 19;:

Authors: Samimi M

Abstract
Merkel cell carcinoma (MCC) is an aggressive skin cancer. Until 2017, patients with advanced disease were typically treated with conventional chemotherapies, with a median response duration of 3 months. Increased evidence of the role of the immune system in controlling this cancer has paved the way for immune-based therapies, with programmed cell death protein 1 (PD-1)/programmed cell death protein ligand 1 (PD-L1) inhibitors at the frontline. Avelumab, an anti-PD-L1 antibody, was the first-ever drug approved in advanced MCC after showing meaningful efficacy in a second-line setting. Objective responses were observed in one-third of patients and, most importantly, were durable with half of patients and one-third of patients still alive at 1 and 2 years, respectively. When used in a first-line setting, PD-1/PD-L1 inhibitors (avelumab, pembrolizumab, nivolumab) are even more promising as objective responses are observed in approximately 50-70% of patients within the first 4-8 weeks of treatment. Safety profiles are acceptable with 10-20% of patients experiencing adverse events grade ≥ 3. PD-1/PD-L1 inhibitors are considered the standard of care in advanced MCC and are currently being investigated in the adjuvant and neoadjuvant settings. However, innovative treatments are still needed in the metastatic setting, as approximately 50% of these patients will not persistently respond to currently available immunotherapies, and no predictors of response are available yet. Therefore, other immunotherapeutic strategies are now being investigated-ideally in combinations-to enhance the various aspects of the immune response against tumoral cells.

PMID: 30784027 [PubMed - as supplied by publisher]

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

Fetched: February 15th, 2019, 5:00am GMT

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

Exp Dermatol. 2019 Feb 13;:

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

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

PMID: 30758073 [PubMed - as supplied by publisher]

Immunotherapy for skin cancer.

Fetched: February 14th, 2019, 5:00am GMT

Immunotherapy for skin cancer.

Int Immunol. 2019 Feb 08;:

Authors: Paulson KG, Lahman M, Chapuis AG, Brownell I

Abstract
Among all tumor types, skin cancers are profoundly sensitive to immunotherapy. Indeed, the recently reported response rates for anti-PD-1 (anti-programmed-death 1) therapy for cutaneous malignant melanomas (MM), Merkel cell carcinomas, basal cell carcinomas, cutaneous squamous cell carcinomas and Kaposi sarcomas are all above 40%. This unique immunogenicity renders skin cancers as a paradigm for tumor-immune interactions and is driven by high mutational burdens, overexpressed tumor antigens and/or viral antigens. However, despite the clear demonstration of immunologic cure of skin cancer in some patients, most tumors develop either early (primary) or late (adaptive) resistance to immunotherapy. Resistance mechanisms are complex, and include contributions of tumor cell-intrinsic, T cell and microenvironment factors that have been recently further elucidated with the advent of single-cell technologies. This review will focus on the exciting progress with immunotherapy for skin cancers to date, and also our current understanding of the mechanisms of resistance to immunotherapy.

PMID: 30753483 [PubMed - as supplied by publisher]

Recent success and limitations of immune checkpoint inhibitors for cancer: a lesson from melanoma.

Fetched: February 14th, 2019, 5:00am GMT

Recent success and limitations of immune checkpoint inhibitors for cancer: a lesson from melanoma.

Virchows Arch. 2019 Feb 12;:

Authors: Ottaviano M, De Placido S, Ascierto PA

Abstract
AbstractSeveral researches have been carried over the last few decades to understand of how cancer evades the immune system and thus to identify therapies that could directly act on patient's immune system in the way of restore or induce a response to cancer. As a consequence, "cancer immunotherapy" is conquering predominantly the modern scenario of the fight against cancer. The recent clinical success of immune checkpoint inhibitors (ICIs) has created an entire new class of anti-cancer drugs and restored interest in the field of immuno-oncology, leading to regulatory approvals of several agents for the treatment of a variety of malignancies. The first to be approved in 2011 was the anti-CTLA-4 antibody ipilimumab for the treatment of unresectable or metastatic melanoma. Subsequently, the anti-PD-1s, nivolumab and pembrolizumab, received regulatory approvals for the treatment of melanoma and several other cancers. More recently, three anti-PD-L1 antibodies have received approval: atezolizumab and durvalumab for locally advanced or metastatic urothelial carcinoma and metastatic non-small cell lung cancer (NSCLC) and avelumab for the treatment of locally advanced or metastatic urothelial carcinoma and metastatic Merkel cell carcinoma. This review, starting from the results of melanoma trials, highlights in turn different ICIs and data for different indications in several malignancies are included under each drug class.

PMID: 30747264 [PubMed - as supplied by publisher]

Permalink for 'Merkel Cell Polyoma Viral Load and Intratumoral CD8+ Lymphocyte Infiltration Predict Overall Survival in Patients With Merkel Cell Carcinoma.'

Merkel Cell Polyoma Viral Load and Intratumoral CD8+ Lymphocyte Infiltration Predict Overall Survival in Patients With Merkel Cell Carcinoma.

Fetched: February 10th, 2019, 5:00am GMT

Merkel Cell Polyoma Viral Load and Intratumoral CD8+ Lymphocyte Infiltration Predict Overall Survival in Patients With Merkel Cell Carcinoma.

Front Oncol. 2019;9:20

Authors: von der Grün J, Winkelmann R, Meissner M, Wieland U, Silling S, Martin D, Fokas E, Rödel C, Rödel F, Balermpas P

Abstract
Introduction: Merkel cell carcinoma (MCC) is linked to the presence of clonally integrated Merkel cell polyomavirus (MCPyV) in up to 80% of the cases. The aim of the study was to determine the prognostic value of baseline MCPyV viral load and lymphocytic infiltration. Methods: MCPyV DNA prevalence, integration status and viral load were determined by specific quantitative real-time PCR in surgical specimens obtained from 49 patients with MCC treated with (n = 22, 45%) or without postoperative radiotherapy (RT). CD8+ tumor infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) status were assessed using immunohistochemistry. MCPyV characteristics and immune marker expression were correlated with clinicopathological factors and overall survival (OS). Results: Median age at diagnosis was 74 (range, 42-100); 51% of the patients were female. One-, three, and five-year OS rates were 83.8, 58.6, and 47.1%, respectively. A positive MCPyV status was associated with female gender (p = 0.042). Tumor localization (head/arms vs. trunk) positively correlated with PD-L1 status (p = 0.011) and combined CD8/PD-L1 expression (p = 0.038). Overall CD8+ infiltration was inversely associated with N-stage (p = 0.048). Stromal TILs correlated significantly with both PD-L1 expression (p = 0.010) and N-stage (p = 0.037). A high viral load (>median) was significantly associated with worse OS (p = 0.029) and high intratumoral CD8+ infiltration with improved OS for the entire cohort (p = 0.045). Conclusion: These data provide important insight on the role of MCPy DNA viral load and TILs in the context of PD-L1 in patients with Merkel cell carcinoma. Future clinical studies should aim to explore the effect of PD-1/PD-L1 immune-checkpoint inhibitors in combination with existing radiotherapy approaches.

PMID: 30733932 [PubMed]

Permalink for 'Durable Tumor Regression and Overall Survival in Patients With Advanced Merkel Cell Carcinoma Receiving Pembrolizumab as First-Line Therapy.'

Durable Tumor Regression and Overall Survival in Patients With Advanced Merkel Cell Carcinoma Receiving Pembrolizumab as First-Line Therapy.

Fetched: February 8th, 2019, 5:00am GMT

Durable Tumor Regression and Overall Survival in Patients With Advanced Merkel Cell Carcinoma Receiving Pembrolizumab as First-Line Therapy.

J Clin Oncol. 2019 Feb 06;:JCO1801896

Authors: Nghiem P, Bhatia S, Lipson EJ, Sharfman WH, Kudchadkar RR, Brohl AS, Friedlander PA, Daud A, Kluger HM, Reddy SA, Boulmay BC, Riker AI, Burgess MA, Hanks BA, Olencki T, Margolin K, Lundgren LM, Soni A, Ramchurren N, Church C, Park SY, Shinohara MM, Salim B, Taube JM, Bird SR, Ibrahim N, Fling SP, Homet Moreno B, Sharon E, Cheever MA, Topalian SL

Abstract
PURPOSE: Merkel cell carcinoma (MCC) is an aggressive skin cancer often caused by the Merkel cell polyomavirus. Clinical trials of programmed cell death-1 pathway inhibitors for advanced MCC (aMCC) demonstrate increased progression-free survival (PFS) compared with historical chemotherapy data. However, response durability and overall survival (OS) data are limited.
PATIENTS AND METHODS: In this multicenter phase II trial (Cancer Immunotherapy Trials Network-09/Keynote-017), 50 adults naïve to systemic therapy for aMCC received pembrolizumab (2 mg/kg every 3 weeks) for up to 2 years. Radiographic responses were assessed centrally per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
RESULTS: Among 50 patients, the median age was 70.5 years, and 64% had Merkel cell polyomavirus-positive tumors. The objective response rate (ORR) to pembrolizumab was 56% (complete response [24%] plus partial response [32%]; 95% CI, 41.3% to 70.0%), with ORRs of 59% in virus-positive and 53% in virus-negative tumors. Median follow-up time was 14.9 months (range, 0.4 to 36.4+ months). Among 28 responders, median response duration was not reached (range, 5.9 to 34.5+ months). The 24-month PFS rate was 48.3%, and median PFS time was 16.8 months (95% CI, 4.6 months to not estimable). The 24-month OS rate was 68.7%, and median OS time was not reached. Although tumor viral status did not correlate with ORR, PFS, or OS, there was a trend toward improved PFS and OS in patients with programmed death ligand-1-positive tumors. Grade 3 or greater treatment-related adverse events occurred in 14 (28%) of 50 patients and led to treatment discontinuation in seven (14%) of 50 patients, including one treatment-related death.
CONCLUSION: Here, we present the longest observation to date of patients with aMCC receiving first-line anti-programmed cell death-1 therapy. Pembrolizumab demonstrated durable tumor control, a generally manageable safety profile, and favorable OS compared with historical data from patients treated with first-line chemotherapy.

PMID: 30726175 [PubMed - as supplied by publisher]

Permalink for 'Detection of Merkel Cell Polyoma Virus and Beta Human Papillomavirus in Multiple Eccrine Poromas in a Patient With Acute Leukemia Treated With Stem Cell Transplant.'

Detection of Merkel Cell Polyoma Virus and Beta Human Papillomavirus in Multiple Eccrine Poromas in a Patient With Acute Leukemia Treated With Stem Cell Transplant.

Fetched: February 8th, 2019, 5:00am GMT

Detection of Merkel Cell Polyoma Virus and Beta Human Papillomavirus in Multiple Eccrine Poromas in a Patient With Acute Leukemia Treated With Stem Cell Transplant.

Am J Dermatopathol. 2017 06;39(6):489-491

Authors: Aung PP, Rady PL, Nagarajan P, Ivan D, Tetzlaff MT, Curry JL, Tyring SK, Prieto VG, Torres-Cabala CA

PMID: 27655121 [PubMed - indexed for MEDLINE]

Permalink for 'Early objective response to avelumab treatment is associated with improved overall survival in patients with metastatic Merkel cell carcinoma.'

Early objective response to avelumab treatment is associated with improved overall survival in patients with metastatic Merkel cell carcinoma.

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

Early objective response to avelumab treatment is associated with improved overall survival in patients with metastatic Merkel cell carcinoma.

Cancer Immunol Immunother. 2019 Feb 05;:

Authors: D'Angelo SP, Hunger M, Brohl AS, Nghiem P, Bhatia S, Hamid O, Mehnert JM, Terheyden P, Shih KC, Brownell I, Lebbé C, Lewis KD, Linette GP, Milella M, Schlichting M, Hennessy MH, Bharmal M

Abstract
BACKGROUND: Response rates are primary endpoints in many oncology trials; however, correlation with overall survival (OS) is not uniform across cancer types, treatments, or lines of therapy. This study explored the association between objective response (OR) and OS in patients with chemotherapy-refractory metastatic Merkel cell carcinoma who received avelumab (anti-PD-L1).
METHODS: Eighty-eight patients enrolled in JAVELIN Merkel 200 (part A; NCT02155647) received i.v. avelumab 10 mg/kg every 2 weeks until confirmed progression, unacceptable toxicity, or withdrawal. Using conditional landmark analyses, we compared OS in patients with and without confirmed OR (RECIST v1.1). We applied a Cox model that included OR as a time-varying covariate and adjusted for age, visceral disease, and number of previous therapies.
RESULTS: Twenty-nine patients had confirmed OR; 20 by study week 7 and 7 more between study weeks 7 and 13. Survival probabilities 18 months after treatment initiation were 90% [95% confidence interval (CI) 65.6-97.4] in patients with OR at week 7 and 26.2% (95% CI 15.7-37.8) in patients without OR but who were alive at week 7. Median OS was not reached in patients with OR and was 8.8 months (95% CI 6.4-12.9) in patients without. Similar results were observed for the week 13 landmark. The adjusted Cox model showed OR was associated with a 95% risk reduction of death [hazard ratio 0.052 (95% CI 0.018-0.152)] compared with a nonresponse.
CONCLUSIONS: Patients with OR by 7 or 13 weeks had significantly longer OS than patients without, confirming that early OR is an endpoint of major importance.

PMID: 30721341 [PubMed - as supplied by publisher]

Permalink for 'Diagnosis and comprehensive therapy for cutaneous neuroendocrine carcinoma of the external auditory canal: a case report and literature review.'

Diagnosis and comprehensive therapy for cutaneous neuroendocrine carcinoma of the external auditory canal: a case report and literature review.

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

Icon for Scientific Electronic Library Online

Diagnosis and comprehensive therapy for cutaneous neuroendocrine carcinoma of the external auditory canal: a case report and literature review.

Braz J Otorhinolaryngol. 2018 Nov - Dec;84(6):799-801

Authors: Xiu Q, Wang XJ, Zhu DD, Meng CD

PMID: 27166275 [PubMed - indexed for MEDLINE]

Pomalidomide increases immune surface marker expression and immune recognition of oncovirus-infected cells.

Fetched: February 6th, 2019, 5:00am GMT

Pomalidomide increases immune surface marker expression and immune recognition of oncovirus-infected cells.

Oncoimmunology. 2019;8(2):e1546544

Authors: Davis DA, Shrestha P, Aisabor AI, Stream A, Galli V, Pise-Masison CA, Tagawa T, Ziegelbauer JM, Franchini G, Yarchoan R

Abstract
Most chronic viruses evade T-cell and natural killer (NK) immunity through downregulation of immune surface markers. Previously we showed that Pomalidomide (Pom) increases surface expression of major histocompatibility complex class I (MHC-I) in Kaposi sarcoma-associated herpesvirus-infected latent and lytic cells and restores ICAM-1 and B7-2 in latent cells. We explored the ability of Pom to increase immune surface marker expression in cells infected by other chronic viruses, including human T-cell leukemia virus type-1 (HTLV-1), Epstein-Barr virus (EBV), human papilloma virus (HPV), Merkel cell polyoma virus (MCV), and human immunodeficiency virus type-1 (HIV-1). Pom increased MHC-1, ICAM-1, and B7-2/CD86 in immortalized T-cell lines productively infected with HTLV-1 and also significantly increased their susceptibility to NK cell-mediated cytotoxicity. Pom enhancement of MHC-I and ICAM-1 in primary cells infected with HTLV-1 was abrogated by knockout of HTLV-1 orf-1. Pom increased expression of ICAM-1, B7-2 and MHC class I polypeptide related sequence A (MICA) surface expression in the EBV-infected Daudi cells and increased their T-cell activation and susceptibility to NK cells. Moreover, Pom increased expression of certain of these surface markers on Akata, Raji, and EBV lymphoblastic cell lines. The increased expression of immune surface markers in these virus-infected lines was generally associated with a decrease in IRF4 expression. By contrast, Pom treatment of HPV, MCV and HIV-1 infected cells did not increase these immune surface markers. Pom and related drugs may be clinically beneficial for the treatment of HTLV-1 and EBV-induced tumors by rendering infected cells more susceptible to both innate and adaptive host immune responses.

PMID: 30713808 [PubMed]

Second primary cancers in patients with acute lymphoblastic, chronic lymphocytic and hairy cell leukaemia.

Fetched: February 3rd, 2019, 5:00am GMT

Second primary cancers in patients with acute lymphoblastic, chronic lymphocytic and hairy cell leukaemia.

Br J Haematol. 2019 Jan 31;:

Authors: Zheng G, Chattopadhyay S, Sud A, Sundquist K, Sundquist J, Försti A, Houlston R, Hemminki A, Hemminki K

Abstract
Improvement of survival in lymphocytic leukaemia has been accompanied by the occurrence of second primary cancer (SPCs). Based on Swedish Family Cancer Database, we applied bi-directional analyses in which relative risks (RRs) were calculated for any SPCs in patients with chronic lymphocytic leukaemia (CLL), acute lymphoblastic leukaemia (ALL) and hairy cell leukaemia (HCL) and the risks of these leukaemias as SPCs. After CLL, RRs were significant for 20 SPCs, and high for skin squamous cell cancer (24·58 for in situ and 7·63 for invasive), Merkel cell carcinoma (14·36), Hodgkin lymphoma (7·16) and Kaposi sarcoma (6·76). Conversely, 15 CLL cancer pairs were reciprocally increased. The increased risks were reciprocal for ALL and four cancers. RR for ALL was 15·35 after myeloid neoplasia. HCL showed reciprocally increased RRs with non-Hodgkin lymphoma and melanoma. The concordance between RRs for bi-directional associations between CLL and different cancers, and HCL and different cancers was highly significant. For CLL (also for HCL), the bi-directional risks with skin cancers and other immune-related cancers suggest the probable involvement of immune dysfunction. For ALL, treatment may contribute to risks of multiple SPCs. Increased risk of ALL after haematological neoplasms may indicate bone marrow dysfunction. These findings may help guide treatment decisions and prognostic assessment.

PMID: 30706458 [PubMed - as supplied by publisher]

Treatment and survival of Merkel cell carcinoma since 1993: a population-based cohort study in the Netherlands.

Fetched: February 2nd, 2019, 5:00am GMT

Treatment and survival of Merkel cell carcinoma since 1993: a population-based cohort study in the Netherlands.

J Am Acad Dermatol. 2019 Jan 28;:

Authors: Uitentuis SE, Louwman MWJ, van Akkooi ACJ, Bekkenk M

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) is a rare and potentially lethal skin-cancer. MCC is known for its potential rapid growth and its propensity to metastasise.
OBJECTIVE: To describe the incidence, treatment and survival of MCC in a population-based setting.
METHODS: All MCC's diagnosed in the Netherlands between 1993 and 2016 were selected from the Netherlands Cancer Registry. Patient and tumour characteristics, therapy and vital status were obtained. Cox' proportional hazards were computed and relative survival analyses were performed.
RESULTS: Our cohort included 1977 patients with MCC. Incidence increased from 0.17/100,000 personyears in 1993 to 0.59/100,000 in 2016. The mean age at diagnosis was 75.5. Most MCC's (59.8%), were treated with surgery alone. Relative five-year survival was low (63.0%) and did not improve. Mortality was higher among males (HR: 1.24, 95%CI: 1.11-1.39), higher age (HR 1.07, 95%CI: 1.06-1.07) and nodal (HR1.26, 95%CI: 1.08-1.48) and distant spread of disease (HR2.44, 95%CI: 1.99-2.99).
LIMITATIONS: We lacked data on cause of death, comorbidity and pathological margins, which may have led to misinterpretation of the data.
CONCLUSION: This study shows continuously increasing incidence rates of MCC in the Netherlands. Survival after MCC diagnosis remained low. Our results emphasise the need for implementation of new therapies.

PMID: 30703452 [PubMed - as supplied by publisher]

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

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

Fetched: February 2nd, 2019, 5:00am GMT

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

Br J Dermatol. 2019 Jan 31;:

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

Abstract
Merkel cell carcinoma (MCC) is an infrequent malignant skin tumour with epithelial and neuroendocrine differentiation. Though it is a highly aggressive malignancy, the distinct molecular pathogenesis of MCC is not yet fully understood. Apart from DNA methylation, histone modification, and microRNA-mediated and long non-coding RNA-mediated regulation, hydroxymethylation may also play an important role in cancer development. Loss of 5-hydoxymethylcytosine (5-hmc) has been reported in a variety of cancers, including skin malignancies such as melanoma. This article is protected by copyright. All rights reserved.

PMID: 30703276 [PubMed - as supplied by publisher]

[Merkel cell carcinoma].

Fetched: February 2nd, 2019, 5:00am GMT

[Merkel cell carcinoma].

Hautarzt. 2019 Jan 30;:

Authors: Drusio C, Becker JC, Schadendorf D, Ugurel S

Abstract
Merkel cell carcinoma is a rare, highly aggressive skin tumor with neuroendocrine features found in older people. The pathogenesis is associated with immunosuppression, chronic UV light exposure and the Merkel cell polyomavirus. Clinically, Merkel cell carcinoma presents as a solitary, cutaneous or subcutaneous, red to bluish node. Due to early lymphogenic metastasis, locoregional metastases are already present in approximately 30% of cases at the time of diagnosis. The frequent local recurrences as well as the regional and distant metastases usually appear within the first 2-3 years after the initial diagnosis. The first treatment after diagnosis consists of complete surgical removal of the primary tumor with wide safety margins as well as a sentinel lymph node biopsy. Subsequently, adjuvant irradiation of the primary site should be performed. By additional radiotherapy of the regional lymph node stations, the rate of locoregional recurrence can be reduced. For systemic therapy of advanced Merkel cell carcinoma checkpoint inhibitors targeted against the PD-1/PD-L1 axis have proven to be highly and durably effective. In contrast the formerly frequently used chemotherapy shows moderate to good response rates but they are as a rule very short-lived.

PMID: 30701288 [PubMed - as supplied by publisher]

Incurable, progressive Merkel cell carcinoma: A single-institution study of 54 cases.

Fetched: February 1st, 2019, 5:00am GMT

Incurable, progressive Merkel cell carcinoma: A single-institution study of 54 cases.

Clin Otolaryngol. 2018 04;43(2):678-682

Authors: Fochtmann-Frana A, Haymerle G, Loewe R, Grasl MC, Pammer J, Rath T, Perisanidis C, Erovic BM

PMID: 28981217 [PubMed - indexed for MEDLINE]

New perspectives in Merkel cell carcinoma.

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

New perspectives in Merkel cell carcinoma.

Curr Opin Oncol. 2019 Jan 28;:

Authors: Del Marmol V, Lebbé C

Abstract
PURPOSE OF REVIEW: Merkel cell carcinoma (MCC), a rapidly progressing skin cancer, has poor prognosis. We reviewed the epidemiology, pathogenesis, diagnosis and treatment of MCC, with a focus on recent therapeutic advancements.
RECENT FINDINGS: Risk factors for MCC, such as old age, immunosuppression, polyomavirus infection and exposure to UV radiation have already been identified, but the underlying mechanisms leading to carcinogenesis still need clarification. On the basis of recent advances, immunotherapy - in particular, inhibition targeting the programmed cell death protein 1/programmed death-ligand 1 (PD1)/PDL1) immune checkpoint blockade - is currently being investigated in the treatment of metastatic MCC. Avelumab, an anti-PDL1 antibody, was the first drug to be approved internationally as second-line monotherapy for patients with advanced MCC, based on results from the JAVELIN Merkel 200 clinical trial. Avelumab has also recently been approved as first-line treatment for advanced MCC in Europe. Pembrolizumab (anti-PD1) in first-line and nivolumab (anti-PD1) in first-line and second-line treatments are two other checkpoint inhibitors that are under investigation, and showing promising results. New innovative therapies are also in development.
SUMMARY: New insights concerning advances in MCC diagnosis and treatment have been highlighted. Immunotherapy for metastatic MCC constitutes a recent breakthrough in an unmet medical need, but alternative therapies should continue to be investigated.

PMID: 30694842 [PubMed - as supplied by publisher]

Permalink for 'Merkel cell polyomavirus Tumor antigens expressed in Merkel cell carcinoma function independently of the ubiquitin ligases Fbw7 and β-TrCP.'

Merkel cell polyomavirus Tumor antigens expressed in Merkel cell carcinoma function independently of the ubiquitin ligases Fbw7 and β-TrCP.

Fetched: January 30th, 2019, 5:00am GMT

Merkel cell polyomavirus Tumor antigens expressed in Merkel cell carcinoma function independently of the ubiquitin ligases Fbw7 and β-TrCP.

PLoS Pathog. 2019 01;15(1):e1007543

Authors: Dye KN, Welcker M, Clurman BE, Roman A, Galloway DA

Abstract
Merkel cell polyomavirus (MCPyV) accounts for 80% of all Merkel cell carcinoma (MCC) cases through expression of two viral oncoproteins: the truncated large T antigen (LT-t) and small T antigen (ST). MCPyV ST is thought to be the main driver of cellular transformation and has also been shown to increase LT protein levels through the activity of its Large-T Stabilization Domain (LSD). The ST LSD was reported to bind and sequester several ubiquitin ligases, including Fbw7 and β-TrCP, and thereby stabilize LT-t and several other Fbw7 targets including c-Myc and cyclin E. Therefore, the ST LSD is thought to contribute to transformation by promoting the accumulation of these oncoproteins. Targets of Fbw7 and β-TrCP contain well-defined, conserved, phospho-degrons. However, as neither MCPyV LT, LT-t nor ST contain the canonical Fbw7 phospho-degron, we sought to further investigate the proposed model of ST stabilization of LT-t and transformation. In this study, we provide several lines of evidence that fail to support a specific interaction between MCPyV T antigens and Fbw7 or β-TrCP by co-immunoprecipitation or functional consequence. Although MCPyV ST does indeed increase LT protein levels through its Large-T Stabilization domain (LSD), this is accomplished independently of Fbw7. Therefore, our study indicates a need for further investigation into the role and mechanism(s) of MCPyV T antigens in viral replication, latency, transformation, and tumorigenesis.

PMID: 30689667 [PubMed - indexed for MEDLINE]

Immune-related adverse events predict the therapeutic efficacy of anti-PD-1 antibodies in cancer patients.

Fetched: January 28th, 2019, 5:00am GMT

Immune-related adverse events predict the therapeutic efficacy of anti-PD-1 antibodies in cancer patients.

Eur J Cancer. 2019 Jan 22;109:21-27

Authors: Rogado J, Sánchez-Torres JM, Romero-Laorden N, Ballesteros AI, Pacheco-Barcia V, Ramos-Leví A, Arranz R, Lorenzo A, Gullón P, Donnay O, Adrados M, Costas P, Aspa J, Alfranca A, Mondéjar R, Colomer R

Abstract
BACKGROUND: Cancer immune therapy has shown remarkable benefit in the treatment of a range of cancer types, although it may initiate autoimmune-related disorders in some patients. We have attempted to establish whether the incidence of irAEs after the use of anti-PD-1 antibodies nivolumab or pembrolizumab in advanced malignancies is associated with anti-PD-1 treatment efficacy.
PATIENTS AND METHODS: We studied patients treated with single-agent nivolumab or pembrolizumab for advanced cancer. irAEs (immune-related adverse events) were identified clinically and graded as per the Common Terminology Criteria for Adverse Events version 4.0. Efficacy was evaluated with objective response rate (ORR, immune-Response Evaluation Criteria in Solid Tumours [RECIST] criteria) progression-free survival (PFS) and overall survival (OS). Tests were performed to determine the association between irAEs and ORR, PFS or OS.
RESULTS: We identified 106 patients. Primary diagnoses were lung cancer (n = 77), melanoma (n = 8), head and neck carcinoma (n = 7), renal carcinoma (n = 5), Hodgkin's lymphoma (n = 3), urothelial carcinoma (n = 3) and gallbladder adenocarcinoma, hepatocellular carcinoma and Merkel cell carcinoma (n = 1 each). IrAEs were observed in 40 patients (37.7%). The most frequent irAEs were hypothyroidism (n = 15), nephritis (n = 5) and hyperthyroidism (n = 4). Objective response was observed in 44 patients (41.5%), and median PFS was 5.5 months (0.5-31 months). Thirty-three of the 40 patients with irAEs had objective response (82.5%) in contrast with 11 of the 66 cases without irAEs (16.6%) (OR 23.5, P < 0.000001). PFS in patients with irAEs was 10 months and 3 months in those without irAEs (HR 2.2, P = 0.016). OS in patients with irAEs was 32 months and 22 in those without irAEs, without statistically significant differences.
CONCLUSION: In advanced cancer treated with single-agent anti-PD-1 antibodies, patients with irAEs showed a markedly improved efficacy over patients without irAEs (ORR of 82.5% and PFS of 10 months vs ORR of 16.6% and PFS of 3 months). Future studies of anti-PD-1 immune-therapy should address this association to explore the underlying biological mechanisms of efficacy.

PMID: 30682533 [PubMed - as supplied by publisher]

Avelumab Immunotherapy: Management of Adverse Events Associated With New Treatment for Merkel Cell Carcinoma.

Fetched: January 28th, 2019, 5:00am GMT

Avelumab Immunotherapy: Management of Adverse Events Associated With New Treatment for Merkel Cell Carcinoma.

Clin J Oncol Nurs. 2019 Feb 01;23(1):E1-E9

Authors: Ugolini H, Bryan J, Hennessy M, Kaufman HL, D'Angelo S

Abstract
BACKGROUND: Metastatic Merkel cell carcinoma (mMCC) is a rare skin cancer with poor prognosis. Avelumab is the first approved treatment option for patients with mMCC. Immune checkpoint inhibitors, such as avelumab, are associated with unique toxicities that can be effectively addressed with prompt recognition and appropriate management.
OBJECTIVES: This article discusses the use of avelumab for the treatment of mMCC and management of associated toxicities.
METHODS: Literature on mMCC disease state and clinical trial data for avelumab were reviewed.
FINDINGS: Avelumab has been investigated in patients with mMCC either following disease progression after one or more prior lines of chemotherapy or no prior systemic therapy. These patients experience clinically meaningful benefit. About 70% of patients receiving avelumab experience treatment-related adverse events. Given the limited benefit of chemotherapy, managing symptoms related to avelumab is key to administering this effective treatment to patients with mMCC.

PMID: 30682006 [PubMed - in process]

Cost Effectiveness of Avelumab for Metastatic Merkel Cell Carcinoma.

Fetched: January 28th, 2019, 5:00am GMT

Cost Effectiveness of Avelumab for Metastatic Merkel Cell Carcinoma.

Pharmacoecon Open. 2019 Jan 24;:

Authors: Bullement A, Nathan P, Willis A, Amin A, Lilley C, Stapelkamp C, Hatswell A, Pescott C, Bharmal M

Abstract
BACKGROUND: Metastatic Merkel cell carcinoma (mMCC) is a rare and aggressive skin cancer. Until recently, there were no licensed treatment options for patients with mMCC, and prognosis was poor. A cost-effectiveness analysis was conducted for avelumab, a newly available treatment option for mMCC, versus standard care (SC), from a UK National Health Service perspective.
METHODS: A partitioned survival model was developed to assess the lifetime costs and effects of avelumab versus SC. Data from the JAVELIN Merkel 200 trial (NCT02155647) were used to inform estimates of quality-adjusted life-years (QALYs). Unit costs and associated frequencies of use were informed by published literature and clinical expert opinion. Results were presented as incremental cost-effectiveness ratios (ICERs, i.e. the cost per QALY gained) for treatment-experienced (TE) and treatment-naïve (TN) patients. Uncertainty was explored through a range of sensitivity analyses.
RESULTS: Discounting costs and QALYs at 3.5% per annum, avelumab was associated with ICERs of £35,274 (TE)/£39,178 (TN) per QALY gained. Probabilistic sensitivity analysis results demonstrated that avelumab was associated with an 88.3% (TE)/69.3% (TN) probability of being cost effective at a willingness-to-pay threshold for end-of-life treatments of £50,000 per QALY gained. Results were most sensitive to alternative survival extrapolations and dosing assumptions.
CONCLUSIONS: The analysis results suggest that avelumab is likely to be a cost-effective treatment option for UK mMCC patients. The results for TN patients are subject to some uncertainty, and a confirmatory analysis will be conducted with more mature data.

PMID: 30680676 [PubMed - as supplied by publisher]

Activation of Protein Kinase C ε in Merkel Cell Polyomavirus-Induced Merkel Cell Carcinoma.

Fetched: January 28th, 2019, 5:00am GMT

Activation of Protein Kinase C ε in Merkel Cell Polyomavirus-Induced Merkel Cell Carcinoma.

JAMA Dermatol. 2017 09 01;153(9):931-932

Authors: Costa A, Mackelfresh J, Gilbert L, Bonner MY, Arbiser JL

PMID: 28564697 [PubMed - indexed for MEDLINE]

Spontaneous Regression of Merkel Cell Carcinoma of the Male Breast with Ongoing Immune Response.

Fetched: January 26th, 2019, 5:00am GMT

Spontaneous Regression of Merkel Cell Carcinoma of the Male Breast with Ongoing Immune Response.

Cureus. 2018 Nov 14;10(11):e3589

Authors: Nijjar Y, Bigras G, Tai P, Joseph K

Abstract
Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine tumor arising predominantly on sun-exposed skin among the elderly. The most common location is the head and neck, followed by the extremities. MCCs are highly aggressive tumors and rarely undergo spontaneous regression. We report a case of MCC which presented as a painless breast lump in an elderly male where the tumor regressed spontaneously after a biopsy.

PMID: 30675444 [PubMed]

Permalink for 'Expression of 3q oncogene SEC62 in atypical fibroxanthoma-immunohistochemical analysis of 41 cases and correlation with clinical, viral and histopathologic features.'

Expression of 3q oncogene SEC62 in atypical fibroxanthoma-immunohistochemical analysis of 41 cases and correlation with clinical, viral and histopathologic features.

Fetched: January 26th, 2019, 5:00am GMT

Expression of 3q oncogene SEC62 in atypical fibroxanthoma-immunohistochemical analysis of 41 cases and correlation with clinical, viral and histopathologic features.

Oncol Lett. 2019 Feb;17(2):1768-1776

Authors: Müller CSL, Kreie L, Bochen F, Pfuhl T, Smola S, Gräber S, Vogt T, Schick B, Linxweiler M

Abstract
Atypical fibroxanthoma (AFX) is a rare mesenchymal tumor with predominance in older male patients located mainly in chronically UV-exposed skin. Differentiation from clinically more aggressive pleomorphic dermal sarcoma (PDS) is still under debate and immunohistochemical markers are not available yet. An immunohistochemical study, including 41 cases of AFX was conducted to investigate the expression of 3q encoded oncogene SEC62 in AFX and determine the associations with histomorphologic, clinical and viral parameters. Our cohort displayed a mean of 79.9 years at the onset of the disease. In total, 90.2% (37/41) AFXs were located in the head and neck area, whereas, four were located at the extremities (9.7%). Tumor diameter ranged between 0.06 and 40 cm2 with a mean of 5.7 cm2. SEC62 expression was markedly increased in lesional tissue compared with the adjacent healthy squamous epithelium. We found significantly higher expression of SEC62 in cases of AFX with tumor necrosis. Tendency of higher Sec62-IRS-scores were found for tumors with higher Clark levels and a tumor size >5 cm2. Sec62 is involved in endoplasmic reticulum stress tolerance and cell migration, and has been identified as a novel prognostic marker for non-small cell lung cancer as well as head and neck squamous cell carcinoma. For the first time, to the best of our knowledge, we suggest a role of 3q oncogene SEC62 in AFX and discuss a potential prognostic relevance in cases of disputable AFX with unfavorable histomorphologic features and may initiate a discussion on Sec62 serving as discriminating marker between AFX and PDS.

PMID: 30675236 [PubMed]

Permalink for 'Influence of age and marital status on stage at diagnosis and survival of patients with Merkel cell carcinoma: A Surveillance, Epidemiology, and End Results registry-based cohort study.'

Influence of age and marital status on stage at diagnosis and survival of patients with Merkel cell carcinoma: A Surveillance, Epidemiology, and End Results registry-based cohort study.

Fetched: January 26th, 2019, 5:00am GMT

Influence of age and marital status on stage at diagnosis and survival of patients with Merkel cell carcinoma: A Surveillance, Epidemiology, and End Results registry-based cohort study.

J Am Acad Dermatol. 2018 Dec;79(6):1146-1148

Authors: Liu MA, Nguyen J, Driver JA

PMID: 29864470 [PubMed - indexed for MEDLINE]

Cytological diagnosis of a rare case of primary Merkel cell carcinoma of the parotid gland.

Fetched: January 26th, 2019, 5:00am GMT

Cytological diagnosis of a rare case of primary Merkel cell carcinoma of the parotid gland.

Cytopathology. 2017 12;28(6):552-554

Authors: Bizzarro T, Buda R, Ricci M, Bernardi L

PMID: 29052284 [PubMed - indexed for MEDLINE]

Association of HLA Antigen Mismatch With Risk of Developing Skin Cancer After Solid-Organ Transplant.

Fetched: January 25th, 2019, 5:00am GMT

Association of HLA Antigen Mismatch With Risk of Developing Skin Cancer After Solid-Organ Transplant.

JAMA Dermatol. 2019 Jan 23;:

Authors: Gao Y, Twigg AR, Hirose R, Roll GR, Nowacki AS, Maytin EV, Vidimos AT, Rajalingam R, Arron ST

Abstract
Importance: Risk factors for the development of skin cancer after solid-organ transplant can inform clinical care, but data on these risk factors are limited.
Objective: To study the association between HLA antigen mismatch and skin cancer incidence after solid-organ transplant.
Design, Setting, and Participants: This retrospective cohort study is a secondary analysis of the multicenter Transplant Skin Cancer Network study of 10 649 adults who underwent a primary solid-organ transplant between January 1, 2003, and December 31, 2003, or between January 1, 2008, and December 31, 2008. These participants were identified through the Scientific Registry of Transplant Recipients standard analysis files, which contain data collected mostly by the Organ Procurement and Transplantation Network. Participants were matched to skin cancer outcomes by medical record review. This study was conducted from August 1, 2016, to July 31, 2017.
Main Outcomes and Measures: The primary outcome was time to diagnosis of posttransplant skin cancer, including squamous cell carcinoma, melanoma, and Merkel cell carcinoma. The HLA antigen mismatch was calculated based on the 2016 Organ Procurement and Transplantation Network guidelines. Risk of skin cancer was analyzed using a multivariate Cox proportional hazards regression model.
Results: In total, 10 649 organ transplant recipients (6776 men [63.6%], with a mean [SD] age of 51 [12] years) contributed 59 923 years of follow-up. For each additional mismatched allele, a 7% to 8% reduction in skin cancer risk was found (adjusted hazard ratio [HR], 0.93; 95% CI, 0.87-0.99; P = .01). Subgroup analysis found the protective effect of HLA antigen mismatch to be statistically significant in lung (adjusted HR, 0.70; 95% CI, 0.56-0.87; P = .001) and heart (adjusted HR, 0.75; 95% CI, 0.60-0.93; P = .008) transplant recipients but not for recipients of liver, kidney, or pancreas. The degree of HLA-DR mismatch, but not HLA-A or HLA-B mismatch, was the most statistically significant for skin cancer risk (adjusted HR, 0.85; 95% CI, 0.74-0.97; P = .01).
Conclusions and Relevance: The HLA antigen mismatch appears to be associated with reductions in the risk of skin cancer after solid-organ transplant among heart and lung transplant recipients; this finding suggests that HLA antigen mismatch activates the tumor surveillance mechanisms that protect against skin cancer in transplant recipients and that skin cancer risk may be higher in patients who received a well-matched organ.

PMID: 30673077 [PubMed - as supplied by publisher]

Successful immunotherapy and irradiation in a HIV-positive patient with metastatic Merkel cell carcinoma.

Fetched: January 25th, 2019, 5:00am GMT

Successful immunotherapy and irradiation in a HIV-positive patient with metastatic Merkel cell carcinoma.

Clin Transl Radiat Oncol. 2019 Feb;15:42-45

Authors: Linge A, Rauschenberg R, Blum S, Spornraft-Ragaller P, Meier F, Troost EGC

Abstract
This case report presents a HIV-positive 60-year old male with Merkel cell carcinoma of his right forearm and pulmonary sarcoidosis, who, after excisions and irradiations of the primary tumour site and subsequent lymph node metastases developed distant metastases. He received radiotherapy to symptomatic mediastinal lymph node metastases followed by Doxorubicin and, after two cycles, by the PD-1 inhibitor Pembrolizumab due to mixed response. Re-staging showed a para-mediastinal, radiotherapy-induced pneumonitis, which was treated by prednisolone due to clinical symptoms. In September 2017, the patient developed a solitary lymph node metastasis next to the right atrium, for which he received stereotactic radiotherapy. The systemic treatment with Pembrolizumab was replaced by the PD-L1 inhibitor Avelumab and is being continued since. The patient has been in complete remission for one year now and the HIV-infection is well-controlled.

PMID: 30671549 [PubMed]

Merkel cell carcinoma of the thigh: case report and review of the literature.

Fetched: January 24th, 2019, 5:00am GMT

Merkel cell carcinoma of the thigh: case report and review of the literature.

Onco Targets Ther. 2019;12:535-540

Authors: Jiang W, Xu J, Wang R, Wang T, Shu Y, Liu L

Abstract
Background: Merkel cell carcinoma (MCC) is a kind of cutaneous neuroendocrine cancer with a poor prognosis. It is characterized by a high rate of recurrence and metastases, including distant metastases and regional nodal metastases. Clinically, MCC often manifests as obvious single painless hard nodules visible in sun irradiation of diameter <2 cm and not uncommonly >2 cm, with rapid growth and metastases, especially lymph node metastases. Due to the aspecific nature of MCC, it is often confused with other skin cancers. Exploring different treatments of MCC is necessary.
Case presentation: The current study describes the case of an 86-year-old retired man, who presented with a 2.5×2.0×1.2 cm red nodule on the right thigh, which was initially diagnosed as subcutaneous small cell cancer. Upon histological and immunohistochemical analysis, the tumor was consistent with a diagnosis of MCC.
Results: Antiangiogenic therapy combining endostar and apatinib was administered and a partial response achieved after 2.0 months of treatment, and 6.5 months of progression-free survival was achieved. Overall survival was 13.0 months.
Conclusion: We believe that antiangiogenic therapy is an extremely effective treatment for MCC, especially for patients who cannot tolerate chemotherapy and radiotherapy.

PMID: 30666132 [PubMed]

Use of Targeted Therapy in the Treatment of Advanced Cutaneous Cancers.

Fetched: January 24th, 2019, 5:00am GMT

Use of Targeted Therapy in the Treatment of Advanced Cutaneous Cancers.

JAMA Dermatol. 2017 06 01;153(6):501-502

Authors: Council ML

PMID: 28403377 [PubMed - indexed for MEDLINE]

Tuberculosis following PD-1 blockade for cancer immunotherapy.

Fetched: January 19th, 2019, 5:00am GMT

Tuberculosis following PD-1 blockade for cancer immunotherapy.

Sci Transl Med. 2019 Jan 16;11(475):

Authors: Barber DL, Sakai S, Kudchadkar RR, Fling SP, Day TA, Vergara JA, Ashkin D, Cheng JH, Lundgren LM, Raabe VN, Kraft CS, Nieva JJ, Cheever MA, Nghiem PT, Sharon E

Abstract
Because of the well-established therapeutic benefit of boosting antitumor responses through blockade of the T cell inhibitory receptor PD-1, it has been proposed that PD-1 blockade could also be useful in infectious disease settings, including Mycobacterium tuberculosis (Mtb) infection. However, in preclinical models, Mtb-infected PD-1-/- mice mount exaggerated TH1 responses that drive lethal immunopathology. Multiple cases of tuberculosis during PD-1 blockade have been observed in patients with cancer, but in humans little is understood about Mtb-specific immune responses during checkpoint blockade-associated tuberculosis. Here, we report two more cases. We describe a patient who succumbed to disseminated tuberculosis after PD-1 blockade for treatment of nasopharyngeal carcinoma, and we examine Mtb-specific immune responses in a patient with Merkel cell carcinoma who developed checkpoint blockade-associated tuberculosis and was successfully treated for the infection. After anti-PD-1 administration, interferon-γ-producing Mtb-specific CD4 T cells became more prevalent in the blood, and a tuberculoma developed a few months thereafter. Mtb-specific TH17 cells, CD8 T cells, regulatory T cells, and antibody abundance did not change before the appearance of the granuloma. These results are consistent with the murine model data and suggest that boosting TH1 function with PD-1 blockade may increase the risk or severity of tuberculosis in humans.

PMID: 30651320 [PubMed - in process]

Cutaneous Malignancy due to Arsenicosis in Bangladesh: 12-Year Study in Tertiary Level Hospital.

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

Cutaneous Malignancy due to Arsenicosis in Bangladesh: 12-Year Study in Tertiary Level Hospital.

Biomed Res Int. 2018;2018:4678362

Authors: Choudhury MIM, Shabnam N, Ahsan T, Ahsan SMA, Kabir MS, Khan RM, Miah MA, Uddin MK, Liton MAR

Abstract
Bangladesh is grappling with the largest mass poisoning of a population in the world due to contamination of drinking water with naturally occurring inorganic arsenic. It is estimated that 75 million people of 59 (out of 64) districts are at risk of drinking contaminated water with arsenic above 50μg/L. Long term exposure to arsenic causes cancers, including skin, lung, and bladder. This is a randomized prospective study to see the prevalence of skin cancer from arsenic affected area of Bangladesh, as well as their variation by geographical area, age, gender, location on the body, and socioeconomic conditions, in outpatient department of plastic surgery unit of Bangabandhu Sheikh Mujib Medical University (BSMMU). A total of 960 patients with skin cancers comprised of 528 males and 432 females were selected for the study from January 2004 to December 2015. In this 12-year study, we found squamous cell carcinoma, basal cell carcinoma, melanoma, and Merkel cell carcinoma to be associated with the ingestion of arsenic contaminated ground water. This is a reflection of a small part of the total national scenario of devastating result of arsenic mediated cancer in terms of skin malignancy. This study will help the future researchers who are contemplating to work on arsenic induced health problem.

PMID: 30643806 [PubMed - in process]

Permalink for 'Update on eighth edition American Joint Committee on Cancer classification for Merkel cell carcinoma and histopathological parameters that determine prognosis.'

Update on eighth edition American Joint Committee on Cancer classification for Merkel cell carcinoma and histopathological parameters that determine prognosis.

Fetched: January 16th, 2019, 5:00am GMT

Update on eighth edition American Joint Committee on Cancer classification for Merkel cell carcinoma and histopathological parameters that determine prognosis.

J Clin Pathol. 2019 Jan 13;:

Authors: Trinidad CM, Torres-Cabala CA, Prieto VG, Aung PP

Abstract
Merkel cell carcinoma (MCC) is a rare primary cutaneous neuroendocrine carcinoma. The annual incidence of MCC is increasing in the USA. Timely diagnosis and proper staging of this tumour are crucial as MCC has high rates of regional recurrence and lymph node and distant metastasis. In this review, we outline the key differences between the tumor node metastasis (TNM) staging criteria for MCC in the seventh and eighth editions of the AJCC Cancer Staging Manual We also discuss histopathological parameters that are not included in the eighth edition of the manual but have been shown in other studies to predict a worse prognosis in patients with MCC. Correct assessment and reporting of these clinically relevant histopathological parameters is of utmost importance for practising pathologists as management differs according to the stage of the tumour. This review aims to increase awareness of all these parameters, and proper recognition would guide the treating clinicians towards the most appropriate treatment options that can be given to patients.

PMID: 30636696 [PubMed - as supplied by publisher]

Permalink for 'Occurrence of newly discovered human polyomaviruses in skin of liver transplant recipients and their relation with SCC in situ and actinic keratosis.'

Occurrence of newly discovered human polyomaviruses in skin of liver transplant recipients and their relation with SCC in situ and actinic keratosis.

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

Occurrence of newly discovered human polyomaviruses in skin of liver transplant recipients and their relation with SCC in situ and actinic keratosis.

Transpl Int. 2019 Jan 10;:

Authors: Wang Y, Keinonen A, Koskenmies S, Pitkänen S, Fyhrquist N, Sadeghi M, Mäkisalo H, Söderlund-Venermo M, Hedman K

Abstract
To date 14 human polyomaviruses (HPyVs) have been identified. The newly found HPyVs have not been examined with regard to post-transplant skin carcinogenesis. To determine the occurrences in skin and possible pathological associations of the HPyVs, we studied their genoprevalences in squamous cell carcinoma (SCC) in situ or actinic keratosis and benign skin in liver transplant recipients (LiTRs); and of healthy skin in immunocompetent adults. We used highly sensitive and specific HPyV PCRs of two types. Overall, Merkel cell polyomavirus (MCPyV), human polyomavirus 6 (HPyV6), human polyomavirus 7 (HPyV7), trichodysplasia spinulosa polyomavirus (TSPyV) and Lyon IARC polyomavirus (LIPyV), were found in 58/221 (26.2%) skin biopsies. MCPyV DNA was detected in 5/14 (35.7%) premalignant vs. 32/127 (25.2%) benign skin of LiTRs, and in 12/80 (15%) healthy skin of immunocompetent adults, with no statistically significant difference in viral DNA prevalence or load. TSPyV DNA was found in a single skin lesion. LIPyV, HPyV6 and HPyV7 DNAs occurred exclusively in benign skin. Overall, the viral findings in premalignant vs. benign skin were alike. The occurrences of HPyVs in skin of LiTRs and immunocompetent individuals speak against a role for any of the 14 HPyVs in SCC development. This article is protected by copyright. All rights reserved.

PMID: 30632206 [PubMed - as supplied by publisher]

Cytokines, Chemokines, and Other Biomarkers of Response for Checkpoint Inhibitor Therapy in Skin Cancer.

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

Cytokines, Chemokines, and Other Biomarkers of Response for Checkpoint Inhibitor Therapy in Skin Cancer.

Front Med (Lausanne). 2018;5:351

Authors: Bridge JA, Lee JC, Daud A, Wells JW, Bluestone JA

Abstract
Immunotherapy for skin malignancies has ushered in a new era for cancer treatments by demonstrating unprecedented durable responses in the setting of metastatic Melanoma. Consequently, checkpoint inhibitors are now the first-line treatment of metastatic melanoma and widely used as adjuvant therapy for stage III disease. With the observation that higher tumor mutational burden correlates with a better response, checkpoint inhibitors are tested in other skin cancer types of known high tumor mutational burden with promising results and recently became the first-ever FDA-approved treatment for metastatic Merkel cell carcinoma. The emerging new standards-of-care will necessitate more precise biomarkers and predictors for treatment response and immune-related adverse events. Measurable immune-related mediators are currently under investigation as factors that promote or block the response to cancer immunotherapy and may provide insights into the underlying immune response to the tumor. Cytokines and chemokines are such mediators and are crucial for facilitating the recruitment and activation of specific subsets of leukocytes within the microenvironment of skin cancers. The exact mechanisms of how these meditators, both immunological and non-immunological, operate in the tumor microenvironment is an area of active research, so to reliable biomarkers of responses to cancer immunotherapy. Here, we will review and summarize the expanding body of literature for immune-related biomarkers pertaining to Melanoma, Basal cell carcinoma, Squamous cell carcinoma, and Merkel cell carcinoma, highlighting clinically relevant checkpoint inhibitor therapy biomarker advancements.

PMID: 30631766 [PubMed]

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

Fetched: January 12th, 2019, 5:00am GMT

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

Thorac Cancer. 2019 Jan 09;:

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

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

PMID: 30628176 [PubMed - as supplied by publisher]

Infectious Entry of Merkel Cell Polyomavirus.

Fetched: January 12th, 2019, 5:00am GMT

Infectious Entry of Merkel Cell Polyomavirus.

J Virol. 2019 Jan 09;:

Authors: Becker M, Dominguez M, Greune L, Soria-Martinez L, Pfleiderer MM, Schowalter R, Buck CB, Blaum BS, Schmidt MA, Schelhaas M

Abstract
Merkel Cell Polyomavirus (MCPyV) is a small, non-enveloped tumor virus associated with an aggressive form of skin cancer, the Merkel cell carcinoma (MCC). MCPyV infections are highly prevalent in the human population with MCPyV virions being continuously shed from human skin. However, the precise host cell tropism(s) of MCPyV remains unclear: MCPyV is able to replicate within a subset of dermal fibroblasts, but MCPyV DNA has also been detected in a variety of other tissues. However, MCPyV appears different from other polyomaviruses as it requires sulfated polysaccharides such as heparan sulfates and/or chondroitin sulfates for initial attachment. Like other polyomaviruses, MCPyV engages sialic acid as a (co-)receptor. To explore the infectious entry process of MCPyV, we analyzed the cell biological determinants of MCPyV entry into A549 cells, a highly transducible lung carcinoma cell line, in comparison to well-studied simian virus 40 and a number of other viruses. Our results indicate that MCPyV enters cells via caveolar/lipid raft-mediated endocytosis but not macropinocytosis, clathrin-mediated endocytosis or glycosphingolipid-enriched carriers. The viruses internalized in small endocytic pits that led the virus to endosomes and from there to the endoplasmic reticulum (ER). Similar to other polyomaviruses, trafficking required microtubular transport, acidification of endosomes, and a functional redox environment. To our surprise, the virus was found to acquire a membrane envelope within endosomes, a phenomenon not reported for other viruses. Only minor amounts of viruses reached the ER, while the majority was retained in endosomal compartments suggesting that endosome-to-ER trafficking is a bottleneck during infectious entry.IMPORTANCE MCPyV is the first polyomavirus directly implicated in the development of an aggressive human cancer, the Merkel Cell Carcinoma (MCC). Although MCPyV is constantly shed from healthy skin, MCC incidence increases among aging and immunocompromised individuals. To date, the events connecting initial MCPyV infection and subsequent transformation still remain elusive. MCPyV differs from other known polyomaviruses concerning its cell tropism, entry receptor requirements, and infection kinetics. In this study, we examined the cellular requirements for endocytic entry as well as the subcellular localization of incoming virus particles. A thorough understanding of the determinants of the infectious entry pathway and the specific biological niche will benefit prevention of virus-derived cancers such as MCC.

PMID: 30626687 [PubMed - as supplied by publisher]

Detection and Characterization of Circulating Tumor Cells in Patients with Merkel Cell Carcinoma.

Fetched: January 12th, 2019, 5:00am GMT

Detection and Characterization of Circulating Tumor Cells in Patients with Merkel Cell Carcinoma.

Clin Chem. 2019 Jan 09;:

Authors: Riethdorf S, Hildebrandt L, Heinzerling L, Heitzer E, Fischer N, Bergmann S, Mauermann O, Waldispühl-Geigl J, Coith C, Schön G, Peine S, Schuler G, Speicher MR, Moll I, Pantel K

Abstract
BACKGROUND: Merkel cell carcinoma (MCC)8 is a rare, aggressive skin cancer with increasing incidence and high mortality rates. MCC has recently become the subject of immune checkpoint therapy, but reliable biomarkers for estimating prognosis, risk stratification, and prediction of response are missing.
METHODS: Circulating tumor cells (CTCs) were detected in peripheral blood from patients with MCC by use of the CellSearch® system. Moreover, CTCs of selected cases were characterized for Merkel cell polyomavirus (MCPyV), chromosomal aberrations, and programed death ligand 1 (PD-L1) production.
RESULTS: Fifty-one patients were tested at first blood draw (baseline), and 16 patients had 2 or 3 consecutive measurements to detect CTCs. At baseline, ≥1 CTC (range, 1-790), >1, or ≥5 CTCs/7.5 mL were detected in 21 (41%), 17 (33%), and 6 (12%) patients, respectively. After a median follow-up of 21.1 months for 50 patients, detection of CTCs correlated with overall survival (≥1, P = 0.030; >1, P < 0.020; and ≥5 CTCs/7.5 mL, P < 0.0001). In multivariate Cox regression analysis, the detection of ≥5 CTCs/7.5 mL adjusted to age and sex compared to that of <5 was associated with a reduced overall survival (P = 0.001, hazard ratio = 17.8; 95% CI, 4.0-93.0). MCPyV DNA and genomic aberrations frequently found in MCC tissues could also be detected in single CTCs. Analyzed CTCs were PD-L1 negative or only weakly positive.
CONCLUSIONS: The presence of CTCs is a prognostic factor of impaired clinical outcome, with the potential to monitor the progression of the disease in real time. Molecular characterization of CTCs might provide new insights into the biology of MCC.

PMID: 30626636 [PubMed - as supplied by publisher]

Cutaneous metastases of pancreatic neuroendocrine carcinoma.

Fetched: January 11th, 2019, 5:00am GMT

Cutaneous metastases of pancreatic neuroendocrine carcinoma.

G Ital Dermatol Venereol. 2018 Oct;153(5):722-724

Authors: Laschinger ME, Naga L, Gaspari AA

Abstract
Neuroendocrine carcinomas with distant metastases are rarely reported in the literature, with cutaneous metastases being among the most infrequently reported sites. The importance of distinguishing metastatic neuroendocrine carcinoma (NEC) from primary neuroendocrine carcinoma in the skin, or Merkel cell carcinoma (MCC), has been stressed in the literature, with CK20 positivity traditionally being reported as the key diagnostic feature of MCC. Our case not only serves as one of the few reported cases of cutaneous metastases of a visceral NEC, but also serves to caution providers as to the use of CK20 positivity as an absolute diagnostic feature. We present a case of a 67-year-old female with widespread cutaneous metastases of a pancreatic NEC. Immunohistochemical staining revealed CK20 positivity, despite visceral origin of the primary tumor. This case serves to highlight not only a rare presentation of cutaneous metastases of a pancreatic neuroendocrine carcinoma, which has yet to be reported in the literature, but also serves as the only report of a pancreatic NEC with CK20 positivity, providing evidence for cautionary use of CK20 staining for diagnostic purposes, particularly for visceral NECs which have been under-represented in the literature.

PMID: 30246953 [PubMed - indexed for MEDLINE]

The first observation of the association of Merkel cell polyomavirus and Merkel cell carcinoma in Brazil.

Fetched: January 10th, 2019, 5:00am GMT

The first observation of the association of Merkel cell polyomavirus and Merkel cell carcinoma in Brazil.

Int J Dermatol. 2019 Jan 08;:

Authors: Neto CF, Oliveira WRP, Costa PVA, Cardoso MK, Barreto PG, Romano CM, Urbano PR

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) is a rare but aggressive primary cutaneous carcinoma with high mortality rates. The present study intends to delineate the epidemiological profile of patients with MCC seen at the Clinics Hospital of the Medical School at the University of São Paulo, Brazil, and its association with Merkel cell polyomavirus (MCPyV).
METHODS: This is a retrospective study. A search was performed in the hospital's medical index for all cases of MCC from January 1994 to December 2012. Among patients with MCC, the available tumoral skin specimens were analyzed with two different techniques of polymerase chain reaction (PCR) (conventional and real-time) for detection of MCPyV DNA. Additionally, paraffin-embedded samples of patients with non-MCC skin cancers were also analyzed. Analyses suitable for categorical data (i.e., x² of Fisher) were used to compare the proportion of patients in each group.
RESULTS: Nineteen patients with MCC and 20 patients with non-MCC skin cancers entered the study. All MCC samples available (13) tested positive for the presence of MCPyV DNA; however, in the non-MCC skin cancer samples, the MCPyV DNA was detected in 4 of 20 samples (20%). MCPyV DNA detection rate was higher in patients with MCC than in the other group, and its analysis was statistically significant (P < 0.01).
CONCLUSIONS: This study demonstrates the association of MCPyV in Brazilian patients with MCC. However, further studies are necessary to determine the exact involvement of MCPyV in MCC pathogenesis and to define the significance of viral DNA detection in non-MCC skin cancers.

PMID: 30620056 [PubMed - as supplied by publisher]

Immune checkpoint blockade for Merkel cell carcinoma: actual findings and unanswered questions.

Fetched: January 10th, 2019, 5:00am GMT

Immune checkpoint blockade for Merkel cell carcinoma: actual findings and unanswered questions.

J Cancer Res Clin Oncol. 2019 Feb;145(2):429-443

Authors: Gallo M, Guarnotta V, De Cicco F, Rubino M, Faggiano A, Colao A, NIKE Group

Abstract
PURPOSE: Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine carcinoma arising from the skin. We aimed to review and deal with some of the most relevant controversial topics on the correct use of immunotherapy for the treatment of MCC.
METHODS: The primary search was carried out via PubMed, EMBASE, and the Cochrane Library (until 31st May, 2018), while other articles and guidelines were retrieved from related papers or those referenced in these papers. Additionally, we performed an extensive search on ClinicalTrials.gov to gather information on the ongoing clinical trials related to this specific topic.
RESULTS: We performed an up-to-date critical review taking into account the results of both retrospective and prospective published studies evaluating these issues: Are there any predictive criteria of response to immunotherapy? What is the correct place of immunotherapy in the treatment algorithm of MCC? What is the best choice after immunotherapy failure? What to do with patients for whom immunotherapy is not been feasible or contraindicated? How long should immunotherapy be prolonged, and what follow-up should be offered after complete response?
CONCLUSION: The therapeutic landscape of MCC is rapidly evolving: many open issues will probably be resolved, and many other questions are likely to arise in the next few years. The results of ongoing prospective clinical trials and of several other studies on these issues are eagerly awaited.

PMID: 30617553 [PubMed - indexed for MEDLINE]

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
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 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 Melanoma
Interventions: Biological: Ipilimumab; Biological: Nivolumab; Drug: Prednisone; Drug: Tacrolimus
Sponsor: National Cancer Institute (NCI)
Not yet 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: Hiral Shah; 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
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

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

Condition: Acute Myeloid Leukemia
Interventions: Drug: PF-04518600; Drug: Avelumab; Drug: Azacitidine; Drug: Utomilumab; Drug: Gemtuzumab Ozogamicin; Drug: Glasdegib
Sponsors: M.D. Anderson Cancer Center; Pfizer
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

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: 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

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

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

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.
Not yet 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.
Not yet 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)
Not yet 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
Not yet 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)
Not yet 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; Metastatic Malignant Neoplasm in the Brain; Metastatic Melanoma; Pathologic Stage IV Cutaneous Melanoma
Interventions: Biological: Ipilimumab; Biological: Pembrolizumab
Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI); Merck Sharp & Dohme Corp.
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 Sarcomatoid Variant; Infiltrating Bladder Urothelial Carcinoma With Giant Cells; Infiltrating Bladder Urothelial Carcinoma, Nested Variant; Infiltrating Bladder Urothelial Carcinoma, Plasmacytoid Variant; Kidney Medullary Carcinoma; Large Cell Neuroendocrine Carcinoma; Metastatic Bladder Carcinoma; Metastatic Bladder Large Cell Neuroendocrine Carcinoma; Metastatic Bladder Small Cell Neuroendocrine Carcinoma; Metastatic Bladder Squamous Cell Carcinoma; Metastatic Infiltrating Bladder Urothelial Carcinoma, Lipid-Cell Variant; Metastatic Kidney Medullary Carcinoma; Metastatic Malignant Genitourinary System Neoplasm; Metastatic Penile Carcinoma; Metastatic Plasmacytoid Urothelial Carcinoma; Metastatic Prostate Small Cell Carcinoma; Metastatic Sarcomatoid Renal Cell Carcinoma; Metastatic Sarcomatoid Urothelial 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)
Not yet 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

Distant Metastases and Long-Term Survival After Complete Resection of Neuroendocrine Tumors of the Appendix

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

Condition: Neuroendocrine Tumors of the Appendix
Intervention: Other: Histopathological review
Sponsor: University Hospital Inselspital, Berne
Not yet recruiting

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

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

Conditions: Melanoma; Cervical Carcinoma; Pancreatic Carcinoma; Triple Negative Breast Cancer; Hepatocellular Carcinoma; Urothelial Carcinoma; Squamous Cell Carcinoma of the Head and Neck; Nasopharyngeal Carcinoma; Renal Cell Carcinoma; Colorectal Carcinoma; Endometrial Carcinoma; Non-small Cell Lung Carcinoma; Small Cell Lung Carcinoma; Gastric or Gastroesophageal Junction Adenocarcinoma; Advanced or Metastatic Solid Tumors
Interventions: Biological: XmAb®22841; Biological: Pembrolizumab (Keytruda®)
Sponsors: Xencor, Inc.; ICON plc
Not yet recruiting

A Study To See Why Patients Agree To or Decline To Have Treatment After Surgery

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

Condition: Cutaneous Melanoma
Interventions: Behavioral: Demographics Questionnaire; Behavioral: Adjuvant Treatment Beliefs Scale10; Behavioral: Functional Assessment of Cancer Therapy - Melanoma (FACT-M)11; Behavioral: Functional Assessment of Chronic Illness Therapy - Treatment Satisfaction - General (FACIT-TS-G)13; Behavioral: Decisional Regret14
Sponsor: Memorial Sloan Kettering Cancer Center
Recruiting

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

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

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

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

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

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

Second-line Therapy for Patients With Progressive Poorly Differentiated Extra-pulmonary Neuroendocrine Carcinoma

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

Conditions: Oncology; Neuroendocrine Carcinoma
Interventions: Drug: Liposomal Irinotecan; Drug: Fluorouracil; Drug: Folinic Acid; Drug: Docetaxel
Sponsors: The Christie NHS Foundation Trust; University of Leeds; Servier; National Institute for Health Research, United Kingdom
Recruiting

Ponatinib in Advanced or Metastatic Medullary Thyroid Cancer

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

Condition: Medullary Thyroid Cancer
Intervention: Drug: Ponatinib
Sponsors: Antonio Fojo; Millennium Pharmaceuticals, Inc.
Not yet recruiting

Endoscopic Ultrasound-guided RadioFrequency Ablation for the Treatment Pancreatic NeuroEndocrine Neoplasms

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

Conditions: Neuroendocrine Tumors; Neuroendocrine Carcinoma; Pancreas Neoplasm; Neuroendocrine Tumor Gastrointestinal, Hormone-Secreting
Intervention: Device: EUS guided radiofrequency ablation
Sponsor: Catholic University of the Sacred Heart
Not yet recruiting

Avadomide (CC-122) in Combination With Nivolumab in Advanced Melanoma

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

Condition: Melanoma
Interventions: Drug: CC-122; Drug: Nivolumab
Sponsors: H. Lee Moffitt Cancer Center and Research Institute; Bristol-Myers Squibb; Celgene Corporation
Not yet recruiting

Chromogranin A as Blood Marker in Cancer Patients

Posted: January 28th, 2019, 3:00pm GMT

Conditions: Gastric Neoplasms; Pancreatic Neoplasms; Small Intestinal Neoplasms; Colorectal Neoplasms
Intervention: Diagnostic Test: BRAHMS CgA II KRYPTOR
Sponsor: Brahms AG
Recruiting

Cushing's Lipodystrophy

Posted: January 28th, 2019, 3:00pm GMT

Condition: Cushing's Syndrome
Intervention: Procedure: Treatment of Cushing's
Sponsors: Columbia University; New York Obesity and Nutrition Research Center
Recruiting

Permalink for 'Role of Gut Microbiome and Fecal Transplant on Medication-Induced GI Complications in Patients With Melanoma or Genitourinary Cancer'

Role of Gut Microbiome and Fecal Transplant on Medication-Induced GI Complications in Patients With Melanoma or Genitourinary Cancer

Posted: January 28th, 2019, 3:00pm GMT

Conditions: Clinical Stage 0 Cutaneous Melanoma AJCC v8; Clinical Stage I Cutaneous Melanoma AJCC v8; Clinical Stage IA Cutaneous Melanoma AJCC v8; Clinical Stage IB Cutaneous Melanoma AJCC v8; Clinical Stage II Cutaneous Melanoma AJCC v8; Clinical Stage IIA Cutaneous Melanoma AJCC v8; Clinical Stage IIB Cutaneous Melanoma AJCC v8; Clinical Stage IIC Cutaneous Melanoma AJCC v8; Clinical Stage III Cutaneous Melanoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Colitis; Diarrhea; Malignant Genitourinary System Neoplasm; Pathologic Stage 0 Cutaneous Melanoma AJCC v8; Pathologic Stage I Cutaneous Melanoma AJCC v8; Pathologic Stage IA Cutaneous Melanoma AJCC v8; Pathologic Stage IB Cutaneous Melanoma AJCC v8; Pathologic Stage II Cutaneous Melanoma AJCC v8; Pathologic Stage IIA Cutaneous Melanoma AJCC v8; Pathologic Stage IIB Cutaneous Melanoma AJCC v8; Pathologic Stage IIC Cutaneous Melanoma AJCC v8; Pathologic Stage III Cutaneous Melanoma AJCC v8; Pathologic Stage IIIA Cutaneous Melanoma AJCC v8; Pathologic Stage IIIB Cutaneous Melanoma AJCC v8; Pathologic Stage IIIC Cutaneous Melanoma AJCC v8; Pathologic Stage IIID Cutaneous Melanoma AJCC v8; Pathologic Stage IV Cutaneous Melanoma AJCC v8
Interventions: Other: Best Practice; Other: Biospecimen Collection; Procedure: Endoscopic Procedure; Procedure: Fecal Microbiota Transplantation; Biological: Infliximab; Other: Laboratory Biomarker Analysis; Drug: Prednisone; Biological: Vedolizumab
Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI)
Not yet recruiting

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

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

Recurrence Rates of Type I Gastric Neuroendocrine Tumors Treated With Long-acting Somatostatin Analogs

Posted: January 23rd, 2019, 3:00pm GMT

Condition: Gastric NET
Intervention: Drug: Octreotide
Sponsor: Peking Union Medical College Hospital
Recruiting

Phase 1 Study of INBRX-105 in Patients With Solid Tumors, Hodgkin or Non-Hodgkin Lymphoma

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

Conditions: Metastatic Solid Tumors; Hodgkin Lymphoma; Non Hodgkin Lymphoma; Non-small Cell Lung Cancer; Melanoma; Head and Neck Squamous Cell Carcinoma; Gastric Adenocarcinoma; Renal Cell Carcinoma; Urothelial Carcinoma; Esophageal Adenocarcinoma
Intervention: Drug: INBRX-105 - PDL1x41BB antibody
Sponsor: Inhibrx, Inc.
Recruiting

Study of Dendritic Cells Pulsed With Tumor Lysate in Advanced Melanoma Dendritic Cells in Advanced Melanoma

Posted: January 14th, 2019, 3:00pm GMT

Condition: Metastatic Melanoma
Intervention: Biological: Dendritic Cells
Sponsors: PrimeVax Immuno-Oncology Inc.; Advocate Lutheran General Hospital
Not yet recruiting

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

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

Study of RP1 Monotherapy and RP1 in Combination With Nivolumab

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

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

Biomarker Study of Pancreatic Neuroendocrine Tumours

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

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

$Permalink for 'Liposomal Irinotecan, Fluorouracil and Leucovorin in Treating Patients With Refractory Advanced High Grade Neuroendocrine Cancer of Gastrointestinal, Unknown, or Pancreatic Origin'$

Liposomal Irinotecan, Fluorouracil and Leucovorin in Treating Patients With Refractory Advanced High Grade Neuroendocrine Cancer of Gastrointestinal, Unknown, or Pancreatic Origin

Posted: November 9th, 2018, 3:00pm GMT

Conditions: Locally Advanced Digestive System Neuroendocrine Carcinoma; Locally Advanced Pancreatic Neuroendocrine Carcinoma; Metastatic Digestive System Neuroendocrine Carcinoma; Metastatic Pancreatic Neuroendocrine Carcinoma; Refractory Digestive System Neuroendocrine Carcinoma; Refractory Pancreatic Neuroendocrine Carcinoma; Unresectable Digestive System Neuroendocrine Carcinoma; Unresectable Pancreatic Neuroendocrine Carcinoma
Interventions: Drug: Fluorouracil; Drug: Leucovorin; Drug: Liposomal Irinotecan; Procedure: Quality-of-Life Assessment
Sponsors: Roswell Park Cancer Institute; National Cancer Institute (NCI); Ipsen
Not yet recruiting

A Phase 1 Study of ZSP1602 in Participants With Advanced Solid Tumors

Posted: November 8th, 2018, 3:00pm GMT

Conditions: Basal Cell Carcinoma; Medulloblastoma; Adenocarcinoma of Esophagogastric Junction; Small Cell Lung Cancer; Neuroendocrine Neoplasm; Glioblastoma
Intervention: Drug: ZSP1602
Sponsor: Guangdong Zhongsheng Pharmaceutical Co., Ltd.
Recruiting

CBL0137 in Treating Patients With Advanced Extremity Melanoma or Sarcoma

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

Conditions: Advanced Cutaneous Melanoma of the Extremity; Advanced Sarcoma of the Extremity; Clinical Stage III Cutaneous Melanoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Pathologic Stage IIIB Cutaneous Melanoma AJCC v8; Pathologic Stage IIIC Cutaneous Melanoma AJCC v8; Pathologic Stage IV Cutaneous Melanoma AJCC v8; Recurrent Cutaneous Melanoma of the Extremity; Recurrent Sarcoma of the Extremity; Stage III Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8; Stage IIIA Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8; Stage IIIB Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8; Stage IV Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8
Intervention: Drug: FACT Complex-targeting Curaxin CBL0137
Sponsors: Roswell Park Cancer Institute; National Cancer Institute (NCI); Incuron
Not yet recruiting

Personalized Neo-antigen Vaccine in Advanced Solid Tumors (NeoPepVac)

Posted: October 23rd, 2018, 2:00pm GMT

Conditions: Malignant Melanoma, Metastatic; Non Small Cell Lung Cancer Metastatic; Kidney Cancer Metastatic
Intervention: Drug: EVAX-01-CAF09b
Sponsor: Herlev Hospital
Recruiting

Enzalutamide and Decitabine in Treating Patients With Metastatic Castration Resistant Prostate Cancer

Posted: October 17th, 2018, 2:00pm GMT

Conditions: Castration Levels of Testosterone; Castration-Resistant Prostate Carcinoma; Metastatic Prostate Carcinoma in the Soft Tissue; Prostate Carcinoma Metastatic in the Bone; PSA Level Greater Than or Equal to Two; PSA Progression; Stage IV Prostate Cancer AJCC v8; Stage IVA Prostate Cancer AJCC v8; Stage IVB Prostate Cancer AJCC v8
Interventions: Drug: Decitabine; Drug: Enzalutamide
Sponsors: Roswell Park Cancer Institute; National Cancer Institute (NCI)
Not yet recruiting

Evaluation of Melatonin Application of Immediate Dental Implant

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

Condition: Immediate Dental Implant
Intervention: Procedure: immediate implant placement
Sponsor: Cairo University
Not yet recruiting

Post-Authorization Long-Term Safety Study of LUTATHERA

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

Condition: Neuroendocrine Tumors
Intervention: Drug: LUTATHERA
Sponsor: Advanced Accelerator Applications
Recruiting

A Study of INCMGA00012 in Participants With Selected Solid Tumors (POD1UM-203)

Posted: September 20th, 2018, 2:00pm GMT

Conditions: Metastatic Non-small Cell Lung Cancer; Locally Advanced Urothelial Cancer; Metastatic Urothelial Cancer; Unresectable Melanoma; Metastatic Melanoma; Locally Advanced Renal Cell Carcinoma; Metastatic Clear-Cell Renal Cell Carcinoma
Intervention: Drug: INCMGA00012
Sponsor: Incyte Corporation
Recruiting

Permalink for 'Young Melanoma Family Facebook Intervention or Healthy Lifestyle Facebook Intervention in Improving Skin Examination in Participants With Melanoma and Their Families'

Young Melanoma Family Facebook Intervention or Healthy Lifestyle Facebook Intervention in Improving Skin Examination in Participants With Melanoma and Their Families

Posted: September 19th, 2018, 2:00pm GMT

Conditions: Clinical Stage 0 Cutaneous Melanoma AJCC v8; Clinical Stage I Cutaneous Melanoma AJCC v8; Clinical Stage IA Cutaneous Melanoma AJCC v8; Clinical Stage IB Cutaneous Melanoma AJCC v8; Clinical Stage II Cutaneous Melanoma AJCC v8; Clinical Stage IIA Cutaneous Melanoma AJCC v8; Clinical Stage IIB Cutaneous Melanoma AJCC v8; Clinical Stage IIC Cutaneous Melanoma AJCC v8; Clinical Stage III Cutaneous Melanoma AJCC v8; First Degree Relative; Pathologic Stage 0 Cutaneous Melanoma AJCC v8; Pathologic Stage I Cutaneous Melanoma AJCC v8; Pathologic Stage IA Cutaneous Melanoma AJCC v8; Pathologic Stage IB Cutaneous Melanoma AJCC v8; Pathologic Stage II Cutaneous Melanoma AJCC v8; Pathologic Stage IIA Cutaneous Melanoma AJCC v8; Pathologic Stage IIB Cutaneous Melanoma AJCC v8; Pathologic Stage IIC Cutaneous Melanoma AJCC v8; Pathologic Stage III Cutaneous Melanoma AJCC v8; Pathologic Stage IIIA Cutaneous Melanoma AJCC v8; Pathologic Stage IIIB Cutaneous Melanoma AJCC v8; Pathologic Stage IIIC Cutaneous Melanoma AJCC v8
Interventions: Other: Informational Intervention; Other: Survey Administration
Sponsors: Rutgers, The State University of New Jersey; National Cancer Institute (NCI)
Not yet recruiting

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

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

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

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

pDNA Intralesional Cancer Vaccine for Cutaneous Melanoma

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

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

A Safety and Tolerability Study of INCAGN02390 in Select Advanced Malignancies

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

Adaptive Tyrosine Kinase Inhibitor (TKI) Therapy In Patients With Thyroid Cancer

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

Conditions: Thyroid Cancer; Thyroid Cancer, Medullary; Differentiated Thyroid Cancer; Papillary Thyroid Cancer; Follicular Thyroid Cancer; Poorly Differentiated Thyroid Gland Carcinoma
Interventions: Drug: Lenvatinib; Drug: Sorafenib; Drug: Cabozantinib; Drug: Vandetanib
Sponsor: H. Lee Moffitt Cancer Center and Research Institute
Recruiting

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

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

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

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

Molecular-Guided Surgery for Pancreatic and GI Neuroendocrine Cancers

Posted: August 9th, 2018, 2:00pm GMT

Conditions: Neuroendocrine Carcinoma of Pancreas; Carcinoid
Intervention: Drug: Gallium Dotatate
Sponsor: University of Alabama at Birmingham
Not yet recruiting

Study of the Combination of CM082 With JS001 in Patients With Advanced Mucosal Melanoma.

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

Condition: Mucosal Melanoma
Intervention: Drug: CM082 plus JS001
Sponsor: AnewPharma
Recruiting

Liquid Biopsy-based Detection of Resistance to Targeted Therapy in Prostate Cancer Patients

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

Condition: Castration-resistant Prostate Cancer
Intervention: Other: Blood samples prior to a new line of AR-targeted therapy
Sponsor: Technische Universität München
Recruiting

$Permalink for 'A GCO Trial Exploring the Efficacy and Safety of Nivolumab Monotherapy or Nivolumab Plus Ipilimumab in Pre-treated Patients With Advanced, Refractory Pulmonary or Gastroenteropancreatic Poorly Differentiated Neuroendocrine Tumors (NECs)'$

A GCO Trial Exploring the Efficacy and Safety of Nivolumab Monotherapy or Nivolumab Plus Ipilimumab in Pre-treated Patients With Advanced, Refractory Pulmonary or Gastroenteropancreatic Poorly Differentiated Neuroendocrine Tumors (NECs)

Posted: July 19th, 2018, 2:00pm GMT

Condition: Neuroendocrine Carcinoma
Interventions: Drug: Nivolumab; Drug: Ipilimumab
Sponsors: Intergroupe Francophone de Cancerologie Thoracique; Federation Francophone de Cancerologie Digestive; GERCOR - Multidisciplinary Oncology Cooperative Group
Recruiting

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

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

Posted: July 12th, 2018, 2:00pm GMT

Condition: Non-Small Cell Bronchopulmonary Carcinoma or Melanoma
Intervention: Radiation: 18FDG PET
Sponsor: Centre Antoine Lacassagne
Recruiting

Permalink for 'Pembrolizumab With Combination Chemotherapy in Treating Participants With Locally Advanced or Metastatic Small Cell/Neuroendocrine Cancers of Urothelium or Prostate'

Pembrolizumab With Combination Chemotherapy in Treating Participants With Locally Advanced or Metastatic Small Cell/Neuroendocrine Cancers of Urothelium or Prostate

Posted: July 11th, 2018, 2:00pm GMT

Conditions: Bladder Small Cell Neuroendocrine Carcinoma; Castration-Resistant Prostate Carcinoma; Metastatic Bladder Urothelial Carcinoma; Metastatic Urethral Urothelial Carcinoma; Prostate Carcinoma Metastatic in the Bone; Prostate Neuroendocrine Neoplasm; Prostate Small Cell Carcinoma; Stage III Bladder Cancer AJCC v8; Stage III Prostate Cancer AJCC v8; Stage III Urethral Cancer AJCC v8; Stage IV Bladder Cancer AJCC v8; Stage IV Prostate Cancer AJCC v8; Stage IV Urethral Cancer AJCC v8; Stage IVA Bladder Cancer AJCC v8; Stage IVB Bladder Cancer AJCC v8; Ureter Small Cell Carcinoma; Urothelial Carcinoma
Interventions: Drug: Carboplatin; Drug: Cisplatin; Drug: Docetaxel; Drug: Etoposide; Biological: Pembrolizumab
Sponsors: Jonsson Comprehensive Cancer Center; National Cancer Institute (NCI)
Recruiting

Olaparib Before Surgery in Treating Participants With Localized Prostate Cancer

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

Conditions: ATM Biallelic Inactivation; ATM Gene Mutation; ATM Monoallelic Inactivation; BRCA1 Biallelic Inactivation; BRCA1 Gene Mutation; BRCA2 Biallelic Inactivation; BRCA2 Gene Mutation; FANCA Biallelic Inactivation; Homologous Recombination Deficiency; PALB2 Biallelic Inactivation; PALB2 Gene Mutation; Prostate Adenocarcinoma Without Evidence of Neuroendocrine Differentiation; Stage I Prostate Cancer AJCC v8; Stage II Prostate Cancer AJCC v8; Stage IIA Prostate Cancer AJCC v8; Stage IIB Prostate Cancer AJCC v8; Stage IIC Prostate Cancer AJCC v8
Interventions: Drug: Olaparib; Procedure: Radical Prostatectomy
Sponsors: University of Washington; National Cancer Institute (NCI)
Recruiting

Permalink for 'A Study of Cetrelimab (JNJ-63723283), a Programmed Cell Death Receptor-1 (PD-1) Inhibitor, Administered in Combination With Apalutamide in Participants With Metastatic Castration-Resistant Prostate Cancer'

A Study of Cetrelimab (JNJ-63723283), a Programmed Cell Death Receptor-1 (PD-1) Inhibitor, Administered in Combination With Apalutamide in Participants With Metastatic Castration-Resistant Prostate Cancer

Posted: June 11th, 2018, 2:00pm GMT

Condition: Castration-Resistant Prostatic Neoplasms
Interventions: Drug: Cetrelimab 480 mg; Drug: Apalutamide 240 mg
Sponsor: Janssen Research & Development, LLC
Recruiting

Adaptive BRAF-MEK Inhibitor Therapy for Advanced BRAF Mutant Melanoma

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

Conditions: Melanoma (Skin); Skin Cancer; Skin Melanoma; Skin Carcinoma
Interventions: Drug: Vemurafenib; Drug: Cobimetinib
Sponsor: H. Lee Moffitt Cancer Center and Research Institute
Recruiting

A Safety and Tolerability Study of INCAGN02385 in Select Advanced Malignancies

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

A Study of XmAb®20717 in Subjects With Selected Advanced Solid Tumors

Posted: May 7th, 2018, 2:00pm GMT

Conditions: Melanoma; Breast Carcinoma; Hepatocellular Carcinoma; Urothelial Carcinoma; Squamous Cell Carcinoma of the Head and Neck; Renal Cell Carcinoma; Colorectal Carcinoma; Non-small Cell Lung Carcinoma; Gastric or Gastroesophageal Junction Adenocarcinoma; Endometrial Carcinoma; Mesothelioma; Neuroendocrine Carcinoma; Cervical Cancer; Small Cell Lung Carcinoma; Squamous Cell Carcinoma of the Anus
Intervention: Biological: XmAb20717
Sponsors: Xencor, Inc.; ICON plc
Recruiting

Safety and Efficacy of IMCnyeso in Advanced NY-ESO-1 and/or LAGE-1A Positive Cancers

Posted: May 3rd, 2018, 2:00pm GMT

Conditions: Melanoma; Advanced NSCLC; Urothelial Carcinoma; Synovial Sarcoma
Intervention: Drug: IMCnyeso
Sponsor: Immunocore Ltd
Recruiting

Permalink for 'AMT-PET in Monitoring Telotristat Etiprate Treatment in Participants With Metastatic Well Differentiated Neuroendocrine Neoplasm'

AMT-PET in Monitoring Telotristat Etiprate Treatment in Participants With Metastatic Well Differentiated Neuroendocrine Neoplasm

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

Conditions: Carcinoid Syndrome; Metastatic Nonfunctional Well Differentiated Neuroendocrine Neoplasm
Interventions: Other: Carbon C 11 Alpha-methyltryptophan; Other: Laboratory Biomarker Analysis; Procedure: Positron Emission Tomography; Drug: Telotristat Etiprate
Sponsors: Barbara Ann Karmanos Cancer Institute; National Cancer Institute (NCI)
Recruiting

SYNERGY-AI: Artificial Intelligence Based Precision Oncology Clinical Trial Matching and Registry

Posted: March 2nd, 2018, 3:00pm GMT

Conditions: Cancer, Metastatic; Cancer; Cancer of Pancreas; Cancer of Liver; Cancer of Stomach; Cancer Liver; Cancer of Rectum; Cancer of Kidney; Cancer of Esophagus; Cancer of Cervix; Cancer of Colon; Cancer of Larynx; Cancer, Lung; Cancer, Breast; Cancer, Advanced; Cancer Prostate; Cancer of Neck; Cancer of Skin; Neuroendocrine Tumors; Carcinoma; Mismatch Repair Deficiency; BRCA Gene Rearrangement; Non Hodgkin Lymphoma; Leukemia; Non Small Cell Lung Cancer; Cholangiocarcinoma; Glioblastoma; Central Nervous System Tumor; Melanoma; Urothelial Carcinoma; Bladder Cancer; Ovarian Cancer; Endometrial Cancer; Testicular Cancer; Breast Cancer
Intervention: Other: Clinical Trial Matching
Sponsor: Massive Bio, Inc.
Recruiting

Gallium Ga 68-DOTATATE PET/CT in Diagnosing Patients With Metastatic Castration Resistant Prostate Cancer

Posted: February 28th, 2018, 3:00pm GMT

Conditions: Castration-Resistant Prostate Carcinoma; Metastatic Prostate Carcinoma; Stage IV Prostate Cancer AJCC v7
Interventions: Procedure: CT (Computed Tomography); Drug: Gallium Ga 68-DOTATATE; Procedure: Positron Emission Tomography
Sponsor: Emory University
Recruiting

The Effects of Liraglutide on Sudomotor Function and Inflammation in Type 2 Diabetes

Posted: February 8th, 2018, 3:00pm GMT

Conditions: Autonomic Nervous System Diseases; Sweat Gland Diseases; Diabetic Neuropathy With Neurologic Complication
Interventions: Drug: Liraglutide 6 mg Solution for Injection; Other: Placebo
Sponsor: Eastern Virginia Medical School
Recruiting

Anti-SEMA4D Monoclonal Antibody VX15/2503 With Nivolumab or Ipilimumab in Treating Patients With Stage III or IV Melanoma

Posted: February 7th, 2018, 3:00pm GMT

Conditions: Metastatic Melanoma; Stage III Cutaneous Melanoma AJCC v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7
Interventions: Biological: Anti-SEMA4D Monoclonal Antibody VX15/2503; Biological: Ipilimumab; Other: Laboratory Biomarker Analysis; Biological: Nivolumab; Other: Pharmacological Study
Sponsors: Jonsson Comprehensive Cancer Center; National Cancer Institute (NCI)
Recruiting

A Phase II Study of BVD-523 in Metastatic Uveal Melanoma

Posted: January 31st, 2018, 3:00pm GMT

Condition: Uveal Melanoma
Intervention: Drug: BVD-523
Sponsors: Dana-Farber Cancer Institute; BioMed Valley Discoveries, Inc
Recruiting

A Study of XmAb®18087 in Subjects With NET and GIST

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

Conditions: Neuroendocrine Tumor; Gastrointestinal Neoplasm
Intervention: Biological: XmAb18087
Sponsors: Xencor, Inc.; ICON plc
Recruiting

CAPTEM or FOLFIRI as SEcond-line Therapy in NEuroendocrine CArcinomas

Posted: January 2nd, 2018, 3:00pm GMT

Condition: Neuroendocrine Carcinoma
Interventions: Drug: CPT-11; Drug: Calcio levofolinate; Drug: 5-Fluorouracil; Drug: Capecitabine; Drug: Temozolomide
Sponsor: Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
Recruiting

Permalink for 'Propranolol Hydrochloride and Pembrolizumab in Treating Patients With Stage IIIC-IV Melanoma That Cannot Be Removed by Surgery'

Propranolol Hydrochloride and Pembrolizumab in Treating Patients With Stage IIIC-IV Melanoma That Cannot Be Removed by Surgery

Posted: December 27th, 2017, 3:00pm GMT

Conditions: Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7
Interventions: Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Drug: Propranolol Hydrochloride
Sponsors: Roswell Park Cancer Institute; National Cancer Institute (NCI)
Recruiting

Gallium 68 Pentixafor in Patients With Neuroendocrine Tumors

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

Condition: Neuroendocrine Tumors
Intervention: Drug: [68Ga]Pentixafor
Sponsors: Yusuf Menda; National Cancer Institute (NCI); National Institutes of Health (NIH); Holden Comprehensive Cancer Center
Recruiting

A Study of PLX2853 in Advanced Malignancies.

Posted: September 29th, 2017, 2:00pm GMT

Conditions: Small Cell Lung Cancer; Uveal Melanoma; Ovarian Clear Cell Carcinoma; Non-Hodgkin Lymphoma; Advanced Malignancies; Solid Tumor; Diffuse Large B Cell Lymphoma; Follicular Lymphoma
Intervention: Drug: PLX2853
Sponsor: Plexxikon
Recruiting

Permalink for 'A Study to Evaluate Patient Experience in the Therapy of Neuroendocrine Tumors Treated With Octreotide Long Acting Release Versus Lanreotide'

A Study to Evaluate Patient Experience in the Therapy of Neuroendocrine Tumors Treated With Octreotide Long Acting Release Versus Lanreotide

Posted: September 21st, 2017, 2:00pm GMT

Condition: Neuroendocrine Tumors
Interventions: Drug: Octreotide; Drug: LAR Lanreotide; Behavioral: Questionnaires
Sponsor: Memorial Sloan Kettering Cancer Center
Recruiting

Permalink for 'Local Control, Quality of Life and Toxicities in Adults With Benign or Indolent Brain Tumors Undergoing Proton Radiation Therapy'

Local Control, Quality of Life and Toxicities in Adults With Benign or Indolent Brain Tumors Undergoing Proton Radiation Therapy

Posted: September 18th, 2017, 2:00pm GMT

Condition: Brain Tumor
Intervention: Radiation: Proton Radiation
Sponsor: Massachusetts General Hospital
Recruiting

PET/CT Imaging of uPAR-expression in Patients With Neuroendocrine Tumors Using 68Ga-NOTA-AE105

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

Condition: Neuroendocrine Tumors
Interventions: Drug: One injection of 68Ga-NOTA-AE105; Device: PET/CT
Sponsor: Rigshospitalet, Denmark
Recruiting

PET/CT Imaging of Angiogenesis in Patients With Neuroendocrine Tumors Using 68Ga-NODAGA-E[c(RGDyK)]2

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

Condition: Neuroendocrine Tumors
Interventions: Drug: One injection of 68Ga-NODAGA-E[c(RGDyK)]2; Device: PET/CT
Sponsor: Rigshospitalet, Denmark
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

Permalink for 'To Evaluate the Optimal Dose of 68Ga-OPS202 as a PET (Positron Emission Tomography) Imaging Agent in Subjects With Gastroenteropancreatic Neuroendocrine Tumour (GEP-NET)'

To Evaluate the Optimal Dose of 68Ga-OPS202 as a PET (Positron Emission Tomography) Imaging Agent in Subjects With Gastroenteropancreatic Neuroendocrine Tumour (GEP-NET)

Posted: July 18th, 2017, 2:00pm GMT

Condition: Gastro-Enteropancreatic Neuroendocrine Tumor
Intervention: Drug: Satoreotide trizoxetan
Sponsor: Ipsen
Recruiting

Phase 1/2 Study of LOXO-195 in Patients With Previously Treated NTRK Fusion Cancers

Posted: July 12th, 2017, 2:00pm GMT

Conditions: Carcinoma, Non-Small-Cell Lung; Thyroid Neoplasms; Sarcoma; Colorectal Neoplasms; Salivary Gland Neoplasms; Biliary Tract Neoplasms; Brain Neoplasm, Primary; Melanoma; Glioblastoma; Bile Duct Neoplasms; Astrocytoma; Head and Neck Squamous Cell Carcinoma; Pontine Glioma; Pancreatic Neoplasms; Ovarian Neoplasms; Carcinoma, Renal Cell; Cholangiocarcinoma; Skin Carcinoma; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Intestinal Neoplasms; Thyroid Cancer; GIST; Malignant Peripheral Nerve Sheath Tumors; Breast Secretory Carcinoma; Uterine Neoplasms; Fibrosarcoma; Infantile Fibrosarcoma; Congenital Mesoblastic Nephroma; Central Nervous System Neoplasms
Intervention: Drug: LOXO-195
Sponsors: Loxo Oncology, Inc.; Bayer
Recruiting

Lu-177-DOTATATE (Lutathera) in Therapy of Inoperable Pheochromocytoma/ Paraganglioma

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

Conditions: Pheochromocytoma; Paraganglioma; Neuroendocrine Tumors; Neuroendocrine Neoplasms
Interventions: Drug: Lu-177-DOTATATE; Drug: Ga-68-DOTATATE; Drug: F-18-FDG; Drug: Amino Acid solution
Sponsor: National Cancer Institute (NCI)
Recruiting

Pembrolizumab for the Treatment of Recurrent High Grade Neuroendocrine Carcinoma

Posted: June 16th, 2017, 2:00pm GMT

Condition: Neuroendocrine Tumors
Intervention: Drug: Pembrolizumab Injection
Sponsors: University of Utah; Merck Sharp & Dohme Corp.
Recruiting

PD-L1 Inhibition as ChecKpoint Immunotherapy for NeuroEndocrine Phenotype Prostate Cancer

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

Condition: Prostate Cancer
Intervention: Drug: Avelumab
Sponsor: Andrew J. Armstrong, MD
Recruiting

Permalink for 'A Phase II Trial of the DNA Methyl Transferase Inhibitor, Guadecitabine (SGI-110), in Children and Adults With Wild Type GIST,Pheochromocytoma and Paraganglioma Associated With Succinate Dehydrogenase Deficiency and HLRCC-associated Kidney Cancer'

A Phase II Trial of the DNA Methyl Transferase Inhibitor, Guadecitabine (SGI-110), in Children and Adults With Wild Type GIST,Pheochromocytoma and Paraganglioma Associated With Succinate Dehydrogenase Deficiency and HLRCC-associated Kidney Cancer

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

Conditions: Paraganglioma; Gastrointestinal Stromal Tumors; Carcinoma, Renal Cell; Renal Neoplasms; Pheochromocytoma
Intervention: Drug: SGI-110 (guadecitabine)
Sponsor: National Cancer Institute (NCI)
Recruiting

Permalink for 'Evaluation of Denosumab in Combination With Immune Checkpoint Inhibitors in Patients With Unresectable or Metastatic Melanoma'

Evaluation of Denosumab in Combination With Immune Checkpoint Inhibitors in Patients With Unresectable or Metastatic Melanoma

Posted: May 22nd, 2017, 2:00pm GMT

Conditions: Melanoma Stage Iv; Melanoma Stage Iii; Melanoma
Interventions: Drug: Denosumab; Drug: Nivolumab; Drug: Ipilimumab
Sponsors: Australia and New Zealand Melanoma Trials Group; Peter MacCallum Cancer Centre, Australia; Amgen; Bristol-Myers Squibb
Recruiting

The ACTIVATE (Adoptive Cell Therapy InVigorated to Augment Tumor Eradication) Trial

Posted: May 18th, 2017, 2:00pm GMT

Conditions: Advanced Ovarian Cancer; Malignant Melanoma
Interventions: Drug: Cyclophosphamide; Drug: Fludarabine; Procedure: Pembrolizumab; Biological: Tumor-Infiltrating Lymphocytes (TILs); Biological: Interleukin-2 (IL-2)
Sponsors: University Health Network, Toronto; Merck Sharp & Dohme Corp.
Recruiting

Pembrolizumab-based Therapy in Previously Treated High Grade Neuroendocrine Carcinomas

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

Condition: High Grade Malignant Neuroendocrine Carcinoma (Diagnosis)
Interventions: Drug: Pembrolizumab; Drug: Irinotecan; Drug: Paclitaxel
Sponsors: University of California, San Francisco; Merck Sharp & Dohme Corp.
Recruiting

CD40 Agonistic Antibody APX005M in Combination With Nivolumab

Posted: April 21st, 2017, 2:00pm GMT

Conditions: Cancer; Non Small Cell Lung Cancer Metastatic; Metastatic Melanoma; Neoplasm of Lung; Melanoma
Interventions: Drug: APX005M; Drug: Nivolumab
Sponsors: Apexigen, Inc.; Bristol-Myers Squibb
Recruiting

Cobimetinib and Atezolizumab in Advanced Rare Tumors

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

Conditions: Malignant Neoplasms of Digestive Organs; Melanoma and Other Malignant Neoplasms of Skin; Appendiceal Adenocarcinoma; Cutaneous Squamous Cell Carcinoma; Small Bowel Adenocarcinoma
Interventions: Drug: Cobimetinib; Drug: Atezolizumab
Sponsors: M.D. Anderson Cancer Center; Genentech, Inc.
Recruiting

LY3022855 With BRAF/MEK Inhibition in Patients With Melanoma

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

Condition: Melanoma
Interventions: Drug: LY3022855; Drug: Vemurafenib; Drug: Cobimetinib
Sponsors: Dana-Farber Cancer Institute; Eli Lilly and Company
Recruiting

Trial of Selumetinib in Patients With Neurofibromatosis Type II Related Tumors

Posted: March 29th, 2017, 2:00pm GMT

Conditions: Neurofibromatosis 2; Vestibular Schwannoma; Meningioma; Ependymoma; Glioma
Intervention: Drug: Selumetinib
Sponsors: Children's Hospital Medical Center, Cincinnati; AstraZeneca
Recruiting

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

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

$Permalink for 'Image Guided Hypofractionated Radiation Therapy, Nelfinavir Mesylate, Pembrolizumab, Nivolumab and Atezolizumab in Treating Patients With Advanced Melanoma, Lung, or Kidney Cancer'$

Image Guided Hypofractionated Radiation Therapy, Nelfinavir Mesylate, Pembrolizumab, Nivolumab and Atezolizumab in Treating Patients With Advanced Melanoma, Lung, or Kidney Cancer

Posted: February 10th, 2017, 3:00pm GMT

Conditions: Metastatic Renal Cell Cancer; Recurrent Melanoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Renal Cell Carcinoma; Stage IV Cutaneous Melanoma AJCC v6 and v7; Stage IV Non-Small Cell Lung Cancer AJCC v7; Stage IV Renal Cell Cancer AJCC v7
Interventions: Drug: Atezolizumab; Radiation: Hypofractionated Radiation Therapy; Other: Laboratory Biomarker Analysis; Drug: Nelfinavir Mesylate; Biological: Nivolumab; Biological: Pembrolizumab
Sponsors: University of Washington; National Cancer Institute (NCI)
Recruiting

Comparison of the diagnostic accuracy of the current guidelines for detecting insulinoma.

Fetched: April 18th, 2019, 5:00am GMT

Comparison of the diagnostic accuracy of the current guidelines for detecting insulinoma.

Eur J Endocrinol. 2019 Apr 01;:

Authors: Dauben L, Simon MC, Strassburger K, Burkart V, Weber K, Schinner S, Roden M, Müssig K

Abstract
OBJECTIVE: Insulinomas are rare pancreatic endocrine tumors characterized by hypoglycemia. Guidelines by the Endocrine Society (ES), the European (ENETS) and the North American (NANETS) Neuroendocrine Tumor Societies provide divergent diagnostic criteria. This study compared the diagnostic accuracy of these different criteria during the 72-h fasting test.
DESIGN: Retrospective cohort study.
METHODS: From 2000 to 2014, 64 patients with a suspected insulinoma underwent a 72-h fasting test and were included in the analysis. This study assessed the diagnostic sensitivity, specificity and accuracy based on venous blood glucose and corresponding insulin levels measured by electrochemiluminescence immunoassay (ECLIA).
RESULTS: Based on 64 individuals (18 with, 46 without insulinoma), the ES criteria provided a diagnostic sensitivity of 0.94 [0.73;1.00], specificity of 0.89 [0.76;0.96] and accuracy of 0.91 [0.81;0.96]. ENETS/NANETS criteria reached a diagnostic sensitivity of 0.78 [0.52;0.94], specificity of 1.00 [0.92;1.00] and accuracy of 0.94 [0.85;0.98].
CONCLUSIONS: These results point to a higher diagnostic sensitivity with less specificity for diagnosing insulinoma by using ES criteria and a higher specificity at lower sensitivity by using ENETS/NANETS criteria. Before considering these results when applying the different criteria in clinical practice, the results should be confirmed in further studies comprising of larger cohorts.

PMID: 30991361 [PubMed - as supplied by publisher]

Paraganglioma presenting as stress cardiomyopathy: case report and literature review.

Fetched: April 18th, 2019, 5:00am GMT

Paraganglioma presenting as stress cardiomyopathy: case report and literature review.

Endocrinol Diabetes Metab Case Rep. 2019 Apr 16;2019:

Authors: Ferreira AG, Nunes da Silva T, Alegria S, Cordeiro MC, Portugal J

Abstract
Pheochromocytoma/paraganglioma (PPGL) are neuroendocrine tumors that can secrete catecholamines. The authors describe a challenging case who presented as stress cardiomyopathy and myocardial infarction (MI). A 76-year-old man, with a medical history of Parkinson's disease, type 2 diabetes mellitus, hypertension, dyslipidaemia and a previous inferior MI in 2001, presented to the emergency department due to chest pain, headaches and vomiting. He also reported worsening blood glucose levels and increasing constipation over the preceding weeks. BP was 185/89 mmHg (no other relevant findings). EKG had ST segment depression in leads V2-V6, T troponin was 600 ng/L (<14) and the echocardiogram showed left ventricular hypokinesia with mildly compromised systolic function. Nevertheless, he rapidly progressed to severe biventricular dysfunction. Coronary angiogram showed a 90% anterior descendent coronary artery occlusion (already present in 2001), which was treated with angioplasty/stenting. In the following days, a very labile BP profile and unexplained sinus tachycardia episodes were observed. Because of sustained severe constipation, the patient underwent an abdominal CT that revealed a retroperitoneal, heterogeneous, hypervascular mass on the right (62 × 35 mm), most likely a paraganglioma. Urinary metanephrines were increased several fold. 68Ga-DOTANOC PET-CT scan showed increased uptake in the abdominal mass (no evidence of disease elsewhere). He was started on a calcium-channel blocker and alpha blockade and underwent surgery with no major complications. Eight months after surgery, the patient has no evidence of disease. Genetic testing was negative for known germline mutations. This was a challenging diagnosis, but it was essential for adequate cardiovascular stabilization and to reduce further morbidity. Learning points: PPGL frequently produces catecholamines and can manifest with several cardiovascular syndromes, including stress cardiomyopathy and myocardial infarction. Even in the presence of coronary artery disease (CAD), PPGL should be suspected if signs or symptoms attributed to catecholamine excess are present (in this case, high blood pressure, worsening hyperglycaemia and constipation). Establishing the correct diagnosis is important for adequate treatment choice. Inodilators and mechanical support might be preferable options (if available) for cardiovascular stabilization prior to alpha blockade and surgery. Laboratory interference should be suspected irrespective of metanephrine levels, especially in the context of treated Parkinson's disease.

PMID: 30991354 [PubMed - as supplied by publisher]

Permalink for 'Colorectal Large Cell Neuroendocrine Carcinoma with lymphoid stroma: further evidence confirming a unique sub-type associated with MLH-1/PMS2 protein loss, BRAF mutation, EBV-negativity and possible better prognosis.'

Colorectal Large Cell Neuroendocrine Carcinoma with lymphoid stroma: further evidence confirming a unique sub-type associated with MLH-1/PMS2 protein loss, BRAF mutation, EBV-negativity and possible better prognosis.

Fetched: April 18th, 2019, 5:00am GMT

Colorectal Large Cell Neuroendocrine Carcinoma with lymphoid stroma: further evidence confirming a unique sub-type associated with MLH-1/PMS2 protein loss, BRAF mutation, EBV-negativity and possible better prognosis.

Histopathology. 2019 Apr 16;:

Authors: Chetty R, Capo-Chichi JM, Serra S

Abstract
Pure large cell neuroendocrine carcinoma (LCNEC) is an uncommon but well recognized primary tumour of the colorectum. It is characterized by large cells organized in a discernible neuroendocrine pattern, >20 mitoses per 10 HPF and/or Ki-67 index > 20% and, coagulative tumour necrosis is invariably present. These features are supplemented by positive neuroendocrine immunohistochemical markers. We wish to highlight 3 primary LCNEC of the colorectum. All 3 patients were elderly females: 79, 85 and 89 years of age who presented with ascending colon (2) and a rectal tumours. All 3 tumours were large ulcerated, polypoid masses (8.5, 7.6 and 5.5 cm; average size 7.2cm) and pT3N2. Histologically, the tumours were composed of packets and nests of cells with rosettes; other areas were in sheets composed of large cells. The mitotic counts were: 23/10HPF, 27/10 and 24/10, respectively. There was no mucosal dysplasia, precursor adenoma or associated adenocarcinoma component. All cases contained mainly peritumoral lymphoid aggregates with smaller numbers of intratumoural lymphocytes. Synaptophysin, chromogranin (less intensely) and epithelial markers were expressed in all cases in the majority of the tumor cells. The Ki-67 proliferative indices were 95%, 100% and 80%, respectively. Two patients survived for 48 and 72 months, while the third is alive after 12 months without evidence of recurrence. These unusual primary colorectal LCNEC with an accompanying lymphoid component, are characterized by loss of MLH-1/PMS-2 proteins, BRAF mutation, MSI and EBV negativity. They also have better overall survival than those reported in LCNEC lacking a lymphoid accompaniment. This article is protected by copyright. All rights reserved.

PMID: 30990915 [PubMed - as supplied by publisher]

Clinical Features of Multiple Endocrine Neoplasia Type 4 - Novel pathogenic variant and review of published cases.

Fetched: April 18th, 2019, 5:00am GMT

Clinical Features of Multiple Endocrine Neoplasia Type 4 - Novel pathogenic variant and review of published cases.

J Clin Endocrinol Metab. 2019 Apr 16;:

Authors: Frederiksen A, Rossing M, Hermann P, Ejersted C, Thakker RV, Nielsen MF

Abstract
CONTEXT: The clinical phenotype of multiple endocrine neoplasia type 4 (MEN4) is undefined due to a limited number of published cases. Knowledge on disease manifestation in MEN4 is essential for developing prevention programs and treatment.
OBJECTIVE: To expand current knowledge of the MEN4 phenotype including assessment of penetrance.
DESIGN: This is a case report and a brief review of previously published MEN4 cases.
PATIENTS: We report a large Danish family with multiple cases of endocrine tumors that segregated with a novel pathogenic variant in the CDKN1B gene.
MAIN OUTCOME/RESULT: The medical history of the proband included primary hyperparathyroidism and Cushing's disease. Genetic analysis identified a novel pathogenic variant in CDKN1B (c.121_122delTT, p.Leu41Asnfs*83). Among the family members, another twelve individuals were identified as carriers of the same variant, which segregated with development of endocrine tumors. Hypercalcaemia due to primary hyperparathyroidism occurred in all thirteen of the available carriers of the genetic variant, and four patients also had functioning or non-functioning pituitary adenomas, while one patient had a metastatic neuroendocrine tumor (carcinoid). Loss-of-heterozygosity (LOH) was detected in two of five parathyroid adenomas, supporting that CDKN1B acts as a tumor suppressor gene. Thirty cases representing 16 different CDKN1B variants have previously been reported, and these cases presented primarily with primary hyperparathyroidism and functioning and non-functioning pituitary tumors.
CONCLUSION: Hypercalcaemia due to primary hyperparathyroidism and pituitary tumors are common in MEN4. Gastro-intestinal neuroendocrine tumors appear to be less prevalent in MEN4 than in multiple endocrine neoplasia type 1.

PMID: 30990521 [PubMed - as supplied by publisher]

Detection of NRG1 gene fusions in solid tumors.

Fetched: April 18th, 2019, 5:00am GMT

Detection of NRG1 gene fusions in solid tumors.

Clin Cancer Res. 2019 Apr 15;:

Authors: Jonna S, Feldman RA, Swensen J, Gatalica Z, Korn WM, Borghaei H, Ma PC, Nieva JJ, Spira AI, VanderWalde AM, Wozniak AJ, Kim ES, Liu SV

Abstract
BACKGROUND: NRG1 gene fusions are rare but potentially actionable oncogenic drivers present in some solid tumors. Details regarding the incidence of these gene rearrangements are lacking. Here, we assessed the incidence of NRG1 fusions across multiple tumor types and described fusion partners.
METHODS: Tumor specimens submitted for molecular profiling at a CLIA-certified genomics laboratory and that underwent fusion testing by anchored multiplex PCR for targeted RNA sequencing were retrospectively identified. The overall and tumor-specific incidence was noted as was the specific fusion partner.
RESULTS: Out of 21,858 tumor specimens profiled from September 2015 to December 2018, 41 cases (0.2%) harbored an NRG1 fusion. Multiple fusion partners were identified. Fusion events were seen across tumor types. The greatest incidence was in non-small cell lung cancer (25), though this represented only 0.3% of non-small cell lung cancer cases tested. Other tumor types harboring an NRG1 fusion included gallbladder cancer, renal cell carcinoma, bladder cancer, ovarian cancer, pancreatic cancer, breast cancer, neuroendocrine tumor, sarcoma, and colorectal cancer.
CONCLUSION: NRG1 fusions can be detected at a low incidence across multiple tumor types with significant heterogeneity in fusion partner.

PMID: 30988082 [PubMed - as supplied by publisher]

Morbidity and mortality of bone metastases in advanced adrenocortical carcinoma: a multicenter retrospective study.

Fetched: April 18th, 2019, 5:00am GMT

Morbidity and mortality of bone metastases in advanced adrenocortical carcinoma: a multicenter retrospective study.

Eur J Endocrinol. 2019 May 01;180(5):311-320

Authors: Berruti A, Libè R, Laganà M, Ettaieb H, Sukkari MA, Bertherat J, Feelders RA, Grisanti S, Cartry J, Mazziotti G, Sigala S, Baudin E, Haak H, Habra MA, Terzolo M

Abstract
Introduction Adrenocortical carcinoma (ACC) is a rare cancer that commonly spreads to the liver, lungs and lymph nodes. Bone metastases are infrequent. Objective The aim of this report was to describe the clinical characteristics, survival perspective, prognostic factors and frequency of adverse skeletal-related events (SREs) in patients with ACC who developed bone metastasis. Methods This is a retrospective, observational, multicenter, multinational study of patients diagnosed with bone metastases from ACC who were treated and followed up in three European countries (France, Italy and The Netherlands) and one center in the United States. Results Data of 156 patients were captured. The median overall survival was 11 months. SREs occurred in 47% of patients: 17% bone fractures, 17% spinal cord compression, 1% hypercalcemia, 12% developed more than one SRE. In multivariate analysis, cortisol hypersecretion was the only prognostic factor significantly associated with a higher mortality risk (hazard ratio (HR) 2.24, 95% confidence interval (CI): 1.19-4.23, P = 0.013) and with the development of a SREs (of border line significance). The administration of antiresorptive therapies (bisphosphonates and denosumab) was associated with a lower risk of death, even if not significant, and their survival benefit appeared confined in patients attaining serum mitotane levels within the therapeutic range. Conclusion Bone metastases in ACC patients are associated with poor prognosis and high risk of SREs. Cortisol hypersecretion was the only prognostic factor suggesting a potential benefit from antisecretory medications. The therapeutic role of bisphosphonates and denosumab to improve patient outcome deserves to be tested in a prospective clinical trial.

PMID: 30970324 [PubMed - indexed for MEDLINE]

Permalink for 'Endoloop ligation after endoscopic mucosal resection using a transparent cap: A novel method to treat small rectal carcinoid tumors.'

Endoloop ligation after endoscopic mucosal resection using a transparent cap: A novel method to treat small rectal carcinoid tumors.

Fetched: April 18th, 2019, 5:00am GMT

Icon for Baishideng Publishing Group Inc.

Endoloop ligation after endoscopic mucosal resection using a transparent cap: A novel method to treat small rectal carcinoid tumors.

World J Gastroenterol. 2019 Mar 14;25(10):1259-1265

Authors: Zhang DG, Luo S, Xiong F, Xu ZL, Li YX, Yao J, Wang LS

Abstract
BACKGROUND: Local endoscopic resection is an effective method for the treatment of small rectal carcinoid tumors, but remnant tumor at the margin after resection remains to be an issue.
AIM: To evaluate the efficacy and safety of resection of small rectal carcinoid tumors by endoloop ligation after cap-endoscopic mucosal resection (LC-EMR) using a transparent cap.
METHODS: Thirty-four patients with rectal carcinoid tumors of less than 10 mm in diameter were treated by LC-EMR (n = 22) or endoscopic submucosal dissection (ESD) (n = 12) between January 2016 and December 2017. Demographic data, complete resection rates, pathologically complete resection rates, operation duration, and postoperative complications were collected. All cases were followed for 6 to 30 mo.
RESULTS: A total of 22 LC-EMR cases and 12 ESD cases were enrolled. The average age was 48.18 ± 12.31 and 46.17 ± 12.57 years old, and the tumor size was 7.23 ± 1.63 mm and 7.50 ± 1.38 mm, respectively, for the LC-EMR and ESD groups. Resection time in the ESD group was longer than that in the LC-EMR group (15.67 ± 2.15 min vs 5.91 ± 0.87 min; P < 0.001). All lesions were completely resected at one time. No perforation or delayed bleeding was observed in either group. Pathologically complete resection (P-CR) rate was 86.36% (19/22) and 91.67% (11/12) in the LC-EMR and ESD groups (P = 0.646), respectively. Two of the three cases with a positive margin in the LC-EMR group received transanal endoscopic microsurgery (TEM) and tumor cells were not identified in the postoperative specimens. The other case with a positive margin chose follow-up without further operation. One case with remnant tumor after ESD received further local ligation treatment. Neither local recurrence nor lymph node metastasis was found during the follow-up period.
CONCLUSION: LC-EMR appears to be an efficient and simple method for the treatment of small rectal carcinoid tumors, which can effectively avoid margin remnant tumors.

PMID: 30886508 [PubMed - indexed for MEDLINE]

Nutritional and vitamin status in patients with neuroendocrine neoplasms.

Fetched: April 18th, 2019, 5:00am GMT

Nutritional and vitamin status in patients with neuroendocrine neoplasms.

World J Gastroenterol. 2019 Mar 14;25(10):1171-1184

Authors: Clement DS, Tesselaar ME, van Leerdam ME, Srirajaskanthan R, Ramage JK

Abstract
Symptoms of gastroenteropancreatic located neuroendocrine neoplasms (GEP-NENs) are often related to food intake and manifest as abdominal pain or diarrhoea which can influence patients nutritional status. Malnutrition is common in cancer patients and influences quality of life, treatment options and survival but is also present in up to 40% of patients with GEP-NENs. As part of malnutrition there are often deficiencies in fat-soluble vitamins, mainly vitamin D. Little knowledge exists on trace elements. Several factors influence the development of malnutrition such as size and localisation of the primary tumour as well as metastases, side effects from treatment but also hormone production of the tumour itself. One of the main influencing factors leading to malnutrition is diarrhoea which leads to dehydration and electrolyte disturbances. Treatment of diarrhoea should be guided by its cause. Screening for malnutrition should be part of routine care in every GEP-NEN patient. Multidisciplinary treatment including dietician support is necessary for all malnourished patients with GEP-NENs.

PMID: 30886501 [PubMed - indexed for MEDLINE]

$Permalink for 'Asymmetric-flow field-flow fractionation technology for exomere and small extracellular vesicle separation and characterization.'$

Asymmetric-flow field-flow fractionation technology for exomere and small extracellular vesicle separation and characterization.

Fetched: April 18th, 2019, 5:00am GMT

Asymmetric-flow field-flow fractionation technology for exomere and small extracellular vesicle separation and characterization.

Nat Protoc. 2019 04;14(4):1027-1053

Authors: Zhang H, Lyden D

Abstract
We describe the protocol development and optimization of asymmetric-flow field-flow fractionation (AF4) technology for separating and characterizing extracellular nanoparticles (ENPs), particularly small extracellular vesicles (sEVs), known as exosomes, and even smaller novel nanoparticles, known as exomeres. This technique fractionates ENPs on the basis of hydrodynamic size and demonstrates a unique capability to separate nanoparticles with sizes ranging from a few nanometers to an undefined level of micrometers. ENPs are resolved by two perpendicular flows-channel flow and cross-flow-in a thin, flat channel with a semi-permissive bottom wall membrane. The AF4 separation method offers several advantages over other isolation methods for ENP analysis, including being label-free, gentle, rapid (<1 h) and highly reproducible, as well as providing efficient recovery of analytes. Most importantly, in contrast to other available techniques, AF4 can separate ENPs at high resolution (1 nm) and provide a large dynamic range of size-based separation. In conjunction with real-time monitors, such as UV absorbance and dynamic light scattering (DLS), and an array of post-separation characterizations, AF4 facilitates the successful separation of distinct subsets of exosomes and the identification of exomeres. Although the whole procedure of cell culture and ENP isolation from the conditioned medium by ultracentrifugation (UC) can take ~3 d, the AF4 fractionation step takes only 1 h. Users of this technology will require expertise in the working principle of AF4 to operate and customize protocol applications. AF4 can contribute to the development of high-quality, exosome- and exomere-based molecular diagnostics and therapeutics.

PMID: 30833697 [PubMed - indexed for MEDLINE]

Early objective response to avelumab treatment is associated with improved overall survival in patients with metastatic Merkel cell carcinoma.

Fetched: April 18th, 2019, 5:00am GMT

Early objective response to avelumab treatment is associated with improved overall survival in patients with metastatic Merkel cell carcinoma.

Cancer Immunol Immunother. 2019 Apr;68(4):609-618

Authors: D'Angelo SP, Hunger M, Brohl AS, Nghiem P, Bhatia S, Hamid O, Mehnert JM, Terheyden P, Shih KC, Brownell I, Lebbé C, Lewis KD, Linette GP, Milella M, Schlichting M, Hennessy MH, Bharmal M

PMID: 30721341 [PubMed - indexed for MEDLINE]

Immune checkpoint inhibitor-induced colitis as a predictor of survival in metastatic melanoma.

Fetched: April 18th, 2019, 5:00am GMT

Immune checkpoint inhibitor-induced colitis as a predictor of survival in metastatic melanoma.

Cancer Immunol Immunother. 2019 Apr;68(4):553-561

Authors: Abu-Sbeih H, Ali FS, Qiao W, Lu Y, Patel S, Diab A, Wang Y

Abstract
BACKGROUND: Gastrointestinal (GI) immune-related adverse events (irAEs) commonly limit immune checkpoint inhibitors' (ICIs) treatment, which is very effective for metastatic melanoma. The independent impact of GI-irAEs on patients' survival is not well studied. We aimed to assess the impact of GI-irAEs on survival rates of patients with metastatic melanoma using multivariate model.
METHODS: This is a retrospective study of patients with metastatic melanoma who developed GI-irAEs from 1/2010 through 4/2018. A number of randomized patients who did not have GI-irAEs were included as controls. Kaplan-Meier curves and log-rank test were used to estimate unadjusted survival durations. The Cox proportional hazards model was used to evaluate survival predictors; irAEs were included as time-dependent variables.
RESULTS: A total of 346 patients were included, 173 patients had GI-irAEs; 124 (72%) received immunosuppression. In multivariate Cox regression, ECOG 2-3 (HR 2.57, 95%CI 1.44-4.57; P < 0.01), LDH ≥ 618 IU/L (HR 2.20, 95% CI 1.47-3.29; P < 0.01), stage M1c (HR 2.21, 95% CI 1.35-3.60; P < 0.01) were associated with worse OS rates. Any grade GI-irAEs (HR 0.53, 95% CI 0.36-0.78; P < 0.01) was associated with improved OS rates. Immunosuppressive treatment did not affect OS (P = 0.15). High-grade diarrhea was associated with improved OS (P = 0.04). Patients who developed GI-irAEs had longer PFS durations on Cox model (HR 0.56, 95% CI 0.41-0.76; P < 0.01).
CONCLUSION: GI-irAEs are associated with improved OS and PFS in patients with metastatic melanoma. Furthermore, higher grades of diarrhea are associated with even better patients' OS rates.

PMID: 30666357 [PubMed - indexed for MEDLINE]

Permalink for 'Adverse events need for hospitalization and systemic immunosuppression in very elderly patients (over 80 years) treated with ipilimumab for metastatic melanoma.'

Adverse events need for hospitalization and systemic immunosuppression in very elderly patients (over 80 years) treated with ipilimumab for metastatic melanoma.

Fetched: April 18th, 2019, 5:00am GMT

Adverse events need for hospitalization and systemic immunosuppression in very elderly patients (over 80 years) treated with ipilimumab for metastatic melanoma.

Cancer Immunol Immunother. 2019 Apr;68(4):545-551

Authors: Leroy V, Gerard E, Dutriaux C, Prey S, Gey A, Mertens C, Beylot-Barry M, Pham-Ledard A

Abstract
BACKGROUND: Checkpoint inhibitors are first-line therapies in melanoma, but safety in older adults has not yet been assessed. Ipilimumab improves survival, but immunologic-related adverse events (AEs) can be threatening, and its use in elderly people raises questions.
AIM: To assess safety in a cohort of very elderly patients treated with ipilimumab.
METHODS: All patients over 80 years treated with ipilimumab for melanoma were retrospectively included. AE occurrence, management, and outcome, as well as response rate at week 16 and overall survival were recorded, and compared to data for a group of younger patients treated in our institution during the same period.
RESULTS: In the elderly group, 23 patients were included with a median age of 82 years [80-90]. AEs amounting to 23 occurred in 15 patients (65%) with 5 grade 3 (22%) and 1 grade 5 (opportunistic infection) AEs. Corticosteroids were required for five (22%) patients, additive immunosuppressive therapy for two, hospitalization for four, and definitive interruption of ipilimumab for three. Median overall survival was 14 months. In the younger group, 29 patients were included with a median age of 58 years. AEs occurred in 15/29 (52%) with 4 grade 3 (19%) and 1 grade 4 (7%). Median OS was 17 months.
CONCLUSION: Serious AEs occurred in 80 + adults at the same rate as observed in our younger patients and as previously reported in younger populations. Ipilimumab can be an option in elderly patients, as patients may benefit from therapy and safety seems to be manageable.

PMID: 30661086 [PubMed - indexed for MEDLINE]

Permalink for 'Correlation of Vascular Endothelial Growth Factor subtypes and their receptors with melanoma progression: A next-generation Tissue Microarray (ngTMA) automated analysis.'

Correlation of Vascular Endothelial Growth Factor subtypes and their receptors with melanoma progression: A next-generation Tissue Microarray (ngTMA) automated analysis.

Fetched: April 18th, 2019, 5:00am GMT

Correlation of Vascular Endothelial Growth Factor subtypes and their receptors with melanoma progression: A next-generation Tissue Microarray (ngTMA) automated analysis.

PLoS One. 2018;13(11):e0207019

Authors: Seyed Jafari SM, Wiedmer C, Cazzaniga S, Frangež Ž, Shafighi M, Beltraminelli H, Weber B, Simon HU, Hunger RE

Abstract
INTRODUCTION: Finding new markers to assess prognosis of melanoma without the necessity to perform a surgical interventions is an important goal in melanoma research. The current study aimed to assess the correlation of clinical course and prognosis of primary and metastatic melanoma with expression of VEGF family and their receptors.
METHODS: A ngTMA block was made from the randomly selected paraffin tissue blocks of the patients with melanocytic nevi, primary and metastatic melanoma. Then sections cut from ngTMA-block were immunohistochemically stained with proper antibodies. Expression of these proteins was investigated using automated image analysis and compared among the study groups.
RESULTS: We analyzed the tissue of 238 patients with following diagnoses: 101 (42.4%) with a diagnosis of nevus, 86 (36.1%) Malignant melanoma and 51 (21.4%) metastasis. Median follow-up time for the malignant lesions was 5.71 years. Among the tested antigen, VEGF-C (p = 0.016), VEGF-R2 (p<0.001) and VEGF-R3 (p = 0.002) were significantly higher expressed in the metastatic tissues. When these scores were assessed in multiple regression models, the only independent factor linked to patient's diagnosis was VEGF-R2 (p<0.001). In addition, groups of highly correlated variables (VEGF-C and VEGF-R3, VEGF-A and VEGF-R1) were found to form separate sub-clusters. On the other side, high values of VEGF-C were associated with both overall and disease-free survival with a statically significant HR of 2.76 (95% CI: 1.27, 5.98; p = 0.01) and 2.82 (95%CI: 1.62, 4.91; p<0.001), respectively.
CONCLUSIONS: This study shows that VEGF-C and VEGF-R2 might represent new prognostic marker in MM. However, further prospective studies are warranted to test their real efficacy as a prognostic marker.

PMID: 30408085 [PubMed - indexed for MEDLINE]

Epigenetic profiling for the molecular classification of metastatic brain tumors.

Fetched: April 18th, 2019, 5:00am GMT

Epigenetic profiling for the molecular classification of metastatic brain tumors.

Nat Commun. 2018 11 06;9(1):4627

Authors: Orozco JIJ, Knijnenburg TA, Manughian-Peter AO, Salomon MP, Barkhoudarian G, Jalas JR, Wilmott JS, Hothi P, Wang X, Takasumi Y, Buckland ME, Thompson JF, Long GV, Cobbs CS, Shmulevich I, Kelly DF, Scolyer RA, Hoon DSB, Marzese DM

Abstract
Optimal treatment of brain metastases is often hindered by limitations in diagnostic capabilities. To meet this challenge, here we profile DNA methylomes of the three most frequent types of brain metastases: melanoma, breast, and lung cancers (n = 96). Using supervised machine learning and integration of DNA methylomes from normal, primary, and metastatic tumor specimens (n = 1860), we unravel epigenetic signatures specific to each type of metastatic brain tumor and constructed a three-step DNA methylation-based classifier (BrainMETH) that categorizes brain metastases according to the tissue of origin and therapeutically relevant subtypes. BrainMETH predictions are supported by routine histopathologic evaluation. We further characterize and validate the most predictive genomic regions in a large cohort of brain tumors (n = 165) using quantitative-methylation-specific PCR. Our study highlights the importance of brain tumor-defining epigenetic alterations, which can be utilized to further develop DNA methylation profiling as a critical tool in the histomolecular stratification of patients with brain metastases.

PMID: 30401823 [PubMed - indexed for MEDLINE]

Permalink for 'Amalgam tattoo versus melanocytic neoplasm - Differential diagnosis of dark pigmented oral mucosa lesions using infrared spectroscopy.'

Amalgam tattoo versus melanocytic neoplasm - Differential diagnosis of dark pigmented oral mucosa lesions using infrared spectroscopy.

Fetched: April 18th, 2019, 5:00am GMT

Amalgam tattoo versus melanocytic neoplasm - Differential diagnosis of dark pigmented oral mucosa lesions using infrared spectroscopy.

PLoS One. 2018;13(11):e0207026

Authors: Laimer J, Henn R, Helten T, Sprung S, Zelger B, Zelger B, Steiner R, Schnabl D, Offermanns V, Bruckmoser E, Huck CW

Abstract
BACKGROUND: Dark pigmented lesions of the oral mucosa can represent a major diagnostic challenge. A biopsy is usually required to determine the nature of such intraoral discolorations. This study investigates the potential use of infrared spectroscopy for differential diagnosis of amalgam tattoos versus benign or malignant melanocytic neoplasms.
MATERIALS AND METHODS: For this retrospective study, formalin-fixed paraffin-embedded tissue (FFPE) specimens of dark pigmented lesions concerning the oral mucosa or the lip were investigated using mid infrared spectroscopy. The samples were chosen from patients who had undergone a mucosal biopsy at the University Hospital Innsbruck (Austria) between the years 2000 and 2017. Principal component analysis was used for data exploration. Evaluation was based on the superimposition of the recorded spectra and the corresponding histologic slides.
RESULTS: In total, 22 FFPE specimens were analyzed. Clear differences were found between amalgam and non-amalgam samples. A general weakening of the penetrating infrared radiation allowed for unspecific discrimination between these two classes. An overall accuracy in predicting the correct class of 95.24% was achieved.
CONCLUSION: Infrared spectroscopy appears to be a suitable technique to differentiate between amalgam tattoos and melanocytic lesions in FFPE samples. It could potentially be applied in vivo, too, serving as a non-invasive diagnostic tool for intraoral dark pigmented lesions.

PMID: 30399191 [PubMed - indexed for MEDLINE]

Cancer cells copy migratory behavior and exchange signaling networks via extracellular vesicles.

Fetched: April 18th, 2019, 5:00am GMT

Cancer cells copy migratory behavior and exchange signaling networks via extracellular vesicles.

EMBO J. 2018 08 01;37(15):

Authors: Steenbeek SC, Pham TV, de Ligt J, Zomer A, Knol JC, Piersma SR, Schelfhorst T, Huisjes R, Schiffelers RM, Cuppen E, Jimenez CR, van Rheenen J

Abstract
Recent data showed that cancer cells from different tumor subtypes with distinct metastatic potential influence each other's metastatic behavior by exchanging biomolecules through extracellular vesicles (EVs). However, it is debated how small amounts of cargo can mediate this effect, especially in tumors where all cells are from one subtype, and only subtle molecular differences drive metastatic heterogeneity. To study this, we have characterized the content of EVs shed in vivo by two clones of melanoma (B16) tumors with distinct metastatic potential. Using the Cre-LoxP system and intravital microscopy, we show that cells from these distinct clones phenocopy their migratory behavior through EV exchange. By tandem mass spectrometry and RNA sequencing, we show that EVs shed by these clones into the tumor microenvironment contain thousands of different proteins and RNAs, and many of these biomolecules are from interconnected signaling networks involved in cellular processes such as migration. Thus, EVs contain numerous proteins and RNAs and act on recipient cells by invoking a multi-faceted biological response including cell migration.

PMID: 29907695 [PubMed - indexed for MEDLINE]

Permalink for 'Medical, demographic and psychological correlates of fear of cancer recurrence (FCR) morbidity in breast, colorectal and melanoma cancer survivors with probable clinically significant FCR seeking psychological treatment through the ConquerFear study.'

Medical, demographic and psychological correlates of fear of cancer recurrence (FCR) morbidity in breast, colorectal and melanoma cancer survivors with probable clinically significant FCR seeking psychological treatment through the ConquerFear study.

Fetched: April 18th, 2019, 5:00am GMT

Medical, demographic and psychological correlates of fear of cancer recurrence (FCR) morbidity in breast, colorectal and melanoma cancer survivors with probable clinically significant FCR seeking psychological treatment through the ConquerFear study.

Support Care Cancer. 2018 Dec;26(12):4207-4216

Authors: Smith A', Sharpe L, Thewes B, Turner J, Gilchrist J, Fardell JE, Girgis A, Tesson S, Descallar J, Bell ML, Beith J, Butow P, ConquerFear Authorship Group

Abstract
PURPOSE: Despite the prevalence of fear of cancer recurrence (FCR), understanding of factors underlying clinically significant FCR is limited. This study examined factors associated with greater FCR morbidity, according to a cognitive processing model, in cancer survivors who screened positively for clinically significant FCR seeking psychological treatment through the ConquerFear trial.
METHODS: Participants had completed treatment for breast, colorectal or melanoma cancer 2 months to 5 years previously and scored ≥ 13/36 on the Fear of Cancer Recurrence Inventory-Short Form (FCRI-SF). Hierarchical regression analyses examined associations between demographic, medical and psychological variables, namely metacognitions (MCQ-30), post-traumatic stress symptoms (IES-R) and FCR (FCRI total score).
RESULTS: Two hundred and ten (95%) of the 222 cancer survivors who consented to the ConquerFear trial completed the baseline questionnaire. Participants were predominantly (89%) breast cancer survivors. The final regression model accounted for 68% of the variance in FCR (demographic and medical variables 13%, metacognitions 26%, post-traumatic stress symptoms 28%). Negative metacognitive beliefs about worry and intrusive post-traumatic stress symptoms were significant individual correlates of FCR, but negative beliefs about worry did not significantly moderate the impact of intrusions on FCR morbidity.
CONCLUSIONS: Results provide partial support for the cognitive processing model of FCR. Psychological factors were found to play an important role in FCR morbidity after controlling for demographic/medical factors. More intrusive thoughts and negative beliefs about worry were strong independent predictors of FCR morbidity. Cancer survivors with clinically significant FCR may benefit from assessment for intrusive thoughts and metacognitions and delivery of trauma- and/or metacognitive-based interventions accordingly.

PMID: 29882025 [PubMed - indexed for MEDLINE]

Permalink for '3-O-Glyceryl-2-O-hexyl ascorbate suppresses melanogenesis by interfering with intracellular melanosome transport and suppressing tyrosinase protein synthesis.'

3-O-Glyceryl-2-O-hexyl ascorbate suppresses melanogenesis by interfering with intracellular melanosome transport and suppressing tyrosinase protein synthesis.

Fetched: April 18th, 2019, 5:00am GMT

3-O-Glyceryl-2-O-hexyl ascorbate suppresses melanogenesis by interfering with intracellular melanosome transport and suppressing tyrosinase protein synthesis.

J Cosmet Dermatol. 2018 Dec;17(6):1209-1215

Authors: Taira N, Katsuyama Y, Yoshioka M, Okano Y, Masaki H

Abstract
BACKGROUND: Ascorbic acid (AsA) has multifunctional benefits on skin beauty, such as the reduction in oxidative stress and the induction of collagen production. Among them, the prevention and improvement of skin pigmentation by AsA is a most important benefit for people. However, it is well known that AsA not only is quite unstable in formulations but it also has a low capability of skin penetration due to its hydrophilic property. In addition, existing water-soluble AsA derivatives that were developed to improve its stability also have low skin penetration.
AIM: To investigate the potential of a newly synthesized amphiphilic derivative of AsA, 3-O-Glyceryl-2-O-hexyl ascorbate (VC-HG), which has an added glyceryl group and a hexyl group, on skin beauty focusing on its skin lightening/whitening effects.
METHODS: DNA microarray analysis and real-time PCR were used to clarify the effects of VC-HG on melanogenesis using B16 mouse melanoma cells. The effects of VC-HG on melanin synthesis, tyrosinase protein levels, and the inhibition of tyrosinase activity were evaluated.
RESULTS: DNA microarray analysis revealed that treatment with VC-HG downregulated the expression of genes encoding tyrosinase and MyosinVa. Further, real-time PCR analysis showed the downregulation of tyrosinase, MyosinVa, Rab27a, and Kinesin mRNAs following VC-HG treatment. In addition, VC-HG caused decreases in tyrosinase protein levels and melanin synthesis.
CONCLUSION: We conclude that VC-HG has an impact on skin lightening/whitening by inhibiting tyrosinase protein synthesis and interfering with intracellular melanosome transport.

PMID: 29115012 [PubMed - indexed for MEDLINE]

Permalink for 'Association between risk factors and detection of cutaneous melanoma in the setting of a population-based skin cancer screening.'

Association between risk factors and detection of cutaneous melanoma in the setting of a population-based skin cancer screening.

Fetched: April 18th, 2019, 5:00am GMT

Association between risk factors and detection of cutaneous melanoma in the setting of a population-based skin cancer screening.

Eur J Cancer Prev. 2018 11;27(6):563-569

Authors: Hübner J, Waldmann A, Eisemann N, Noftz M, Geller AC, Weinstock MA, Volkmer B, Greinert R, Breitbart EW, Katalinic A

Abstract
Early detection is considered to improve the prognosis of cutaneous melanoma. The value of population-based screening for melanoma, however, is still controversial. The aim of this study was to evaluate the predictive power of established risk factors in the setting of a population-based screening and to provide empirical evidence for potential risk stratifications. We reanalyzed data (including age, sex, risk factors, and screening results) of 354 635 participants in the Skin Cancer Research to provide Evidence for Effectiveness of Screening in Northern Germany (SCREEN)project conducted in the German state of Schleswig-Holstein (2003-2004). In multivariable analysis, atypical nevi [odds ratio (OR): 17.4; 95% confidence interval (CI): 14.4-20.1], personal history of melanoma (OR: 5.3; 95% CI: 3.6-7.6), and multiple (≥40) common nevi (OR: 1.3; 95% CI: 1.1-1.6) were associated with an increased risk of melanoma detection. Family history and congenital nevi were not significantly associated with melanoma detection in the SCREEN. The effects of several risk-adapted screening strategies were evaluated. Hypothesizing a screening of individuals aged more than or equal to 35 years, irrespective of risk factors (age approach), the number needed to screen is 559 (95% CI: 514-612), whereas a screening of adults (aged ≥20) with at least one risk factor (risk approach) leads to a number needed to screen of 178 (95% CI: 163-196). Converted into one screen-detected melanoma, the number of missed melanomas is 0.15 (95% CI: 0.12-0.18) with the age approach and 0.22 (95% CI: 0.19-0.26) with the risk approach. The results indicate that focusing on individuals at high risk for melanoma may improve the cost-effectiveness and the benefit-to-harm balance of melanoma screening programs.

PMID: 28692584 [PubMed - indexed for MEDLINE]

VISUAL VIGNETTE.

Fetched: April 18th, 2019, 5:00am GMT

VISUAL VIGNETTE.

Endocr Pract. 2017 Oct;23(10):1276

Authors: Yu R, Quon A, Hecht JR

PMID: 28332878 [PubMed - indexed for MEDLINE]

Permalink for 'Survival comparison between primary hepatic neuroendocrine neoplasms and primary pancreatic neuroendocrine neoplasms and the analysis on prognosis-related factors.'

Survival comparison between primary hepatic neuroendocrine neoplasms and primary pancreatic neuroendocrine neoplasms and the analysis on prognosis-related factors.

Fetched: April 16th, 2019, 5:00am GMT

Survival comparison between primary hepatic neuroendocrine neoplasms and primary pancreatic neuroendocrine neoplasms and the analysis on prognosis-related factors.

Hepatobiliary Pancreat Dis Int. 2019 Apr 05;:

Authors: Li MX, Li QY, Xiao M, Wan DL, Chen XH, Zhou L, Xie HY, Zheng SS

Abstract
BACKGROUND: Primary hepatic neuroendocrine neoplasms (PHNENs) are extremely rare and few articles have compared the prognosis of PHNENs with other neuroendocrine neoplasms (NENs). This study aimed to investigate the different prognosis between PHNENs and pancreatic NEN (PanNENs) and evaluate the relevant prognosis-related factors.
METHODS: From January 2012 to October 2016, a total of 44 NENs patients were enrolled and divided into two groups according to the primary tumor location which were named group PHNENs (liver; n = 12) and group PanNENs (pancreas; n = 32). Demographic, clinical characteristics and survival data were compared between the two groups with Kaplan-Meier method and log-rank tests. Prognostic factors were analyzed using the Cox regression model.
RESULTS: The overall survival of group PHNENs and group PanNENs were 25.4 ± 6.7 months and 39.8 ± 3.7 months, respectively (P = 0.037). The cumulative survival of group PanNENs was significantly higher than that of group PHNENs (P = 0.029). Univariate analysis revealed that sex, albumin, total bilirubin, total bile acid, aspartate aminotransferase, alkaline phosphatase, α-fetoprotein and carbohydrate antigen 19-9, histological types, treatments and primary tumor site were the prognostic factors. Further multivariate analysis indicated that albumin (P = 0.008), histological types NEC (P = 0.035) and treatments (P = 0.005) were the independent prognostic factors. Based on the histological types, the cumulative survival of patients with well-differentiated neuroendocrine tumor was significant higher than that of patients with poorly differentiated neuroendocrine carcinoma in group PHNENs (P = 0.022), but not in group PanNENs (P > 0.05). According to the different treatments, patients who received surgery had significantly higher cumulative survival than those with conservative treatment in both groups (P < 0.05).
CONCLUSIONS: PHNENs have lower survival compared to PanNENs. Histological types and treatments affect the prognosis. Surgical resection still remains the first line of treatment for resectable lesions and can significantly improve the survival.

PMID: 30981633 [PubMed - as supplied by publisher]

Metastases to the breast, an uncommon diagnosis: what do radiologists need to know?

Fetched: April 16th, 2019, 5:00am GMT

Metastases to the breast, an uncommon diagnosis: what do radiologists need to know?

Radiologia. 2019 Apr 10;:

Authors: Pesce K, Chico MJ, Delgado JS, Sierra ACZ, Hadad C, Wernicke A

Abstract
OBJECTIVE: To analyze the imaging characteristics of histologically diagnosed metastases to the breast.
MATERIAL AND METHODS: We selected patients histologically diagnosed with metastases to the breast in our diagnostic and interventional breast imaging unit between March 2010 and September 2018.
RESULTS: A total of 9 patients (all women; mean age, 60 y; age range, 28-89 y) were diagnosed with metastases to the breast. In 1 (11.11%) case, the primary disease was diagnosed from the breast lesion. The primary tumors were melanoma (n=5), neuroendocrine tumor (n=2, one from the small bowel and one from the cervix), lung adenocarcinoma (n=1), and ovarian cancer (n=1). The clinical and imaging manifestations depend on the type of dissemination of disease and can simulate benign and malignant primary breast lesions.
CONCLUSION: There is no specific imaging pattern for metastases to the breast that would help to orient the diagnosis. It is important to consider this etiological possibility if the patient has a history of a primary tumor in another organ.

PMID: 30981417 [PubMed - as supplied by publisher]

Diagnostic challenge in a metastatic pulmonary adenocarcinoma with neuroendocrine differentiation to breast and skin.

Fetched: April 15th, 2019, 5:00am GMT

Diagnostic challenge in a metastatic pulmonary adenocarcinoma with neuroendocrine differentiation to breast and skin.

Cytopathology. 2019 Apr 12;:

Authors: Mitra S, Purkait S, Kundoo A, Behera G, Patra S

Abstract
Malignancy to the breast is a rare form of breast malignancy (<1% of all breast tumors) with difficult diagnosis and often dismal prognosis. Melanoma, hematological malignancies and rhabdomyosarcoma commonly affect the breast secondarily although the carcinomas of pulmonary, ovarian and renal origin are also reported to metastatize to the breast. The metastatic symptoms could be the first symptom to the patient and becomes a diagnostic challenge for both the clinician and the pathologist. Such cases highlight the importance of the combinatorial diagnostic approach involving the physicians, radiologist and pathologist. This article is protected by copyright. All rights reserved.

PMID: 30980438 [PubMed - as supplied by publisher]

Permalink for 'The role of multimodal imaging in guiding resectability and cytoreduction in pancreatic neuroendocrine tumors: focus on PET and MRI.'

The role of multimodal imaging in guiding resectability and cytoreduction in pancreatic neuroendocrine tumors: focus on PET and MRI.

Fetched: April 15th, 2019, 5:00am GMT

The role of multimodal imaging in guiding resectability and cytoreduction in pancreatic neuroendocrine tumors: focus on PET and MRI.

Abdom Radiol (NY). 2019 Apr 12;:

Authors: Rozenblum L, Mokrane FZ, Yeh R, Sinigaglia M, Besson F, Seban RD, Chougnet CN, Revel-Mouroz P, Zhao B, Otal P, Schwartz LH, Dercle L

Abstract
Pancreatic neuroendocrine tumors (pNETs) are rare neoplasms that secrete peptides and neuro-amines. pNETs can be sporadic or hereditary, syndromic or non-syndromic with different clinical presentations and prognoses. The role of medical imaging includes locating the tumor, assessing its extent, and evaluating the feasibility of curative surgery or cytoreduction. Pancreatic NETs have very distinctive phenotypes on CT, MRI, and PET. PET have been demonstrated to be very sensitive to detect either well-differentiated pNETs using 68Gallium somatostatin receptor (SSTR) radiotracers, or more aggressive undifferentiated pNETS using 18F-FDG. A comprehensive interpretation of multimodal imaging guides resectability and cytoreduction in pNETs. The imaging phenotype provides information on the differentiation and proliferation of pNETs, as well as the spatial and temporal heterogeneity of tumors with prognostic and therapeutic implications. This review provides a structured approach for standardized reading and reporting of medical imaging studies with a focus on PET and MR techniques. It explains which imaging approach should be used for different subtypes of pNET and what a radiologist should be looking for and reporting when interpreting these studies.

PMID: 30980115 [PubMed - as supplied by publisher]

SET domain containing 1B gene (SETD1B) is mutated in primary hepatic neuroendocrine tumors.

Fetched: April 14th, 2019, 5:00am GMT

SET domain containing 1B gene (SETD1B) is mutated in primary hepatic neuroendocrine tumors.

Int J Cancer. 2019 Apr 11;:

Authors: Yang P, Huang X, Lai C, Li L, Li T, Huang P, Ouyang S, Yan J, Cheng S, Lei G, Wang Z, Yu L, Hong Z, Li R, Dong H, Wang C, Yu Y, Wang X, Li X, Wang L, Lv F, Yin Y, Yang H, Song J, Gao Q, Wang X, Zhang S

Abstract
Primary hepatic neuroendocrine tumors (PHNETs) are extremely rare NETs originating from the liver. These tumors are associated with heterogeneous prognosis, and few treatment targets for PHNETs have been identified. Because the major genetic alterations in PHNET are still largely unknown, we performed whole-exome sequencing of 22 paired tissues from PHNET patients and identified 22 recurring mutations of somatic genes involved in the following activities: epigenetic modification (BPTF, MECP2 and WDR5), cell cycle (TP53, ATM, MED12, DIDO1 and ATAD5) and neural development (UBR4, MEN1, GLUL and GIGYF2). Here, we show that TP53 and the SET domain containing the 1B gene (SETD1B) are the most frequently mutated genes in this set of samples (3/22 subjects, 13.6%). A biological analysis suggests that one of the three SETD1B mutants, A1054del, promotes cell proliferation, migration and invasion compared with wild-type SETD1B. Our work unveils that SETD1B A1054del mutant is functional in PHNET and implicates genes including TP53 in the disease. Our findings thus characterize the mutational landscapes of PHNET and implicate novel gene mutations linked to PHNET pathogenesis and potential therapeutic targets. This article is protected by copyright. All rights reserved.

PMID: 30977120 [PubMed - as supplied by publisher]

Large cell neuroendocrine carcinoma of the endometrium: a report and review of the literature.

Fetched: April 14th, 2019, 5:00am GMT

Large cell neuroendocrine carcinoma of the endometrium: a report and review of the literature.

Gynecol Oncol Rep. 2019 May;28:96-100

Authors: Jenny C, Kimball K, Kilgore L, Boone J

Abstract
Large-cell neuroendocrine tumor of the endometrium is a rare tumor type which is difficult to diagnose. Our routine tissue sampling is often non-productive and these tumors can be mistaken for other poorly differentiated carcinomas. Sites of metastatic disease sometimes confuse the identification of the primary organ, and histological diagnosis requires a choice of neuroendocrine biomarkers. In addition, there are no published diagnostic criteria for LCNEC of the endometrium and diagnostic criteria must be translated from the WHO classification of tumors of the lung. Once a diagnosis is reached, there are no large series to direct treatment. Consensus opinion appears to favor surgery for early stage disease followed by chemotherapy with etoposide and platinum-based agents. While there are many hurdles to overcome, the proper diagnosis of LCNEC of the endometrium is of utmost importance in a disease characterized by rapid progression and poor prognosis. We examine a case of large cell neuroendocrine tumor of the endometrium with rapid progression over a period of two months which precluded her planned chemotherapy.

PMID: 30976646 [PubMed]

Endoscopic Resection of a Rectal Neuroendocrine Tumor: Hybrid Endoscopic Submucosal Dissection.

Fetched: April 14th, 2019, 5:00am GMT

Endoscopic Resection of a Rectal Neuroendocrine Tumor: Hybrid Endoscopic Submucosal Dissection.

GE Port J Gastroenterol. 2019 Mar;26(2):131-133

Authors: Gravito-Soares M, Gravito-Soares E, Amaro P, Cunha I, Fraga J, Tomé L

PMID: 30976620 [PubMed]

Mixed Adenoneuroendocrine Tumor of the Rectum in an Ulcerative Colitis Patient.

Fetched: April 14th, 2019, 5:00am GMT

Mixed Adenoneuroendocrine Tumor of the Rectum in an Ulcerative Colitis Patient.

GE Port J Gastroenterol. 2019 Mar;26(2):125-127

Authors: Gaspar R, Santos-Antunes J, Marques M, Liberal R, Melo D, Pereira P, Lopes S, Macedo G

Abstract
Patients with inflammatory bowel disease present a higher risk of colorectal cancer, especially patients with a high degree of disease activity. Although rare, carcinoid tumors can also be associated with inflammatory bowel disease. Mixed adenoneuroendocrine tumor is defined as a neoplasm with dual differentiation (neuroendocrine and adenoma) with each component accounting for at least 30% of the tumor. We present a case of a mixed adenoneuroendocrine tumor in a patient with inflammatory bowel disease.

PMID: 30976618 [PubMed]

Histological variants in non-muscle invasive bladder cancer.

Fetched: April 14th, 2019, 5:00am GMT

Histological variants in non-muscle invasive bladder cancer.

Transl Androl Urol. 2019 Feb;8(1):34-38

Authors: Baumeister P, Zamboni S, Mattei A, Antonelli A, Simeone C, Mordasini L, DiBona C, Moschini M

Abstract
Several studies evaluated the role of histological variants on oncological outcomes after radical cystectomy (RC) and they were found significantly associated with worse recurrence and survival. Sparse data exists regarding the role variant histology in non-muscle invasive diseases: assessing their relationship with recurrence and progression is important to understand the most effective treatment and follow-up schedule. For these reasons, the aim of the present non-systematic review was to assess the literature on variant histology in non-muscle invasive bladder cancer (BCa). The diagnosis of presence variant histology at transurethral resection (TUR) specimens challenging for pathologists and several studies published in literature evaluated concordance between TUR and RC specimen with discordant results. These differences are probably related to diversity in collection of samples and pathological evaluation and underline the necessity to have good tissue-sample and a pathologic evaluation performed by expert and dedicated uropathologists. Treatment of BCa with variant histology shall include immediate RC in case of plasmacitoid, pure squamous, micropapillary and sarcomatoid variants. The neuroendocrine differentiation, therefore, showed chemosensitiveness, and RC preceded by neoadjuvant chemotherapy should be proposed. Intravesical instillations with Bacillus Calmette Guerin (BCG) can be suggested in very selected cases of nested and glandular variants.

PMID: 30976566 [PubMed]

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

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

Fetched: April 14th, 2019, 5:00am GMT

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

Mod Pathol. 2019 Apr 11;:

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

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

PMID: 30976104 [PubMed - as supplied by publisher]

Permalink for 'Clinicopathological characteristics and risk factors for recurrence of well-differentiated pancreatic neuroendocrine tumors after radical surgery: a case-control study.'

Clinicopathological characteristics and risk factors for recurrence of well-differentiated pancreatic neuroendocrine tumors after radical surgery: a case-control study.

Fetched: April 14th, 2019, 5:00am GMT

Clinicopathological characteristics and risk factors for recurrence of well-differentiated pancreatic neuroendocrine tumors after radical surgery: a case-control study.

World J Surg Oncol. 2019 Apr 11;17(1):66

Authors: Zhang P, Li YL, Qiu XD, Luo J, Shi YF, Sun YL, Su F, Qi ZR, Tan HY

Abstract
BACKGROUND: Well-differentiated pancreatic neuroendocrine tumors (PanNETs) usually have a good prognosis; however, there are patients that experience recurrence after curative resection.
AIM: To explore recurrence-related risk factors by analyzing clinicopathological data of PanNETs after radical surgery.
METHODS: Clinical and pathological data from 47 patients with well-differentiated PanNETs at China-Japan Friendship Hospital from January 2012 to March 2016 were analyzed retrospectively. Univariate and multivariate analyses of the risk factors of PanNETs for postoperative recurrence were conducted.
RESULTS: Among the 47 patients with well-differentiated PanNETs, there were 38 cases with non-functioning tumors, 9 cases with functional tumors (6 insulinomas, 1 gastrinoma, 1 glucagonoma, and 1 VIPomas). There are 17 cases (36.2%) in the pancreatic head, 17 (36.2%) in the body and tail, 9 (19.1%) in the tail, and 4 (8.5%) in the body. The median tumor size was 3.65 (IQR 2-5.5) cm. Fourteen cases (29.8%) were NET G1, and 33 cases (70.2%) were NET G2. In regard to the clinical stage, 9 (19.1%) cases were IA, 14 (29.8%) cases were IB, 7 (14.9%) cases were IIA, 14 (29.8%) cases were IIB, and 3 cases unknown. There were 17 patients who presented with postoperative recurrence. Univariate analysis showed that AJCC TNM staging, Ki67 index, vascular invasion, margin status, and the regional stage of the tumors are related to the recurrence of patients with PanNETs (p < 0.05). The results of multivariate analysis showed that Ki67 index ≥ 10% is an independent risk factor for the postoperative recurrence of PanNETs (p < 0.05).
CONCLUSION: The Ki67 index ≥ 10% is an independent risk factor for recurrence in well-differentiated PanNETs after radical surgery, and close surveillance for these patients may be needed.

PMID: 30975157 [PubMed - in process]

INSM1 Expression in Peripheral Neuroblastic Tumors and Other Embryonal Neoplasms.

Fetched: April 14th, 2019, 5:00am GMT

INSM1 Expression in Peripheral Neuroblastic Tumors and Other Embryonal Neoplasms.

Pediatr Dev Pathol. 2019 Apr 11;:1093526619843725

Authors: Wang H, Krishnan C, Charville GW

Abstract
Insulinoma-associated protein 1 (INSM1) is a transcription factor that functions in neuroepithelial tissue development and shows expression in neuroendocrine neoplasms. Given the role of INSM1 in controlling differentiation of the sympatho-adrenal lineage, we hypothesized that INSM1 expression would define a subset of neuroblastic tumors. This study aimed to characterize the immunohistochemical profile of INSM1 in a cohort of peripheral neuroblastic tumors and compare INSM1 expression in these tumors to that seen in other embryonal neoplasms, using both tissue microarrays and whole-slide histologic sections. INSM1 showed nuclear expression in 39/50 (78%) peripheral neuroblastic tumors, including 27/32 (84%) neuroblastomas, 9/9 (100%) ganglioneuroblastomas, and 3/9 (33%) ganglioneuromas. Altogether, 70% of peripheral neuroblastic tumors showed anti-INSM1 immunoreactivity in more than 20% of tumor nuclei. Although no non-neuroblastic tumors in this study exhibited INSM1 expression in more than 20% of nuclei, focal or patchy staining was identified in 7/14 (50%) rhabdomyosarcomas, 7/22 (32%) nephroblastomas, and 4/20 (20%) Ewing sarcomas. The absence of INSM1 expression in peripheral neuroblastic tumors was restricted to undifferentiated and poorly differentiated neuroblastomas, as well as mature ganglioneuromas, mimicking the transient INSM1 expression seen in sympatho-adrenal differentiation during normal development. No significant association between MYCN amplification status and INSM1 expression was observed. We found that all 3 INSM1-negative neuroblastoma patients with available follow-up were alive at a median of 15 years, in comparison to 9 of 13 INSM1-positive neuroblastoma patients living at a median of 5 years. Additional studies are needed to determine whether INSM1 expression is indicative of a clinically significant differentiation state in neuroblastoma.

PMID: 30975032 [PubMed - as supplied by publisher]

Histologic predictors of invasion in partially biopsied lentigo maligna melanoma.

Fetched: April 14th, 2019, 5:00am GMT

Histologic predictors of invasion in partially biopsied lentigo maligna melanoma.

J Am Acad Dermatol. 2019 Apr;80(4):1150-1152

Authors: Aouidad I, Fargeas C, Romero P, Sei JF, Chaussade V, Beauchet A, Clerici T, Zimmermann U, Saiag P, Funck-Brentano E

PMID: 30879481 [PubMed - indexed for MEDLINE]

Merkel cell carcinoma incidence, trends, and survival rates among adults aged ≥50 years from United States Cancer Statistics.

Fetched: April 14th, 2019, 5:00am GMT

Merkel cell carcinoma incidence, trends, and survival rates among adults aged ≥50 years from United States Cancer Statistics.

J Am Acad Dermatol. 2019 Apr;80(4):1154-1156

Authors: Freeman MB, Holman DM, Qin J, Lunsford NB

PMID: 30876535 [PubMed - indexed for MEDLINE]

Recent dermatology visit is associated with thinner Breslow depth nodular melanomas.

Fetched: April 14th, 2019, 5:00am GMT

Recent dermatology visit is associated with thinner Breslow depth nodular melanomas.

J Am Acad Dermatol. 2019 Apr;80(4):1143-1144

Authors: Wei EX, Chen L, Ma F, Keri J, Hu S

PMID: 30876534 [PubMed - indexed for MEDLINE]

Extremity nevus count is an independent risk factor for basal cell carcinoma and melanoma, but not squamous cell carcinoma.

Fetched: April 14th, 2019, 5:00am GMT

Extremity nevus count is an independent risk factor for basal cell carcinoma and melanoma, but not squamous cell carcinoma.

J Am Acad Dermatol. 2019 Apr;80(4):970-978

Authors: Wei EX, Li X, Nan H

Abstract
BACKGROUND: The presence of nevi portends an increased risk for melanoma.
OBJECTIVE: We sought to examine the association between extremity nevus count and the risk of melanoma and keratinocyte cancers.
METHODS: We evaluated prospective cohorts of 176,317 women (the Nurses' Health Study, 1986-2012 and the Nurses' Health Study 2, 1989-2013) and 32,383 men (Health Professionals Follow-up Study, 1986-2012). Information on nevus count (none, 1-5, 6-14, ≥15) on the extremity was collected at baseline.
RESULTS: There were 1704 incident cases of melanoma, 2296 incident cases of squamous cell carcinoma, and 30,457 incident cases of basal cell carcinoma, with a total of 4,655,043 person-years for melanoma and 4,267,708 person-years for keratinocyte cancers. The presence of an extremity nevus was associated with an increased risk of melanoma in all anatomic areas and increased risk of basal cell carcinoma (BCC). Individuals with ≥15 nevi had the highest risk of melanoma and BCC compared to those without any extremity nevi (melanoma hazard ratio 2.79 [95% confidence interval 2.04-3.83]; BCC HR 1.40 [95% confidence interval 1.32-1.49]). No significant association was observed for squamous cell carcinoma.
LIMITATIONS: Limitations of our study included self-reported nevus count and detection bias.
CONCLUSIONS: Extremity nevus count is a helpful clinical marker in risk-stratifying individuals for BCC and melanoma on all body sites.

PMID: 30713015 [PubMed - indexed for MEDLINE]

[A Case of Gastric Schwannoma with Regional Lymphadenopathy].

Fetched: April 14th, 2019, 5:00am GMT

[A Case of Gastric Schwannoma with Regional Lymphadenopathy].

Gan To Kagaku Ryoho. 2018 Dec;45(13):1952-1954

Authors: Nose Y, Takeno A, Masuzawa T, Toya K, Yukawa Y, Mori R, Kawai K, Sakamoto T, Murakami K, Naito A, Katsura Y, Ohmura Y, Kagawa Y, Takeda Y, Murata K

Abstract
Schwannomas are rarely observed in the gastrointestinal tract. A 63-year-old man was referred to our hospital with gastric submucosal tumor with central ulceration by upper gastrointestinal endoscopy. Biopsy was performed, but pathological diagnosis was not obtained. A contrast-enhanced computed tomography scan of the abdomen revealed a round mass in the lower part of the stomach and regional lymphadenopathies. A distal gastrectomy with dissection of the regional lymph nodes (D2)was performed. The submucosal tumor measuring 67×49mm was resected. Histopathological examination revealed spindle-shaped cells arranged in palisades. The specimen was positive for S-100 protein, but negative for desmin, SMA, c-kit, and CD34. No tumor cells were found in the resected enlarged lymph nodes, indicating reactive lymphadenopathies. Based on these findings, the tumor was identified as a benign gastric schwannoma. Our patient shows no recurrence at 6 month follow-up.

PMID: 30692408 [PubMed - indexed for MEDLINE]

Time to reconsider the role of sentinel lymph node biopsy in melanoma.

Fetched: April 14th, 2019, 5:00am GMT

Time to reconsider the role of sentinel lymph node biopsy in melanoma.

J Am Acad Dermatol. 2019 Apr;80(4):1168-1171

Authors: Bigby M, Zagarella S, Sladden M, Popescu CM

Abstract
The Multicenter Selective Lymphadenectomy Trials indicate that there are no overall or melanoma-specific survival advantages to performing sentinel lymph node biopsy (SLNB) followed by immediate completion lymph node dissection compared with wide excision and observation for patients with positive sentinel nodes. These results make SLNB solely a staging procedure. The role of SLNB in the management of patients with melanoma deserves reappraisal. The potential marginal benefit of SLNB beyond the clinical and pathologic features of the melanoma has not been well studied. The use of sentinel lymph node status alone to accept and stratify patients into trials or to receive adjuvant treatment is not rational.

PMID: 30471314 [PubMed - indexed for MEDLINE]

Trends in incidence of cutaneous malignant melanoma in Canada: 1992-2010 versus 2011-2015.

Fetched: April 14th, 2019, 5:00am GMT

Trends in incidence of cutaneous malignant melanoma in Canada: 1992-2010 versus 2011-2015.

J Am Acad Dermatol. 2019 Apr;80(4):1157-1159

Authors: Ghazawi FM, Le M, Alghazawi N, Rahme E, Moreau L, Netchiporouk E, Zubarev A, Roshdy O, Glassman SJ, Sasseville D, Litvinov IV

PMID: 30395916 [PubMed - indexed for MEDLINE]

Permalink for 'Treatment of primary nonmetastatic melanoma at high-volume academic facilities is associated with improved long-term patient survival.'

Treatment of primary nonmetastatic melanoma at high-volume academic facilities is associated with improved long-term patient survival.

Fetched: April 14th, 2019, 5:00am GMT

Treatment of primary nonmetastatic melanoma at high-volume academic facilities is associated with improved long-term patient survival.

J Am Acad Dermatol. 2019 Apr;80(4):979-989

Authors: Cheraghlou S, Agogo GO, Girardi M

Abstract
BACKGROUND: Previous studies of cancer care have demonstrated improved long-term patient outcomes for those treated at high-volume centers. The influence of treatment center characteristics on outcomes for primary nonmetastatic melanoma is not currently established.
OBJECTIVE: We aimed to investigate the association of cancer treatment center case volume and academic affiliation with long-term patient survival for cases of primary nonmetastatic melanoma.
METHODS: Cases of melanoma diagnosed in US adults from 2004 to 2014 and included in the National Cancer Database were identified. Hospitals were grouped by yearly case-volume quartile: bottom quartile, 2 middle quartiles, and top quartile.
RESULTS: Facility case volume was significantly associated with long-term patient survival (P < .0001). The 5-year survival rates were 76.8%, 81.9%, and 86.4% for patients treated at institutions in the bottom, middle, and top quartiles of case volume, respectively. On multivariate analysis, treatment at centers in both middle quartiles (hazard ratio, 0.834; 95% confidence interval, 0.778-0.895) and in the top quartile (hazard ratio, 0.691; 95% confidence interval, 0.644-0.741) of case volume was associated with improved survival relative to that of patients treated at hospitals in the bottom quartile of case volume. Academic affiliation was associated with improved outcomes for top-quartile- but not middle-quartile-volume facilities.
LIMITATIONS: Disease-specific survival was not available.
CONCLUSIONS: Treatment at a high-volume facility is associated with improved long-term patient survival for melanoma. High-volume academic centers have improved patient outcomes compared with other high-volume centers.

PMID: 30365997 [PubMed - indexed for MEDLINE]

Hypercalcemia and cancer: Differential diagnosis and treatment.

Fetched: April 14th, 2019, 5:00am GMT

Hypercalcemia and cancer: Differential diagnosis and treatment.

CA Cancer J Clin. 2018 09;68(5):377-386

Authors: Zagzag J, Hu MI, Fisher SB, Perrier ND

Abstract
Incidentally detected hypercalcemia usually presents in an indolent manner and is most likely caused by primary hyperparathyroidism. In contrast, hypercalcemia in the patient with a history of cancer presents in a wide range of clinical settings and may be severe enough to warrant hospitalization. This form of hypercalcemia is usually secondary to hypercalcemia of malignancy and can be fatal. Hypercalcemia of malignancy is most commonly mediated by tumoral production of parathyroid hormone-related protein or by cytokines activating osteoclast degradation of bone. The initial workup, differential diagnoses, confirmatory laboratory testing, imaging, and medical and surgical management of hypercalcemia are described in the patient with cancer.

PMID: 30240520 [PubMed - indexed for MEDLINE]

Predominance of oral mucosal melanoma in areas of high mechanical stress.

Fetched: April 14th, 2019, 5:00am GMT

Predominance of oral mucosal melanoma in areas of high mechanical stress.

J Am Acad Dermatol. 2019 Apr;80(4):1133-1135

Authors: Rambhia PH, Stojanov IJ, Arbesman J

PMID: 30138653 [PubMed - indexed for MEDLINE]

[Epidemiology of neuroendocrine neoplasms].

Fetched: April 14th, 2019, 5:00am GMT

[Epidemiology of neuroendocrine neoplasms].

Khirurgiia (Mosk). 2016;(9):94-100

Authors: Kochatkov AV, Kovalenko ZA

PMID: 28635722 [PubMed - indexed for MEDLINE]

Bronchial Carcinoid Tumors with Massive Osseous Metaplasia: A Case Report and Review of the Literature.

Fetched: April 14th, 2019, 5:00am GMT

Bronchial Carcinoid Tumors with Massive Osseous Metaplasia: A Case Report and Review of the Literature.

Turk Patoloji Derg. 2019 Apr 12;:

Authors: Özşen M, Yalçinkaya U, Akyildiz EÜ, Bayram AS, Gökalp G

Abstract
Bronchial carcinoid tumors are primary lung neoplasms thought to originate from neuroendocrine cells, i.e. Kulchitsky cells, in the bronchial mucosa, although the type of cellular origin has not been clearly understood. A 61-year-old male patient underwent surgery and microscopic examination of the specimen revealed an anastomosing trabecular bony structure among the nests of tumor cells with round nucleus, granular chromatin, and large eosinophilic cytoplasm. Our case has been deemed worthy of being presented as bronchial carcinoid tumor with exaggerated osseous metaplasia.

PMID: 30977863 [PubMed - as supplied by publisher]

Permalink for 'Value of fluorine-18-fluorodeoxyglucose PET/CT in localizing the primary lesion in adrenocorticotropic hormone-dependent Cushing syndrome.'

Value of fluorine-18-fluorodeoxyglucose PET/CT in localizing the primary lesion in adrenocorticotropic hormone-dependent Cushing syndrome.

Fetched: April 13th, 2019, 5:00am GMT

Value of fluorine-18-fluorodeoxyglucose PET/CT in localizing the primary lesion in adrenocorticotropic hormone-dependent Cushing syndrome.

Nucl Med Commun. 2019 May;40(5):539-544

Authors: Zhou J, Ju H, Zhu L, Pan Y, Lv J, Zhang Y

Abstract
OBJECTIVE: This study aimed to present a proper understanding of the fluorine-18-fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) value in localizing the primary lesion in adrenocorticotropic hormone (ACTH)-dependent Cushing syndrome in a relatively large case cohort.
PATIENTS AND METHODS: This retrospective study included 47 patients with ACTH-dependent Cushing syndrome, who underwent an F-FDG PET/CT examination in our hospital from November 2010 to January 2018. The serum cortisol, 24 h urine cortisol, serum ACTH, and high-dose dexamethasone suppression test were measured in all the patients. Bilateral inferior petrosal sinus sampling was performed in 28/47 patients. Pituitary magnetic resonance imaging and whole-body F-FDG PET/CT were performed in all patients.
RESULTS: Serum ACTH at 8 a.m. higher than 161.8 pg/ml as the cut-off value showed the best diagnostic accuracy (73.9%) for the successful localization of the primary lesions. In Cushing disease patients, the pituitary maximum standardized uptake value F-FDG PET/CT (n=11) did not show significant differences compared with that in ectopic ACTH syndrome (EAS) patients (n=20). In terms of EAS, the descending order of maximum standardized uptake value was 13.2±8.3 (4.8-26.4) in pancreatic neuroendocrine tumors (n=4), 7.1±2.4 (3.5-10.1) in mediastinal carcinoid (n=11), and 2.0±0.1 (1.9-2.2) in bronchial carcinoid (n=4). This study first reported the F-FDG PET/CT images of ACTH-secreting olfactory neuroblastoma.
CONCLUSION: Serum ACTH level determines the success rate of localization of the primary ACTH-secreting tumor in ACTH-dependent syndrome. F-FDG PET/CT plays a role in localizing the site for EAS, although it plays a limited role in Cushing disease.

PMID: 30973841 [PubMed - in process]

Multimodality Imaging of Ileal Neuroendocrine (Carcinoid) Tumor.

Fetched: April 13th, 2019, 5:00am GMT

Multimodality Imaging of Ileal Neuroendocrine (Carcinoid) Tumor.

AJR Am J Roentgenol. 2019 Apr 11;:1-9

Authors: Gupta A, Lubner MG, Menias CO, Mellnick VM, Elsayes KM, Pickhardt PJ

Abstract
OBJECTIVE: The purpose of this article is to provide a multimodality imaging review of ileal carcinoid tumor.
CONCLUSION: Ileal carcinoid tumors display a variety of radiologic findings. Delay in diagnosis is common because of initial nonspecific symptoms and subtle imaging findings. Reviewing the multimodality imaging appearance of the primary tumor, metastatic disease, and associated ancillary findings can help improve patient care.

PMID: 30973780 [PubMed - as supplied by publisher]

Neuroendocrine Tumor Therapy with Lutetium-177: A Literature Review.

Fetched: April 13th, 2019, 5:00am GMT

Neuroendocrine Tumor Therapy with Lutetium-177: A Literature Review.

Cureus. 2019 Jan 30;11(1):e3986

Authors: Maqsood MH, Tameez Ud Din A, Khan AH

Abstract
The worldwide incidence of neuroendocrine tumors (NETs) has been increasing. They are a very diverse group of tumors which are commonly found in the gastrointestinal and bronchopulmonary tracts. These tumors usually express somatostatin receptors. Therefore, somatostatin analogs are used for symptom relief as well as treatment. Of the many therapeutic options available, peptide receptor radionuclide therapy (PRRT) has been shown to be very promising. In January 2018, the Food Drug and Authority (FDA) approved 177Lu-Dotatate for use in gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Lutetium is a lower energy beta-emitting radionuclide. The therapeutic use of lutetium-177 (177Lu) has shown better results in advanced gastroenteropancreatic and bronchial neuroendocrine tumors when compared with other therapies available. Adverse effects associated with this therapy include myelotoxicity and nephrotoxicity as the radiopeptides are reabsorbed and accumulate in the renal interstitium. Everolimus is a good and safe option in patients pretreated with 177Lu-Dotatate. Lutetium, in combination with somatostatin analogs, has proven efficacy to treat gastroenteropancreatic neuroendocrine tumors in candidates with somatostatin receptor-positive advanced tumors and normal renal function. This therapy has great potential as it decreases tumor size, improves symptoms, and improves quality of life.

PMID: 30972265 [PubMed]

Signet ring: A rare morphology of metastatic neuroendocrine tumor.

Fetched: April 13th, 2019, 5:00am GMT

Signet ring: A rare morphology of metastatic neuroendocrine tumor.

Indian J Pathol Microbiol. 2019 Apr-Jun;62(2):335-336

Authors: Madakshira MG, Radotra BD, Singh V

PMID: 30971572 [PubMed - in process]

SOX9 is a dose-dependent metastatic fate determinant in melanoma.

Fetched: April 13th, 2019, 5:00am GMT

SOX9 is a dose-dependent metastatic fate determinant in melanoma.

J Exp Clin Cancer Res. 2019 Jan 14;38(1):17

Authors: Yang X, Liang R, Liu C, Liu JA, Cheung MPL, Liu X, Man OY, Guan XY, Lung HL, Cheung M

Abstract
BACKGROUND: In this research, we aimed to resolve contradictory results whether SOX9 plays a positive or negative role in melanoma progression and determine whether SOX9 and its closely related member SOX10 share the same or distinct targets in mediating their functions in melanoma.
METHODS: Immunofluorescence, TCGA database and qPCR were used to analyze the correlation between the expression patterns and levels of SOX9, SOX10 and NEDD9 in melanoma patient samples. AlamarBlue, transwell invasion and colony formation assays in melanoma cell lines were conducted to investigate the epistatic relationship between SOX10 and NEDD9, as well as the effects of graded SOX9 expression levels. Lung metastasis was determined by tail vein injection assay. Live cell imaging was conducted to monitor dynamics of melanoma migratory behavior. RHOA and RAC1 activation assays measured the activity of Rho GTPases.
RESULTS: High SOX9 expression was predominantly detected in patients with distant melanoma metastases whereas SOX10 was present in the different stages of melanoma. Both SOX9 and SOX10 exhibited distinct but overlapping expression patterns with metastatic marker NEDD9. Accordingly, SOX10 was required for NEDD9 expression, which partly mediated its oncogenic functions in melanoma cells. Compensatory upregulation of SOX9 expression in SOX10-inhibited melanoma cells reduced growth and migratory capacity, partly due to elevated expression of cyclin-dependent kinase inhibitor p21 and lack of NEDD9 induction. Conversely, opposite phenomenon was observed when SOX9 expression was further elevated to a range of high SOX9 expression levels in metastatic melanoma specimens, and that high levels of SOX9 can restore melanoma progression in the absence of SOX10 both in vitro and in vivo. In addition, overexpression of SOX9 can also promote invasiveness of the parental melanoma cells by modulating the expression of various matrix metalloproteinases. SOX10 or high SOX9 expression regulates melanoma mesenchymal migration through the NEDD9-mediated focal adhesion dynamics and Rho GTPase signaling.
CONCLUSIONS: These results unravel NEDD9 as a common target for SOX10 or high SOX9 to partly mediate their oncogenic events, and most importantly, reconcile previous discrepancies that suboptimal level of SOX9 expression is anti-metastatic whereas high level of SOX9 is metastatic in a heterogeneous population of melanoma.

PMID: 30642390 [PubMed - indexed for MEDLINE]

[Spinal Schwannoma with Entering-and-exiting-nerve Sign:Report of One Case].

Fetched: April 13th, 2019, 5:00am GMT

[Spinal Schwannoma with Entering-and-exiting-nerve Sign:Report of One Case].

Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2018 Dec 20;40(6):850-852

Authors: Xie XH, Liu MQ, Li BG, Chen ZY

Abstract
Peripheral neurogenic tumors can be featured by entering-and-exiting-nerve sign,which,however,is rarely seen in patients with spinal schwannoma. In this article we report a spinal schwannoma case with entering-and-exiting-nerve sign.

PMID: 30606401 [PubMed - indexed for MEDLINE]

Network assessment of demethylation treatment in melanoma: Differential transcriptome-methylome and antigen profile signatures.

Fetched: April 13th, 2019, 5:00am GMT

Network assessment of demethylation treatment in melanoma: Differential transcriptome-methylome and antigen profile signatures.

PLoS One. 2018;13(11):e0206686

Authors: Jiang Z, Cinti C, Taranta M, Mattioli E, Schena E, Singh S, Khurana R, Lattanzi G, Tsinoremas NF, Capobianco E

Abstract
BACKGROUND: In melanoma, like in other cancers, both genetic alterations and epigenetic underlie the metastatic process. These effects are usually measured by changes in both methylome and transcriptome profiles, whose cross-correlation remains uncertain. We aimed to assess at systems scale the significance of epigenetic treatment in melanoma cells with different metastatic potential.
METHODS AND FINDINGS: Treatment by DAC demethylation with 5-Aza-2'-deoxycytidine of two melanoma cell lines endowed with different metastatic potential, SKMEL-2 and HS294T, was performed and high-throughput coupled RNA-Seq and RRBS-Seq experiments delivered differential profiles (DiP) of both transcriptomes and methylomes. Methylation levels measured at both TSS and gene body were studied to inspect correlated patterns with wide-spectrum transcript abundance levels quantified in both protein coding and non-coding RNA (ncRNA) regions. The DiP were then mapped onto standard bio-annotation sources (pathways, biological processes) and network configurations were obtained. The prioritized associations for target identification purposes were expected to elucidate the reprogramming dynamics induced by the epigenetic therapy. The interactomic connectivity maps of each cell line were formed to support the analysis of epigenetically re-activated genes. i.e. those supposedly silenced by melanoma. In particular, modular protein interaction networks (PIN) were used, evidencing a limited number of shared annotations, with an example being MAPK13 (cascade of cellular responses evoked by extracellular stimuli). This gene is also a target associated to the PANDAR ncRNA, therapeutically relevant because of its aberrant expression observed in various cancers. Overall, the non-metastatic SKMEL-2 map reveals post-treatment re-activation of a richer pathway landscape, involving cadherins and integrins as signatures of cell adhesion and proliferation. Relatively more lncRNAs were also annotated, indicating more complex regulation patterns in view of target identification. Finally, the antigen maps matched to DiP display other differential signatures with respect to the metastatic potential of the cell lines. In particular, as demethylated melanomas show connected targets that grow with the increased metastatic potential, also the potential target actionability seems to depend to some degree on the metastatic state. However, caution is required when assessing the direct influence of re-activated genes over the identified targets. In light of the stronger treatment effects observed in non-metastatic conditions, some limitations likely refer to in silico data integration tools and resources available for the analysis of tumor antigens.
CONCLUSION: Demethylation treatment strongly affects early melanoma progression by re-activating many genes. This evidence suggests that the efficacy of this type of therapeutic intervention is potentially high at the pre-metastatic stages. The biomarkers that can be assessed through antigens seem informative depending on the metastatic conditions, and networks help to elucidate the assessment of possible targets actionability.

PMID: 30485296 [PubMed - indexed for MEDLINE]

Human tumor genomics and zebrafish modeling identify SPRED1 loss as a driver of mucosal melanoma.

Fetched: April 13th, 2019, 5:00am GMT

Human tumor genomics and zebrafish modeling identify SPRED1 loss as a driver of mucosal melanoma.

Science. 2018 11 30;362(6418):1055-1060

Authors: Ablain J, Xu M, Rothschild H, Jordan RC, Mito JK, Daniels BH, Bell CF, Joseph NM, Wu H, Bastian BC, Zon LI, Yeh I

Abstract
Melanomas originating from mucosal surfaces have low mutation burden, genomic instability, and poor prognosis. To identify potential driver genes, we sequenced hundreds of cancer-related genes in 43 human mucosal melanomas, cataloging point mutations, amplifications, and deletions. The SPRED1 gene, which encodes a negative regulator of mitogen-activated protein kinase (MAPK) signaling, was inactivated in 37% of the tumors. Four distinct genotypes were associated with SPRED1 loss. Using a rapid, tissue-specific CRISPR technique to model these genotypes in zebrafish, we found that SPRED1 functions as a tumor suppressor, particularly in the context of KIT mutations. SPRED1 knockdown caused MAPK activation, increased cell proliferation, and conferred resistance to drugs inhibiting KIT tyrosine kinase activity. These findings provide a rationale for MAPK inhibition in SPRED1-deficient melanomas and introduce a zebrafish modeling approach that can be used more generally to dissect genetic interactions in cancer.

PMID: 30385465 [PubMed - indexed for MEDLINE]

Treatment and outcomes in pheochromocytomas and paragangliomas: a study of 110 cases from a single center.

Fetched: April 13th, 2019, 5:00am GMT

Treatment and outcomes in pheochromocytomas and paragangliomas: a study of 110 cases from a single center.

Endocrine. 2018 12;62(3):566-575

Authors: Falhammar H, Kjellman M, Calissendorff J

Abstract
PURPOSE: Many pheochromocytomas and paragangliomas (PPGLs) are nowadays diagnosed as incidentalomas or by screening. This may have changed outcomes.
METHODS: We reviewed 110 consecutive cases of PPGLs. Two cases with concurrent ectopic ACTH-syndrome were excluded.
RESULTS: Sixty-five percent had presented as incidentalomas, 30% as symptomatic PPGLs, and 5% had been screened (previously diagnosed MEN2A). Doxazosin was used in 79%, phenoxybenzamine in 18%, intravenous phentolamine in 1%, and no alpha-blockade in the rest. Laparoscopic surgery was performed in 70%, but 11% were converted to open surgery. Complications of surgery were seen in 20%, and length of stay after surgery was 4 days (2-8) with no correlation with alpha-blockade dose or time. In the whole cohort glycemic disturbances decreased by surgery (47% vs. 9%, P < 0.001). During 9.6 ± 7.2-year (median 8[4-13]) follow-up, 7% developed a new PPGL, 5% a PPGL-metastasis (KI67 > 2% n = 2; KI67 ≤ 1% n = 3; tumor size ≥ 95 mm n = 4), and 13% died (metastatic pheochromocytoma n = 2, hypertensive crisis n = 1, heart failure n = 2, other malignancies n = 5, and unclear n = 4). Surgery improved blood pressure and glycemic disturbances in the incidentaloma and the symptomatic PPGL. Recurrence was more common in the screening group. The symptomatic PPGL group was more likely to die of a PPGL-related cause. Surgery was more challenging in the paragangliomas, with less improvement in glycemic control than in the pheochromocytoma group. However, blood pressure and long-term outcomes were similar.
CONCLUSION: The outcomes seemed slightly better than previous studies. Long-term prognosis was similar between pheochromocytomas and paragangliomas.

PMID: 30220006 [PubMed - indexed for MEDLINE]

SSTR2A expression in medullary thyroid carcinoma is correlated with longer survival.

Fetched: April 13th, 2019, 5:00am GMT

SSTR2A expression in medullary thyroid carcinoma is correlated with longer survival.

Endocrine. 2018 12;62(3):639-647

Authors: de Vries LH, Lodewijk L, Willems SM, Dreijerink KMA, de Keizer B, van Diest PJ, Schepers A, Bonenkamp HJ, van Engen-van Grunsven IACH, Kruijff S, van Hemel BM, Links TP, Nieveen van Dijkum EJM, van Eeden S, Valk GD, Borel Rinkes IHM, Vriens MR

Abstract
PURPOSE: Medullary thyroid carcinoma (MTC) derives from the parafollicular C-cells of the thyroid gland. Somatostatin receptors (SSTRs) are expressed in various neuroendocrine tumours including MTC. The aim of this study was to evaluate SSTR2A as a prognostic factor for MTC, to study distribution of SSTR2A expression within tumours and to compare expression of SSTR2A between primary tumours and corresponding lymph node metastases.
METHODS: Patients who underwent surgery between 1988 and 2014 for MTC from five tertiary referral centres in The Netherlands were included. In total, primary tumours of 114 patients and lymph node metastases of 34 patients were analysed for expression of SSTR2A using a tissue microarray, and correlated with clinicopathological variables and survival.
RESULTS: The mean age of patients was 45.5 years (SD 16.2), 55 patients were male (49.5%). Primary tumours of 58 patients (50.9%) showed SSTR2A expression. In multivariate Cox-regression analysis, SSTR2A positivity correlated independently with better overall survival (OS) (HR 0.3; 95% CI 0.1-1.0). In stage IV MTC patients, 10-year survival rates for SSTR2A-negative and positive patients were 43% and 96%, respectively. In 53.9% of patients with lymph node metastases, expression in primary tumour and lymph node metastases differed.
CONCLUSION: SSTR2A expression is correlated with longer OS in MTC, especially for stage IV patients, suggesting that SSTR2A expression might be a useful prognostic factor in MTC. The SSTR2A status of the primary MTC does not predict expression in lymph node metastases.

PMID: 30128959 [PubMed - indexed for MEDLINE]

Primary pulmonary malignant melanoma: Case report and literature review.

Fetched: April 13th, 2019, 5:00am GMT

Primary pulmonary malignant melanoma: Case report and literature review.

Thorac Cancer. 2018 09;9(9):1185-1189

Authors: Shi Y, Bing Z, Xu X, Cui Y

Abstract
Primary malignant melanoma of the lung is an extremely rare pulmonary carcinoma. Only 45 cases have been reported in the literature. Herein, we report a case of a 46-year-old male patient with an O Rh negative blood type who presented with pulmonary bronchial symptoms and underwent lobectomy. Genetic testing was also performed but no targetable mutations were found, and the patient's PD-L1 RNA level was low. He developed brain metastasis four months after surgery and received radiotherapy but died 21 months after diagnosis. We review the published cases of this rare pulmonary lesion.

PMID: 30062692 [PubMed - indexed for MEDLINE]

Permalink for 'Gamma Knife Radiosurgery for Metastatic Brain Tumors from Malignant Melanomas: A Japanese Multi-Institutional Cooperative and Retrospective Cohort Study (JLGK1501).'

Gamma Knife Radiosurgery for Metastatic Brain Tumors from Malignant Melanomas: A Japanese Multi-Institutional Cooperative and Retrospective Cohort Study (JLGK1501).

Fetched: April 13th, 2019, 5:00am GMT

Gamma Knife Radiosurgery for Metastatic Brain Tumors from Malignant Melanomas: A Japanese Multi-Institutional Cooperative and Retrospective Cohort Study (JLGK1501).

Stereotact Funct Neurosurg. 2018;96(3):162-171

Authors: Matsunaga S, Shuto T, Yamamoto M, Yomo S, Kondoh T, Kobayashi T, Sato M, Okamoto H, Serizawa T, Nagano O, Kenai H, Obara T, Iwai Y, Yasuda S, Hasegawa T, Kubo K, Shidoh S, Mori K, Hayashi M, Inoue A, Onoue S, Gondo M

Abstract
BACKGROUND: The incidences of metastatic brain tumors from malignant melanomas have increased and survival has been prolonged by novel molecular targeted agents and immunotherapy. However, malignant melanomas are uncommon in Asian populations.
OBJECTIVES: We retrospectively analyzed treatment efficacy and identified prognostic factors impacting tumor control and survival in Japanese melanoma patients with brain metastases treated with gamma knife radiosurgery (GKRS).
METHODS: We retrospectively reviewed the medical records of 177 patients with 1,500 tumors who underwent GKRS for brain metastases from malignant melanomas. This study was conducted by the Japanese Leksell Gamma Knife Society (JLGK1501).
RESULTS: Six and 12 months after GKRS, the cumulative incidences of local tumor recurrence were 9.2 and 13.8%. Intratumoral hemorrhage (p < 0.0001) and larger tumor volume (p = 0.001) in GKRS were associated with significantly poorer local control outcomes. The use of immune checkpoint inhibitors before GKRS was significantly associated with symptomatic adverse events (p = 0.037). The median overall survival time after the initial GKRS was 7.3 months. Lower Karnofsky performance status scores (p = 0.016), uncontrolled primary cancer (p < 0.0001), and multiple brain metastases (p = 0.014) significantly influenced unfavorable overall survival outcomes. The cumulative incidences of neurological death 6 and 12 months after GKRS were 9.7 and 17.4%, those of neurological deterioration were 14.2 and 19.6%, and those of new tumor appearance were 34.5 and 40.5%.
CONCLUSIONS: The results of the present multicenter study suggest that GKRS is a relatively effective and safe modality for control of tumor progression in Japanese patients with brain metastases from malignant melanomas.

PMID: 29969770 [PubMed - indexed for MEDLINE]

Enhancing radiosensitivity of melanoma cells through very high dose rate pulses released by a plasma focus device.

Fetched: April 13th, 2019, 5:00am GMT

Enhancing radiosensitivity of melanoma cells through very high dose rate pulses released by a plasma focus device.

PLoS One. 2018;13(6):e0199312

Authors: Buontempo F, Orsini E, Zironi I, Isolan L, Cappellini A, Rapino S, Tartari A, Mostacci D, Cucchi G, Martelli AM, Sumini M, Castellani G

Abstract
Radiation therapy is a useful and standard tumor treatment strategy. Despite recent advances in delivery of ionizing radiation, survival rates for some cancer patients are still low because of recurrence and radioresistance. This is why many novel approaches have been explored to improve radiotherapy outcome. Some strategies are focused on enhancement of accuracy in ionizing radiation delivery and on the generation of greater radiation beams, for example with a higher dose rate. In the present study we proposed an in vitro research of the biological effects of very high dose rate beam on SK-Mel28 and A375, two radioresistant human melanoma cell lines. The beam was delivered by a pulsed plasma device, a "Mather type" Plasma Focus for medical applications. We hypothesized that this pulsed X-rays generator is significantly more effective to impair melanoma cells survival compared to conventional X-ray tube. Very high dose rate treatments were able to reduce clonogenic efficiency of SK-Mel28 and A375 more than the X-ray tube and to induce a greater, less easy-to-repair DNA double-strand breaks. Very little is known about biological consequences of such dose rate. Our characterization is preliminary but is the first step toward future clinical considerations.

PMID: 29958291 [PubMed - indexed for MEDLINE]

Clinical significance of RET and RAS mutations in sporadic medullary thyroid carcinoma: a meta-analysis.

Fetched: April 13th, 2019, 5:00am GMT

Clinical significance of RET and RAS mutations in sporadic medullary thyroid carcinoma: a meta-analysis.

Endocr Relat Cancer. 2018 06;25(6):633-641

Authors: Vuong HG, Odate T, Ngo HTT, Pham TQ, Tran TTK, Mochizuki K, Nakazawa T, Katoh R, Kondo T

Abstract
There are ongoing debates with respect to the prognostic roles of molecular biomarkers in sporadic medullary thyroid carcinoma (MTC). In this study, we aimed at investigating the prognostic value of RET and RAS mutations - the two most common mutations in sporadic MTCs. A search was conducted in four electronic databases. Relevant data were extracted and pooled into odds ratios (OR), mean differences (MD) and corresponding 95% confidence intervals (CI) using the random-effect model. We used Egger's regression test and visual of funnel plots to assess the publication bias. From 2581 studies, we included 23 studies with 964 MTCs for meta-analysis. Overall, the presence of RET mutation was associated with an elevated risk for lymph node metastasis (OR = 3.61; 95% CI = 2.33-5.60), distant metastasis (OR = 2.85; 95% CI = 1.64-4.94), advanced tumor stage (OR = 3.25; 95% CI = 2.02-5.25), tumor recurrence (OR = 3.01; 95% CI = 1.65-5.48) and patient mortality (OR = 2.43; 95% CI = 1.06-5.57). RAS mutation had no significant prognostic value in predicting tumor aggressiveness. To summarize, our results affirmed that RET mutation is a reliable molecular biomarker to identify a group of highly aggressive sporadic MTCs. It can help clinicians better assess patient prognosis and select appropriate treatment decisions.

PMID: 29615431 [PubMed - indexed for MEDLINE]

Merkel cell carcinoma in a patient with relapsing-remitting multiple sclerosis treated with fingolimod.

Fetched: April 13th, 2019, 5:00am GMT

Merkel cell carcinoma in a patient with relapsing-remitting multiple sclerosis treated with fingolimod.

J Neurol Sci. 2017 10 15;381:296-297

Authors: Calvi A, De Riz M, Lecchi E, Pietroboni A, Ghezzi L, Scarioni M, Carandini T, Pellegrinelli A, Maurichi A, Galimberti D, Scarpini E

PMID: 28991701 [PubMed - indexed for MEDLINE]

Polymyositis induced by PD-1 blockade in a patient in hepatitis B remission.

Fetched: April 13th, 2019, 5:00am GMT

Polymyositis induced by PD-1 blockade in a patient in hepatitis B remission.

J Neurol Sci. 2017 10 15;381:22-24

Authors: Ogawa T, Ishitsuka Y, Koguchi-Yoshioka H, Tanaka R, Fujisawa Y, Ishii A, Tamaoka A, Fujimoto M

PMID: 28991685 [PubMed - indexed for MEDLINE]

Holmium-166 Microsphere Radioembolization of Hepatic Malignancies.

Fetched: April 9th, 2019, 5:00am GMT

Holmium-166 Microsphere Radioembolization of Hepatic Malignancies.

Semin Nucl Med. 2019 May;49(3):237-243

Authors: Reinders MTM, Smits MLJ, van Roekel C, Braat AJAT

Abstract
Holmium microspheres have recently become available in the European market as the third type of microspheres for radioembolization of unresectable liver malignancies. Holmium microspheres come with a dedicated administration system, and since these microspheres contain holmium-166 (166Ho) instead of yttrium-90, unique dosing and imaging possibilities have become available as well. In addition, a scout dose of 166Ho microspheres (Conformité Européenne mark is now granted and not pending anymore) can be used instead of 99mTc-macroaggragated albumin during the preparatory angiography procedure. So far, two prospective phase I and phase II clinical studies have been performed on 166Ho radioembolization in a population of liver metastases from mixed origins. These studies showed that a mean whole-liver dose of 60 Gy is safe and induces tumor response. Ongoing trials investigate the effect of 166Ho radioembolization in patients with neuroendocrine tumor metastases, hepatocellular carcinoma, and colorectal cancer metastases. Data derived from these studies will be used to refine the dosing schedule of 60 Gy to the whole liver and determine the optimal level of activity for each patient. This paper discusses several basics and provides an overview of relevant dosing aspects, technical aspects of performing holmium radioembolization, as well as a summary of completed and ongoing clinical studies and the upcoming developments regarding these microspheres.

PMID: 30954190 [PubMed - in process]

Peptide receptor radionuclide therapy in patients with medullary thyroid carcinoma: predictors and pitfalls.

Fetched: April 8th, 2019, 5:00am GMT

Peptide receptor radionuclide therapy in patients with medullary thyroid carcinoma: predictors and pitfalls.

BMC Cancer. 2019 Apr 05;19(1):325

Authors: Beukhof CM, Brabander T, van Nederveen FH, van Velthuysen MF, de Rijke YB, Hofland LJ, Franssen GJH, Fröberg LAC, Kam BLR, Visser WE, de Herder WW, Peeters RP

Abstract
BACKGROUND: For progressive metastatic medullary thyroid carcinoma (MTC), the available treatment options with tyrosine kinase inhibitors result in grade 3-4 adverse events in a large number of patients. Peptide Receptor Radionuclide Therapy (PRRT), which has also been suggested to be a useful treatment for MTC, is usually well tolerated, but evidence on its effectivity is very limited.
METHODS: Retrospective evaluation of treatment effects of PRRT in a highly selected group of MTC patients, with progressive disease or refractory symptoms. In addition, a retrospective evaluation of uptake on historical 111In-DTPA-octreotide scans was performed in patients with detectable tumor size > 1 cm.
RESULTS: Over the last 17 years, 10 MTC patients were treated with PRRT. Four out of 10 patients showed stable disease at first follow-up (8 months after start of therapy) whereas the other 6 were progressive. Patients with stable disease were characterized by a combination of both a high uptake on 111In-DTPA-octreotide scan (uptake grade ≥ 3) and a positive somatostatin receptor type 2a (SSTR2a) expression of the tumor by immunohistochemistry. Retrospective evaluation of historical 111In-DTPA-octreotide scans of 35 non-treated MTC patients revealed low uptake (uptake grade 1) in the vast majority of patients 31/35 (89%) with intermediate uptake (uptake grade 2) in the remaining 4/35 (11%).
CONCLUSIONS: PRRT using 177Lu-octreotate could be considered as a treatment in those patients with high uptake on 111In-DTPA-octreotide scan (uptake grade 3) and positive SSTR2a expression in tumor histology. Since this high uptake was present in a very limited number of patients, this treatment is only suitable in a selected group of MTC patients.

PMID: 30953466 [PubMed - in process]

Permalink for 'Five-year Recurrence-free Survival After Surgery Followed by Oral Chemotherapy for Gastric Cancer With Portal Vein Tumor Thrombosis.'

Five-year Recurrence-free Survival After Surgery Followed by Oral Chemotherapy for Gastric Cancer With Portal Vein Tumor Thrombosis.

Fetched: April 8th, 2019, 5:00am GMT

Five-year Recurrence-free Survival After Surgery Followed by Oral Chemotherapy for Gastric Cancer With Portal Vein Tumor Thrombosis.

Anticancer Res. 2019 Apr;39(4):2233-2238

Authors: Yoshida Y, Beppu T, Kinoshita K, Sato N, Akahoshi S, Yuki H, Saito S, Kitaoka M, Nasu J

Abstract
Gastric cancer with portal vein tumor thrombosis (GC-PVTT) is a rare condition with a very poor prognosis. A 64-year-old man with GC-PVTT was admitted to our hospital. His carcinoembryonic antigen level was slightly elevated (17.4 ng/ml). Upper gastrointestinal endoscopy showed a type-2 gastric lesion (45 mm × 40 mm) in the gastric antrum. The PVTT originated from the main gastric tumor and continued to the superior mesenteric vein. Fluorodeoxyglucose-positron emission tomography showed high uptake both by the main tumor and PVTT. A distal gastrectomy with D2 lymphadenectomy was performed with simultaneous removal of the PVTT. Pathological examination showed a poorly differentiated adenocarcinoma with neuroendocrine differentiation. Adjuvant chemotherapy with S-1 was administered for 1 year. The patient survived for >5 years with no recurrence. Surgical gastrectomy and complete removal of the PVTT followed by S-1 chemotherapy could be a treatment option that offers improved long-term survival for patients with GC-PVTT.

PMID: 30952772 [PubMed - in process]

Frequent and Specific Involvement of Changes of the p16-RB Pathway in Esophageal Neuroendocrine Carcinoma.

Fetched: April 8th, 2019, 5:00am GMT

Frequent and Specific Involvement of Changes of the p16-RB Pathway in Esophageal Neuroendocrine Carcinoma.

Anticancer Res. 2019 Apr;39(4):1927-1934

Authors: Fujimasa K, Ohike N, Norose T, Isobe T, Kikuchi K, Otsuka K, Murakami M, Takimoto M

Abstract
AIM: This study investigated the immunohistochemical expression of retinoblastoma (RB) protein and p16 protein in 10 neuroendocrine carcinomas (NECs), in comparison to two mixed-type NECs; 28 squamous cell carcinomas (SCCs), and 12 carcinosarcomas (CSs) from patients with esophageal cancer.
MATERIALS AND METHODS: Immunohistochemical staining was performed using the avidin-biotin complex detection method. The staining was evaluated as diffusely positive, heterogeneous (in 5-95% of tumor cells), or diffusely negative.
RESULTS: The combination of a diffuse loss of RB and the diffuse overexpression of p16, which is found in highly aggressive malignant tumors and is considered to convincingly suggest changes in the p16-RB pathway, was found in all NECs (10/10). In contrast no mixed-type NECs, one SCC and one CS showed this finding. Coexisting intraepithelial carcinoma was detected in seven NECs and only one lesion showed the combination of diffuse RB loss and p16 overexpression.
CONCLUSION: These data suggest that changes in the p16-RB pathway were universally and specifically involved in the development and invasion of esophageal NECs and that it may be a useful diagnostic marker and a potential therapeutic target.

PMID: 30952735 [PubMed - in process]

Molecular characterization of neuroendocrine-like bladder cancer.

Fetched: April 8th, 2019, 5:00am GMT

Molecular characterization of neuroendocrine-like bladder cancer.

Clin Cancer Res. 2019 Apr 05;:

Authors: Batista da Costa J, Gibb EA, Bivalacqua TJ, Liu Y, Oo HZ, Miyamoto DT, Alshalalfa M, Davicioni E, Wright JL, Dall'Era M, Douglas J, Boormans JL, van der Heijden MS, Wu CL, van Rhijn BW, Gupta S, Grivas P, Mouw KW, Murugan P, Fazli L, Ra S, Konety BR, Seiler R, Daneshmand S, Mian OY, Efstathiou JA, Lotan Y, Black PC

Abstract
PURPOSE: Neuroendocrine (NE) bladder carcinoma is a rare and aggressive variant. Molecular subtyping studies have found that 5-15% of muscle-invasive bladder cancer (MIBC) have transcriptomic patterns consistent with NE bladder cancer in the absence of NE histology. The clinical implications of this NE-like subtype have not been explored in depth.
EXPERIMENTAL DESIGN: Transcriptome-wide expression profiles were generated for MIBC collected from seven institutions and clinical-use of Decipher Bladder. Using unsupervised clustering, we generated a clustering solution on a prospective training cohort (PTC; n=175), developed single-sample classifiers to predict NE tumors, and evaluated the resultant models on a testing radical cystectomy (RC) cohort (n=225). A random forest model was finalized and applied to five validation cohorts (n=1302). Uni- and multivariable survival analyses were used to characterize clinical outcomes.
RESULTS: In the training cohort (PTC), hierarchical clustering using an 84 gene panel showed a cluster of eight patients (4.6%) with highly heterogeneous expression of NE markers in the absence of basal or luminal marker expression. NE-like tumors were identified in 1% to 7.1% of cases in validation cohorts. Patients with NE-like tumors had significantly worse 1-year progression free survival (65% NE-like vs 82% overall; p=0.046) and, after adjusting for clinical and pathological factors, had a 6.4-fold increased risk of all-cause mortality (p=0.001). IHC confirmed the neuronal character of these tumors.
CONCLUSION: A single patient classifier was developed that identifies patients with histological urothelial cancer harboring a NE transcriptomic profile. These tumors represent a high-risk subgroup of MIBC which may require different treatment.

PMID: 30952638 [PubMed - as supplied by publisher]

Paraneoplastic Cast Nephropathy Associated With Pancreatic Mixed Acinar-Neuroendocrine Carcinoma: A Case Report.

Fetched: April 8th, 2019, 5:00am GMT

Paraneoplastic Cast Nephropathy Associated With Pancreatic Mixed Acinar-Neuroendocrine Carcinoma: A Case Report.

Am J Kidney Dis. 2019 Apr 02;:

Authors: Nasr SH, Wehbe E, Said SM, Dasari S, Quoc T, Kurtin PJ

Abstract
Acute kidney injury is common in patients with cancer and may result from sepsis, obstruction, radiotherapy, chemotherapeutic agents, and nonsteroidal anti-inflammatory drugs. Rare reports of acute kidney injury due to cast nephropathy in patients with pancreatic acinar cell carcinoma have been described, but a pathogenetic link between cast nephropathy and carcinoma was not established. We report a patient with pancreatic mixed acinar-neuroendocrine carcinoma who developed severe acute kidney injury. Kidney biopsy showed cast nephropathy characterized by fractured periodic acid-Schiff-negative casts, associated with mononuclear and giant cell reaction. The patient did not have multiple myeloma and casts did not show immunoglobulin light chain restriction on immunofluorescence. Analysis using liquid chromatography-tandem mass spectrometry and immunohistochemistry identified 2 acinar cell-specific proteins, regenerating islet-derived 1α and carboxypeptidase A1, in both tubular casts and tumor cells. Thus, this case demonstrates that solid tumor-specific proteins can be nephropathic by obstructing renal tubules, resulting in acute kidney injury, a previously proposed but not characterized pathophysiologic mechanism for paraneoplastic nephropathy associated with carcinoma.

PMID: 30952487 [PubMed - as supplied by publisher]

Permalink for 'Effect of clinicopathologic features on survival of patients with thymic carcinomas and thymic neuroendocrine tumors: A population-based analysis.'

Effect of clinicopathologic features on survival of patients with thymic carcinomas and thymic neuroendocrine tumors: A population-based analysis.

Fetched: April 8th, 2019, 5:00am GMT

Effect of clinicopathologic features on survival of patients with thymic carcinomas and thymic neuroendocrine tumors: A population-based analysis.

Curr Probl Cancer. 2019 Mar 29;:

Authors: Song Q, Zhang LL, Qi Y, Xing KL, Wu XH

Abstract
BACKGROUND: Thymic carcinomas (TCs) and thymic neuroendocrine tumors (TNETs) are aggressive cancers with poor survival outcome and limited investigation. This study is to investigate clinicopathologic features on TC and TNET patients' prognosis of a large cohort.
MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results database were used to identify a total of 362 TC and TNET patients with documented clinicopathologic features we investigated. The characteristics and overall survival of the TC and TNET patients were studied.
RESULTS: Two hundred and forty TC and 122 TNET patients were identified. For the entire cohort of TC and TNET, histologic type (P < 0.001), tumor size (P = 0.015), Masaoka-Koga stage (P = 0.008), regional node positive (P = 0.004), surgery of primary site (P < 0.001), lymph node surgery (P = 0.013), and chemotherapy (P = 0.001) were considered as significant clinicopathologic features that could affect prognosis of TC and TNET patients in univariate analysis. More importantly, histologic type (P < 0.001), regional nodes positive (P = 0.03) and surgery of primary site (P < 0.001) were able to independently predict overall survival of those patients. In addition, for the cohort of TC, we found that regional nodes positive (P = 0.034) and surgery of primary site (P = 0.001) could be independent predictors of TC patients' survival.
CONCLUSION: Regional nodes detection is essential for TC and TNET patients. Surgery of primary site is the preferred primary treatment for those patients.

PMID: 30952367 [PubMed - as supplied by publisher]

Permalink for 'A comparison of adult rhabdomyosarcoma and high grade neuroendocrine carcinoma of the urinary bladder reveals novel PPP1R12A fusions in rhabdomyosarcoma.'

A comparison of adult rhabdomyosarcoma and high grade neuroendocrine carcinoma of the urinary bladder reveals novel PPP1R12A fusions in rhabdomyosarcoma.

Fetched: April 6th, 2019, 5:00am GMT

A comparison of adult rhabdomyosarcoma and high grade neuroendocrine carcinoma of the urinary bladder reveals novel PPP1R12A fusions in rhabdomyosarcoma.

Hum Pathol. 2019 Apr 01;:

Authors: Gupta S, Sosa CP, Kosari F, Folpe A, Bhinge KN, Yang L, Agahi A, Johnson SH, Frank I, Boorjian SA, Hansel DE, Al-Ahmadie HA, Reuter VE, Vasmatzis G, Jimenez RE, Herrera-Hernandez L, Cheville JC

Abstract
Some rhabdomyosarcomas and sarcomatoid carcinomas with heterologous rhabdomyosarcomatous elements resemble high-grade neuroendocrine carcinoma, creating a diagnostic difficulty. The purpose of this study was to characterize the overlap of adult genitourinary rhabdomyosarcomas, excluding those occurring at paratesticular sites, with high-grade neuroendocrine carcinoma and identify features helpful in their separation. Seventeen cases of rhabdomyosarcoma (eleven from the urinary bladder and three each from kidney and prostate) were compared to ten cases of high-grade neuroendocrine carcinoma from the urinary bladder. These tumors were analyzed by immunohistochemistry for desmin, MyoD1, myogenin, chromogranin, synaptophysin, CD56, TTF1 and ASCL1 and RNAseq was performed on four cases of bladder rhabdomyosarcoma (two rhabdomyosarcomas and two sarcomatoid-rhabdomyosarcoma) and ten cases of bladder high-grade neuroendocrine carcinoma. This was compared to public data from 414 typical urothelial carcinomas from The Cancer Genome Atlas dataset. Morphologic and immunophenotypic overlap with high-grade neuroendocrine carcinoma was seen in half of the bladder tumors, which included four rhabdomyosarcomas and two sarcomatoid-rhabdomyosarcoma. RNAseq confirmed expression of neuroendocrine markers in these cases (two rhabdomyosarcomas and two sarcomatoid-rhabdomyosarcoma). Differential neuroendocrine differentiation was highlighted by ASCL1 protein expression only in high-grade neuroendocrine carcinoma. Moreover, both a pure alveolar rhabdomyosarcoma and sarcomatoid-rhabdomyosarcoma of the urinary bladder demonstrated a fusion involving PPP1R12A. In summary, adult rhabdomyosarcomas of the urinary bladder are molecularly distinct from high-grade neuroendocrine carcinomas based on specific patterns of expression of myogenic and epithelial to mesenchymal transition-related transcription factors as well as the presence of a novel PPP1R12A fusion which is seen in a subset of cases.

PMID: 30946934 [PubMed - as supplied by publisher]

Periprocedural Management of Patients Undergoing Liver Resection or Embolotherapy for Neuroendocrine Tumor Metastases.

Fetched: April 6th, 2019, 5:00am GMT

Periprocedural Management of Patients Undergoing Liver Resection or Embolotherapy for Neuroendocrine Tumor Metastases.

Pancreas. 2019 Apr 03;:

Authors: Kwon DH, Paciorek A, Mulvey CK, Chan H, Fidelman N, Meng L, Nakakura EK, Zhang L, Bergsland EK, Van Loon K

Abstract
OBJECTIVES: The objective of this study was to describe the periprocedural management of patients with well-differentiated neuroendocrine tumors with hepatic metastases who underwent liver-directed procedures.
METHODS: We performed a retrospective review of patients with metastatic neuroendocrine tumors who underwent liver resection, ablation, or embolotherapy at a single center from 2012 to 2016. The primary outcome was occurrence of documented carcinoid crisis (CC) or hemodynamic instability (HDI), defined as 10 minutes or more of systolic blood pressure less than 80 or greater than 180 mm Hg, or pulse greater than 120 beats per minute.
RESULTS: We identified 75 patients who underwent liver resection/ablation (n = 38) or embolotherapy (n = 37). Twenty-four patients (32%) experienced CC or HDI (CC/HDI); CC occurred in 3 patients. No clinicopathologic or procedural factors, including procedure type, octreotide or long-acting somatostatin analog use, and history of carcinoid syndrome, were associated with CC/HDI. Grades 2 to 4 complications were reported in 42% of patients who experienced CC/HDI versus in 16% of patients who did not experience CC/HDI (P < 0.05).
CONCLUSIONS: A significant portion of patients developed CC/HDI, and these patients were more likely to develop severe postprocedural complications. Periprocedural octreotide use was not associated with lower CC/HDI occurrence, but continued use is advised given its safety profile until additional studies definitively demonstrate lack of benefit.

PMID: 30946246 [PubMed - as supplied by publisher]

Permalink for 'Loss of Menin Expression by Immunohistochemistry in Pancreatic Neuroendocrine Tumors: Comparison Between Primary and Metastatic Tumors.'

Loss of Menin Expression by Immunohistochemistry in Pancreatic Neuroendocrine Tumors: Comparison Between Primary and Metastatic Tumors.

Fetched: April 6th, 2019, 5:00am GMT

Loss of Menin Expression by Immunohistochemistry in Pancreatic Neuroendocrine Tumors: Comparison Between Primary and Metastatic Tumors.

Pancreas. 2019 Apr 03;:

Authors: Samdani RT, Wasylishen AR, Halperin DM, Dasari A, Yao JC, Rashid A, Estrella JS

Abstract
OBJECTIVES: Molecular characterization of sporadic pancreatic neuroendocrine tumors (PanNETs) demonstrates frequent alterations in MEN1. As the role of menin immunohistochemistry as a potential biomarker is being developed, knowledge of whether the pattern of menin expression is the same in primary tumors and distant metastases may help in patient care. Therefore, we compared patterns of menin expression in matched primary tumors and metastases.
METHODS: We evaluated loss of menin nuclear expression by immunohistochemistry in 44 matched samples of primary and metastatic PanNETs and concordance in staining pattern between primary and metastatic tumors.
RESULTS: Menin nuclear expression was lost in 18 (41%) of 44 primary tumors and 17 (39%) of 44 metastases. Concordant loss of menin expression was observed in 41 cases (93%); discordance was observed in 3 cases (7%; 95% confidence interval, 1.4%-18.7%), including 2 with loss in the primary tumor but not the metastasis.
CONCLUSIONS: The concordance of menin staining between primary tumor and metastasis in most cases suggests that menin loss is an early event in PanNET tumorigenesis. The discordant expression observed in a small subset may be a source of menin-directed therapy failure; thus, repeat assessment of metastases may be helpful for treatment selection.

PMID: 30946241 [PubMed - as supplied by publisher]

Predicting Survival of Small Intestine Neuroendocrine Tumors: Experience From a Major Referral Center.

Fetched: April 6th, 2019, 5:00am GMT

Predicting Survival of Small Intestine Neuroendocrine Tumors: Experience From a Major Referral Center.

Pancreas. 2019 Apr 03;:

Authors: Kelly S, Aalberg J, Agathis A, Phillips K, Haile S, Haines K, Kang Kim M, Divino CM

Abstract
OBJECTIVE: Neuroendocrine tumors (NETs) comprise 41.8% of small intestine malignancies. The NET nomogram is a 15-item prognostic tool that includes relevant factors for guiding management decisions. This is the first external validation of this tool among American patients at a tertiary treatment center.
METHODS: Patients who underwent surgical intervention from 2005 to 2017 were screened by retrospective chart review. Nomogram scores were calculated following the methods outlined by Modlin et al (Neuroendocrinology. 2010;92:143-157). Validation assessed the association between nomogram scores and survival using Wilcoxon test and Cox regression.
RESULTS: Among the 121 patients selected, the NET nomogram significantly predicted survival as a continuous variable (P < 0.01) and when dichotomized using 83 points to distinguish low-risk versus high-risk groups (P < 0.01). However, the nomogram was not universally applicable as even at our specialty center, variables such as chromogranin A and urinary 5-hydroxyindoleacetic acid are not routinely collected, whereas others, like tumor grade, do not reflect the most recently updated classifications.
CONCLUSION: The NET nomogram accurately identified patients at low and high risk of death. However, revision to update prognosticators could improve its usefulness for predicting survival of small intestine NETs.

PMID: 30946234 [PubMed - as supplied by publisher]

Outcomes of laparoscopic tumor ablation for neuroendocrine liver metastases: a 20-year experience.

Fetched: April 6th, 2019, 5:00am GMT

Outcomes of laparoscopic tumor ablation for neuroendocrine liver metastases: a 20-year experience.

Surg Endosc. 2019 Apr 03;:

Authors: Kose E, Kahramangil B, Aydin H, Donmez M, Takahashi H, Aucejo F, Siperstein A, Berber E

Abstract
BACKGROUND: Since neuroendocrine tumors have an indolent behavior, studies looking at oncologic outcomes should report a long-term follow-up. Over the years, we have been treating selected patients with neuroendocrine liver metastases (NELM) with laparoscopic ablation (LA) and reported favorable local tumor control. The aim of this study is to see whether this local efficacy translates into long-term oncologic outcomes.
METHODS: This was an IRB-approved study of patients who underwent LA for NELM at a single center. Overall and progression-free survivals were analyzed using Kaplan-Meier and Cox proportional hazards model.
RESULTS: Study included 58 women and 71 men with a median age of 58 (IQR 47-67) years. Tumor type included carcinoid (n = 92), pancreatic islet cell (n = 28), and medullary thyroid cancer (n = 9). There was a median of 6 (IQR 3-8) tumors, measuring 1.6 (IQR 1.1-2.4) cm. At a median follow-up of 73 (IQR 34-135) months, local liver recurrence per patient, new liver recurrence, and new extrahepatic recurrence rates were 22, 68, and 33%, respectively. Local tumor recurrence per lesion was 5% (n = 42/770). Median overall survival was 125 months, with 5-year, and 10-year overall survivals being, 76%, and 59%, respectively; and median disease-free survival was 13 months, with 5-year, and 10-year progression-free survivals being 26%, and 6%, respectively. On Cox proportional hazards model, overall survival was independently predicted by tumor size, grade, and resection status of primary.
CONCLUSION: To our knowledge, this is the largest single-center experience with the longest follow-up regarding the utilization of LA for NELM. Our results demonstrate that in selected patients, LA achieves a 95% local tumor control and 59% 10-year overall survival.

PMID: 30945061 [PubMed - as supplied by publisher]

Prognostic Threshold of Neuroendocrine Differentiation in Gastric Carcinoma: a Clinicopathological Study of 945 Cases.

Fetched: April 6th, 2019, 5:00am GMT

Icon for The Korean Gastric Cancer Association

Prognostic Threshold of Neuroendocrine Differentiation in Gastric Carcinoma: a Clinicopathological Study of 945 Cases.

J Gastric Cancer. 2019 Mar;19(1):121-131

Authors: Zou Y, Chen L, Wang X, Chen Y, Hu L, Zeng S, Wang P, Li G, Huang M, Wang L, He S, Li S, Jian L, Zhang S

Abstract
Purpose: The significance of neuroendocrine differentiation (NED) in gastric carcinoma (GC) is controversial, leading to ambiguous concepts in traditional classifications. This study aimed to determine the prognostic threshold of meaningful NED in GC and clarify its unclear features in existing classifications.
Materials and Methods: Immunohistochemical staining for synaptophysin, chromogranin A, and neural cell adhesion molecule was performed for 945 GC specimens. Survival analysis was performed using the log-rank test and univariate/multivariate models with percentages of NED (PNED) and demographic and clinicopathological parameters.
Results: In total, 275 (29.1%) cases were immunoreactive to at least 1 neuroendocrine (NE) marker. GC-NED was more common in the upper third of the stomach. PNED, and Borrmann's classification and tumor, lymph node, metastasis stages were independent prognostic factors. The cutoff PNED was 10%, beyond which patients had significantly worse outcomes, although the risk did not increase with higher PNED. Tumors with ≥10% NED tended to manifest as Borrmann type III lesion with mixed/diffuse morphology and poorer histological differentiation; the NE components in this population mainly grew in insulae/nests, which differed from the predominant growth pattern (glandular/acinar) in GC with <10% NED.
Conclusions: GC with ≥10% NED should be classified as a distinct subtype because of its worse prognosis, and more attention should be paid to the necessity of additional therapeutics for NE components.

PMID: 30944765 [PubMed]

The 1, 2, 3, 4 of carcinoid heart disease: Comprehensive cardiovascular imaging is the mainstay of complex surgical treatment.

Fetched: April 6th, 2019, 5:00am GMT

The 1, 2, 3, 4 of carcinoid heart disease: Comprehensive cardiovascular imaging is the mainstay of complex surgical treatment.

Oncol Lett. 2019 May;17(5):4126-4132

Authors: Balanescu DV, Donisan T, Lopez-Mattei J, Hassan S, Kim P, Dasari A, Halperin D, Yao J, Kar B, Gregoric I, Balanescu SM, Iliescu C

Abstract
Carcinoid heart disease (CHD) is a rare complication of neuroendocrine tumors, most commonly involving the tricuspid and pulmonary valves. The mitral and aortic valves can also be affected, albeit rarely, in certain circumstances such as the presence of a patent foramen ovale. Transthoracic echocardiogram is generally considered the key imaging modality, but cardiac magnetic resonance can add valuable information, particularly in the assessment of pulmonary valve function or multivalvular disease. Previously, surgical management of CHD carried high mortality, as a result of less advanced surgical techniques and of late intervention, reserved for cases of severely symptomatic heart failure. Modern approaches are associated with significantly improved survival rates, even in multivalvular, complex cases. Valve replacement can provide survival benefits in patients with CHD, but the optimal timing for the intervention is uncertain, with data suggesting a trend of improved survival with earlier intervention. A comprehensive imaging assessment may contribute to establishing optimal surgical timing. This approach may shift the main driver of mortality from the cardiac involvement to the primary malignancy and lead to improved outcomes. We present a series of imaging findings in CHD patients who have successfully undergone simultaneous surgical replacement with bioprosthetic valves of 1 to 4 heart valves. The surgical decision in these patients was based on a multimodality cardiovascular approach, including transthoracic and transesophageal echocardiography and cardiac magnetic resonance. The patients had uncomplicated postoperative courses, significant symptomatic relief from heart failure symptoms, and there was no cardiovascular mortality. Early recognition of CHD with a multimodality approach may improve outcome, even in complex cases. Bioprosthetic valves are generally preferred in CHD due to decreased need for anticoagulation, despite concern for premature degeneration. A collaboration between the Oncology and Cardiology teams is essential for the long-term management of CHD patients.

PMID: 30944605 [PubMed]

Network meta-analysis of therapies for previously untreated advanced BRAF-mutated melanoma.

Fetched: April 6th, 2019, 5:00am GMT

Network meta-analysis of therapies for previously untreated advanced BRAF-mutated melanoma.

Cancer Treat Rev. 2019 Mar;74:43-48

Authors: Zoratti MJ, Devji T, Levine O, Thabane L, Xie F

Abstract
BACKGROUND: The spectrum of treatment options for patients with metastatic BRAF-mutated melanoma is broad, spanning multiple treatment classes. However, there is a lack of head-to-head evidence comparing targeted and immunotherapies. The purpose of this study is to conduct a network meta-analysis (NMA) in previously untreated, BRAF-mutated melanoma patients and estimate the relative efficacy of systemic therapies for this patient population at the treatment level.
METHODS: The literature review included searches of MEDLINE, EMBASE, and the Cochrane Central Registry of Controlled Trials (CENTRAL) to November 2018. Randomized controlled trials of previously untreated patients with advanced melanoma were eligible if at least one intervention was either a targeted or immune therapy. Relative treatment effects were estimated by fixed effect Bayesian NMAs on progression-free survival (PFS) and overall survival (OS), based on the hazard ratio.
RESULTS: Combination dabrafenib with trametinib (HR 0.22 [95% CrI 0.17, 0.28] vs dacarbazine) and combination vemurafenib with cobimetinib (HR 0.22 [95% CrI 0.17, 0.29] vs dacarbazine) were likely to rank as the most favorable treatment options for PFS, while combination nivolumab with ipilimumab was likely to be the most efficacious in terms of OS (HR 0.33 [0.24, 0.47] vs dacarbazine).
CONCLUSIONS AND RELEVANCE: The findings highlight the efficacy of combination PD-1 with CTLA-4 inhibitors and combination BRAF with MEK inhibitors in the treatment of advanced melanoma. However, as few trials informed each treatment comparison, research is needed to further refine our understanding of this complex and rapidly evolving treatment landscape.

PMID: 30798169 [PubMed - indexed for MEDLINE]

Comparative efficacy and safety of combination therapies for advanced melanoma: a network meta-analysis.

Fetched: April 6th, 2019, 5:00am GMT

Comparative efficacy and safety of combination therapies for advanced melanoma: a network meta-analysis.

BMC Cancer. 2019 Jan 09;19(1):43

Authors: An Q, Liu Z

Abstract
BACKGROUND: Currently, the major treatment modalities of advanced melanoma are immune check point and mitogen-activated protein kinase (MAPK) pathway inhibitors. As lacking head-to-head randomizedcontrolled trials (RCTs) comparing immune check point and MAPK pathway inhibitors, we evaluated the efficacy and toxicity with different treatment combinations of immune check point or MAPK pathway inhibitors for advanced melanoma by network meta-analysis.
METHODS: We searched for RCTs in Pubmed, Embase, Ovid MEDLINE, Web of Science and Cochrane Central Register for Controlled Trials through March 2017. Two reviewers performed a network meta-analysis by assessing the hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), as well as by evaluating serious adverse events (SAEs).
RESULTS: Twenty-four eligible RCTs involving 10,951 patients assigned to 11 treatment modalities were included. The combination of BRAF and MEK inhibitors demonstrated an improved OS benefit compared with all the other treatments except programmed death-1/ligand-1 (PD-1/L1) blockade because the difference in OS between the BRAF-MEK inhibitor combination and PD-1 blockade (HR: 0.85; 95% credible interval (CrI): 0.59, 1.21) was not significant. For PFS, the BRAF and MEK inhibitor combination showed a significant advantage compared with other treatments apart from the combination of PD-1/L1 and cytotoxic T lymphocyte-associated antigen-4(CTLA-4) blockade (HR:0.61; 95% CrI: 0.30, 1.25). The MEK inhibitor combined with chemotherapy was associated with the highest risk of SAEs (HR: 1.76 95% CrI: 1.21, 2.48).
CONCLUSIONS: The combination of BRAF and MEK inhibitors exhibited a survival advantage in OS and PFS and comparable risk of toxicity compared with chemotherapy.

PMID: 30626368 [PubMed - indexed for MEDLINE]

Permalink for 'Optimization and in-vitro/in-vivo evaluation of doxorubicin-loaded chitosan-alginate nanoparticles using a melanoma mouse model.'

Optimization and in-vitro/in-vivo evaluation of doxorubicin-loaded chitosan-alginate nanoparticles using a melanoma mouse model.

Fetched: April 6th, 2019, 5:00am GMT

Optimization and in-vitro/in-vivo evaluation of doxorubicin-loaded chitosan-alginate nanoparticles using a melanoma mouse model.

Int J Pharm. 2019 Feb 10;556:1-8

Authors: Yoncheva K, Merino M, Shenol A, Daskalov NT, Petkov PS, Vayssilov GN, Garrido MJ

Abstract
The present study evaluates the potential of encapsulated doxorubicin to reduce both the viability of melanoma cells and the tumor growth in a mouse melanoma model. The prepared doxorubicin loaded chitosan/alginate nanoparticles possessed mean diameter around 300 nm and negative zeta-potential. Classical molecular dynamic simulations revealed that the high encapsulation efficiency (above 90%) was mainly due to electrostatic interaction between doxorubicin and sodium alginate, although dipole-dipole and hydrophobic interactions might also contribute. The in vitro dissolution tests showed slower doxorubicin release in slightly alkaline medium (pH = 7.4) and faster release in acid one (pH = 5.5), indicating that higher concentration of doxorubicin might reach the acidic tumor tissue. The free and the encapsulated doxorubicin decreased the viability of melanoma cell lines (B16-F10 and B16-OVA) in a similar degree. However, the cytotoxic effect of the encapsulated doxorubicin still occurred in the more resistant B16-F10 cells even after removing the extracellular drug. The experiments on a syngeneic melanoma mouse model revealed that free and encapsulated doxorubicin elicited the control of the tumor growth (dose of 3 mg/kg). Thus, the encapsulation of doxorubicin into chitosan/alginate nanoparticles could be considered advantageous because of the better intracellular accumulation and longer cytotoxic effect on the investigated melanoma cells.

PMID: 30529664 [PubMed - indexed for MEDLINE]

Algal oil rich in n-3 polyunsaturated fatty acids suppresses B16F10 melanoma lung metastasis by autophagy induction.

Fetched: April 6th, 2019, 5:00am GMT

Algal oil rich in n-3 polyunsaturated fatty acids suppresses B16F10 melanoma lung metastasis by autophagy induction.

Food Funct. 2018 Dec 13;9(12):6179-6186

Authors: Tan RH, Wang F, Fan CL, Zhang XH, Zhao JS, Zhang JJ, Yang Y, Xi Y, Zou ZQ, Bu SZ

Abstract
Melanoma is a malignant tumor that arises from epidermal melanocytes with high morbidity and mortality, and currently, there are no effective conventional genotoxic treatments or systematic treatment. Increasing evidence shows that n-3 polyunsaturated fatty acids (PUFAs) exhibit anti-melanoma activity, but their anti-melanoma mechanism remains elusive. Here, C57BL/6 mice were injected with B16F10 melanoma cells via a tail vein to establish a lung metastasis model. n-3 PUFAs were significantly increased in lung metastatic tissues from mice treated with algal oil, especially rich in docosahexaenoic acid (DHA). Algal oil treatment significantly suppressed pulmonary metastases and outgrowth of melanoma cells, which was associated with autophagy induction, as evidenced by an increase in LC3-II levels. In addition, algae oil-triggered autophagy was mediated by inactivation of the mammalian target of rapamycin (mTOR) and p38 mitogen-activated protein (MAP) kinase, and activation of c-Jun N-terminal kinases (JNKs), which led to a decrease in p62 accumulation and decreased secretion of proinflammatory cytokine interleukin-1β (IL-1β). These results suggest that algal oil exerts its antitumourigenic activities via autophagy-mediated p62 elimination and anti-inflammatory properties.

PMID: 30450498 [PubMed - indexed for MEDLINE]

Differences in cutaneous melanoma treatment and patient satisfaction.

Fetched: April 6th, 2019, 5:00am GMT

Differences in cutaneous melanoma treatment and patient satisfaction.

PLoS One. 2018;13(10):e0205517

Authors: Wikstrom JD, Lundeberg L, Frohm-Nilsson M, Girnita A

Abstract
Although clinical guidelines exist, the management of patients with cutaneous melanoma (CM) is a complex process that may vary between different care providers with potential dysfunctions ultimately mirrored in the overall patient satisfaction. The aim of the present study was to investigate the CM management as related to lead times, surgical quality and diagnosis communication with the hypothesis that the care may differ between providers and disparities may impact patient satisfaction. Medical records of 181 patients were retrospectively analyzed with parallel patient satisfaction evaluation by telephone interviews. Overall mean lead times from initial diagnosis until completion of all surgery and histopathology reports were 80-100 days and delays occurred at every step of the process. General practitioners performed excision biopsies faster however this was mitigated by slower histopathology processing. University level CM care showed less lag time between excision biopsy, wide local excision for thick melanomas and histopathology confirmation. University level care operated with twice the surgical margin as compared to general practitioners and non-university level specialists. Male patients had larger excision biopsy margins and significantly shorter lead times than female patients. Patient satisfaction rates were generally higher in the academic hospitals as compared to general practitioners and non-university dermatology clinics. Surprisingly, there was no correlation between lead times and patient satisfaction. Taken together, CM show substantial variation and caution should be practiced when using patient satisfaction as a quality indicator.

PMID: 30359387 [PubMed - indexed for MEDLINE]

Permalink for 'Acquisition of resistance to vemurafenib leads to interleukin-10 production through an aberrant activation of Akt in a melanoma cell line.'

Acquisition of resistance to vemurafenib leads to interleukin-10 production through an aberrant activation of Akt in a melanoma cell line.

Fetched: April 6th, 2019, 5:00am GMT

Acquisition of resistance to vemurafenib leads to interleukin-10 production through an aberrant activation of Akt in a melanoma cell line.

J Dermatol. 2018 Dec;45(12):1434-1439

Authors: Inozume T, Tsunoda T, Morisaki T, Harada K, Shirasawa S, Kawamura T

Abstract
Serine/threonine-protein kinase B-Raf (BRAF) inhibitors are very effective in treating melanoma with BRAF mutations. BRAF inhibitors suppress aberrant growth of melanoma cells caused by BRAF mutations. BRAF mutations reportedly result in melanoma cells releasing immunosuppressive factors, and BRAF inhibitors elicit anti-melanoma immune responses by reducing such factors. However, immunological characteristics of tumor cells that acquire resistance to BRAF inhibitors remain unknown. Here, we compared immunological characteristics between a melanoma cell line and its vemurafenib-resistant subline. No differences were observed in the status of BRAF mutations, expression of surface molecules related to antitumor T-cell responses or recognition by human leukocyte antigen-A*0201-matched melanoma-specific cytotoxic T lymphocytes in a short-term co-culture assay. However, resistant tumor cells released high amounts of interleukin-10 depending on aberrant activation of Akt signaling, and dendritic cell functions were considerably suppressed by culture supernatants of the resistant cells. Our findings demonstrated a novel immunological mechanism contributing to tumor growth owing to drug resistance to BRAF inhibitors.

PMID: 30222203 [PubMed - indexed for MEDLINE]

Profile fluctuation of peripheral blood in advanced melanoma patients treated with nivolumab.

Fetched: April 6th, 2019, 5:00am GMT

Profile fluctuation of peripheral blood in advanced melanoma patients treated with nivolumab.

J Dermatol. 2018 Dec;45(12):1452-1455

Authors: Saito R, Sawada Y, Saito-Sasaki N, Yamamoto K, Yoshioka H, Ohmori S, Yoshioka M, Okada E, Nakamura M

Abstract
Melanoma is a malignant tumor of the melanocytes with an unfavorable clinical behavior. Nivolumab, a representative anti-programmed death 1 (PD-1) antibody, has recently been used for the treatment of metastatic malignant melanoma. However, there have been few appropriate biomarkers predicting the effect of nivolumab before the administration. Furthermore, the detailed characteristics of peripheral blood mononuclear cell (PBMC) profiles during nivolumab treatment remains unclear. In this study, we investigated fluctuations of PBMC profile during nivolumab treatment. PBMC analysis showed T-helper (Th)2-dominant conditions after a first course of nivolumab treatment. In a favorable case treated with nivolumab, a Th1/T-cytotoxic 1 shift was observed after nivolumab was administrated. These results suggest that flow cytometric analysis of PBMC may be helpful for the treatment of nivolumab.

PMID: 30204257 [PubMed - indexed for MEDLINE]

The Puzzle of Predicting Response to Immune Checkpoint Blockade.

Fetched: April 6th, 2019, 5:00am GMT

The Puzzle of Predicting Response to Immune Checkpoint Blockade.

EBioMedicine. 2018 07;33:18-19

Authors: Onyshchenko M

PMID: 29934042 [PubMed - indexed for MEDLINE]

Permalink for 'siRNA - Mediated LRP/LR knock-down reduces cellular viability of malignant melanoma cells through the activation of apoptotic caspases.'

siRNA - Mediated LRP/LR knock-down reduces cellular viability of malignant melanoma cells through the activation of apoptotic caspases.

Fetched: April 6th, 2019, 5:00am GMT

siRNA - Mediated LRP/LR knock-down reduces cellular viability of malignant melanoma cells through the activation of apoptotic caspases.

Exp Cell Res. 2018 07 01;368(1):1-12

Authors: Rebelo TM, Vania L, Ferreira E, Weiss SFT

Abstract
The 37 kDa/67 kDa laminin receptor (LRP/LR) is over-expressed in tumor cells and has been implicated in several tumourigenic processes such as metastasis and telomerase activation, however, more importantly the focus of the present study is on the maintenance of cellular viability and the evasion of apoptosis. The aim of the study was to investigate the role of LRP/LR on the cellular viability of early (A375) and late stage (A375SM) malignant melanoma cells. Flow cytometry and western blot analysis revealed that A375SM cells contain more cell-surface and total LRP/LR levels in comparison to the A375 cells, respectively. In order to determine the effect of LRP/LR on cell viability and apoptosis, LRP was down-regulated via siRNA technology. MTT assays revealed that LRP knock-down led to significant reductions in the viability of A375 and A375SM cells. Confocal microscopy indicated nuclear morphological changes suggestive of apoptotic induction in both cell lines and Annexin-V FITC/PI assays confirmed this observation. Additionally, caspase-3 activity assays revealed that apoptosis was induced in both cell lines after siRNA-mediated down-regulation of LRP. Caspase-8 and -9 activity assays suggested that post LRP knock-down; A375 cells undergo apoptosis solely via the extrinsic pathway, while A375SM cells undergo apoptosis via the intrinsic pathway.
IMPLICATIONS: siRNAs mediated LRP knock-down might represent a powerful alternative therapeutic strategy for the treatment of malignant melanoma through the induction of apoptosis.

PMID: 29653110 [PubMed - indexed for MEDLINE]

A Pck1-directed glycogen metabolic program regulates formation and maintenance of memory CD8+ T cells.

Fetched: April 6th, 2019, 5:00am GMT

A Pck1-directed glycogen metabolic program regulates formation and maintenance of memory CD8+ T cells.

Nat Cell Biol. 2018 01;20(1):21-27

Authors: Ma R, Ji T, Zhang H, Dong W, Chen X, Xu P, Chen D, Liang X, Yin X, Liu Y, Ma J, Tang K, Zhang Y, Peng Y, Lu J, Zhang Y, Qin X, Cao X, Wan Y, Huang B

Abstract
CD8+ memory T (Tm) cells are fundamental for protective immunity against infections and cancers 1-5 . Metabolic activities are crucial in controlling memory T-cell homeostasis, but mechanisms linking metabolic signals to memory formation and survival remain elusive. Here we show that CD8+ Tm cells markedly upregulate cytosolic phosphoenolpyruvate carboxykinase (Pck1), the hub molecule regulating glycolysis, tricarboxylic acid cycle and gluconeogenesis, to increase glycogenesis via gluconeogenesis. The resultant glycogen is then channelled to glycogenolysis to generate glucose-6-phosphate and the subsequent pentose phosphate pathway (PPP) that generates abundant NADPH, ensuring high levels of reduced glutathione in Tm cells. Abrogation of Pck1-glycogen-PPP decreases GSH/GSSG ratios and increases levels of reactive oxygen species (ROS), leading to impairment of CD8+ Tm formation and maintenance. Importantly, this metabolic regulatory mechanism could be readily translated into more efficient T-cell immunotherapy in mouse tumour models.

PMID: 29230018 [PubMed - indexed for MEDLINE]

The two-hit hypothesis and paraganglioma of the head and neck.

Fetched: April 6th, 2019, 5:00am GMT

The two-hit hypothesis and paraganglioma of the head and neck.

J Laryngol Otol. 2017 Jul;131(7):563

Authors: Hussain M, Fisher E, Youngs R, Fishman J

PMID: 28583225 [PubMed - indexed for MEDLINE]

Animal Models of Uveal Melanoma for Localized Interventions.

Fetched: April 6th, 2019, 5:00am GMT

Animal Models of Uveal Melanoma for Localized Interventions.

Crit Rev Oncog. 2017;22(3-4):187-194

Authors: Bontzos G, Detorakis ET

Abstract
Uveal melanoma is the most common primary intraocular malignancy in adults, carrying a significant risk for death from metastatic disease. Treatment efforts aim toward local tumor control and early detection and management of metastases. Animal models are a valuable tool in the study of the molecular, genetic, and cellular events associated with the development of uveal melanoma and the evaluation of the therapeutic potential for various treatment methods. So far, several spontaneous, transgenetic, or induced animal models have been used, each presenting distinct advantages and disadvantages. This review article systematically presents an analysis of these animal models aimed at localized interventions; We aim to assist researchers with the selection of the optimal animal model based on their particular research targets.

PMID: 29604898 [PubMed - indexed for MEDLINE]

Effects of novel somatostatin-dopamine chimeric drugs in 2D and 3D cell culture models of neuroendocrine tumors.

Fetched: April 4th, 2019, 5:00am GMT

Effects of novel somatostatin-dopamine chimeric drugs in 2D and 3D cell culture models of neuroendocrine tumors.

Endocr Relat Cancer. 2019 Apr 01;:

Authors: Herrera Martínez AD, van den Dungen R, Dogan F, van Koetsveld PM, Culler M, de Herder WW, Luque RM, Feelders RA, Hofland L

Abstract
Control of symptoms related to hormonal hypersecretion by functioning neuroendocrine tumors (NETs) is challenging. New therapeutic options are required. Since novel in vitro tumor models seem to better mimic the tumor in vivo conditions, we aimed to study the effect of somatostatin and dopamine receptor agonists (octreotide and cabergoline, respectively) and novel somatostatin-dopamine chimeric multi-receptor drugs (BIM-065, BIM-23A760) using 2D (monolayer) and 3D (spheroids) cultures.
METHODS: Dose-response studies in 2D and 3D human pancreatic NET cell cultures (BON-1 and QGP-1) were performed under serum-containing and serum-deprived conditions. Cell proliferation, somatostatin and dopamine receptors expression (sst and D2R), apoptosis, lactate dehydrogenase, as well as serotonin and chromogranin-A (CgA) release were assessed.
RESULTS: 3D-cultures of BON-1/QGP-1 allowed better cell survival than 2D-cultures in serum-deprived conditions. Sst and D2R mRNA levels were significantly higher in the 3D-model vs. 2D-model. Octreotide/cabergoline/BIM-065/BIM-23A760 treatment did not affect cell-growth or spheroid size. In BON-1 2D-cultures, only BIM-23A760 significantly inhibited CgA release, being this effect more pronounced in 3D-cultures. In BON-1 2D-cultures, cabergoline/BIM-065/BIM-23A760 treatment decreased serotonin release (maximal effect up to 40%), being this effect again more potent in 3D-cultures (up to 67% inhibition; with BIM-23A760 having the most potent effects). In QGP-1, cabergoline/BIM-065 treatment decreased serotonin release only in the 3D-model.
CONCLUSIONS: Cultures of NET 3D-spheroids represent a promising method for evaluating cell-proliferation and secretion in NET cell-line models. Compared to 2D-models, 3D-models grow relatively serum-independent. In 3D-model, sst-D2R multi-receptor targeting drugs inhibit CgA and serotonin secretion, but not NET cell-growth.

PMID: 30939452 [PubMed - as supplied by publisher]

An Unusual Presentation of Merkel Cell Carcinoma in a HIV Patient: A Case Report and Literature Review.

Fetched: April 4th, 2019, 5:00am GMT

An Unusual Presentation of Merkel Cell Carcinoma in a HIV Patient: A Case Report and Literature Review.

J Investig Med High Impact Case Rep. 2019 Jan-Dec;7:2324709619836695

Authors: Ramachandran P, Erdinc B, Gotlieb V

PMID: 30938171 [PubMed - in process]

A Rare Case of Mixed Adenoneuroendocrine Carcinoma of the Ileocecal Valve.

Fetched: April 4th, 2019, 5:00am GMT

A Rare Case of Mixed Adenoneuroendocrine Carcinoma of the Ileocecal Valve.

Cureus. 2019 Jan 23;11(1):e3942

Authors: Gonzalez HH, Skrove JL, Sharma R, Sobrado J

Abstract
Mixed adenoneuroendocrine carcinoma (MANEC) is an uncommon neoplasm with uncertain pathophysiology. In order to be classified as MANEC, the tumor must contain at least 30% neuroendocrine cells and 30% adenocarcinoma. The standardization of MANEC treatment has historically been difficult due to the lack of diagnostic histological classification. In 2010, the World Health Organization (WHO) finally recognized this uncommon condition as a specific colon cancer entity in the hopes of better specifying treatment options in the future. We present a case of high-grade MANEC of the cecum with metastasis in 3/10 lymph nodes to further characterize the diagnostic modalities and treatment options of the disease. MANECs only account for 3%-9.6% of all colorectal cancers and only eight cases have been reported in the cecum to date, making the following case report exceptionally rare.

PMID: 30937240 [PubMed]

Acute Paraplegia Revealing a Hemorrhagic Cauda Equina Paragangliomas.

Fetched: April 4th, 2019, 5:00am GMT

Acute Paraplegia Revealing a Hemorrhagic Cauda Equina Paragangliomas.

Asian J Neurosurg. 2019 Jan-Mar;14(1):245-248

Authors: Ghedira K, Matar N, Bouali S, Zehani A, Jemel H

Abstract
Cauda equina paragangliomas are rare neuroendocrine benign and slow-growing tumors. Acute paraplegia, occurring because of sudden intratumoral hemorrhage, represents an extremely rare clinical picture of this disease. We report the case of a 64-year-old male presenting with a 5-day acute lower back pain, sciatica, and leg weakness. Spinal imaging showed an intradural mass of the cauda equina region and an emergent surgical treatment was achieved. The lesion was removed "en bloc," and subarachnoid blood was noticed during surgery. The postoperative course was uneventful, with complete regression of pain and progressive motor recovery. The histological study revealed typical microscopic and immunohistochemical features of paragangliomas.

PMID: 30937045 [PubMed]

Permalink for 'NCL1, A Highly Selective Lysine-Specific Demethylase 1 Inhibitor, Suppresses Castration-Resistant Prostate Cancer Growth via Regulation of Apoptosis and Autophagy.'

NCL1, A Highly Selective Lysine-Specific Demethylase 1 Inhibitor, Suppresses Castration-Resistant Prostate Cancer Growth via Regulation of Apoptosis and Autophagy.

Fetched: April 4th, 2019, 5:00am GMT

NCL1, A Highly Selective Lysine-Specific Demethylase 1 Inhibitor, Suppresses Castration-Resistant Prostate Cancer Growth via Regulation of Apoptosis and Autophagy.

J Clin Med. 2019 Mar 31;8(4):

Authors: Etani T, Naiki T, Naiki-Ito A, Suzuki T, Iida K, Nozaki S, Kato H, Nagayasu Y, Suzuki S, Kawai N, Yasui T, Takahashi S

Abstract
Recent studies have shown that epigenetic alterations lead to oncogenic activation, thus indicating that these are therapeutic targets. Herein, we analyzed the efficacy and therapeutic potential of our developed histone lysine demethylase 1 (LSD1) inhibitor, NCL1, in castration-resistant prostate cancer (CRPC). The CRPC cell lines 22Rv1, PC3, and PCai1CS were treated with NCL1, and LSD1 expression and cell viability were assessed. The epigenetic effects and mechanisms of NCL1 were also evaluated. CRPC cells showed strong LSD1 expression, and cell viability was decreased by NCL1 in a dose-dependent manner. Chromatin immunoprecipitation analysis indicated that NCL1 induced histone H3 lysine 9 dimethylation accumulation at promoters of P21. As shown by Western blot and flow cytometry analyses, NCL1 also dose-dependently induced caspase-dependent apoptosis. The stimulation of autophagy was observed in NCL1-treated 22Rv1 cells by transmission electron microscopy and LysoTracker analysis. Furt

Rare Cancer News & Clinical Trials » Endocrine/Neuroendocrine

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