Rare Cancer News & Clinical Trials » Endocrine/Neuroendocrine

Endocrine/Neuroendocrine (528 unread)

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

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

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

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

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

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

PMID: 30588655 [PubMed - indexed for MEDLINE]

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

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

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

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

Cancer Immunol Res. 2019 Aug 12;:

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

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

PMID: 31405946 [PubMed - as supplied by publisher]

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

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

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

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

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

Authors: Goto K

PMID: 28841242 [PubMed - indexed for MEDLINE]

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

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

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

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

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

PMID: 28256019 [PubMed - indexed for MEDLINE]

Merkel Cell Polyomavirus Small T Antigen Induces DNA Damage Response.

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

Merkel Cell Polyomavirus Small T Antigen Induces DNA Damage Response.

Intervirology. 2019 Aug 09;:1-5

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

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

PMID: 31401636 [PubMed - as supplied by publisher]

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

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

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

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

Clin Cancer Res. 2019 Aug 09;:

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

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

PMID: 31399473 [PubMed - as supplied by publisher]

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

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

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

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

Cells. 2019 Jul 31;8(8):

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

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

PMID: 31370278 [PubMed - in process]

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

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

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

Front Med (Lausanne). 2019;6:160

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

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

PMID: 31355203 [PubMed]

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

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

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

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

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

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

PMID: 30255436 [PubMed - indexed for MEDLINE]

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

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

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

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

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

PMID: 29797735 [PubMed - indexed for MEDLINE]

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

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

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

Oral Maxillofac Surg. 2019 Jul 24;:

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

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

PMID: 31342210 [PubMed - as supplied by publisher]

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

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

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

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

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

PMID: 30148734 [PubMed - indexed for MEDLINE]

Incidental Merkel Cell Carcinoma Encountered During Mohs Surgery.

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

Incidental Merkel Cell Carcinoma Encountered During Mohs Surgery.

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

Authors: Mafee M, Bennett DD, Swanson AM

PMID: 29933296 [PubMed - indexed for MEDLINE]

BK polyomavirus is a cause of bladder cancer.

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

BK polyomavirus is a cause of bladder cancer.

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

Authors: Starrett GJ, Buck CB

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

PMID: 31336246 [PubMed - as supplied by publisher]

Iatrogenic solid tumors following immunosuppressive therapy.

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

Iatrogenic solid tumors following immunosuppressive therapy.

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

Authors: Dantey K, Pantanowitz L

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

PMID: 29066044 [PubMed - indexed for MEDLINE]

Skin ultrasound features of Merkel cell carcinoma.

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

Skin ultrasound features of Merkel cell carcinoma.

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

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

PMID: 28045198 [PubMed - indexed for MEDLINE]

Endoscopic ultrasound diagnosis of Merkel cell carcinoma metastasising to pancreas.

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

Endoscopic ultrasound diagnosis of Merkel cell carcinoma metastasising to pancreas.

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

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

PMID: 29665210 [PubMed - indexed for MEDLINE]

Merkel cell carcinoma: morphologic aspects on reflectance confocal microscopy.

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

Merkel cell carcinoma: morphologic aspects on reflectance confocal microscopy.

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

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

PMID: 28502121 [PubMed - indexed for MEDLINE]

Immune checkpoint inhibitors in older adults with melanoma or cutaneous malignancies: The Wilmot Cancer Institute experience.

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

Immune checkpoint inhibitors in older adults with melanoma or cutaneous malignancies: The Wilmot Cancer Institute experience.

J Geriatr Oncol. 2019 Jul 11;:

Authors: Archibald WJ, Victor AI, Strawderman MS, Maggiore RJ

Abstract
OBJECTIVES: The purpose of this study was to explore the associations between age and frailty with immune-related adverse events (irAEs) among patients with cutaneous malignancies receiving immune checkpoint inhibitor (ICI) therapy.
METHODS: A retrospective review of all patients receiving ipilimumab, nivolumab, or pembrolizumab for treatment of cutaneous malignancies at the Wilmot Cancer Institute between 1 Jan 2011 and 3 Apr 2017.
RESULTS: A total of 120 patients (age <70 N = 68, age ≥70 N = 52; range, 26-93) were identified. 44.1%[95%CI:32-57%] of patients age <70 and 31.4%[95%CI:19-46%] of patients age ≥70 experienced ≥1 irAE on 1st line ICI therapy (P = 0.158). A total of 3 adults died of irAEs (2 age ≥70; 1 age <70). Patients ≥70 were more frequently treated with anti-PD-1 monotherapy than dual checkpoint blockade or ipilimumab (P < 0.01) in the first line setting. Among patients on first line anti-PD-1 monotherapy for cutaneous melanoma, 21 were age <70 and 20 were age ≥70, with similar observed rates of irAEs (52.4%[95%CI 29.8-74.3] and 63.2%[95%CI 38.4-83.7]). Indirect frailty markers in patients age ≥70 such as having fallen in the prior six months, ECOG PS ≥2 or Charlson comorbidity scores ≥11 experienced similar rates of response and toxicity. Among 9 patients with a PS = 3, 8 died, 6 due to progressive disease. No deaths due to irAEs occurred in this frail subgroup.
CONCLUSION: Anti-PD-1 monotherapy for older adults with cutaneous malignancies have similar response and irAE rates when compared to those of younger patients. Deaths from disease progression were more frequent than those from toxicity in both age subgroups.

PMID: 31303463 [PubMed - as supplied by publisher]

What's new in HIV dermatology?

Fetched: July 14th, 2019, 5:01am GMT

What's new in HIV dermatology?

F1000Res. 2019;8:

Authors: Coates SJ, Leslie KS

Abstract
HIV has long been associated with a number of inflammatory, infectious, and neoplastic skin conditions. In the era of anti-retroviral therapy, we have discovered even more about the relationship between skin disease and chronic immunosuppression. In particular, clinicians still face the propensity of persons living with HIV to develop difficult-to-control viral infections, chronic skin inflammation, and pruritus and-particularly as patients age-various types of skin cancers. Here, we summarize recent updates in the field of HIV dermatology and make recommendations to providers caring for these patients.

PMID: 31297183 [PubMed - in process]

Atypical case of Merkel cell carcinoma difficult to diagnose clinically.

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

Atypical case of Merkel cell carcinoma difficult to diagnose clinically.

J Dermatol. 2017 Jul;44(7):e158-e159

Authors: Kinoshita Y, Hoashi T, Okazaki S, Kataoka K, Nako T, Mayumi N, Kouno T, Funasaka Y, Ansai SI, Saeki H

PMID: 28328104 [PubMed - indexed for MEDLINE]

Permalink for 'Second primary cancers in patients with invasive and in situ squamous cell skin carcinoma, Kaposi sarcoma and Merkel cell carcinoma: role for immune mechanisms?'

Second primary cancers in patients with invasive and in situ squamous cell skin carcinoma, Kaposi sarcoma and Merkel cell carcinoma: role for immune mechanisms?

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

Second primary cancers in patients with invasive and in situ squamous cell skin carcinoma, Kaposi sarcoma and Merkel cell carcinoma: role for immune mechanisms?

J Invest Dermatol. 2019 Jul 06;:

Authors: Chattopadhyay S, Hemminki A, Försti A, Sundquist K, Sundquist J, Hemminki K

Abstract
Second primary cancers (SPCs) are becoming a common cancer entity, which may interfere with survival in relatively benign first primary cancers. We wanted to examine the hypothesis that immune dysfunction may contribute to SPCs by assessing SPCs associated with known immune responsive skin cancers, invasive and in situ squamous cell carcinoma (SCC), Kaposi sarcoma (KS) and Merkel cell carcinoma (MCC). Cancers were identified from the Swedish Cancer Registry from the years 1958 through to 2015. Standardized relative risks (RRs) were calculated bi-directionally for any SPC after skin cancer and for skin cancer as SPC. Over 80,000 first primary cancers were identified for each of invasive and in situ SCC of the skin. Bi-directional increased risks were observed for 26 cancers associated with invasive skin cancer; the Spearman rank correlation was 0.72 (P=4.6x10-5). The highest bidirectional RRs were for invasive and in situ skin cancer as SPCs (14.59 and 16.71). Remarkably high risks for second in situ SCC of the skin were found after KS (685.68) and MCC (117.23). The high systematic bi-directional risks between immune responsive skin cancers and most other cancers suggest that immune suppression is a key mechanism contributing to an increased risk of SPCs.

PMID: 31288011 [PubMed - as supplied by publisher]

$Permalink for 'Rescue therapy for patients with anti-PD-1-refractory Merkel cell carcinoma: a multicenter, retrospective case series.'$

Rescue therapy for patients with anti-PD-1-refractory Merkel cell carcinoma: a multicenter, retrospective case series.

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

Rescue therapy for patients with anti-PD-1-refractory Merkel cell carcinoma: a multicenter, retrospective case series.

J Immunother Cancer. 2019 Jul 08;7(1):170

Authors: LoPiccolo J, Schollenberger MD, Dakhil S, Rosner S, Ali O, Sharfman WH, Silk AW, Bhatia S, Lipson EJ

Abstract
Merkel cell carcinoma (MCC) is a rare but clinically aggressive cancer with a high mortality rate. In recent years, antibodies blocking the interactions among PD-1 and its ligands have generated durable tumor regressions in patients with advanced MCC. However, there is a paucity of data regarding effective therapy for patients whose disease is refractory to PD-1 pathway blockade. This retrospective case series describes a heterogeneous group of patients treated with additional immune checkpoint blocking therapy after MCC progression through anti-PD-1. Among 13 patients treated with anti-CTLA-4, alone or in combination with anti-PD-1, objective responses were seen in 4 (31%). Additionally, one patient with MCC refractory to anti-PD-1 and anti-CTLA-4 experienced tumor regression with anti-PD-L1. Our report - the largest case series to date describing this patient population - provides evidence that sequentially-administered salvage immune checkpoint blocking therapy can potentially activate anti-tumor immunity in patients with advanced anti-PD-1-refractory MCC and provides a strong rationale for formally testing these agents in multicenter clinical trials. Additionally, to the best of our knowledge, our report is the first to demonstrate possible anti-tumor activity of second-line treatment with a PD-L1 antibody in a patient with anti-PD-1-refractory disease.

PMID: 31287031 [PubMed - in process]

MCPyV Large T antigen induced atonal homolog 1 (ATOH1) is a lineage-dependency oncogene in Merkel cell carcinoma.

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

MCPyV Large T antigen induced atonal homolog 1 (ATOH1) is a lineage-dependency oncogene in Merkel cell carcinoma.

J Invest Dermatol. 2019 Jul 05;:

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

Abstract
Despite the fact that the transcription factor atonal homolog 1 (ATOH1) is a master regulator of Merkel cell development, its role in Merkel cell carcinoma (MCC) carcinogenesis remains controversial. Here, we provide several lines of evidence that ATOH1 is a lineage-dependency oncogene in MCC. Luciferase assays revealed binding of ATOH1 and subsequent activation to the promoter of miR-375, i.e. one of the most abundant microRNAs in MCCs. Overexpression of ATOH1 in variant MCC cell lines and fibroblasts induced miR-375 expression, whereas ATOH1 knockdown in classical MCC cell lines reduced miR-375 expression. Moreover, ATOH1 overexpression in these cells changed their growth characteristics from adherent to suspension/ spheroidal growth, i.e., resembling the neuroendocrine growth pattern of classical MCC cell lines. Notably, ectopic expression of different Merkel cell polyomavirus (MCPyV) derived truncated large T antigens induced ATOH1 expression in fibroblasts, which was paralleled by miR-375 expression and similar morphologic changes. In summary, MCPyV associated carcinogenesis is likely to induce the characteristic neuroendocrine features of MCC via induction of ATOH1; thus, ATOH1 can be regarded as a lineage-dependency oncogene in MCC.

PMID: 31283928 [PubMed - as supplied by publisher]

Permalink for 'Detection of human papillomaviruses and human polyomaviruses in immunosuppressed and immunocompetent individuals with actinic cheilitis: a case series.'

Detection of human papillomaviruses and human polyomaviruses in immunosuppressed and immunocompetent individuals with actinic cheilitis: a case series.

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

Detection of human papillomaviruses and human polyomaviruses in immunosuppressed and immunocompetent individuals with actinic cheilitis: a case series.

J Eur Acad Dermatol Venereol. 2019 Jul 07;:

Authors: Neto Pimentel DR, Montosa Nunes E, Termini L, Almeida Lima Nunes R, Mendoza Lopez RV, Ferreira S, Boccardo E, Mann Prado JC, Enokihara MMSES, Sichero L, Tomimori J

Abstract
Actinic cheilitis (AC) is considered a precancerous lesion of the lip.1 Renal transplant recipients (RTR) have a higher susceptibility to human papillomavirus (HPV) infections and lip squamous cell carcinoma (SCC). 2 Over 200 HPV types were described and most cluster within the α-, β- and γ-HPV genera. 3 Merkel Cell Polyomavirus (MCPyV) and several HPVs are associated with skin affections including cancer. 2 We evaluated the association of MCPyV, HPVs and related biomarkers with AC. This article is protected by copyright. All rights reserved.

PMID: 31281986 [PubMed - as supplied by publisher]

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

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

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

Oral Oncol. 2019 Jul 02;:

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

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

PMID: 31277904 [PubMed - as supplied by publisher]

Fading Signals: How Long Does Antigenicity in Immunohistochemical Staining Last?

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

Fading Signals: How Long Does Antigenicity in Immunohistochemical Staining Last?

Skinmed. 2017;15(4):277-279

Authors: John AM, Holahan HM, Singh P, Handler MZ, Chung S, Lambert WC

PMID: 28859738 [PubMed - indexed for MEDLINE]

Merkel Cell Carcinoma Metastasis to Stomach: an Infrequent Culmination of a Rare Neoplasm.

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

Merkel Cell Carcinoma Metastasis to Stomach: an Infrequent Culmination of a Rare Neoplasm.

J Gastrointest Cancer. 2018 Mar;49(1):78-80

Authors: Kini JR, Tapadia R, Shenoy S

PMID: 27377389 [PubMed - indexed for MEDLINE]

In Response.

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

In Response.

Am J Dermatopathol. 2019 07;41(7):535

Authors: Peña Zúñiga EB

PMID: 30299274 [PubMed - indexed for MEDLINE]

Treatment Patterns, Overall Survival, and Total Healthcare Costs of Advanced Merkel Cell Carcinoma in the USA.

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

Treatment Patterns, Overall Survival, and Total Healthcare Costs of Advanced Merkel Cell Carcinoma in the USA.

Appl Health Econ Health Policy. 2019 Jun 28;:

Authors: Steuten L, Garmo V, Phatak H, Sullivan SD, Nghiem P, Ramsey SD

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) is a rare and aggressive type of cancer with poor outcomes.
OBJECTIVE: To describe treatment patterns, overall survival, and healthcare costs associated with advanced MCC (aMCC) using data from Medicare enrollees who received an aMCC diagnosis in the USA States between 2006 and 2013.
METHODS: Surveillance, Epidemiology, and End Results (SEER)-Medicare data from 2006 to 2013 were used to describe treatment patterns, 1- and 5-year overall survival, and total healthcare costs for the periods 12 months before aMCC diagnosis and 4-12 months afterward in patients aged ≥ 65 years.
RESULTS: We identified 257 patients with an aMCC diagnosis, of whom 51% had stage IIIb disease and 49% had stage IV. Within 4 months after diagnosis, 84% of patients (n = 216) received treatment; 45% (n = 115) received surgery, 48% (n = 124) radiation therapy, and 31% (n = 80) chemotherapy. Second-line chemotherapy was administered in 33% of patients (n = 26) receiving first-line chemotherapy. Median overall survival was 27 months in patients whose aMCC was diagnosed at stage IIIb and 12 months in patients whose aMCC was diagnosed at stage IV. Median total 12-month direct healthcare costs were US$48,006 (25th-75th percentile range = US$30,594-US$69,797) per patient. Total costs were highest in patients receiving chemotherapy, either alone or combined with radiation and/or surgery (US$52,854; 25th-75th percentile range = US$34,473-US$71,987).
CONCLUSION: Most patients with aMCC received initial treatment, including surgery, radiation, and/or chemotherapy, and approximately one-third of those receiving chemotherapy received second-line chemotherapy. Total 12-month direct healthcare costs were highest in patients who received chemotherapy alone or combined with radiation and/or surgery. These poor survival results and high treatment costs highlight the need for effective new aMCC therapies.

PMID: 31250217 [PubMed - as supplied by publisher]

$Permalink for 'Pre-treated Anti-PD-1 Refractory Merkel Cell Carcinoma Successfully Treated with the Combination of PD-1/PD-L1 Axis Inhibitors and TVEC: A Report of Two Cases.'$

Pre-treated Anti-PD-1 Refractory Merkel Cell Carcinoma Successfully Treated with the Combination of PD-1/PD-L1 Axis Inhibitors and TVEC: A Report of Two Cases.

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

Icon for Silverchair Information Systems

Pre-treated Anti-PD-1 Refractory Merkel Cell Carcinoma Successfully Treated with the Combination of PD-1/PD-L1 Axis Inhibitors and TVEC: A Report of Two Cases.

Ann Oncol. 2019 Jun 10;:

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

PMID: 31250007 [PubMed - as supplied by publisher]

Merkel Cell Carcinoma of the Eyelids (Clinical-Histological Study).

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

Merkel Cell Carcinoma of the Eyelids (Clinical-Histological Study).

Cesk Slov Oftalmol. 2019;74(5):198-205

Authors: Krásný J, Šach J, Kolín V, Zikmund J

Abstract
AIM: To get acquainted with the issues of Merkel cell carcinoma (MCC) when the eyelid is affected and with its surgical solution.
MATERIALS: MCC of the right upper eyelid was at the Department of Ophthalmology in the Faculty Hospital Královské Vinohrady in Prague (Czech Republic, EU) in 1998 woman 78 year. Another cases of the MCC on the left upper eyelid were observed in two women aged 48 and 67 years and they were pick up in a retrospective study covered 1033 operated tumors eyelids years 2007 - 2015. 47,5% of operated tumors were benign and 52,5% malignant. Most common malignant processes were basal cell carcinoma in 77,3% and squamous cell carcinoma at 15,7%.
RESULTS: The oldest patient died after three years of cardiopulmonary failure. 48 year old patient (age of diagnosis MCC) has been monitoring for five years without proven recurrence or metastasis dissemination. Oncological initial staging was negative regarding. An ultrasound examination of the lymphatic system of the neck was followed every six months. Another 67 year old patient (age of diagnosis MCC) was followed for 2,5 years. There was a suspicion of a metastatic process in the same side salivary gland and lungs, therefore chemotherapy was performed. Definitely, this process has not been proven. Now there is continuing follow up without sings of local recurrence or metastatic dissemination.
CONCLUSION: The authors confirmed a rare occurrence of MCC, and only 0,37% among malignant eyelids tumors. Essential importance for successful treatment is a sufficiently radical excision supported by histological verification and a subsequent plastic surgery of the eyelid is also necessary. Key words: Merkel cell carcinoma, tumor of eyelid, ultrasound examination of nodes.

PMID: 31234633 [PubMed - indexed for MEDLINE]

Expression of 15-lipoxygenase-1 in Merkel cell carcinoma is linked to advanced disease.

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

Expression of 15-lipoxygenase-1 in Merkel cell carcinoma is linked to advanced disease.

Clin Otolaryngol. 2018 10;43(5):1335-1344

Authors: Fochtmann-Frana A, Haymerle G, Schachner H, Pammer J, Loewe R, Kerjaschki D, Perisanidis C, Erovic BM

Abstract
BACKGROUND: The purpose of this study was to determine whether the expression of 15-lipoxygenase-1 (ALOX15) in primary tumour specimens predicts lymph node metastasis and subsequently clinical outcome in Merkel cell carcinoma (MCC) patients.
METHODS: A retrospective medical chart review of 33 patients was performed between 1994 and 2014. Eleven out of 33 (33%) Patients with primary MCC stages I and II were categorised as group I. Twenty two out of 33 (67%) Patients with regional lymph node metastases and/or distant metastases were defined as group II. All available tumour samples were immunostained for ALOX15, Podoplanin and MCPyV large T-protein antibody.
RESULTS: ALOX15 expression was observed in 19/23 (83%) primary tumour samples and in all lymph node metastasis. Primary tumours in patients with stage III and IV disease showed a higher expression rate of ALOX15 compared to patients with early stage disease (11/12 (92%) and 8/11 (73%), respectively). In group I, five patients (45%) were MCPyV positive, whereas in group II, 15 patients (68%) were MCPyV positive. The median lymphatic vessel density in ALOX15 negative group I primary tumour samples was lower compared to the median lymphatic vessel density in ALOX15 positive group I primary tumour probes (2.7 range, 1-4.3 vs 4.7 range, 4.0-7.3). Furthermore, all 17 samples of MCC metastases showed ALOX15 expression with a median lymphatic vessel density (not lymph node metastases) of 5.3 (range 2.0-7.3).
CONCLUSION: In the current study, we were able to show ALOX15 expression in the primary MCC sample and the metastasis sample. Based on the findings of the current study, expression rate of ALOX15 in primary MCC and metastases is possibly linked to an increased lymphatic vessel density.

PMID: 29992788 [PubMed - indexed for MEDLINE]

Complete Spontaneous Regression of the Primary Tumor in Merkel Cell Carcinoma.

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

Complete Spontaneous Regression of the Primary Tumor in Merkel Cell Carcinoma.

Actas Dermosifiliogr. 2018 Oct;109(8):752-754

Authors: Marcoval J, Valentí-Medina F, Penín RM, Bermejo J

PMID: 29631722 [PubMed - indexed for MEDLINE]

The Effect of Time to Postoperative Radiation Therapy on Survival in Resected Merkel Cell Carcinoma.

Fetched: June 29th, 2019, 5:00am GMT

The Effect of Time to Postoperative Radiation Therapy on Survival in Resected Merkel Cell Carcinoma.

Am J Clin Oncol. 2019 Jun 24;:

Authors: Shinde A, Verma V, Jones BL, Li R, Glaser S, Freeman M, Melstrom L, Kang R, Parvathaneni U, Modi B, Amini A

Abstract
OBJECTIVES: Delays from surgery to adjuvant radiation therapy (aRT) are associated with poorer prognosis in multiple neoplasms. Presently, no data exist for Merkel cell carcinoma (MCC). The authors sought to assess the time interval from surgery to aRT and effect on outcomes in MCC.
MATERIALS AND METHODS: The National Cancer Database was queried for histologically confirmed nonmetastatic MCC status post resection and aRT diagnosed between 2004 and 2015 who received aRT within 24 weeks of surgery. Kaplan-Meier analysis assessed univariate overall survival (OS); multivariable Cox proportional hazards modeling assessed multivariate OS; χ and logistic regression assessed differences in baseline characteristics and predictors of delayed aRT.
RESULTS: Of 5952 patients meeting criteria, 13% commenced aRT within 4 weeks, 48% between 4 and 7 weeks, 23% between 8 and 11 weeks, 11% between 12 and 15 weeks, and 6% between 16 and 24 weeks. There were no differences in OS on the basis of the surgery-aRT interval (P=0.99). Predictors of worse OS on the multivariate analysis included advanced age, greater comorbidities, male sex, lower regional income, earlier year of diagnosis, more advanced tumor and nodal staging, positive margins, head and neck location, and treatment at community facilities (P<0.05 for all). Factors predictive of delayed aRT were identified. Subset analyses on these factors, such as receipt of chemotherapy or positive lymph nodes, did not demonstrate that the timing of aRT affected survival (P≥0.37).
CONCLUSION: This study of a contemporary national database revealed that delays from resection to aRT were not associated with survival in MCC, somewhat discordant from other malignancies such as squamous cell carcinoma.

PMID: 31246585 [PubMed - as supplied by publisher]

Permalink for 'SATB2 in Neuroendocrine Neoplasms: Strong Expression is Restricted to Well-Differentiated Tumors of Lower Gastrointestinal Tract Origin and is More Frequent in Merkel Cell Carcinoma among Poorly Differentiated Carcinomas.'

SATB2 in Neuroendocrine Neoplasms: Strong Expression is Restricted to Well-Differentiated Tumors of Lower Gastrointestinal Tract Origin and is More Frequent in Merkel Cell Carcinoma among Poorly Differentiated Carcinomas.

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

SATB2 in Neuroendocrine Neoplasms: Strong Expression is Restricted to Well-Differentiated Tumors of Lower Gastrointestinal Tract Origin and is More Frequent in Merkel Cell Carcinoma among Poorly Differentiated Carcinomas.

Histopathology. 2019 Jun 24;:

Authors: Bellizzi AM

Abstract
AIMS: Special AT-rich sequence-binding protein 2 (SATB2) is a transcriptional regulator with critical roles in brain, craniofacial, and skeletal development. It has emerged as a key marker of lower gastrointestinal (GI) tract columnar epithelial and osteoblastic differentiation. Transcription factor immunohistochemistry is useful in assigning site of origin in well-differentiated neuroendocrine tumors (NETs) and has had a limited role in poorly differentiated neuroendocrine carcinomas (NECs).
METHODS AND RESULTS: Tissue microarrays were constructed from the following: 317 NETs (37 thyroid, 46 lung, 12 duodenum, 70 pancreas, 106 jejunoileum, 24 appendix, 5 rectosigmoid), 44 pheochromocytomas/paragangliomas, and 79 NECs (29 Merkel cell, 30 lung, 20 extrapulmonary visceral); 9 appendiceal and 19 rectal NETs were examined in whole sections. SATB2 immunohistochemistry was scored for extent (%) and intensity (0-3+) with an H-score calculated. SATB2 was expressed by 96% of rectosigmoid, 79% of appendiceal, and only 7% of other well-differentiated neoplasms (p<0.0001). Expression in lower GI tract NETs (median H-score=255) was stronger than in other positive tumors (median H-score=7) (p<0.0001). Any SATB2 expression was 86% sensitive/93% specific for lower GI tract origin. SATB2 was expressed by 79% of Merkel cell (median H-score=300), 33% of lung (median H-score=23), and 60% of extrapulmonary visceral (median H-score=110) NECs, with stronger expression in Merkel cell carcinoma (p<0.001). At an H-score cutoff of ≥150, SATB2 was 69% sensitive/90% specific for Merkel cell carcinoma.
CONCLUSIONS: SATB2 is frequently, strongly expressed by lower GI tract NETs; we have adopted it as our rectal NET marker. Relatively frequent, strong expression in Merkel cell carcinoma may have value in assigning NEC site of origin. This article is protected by copyright. All rights reserved.

PMID: 31233624 [PubMed - as supplied by publisher]

Cancer Testis Antigens as Biomarkers for Merkel Cell Carcinoma; Pitfalls and Opportunities.

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

Cancer Testis Antigens as Biomarkers for Merkel Cell Carcinoma; Pitfalls and Opportunities.

J Cutan Pathol. 2019 Jun 20;:

Authors: Dasgeb B, Mehregan D, Ring C, Nartker N, Brownell I

Abstract
BACKGROUND: The prognosis and treatment options for metastatic Merkel cell carcinoma (MCC) are poor. The immune-privileged status of cancer-testis (CT) antigens impart tumor specificity, making them ideal candidates for targeted immunotherapy. We investigate the usefulness of the CT antigens SPA17 (SP-17), IGF2BP3 (IMP-3), and TMEFF1 as potential MCC biomarkers and evaluate their possible utility in immunotherapy and molecularly targeted image-guided treatment.
METHODS: The CT antigens SP-17, IMP-3, and TMEFF1 were selected using transcriptome profiling to identify CT antigens expressed in MCC tumors. Antibodies directed against these CT antigens were stained. Twelve normal skin tissue samples were used as a control. The average percentage of positive cells in each tumor was computed.
RESULTS: 12 of 14 (86%) MCC cases showed crisp nuclear staining for SP-17 with 2.06% of cells staining positive. IMP-3 showed crisp, perinuclear staining in all 14 MCC cases with 52.93% MCC cells staining positive. TMEFF1 demonstrated perinuclear staining in all 14 MCC cases with 96.51% of tumor cells staining positive.
CONCLUSIONS: CT antigens were found to be expressed in both Merkel cell carcinoma and some control tissues. SP-17 was the most specific yet the least sensitive. IMP-3 and TMEFF1 were both sensitive but not specific. Cancer testis antigens may represent valuable treatment targets in Merkel cell carcinoma. This article is protected by copyright. All rights reserved.

PMID: 31218705 [PubMed - as supplied by publisher]

Merkel Cell Carcinoma in Kidney Transplant Recipients in Ireland 1964-2018.

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

Merkel Cell Carcinoma in Kidney Transplant Recipients in Ireland 1964-2018.

Br J Dermatol. 2019 Jun 17;:

Authors: Keeling E, Murray SL, Williams Y, Sexton DJ, O'Kelly P, Deady S, O'Leary E, Dorman A, Roche M, Ni Raghallaigh S, McCormick A, Moloney FJ, O'Neill JP, Conlon PJ

Abstract
Merkel cell carcinoma (MCC), an aggressive neuroendocrine carcinoma, typically occurs in fair-skinned male patients, on sun-exposed skin. Although rare, from 2000 to 2013, a 95% increase in incidence for MCC has been documented with further increases projected1 . There is a paucity of data pertaining to the epidemiology of MCC in organ transplant recipients (OTR). Therefore we describe the national experience of MCC in kidney transplant recipients (KTR) in Ireland. This article is protected by copyright. All rights reserved.

PMID: 31206594 [PubMed - as supplied by publisher]

Application of PD-1 Blockade in Cancer Immunotherapy.

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

Application of PD-1 Blockade in Cancer Immunotherapy.

Comput Struct Biotechnol J. 2019;17:661-674

Authors: Wu X, Gu Z, Chen Y, Chen B, Chen W, Weng L, Liu X

Abstract
The programmed cell death protein 1 (PD-1) pathway has received considerable attention due to its role in eliciting the immune checkpoint response of T cells, resulting in tumor cells capable of evading immune surveillance and being highly refractory to conventional chemotherapy. Application of anti-PD-1/PD-L1 antibodies as checkpoint inhibitors is rapidly becoming a promising therapeutic approach in treating tumors, and some of them have successfully been commercialized in the past few years. However, not all patients show complete responses and adverse events have been noted, suggesting a better understanding of PD-1 pathway mediated immunosuppression is needed to predict patient response and improve treatment efficacy. Here, we review the progresses on the studies of the mechanistic role of PD-1 pathway in the tumor immune evasion, recent clinical development and commercialization of PD-1 pathway inhibitors, the toxicities associated with PD-1 blockade observed in clinical trials as well as how to improve therapeutic efficacy and safety of cancer immunotherapy.

PMID: 31205619 [PubMed]

Recurrent Merkel cell carcinoma of the gluteal region: A case report.

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

Recurrent Merkel cell carcinoma of the gluteal region: A case report.

Dermatol Ther. 2019 01;32(1):e12749

Authors: Turkkan G, Agdogan O, Saynak M, Uygun AC, Ustun F

Abstract
Merkel cell carcinoma (MCC) is a rare malignant tumor of the skin. The development of MCC on non-sun-exposed skin is extremely rare, with few cases reported in the literature. The present authors aimed to highlight the characteristic features and treatment options of this tumor. The present authors present a 50-year-old man who developed MCC on the left gluteal region (non-sun-exposed skin). After surgery with clear margins, adjuvant radiotherapy was given. Three months after radiotherapy, lymphatic recurrence was observed and he was treated with chemotherapy. On follow-up, systemic metastases were found and palliative treatment was planned.

PMID: 30238578 [PubMed - indexed for MEDLINE]

Permalink for 'Morphologic and immunophenotypical features distinguishing Merkel cell polyomavirus-positive and negative Merkel cell carcinoma.'

Morphologic and immunophenotypical features distinguishing Merkel cell polyomavirus-positive and negative Merkel cell carcinoma.

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

Morphologic and immunophenotypical features distinguishing Merkel cell polyomavirus-positive and negative Merkel cell carcinoma.

Mod Pathol. 2019 Jun 14;:

Authors: Kervarrec T, Tallet A, Miquelestorena-Standley E, Houben R, Schrama D, Gambichler T, Berthon P, Le Corre Y, Hainaut-Wierzbicka E, Aubin F, Bens G, Tabareau-Delalande F, Beneton N, Fromont G, Arbion F, Leteurtre E, Herfs M, Touzé A, Samimi M, Guyétant S

Abstract
In 2008, Feng et al. identified Merkel cell polyomavirus integration as the primary oncogenic event in ~80% of Merkel cell carcinoma cases. The remaining virus-negative Merkel cell carcinoma cases associated with a high mutational load are most likely caused by UV radiation. The current study aimed to compare the morphological and immunohistochemical features of 80 virus-positive and 21 virus-negative Merkel cell carcinoma cases. Microscopic evaluation revealed that elongated nuclei-similar to the spindle-shape variant of small cell lung cancer-were less frequent in Merkel cell polyomavirus-positive Merkel cell carcinoma compared to the virus-negative subset (p = 0.005). Moreover, virus-negative cases more frequently displayed a "large-cell neuroendocrine carcinoma" phenotype with larger cell size (p = 0.0026), abundant cytoplasm (p = 4×10-7) and prominent nucleoli (p = 0.002). Analysis of immunohistochemical data revealed frequent positivity for thyroid transcription factor 1 and cytokeratin 7, either absence or overexpression of p53, as well as frequent lack of neurofilament expression in virus-negative cases. By contrast, cytokeratin 8, 18 and 20 and a CD99 with a dot pattern as well as high EMA expression were identified as characteristic features of virus-positive Merkel cell carcinoma. In particular, the CD99 dot-like expression pattern was strongly associated with presence of the Merkel cell polyomavirus in Merkel cell carcinoma (sensitivity = 81%, specificity = 90%, positive likelihood ratio = 8.08). To conclude, virus-positive and -negative Merkel cell carcinoma are characterized by distinct morphological and immunohistochemical features, which implies a significant difference in tumor biology and behavior. Importantly, we identified the CD99 staining pattern as a marker indicating the virus status of this skin cancer.

PMID: 31201352 [PubMed - as supplied by publisher]

Multiple Epidermal Cysts of the Scalp: Dermatosurgical Approach with Favourable Outcome!

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

Multiple Epidermal Cysts of the Scalp: Dermatosurgical Approach with Favourable Outcome!

Open Access Maced J Med Sci. 2019 May 15;7(9):1509-1511

Authors: Tchernev G, Temelkova I, Yungareva I, Wollina U

Abstract
BACKGROUND: Epidermal cysts are subcutaneous tissue formations that are most commonly located in the area of scalp, trunk and face. In addition to single ones, the cysts may also be multiple, located near each other. Although they are considered to be a cystic ectasia of the hair infundibulum and mainly affect hairy parts, they can also be seen in the area of palms and feet as a result of trauma. Rare extracutaneous localisations are also described in the medical literature, affecting the oral cavity, intraosseous, cerebrum and sublingual epidermoid cyst. Although the majority of epidermal cysts are benign, a malignant transformation may also occur in the direction of development of squamous cell carcinoma, basal cell carcinoma or Merkel cell carcinoma. Clinically, they are presented as benign lesions, and only histological examination may reveal their malignant potential. Therefore, their surgical removal and subsequent histology are of paramount importance for the elucidation of their origin.
CASE PRESENTATION: An 88-year old patient was hospitalized for surgical removal of two tumorous formations in the head area which have been available for many years. During the dermatological examination in the frontal and parietal area of the head, the presence of two oval pink cystic neoplasms, clinically suspected for epidermal cysts, was found. The lesion located in the frontal area was removed by elliptical excision. The resulting surgical defect was closed by undermining the wound edges and mobilisation of the released skin to the middle of the defect, as the latter being closed by single interrupted sutures. In the second surgical session, the lesion located in the parietal region of the head was also removed under local anaesthesia. A so-called island flap was performed in which the tumour formation was removed by oval excision followed by contouring a triangle in the distal direction and transposition of the undermined triangle to the oval surgical defect. The resulting defect was recovered by single interrupted sutures.
CONCLUSION: First-line treatment of epidermal cysts is surgical excision, and it is important to remove the cyst wall to minimise the risk of relapses and recurrence. Other treatment options include laser therapy with CO2, erbium-YAG laser or intralesional drainage injection of triamcinolone acetonide.

PMID: 31198464 [PubMed]

[What's new in oncodermatology?]

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

[What's new in oncodermatology?]

Ann Dermatol Venereol. 2018 Dec;145 Suppl 7:VIIS40-VIIS46

Authors: Robert C

Abstract
This year again, several breaking news were published in our field of oncodermatology, especially in the domain of immunotherapy. Many works have reported results on predictive biomarker identification. Concerning melanoma treatment, we were disappointed by the negative results of the phase III trial evaluating the IDO1 inhibitor epacadostat + pembrolizumab versus pembrolizumab. However, many promising preliminary results involving the combinations of anti-PD1 and innate immunity activators have been published. We also have a new anti-BRAF + anti-MEK combination: encorafenib + binimetinib with a good benefit/risk ratio and a particularly favorable safety profile as compared with existing similar combinations. Major steps forward were obtained for locally advanced Merkel cell carcinoma and squamous cell carcinoma with anti-PDL-1 avelumab and anti-PD1 cemiplimab respectively.

PMID: 30583756 [PubMed - indexed for MEDLINE]

Permalink for 'Investigation of the Diagnostic Precision and Utility of Sentinel Lymph Node Biopsy in the Treatment of Patients with Merkel Cell Carcinoma.'

Investigation of the Diagnostic Precision and Utility of Sentinel Lymph Node Biopsy in the Treatment of Patients with Merkel Cell Carcinoma.

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

Investigation of the Diagnostic Precision and Utility of Sentinel Lymph Node Biopsy in the Treatment of Patients with Merkel Cell Carcinoma.

Am Surg. 2018 May 01;84(5):e173-e175

Authors: Lamb EP, Shaw FR, Fleming MD

PMID: 30454322 [PubMed - indexed for MEDLINE]

Merkel cell polyomavirus oncoproteins induce microRNAs that suppress multiple autophagy genes.

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

Merkel cell polyomavirus oncoproteins induce microRNAs that suppress multiple autophagy genes.

Int J Cancer. 2019 Jun 10;:

Authors: Kumar S, Xie H, Shi H, Gao J, Juhlin CC, Björnhagen V, Höög A, Lee L, Larsson C, Lui WO

Abstract
Viruses can inhibit host autophagy through multiple mechanisms, and evasion of autophagy plays an important role in immune suppression and viral oncogenesis. Merkel cell polyomavirus (MCPyV) T-antigens are expressed and involved in the pathogenesis of a large proportion of Merkel cell carcinoma (MCC). Yet, how MCPyV induces tumorigenesis is not fully understood. Herein, we show that MCPyV T-antigens induce miR-375, miR-30a-3p and miR-30a-5p expressions, which target multiple key genes involved in autophagy, including ATG7, SQSTM1 (p62) and BECN1. In MCC tumors, low expression of ATG7 and p62 are associated with MCPyV-positive tumors. Ectopic expression of MCPyV small T-antigen and truncated large T-antigen (LT), but not the wild-type LT, resulted in autophagy suppression, suggesting the importance of autophagy evasion in MCPyV-mediated tumorigenesis. Torin-1 treatment induced cell death, which was attenuated by autophagy inhibitor, but not pan-caspase inhibitor, suggesting a potential role of autophagy in promoting cell death in MCC. Conceptually, our study shows that MCPyV oncoproteins suppress autophagy to protect cancer cells from cell death, which contribute to a better understanding of MCPyV-mediated tumorigenesis and potential MCC treatment. This article is protected by copyright. All rights reserved.

PMID: 31180579 [PubMed - as supplied by publisher]

Permalink for 'Diffuse lichen planus-like keratoses and clinical pseudo-progression associated with avelumab treatment for Merkel cell carcinoma, a case report.'

Diffuse lichen planus-like keratoses and clinical pseudo-progression associated with avelumab treatment for Merkel cell carcinoma, a case report.

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

Diffuse lichen planus-like keratoses and clinical pseudo-progression associated with avelumab treatment for Merkel cell carcinoma, a case report.

BMC Cancer. 2019 Jun 04;19(1):539

Authors: Cardis MA, Jiang H, Strauss J, Gulley JL, Brownell I

Abstract
BACKGROUND: Avelumab is an anti-programmed cell death ligand 1 (PD-L1) antibody approved for treatment of Merkel cell carcinoma (MCC) and locally advanced or metastatic urothelial carcinoma. It shares a similar side effect profile to other immune checkpoint inhibitors, including immune-related adverse reactions in the skin. These adverse skin reactions can present as a morbilliform exanthem, lichenoid dermatitis, vitiligo, autoimmune bullous disorder, among others.
CASE PRESENTATION: We describe a patient with advanced MCC successfully treated with avelumab who developed acute onset diffuse lichen planus-like keratoses (LPLK) at sites of existing seborrheic keratoses (SK) and lentigines. Histopathology of an affected SK revealed papillomatous epidermal hyperplasia with lichenoid interface changes, numerous dyskeratotic keratinocytes and intermittent hypergranulosis. The findings resembled lichen planus (LP) arising in an SK. Onset of the skin symptoms corresponded with an inflammatory cancer response (clinical pseudo-progression), and the eruption improved as overall tumor burden decreased. The patient's pruritus was treated with topical steroids and cyrotherapy for individual symptomatic lesions.
CONCLUSION: Diffuse LPLK is a distinct immune-related reaction pattern associated with PD-L1/PD-1 checkpoint blockade. This is an important side effect to be aware of as LPLK frequently mimic keratinocytic neoplasms. Further observation is needed to assess the prevalence and significance of this immune therapy-associated adverse reaction.

PMID: 31164102 [PubMed - in process]

Unusual Merkel cell carcinoma: the great pretender.

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

Unusual Merkel cell carcinoma: the great pretender.

G Ital Dermatol Venereol. 2018 Jun;153(3):437-438

Authors: Peccerillo F, Pagliarello C, Zambito Spadaro F, Ricci R, Feliciani C, Fabrizi G

PMID: 28121080 [PubMed - indexed for MEDLINE]

PD-1 and PD-L1 inhibitors in the treatment of non-melanoma skin cancer: a systematic review.

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

PD-1 and PD-L1 inhibitors in the treatment of non-melanoma skin cancer: a systematic review.

J Am Acad Dermatol. 2019 Jun 01;:

Authors: Choi FD, Kraus CN, Elsensohn AN, Carley SK, Lehmer LM, Nguyen RT, Linden KG, Shiu J

Abstract
BACKGROUND: Immunotherapy using PD-1 or PD-L1 inhibitors has been increasingly reported in a variety of non-melanoma skin cancers (NMSCs).
OBJECTIVE: To analyze the evidence of PD-1 and PD-L1 inhibitors in the treatment of non-melanoma skin cancer.
METHODS: A primary literature search was conducted with PubMed, Cochrane Library EMBASE, Web of Science, and CINAHL through October 28, 2018 to include studies on the use of PD-1 or PD-L1 inhibitor in human subjects for non-melanoma skin cancer. Two reviewers independently performed study selection, data extraction and critical appraisal.
RESULTS: Fifty-one articles were included in this systematic review. The most robust evidence was in the treatment of Merkel cell carcinoma and cutaneous squamous cell carcinomas, as supported by phase 1 and 2 clinical trials. Treatment of basal cell carcinoma, cutaneous sarcoma, sebaceous carcinoma and malignant peripheral nerve sheath tumor also showed benefit with PD-1/PD-L1 inhibitors but data is limited. There does not appear to be efficacy for PD-1/PD-L1 inhibitors in cutaneous lymphomas.
LIMITATIONS: More investigation is needed to determine the efficacy, tumor responsiveness, and the safety profile of PD-1 and PD-L1 inhibitors in NMSC.
CONCLUSION: PD-1 and PD-L1 inhibitors exhibit treatment efficacy in a variety of non-melanoma skin cancers.

PMID: 31163235 [PubMed - as supplied by publisher]

Dermoscopy improves diagnostic accuracy for clinically amelanotic nodules.

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

Dermoscopy improves diagnostic accuracy for clinically amelanotic nodules.

Australas J Dermatol. 2019 Feb;60(1):45-49

Authors: Lin MJ, Xie C, Pan Y, Jalilian C, Kelly JW

Abstract
BACKGROUND/OBJECTIVES: Amelanotic nodular melanomas are notoriously difficult to diagnose and are responsible for a disproportionate burden of melanoma mortality. It is important to distinguish them from other amelanotic nodules. This study aimed to describe the dermoscopic features of a series of nodular melanomas and other amelanotic nodules and to determine whether dermoscopy improves diagnostic accuracy.
METHOD: Retrospective analysis of 150 clinically amelanotic nodules with macroscopic and dermoscopic images.
RESULTS: In terms of classifying the nodules as malignant, dermoscopy was superior to unaided eye (specificity 89%; 95% CI 71-98% vs 67%; 95% CI 46-83%, P = 0.03). Dermoscopy enhanced sensitivity for the diagnosis of both amelanotic melanoma and SCC. In 19% of cases, using dermoscopy, the most likely diagnosis was changed from incorrect to correct. This included 26% of amelanotic melanomas which had a macroscopic misdiagnosis overturned to the correct diagnosis. Polymorphous vascular structures were more common in malignant nodules. 76% of amelanotic melanomas/Merkel cell carcinomas had polymorphous vessels compared with 38% of SCCs/KAs/BCCs and 22% of benign nodules (P < 0.001).
CONCLUSION: Dermoscopy improves diagnostic accuracy for amelanotic melanomas and other amelanotic nodules. Although dermoscopy improves diagnostic accuracy for amelanotic melanomas, these aggressive melanomas remain diagnostically difficult.

PMID: 30123971 [PubMed - indexed for MEDLINE]

Permalink for 'Merkel Cell Carcinoma of the Head in a Young African Albino Woman with HIV/HTLV-1 Coinfection Associated with Multiple Squamous Cell Carcinomas.'

Merkel Cell Carcinoma of the Head in a Young African Albino Woman with HIV/HTLV-1 Coinfection Associated with Multiple Squamous Cell Carcinomas.

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

Merkel Cell Carcinoma of the Head in a Young African Albino Woman with HIV/HTLV-1 Coinfection Associated with Multiple Squamous Cell Carcinomas.

Case Rep Dermatol. 2019 Jan-Apr;11(1):113-122

Authors: Tenea D, Dinkel J, Becker JC, van der Walt E

Abstract
Merkel cell carcinoma (MCC) is a rare cutaneous neoplasm of presumed neuroendocrine origin, with aggressive behavior and poor prognosis, that tends to have an increased incidence among elderly Caucasians and immunosuppressed individuals. MCC is either associated with a clonal integration of the Merkel cell polyoma virus into the host genome or with genomic alterations caused by chronic UV exposure. Tumors of either carcinogenesis show epithelial, neuroendocrine, and B-lymphoid lineage markers. HIV-infected African albinos have a higher risk of developing skin cancers, including MCC, in comparison with the general population. We report a case of MCC of the head in a young albino woman with a HIV/HTLV-1 coinfection. The patient also suffered from multiple squamous cell carcinomas of the scalp, face, lip, and ears, suggesting an UV carcinogenesis of MCC. The purpose of this case report is to emphasize the relationship between immunosuppression (HIV/HTLV-1 coinfection, chronic sun exposure, ocular-cutaneous albinism, pregnancy) and MCC. It highlights the importance of early diagnosis, dermatological screening with a risk-stratified surveillance, particularly in immunosuppressed albino patients in sub-Saharan Africa, and multidisciplinary management of this biologically unique cutaneous cancer.

PMID: 31143109 [PubMed]

Metastatic Merkel cell carcinoma and myasthenia gravis: contraindication for therapy with immune checkpoint inhibitors?

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

Metastatic Merkel cell carcinoma and myasthenia gravis: contraindication for therapy with immune checkpoint inhibitors?

J Immunother Cancer. 2019 May 29;7(1):141

Authors: Zaremba A, Chorti E, Jockenhöfer F, Bolz S, Sirin S, Glas M, Becker JC, Ugurel S, Roesch A, Schadendorf D, Livingstone E, Hagenacker T, Zimmer L

Abstract
BACKGROUND: PD-1/PD-L1 inhibitors are promising approaches for advanced Merkel cell carcinoma (MCC). Nevertheless, these inhibitors bear a high risk for induction of immune-related adverse events (irAEs), particularly flares of preexisting autoimmune diseases. Neurological irAEs of PD-1/PD-L1 inhibitors are possibly underestimated and potentially fatal toxicities. Additionally, exacerbations of preexisting myasthenia gravis (MG) with a high MG-specific-related mortality have been reported.
CASE PRESENTATION: A 61-year-old woman with a history of MG since 2005 was treated with azathioprine and pyridostigmine after thymectomy. In March 2016, she was diagnosed with MCC. Six months later the tumor had progressed to stage IV and metastases were detected in lymph nodes and the pancreas. The immunosuppressive therapy was therefore changed to mycophenolatmofetil (MMF) and an immune checkpoint blockade with the PD-1 inhibitor pembrolizumab was initiated in November 2016. Due to MMF-induced liver toxicity, MMF was switched to cyclosporine A (CsA) with normalized liver transaminases six weeks later. After six cycles of pembrolizumab the patient achieved a partial response. Follow up analysis sixty-five weeks later revealed a long-lasting tumor response with a partial remission of pancreatic and inguinal metastases and no flare of MG.
CONCLUSIONS: Patients with a preexisting MG can be considered for treatment with immune checkpoint inhibitors if they have a life-threatening cancer and if other effective, long-lasting treatment options are not available. The risks and benefits of therapy should be weighed in a multidisciplinary setting and should be discussed thoroughly with the patient. Exacerbation of underlying MG can be potentially life-threatening and requires close monitoring in collaboration with neuromuscular specialists.

PMID: 31142383 [PubMed - in process]

Permalink for 'Usefulness of ulceration and hyperkeratosis as clinical predictors of Merkel cell polyomavirus-negative and combined Merkel cell carcinoma: A retrospective study.'

Usefulness of ulceration and hyperkeratosis as clinical predictors of Merkel cell polyomavirus-negative and combined Merkel cell carcinoma: A retrospective study.

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

Usefulness of ulceration and hyperkeratosis as clinical predictors of Merkel cell polyomavirus-negative and combined Merkel cell carcinoma: A retrospective study.

J Dermatol. 2019 Feb;46(2):103-109

Authors: Nagase K, Kimura-Kaku H, Inoue T, Shinogi T, Narisawa Y

Abstract
Merkel cell carcinoma is a rare neuroendocrine carcinoma of the skin that is associated with Merkel cell polyomavirus (MCPyV). The clinical appearance and demographic characteristics of this tumor have been described using the mnemonic AEIOU: asymptomatic, expanding rapidly, immune suppression, older than 50 years, and ultraviolet-exposed fair skin. In addition, MCC can be categorized based on morphology as pure MCC or combined MCC that exhibits neuroendocrine and other phenotypic elements. There is limited information regarding the clinical characteristics and prognosis of combined MCC. This retrospective study aimed to identify factors, such as ulceration or hyperkeratosis, that could predict MCPyV status and morphological variants. Twenty patients with MCC were divided into groups based on MCPyV status and morphology: MCPyV-positive or MCPyV-negative MCC and pure or combined MCC. The patients' MCPyV status was immunohistochemically determined using the CM2B4 antibody to the MCPyV large T-antigen. The patients' clinicopathological characteristics were evaluated to identify predictors of MCPyV-negative MCC and combined MCC. The presence of ulceration/hyperkeratosis predicted the presence of MCPyV-negative MCC (80% of cases) and combined MCC (50% of cases). None of the 10 patients with MCPyV-positive MCC had ulceration/hyperkeratosis. The clinical presence of ulceration/hyperkeratosis may help guide the diagnosis of MCPyV-negative MCC and combined MCC.

PMID: 30565285 [PubMed - indexed for MEDLINE]

Development of predictive models to identify advanced-stage cancer patients in a US healthcare claims database.

Fetched: May 29th, 2019, 5:00am GMT

Development of predictive models to identify advanced-stage cancer patients in a US healthcare claims database.

Cancer Epidemiol. 2019 May 22;61:30-37

Authors: Esposito DB, Russo L, Oksen D, Yin R, Desai VCA, Lyons JG, Verpillat P, Peñalvo JL, Lamy FX, Lanes S

Abstract
BACKGROUND: Although healthcare databases are a valuable source for real-world oncology data, cancer stage is often lacking. We developed predictive models using claims data to identify metastatic/advanced-stage patients with ovarian cancer, urothelial carcinoma, gastric adenocarcinoma, Merkel cell carcinoma (MCC), and non-small cell lung cancer (NSCLC).
METHODS: Patients with ≥1 diagnosis of a cancer of interest were identified in the HealthCore Integrated Research Database (HIRD), a United States (US) healthcare database (2010-2016). Data were linked to three US state cancer registries and the HealthCore Integrated Research Environment Oncology database to identify cancer stage. Predictive models were constructed to estimate the probability of metastatic/advanced stage. Predictors available in the HIRD were identified and coefficients estimated by Least Absolute Shrinkage and Selection Operator (LASSO) regression with cross-validation to control overfitting. Classification error rates and receiver operating characteristic curves were used to select probability thresholds for classifying patients as cases of metastatic/advanced cancer.
RESULTS: We used 2723 ovarian cancer, 6522 urothelial carcinoma, 1441 gastric adenocarcinoma, 109 MCC, and 12,373 NSCLC cases of early and metastatic/advanced cancer to develop predictive models. All models had high discrimination (C > 0.85). At thresholds selected for each model, PPVs were all >0.75: ovarian cancer = 0.95 (95% confidence interval [95% CI]: 0.94-0.96), urothelial carcinoma = 0.78 (95% CI: 0.70-0.86), gastric adenocarcinoma = 0.86 (95% CI: 0.83-0.88), MCC = 0.77 (95% CI 0.68-0.89), and NSCLC = 0.91 (95% CI 0.90 - 0.92).
CONCLUSION: Predictive modeling was used to identify five types of metastatic/advanced cancer in a healthcare claims database with greater accuracy than previous methods.

PMID: 31128428 [PubMed - as supplied by publisher]

No Association between Merkel Cell Polymavirus Infection and Keratoacanthoma in Korean Patients

Fetched: May 29th, 2019, 5:00am GMT

No Association between Merkel Cell Polymavirus Infection and Keratoacanthoma in Korean Patients

Asian Pac J Cancer Prev. 2019 May 25;20(5):1299-1301

Authors: Kim DK

Abstract
Objectives: Keratoacanthoma (KA) is a relatively common benign tumor and resembles squamous cell carcinoma (SCC). The definitive cause of KA remains unclear, but trauma, ultraviolet light, chemical carcinogens, human papillomavirus, genetic factors, and immunocompromised status have been implicated as etiologic or triggering factors. Merkel cell polyomavirus (MCPyV) is suspected to cause the majority of cases of Merkel cell carcinoma (MCC). MCPyV-DNA was found significantly more frequently in MCC and only found in about one fourth of KAs. In a recent study, MCPyV was found in Korean patients with MCC. The aim of this study was to determine the presence of MCPyV in Korean patients with KA. Methods: Paraffin-embedded tissue samples were analyzed for the presence of MCPyV-DNA by polymerase chain reaction (PCR). A total of 105 KA samples were analyzed. Results: A study of MCPyV has not been reported about KA in Korean cases. In the present study the MCPyV was not detected with KA in the Korean patients. Conclusions: This supports that KA and MCPyV are not related to each other and MCVyP is not a major factor in the pathogenesis of KA.

PMID: 31127879 [PubMed - in process]

FDG-PET/CT for Spontaneous Regression of Metastatic Merkel Cell Carcinoma: Friend or Foe?

Fetched: May 29th, 2019, 5:00am GMT

FDG-PET/CT for Spontaneous Regression of Metastatic Merkel Cell Carcinoma: Friend or Foe?

Isr Med Assoc J. 2019 Jan;21(1):63-64

Authors: Berkowitz AS, Neuman T, Frenkel S, Eliashar R, Weinberger JM, Hirshoren N

Abstract

PMID: 30685912 [PubMed - indexed for MEDLINE]

Merkel cells in extraocular sebaceous carcinoma.

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

Merkel cells in extraocular sebaceous carcinoma.

J Cutan Pathol. 2019 Mar;46(3):171-174

Authors: Fernandez-Flores A, Cassarino DS

Abstract
INTRODUCTION: Mature sebaceous glands do not contain Merkel cells. Neither do sebaceous tumors in the vast majority of cases. Recently, however, it was showed that rare sebaceous adenomas with a carcinoid-like or labyrinthine pattern can contain intratumoral Merkel cells. Our purpose in this study is to examine for the presence of Merkel cells in extraocular sebaceous carcinomas.
METHODS: Nineteen cases of extraocular sebaceous carcinoma were retrospectively studied with cytokeratin 20.
RESULTS: One out of 19 cases (5.3%) contained Merkel cells in the basal layers of the tumoral nests of a sebaceous carcinoma from the cheek of a 76-year-old woman.
CONCLUSIONS: Merkel cells are rarely evident in extraocular sebaceous carcinoma, and therefore, their evidence does not exclude this diagnosis.

PMID: 30362151 [PubMed - indexed for MEDLINE]

Molecular and immune targets for Merkel cell carcinoma therapy and prevention.

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

Molecular and immune targets for Merkel cell carcinoma therapy and prevention.

Mol Carcinog. 2019 May 22;:

Authors: Cohen L, Tsai KY

Abstract
Merkel cell carcinoma (MCC) is a rare neuroendocrine carcinoma of the skin, for which the exact mechanisms of carcinogenesis remain unknown. Therapeutic options for this highly aggressive malignancy have historically been limited in both their initial response and response durability. Recent improvements in our understanding of MCC tumor biology have expanded therapeutic options for these patients, namely through the use of immunotherapies such as immune checkpoint inhibitors. Further elucidation of the tumor mutational landscape has identified molecular targets for therapies, which have demonstrated success in other cancer types. In this review, we discuss both current and investigational immune and molecular targets of therapy for MCC.

PMID: 31116890 [PubMed - as supplied by publisher]

Management of Sentinel Lymph Node Metastasis in Merkel Cell Carcinoma: Completion Lymphadenectomy, Radiation, or Both?

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

Management of Sentinel Lymph Node Metastasis in Merkel Cell Carcinoma: Completion Lymphadenectomy, Radiation, or Both?

Ann Surg Oncol. 2019 Feb;26(2):379-385

Authors: Perez MC, Oliver DE, Weitman ES, Boulware D, Messina JL, Torres-Roca J, Cruse CW, Gonzalez RJ, Sarnaik AA, Sondak VK, Wuthrick EJ, Harrison LB, Zager JS

Abstract
BACKGROUND: Approximately 30% of patients with clinically localized Merkel cell carcinoma (MCC) show nodal involvement on sentinel lymph node biopsy (SLNB). Optimal management of SLNB-positive disease has not been defined. This study compared outcomes after completion lymphadenectomy (CLND), radiation, and combined CLND plus radiation after a positive SLNB.
METHODS: All patients treated at a single institution for SLNB-positive MCC (1998-2015) were retrospectively evaluated, with examination of patient demographics, clinicopathologic characteristics, outcomes, and regional toxicity.
RESULTS: The study identified 71 evaluable patients with SLNB-positive disease. The median age of these patients was 76 years, and 76.1% were men. Of the 71 patients, 11 (15.5%) underwent CLND, 40 (56.3%) received radiation, and 20 (28.2%) underwent CLND plus postoperative radiation. Lymphovascular invasion was significantly more common in the radiation-alone cohort (p = 0.04). For the three cohorts, the median percentages of nodal involvement were respectively 2, 10, and 30% (p = 0.06). After a median follow-up period of 22.3 months, four patients had recurrence in their regional nodal basin (3 radiation-alone patients and 1 CLND + radiation patient). The three cohorts did not differ significantly in the development of distant metastases (p = 0.68) or overall survival (p = 0.72). Six patients experienced surgical-site infections (2 CLND and 4 CLND + radiation patients), and three patients experienced symptomatic lymphedema (1 CLND patient and 2 CLND + radiation patients).
CONCLUSIONS: Regional failure was infrequent (≤ 10%) regardless of treatment, and morbidity appeared to be low with all approaches. Given that multiple treatment approaches can be successful in treating micrometastatic MCC, future efforts should be directed at refining criteria for allocating patients to a specific method, or possibly no further nodal basin treatment, in an effort to maximize regional control at the lowest cost and morbidity.

PMID: 30311164 [PubMed - indexed for MEDLINE]

Completion Lymph Node Dissection or Radiation Therapy for Sentinel Node Metastasis in Merkel Cell Carcinoma.

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

Completion Lymph Node Dissection or Radiation Therapy for Sentinel Node Metastasis in Merkel Cell Carcinoma.

Ann Surg Oncol. 2019 Feb;26(2):386-394

Authors: Lee JS, Durham AB, Bichakjian CK, Harms PW, Hayman JA, McLean SA, Harms KL, Burns WR

Abstract
BACKGROUND: For sentinel lymph node (SLN) metastasis from Merkel cell carcinoma (MCC), the benefit of completion lymph node dissection (CLND) versus radiation therapy (RT) is unclear. This study compares outcomes for patients with SLN metastasis undergoing CLND or RT. We also evaluated positive non-SLNs as a prognostic factor.
METHODS: Using a prospective database, we identified MCC patients with SLN metastasis who underwent CLND or RT. At our institution, CLND was recommended for patients with acceptable perioperative risk, while therapeutic RT was offered to those with high perioperative risk. Primary outcomes were MCC-specific survival (MCCSS), disease-free survival (DFS), nodal recurrence-free survival (NRFS), and distant recurrence-free survival (DRFS).
RESULTS: From 2006 to 2017, 163 patients underwent CLND (n = 137) or RT (n = 26). Median follow-up was 1.9 years. CLND had no significant differences for MCCSS (5-year survival 71% vs. 64%, p = 1.0), DFS (52% vs. 61%, p = 0.8), NRFS (76% vs. 91%, p = 0.3), or DRFS (65% vs. 75%, p = 0.3) compared with RT. Patients with positive non-SLNs (n = 44) had significantly worse MCCSS (5-year survival 39% vs. 87%, p < 0.001), DFS (35% vs. 60%, p = 0.005), and DRFS (54% vs. 71%, p = 0.03) compared with negative non-SLNs (n = 93). Multivariate analysis showed positive non-SLNs were independently associated with MCCSS, DFS, and DRFS.
CONCLUSIONS: CLND and RT may have similar outcomes for MCC patients with SLN metastasis when treatment aligns with our institutional practices. For patients undergoing CLND, positive non-SLNs is an important prognostic factor associated with poor survival and distant recurrence. This high-risk group should be considered for adjuvant systemic therapy trials.

PMID: 30556118 [PubMed - indexed for MEDLINE]

Permalink for 'Management of Regional Lymph Nodes in Patients with Merkel Cell Carcinoma Following a Positive Sentinel Node Biopsy: Less May be More, But is Either Enough?'

Management of Regional Lymph Nodes in Patients with Merkel Cell Carcinoma Following a Positive Sentinel Node Biopsy: Less May be More, But is Either Enough?

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

Management of Regional Lymph Nodes in Patients with Merkel Cell Carcinoma Following a Positive Sentinel Node Biopsy: Less May be More, But is Either Enough?

Ann Surg Oncol. 2019 Feb;26(2):315-317

Authors: Hruby G, Guminski A, Thompson JF

Abstract

PMID: 30483975 [PubMed - indexed for MEDLINE]

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

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

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

J Am Acad Dermatol. 2019 May 16;:

Authors: Elias ML, Lambert WC, Schwartz RA

PMID: 31103565 [PubMed - as supplied by publisher]

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

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

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

Am J Surg Pathol. 2019 May 13;:

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

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

PMID: 31094923 [PubMed - as supplied by publisher]

Mohs Micrographic Surgery: Past, Present, and Future.

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

Mohs Micrographic Surgery: Past, Present, and Future.

Dermatol Surg. 2019 03;45(3):329-339

Authors: Cohen DK, Goldberg DJ

Abstract
BACKGROUND: Mohs micrographic surgery (MMS) is a frequently used technique that provides total margin visualization for treatment of skin neoplasms.
OBJECTIVE: To provide a comprehensive review of MMS literature, focusing on its origins, evidence behind present-day uses of MMS, and future directions.
METHODS: A literature search was conducted using PubMed to identify articles pertaining to MMS.
RESULTS: The fresh frozen technique led to widespread use of MMS in the 1970s. One randomized controlled trial and several large prospective studies have demonstrated low recurrence rates for treatment of nonmelanoma skin cancer (NMSC). MMS, when compared with surgical excision, also achieved a statistically significant higher cure rate for treatment of recurrent NMSC. Studies have demonstrated low recurrence for the treatment of melanoma and melanoma in situ with MMS. MMS has also been shown to effectively treat several rare cutaneous neoplasms. The future of MMS is likely to include the adoption of noninvasive imaging, immunostaining, and digital technology.
CONCLUSION: Mohs micrographic surgery is an effective treatment modality for numerous cutaneous neoplasms. It has achieved statistically significant superiority to surgical excision for the treatment of recurrent and high-risk NMSC. The future is likely to see increased use of noninvasive imaging, immunostaining, and digital technology.

PMID: 30608296 [PubMed - indexed for MEDLINE]

Merkel Cell Carcinoma: Updates on Staging and Management.

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

Merkel Cell Carcinoma: Updates on Staging and Management.

Dermatol Clin. 2019 Jul;37(3):269-277

Authors: Cornejo C, Miller CJ

Abstract
Merkel cell carcinoma is an aggressive neuroendocrine carcinoma with increasing incidence over the past few decades. The TNM Staging System used for Merkel cell carcinoma was updated by the American Joint Committee on Cancer in 2017. Clinical practice guidelines were updated by the National Comprehensive Cancer Network on August 31, 2018. This article reviews the most recent evidence-based updates on staging and management.

PMID: 31084721 [PubMed - in process]

Neurofilament is superior to cytokeratin 20 in supporting cutaneous origin for neuroendocrine carcinoma.

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

Neurofilament is superior to cytokeratin 20 in supporting cutaneous origin for neuroendocrine carcinoma.

Histopathology. 2019 Feb;74(3):504-513

Authors: Stanoszek LM, Chan MP, Palanisamy N, Carskadon S, Siddiqui J, Patel RM, Harms KL, Lowe L, Fullen DR, Harms PW

Abstract
AIM: Primary cutaneous neuroendocrine carcinoma, or Merkel cell carcinoma (MCC), cannot be distinguished morphologically from small-cell neuroendocrine carcinomas (SmCC) from other sites. Immunohistochemistry is required to confirm cutaneous origin, and is also used for detection of sentinel lymph node (SLN) metastases of MCC. Cytokeratin 20 (CK20) expression is commonly used for these purposes, but is negative in some MCC cases, and has unclear specificity. We evaluated immunohistochemistry for neurofilament and CK20 in MCC compared with SmCC from other sites.
METHODS AND RESULTS: We evaluated neurofilament expression in 55 MCC specimens from 39 unique patients, including nine CK20-negative MCC tumours. Neurofilament expression was observed in 42 of 55 (76.4%) MCC cases, including seven of nine (77.8%) CK20-negative MCC cases. Neurofilament was expressed in nine of 12 (75%) Merkel cell polyomavirus-positive tumours and five of 10 (50%) virus-negative tumours. Compared to a standard immunohistochemical panel (cytokeratin cocktail and CK20), neurofilament was 87.5% sensitive for detecting SLN metastases. Neurofilament and CK20 expression was also assessed in 61 extracutaneous SmCC from 60 unique patients, with primary sites including lung (27), bladder (18), cervix (3), gastrointestinal tract (3), sinonasal tract (2) and other sites (7). The specificity of neurofilament and CK20 for MCC versus non-cutaneous SmCC was 96.7% and 59.0%, respectively.
CONCLUSIONS: Neurofilament has superior specificity to CK20 in distinguishing MCC from non-cutaneous SmCC. Neurofilament is frequently expressed in CK20- and virus-negative MCC tumours. Limitations of neurofilament immunohistochemistry include lower sensitivity than CK20 and subtle staining in some tumours. However, our findings indicate that neurofilament is useful for excluding non-cutaneous SmCC.

PMID: 30239030 [PubMed - indexed for MEDLINE]

Avelumab in gastric cancer.

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

Avelumab in gastric cancer.

Immunotherapy. 2019 May 06;:

Authors: Roviello G, D'Angelo A, Generali D, Pittacolo M, Ganzinelli M, Iezzi G, Manzini N, Sobhani N

Abstract
Gastric cancer (GC) is the fifth most common malignancy and the third cause of cancer-related deaths worldwide. Currently, surgery and chemotherapy remain the main therapeutic options and the prognosis of the disease is still poor in the metastatic setting. Avelumab is a human IgG1 antibody directed against PD-L1 approved for Merkel cell carcinoma and urothelial carcinoma that could be useful also for the treatment of GC. This review describes the chemical structure, the pharmacologic properties and the current knowledge of the efficacy of avelumab in the treatment of GC from the data available on the first and later phase clinical trials. The ongoing studies testing this drug either alone or in combination with other drugs are also described.

PMID: 31060469 [PubMed - as supplied by publisher]

[Carcinoma of unknown primary. Case no. 3].

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

[Carcinoma of unknown primary. Case no. 3].

Ann Pathol. 2018 Jun;38(3):174-178

Authors: Selves J

PMID: 29929743 [PubMed - indexed for MEDLINE]

S2k guidelines for Merkel cell carcinoma (MCC, neuroendocrine carcinoma of the skin) - update 2018.

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

S2k guidelines for Merkel cell carcinoma (MCC, neuroendocrine carcinoma of the skin) - update 2018.

J Dtsch Dermatol Ges. 2019 May 06;:

Authors: Becker JC, Eigentler T, Frerich B, Gambichler T, Grabbe S, Höller U, Klumpp B, Loquai C, Krause-Bergmann A, Müller-Richter U, Pföhler C, Schneider-Burrus S, Stang A, Terheyden P, Ugurel S, Veith J, Mauch C

Abstract
Merkel cell carcinoma (MCC, ICD-O M8247 / 3) is a rare malignant primary skin tumor with epithelial and neuroendocrine differentiation. The neoplastic cells share many morphological, immunohistochemical and ultrastructural characteristics with Merkel cells of the skin. The diagnosis of MCC is rarely made on clinical grounds. Histological and immunohistochemical studies are usually required to confirm the clinical suspicion. Given the frequent occurrence of occult lymph node metastasis, sentinel lymph node biopsy should be performed once distant metastasis has been ruled out by cross-sectional imaging. Primary tumors without evidence of organ metastases are treated with complete surgical excision with appropriate surgical margins. Radiation therapy should be considered at all stages of the disease. For advanced MCC that is no longer amenable to curative treatment by surgery or radiation therapy, there is currently no established systemic therapy for which an improvement in recurrence-free survival or overall survival has been demonstrated in a prospective randomized trial. However, immunotherapy using PD-1/PD-L1 blockade seems to be superior to chemotherapy. Various factors warrant that further diagnostic and therapeutic interventions be determined by an interdisciplinary tumor board. These factors include the tumor's aggressiveness, the frequent indication for sentinel lymph node biopsy along with the frequent occurrence in the head and neck region, the potential indication for adjuvant radiation therapy as well as the complexity of the required diagnostic workup.

PMID: 31056838 [PubMed - as supplied by publisher]

Permalink for 'Successful treatment of an elderly Langerhans cell sarcoma patient by EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) chemotherapy.'

Successful treatment of an elderly Langerhans cell sarcoma patient by EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) chemotherapy.

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

Successful treatment of an elderly Langerhans cell sarcoma patient by EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) chemotherapy.

J Clin Exp Hematop. 2018 12 13;58(4):184-187

Authors: Matsukawa T, Suto K, Miyoshi H, Oshimi K, Ohshima K, Miyagishima T

PMID: 30305476 [PubMed - indexed for MEDLINE]

Permalink for 'Expanding the Indication for Novel Theranostic 177Lu-Dotatate Peptide Receptor Radionuclide Therapy: Proof-of-Concept of PRRT in Merkel Cell Cancer.'

Expanding the Indication for Novel Theranostic 177Lu-Dotatate Peptide Receptor Radionuclide Therapy: Proof-of-Concept of PRRT in Merkel Cell Cancer.

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

Expanding the Indication for Novel Theranostic 177Lu-Dotatate Peptide Receptor Radionuclide Therapy: Proof-of-Concept of PRRT in Merkel Cell Cancer.

Case Rep Oncol. 2019 Jan-Apr;12(1):98-103

Authors: Kasi PM, Sharma A, Jain MK

Abstract
The field of theranostics is a new nuclear medicine tool being utilized in the treatment of different types of cancers. It couples receptor-specific based imaging predicting and guiding response to receptor-specific based radionuclide therapies. For example, somatostatin-receptor based imaging (Gallium; 68Ga-dotatate scan) is now predicting and guiding the use of treatment with the somatostatin-receptor radiolabeled somatostatin analog (peptide receptor radionuclide therapy PRRT - Lutetium; 177Lu-Dotatate) for neuroendocrine tumors that express the somatostatin receptors. The United States Food and Drug Administration approved the use of 177Lu-Dotatate PRRT for somatostatin-receptor-positive gastroenteropancreatic neuroendocrine tumors only. Here we show proof of concept and results of an outstanding response to this novel therapy in conjunction with immunotherapy in a refractory cancer type where it has not been approved (Merkel Cell Cancer). Our results and data provide proof of principle for considering the use of this novel therapy in a tumor-agnostic approach; similar to approval of immunotherapy for mismatch repair deficient tumors. The response demonstrated has also been unprecedented, likely secondary to use of PRRT with immunotherapy. These observations have profound and broad implications on how to move this novel field of theranostics forward for treatment of many cancer-types.

PMID: 31043945 [PubMed]

$Permalink for 'Rescue of Immunotherapy-Refractory Metastatic Merkel Cell Carcinoma With Conventionally Fractionated Radiotherapy and Concurrent Pembrolizumab.'$

Rescue of Immunotherapy-Refractory Metastatic Merkel Cell Carcinoma With Conventionally Fractionated Radiotherapy and Concurrent Pembrolizumab.

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

Rescue of Immunotherapy-Refractory Metastatic Merkel Cell Carcinoma With Conventionally Fractionated Radiotherapy and Concurrent Pembrolizumab.

Front Oncol. 2019;9:223

Authors: Bloom BC, Augustyn A, Pezzi TA, Menon H, Mayo LL, Shah SJ, Schwartz DL, Chmura SJ, Johnson FM, Welsh JW, Chun SG

Abstract
Merkel cell carcinoma has historically had dismal prognosis with limited cytotoxic chemotherapy options that provide durable control of metastatic disease. The advent of anti-programmed death protein (anti-PD1)/anti-programmed death-ligand 1 (anti-PD-L1) directed immunotherapy has shown initial promise in Merkel cell carcinoma and radiation might augment immune responses. We present a case report of a 70-year-old male who underwent resection of Merkel cell carcinoma of the right thigh with a close margin and positive right inguinal involvement. Due to high-risk features, the patient was treated with adjuvant radiation to the right groin and with systemic carboplatin/etoposide, but developed local failure requiring salvage surgical resection. The patient then developed metastatic disease with biopsy proven retroperitoneal involvement refractory to doxorubicin/cyclophosphamide chemotherapy. The patient was then transitioned to single-agent pembrolizumab with a partial response for 10 months until developing progressive disease involving the left inguinal and left external iliac nodal regions. The progressive left inguinal/pelvic disease was treated with conventionally fractionated intensity modulated radiation therapy to a dose of 45 Gy delivered in 25 fractions. Following radiation therapy, the patient had complete response of all sites of disease throughout the body on imaging by RECIST criteria including retroperitoneal and mediastinal disease outside the radiation field. At 20 months post-radiation, the patient remains on pembrolizumab without evidence of disease on imaging. Herein, we present a case of durable response of metastatic Merkel cell carcinoma treated with concurrent radiation and pembrolizumab, providing evidence that radiation might improve systemic responses to anti-PD1/PD-L1 directed immune therapy. Ongoing prospective trials evaluating the utility of radiation in conjunction with immunotherapy for Merkel cell carcinoma are anticipated to provide clarity on the frequency and durability of abscopal responses when radiation is combined with immune checkpoint inhibitors.

PMID: 31024834 [PubMed]

TLR4 in skin cancer: From molecular mechanisms to clinical interventions.

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

TLR4 in skin cancer: From molecular mechanisms to clinical interventions.

Mol Carcinog. 2019 Apr 24;:

Authors: Dickinson SE, Wondrak GT

Abstract
The health and economic burden imposed by skin cancer is substantial, creating an urgent need for the development of improved molecular strategies for its prevention and treatment. Cutaneous exposure to solar ultraviolet (UV) radiation is a causative factor in skin carcinogenesis, and TLR4-dependent inflammatory dysregulation is an emerging key mechanism underlying detrimental effects of acute and chronic UV exposure. Direct and indirect TLR4 activation, upstream of inflammatory signaling, is elicited by a variety of stimuli, including pathogen-associated molecular patterns (such as lipopolysaccharide) and damage-associated molecular patterns (such as HMGB1) that are formed upon exposure to environmental stressors, such as solar UV. TLR4 involvement has now been implicated in major types of skin malignancies, including nonmelanoma skin cancer, melanoma and Merkel cell carcinoma. Targeted molecular interventions that positively or negatively modulate TLR4 signaling have shown promise in translational, preclinical, and clinical investigations that may benefit skin cancer patients in the near future.

PMID: 31020719 [PubMed - as supplied by publisher]

Merkel cell carcinoma: an aggressive cutaneous carcinoma with rare metastasis to the thyroid gland.

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

Merkel cell carcinoma: an aggressive cutaneous carcinoma with rare metastasis to the thyroid gland.

BMJ Case Rep. 2019 Apr 23;12(4):

Authors: Vaiciunaite D, Beddell G, Ivanov N

Abstract
Merkel cell carcinoma (MCC) is an aggressive and rare neuroendocrine cutaneous carcinoma with poor prognosis and with increasing morbidity and mortality in cases of distant metastasis. Given the rarity of MCC, optimal treatment is not well established. Treatment usually consists of multidisciplinary management with local excision of the primary tumour. Imaging studies are essential for accurate staging and monitoring of disease progression. The incidence of local recurrence is highest in the first 2 years and ranges from 27% to 60%. Distant metastasis is most common in the skin, liver, bone, lung/pleura, brain or distant lymph nodes. The thyroid gland is a rare site of metastasis for MCC with only two case reports published to date. Our patient had a repeat 2-[18F]-fluoro-2-deoxy-d-glucose-postiron emission tomography/CT after the discovery of recurrence of MCC. The high-intensity maximal standardised uptake value of 10.9 in the thyroid isthmus is consistent with malignancy. This case report describes an exceedingly rare thyroid metastasis secondary to MCC.

PMID: 31015241 [PubMed - in process]

Merkel cell carcinoma of the eyelid and orbit.

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

Merkel cell carcinoma of the eyelid and orbit.

Cesk Slov Oftalmol. Spring 2018;74(1):37-43

Authors: Furdová A, Michalková M, Javorská L

Abstract
The incidence of Merkel cell carcinoma has tended to increase worldwide in recent years. Merkel cell carcinoma is a rare tumor of the skin that occurs mainly in the sun exposed sites. The malignant reversal of Merkel cells is currently associated with an infection caused by a Merkel cell polyomavirals. In some cases, the disease may have a relatively inconspicuous clinical picture in the initial phase, which is in contrast to its extensive microscopic propagation. For this reason, the risk of late diagnosis or insufficient primary surgery is increased. The diagnostic standard is histological and, in particular, immunohistochemical examination of tumor tissue samples. Merkel cell carcinoma is a marked tendency to local recurrence and early development of metastases in regional lymph nodes, followed by generalization. The basis of treatment is radical excision of the tumor by in most cases by adjuvant radiotherapy targeted at primary place of occurrence and the area of regional draining lymph nodes. The effectiveness of different chemotherapeutic protocols in Merkel cell carcinoma is mostly low and the median survival is low. From a prognostic point of view, Merkel cell carcinoma plays the most important role of staging the tumor at the time of capture. The suspected lesions in the area around the eye, eyelid and orbit need to indicate adequate therapeutic approach that the detection of the disease at the earliest stage. The authors describe the clinical experience in 2 patients with Merkel cell carcinoma of the eyelid and orbit. Key words: eyelid tumors, tumors of the orbit, Merkel cell carcinoma.

PMID: 30541295 [PubMed - indexed for MEDLINE]

Permalink for 'Advances in the Understanding of Skin Cancer: Ultraviolet Radiation, Mutations, and Antisense Oligonucleotides as Anticancer Drugs.'

Advances in the Understanding of Skin Cancer: Ultraviolet Radiation, Mutations, and Antisense Oligonucleotides as Anticancer Drugs.

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

Advances in the Understanding of Skin Cancer: Ultraviolet Radiation, Mutations, and Antisense Oligonucleotides as Anticancer Drugs.

Molecules. 2019 Apr 17;24(8):

Authors: Laikova KV, Oberemok VV, Krasnodubets AM, Gal'chinsky NV, Useinov RZ, Novikov IA, Temirova ZZ, Gorlov MV, Shved NA, Kumeiko VV, Makalish TP, Bessalova EY, Fomochkina II, Esin AS, Volkov ME, Kubyshkin AV

Abstract
Skin cancer has always been and remains the leader among all tumors in terms of occurrence. One of the main factors responsible for skin cancer, natural and artificial UV radiation, causes the mutations that transform healthy cells into cancer cells. These mutations inactivate apoptosis, an event required to avoid the malignant transformation of healthy cells. Among these deadliest of cancers, melanoma and its 'younger sister', Merkel cell carcinoma, are the most lethal. The heavy toll of skin cancers stems from their rapid progression and the fact that they metastasize easily. Added to this is the difficulty in determining reliable margins when excising tumors and the lack of effective chemotherapy. Possibly the biggest problem posed by skin cancer is reliably detecting the extent to which cancer cells have spread throughout the body. The initial tumor is visible and can be removed, whereas metastases are invisible to the naked eye and much harder to eliminate. In our opinion, antisense oligonucleotides, which can be used in the form of targeted ointments, provide real hope as a treatment that will eliminate cancer cells near the tumor focus both before and after surgery.

PMID: 30999681 [PubMed - in process]

$Permalink for 'MHC class-I downregulation in PD-1/PD-L1 inhibitor refractory Merkel cell carcinoma and its potential reversal by histone deacetylase inhibition: a case series.'$

MHC class-I downregulation in PD-1/PD-L1 inhibitor refractory Merkel cell carcinoma and its potential reversal by histone deacetylase inhibition: a case series.

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

MHC class-I downregulation in PD-1/PD-L1 inhibitor refractory Merkel cell carcinoma and its potential reversal by histone deacetylase inhibition: a case series.

Cancer Immunol Immunother. 2019 Apr 16;:

Authors: Ugurel S, Spassova I, Wohlfarth J, Drusio C, Cherouny A, Melior A, Sucker A, Zimmer L, Ritter C, Schadendorf D, Becker JC

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive skin cancer in which PD-1/PD-L1 blockade has shown remarkable response rates. However, a significant proportion of patients shows primary or secondary resistance against PD-1/PD-L1 inhibition, with HLA class-I downregulation and insufficient influx of CD8+ T cells into the tumor as possible immune escape mechanisms. Histone deacetylase inhibitors (HDACi) have been demonstrated to reverse low HLA class-I expression caused by epigenetic downregulation of the antigen machinery (APM) in vitro and in pre-clinical models in vivo.
CASE PRESENTATIONS: We report four cases of patients with metastatic MCC who did not respond to immunotherapy by PD-1/PD-L1 blockade. Two of the patients received, subsequently, the HDACi panobinostat in combination with PD-1/PD-L1 blockade. Tumor biopsies of the patients were analyzed for cellular and molecular markers of antigen processing and presentation as well as the degree of T-cell infiltration.
RESULTS AND CONCLUSION: Low expression of APM-related genes associated with low HLA class-I surface expression was observed in all MCC patients, progressing on PD-1/PD-L1 blockade. In one evaluable patient, of the two treated with the combination therapy of the HDACi, panobinostat and PD-1/PD-L1 blockade, reintroduction of HLA class-I-related genes, enhanced HLA class-I surface expression, and elevated CD8+ T-cell infiltration into the MCC tumor tissue were observed; however, these changes did not translate into a clinical benefit. Our findings suggest that HDACi may be useful to overcome HLA class-I downregulation as a resistance mechanism against anti-PD-1/PD-L1 antibodies in MCC patients. Prospective clinical trials are needed to evaluate this notion.

PMID: 30993371 [PubMed - as supplied by publisher]

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]

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

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

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

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

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

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

Adoptive Transfer of Tumor Infiltrating Lymphocytes for Advanced Solid Cancers

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

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

High-Risk Skin Cancers With Atezolizumab Plus NT-I7

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

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

AMPLIFYing NEOepitope-specific VACcine Responses in Progressive Diffuse Glioma

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

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

Evaluate Efficacy of Avelumab, haNK and N-803 in Subjects With Progressed MCC on or After Checkpoint Inhibitor Therapy.

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

Condition: Merkel Cell Carcinoma
Interventions: Biological: Avelumab; Biological: N-803; Biological: haNK™
Sponsors: NantKwest, Inc.; NantCell, Inc.
Not yet recruiting

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

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

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

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

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

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

Conditions: Clinical Stage III Cutaneous Melanoma AJCC v8; Clinical Stage III Merkel Cell Carcinoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Clinical Stage IV Merkel Cell Carcinoma AJCC v8; High-Frequency Microsatellite Instability; Kidney Transplant Recipient; 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)
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; Castration-resistant Prostate Cancer
Interventions: Drug: AB928; Drug: AB122
Sponsor: Arcus Biosciences, Inc.
Recruiting

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

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

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

A Study of INCMGA00012 in Metastatic Merkel Cell Carcinoma

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

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

Lymph Node Identification in Skin Malignancy Using ICG Transcutaneously Study

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

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

A Safety and Tolerability Study of INCAGN02385 in Select Advanced Malignancies

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Intra-Peritoneal Local Anaesthetics in Ovarian Cancer

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

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

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

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

Conditions: Stage IV Non-small Cell Lung Cancer; Stage IV Malignant Melanoma
Intervention: Other: Plasma sample collection
Sponsor: OncoHost Ltd.
Not yet recruiting

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

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

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

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

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

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

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

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

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

TAS-102 in Extrapulmonary Neuroendocrine Carcinoma

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

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

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

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

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

A Study of SGN-CD228A in Advanced Solid Tumors

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

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

68Ga-DOTATATE PET/CT in Neuroendocrine Tumor

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

Condition: Neuroendocrine Tumors
Intervention: Drug: 68Ga-DOTATATE
Sponsor: Peking Union Medical College Hospital
Recruiting

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

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

Conditions: Ganglioneuroblastoma; Ganglioneuroma; Metastatic Neuroblastoma
Interventions: Procedure: Computed Tomography; Drug: Gallium Ga 68-DOTATATE; Procedure: Positron Emission Tomography
Sponsors: Mayo Clinic; National Cancer Institute (NCI)
Not yet recruiting

Improving Skin Cancer Management With Artificial Intelligence (04.17 SMARTI)

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

Conditions: Skin Cancer; Melanoma (Skin)
Intervention: Device: Molemap Skin Cancer Triage Artificial Intelligence Device
Sponsors: Melanoma and Skin Cancer Trials Limited; Molemap Australia Pty Ltd; Monash University
Not yet recruiting

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

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

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

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

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

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

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

The Master Registry of Oncology Outcomes Associated With Testing and Treatment

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

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

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

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

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

Dynamic Whole Body Positron Emission Tomography/Computed Tomography Imaging

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

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

Sonidegib and Pembrolizumab in Treating Patients With Advanced Solid Tumors

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

Conditions: Clinical Stage III Cutaneous Melanoma AJCC v8; Clinical Stage III Gastric Cancer AJCC v8; Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Clinical Stage IV Gastric Cancer AJCC v8; Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IVA Gastric Cancer AJCC v8; Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IVB Gastric Cancer AJCC v8; Clinical Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8; High-Frequency Microsatellite Instability; Locally Advanced Urothelial Carcinoma; Metastatic Gastric Adenocarcinoma; Metastatic Gastroesophageal Junction Adenocarcinoma; Metastatic Head and Neck Squamous Cell Carcinoma; Metastatic Lung Non-Small Cell Carcinoma; Metastatic Malignant Solid Neoplasm; Metastatic Melanoma; Metastatic Pancreatic Adenocarcinoma; Metastatic Urothelial Carcinoma; Mismatch Repair Deficiency; Pathologic Stage III Cutaneous Melanoma AJCC v8; Pathologic Stage III Gastric Cancer AJCC v8; Pathologic Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IIIA Gastric Cancer AJCC v8; Pathologic Stage IIIA Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IIIB Gastric Cancer AJCC v8; Pathologic Stage IIIB Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IIIC Gastric Cancer AJCC v8; Pathologic Stage IV Cutaneous Melanoma AJCC v8; Pathologic Stage IV Gastric Cancer AJCC v8; Pathologic Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8; PD-L1 Positive; Progressive Disease; Recurrent Head and Neck Squamous Cell Carcinoma; Refractory Lung Non-Small Cell Carcinoma; Refractory Pancreatic Adenocarcinoma; Stage II Pancreatic Cancer AJCC v8; Stage IIA Pancreatic Cancer AJCC v8; Stage IIB Pancreatic Cancer AJCC v8; Stage III Pancreatic Cancer AJCC v8; Stage IV Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8; Stage IV Lung Cancer AJCC v8; Stage IV Pancreatic Cancer AJCC v8; Stage IVA Lung Cancer AJCC v8; Stage IVB Lung Cancer AJCC v8; Unresectable Malignant Solid Neoplasm; Unresectable Melanoma; Unresectable Pancreatic Adenocarcinoma
Interventions: Biological: Pembrolizumab; Drug: Sonidegib
Sponsors: Mayo Clinic; National Cancer Institute (NCI)
Not yet recruiting

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

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

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

Conditions: Melanoma Stage III; Melanoma Stage IV
Interventions: Drug: Nivolumab; Drug: BMS-986205; Drug: Ipilimumab
Sponsors: Dana-Farber Cancer Institute; Bristol-Myers Squibb
Not yet recruiting

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

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

Conditions: Brain Metastases; Melanoma; Lung Cancer; Breast Cancer
Interventions: Drug: Dexamethasone; Drug: Metformin
Sponsors: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano; University of Milan
Not yet recruiting

3TMPO (Triple-Tracer Strategy Against Metastatic Prostate Cancer

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

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

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

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

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

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

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

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

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

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

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

Cryoablation of Bone Metastases From Endocrine Tumors

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

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

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

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

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

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

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

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

Conditions: KRAS Gene Mutation; Metastatic Colorectal Carcinoma; NRAS Gene Mutation; Stage III Colorectal Cancer AJCC v8; Stage IIIA Colorectal Neuroendocrine Tumor AJCC v8; Stage IIIB Colorectal Cancer AJCC v8; Stage IIIC Colorectal Cancer AJCC v8; Stage IV Colorectal Cancer AJCC v8; Stage IVA Colorectal Cancer AJCC v8; Stage IVB Colorectal Cancer AJCC v8; Stage IVC Colorectal Cancer AJCC v8; Unresectable Carcinoma
Interventions: Drug: Binimetinib; Drug: Palbociclib; Drug: Trifluridine and Tipiracil Hydrochloride
Sponsors: Academic and Community Cancer Research United; National Cancer Institute (NCI)
Not yet recruiting

PDR001 + Panobinostat for Melanoma and NSCLC

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

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

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

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

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

Conditions: Neuroendocrine Tumors; Neuroendocrine Neoplasm; Gastroenteropancreatic Neuroendocrine Tumor
Interventions: Drug: Nivolumab; Drug: Carboplatin; Drug: Etoposide
Sponsor: Grupo Espanol de Tumores Neuroendocrinos
Not yet recruiting

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

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

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

CT Radiomic Features of Pancreatic Neuroendocrine Neoplasms

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

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

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

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

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

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

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

Condition: Melanoma
Interventions: Biological: hu14.18-IL2; Radiation: Radiation Therapy; Biological: Nivolumab; Biological: Ipilimumab
Sponsors: University of Wisconsin, Madison; National Cancer Institute (NCI); Bristol-Myers Squibb; Apeiron Biologics; Provenance Biopharmaceuticals
Not yet recruiting

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

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

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

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

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

Condition: Pancreatic Neuroendocrine Tumor
Intervention:
Sponsor: Ipsen
Recruiting

A Phase 1/2 Study of IDE196 in Patients With Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions

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

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

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

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

Condition: Advanced Melanoma
Interventions: Biological: JS001(Toripalimab Injection); Drug: Axitinib
Sponsor: Beijing Cancer Hospital
Recruiting

Adoptive Transfer of Tumor Infiltrating Lymphocytes for Advanced Solid Cancers

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

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

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

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

Dosimetry Guided PRRT With 177Lu-DOTATATE in Children

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Conditions: Metastatic Prostate Adenocarcinoma; Prostate Adenocarcinoma With Focal Neuroendocrine Differentiation; Recurrent Prostate Carcinoma; Stage IVB Prostate Cancer AJCC v8
Interventions: Drug: Abiraterone Acetate; Drug: Apalutamide; Drug: Leuprolide Acetate; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Radiation: Stereotactic Body Radiation Therapy
Sponsors: Jonsson Comprehensive Cancer Center; National Cancer Institute (NCI)
Not yet recruiting

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

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

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

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

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

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

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

Survivin Long Peptide Vaccine in Treating Patients With Metastatic Neuroendocrine Tumors

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

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

DEBOXA for Inoperable NET Liver Metastases

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

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

68Ga-DOTATATE PET for Management of Neuroendocrine Tumors

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

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

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

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

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

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

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

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

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

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

Conditions: Bladder Adenocarcinoma; Bladder Mixed Adenocarcinoma; Bladder Small Cell Carcinoma; Bladder Squamous Cell Carcinoma; Bone Lesion; 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 Carcinoma; Metastatic Bladder Squamous Cell Carcinoma; Metastatic Infiltrating Bladder Urothelial Carcinoma, Clear Cell Variant; Metastatic Infiltrating Bladder Urothelial Carcinoma, Lipid-Rich Variant; Metastatic Infiltrating Bladder Urothelial Carcinoma, Micropapillary Variant; Metastatic Infiltrating Bladder Urothelial Carcinoma, Plasmacytoid Variant; Metastatic Infiltrating Bladder Urothelial Carcinoma, Sarcomatoid Variant; Metastatic Kidney Medullary Carcinoma; Metastatic Malignant Genitourinary System Neoplasm; Metastatic Penile Carcinoma; Metastatic Prostate Small Cell Carcinoma; Metastatic Sarcomatoid Renal Cell Carcinoma; Papillary Renal Cell Carcinoma; Sarcomatoid Renal Cell Carcinoma; Stage IV Bladder Cancer AJCC v8; Stage IV Penile Cancer AJCC v8; Stage IV Prostate Cancer AJCC v8; Stage IV Renal Cell Cancer AJCC v8; Stage IVA Bladder Cancer AJCC v8; Stage IVA Prostate Cancer AJCC v8; Stage IVB Bladder Cancer AJCC v8; Stage IVB Prostate Cancer AJCC v8; Testicular Leydig Cell Tumor; Testicular Sertoli Cell Tumor
Interventions: Drug: Cabozantinib; Drug: Cabozantinib S-malate; Biological: Ipilimumab; Biological: Nivolumab
Sponsor: National Cancer Institute (NCI)
Recruiting

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

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

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

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

The Lyon Real World Evidence in Metastatic NeuroEndocrine Tumours

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

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

Inhaled Essential Oil Effect on Common QOL Concerns During Cancer Treatment

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

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

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; Prostate Carcinoma; MSI-H; Mismatch Repair Deficiency
Interventions: Biological: XmAb®22841; Biological: Pembrolizumab (Keytruda®)
Sponsors: Xencor, Inc.; ICON Clinical Research
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; Behavioral: Clinician Preference for Treatment
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
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

Permalink for 'This Study is a Phase II Study of AZD6738 in Combination With Durvalumab in Patients With Solid Tumor (Cohort A (N=30): GC Who Have Failed Secondary Chemotherapy Treatments Regimen; Cohort B (B=30): Melanoma Patients Who Have Failed to IO)'

This Study is a Phase II Study of AZD6738 in Combination With Durvalumab in Patients With Solid Tumor (Cohort A (N=30): GC Who Have Failed Secondary Chemotherapy Treatments Regimen; Cohort B (B=30): Melanoma Patients Who Have Failed to IO)

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

Conditions: Gastric Adenocarcinoma; Malignant Melanoma
Interventions: Drug: AZD6738; Drug: Durvalumab
Sponsor: Samsung Medical Center
Not yet recruiting

Study of RP1 Monotherapy and RP1 in Combination With Nivolumab

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

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

A Study of XmAb®23104 in Subjects With Selected Advanced Solid Tumors (DUET-3)

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

Conditions: Melanoma (Excluding Uveal Melanoma); Cervical Carcinoma; Pancreatic Carcinoma; Breast Carcinoma That is Estrogen Receptor, Progesterone Receptor, and Her2 Negative; 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 Cancer; Gastric or Gastroesophageal Junction Adenocarcinoma; Advanced Solid Tumors
Intervention: Biological: XmAb®23104
Sponsors: Xencor, Inc.; ICON plc
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
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
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

Bronchoscopic Laser Ablation of Peripheral Lung Tumors

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

Conditions: Lung Carcinoid Tumor; Lung Non-Small Cell Carcinoma; Metastatic Lung Carcinoma; Stage IV Lung Cancer AJCC v8; Stage IVA Lung Cancer AJCC v8; Stage IVB Lung Cancer AJCC v8
Interventions: Procedure: Cone-Beam Computed Tomography; Procedure: Conventional Surgery; Procedure: Laser Ablation
Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI)
Recruiting

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

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

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

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

Exploration of Molecular Biomarkers for Lu-177 DOTATATE Therapy in Midgut Neuroendocrine Tumor

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

Condition: Midgut Neuroendocrine Tumors
Intervention: Biological: non-drug intervention type
Sponsor: University Hospital, Toulouse
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

Small cell and large cell neuroendocrine carcinoma of the larynx: A comparative analysis.

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

Small cell and large cell neuroendocrine carcinoma of the larynx: A comparative analysis.

Cancer Treat Rev. 2019 Aug 08;78:42-51

Authors: Strojan P, Hernandez-Prera JC, Beitler JJ, Eisbruch A, Saba NF, Mendenhall WM, Nieto CS, Smee R, Rinaldo A, Ferlito A

Abstract
The poorly differentiated neuroendocrine carcinomas (NECs) of the larynx are rare tumors that comprise of a small cell-type (SCNEC) and a large cell-type (LCNEC). In order to consolidate the current knowledge about their characteristics and management a systematic review of the available literature was performed. The PubMed/Medline and Scopus databases search resulted in 141 articles published between 1972 and 2019, describing 273 patients: 230 cases were of SCNEC histology (84.2%) and 43 cases were LCNECs (15.8%). Comparing both histological entities, patients with LCNECs were older (63.2 vs. 58.7 years, p = 0.036) than SCNEC patients and had more often primary tumor in a supraglottic larynx (79.5 vs. 56.1%, p = 0.039), advanced-stage neck disease (N2-3, 56.8 vs. 40%, p = 0.061), surgery-based treatment (83.7 vs. 51.9%, p < 0.001) and had no radiotherapy (44.2 vs. 29%, p = 0.071). At presentation, systemic metastases were diagnosed in 12.1% of the patients, whereas disease relapse was experienced by two-thirds (65.3%) of those initially staged M0; systemic relapse, alone or in combination with local/regional recurrence, was the most frequent type of failure (in 71.9%). On multivariate analysis, more advanced disease stage and SCNEC histology adversely influenced disease-specific survival. Wide variations in the pattern of care, including radiotherapy doses and chemotherapy regimens, were found among long-term survivors without known disease at ≥ 24 months of follow-up (N = 36). We conclude that the most effective treatment for poorly differentiated NECs has yet to be determined.

PMID: 31437725 [PubMed - as supplied by publisher]

Permalink for 'Insulinoma-associated protein 1 is a novel diagnostic marker of small cell lung cancer in bronchial brushing and cell block cytology from pleural effusions: Validity and reliability with cutoff value.'

Insulinoma-associated protein 1 is a novel diagnostic marker of small cell lung cancer in bronchial brushing and cell block cytology from pleural effusions: Validity and reliability with cutoff value.

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

Insulinoma-associated protein 1 is a novel diagnostic marker of small cell lung cancer in bronchial brushing and cell block cytology from pleural effusions: Validity and reliability with cutoff value.

Cancer Cytopathol. 2019 Aug 22;:

Authors: Abe H, Takase Y, Sadashima E, Fukumitsu C, Murata K, Ito T, Kawahara A, Naito Y, Akiba J

Abstract
BACKGROUND: In recent years, insulinoma-associated protein 1 (INSM1) has been shown to be a key regulator of neuroendocrine development, and it has been evaluated for diagnostic use in some organs.
METHODS: To evaluate the relationship between INSM1 and synaptophysin, and to confirm the cutoff value using receiver operating characteristic curve (ROC) analysis, the authors performed INSM1 immunocytochemistry using cell block (CB) samples from 53 cases of bronchial brushings and 32 cases of pleural effusions (29 small cell lung cancer [SCLC] specimens and 56 non-small cell lung cancer specimens). The marker expression ratio was calculated by counting the positive tumor cells, and the tumor proportion score (TPS) was applied.
RESULTS: INSM1 was expressed in all SCLC specimens, but generally was expressed in <10% of tumor cells in adenocarcinomas. In bronchial brushing samples of SCLC, the INSM1 TPS was 37.5% (staining of >50%), 25.0% (staining of 25%-50%), 29.5% (staining of 10%-25%), and 8.3% (staining of 1%-10%). There were 3 cases (12.5%) with no detectable synaptophysin expression, although the correlation between nuclear INSM1 expression and cytoplasmic synaptophysin expression was statistically significant (P < .001). Receiver operating characteristic curve analysis indicated that 8.68% was the best cutoff value for INSM1, and the sensitivity and specificity between SCLC and non-small cell lung cancer for expression of INSM1 were 95.8% and 100.0%, respectively, in bronchial brushing samples at that cutoff value.
CONCLUSIONS: INSM1 is a novel diagnostic marker for SCLC, and is useful in both bronchial brushing and pleural effusion cytology specimens. Because INSM1 generally is expressed in <10% of tumor cells in adenocarcinomas, determining an accurate cutoff value for INSM1 is important in the diagnosis of SCLC.

PMID: 31436913 [PubMed - as supplied by publisher]

The forgotten role of adjuvant immune checkpoint inhibitors in preventing melanoma brain metastasis.

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

The forgotten role of adjuvant immune checkpoint inhibitors in preventing melanoma brain metastasis.

Immunotherapy. 2018 11;10(15):1289-1291

Authors: El Rassy E, Farhat F, Kattan J

PMID: 30474477 [PubMed - indexed for MEDLINE]

Efficacy and safety of PD-1 inhibitors for treating advanced melanoma: a systematic review and meta-analysis.

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

Efficacy and safety of PD-1 inhibitors for treating advanced melanoma: a systematic review and meta-analysis.

Immunotherapy. 2018 11;10(15):1293-1302

Authors: Li J, Gu J

Abstract
AIM: We conducted a meta-analysis to systematically review the efficacy and safety of programmed cell death 1 (PD-1) inhibitors for advanced melanoma.
STUDY DESIGN: The relevant studies of the randomized controlled trials in melanoma patients treated with PD-1 inhibitors were retrieved and the systematic evaluation was conducted. Databases were searched till June 2018.
RESULTS: PD-1 inhibitors significantly improved the progression-free survival, overall survival and overall response rate in patients with advanced melanoma. Progression-free survival, overall survival and overall response rate did not vary significantly according to PD-L1 status, V-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations and type of drug, but varied significantly by control therapy. PD-1 inhibitors were associated with a decreased risk of adverse events compared with ipilimumab, but an increased risk of immune-related events compared with chemotherapy.
CONCLUSION: The PD-1 inhibitors-containing therapy was efficacious in treating advanced melanoma.

PMID: 30474476 [PubMed - indexed for MEDLINE]

scFTD-seq: freeze-thaw lysis based, portable approach toward highly distributed single-cell 3' mRNA profiling.

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

scFTD-seq: freeze-thaw lysis based, portable approach toward highly distributed single-cell 3' mRNA profiling.

Nucleic Acids Res. 2019 02 20;47(3):e16

Authors: Dura B, Choi JY, Zhang K, Damsky W, Thakral D, Bosenberg M, Craft J, Fan R

Abstract
Cellular barcoding of 3' mRNAs enabled massively parallel profiling of single-cell gene expression and has been implemented in droplet and microwell based platforms. The latter further adds the value for compatibility with low input samples, optical imaging, scalability, and portability. However, cell lysis in microwells remains challenging despite the recently developed sophisticated solutions. Here, we present scFTD-seq, a microchip platform for performing single-cell freeze-thaw lysis directly toward 3' mRNA sequencing. It offers format flexibility with a simplified, widely adoptable workflow that reduces the number of preparation steps and hands-on time, with the quality of data and cost per sample matching that of the state-of-the-art scRNA-seq platforms. Freeze-thaw, known as an unfavorable lysis method resulting in possible RNA fragmentation, turns out to be fully compatible with 3' scRNA-seq. We applied it to the profiling of circulating follicular helper T cells implicated in systemic lupus erythematosus pathogenesis. Our results delineate the heterogeneity in the transcriptional programs and effector functions of these rare pathogenic T cells. As scFTD-seq decouples on-chip cell isolation and library preparation, we envision it to allow sampling at the distributed sites including point-of-care settings and downstream processing at centralized facilities, which should enable wide-spread adoption beyond academic laboratories.

PMID: 30462277 [PubMed - indexed for MEDLINE]

Permalink for 'Rapid complete remission of metastatic melanoma after first-line treatment with nivolumab plus tumor-infiltrating lymphocytes.'

Rapid complete remission of metastatic melanoma after first-line treatment with nivolumab plus tumor-infiltrating lymphocytes.

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

Rapid complete remission of metastatic melanoma after first-line treatment with nivolumab plus tumor-infiltrating lymphocytes.

Immunotherapy. 2018 09;10(13):1133-1136

Authors: Zhao L, Yang Y, Li W, Han L, Lin H, Gao Q

Abstract
Melanoma is the most common type of skin cancer in both men and women in the USA. The standard treatment modality for advanced melanoma is immunotherapy, either alone or in combination. As single-agent immunotherapy is usually inadequate, combined immunotherapy might be a good choice and combined treatment modalities appropriate for melanoma need to be explored. Herein, we report a case of metastatic melanoma successfully treated with combined therapy of tumor-infiltrating lymphocytes and nivolumab. Complete remission was achieved approximately 4 months after the initiation of treatment. The treatment was well tolerated and only grade 1 fatigue occurred. The patient was still on complete remission 1 year after stopping the treatment. Our result showed that this treatment modality might be an ideal option for patients with metastatic melanoma.

PMID: 30236024 [PubMed - indexed for MEDLINE]

Dual TLR agonist nanodiscs as a strong adjuvant system for vaccines and immunotherapy.

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

Dual TLR agonist nanodiscs as a strong adjuvant system for vaccines and immunotherapy.

J Control Release. 2018 07 28;282:131-139

Authors: Kuai R, Sun X, Yuan W, Ochyl LJ, Xu Y, Hassani Najafabadi A, Scheetz L, Yu MZ, Balwani I, Schwendeman A, Moon JJ

Abstract
Recent studies have shown that certain combinations of Toll-like receptor (TLR) agonists can induce synergistic immune activation. However, it remains challenging to achieve such robust responses in vivo in a manner that is effective, facile, and amenable for clinical translation. Here, we show that MPLA, a TLR4 agonist, and CpG, a TLR9 agonist, can be efficiently co-loaded into synthetic high-density lipoprotein nanodiscs, forming a potent adjuvant system (ND-MPLA/CpG) that can be readily combined with a variety of subunit antigens, including proteins and peptides. ND-MPLA/CpG significantly enhanced activation of dendritic cells, compared with free dual adjuvants or nanodiscs delivering a single TLR agonist. Importantly, mice immunized with physical mixtures of protein antigens ND-MPLA/CpG generated strong humoral responses, including induction of IgG responses against protein convertase subtilisin/kexin 9 (PCSK9), leading to 17-30% reduction of the total plasma cholesterol levels. Moreover, ND-MPLA/CpG exerted strong anti-tumor efficacy in multiple murine tumor models. Compared with free adjuvants, ND-MPLA/CpG admixed with ovalbumin markedly improved antigen-specific CD8+ T cell responses by 8-fold and promoted regression of B16F10-OVA melanoma (P < 0.0001). Furthermore, ND-MPLA/CpG admixed with E7 peptide antigen elicited ~20% E7-specific CD8+ T cell responses and achieved complete regression of established TC-1 tumors in all treated animals. Taken together, our work highlights the simplicity, versatility, and potency of dual TLR agonist nanodiscs for applications in vaccines and cancer immunotherapy.

PMID: 29702142 [PubMed - indexed for MEDLINE]

Permalink for 'First person: Antoni Ribas, MD, PhD: The physician-scientist from the University of California at Los Angeles researches how new therapies for patients with advanced malignant melanoma can help to overcome resistance to treatment.'

First person: Antoni Ribas, MD, PhD: The physician-scientist from the University of California at Los Angeles researches how new therapies for patients with advanced malignant melanoma can help to overcome resistance to treatment.

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

First person: Antoni Ribas, MD, PhD: The physician-scientist from the University of California at Los Angeles researches how new therapies for patients with advanced malignant melanoma can help to overcome resistance to treatment.

Cancer. 2018 03 15;124(6):1097-1098

Authors: Printz C

PMID: 29509327 [PubMed - indexed for MEDLINE]

Indocyanine green and fluorescence lymphangiography for sentinel node identification in patients with melanoma.

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

Indocyanine green and fluorescence lymphangiography for sentinel node identification in patients with melanoma.

Am J Surg. 2018 09;216(3):558-561

Authors: Pameijer CR, Leung A, Neves RI, Zhu J

Abstract
BACKGROUND: Infrared fluorescence imaging with indocyanine green (ICG) is a novel method for sentinel node localization. Our objective was to assess ICG and fluorescence imaging for preoperative and intraoperative utility.
METHODS: 87 eligible patients participated in this prospective study. All patients received injection of ICG dye in addition to both methylene blue and 99mTc. Each sentinel node was assessed for the presence of each dye.
RESULTS: ICG was visible prior to incision in 44% of subjects. 99mTc identified a mean of 1.89 SLN per patient. ICG identified a mean of 1.87 SLN while methylene blue (MB) dye identified a mean of 0.71 SLN. 99mTc and ICG identified the same number of sentinel nodes per patient (P = .73) while methylene blue was inferior in its ability to localize sentinel nodes (P < .001).
CONCLUSION: Our findings indicate that ICG/fluorescence imaging has limited ability to identify the nodal basin preoperatively, but is equivalent to 99mTc for intraoperative identification of sentinel nodes and superior to MB.

PMID: 29395022 [PubMed - indexed for MEDLINE]

Low-grade Appendiceal Mucinous Neoplasm and Endometriosis: Incidental Coincident Pathologies at Cesarean Section.

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

Low-grade Appendiceal Mucinous Neoplasm and Endometriosis: Incidental Coincident Pathologies at Cesarean Section.

Int J Gynecol Pathol. 2019 Aug 19;:

Authors: Yohannes N, Watkins JC, Weeks AG, Osmundson SS, Shi C, Kovach AE

Abstract
Incidental pathologic findings at the time of Cesarean section are exceedingly uncommon. Similarly, occult low-grade appendiceal mucinous neoplasms and other noninflammatory, non-neoplastic appendiceal pathologies are rare, although appendiceal neoplasia, most commonly well-differentiated neuroendocrine tumors, may be found during evaluation of acute appendicitis. Here we report the first case of incidental coincident low-grade appendiceal mucinous tumor and endometriosis involving the appendix at the time of Cesarean section. We highlight pitfalls in the histopathologic evaluation of these processes, particularly given the setting of decidualization of ectopic endometrial stroma, as well as the prognostic implications of low-grade appendiceal mucinous tumors to emphasize the importance of clinicopathologic correlation and careful intraoperative examination of the appendix and other visible structures during Cesarean section.

PMID: 31433375 [PubMed - as supplied by publisher]

Ovarian Steroid Cell Tumor in an Adolescent With Von Hippel-Lindau Syndrome: A Case Report and Review of the Literature.

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

Ovarian Steroid Cell Tumor in an Adolescent With Von Hippel-Lindau Syndrome: A Case Report and Review of the Literature.

Int J Gynecol Pathol. 2019 Aug 19;:

Authors: Marques A, Portugal R

Abstract
Von Hippel-Lindau (VHL) syndrome is an autosomal dominant genetic disorder caused by germline mutation of the VHL gene. It is associated with multiple neoplasias including hemangioblastoma, clear cell renal cell carcinoma, pheochromocytoma, and neuroendocrine tumors. Ovarian tumors are extremely rare in this syndrome. We describe the case of a 16-yr-old girl with a previous diagnosis of bilateral pheochromocytoma and several pancreatic neuroendocrine tumors in VHL syndrome context. Follow-up abdominal-pelvic magnetic resonance imaging revealed a 33 mm, well-circumscribed nodule in the right ovary. The patient was submitted to laparoscopic right salpingo-oophorectomy. Microscopically, the tumor consisted of polygonal cells with abundant microvacuolized clear cytoplasm arranged in a solid pattern. The neoplastic cells were immunohistochemically positive for inhibin and calretinin. A diagnosis of ovarian steroid cell tumor was made. Only 4 cases with this association have been reported to date. Of the previously described cases, only one concerns a child; the others were all adult women. All of them had a previous diagnosis of VHL syndrome and presented with secondary amenorrhea and/or hirsutism due to testosterone-secreting ovarian steroid cell tumors. Although extremely rare, the association between VHL syndrome and ovarian steroid cell tumor has been reported, and our case suggests there is a link between the 2 entities.

PMID: 31433374 [PubMed - as supplied by publisher]

The impact of angiogenesis inhibitors on survival of patients with small cell lung cancer.

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

The impact of angiogenesis inhibitors on survival of patients with small cell lung cancer.

Cancer Med. 2019 Aug 21;:

Authors: Shi X, Dong X, Young S, Chen AM, Liu X, Zheng Z, Huang K, Lu D, Feng S, Morahan G, Cai K

Abstract
BACKGROUND: Small cell lung cancer (SCLC) is a highly invasive and lethal neuroendocrine tumor. Antiangiogenic drugs have been reported in the treatment of SCLC. We aimed to provide a comprehensive evaluation of the impact of angiogenic inhibitors on SCLC survival using network meta-analysis.
METHODS: The impact of five angiogenesis inhibitors, that is, vandetanib (Van), bevacizumab (Bev), Rh-endostatin (End), sunitinib (Sun), and thalidomide (Tha), on progression-free survival (PFS) and overall survival (OS) was evaluated by conducting a network meta-analysis. RNA sequencing data were downloaded from publicly available databases.
RESULTS: Nine phase II and III randomized controlled trials (RCTs), that involved 1599 participants, that investigated angiogenesis inhibitors in the treatment of SCLC were included in this meta-analysis. Sun and Bev achieved better PFS than Tha (Bev VS. Tha, HR = 0.88, 95% CI: 0.79-0.98, Sun VS. Tha, HR = 0.80, 95% CI: 0.65-1.00). Moreover, Sun and Bev were superior to placebo in terms of PFS (Bev VS. Placebo, HR = 0.89, 95%CI: 0.81-0.97, Sun VS. Placebo, HR = 0.81, 95% CI: 0.66-1.00). Based on this study, we found no significant difference of OS of SCLC. The angiogenesis pathway and expression of target genes were globally deactivated in SCLC tissue.
CONCLUSION: Results of this network meta-analysis indicate that the PFS outcome of SCLC with Sun or Bev drugs is superior to that of Tha. The improved therapeutic impact of angiogenesis inhibitors on SCLC needs more evidence, such as long-term observation in clinical trials, to be validated.

PMID: 31433125 [PubMed - as supplied by publisher]

New cytotoxic cembranolides from an Okinawan soft coral, Lobophytum sp.

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

New cytotoxic cembranolides from an Okinawan soft coral, Lobophytum sp.

Fitoterapia. 2019 Jul;136:104162

Authors: Roy PK, Roy S, Ueda K

Abstract
Three new cembranolides (1-3) were isolated from an Okinawan soft coral, Lobophytum sp., together with the known cembranolide diterpenoids (4-9). Their structures were determined by extensive analysis of spectroscopic data (1D and 2D NMR, IR, and MS), molecular modeling, and comparison with data reported elsewhere. All compounds contain an α-methylene-γ-lactone ring adjacent to a cembrane, and some of them (1, 6-8) have an epoxide ring as well. The new metabolites were evaluated for cytotoxicity against HeLa, A459, B16-F10, and RAW 264.7 cells and anti-inflammatory effect in LPS-stimulated inflammatory RAW 264.7 macrophage cells.

PMID: 31075489 [PubMed - indexed for MEDLINE]

Nanostructured SL9-CpG Lipovaccines Elicit Immune Response for the Treatment of Melanoma.

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

Nanostructured SL9-CpG Lipovaccines Elicit Immune Response for the Treatment of Melanoma.

Int J Mol Sci. 2019 May 05;20(9):

Authors: Mu LM, Liu L, Liu R, Du YF, Luo Q, Xu JR, Xie Y, Lu WL

Abstract
Antigen peptides and adjuvants have been extensively investigated for cancer immunotherapy, and they are expected to elicit specific immune responses for cancer treatment. However, the anti-cancer efficacy of antigen peptide and adjuvant-based cancer vaccines has been limited due to the inefficient delivery to draining lymph nodes after administration. Therefore, it is necessary to develop a suitable delivery system to transport antigen peptides and adjuvants. Here, we report a novel type of nanostructured lipovaccines for the treatment of melanoma by delivering antigen peptide (SL9) and oligodeoxynucleotide adjuvant (CpG) to the lymphatic vessels and to the draining lymph node. The SL9-CpG lipovaccines were characterized using dynamic laser scattering (DLS) and transmission electron microscopy (TEM). The lymph uptake, immune response elicitation and treatment effects were evaluated on melanoma-bearing C57BL/6 mice using flow cytometry (FCM), enzyme-linked immunosorbent assay (ELISA) and tumor inhibitory efficacy. The SL9-CpG lipovaccines were uniform with a nanoscale size (~70 nm), had high encapsulation efficiency, and exhibited effective lymph uptake, resulting in activation of specific cytotoxic CD8+ T cells, and release of IFN-γ, and a robust inhibition of tumor growth. Therefore, the nanostructured SL9-CpG lipovaccines offer a promising strategy for melanoma treatment.

PMID: 31060324 [PubMed - indexed for MEDLINE]

Permalink for 'Occurrence of non-toxic bioemulsifiers during polyhydroxyalkanoate production by Pseudomonas strains valorizing crude glycerol by-product.'

Occurrence of non-toxic bioemulsifiers during polyhydroxyalkanoate production by Pseudomonas strains valorizing crude glycerol by-product.

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

Occurrence of non-toxic bioemulsifiers during polyhydroxyalkanoate production by Pseudomonas strains valorizing crude glycerol by-product.

Bioresour Technol. 2019 Jun;281:31-40

Authors: Kourmentza C, Araujo D, Sevrin C, Roma-Rodriques C, Lia Ferreira J, Freitas F, Dionisio M, Baptista PV, Fernandes AR, Grandfils C, Reis MAM

Abstract
While screening for polyhydroxyalkanoate (PHA) producing strains, using glycerol rich by-product as carbon source, it was observed that extracellular polymers were also secreted into the culture broth. The scope of this study was to characterize both intracellular and extracellular polymers, produced by Pseudomonas putida NRRL B-14875 and Pseudomonas chlororaphis DSM 50083, mostly focusing on those novel extracellular polymers. It was found that they fall into the class of bioemulsifiers (BE), as they showed excellent emulsion stability against different hydrocarbons/oils at various pH conditions, temperature and salinity concentrations. Cytotoxicity tests revealed that BE produced by P. chlororaphis inhibited the growth of highly pigmented human melanoma cells (MNT-1) by 50% at concentrations between 150 and 200 μg/mL, while no effect was observed on normal skin primary keratinocytes and melanocytes. This is the first study reporting mcl-PHA production by P. putida NRRL B-14785 and bioemulsifier production from both P. putida and P. chlororaphis strains.

PMID: 30798087 [PubMed - indexed for MEDLINE]

Permalink for 'Inter- and intrapatient heterogeneity of indoleamine 2,3-dioxygenase expression in primary and metastatic melanoma cells and the tumour microenvironment.'

Inter- and intrapatient heterogeneity of indoleamine 2,3-dioxygenase expression in primary and metastatic melanoma cells and the tumour microenvironment.

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

Inter- and intrapatient heterogeneity of indoleamine 2,3-dioxygenase expression in primary and metastatic melanoma cells and the tumour microenvironment.

Histopathology. 2019 May;74(6):817-828

Authors: Gide TN, Allanson BM, Menzies AM, Ferguson PM, Madore J, Saw RPM, Thompson JF, Long GV, Wilmott JS, Scolyer RA

Abstract
AIMS: Indoleamine 2,3-dioxygenase (IDO), an immunomodulatory enzyme, facilitates immune escape by tumours and promotes tumour progression. IDO inhibitors with and without additional anti-PD-1 therapy have been evaluated in recent and ongoing melanoma clinical trials, but IDO expression in melanoma tumours, and therefore its potential role as a predictive biomarker remains unknown. This study sought to evaluate IDO expression in immunotherapy-naive metastatic melanoma patients in order to determine patterns of expression in corresponding primary melanomas, locoregional metastases and distant metastases.
METHODS AND RESULTS: Here, we evaluated IDO expression using immunohistochemistry in 99 melanoma tumour samples from 43 immunotherapy-naive patients with metastatic melanoma to determine patterns of expression in primary melanomas (n = 29), locoregional metastases (n = 36) and distant metastases (n = 34). Thirty-seven per cent of patients demonstrated tumour IDO expression in at least one specimen. Twelve of 35 patients (34%) with longitudinal specimens (i.e. two or more separate specimens from different disease stages in the same patient) displayed heterogeneous IDO staining between samples. Tumour IDO expression positively correlated with tumour-infiltrating lymphocyte (TIL) score as well as the number of IDO-expressing mononuclear cells in the primary melanoma (P < 0.0001 and P = 0.0011, respectively) and nodal metastases (P = 0.049 and P = 0.037, respectively), but not in distant metastases. Furthermore, tumour IDO expression correlated positively with PD-L1 expression by melanoma cells among all specimens (P = 0.0073).
CONCLUSIONS: Therefore, while assessment of tumour IDO expression warrants evaluation in melanoma patient cohorts treated with IDO inhibitors dosed at levels proven to inhibit the target by pharmacodynamic assessment, its utility as a biomarker may be limited by intertumoral heterogeneity.

PMID: 30589949 [PubMed - indexed for MEDLINE]

Permalink for 'Comparison of melanoma gene expression score with histopathology, fluorescence in situ hybridization, and SNP array for the classification of melanocytic neoplasms.'

Comparison of melanoma gene expression score with histopathology, fluorescence in situ hybridization, and SNP array for the classification of melanocytic neoplasms.

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

Comparison of melanoma gene expression score with histopathology, fluorescence in situ hybridization, and SNP array for the classification of melanocytic neoplasms.

Mod Pathol. 2018 11;31(11):1733-1743

Authors: Reimann JDR, Salim S, Velazquez EF, Wang L, Williams KM, Flejter WL, Brooke L, Sunder S, Busam KJ

Abstract
While most melanomas can be distinguished from nevi by histopathology, the histology is ambiguous for some melanocytic tumors, contributing to diagnostic uncertainty. Therefore molecular assays, including FISH or SNP array, and more recently a gene expression test (myPath, Myriad Genetics) have been proposed to aid in the work-up of ambiguous tumors. Two hundred and sixty-eight prospectively submitted cases were gathered, with the goal of comparing the myPath assay to morphologic diagnosis in (1) morphologically unequivocal cases (198), and to morphologic diagnosis and FISH in (2) morphologically ambiguous cases (70). Melanoma FISH was performed using probes for 6p25, 6q23, 11q13, Cep6, 9p21, and Cep9 and scored according to established criteria. The myPath assay was scored by the manufacturer as benign, indeterminate, or malignant. In the unequivocal group, myPath assay showed 75% agreement with morphologic diagnosis, with 67% sensitivity and 81% specificity. In the ambiguous group, FISH and myPath showed 69% inter-test agreement. For these cases agreement with histopathologic interpretation was 84% for FISH and 74% for myPath. Sensitivity and specificity of FISH was 61 and 100%, 50 and 93% for myPath, respectively. Cases from both groups in which myPath was discordant with either morphologic diagnosis and/or FISH (81/268 cases), were submitted for evaluation by two experienced dermatopathologist and also by SNP-array. SNP-array results correlated better than FISH, which correlated better than myPath, with the morphologic interpretation. Our findings document that molecular diagnostics show good correlation with consensus diagnoses, but discordant results occur, and vary in level of correlation with consensus interpretations. Studies with long-term outcomes data within specific ambiguous lesion subsets are required to establish the accuracy of this test, as each molecular diagnostic technique has limitations based on both lack of clinical outcomes data in ambiguous melanocytic tumors and in terms of their sensitivity and specificity in melanocytic lesion subtypes.

PMID: 29955141 [PubMed - indexed for MEDLINE]

Permalink for 'S100B and LDH as early prognostic markers for response and overall survival in melanoma patients treated with anti-PD-1 or combined anti-PD-1 plus anti-CTLA-4 antibodies.'

S100B and LDH as early prognostic markers for response and overall survival in melanoma patients treated with anti-PD-1 or combined anti-PD-1 plus anti-CTLA-4 antibodies.

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

S100B and LDH as early prognostic markers for response and overall survival in melanoma patients treated with anti-PD-1 or combined anti-PD-1 plus anti-CTLA-4 antibodies.

Br J Cancer. 2018 08;119(3):339-346

Authors: Wagner NB, Forschner A, Leiter U, Garbe C, Eigentler TK

Abstract
BACKGROUND: Immunotherapy with PD-1 antibodies has greatly increased prognosis of patients with advanced melanoma. Identifying biomarkers that predict overall survival (OS) and response to immunotherapy is important.
METHODS: OS and best overall response according to RECIST version 1.1 were analysed, and S100B and lactate dehydrogenase (LDH) serum levels were assessed retrospectively in 152 patients treated with anti-PD-1, and in 86 patients treated with anti-PD-1 plus anti-CTLA-4 antibodies at University Hospital Tuebingen, Germany.
RESULTS: In the pembrolizumab group, patients with elevated baseline S100B or LDH exhibited significantly impaired OS compared with patients with normal S100B (1-year OS: 51.1% vs 83.1%, log-rank P < .0001) and normal LDH (1-year OS: 44.4% vs 80.8%, P = .00022), respectively. LDH increases of >25% and S100B increases of >145% compared to baseline were significantly associated with impaired OS (both P < .0001). In patients treated with ipilimumab and nivolumab, baseline S100B and increasing S100B levels of >145% as well as baseline LDH were associated with impaired OS (P < .0001, P = .00060, and P = .0050, respectively), whereas increasing LDH of >25% was not (P = .64).
CONCLUSIONS: S100B could serve as a strong baseline marker for OS in melanoma patients receiving anti-PD-1 therapy. Rising S100B levels during the first weeks of therapy could help guide treatment decisions.

PMID: 29950611 [PubMed - indexed for MEDLINE]

Synchronous Presentation of Pheochromocytoma and Epidermoid Lung Carcinoma.

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

Synchronous Presentation of Pheochromocytoma and Epidermoid Lung Carcinoma.

Ann Thorac Surg. 2018 08;106(2):e99

Authors: Gregory J, Bennani S, Freche G, Mansuet-Lupo A, Revel MP, Chassagnon G

PMID: 29551630 [PubMed - indexed for MEDLINE]

5-Fluorouracil ethosomes - skin deposition and melanoma permeation synergism with microwave.

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

5-Fluorouracil ethosomes - skin deposition and melanoma permeation synergism with microwave.

Artif Cells Nanomed Biotechnol. 2018;46(sup1):568-577

Authors: Khan NR, Wong TW

Abstract
This study focuses on the use of ethosome and microwave technologies to facilitate skin penetration and/or deposition of 5-fluorouracil in vitro and in vivo. Low ethanol ethosomes were designed and processed by mechanical dispersion technique and had their size, zeta potential, morphology, drug content and encapsulation efficiency characterized. The skin was pre-treated with microwave at 2450 MHz for 2.5 min with ethosomes applied topically and subjected to in vitro and in vivo skin drug permeation as well as retention evaluation. The drug and/or ethosomes cytotoxicity, uptake and intracellular trafficking by SKMEL-28 melanoma cell culture were evaluated. Pre-treatment of skin by microwave promoted significant drug deposition in skin from ethosomes in vitro while keeping the level of drug permeation unaffected. Similar observations were obtained in vivo with reduced drug permeation into blood. Combination ethosome and microwave technologies enhanced intracellular localization of ethosomes through fluidization of cell membrane lipidic components as well as facilitating endocytosis by means of clathrin, macropinocytosis and in particularly lipid rafts pathways. The synergistic use of microwave and ethosomes opens a new horizon for skin malignant melanoma treatment.

PMID: 29378453 [PubMed - indexed for MEDLINE]

Management of Well-Differentiated High-Grade (G3) Neuroendocrine Tumors.

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

Management of Well-Differentiated High-Grade (G3) Neuroendocrine Tumors.

Curr Treat Options Oncol. 2019 Aug 19;20(9):74

Authors: Sonbol MB, Halfdanarson TR

Abstract
OPINION STATEMENT: In 2017, the World Health Organization (WHO) classification for pancreatic NET was updated to include a new category of well-differentiated high-grade (Ki 67 > 20%) pancreatic tumors (NET G3), distinct from high-grade poorly differentiated neuroendocrine carcinoma (NEC). NET G3 are considered a molecularly, radiologically, and prognostically distinct entity compared to NEC and NET G1/G2. The optimal first-line management in NET G3 and sequencing therapies remains a challenge awaiting future trials taking into consideration the unique characteristics of this category. In this review, we aim to summarize the current evidence in the management of NET G3.

PMID: 31428952 [PubMed - in process]

Cushing Syndrome Secondary to Primary Neuroendocrine Lung Carcinoma.

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

Cushing Syndrome Secondary to Primary Neuroendocrine Lung Carcinoma.

Case Rep Endocrinol. 2019;2019:1989260

Authors: Zainal A, Akinsola O, Rajamani K

Abstract
Cushing syndrome (CS) is a disorder characterized by a result of chronic exposure to excessive glucocorticoids. This article describes a case of a 30-year-old female presenting with fatigue, abdominal striae, unintentional weight gain, and lipodystrophy. A rare diagnosis of ectopic adrenocorticotropic-dependent CS was determined and a neuroendocrine lung tumor (NET) was discovered on chest x-ray. After surgical resection, pathology confirmed lung NET that stained positive for adrenocorticotropic hormone (ACTH). The patient's symptoms fully resolved. The authors aim to urge clinicians to maintain a high index of suspicion for ectopic ACTH secretion (EAS) through a multimodal approach when caring for patients with CS.

PMID: 31428483 [PubMed]

shRNA-WT1 Potentiates Anticancer Effects of Gemcitabine and Cisplatin Against B16F10 Lung Metastases In Vitro and In Vivo.

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

shRNA-WT1 Potentiates Anticancer Effects of Gemcitabine and Cisplatin Against B16F10 Lung Metastases In Vitro and In Vivo.

In Vivo. 2019 May-Jun;33(3):777-785

Authors: Zapata-Benavides P, Thompson-Armendariz FG, Arellano-Rodríguez M, Franco-Molina MA, Mendoza-Gamboa E, Saavedra-Alonso S, Zacarias-Hernández JL, Trejo-Avila LM, Rodríguez-Padilla C

Abstract
BACKGROUND/AIM: High expression level of Wilm's tumor gene (WT1) in several types of tumors appears to confer disruption of apoptosis and resistance to chemotherapeutic drugs, and correlate with poor outcome. The aim of this work was to determine if down-regulation of WT1 expression results in decreased cell proliferation and the increased action of different types of drugs, both in vitro in B16F10 cells, and in vivo in C57BL/6 mice.
MATERIALS AND METHODS: Inhibition of cell proliferation by short hairpin RNA against WT1 (shRNA-WT1), cisplatin, and gemcitabine in B16F10 cells in vitro was determined by the MTT assay and analysis of clonogenic survival. The apoptosis rate was determined by flow cytometry for annexin-V- fluorescein isothiocyante and propidium iodide.
RESULTS: Compared to treatment with shRNA-WT1 alone, treatment with shRNA-WT1 in combination with drugs had a synergistic inhibitory effect on B16F10 cell proliferation, particularly for the combination of cisplatin and gemcitabine at their 25% cytotoxic concentrations in vitro. Furthermore, mice treated with shRNA-WT1 in combination with cisplatin and gemcitabine were protected in the same way as those treated with the drugs alone, but were in better physical condition.
CONCLUSION: Decreased WT1 expression induces cell death and potentiates the action of anticancer drugs by inducing synergistic effects both in vitro and in vivo, which may be an attractive strategy in lung cancer therapy.

PMID: 31028197 [PubMed - indexed for MEDLINE]

Permalink for 'Effect of electrochemotherapy with betulinic acid or cisplatin on regulation of heat shock proteins in metastatic human carcinoma cells in vitro.'

Effect of electrochemotherapy with betulinic acid or cisplatin on regulation of heat shock proteins in metastatic human carcinoma cells in vitro.

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

Effect of electrochemotherapy with betulinic acid or cisplatin on regulation of heat shock proteins in metastatic human carcinoma cells in vitro.

Oncol Rep. 2019 Jun;41(6):3444-3454

Authors: Mączyńska J, Choromańska A, Kutkowska J, Kotulska M, Zalewski M, Zalewski J, Kulbacka J, Saczko J

Abstract
Betulinic acid (BTA) is naturally occurring triterpene that has received interest as a novel therapeutic substance with cytotoxicity towards a number of cancer cell lines. Despite the wide spectrum of biological and pharmacological effects, its effect may be limited its lipophobic properties. Therefore, strategies to improve the access of BTA to the cells are required to enhance the anticancer effects. Electroporation (EP) enables increased inflow of drugs into cancer cells, even at low doses, which may reduce the side effects caused by high doses of chemotherapy. The potential application of BTA in electrochemotherapy (ECT) in metastatic type of cancers was investigated in the present study. The efficacy of BTA with EP was estimated using a cell survival assay (MTT assay), microscopical morphology analysis and the immunocytochemical expression of heat shock proteins (HSPs). HSPs are molecules that protect the cell from harmful environmental, chemical and physical stresses, and ensure cell survival, recovery and proper functioning. HSP expression is induced various stress factors. Therefore, the expression of HSP27 and HSP70 was evaluated after cells were exposed to an external pulsed electric field and anticancer drugs. Facilitated drug delivery and the anticancer effect on metastatic tumor cells were evaluated in vitro. The effect of BTA was compared with cisplatin (CP), a standard cytostatic agent. Two different metastatic cancer cell lines were used, an ovary adenocarcinoma cell line (SW626) and melanoma cell line (Me45). BTA combined with EP exhibited similar efficacy to CP with EP after 24 and 48 h in SW626 and Me45 cancer cells. Me45 cells also had high HSP27 and low HSP70 immunosignals post‑ECT treatment. ECT caused increased expression of HSP27 and HSP70 proteins in SW626 cells, which were less sensitive to ECT than the Me45 melanoma cell line. The results indicate that BTA may be efficiently applied instead of CP in ECT approaches, but its activity differs between tumor cell lines.

PMID: 31002374 [PubMed - indexed for MEDLINE]

Permalink for 'Zwitterionic Gadolinium(III)-Complexed Dendrimer-Entrapped Gold Nanoparticles for Enhanced Computed Tomography/Magnetic Resonance Imaging of Lung Cancer Metastasis.'

Zwitterionic Gadolinium(III)-Complexed Dendrimer-Entrapped Gold Nanoparticles for Enhanced Computed Tomography/Magnetic Resonance Imaging of Lung Cancer Metastasis.

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

Zwitterionic Gadolinium(III)-Complexed Dendrimer-Entrapped Gold Nanoparticles for Enhanced Computed Tomography/Magnetic Resonance Imaging of Lung Cancer Metastasis.

ACS Appl Mater Interfaces. 2019 May 01;11(17):15212-15221

Authors: Liu J, Xiong Z, Zhang J, Peng C, Klajnert-Maculewicz B, Shen M, Shi X

Abstract
Design of dual mode or multimode contrast agents or nanoplatforms with antifouling properties is crucial for improved cancer diagnosis since the antifouling materials are able to escape the clearance of the reticuloendothelial system with improved pharmacokinetics. Herein, we present the creation of zwitterionic gadolinium(III) (Gd(III))-complexed dendrimer-entrapped gold nanoparticles (Au DEN) for enhanced dual mode computed tomography (CT)/magnetic resonance (MR) imaging of lung cancer metastasis. In the present work, poly(amidoamine) (PAMAM) dendrimers of generation 5 were partially decorated with carboxybetanie acrylamide (CBAA), 2-methacryloyloxyethyl phosphorylcholine (MPC), and 1,3-propane sultone (1,3-PS), respectively at different degrees, then used to entrap Au NPs within their interiors, and finally acetylated to cover their remaining amine termini. Through protein resistance, macrophage cellular uptake, and pharmacokinetics assays, we show that zwitterionic Au DEN modified with 1,3-PS exhibit the best antifouling property with the longest half-decay time (37.07 h) when compared to the CBAA- and MPC-modified Au DEN. Furthermore, with the optimized zwitterion type, we then prepared zwitterionic Gd(III)-loaded Au DEN modified with arginine-glycine-aspartic acid peptide for targeted dual mode CT/MR imaging of a lung cancer metastasis model. We disclose that the designed multifunctional Au DEN having an Au core size of 2.7 nm and a surface potential of 7.6 ± 0.9 mV display a good X-ray attenuation property, relatively high r1 relaxivity (13.17 mM s-1), acceptable cytocompatibility, and targeting specificity to αvβ3 integrin-expressing cancer cells and enable effective dual mode CT/MR imaging of a lung cancer metastasis model in vivo. The developed multifunctional zwitterion-functionalized Au DEN may be potentially adopted as an effective nanoprobe for enhanced dual-modal CT/MR imaging of other cancer types.

PMID: 30964632 [PubMed - indexed for MEDLINE]

Permalink for 'Weighted correlation network and differential expression analyses identify candidate genes associated with BRAF gene in melanoma.'

Weighted correlation network and differential expression analyses identify candidate genes associated with BRAF gene in melanoma.

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

Weighted correlation network and differential expression analyses identify candidate genes associated with BRAF gene in melanoma.

BMC Med Genet. 2019 03 29;20(1):54

Authors: Zhao B, You Y, Wan Z, Ma Y, Huo Y, Liu H, Zhou Y, Quan W, Chen W, Zhang X, Li F, Zhao Y

Abstract
BACKGROUND: Primary cutaneous malignant melanoma is a cancer of the pigment cells of the skin, some of which are accompanied by BRAF mutation. Melanoma incidence and mortality rates have been rising around the world. As the current knowledge about pathogenesis, clinical and genetic features of cutaneous melanoma is not very clear, we aim to use bioinformatics to identify the potential key genes involved in the expression and mutation status of BRAF.
METHODS: Firstly, we used UCSC public hub datasets of melanoma (Lin et al., Cancer Res 68(3):664, 2008) to perform weighted genes co-expression network analysis (WGCNA) and differentially expressed genes analysis (DEGs), respectively. Secondly, overlapping genes between significant gene modules and DEGs were screened and validated at transcriptional levels and overall survival in TCGA and GTEx datasets. Lastly, the functional enrichment analysis was accomplished to find biological functions on the web-server database.
RESULTS: We performed weighted correlation network and differential expression analyses, using gene expression data in melanoma samples. We identified 20 genes whose expression was correlated with the mutation status of BRAF. For further validation, three of these genes (CYR61, DUSP1, and RNASE4) were found to have similar expression patterns in skin tumors from TCGA compared with normal skin samples from GTEx. We also found that weak expression of these three genes was associated with worse overall survival in the TCGA data. These three genes were involved in the nucleic acid metabolic process.
CONCLUSION: In this study, CYR61, DUSP1, and RNASE4 were identified as potential genes of interest for future molecular studies in melanoma, which would improve our understanding of its causes and underlying molecular events. These candidate genes may provide a promising avenue of future research for therapeutic targets in melanoma.

PMID: 30925905 [PubMed - indexed for MEDLINE]

Significance of survivin mRNA blood levels in patients with melanoma.

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

Significance of survivin mRNA blood levels in patients with melanoma.

J BUON. 2018 12;23(7):96-103

Authors: Samarkos M, Papaxoinis G, Athanasoula K, Benopoulou Ο, Bouros S, Anastasopoulou A, Diamantopoulos P, Gogas H, Mantzourani M

Abstract
PURPOSE: Survivin represents a key anti-apoptotic molecule that is highly expressed in the vast majority of tumors. The aim of the study was to examine the significance of survivin mRNA blood levels in melanoma patients.
METHODS: In this prospective translational research study, survivin mRNA blood levels were measured in melanoma patients treated with adjuvant interferon or systemic treatment for advanced disease.
RESULTS: Sixty-four patients with melanoma and 40 healthy controls were included. The majority of them had tumor stages III and IV. The upper 95% confidence interval (95%CI) of survivin levels in controls was set as normal cut-off. Fifty-two (81.3%) patients had survivin levels above normal cut-off. Melanoma patients had higher survivin levels than controls (p<0.0001). Survivin levels were non-significantly higher in stage III compared to stage IV patients. Patients with survivin levels above vs. below median had median progression-free survival (PFS) 19.5 months vs. 7.4 months (p=0.045), but median overall survival (OS) not reached vs. 18.4 months (p=0.091). Cox proportional hazard models showed that only tumor stage was associated with PFS and OS. There was no statistically significant change in survivin levels between baseline and during treatment (p=0.845) or during follow-up (p=0.101).
CONCLUSION: Although melanoma patients had significantly higher survivin levels than controls, the study showed that survivin mRNA blood levels did not represent an independent prognostic factor for patients with melanoma. The role of circulating survivin should be further examined in larger studies.

PMID: 30722117 [PubMed - indexed for MEDLINE]

Permalink for 'Rapid liquid biopsy for Mohs surgery: rare target cell separation from surgical margin lavage fluid with a high recovery rate and selectivity.'

Rapid liquid biopsy for Mohs surgery: rare target cell separation from surgical margin lavage fluid with a high recovery rate and selectivity.

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

Rapid liquid biopsy for Mohs surgery: rare target cell separation from surgical margin lavage fluid with a high recovery rate and selectivity.

Lab Chip. 2019 03 13;19(6):974-983

Authors: Zhou W, Liu Y, Ran M, Zhao X, Li H, Li H, Wang W

Abstract
In melanoma surgery, it is difficult to identify residual scattered tumor cells at the surgical margin because of invasive growth. Mohs surgery, widely applied to increase the cure rate and decrease the recurrence rate of melanoma, involves examination of the tissue for tumor cells after tissue removal. Here, we established a liquid biopsy platform for rapid (<5 h), sensitive examination of residual tumor cells at the margin after Mohs surgery using clinical samples from patients with pigment nevus for a demonstration. The design involved highly sensitive, selective rare target cell separation from surgical margin lavage fluid (SMLF) through micropore-arrayed filtration. High recovery rates (86.7% ± 16.3% and 72.7% ± 46.7%, respectively) for separation of spiked 5 A375s (cultured human melanoma cells) and 1 A375 from 1 mL PBS were achieved for this platform. Detection of SMLF samples from patients with pigment nevus was performed, and many (66-7420) Melan-A-positive target cells were successfully recovered and identified, demonstrating the application performance of this rapid liquid biopsy for Mohs surgery in clinical practice. Moreover, a high-selectivity separation of larger target A375 cells from smaller background Jurkat cells was achieved with a high enrichment factor (4.2 ± 1.1). In clinical practice, high selectivity contributes to effective depletion of red blood cells (RBCs), thus ensuring verification of target cells from samples with severe RBC contamination. Furthermore, target cells were obtained with high purity (2.7-35.2%). The capability of this method for rare-cell separation with a high recovery rate and good selectivity may facilitate improvement of performance of Mohs surgery for real clinical practice, including shortening examination time and increasing detection sensitivity.

PMID: 30694285 [PubMed - indexed for MEDLINE]

Permalink for 'Demethylation by low-dose 5-aza-2'-deoxycytidine impairs 3D melanoma invasion partially through miR-199a-3p expression revealing the role of this miR in melanoma.'

Demethylation by low-dose 5-aza-2'-deoxycytidine impairs 3D melanoma invasion partially through miR-199a-3p expression revealing the role of this miR in melanoma.

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

Demethylation by low-dose 5-aza-2'-deoxycytidine impairs 3D melanoma invasion partially through miR-199a-3p expression revealing the role of this miR in melanoma.

Clin Epigenetics. 2019 01 16;11(1):9

Authors: Desjobert C, Carrier A, Delmas A, Marzese DM, Daunay A, Busato F, Pillon A, Tost J, Riond J, Favre G, Etievant C, Arimondo PB

Abstract
BACKGROUND: Efficient treatments against metastatic melanoma dissemination are still lacking. Here, we report that low-cytotoxic concentrations of 5-aza-2'-deoxycytidine, a DNA demethylating agent, prevent in vitro 3D invasiveness of metastatic melanoma cells and reduce lung metastasis formation in vivo.
RESULTS: We unravelled that this beneficial effect is in part due to MIR-199A2 re-expression by promoter demethylation. Alone, this miR showed an anti-invasive and anti-metastatic effect. Throughout integration of micro-RNA target prediction databases with transcriptomic analysis after 5-aza-2'-deoxycytidine treatments, we found that miR-199a-3p downregulates set of genes significantly involved in invasion/migration processes. In addition, analysis of data from melanoma patients showed a stage- and tissue type-dependent modulation of MIR-199A2 expression by DNA methylation.
CONCLUSIONS: Thus, our data suggest that epigenetic- and/or miR-based therapeutic strategies can be relevant to limit metastatic dissemination of melanoma.

PMID: 30651148 [PubMed - indexed for MEDLINE]

Intraparotid Facial Nerve Schwannoma in a Nine-Year-Old Patient: Diagnosis, Classification, and Surgical Approach Stages.

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

Intraparotid Facial Nerve Schwannoma in a Nine-Year-Old Patient: Diagnosis, Classification, and Surgical Approach Stages.

J Craniofac Surg. 2019 Mar/Apr;30(2):516-518

Authors: Gumussoy M, Ekmekci S

Abstract
Intraparotid facial nerve schwannoma (IFNS) is rarely observed in children compared with adults. Only a few cases have been reported in the literature. After radiological imaging and fine needle aspiration biopsy, an IFNS diagnosis may be skipped and confused with pleomorphic adenoma, which has a high prevalence among patients who have a mass in the parotid gland. The probability of IFNS can be recognized by a close relation between the mass and the facial nerve during the application of parotidectomy and by the frozen biopsy of the mass. The surgeon evaluates the mass and faces with surgical mass excison and facial nerve reconstruction according to the relation between the mass and the facial nerve because there is no diagnostic method for the presurgery diagnosis of IFNS. Therefore, the surgeon should be prepared for the possibility of functional lossin the facial nerve during parotidectomy. This article presents the case of a 9-year-old patient with an IFNS diagnosis who had a surgical operation in our clinic, and the algorithm designed according to the literature for the diagnosis and surgical classification of IFNS, as well as the approaches to facial nerve reconstruction.

PMID: 30507869 [PubMed - indexed for MEDLINE]

Strain-specific metastatic phenotypes in pheochromocytoma allograft mice

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

Strain-specific metastatic phenotypes in pheochromocytoma allograft mice

Endocr Relat Cancer. 2018 10 05;25(12):993-1004

Authors: Ullrich M, Liers J, Peitzsch M, Feldmann A, Bergmann R, Sommer U, Richter S, Bornstein SR, Bachmann M, Eisenhofer G, Ziegler CG, Pietzsch J

Abstract
Somatostatin receptor-targeting endoradiotherapy offers potential for treating metastatic pheochromocytomas and paragangliomas, an approach likely to benefit from combination radiosensitization therapy. To provide reliable preclinical in vivo models of metastatic disease, this study characterized the metastatic spread of luciferase-expressing mouse pheochromocytoma (MPC) cells in mouse strains with different immunologic conditions. Bioluminescence imaging showed that, in contrast to subcutaneous non-metastatic engraftment of luciferase-expressing MPC cells in NMRI-nude mice, intravenous cell injection provided only suboptimal metastatic spread in both NMRI-nude mice and hairless SCID (SHO) mice. Treatment of NMRI-nude mice with anti-Asialo GM1 serum enhanced metastatic spread due to substantial depletion of natural killer (NK) cells. However, reproducible metastatic spread was only observed in NK cell-defective SCID/beige mice and in hairless immunocompetent SKH1 mice bearing disseminated or liver metastases, respectively. Liquid chromatography tandem mass spectrometry of urine samples showed that subcutaneous and metastasized tumor models exhibit comparable renal monoamine excretion profiles characterized by increasing urinary dopamine, 3-methoxytyramine, norepinephrine and normetanephrine. Metastases-related epinephrine and metanephrine were only detectable in SCID/beige mice. Positron emission tomography and immunohistochemistry revealed that all metastases maintained somatostatin receptor-specific radiotracer uptake and immunoreactivity, respectively. In conclusion, we demonstrate that intravenous injection of luciferase-expressing MPC cells into SCID/beige and SKH1 mice provides reproducible and clinically relevant spread of catecholamine-producing and somatostatin receptor-positive metastases. These standardized preclinical models allow for precise monitoring of disease progression and should facilitate further investigations on theranostic approaches against metastatic pheochromocytomas and paragangliomas.

PMID: 30288966 [PubMed - indexed for MEDLINE]

Risk of sun-induced skin cancers in patients with alopecia areata, alopecia totalis and alopecia universalis.

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

Risk of sun-induced skin cancers in patients with alopecia areata, alopecia totalis and alopecia universalis.

J Eur Acad Dermatol Venereol. 2018 Nov;32(11):e409-e411

Authors: Conic RRZ, Miller R, Piliang M, Bergfeld W, Atanaskova Mesinkovska N

PMID: 29679494 [PubMed - indexed for MEDLINE]

Permalink for 'Magnetic core mesoporous silica nanoparticles doped with dacarbazine and labelled with 99mTc for early and differential detection of metastatic melanoma by single photon emission computed tomography.'

Magnetic core mesoporous silica nanoparticles doped with dacarbazine and labelled with 99mTc for early and differential detection of metastatic melanoma by single photon emission computed tomography.

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

Magnetic core mesoporous silica nanoparticles doped with dacarbazine and labelled with 99mTc for early and differential detection of metastatic melanoma by single photon emission computed tomography.

Artif Cells Nanomed Biotechnol. 2018;46(sup1):1080-1087

Authors: Portilho FL, Helal-Neto E, Cabezas SS, Pinto SR, Dos Santos SN, Pozzo L, Sancenón F, Martínez-Máñez R, Santos-Oliveira R

Abstract
Cancer is responsible for more than 12% of all causes of death in the world, with an annual death rate of more than 7 million people. In this scenario melanoma is one of the most aggressive ones with serious limitation in early detection and therapy. In this direction we developed, characterized and tested in vivo a new drug delivery system based on magnetic core-mesoporous silica nanoparticle that has been doped with dacarbazine and labelled with technetium 99 m to be used as nano-imaging agent (nanoradiopharmaceutical) for early and differential diagnosis and melanoma by single photon emission computed tomography. The results demonstrated the ability of the magnetic core-mesoporous silica to be efficiently (>98%) doped with dacarbazine and also efficiently labelled with 99mTc (technetium 99 m) (>99%). The in vivo test, using inducted mice with melanoma, demonstrated the EPR effect of the magnetic core-mesoporous silica nanoparticles doped with dacarbazine and labelled with technetium 99 metastable when injected intratumorally and the possibility to be used as systemic injection too. In both cases, magnetic core-mesoporous silica nanoparticles doped with dacarbazine and labelled with technetium 99 metastable showed to be a reliable and efficient nano-imaging agent for melanoma.

PMID: 29482360 [PubMed - indexed for MEDLINE]

Metastatic brain carotid body paraganglioma with endocrine activity: a case report and literature review.

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

Metastatic brain carotid body paraganglioma with endocrine activity: a case report and literature review.

Br J Neurosurg. 2019 Jun;33(3):269-271

Authors: Wang X, Zhu X, Chen J, Liu Y, Mao Q

Abstract
A woman with hypertension and hyperglycemia was diagnosed a metastatic brain carotid body paraganglioma. Her blood pressure, glucose, and norepinephrine were normal after craniotomy. Although most carotid body tumors are benign, a few show distant metastasis. This is the first reported case of intracerebral metastases from a carotid body tumor.

PMID: 28498000 [PubMed - indexed for MEDLINE]

Primary neuroendocrine tumor in the presacral region: A case report.

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

Primary neuroendocrine tumor in the presacral region: A case report.

World J Clin Cases. 2019 Jul 26;7(14):1884-1891

Authors: Zhang R, Zhu Y, Huang XB, Deng C, Li M, Shen GS, Huang SL, Huangfu SH, Liu YN, Zhou CG, Wang L, Zhang Q, Deng Y, Jiang B

Abstract
BACKGROUND: Primary neuroendocrine tumors (NETs) in the presacral region are extremely rare, some of which are caused by other primary tumors or metastatic rectal carcinoids. Nevertheless, cases of NETs have been increasing in recent years. This report describes the first primary neuroendocrine tumor in the presacral region that was found at our hospital within the last five years.
CASE SUMMARY: The patient was identified as a 36-year-old woman with a presacral mass and pelvic floor pain. A digital rectal examination revealed a presacral mass with unclear margins and obvious tenderness. Magnetic resonance imaging (MRI) demonstrated a 57 mm × 29 mm presacral lump. An ultrasound-guided needle biopsy confirmed a well-differentiated neuroendocrine tumor. No other primary or metastatic tumors were found.
CONCLUSION: Comprehensive consideration of our case report and literature reported by others suggests that a conclusive diagnosis of NETs should be based on computed tomography/MRI and pathological examinations. The treatment of primary NETs in the presacral region mainly relies on surgical procedures with follow-up.

PMID: 31417935 [PubMed]

Colorectal neuroendocrine carcinoma: A case report and review of the literature.

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

Colorectal neuroendocrine carcinoma: A case report and review of the literature.

World J Clin Cases. 2019 Jul 26;7(14):1865-1875

Authors: Yoshida T, Kamimura K, Hosaka K, Doumori K, Oka H, Sato A, Fukuhara Y, Watanabe S, Sato T, Yoshikawa A, Tomidokoro T, Terai S

Abstract
BACKGROUND: Colorectal neuroendocrine carcinoma (NEC) is a rare tumor that demonstrates aggressive growth pattern with ingrowth into the tract, metastasis to the other organs, and invasion to the surrounding organs; these clinical characteristics result in poor prognosis. Surgical resection appears as an effective approach; however, because it is difficult to accurately diagnose NEC during the early stage and owing to its aggressive growth pattern, development of a reliable standard chemotherapy regimen and management strategies are essential.
CASE SUMMARY: Here, we report the case of patient with NEC showing an aggressive growth pattern that resulted in the rupture of the tumor to the outside the colon after stenting of the internal colonic stenosis. In addition, the tumor invaded into the duodenum, thereby causing duodenal stenosis that required an additional stent in the duodenum. This aggressive growth pattern is one of the main features of the NEC that is different from adenocarcinoma. To clarify the clinical characteristics, we reviewed 60 recently reported cases, including data on tumor location, size, treatment, and prognosis.
CONCLUSION: We consider that the information presented here is of great significance for the diagnosis, treatment, and management of symptoms of the patients with NEC.

PMID: 31417933 [PubMed]

Primary Mediastinal Small Cell Neuroendocrine Carcinoma Presenting with Superior Vena Cava Syndrome.

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

Primary Mediastinal Small Cell Neuroendocrine Carcinoma Presenting with Superior Vena Cava Syndrome.

Cureus. 2019 Jun 10;11(6):e4873

Authors: Costanzo LR, Kewan T, Kerwin K, Daw H

Abstract
A mediastinal small cell neuroendocrine carcinoma (MSCNC) is a rare form of neuroendocrine malignancy. Diagnosis is challenging and requires pathological identification and imaging studies. These tumors are aggressive and recurrence and metastases frequently complicate patient management. Here, we present a case of superior vena cava (SVC) syndrome secondary to circumferential compression by a primary MSCNC.

PMID: 31417818 [PubMed]

Recognizing intrapancreatic accessory spleen via EUS: Interobserver variability.

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

Recognizing intrapancreatic accessory spleen via EUS: Interobserver variability.

Endosc Ultrasound. 2019 Aug 13;:

Authors: Kim GE, Morris JD, Anand N, DePalma F, Greenwald BD, Kim RE, Laczek J, Lee WJ, Papadopoulas I, Uradomo L, Young P, Darwin PE

Abstract
Background and Objective: Accessory spleen (AS) may be encountered as an intrapancreatic lesion on EUS. This can look similar to other pancreatic pathologies and may lead to unnecessary interventions. The goal of this study was to evaluate the accuracy of EUS in distinguishing intrapancreatic AS (IPAS) from other pancreatic lesions.
Materials and Methods: Twelve sets of endoscopic images of the spleen and various pancreatic lesions confirmed on histology or cytology were gathered. Ten endosonographers were asked to characterize and identify the lesions. The responses were analyzed via Excel and the interobserver agreement was analyzed using Gwet's agreement coefficient statistic via Stata I/C v15.
Results: In our sample, the interobserver agreement was 0.37 (-+1-1; 0-0.2 poor, 0.2-0.4 fair, 0.4-0.6 moderate, 0.6-0.8 substantial, and 0.8-1.0 almost perfect) for determining whether or not the pancreatic lesion is IPAS. The reviewers were able to correctly determine IPAS endosonographically with a sensitivity of 77%, specificity of 74%, and positive and negative predictive values of 50% and 92%, respectively.
Conclusion: There is a moderate-to-substantial interobserver agreement in describing the sonographic characteristics of the pancreatic lesions, such as the shape, echogenicity compared to spleen, echotexture, and border of the lesions. However, the interobserver agreement is only fair when deciding if the pancreatic lesion is an IPAS. The similar profile of IPAS and pancreatic neuroendocrine tumor could confound the diagnosis of IPAS, thus contributing to the decreased interobserver agreement. This study demonstrates that EUS criteria alone are not accurate for IPAS diagnosis. Fine-needle aspiration (FNA) may be required for a confirmatory diagnosis.

PMID: 31417068 [PubMed - as supplied by publisher]

Upregulation of erythropoietin and erythropoietin receptor in castration-resistant progression of prostate cancer.

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

Upregulation of erythropoietin and erythropoietin receptor in castration-resistant progression of prostate cancer.

Asian J Androl. 2019 Aug 09;:

Authors: Ye C, Chen GH, Chen X, Qin SF, Shi MF, Zhou T

Abstract
Hypoxia-induced erythropoietin signaling plays an important role in tumor growth and invasion. In the present study, we investigated the contribution of erythropoietin signaling pathway to castration-resistant prostate cancer and the development of a neuroendocrine phenotype. Immunohistochemical staining showed that the erythropoietin and erythropoietin receptor scores in castration-resistant prostate cancer and androgen-dependent prostate cancer were 7.55 versus 4.5 and 7.45 versus 5.9,respectively (P < 0.001). Furthermore, a cell proliferation assay was conducted, and the differential expression of erythropoietin and erythropoietin receptor in LNCaP cells and hypoxia-induced LNCaP cells was evaluated using western blot and quantitative real-time PCR. The proliferation capacity of hypoxia-induced LNCaP cells was similar in cultures of both fetal bovine serum and charcoal-stripped fetal bovine serum, suggesting that LNCaP cells acquired hypoxia-induced androgen-independent growth. After 2 weeks of hypoxic culture, LNCaP cells showed a neuroendocrine cell change and increased expression of neuron-specific enolase, erythropoietin, and erythropoietin receptor; knockdown of erythropoietin receptor reversed the hypoxia-induced upregulation of neuron-specific enolase in the LNCaP cells. In conclusion, the concurrent upregulation of erythropoietin and erythropoietin receptor in castration-resistant prostate cancer suggests that the erythropoietin/erythropoietin receptor autocrine loop plays an important role in the progression of castration resistance and is responsible for the development of a neuroendocrine phenotype.

PMID: 31417010 [PubMed - as supplied by publisher]

Pheochromocytoma and Paraganglioma.

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

Pheochromocytoma and Paraganglioma.

N Engl J Med. 2019 08 08;381(6):552-565

Authors: Neumann HPH, Young WF, Eng C

PMID: 31390501 [PubMed - indexed for MEDLINE]

Appropriate excision margins for cutaneous melanomas.

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

Appropriate excision margins for cutaneous melanomas.

Lancet. 2019 08 10;394(10197):445-446

Authors: Thompson JF, Friedman EB

PMID: 31280970 [PubMed - indexed for MEDLINE]

Rottlerin Reduces cAMP/CREB-Mediated Melanogenesis via Regulation of Autophagy.

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

Rottlerin Reduces cAMP/CREB-Mediated Melanogenesis via Regulation of Autophagy.

Int J Mol Sci. 2019 Apr 27;20(9):

Authors: Qomaladewi NP, Kim MY, Cho JY

Abstract
Melanogenesis is the sequential process of melanin production by melanocytes in order to protect the skin from harmful stimuli. Melanogenesis is disrupted by radiation exposure, which results in the differentiation of melanocytes into melanoma. Recently, some methods have been developed to maintain the instability of melanogenesis in melanoma by activating cellular autophagy. However, there is still a lack of knowledge about how autophagy is involved in the regulation of melanogenesis in melanoma cells. Here, we used rottlerin as an autophagy inducer to investigate the role of the cyclic adenosine monophosphate (cAMP)/cAMP response element binding (CREB) signaling pathway in melanogenesis. We found that rottlerin can inhibit melanin production by targeting cAMP, which is initially activated by alpha-melanocyte stimulating hormone (α-MSH). Our findings suggest that rottlerin has a pivotal role as an autophagy inducer in the regulation of melanogenesis by targeting the cAMP/CREB signaling pathway.

PMID: 31035588 [PubMed - indexed for MEDLINE]

The Role of Autophagy in Liver Epithelial Cells and Its Impact on Systemic Homeostasis.

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

The Role of Autophagy in Liver Epithelial Cells and Its Impact on Systemic Homeostasis.

Nutrients. 2019 Apr 11;11(4):

Authors: Tomaipitinca L, Mandatori S, Mancinelli R, Giulitti F, Petrungaro S, Moresi V, Facchiano A, Ziparo E, Gaudio E, Giampietri C

Abstract
: Autophagy plays a role in several physiological and pathological processes as it controls the turnover rate of cellular components and influences cellular homeostasis. The liver plays a central role in controlling organisms' metabolism, regulating glucose storage, plasma proteins and bile synthesis and the removal of toxic substances. Liver functions are particularly sensitive to autophagy modulation. In this review we summarize studies investigating how autophagy influences the hepatic metabolism, focusing on fat accumulation and lipids turnover. We also describe how autophagy affects bile production and the scavenger function within the complex homeostasis of the liver. We underline the role of hepatic autophagy in counteracting the metabolic syndrome and the associated cardiovascular risk. Finally, we highlight recent reports demonstrating how the autophagy occurring within the liver may affect skeletal muscle homeostasis as well as different extrahepatic solid tumors, such as melanoma.

PMID: 30979078 [PubMed - indexed for MEDLINE]

Long non-coding RNA TUG1 recruits miR‑29c‑3p from its target gene RGS1 to promote proliferation and metastasis of melanoma cells.

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

Long non-coding RNA TUG1 recruits miR‑29c‑3p from its target gene RGS1 to promote proliferation and metastasis of melanoma cells.

Int J Oncol. 2019 Apr;54(4):1317-1326

Authors: Wang Y, Liu G, Ren L, Wang K, Liu A

Abstract
Melanoma is an aggressive type of skin cancer, characterized by high mortality rates worldwide. Therefore, the identification of new diagnostic markers and therapeutic targets for melanoma is imperative. Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) play important roles in tumor initiation and progression. It was recently reported that the expression of lncRNA taurine upregulated 1 (TUG1) was relatively higher in cancer compared with that in normal cells, and that TUG1 promoted the progression of various cancers. However, the pattern of expression and mechanism of action of TUG1 in melanoma remain unclear. The aim of the present study was to investigate whether TUG1 expression is relatively higher in melanoma tissues and whether this expression is correlated with poor overall survival. Knockdown of TUG1 was found to suppress melanoma cell growth and metastasis and induce cell apoptosis. By contrast, the overexpression of TUG1 promoted the growth and metastasis of melanoma cells, and inhibited their apoptosis. In addition, the results of the present study indicated that TUG1 sequestered endogenous miR‑29c‑3p and that it was able to suppress its expression. Furthermore, it was observed that miR‑29c‑3p could reverse the promoting effect of TUG1 on melanoma progression, which may be associated with the positive regulation of regulator of G-protein signaling 1 (RGS1), a target gene of miR‑29c‑3p. Taken together, the data of the present study demonstrated that TUG1 promoted proliferation and invasion and suppressed apoptosis in melanoma cells by regulating miR‑29c‑3p and its target gene, RGS1. Therefore, lncRNA TUG1 appears to be a promising diagnostic marker for melanoma patients.

PMID: 30720136 [PubMed - indexed for MEDLINE]

Permalink for 'Myrtenal-induced V-ATPase inhibition - A toxicity mechanism behind tumor cell death and suppressed migration and invasion in melanoma.'

Myrtenal-induced V-ATPase inhibition - A toxicity mechanism behind tumor cell death and suppressed migration and invasion in melanoma.

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

Myrtenal-induced V-ATPase inhibition - A toxicity mechanism behind tumor cell death and suppressed migration and invasion in melanoma.

Biochim Biophys Acta Gen Subj. 2019 01;1863(1):1-12

Authors: Martins BX, Arruda RF, Costa GA, Jerdy H, de Souza SB, Santos JM, de Freitas WR, Kanashiro MM, de Carvalho ECQ, Sant'Anna NF, Antunes F, Martinez-Zaguilan R, Souad S, Okorokova-Façanha AL, Façanha AR

Abstract
BACKGROUND: Metastatic tumor cells have acidic extracellular pH and differential electrochemical H+ gradients generated across their cell membranes by V-type H+-ATPases. This study shows that inhibition of the V-ATPases by the plant-derived monoterpene Myrtenal results in tumor cell death and decreased metastatic dissemination in mice.
METHODS: The Myrtenal anticancer toxicity was evaluated in vitro using murine (B16F0 and B16F10) and human (SkMel-5) melanoma cell lines, and in in vivo mouse metastatic dissemination model. Proton flux and extracellular acidification were directly evaluated at the surface of living cells using a non-invasive selective ion electrode approach.
RESULTS: The inhibition of V-ATPases by 100 μM Myrtenal disrupted the electrochemical H+ gradient across the cell membranes, strongly induced cell death (4-5 fold), and decreased tumor cells migration and invasion in vitro. Myrtenal (15 mg/kg) also significantly reduced metastasis induced by B16F10 in vivo, further reinforcing that V-ATPase is a molecular target to halt the progression of cancers.
CONCLUSIONS: These data revealed the therapeutic potential of Myrtenal as inhibitor of melanoma progression proposing a mechanism of action by which once inhibited by this monoterpene the proton pumps fail to activate cancer-related differential electrochemical gradients and H+ fluxes across the tumor cell membranes, disrupting pH signatures inherent in tumor progression, resulting in reprogrammed cell death and metastasis inhibition.
GENERAL SIGNIFICANCE: The work represents a new mechanistic strategy for contention of melanoma, the most aggressive and deadly form of cutaneous neoplasm, and highlights Myrtenal, other related monoterpenes and derivatives as promising proton pump inhibitors with high chemotherapeutic potential.

PMID: 30279148 [PubMed - indexed for MEDLINE]

A cloning and expression system to probe T-cell receptor specificity and assess functional avidity to neoantigens.

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

A cloning and expression system to probe T-cell receptor specificity and assess functional avidity to neoantigens.

Blood. 2018 11 01;132(18):1911-1921

Authors: Hu Z, Anandappa AJ, Sun J, Kim J, Leet DE, Bozym DJ, Chen C, Williams L, Shukla SA, Zhang W, Tabbaa D, Steelman S, Olive O, Livak KJ, Kishi H, Muraguchi A, Guleria I, Stevens J, Lane WJ, Burkhardt UE, Fritsch EF, Neuberg D, Ott PA, Keskin DB, Hacohen N, Wu CJ

Abstract
Recent studies have highlighted the promise of targeting tumor neoantigens to generate potent antitumor immune responses and provide strong motivation for improving our understanding of antigen-T-cell receptor (TCR) interactions. Advances in single-cell sequencing technologies have opened the door for detailed investigation of the TCR repertoire, providing paired information from TCRα and TCRβ, which together determine specificity. However, a need remains for efficient methods to assess the specificity of discovered TCRs. We developed a streamlined approach for matching TCR sequences with cognate antigen through on-demand cloning and expression of TCRs and screening against candidate antigens. Here, we first demonstrate the system's capacity to identify viral-antigen-specific TCRs and compare the functional avidity of TCRs specific for a given antigen target. We then apply this system to identify neoantigen-specific TCR sequences from patients with melanoma treated with personalized neoantigen vaccines and characterize functional avidity of neoantigen-specific TCRs. Furthermore, we use a neoantigen-prediction pipeline to show that an insertion-deletion mutation in a putative chronic lymphocytic leukemia (CLL) driver gives rise to an immunogenic neoantigen mut-MGA, and use this approach to identify the mut-MGA-specific TCR sequence. This approach provides a means to identify and express TCRs, and then rapidly assess antigen specificity and functional avidity of a reconstructed TCR, which can be applied for monitoring antigen-specific T-cell responses, and potentially for guiding the design of effective T-cell-based immunotherapies.

PMID: 30150207 [PubMed - indexed for MEDLINE]

MHC Expression Predicts Checkpoint Blockade Response.

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

MHC Expression Predicts Checkpoint Blockade Response.

Cancer Discov. 2018 09;8(9):1052

Authors:

Abstract
MHC expression may affect response to immune checkpoint inhibitors in patients with advanced melanoma. In a recent retrospective analysis, patients with low MHC class I expression responded to a PD-1 inhibitor, but were less likely to respond to a CTLA4 inhibitor than patients with higher MHC class I expression.

PMID: 30087097 [PubMed - indexed for MEDLINE]

Retinal Imaging of an Optic Tract Lesion: OCT Angiography of Structural and Functional Defects.

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

Retinal Imaging of an Optic Tract Lesion: OCT Angiography of Structural and Functional Defects.

Ophthalmology. 2018 05;125(5):756

Authors: Micieli JA, Newman NJ, Biousse V

PMID: 29681298 [PubMed - indexed for MEDLINE]

Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia Syndrome Treated With Sirolimus.

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

Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia Syndrome Treated With Sirolimus.

Ann Intern Med. 2018 08 07;169(3):197-198

Authors: Russier M, Plantier L, Derot G, de Muret A, Marchand-Adam S

PMID: 29632951 [PubMed - indexed for MEDLINE]

Clinical Predictors of Regression of Choroidal Melanomas after Brachytherapy: A Growth Curve Model.

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

Clinical Predictors of Regression of Choroidal Melanomas after Brachytherapy: A Growth Curve Model.

Ophthalmology. 2018 05;125(5):747-754

Authors: Rashid M, Heikkonen J, Singh AD, Kivelä TT

Abstract
PURPOSE: To build multivariate models to assess correctly and efficiently the contribution of tumor characteristics on the rate of regression of choroidal melanomas after brachytherapy in a way that adjusts for confounding and takes into account variation in tumor regression patterns.
DESIGN: Modeling of longitudinal observational data.
PARTICIPANTS: Ultrasound images from 330 of 388 consecutive choroidal melanomas (87%) irradiated from 2000 through 2008 at the Helsinki University Hospital, Helsinki, Finland, a national referral center.
METHODS: Images were obtained with a 10-MHz B-scan during 3 years of follow-up. Change in tumor thickness and cross-sectional area were modeled using a polynomial growth-curve function in a nested mixed linear regression model considering regression pattern and tumor levels. Initial tumor dimensions, tumor-node-metastasis (TNM) stage, shape, ciliary body involvement, pigmentation, isotope, plaque size, detached muscles, and radiation parameters were considered as covariates.
MAIN OUTCOME MEASURES: Covariates that independently predict tumor regression.
RESULTS: Initial tumor thickness, largest basal diameter, ciliary body involvement, TNM stage, tumor shape group, break in Bruch's membrane, having muscles detached, and radiation dose to tumor base predicted faster regression, whether considering all tumors or those that regressed in a pattern compatible with exponential decay. Dark brown pigmentation was associated with slower regression. In multivariate modeling, initial tumor thickness remained the predominant and robust predictor of tumor regression (P < 0.0001). In addition, use of ruthenium isotope as opposed to iodine isotope (P = 0.018) independently contributed to faster regression of tumor thickness. For both isotopes considered alone, initial tumor thickness was the sole clinical predictor of regression (P < 0.0001).
CONCLUSIONS: Regression of choroidal melanoma after brachytherapy was associated with several clinical tumor and treatment parameters, most of which were shown to reflect initial tumor size. An independent predictor of regression of tumor thickness was the isotope used. These 2 covariates need to be adjusted for when exploring the associations with the rate of regression of histopathologic or genetic features of the tumor. Our model allows such future analyses efficiently without matching.

PMID: 29499831 [PubMed - indexed for MEDLINE]

The effect of timing of stereotactic radiosurgery treatment of melanoma brain metastases treated with ipilimumab.

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

The effect of timing of stereotactic radiosurgery treatment of melanoma brain metastases treated with ipilimumab.

J Neurosurg. 2017 Nov;127(5):1007-1014

Authors: Cohen-Inbar O, Shih HH, Xu Z, Schlesinger D, Sheehan JP

Abstract
OBJECTIVE Melanoma represents the third most common cause of CNS metastases. Immunotherapy has evolved as a treatment option for patients with Stage IV melanoma. Stereotactic radiosurgery (SRS) also elicits an immune response within the brain and may interact with immunotherapy. The authors report on a cohort of patients treated for brain metastases with immunotherapy and evaluate the effect of SRS timing on the intracranial response. METHODS All consecutively treated melanoma patients receiving ipilimumab and SRS for treatment of brain metastases at the University of Virginia between 2009 and 2014 were included in this retrospective analysis; data from 46 patients harboring 232 brain metastases were reviewed. The median duration of clinical follow-up was 7.9 months (range 3-42.6 months). The median age of the patients was 63 years (range 24.3-83.6 years). Thirty-two patients received SRS before or during ipilimumab cycles (Group A), whereas 14 patients received SRS after ipilimumab treatment (Group B). Radiographic and clinical responses were assessed at approximately 3-month intervals after SRS. RESULTS The 2 cohorts were comparable in pertinent baseline characteristics with the exception of SRS timing relative to ipilimumab. Local recurrence-free duration (LRFD) was significantly longer in Group A (median 19.6 months, range 1.1-34.7 months) than in Group B patients (median 3 months, range 0.4-20.4 months) (p = 0.002). Post-SRS perilesional edema was more significant in Group A. CONCLUSIONS The effect of SRS and ipilimumab on LRFD seems greater when SRS is performed before or during ipilimumab treatments. The timing of immunotherapy and SRS may affect LRFD and postradiosurgical edema. The interactions between immunotherapy and SRS warrant further investigation so as to optimize the therapeutic benefits and mitigate the risks associated with multimodality, targeted therapy.

PMID: 28059663 [PubMed - indexed for MEDLINE]

Patient- versus physician-reported facial disability in vestibular schwannoma: an international cross-sectional study.

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

Patient- versus physician-reported facial disability in vestibular schwannoma: an international cross-sectional study.

J Neurosurg. 2017 Nov;127(5):1015-1024

Authors: Tveiten ØV, Carlson ML, Goplen F, Myrseth E, Driscoll CLW, Mahesparan R, Link MJ, Lund-Johansen M

Abstract
OBJECTIVE Patient-reported outcomes are increasingly used in studies of vestibular schwannoma (VS); however, few studies have examined self-evaluated facial nerve function and its relation to physician-reported outcomes. The primary objective of this study was to compare patient self-evaluations of facial disability with physician-evaluated facial nerve status and with self-evaluations of a healthy control group. The second objective was to provide insight into the controversial subject of the optimal initial management of small- and medium-sized VSs; consequently, the authors compared patient-reported facial nerve disability following treatment via observation (OBS), Gamma Knife surgery (GKS), or microsurgery (MS). Lastly, the authors sought to identify risk factors for facial nerve dysfunction following treatment for small- and medium-sized VSs. METHODS All patients with a VS 3 cm or smaller that was singly treated with OBS, GKS, or MS at either of 2 independent treatment centers between 1998 and 2008 were retrospectively identified. Longitudinal facial nerve measures and clinical data, including facial nerve evaluation according to the House-Brackmann (HB) grading system, were extracted from existing VS databases. Supplementing the objective data were Facial Disability Index (FDI) scores, which were obtained via survey of patients a mean of 7.7 years after initial treatment. RESULTS The response rate among the 682 eligible patients was 79%; thus, data from a total of 539 patients were analyzed. One hundred forty-eight patients had been managed by OBS, 247 with GKS, and 144 with MS. Patients who underwent microsurgery had larger tumors and were younger than those who underwent OBS or GKS. Overall, facial nerve outcomes were satisfactory following treatment, with more than 90% of patients having HB Grade I function at the last clinical follow-up. Treatment was the major risk factor for facial nerve dysfunction. Almost one-fifth of the patients treated with MS had an objective decline in facial nerve function, whereas only 2% in the GKS group and 0% in the OBS cohort had a decline. The physical subscale of the FDI in the VS patients was highly associated with HB grade; however, the social/well-being subscale of the FDI was not. Thus, any social disability caused by facial palsy was not detectable by use of this questionnaire. CONCLUSIONS The majority of patients with small- and medium-sized VSs attain excellent long-term facial nerve function and low facial nerve disability regardless of treatment modality. Tumor size and microsurgical treatment are risk factors for facial nerve dysfunction and self-reported disability. The FDI questionnaire is sensitive to the physical but not the social impairment associated with facial dysfunction.

PMID: 27911236 [PubMed - indexed for MEDLINE]

Prognostic factors and survival in MEN1 patients with gastrinomas: Results from the DutchMEN study group (DMSG).

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

Prognostic factors and survival in MEN1 patients with gastrinomas: Results from the DutchMEN study group (DMSG).

J Surg Oncol. 2019 Aug 10;:

Authors: van Beek DJ, Nell S, Pieterman CRC, de Herder WW, van de Ven AC, Dekkers OM, van der Horst-Schrivers AN, Drent ML, Bisschop PH, Havekes B, Borel Rinkes IHM, Vriens MR, Valk GD

Abstract
BACKGROUND AND OBJECTIVES: Gastrinomas are the most prevalent functioning neuroendocrine tumors (NET) in multiple endocrine neoplasia type 1 (MEN1). Guidelines suggest medical therapy in most patients, but surgery may be considered in a subgroup. Currently, factors to guide management are necessary. This population-based cohort study assessed prognostic factors of survival in patients with MEN1-related gastrinomas.
METHODS: Patients with MEN1 having gastrinomas were identified in the Dutch MEN1 database from 1990 to 2014 based on fasting serum gastrin (FSG) levels and/or pathology. Predictors of overall survival were assessed using Cox regression.
RESULTS: Sixty-three patients with gastrinoma (16% of the MEN1 population) were identified. Five- and 10-year overall survival rates were 83% and 65%, respectively. Prognostic factors associated with overall survival were initial FSG levels ≥20x upper limit of normal (ULN) (hazard ratio [HR], 6.2 [95% confidence interval, 1.7-23.0]), pancreatic NET ≥2 cm (HR 4.5; [1.5-13.1]), synchronous liver metastases (HR 8.9; [2.1-36.7]), gastroduodenoscopy suspicious for gastric NETs (HR 12.7; [1.4-115.6]), and multiple concurrent NETs (HR 5.9; [1.2-27.7]).
CONCLUSION: Life expectancy of patients with MEN1 gastrinoma is reduced. FSG levels and pancreatic NETs ≥2 cm are prognostic factors. FSG levels might guide surveillance intensity, step-up to additional diagnostics, or provide arguments in selecting patients who might benefit from surgery.

PMID: 31401809 [PubMed - as supplied by publisher]

Lymphovascular Invasion Predicts Lymph Node Involvement in Small Pancreatic Neuroendocrine Tumors.

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

Lymphovascular Invasion Predicts Lymph Node Involvement in Small Pancreatic Neuroendocrine Tumors.

Neuroendocrinology. 2019 Aug 09;:

Authors: Blakely A, Lafaro K, Li D, Kessler J, Chang S, Ituarte P, Lee B, Singh G

Abstract
INTRODUCTION: Pancreatic neuroendocrine tumors (PNETs) are increasing in incidence, and prognostic factors continue to evolve. The benefit of lymphadenectomy for PNETs ≤2 cm remains unclear. We sought to determine the significance of lymphovascular invasion (LVI) for small PNETs.
METHODS: The National Cancer Database was queried for patients with PNETs ≤2 cm and with ≥1 evaluated lymph node (LN), years 2004-2015. Demographic, clinical, and treatment characteristics were analyzed. Multivariate logistic regression was performed to identify predictors of LN positivity.
RESULTS: Among 2,499 patients identified, tumor location was delineated as the head (26%), body (18%), tail (38%), or unspecified (18%); 74% were well-differentiated versus 10% moderate, 2% poor, and 14% unknown. LVI occurred in 11%. A median of 9 LN were evaluated; overall positivity was 18%. Mean survival was significantly longer in node-negative patients (115 versus 95 months, log-rank p<0.0001). LVI was the strongest predictor of node involvement (OR 10.4, p<0.0001) when controlling for tumor size, grade, and location. Subset analysis of patients with known LVI status, grade, location, and mitoses found that LVI was more likely in the setting of moderate-to-high tumor grade, 1-2 cm size, pancreatic head location, and high mitotic rate. Among patients with ≥2 of these four factors, 25% were node-positive.
CONCLUSIONS: Presence of LVI was the strongest predictor of node positivity. LVI on endoscopic biopsy should prompt resection and regional lymph node dissection to fully stage patients with small PNETs. Patients with other high-risk factors should also be considered for resection and regional lymphadenectomy.

PMID: 31401633 [PubMed - as supplied by publisher]

Permalink for 'Rare Site Primary Soft tissue Neuroendocrine Tumour with metastases and near-complete resolution with 177Lu-DOTATATE: documenting a Promising Clinical Application of Peptide Receptor Radionuclide Therapy.'

Rare Site Primary Soft tissue Neuroendocrine Tumour with metastases and near-complete resolution with 177Lu-DOTATATE: documenting a Promising Clinical Application of Peptide Receptor Radionuclide Therapy.

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

Rare Site Primary Soft tissue Neuroendocrine Tumour with metastases and near-complete resolution with 177Lu-DOTATATE: documenting a Promising Clinical Application of Peptide Receptor Radionuclide Therapy.

J Nucl Med Technol. 2019 Aug 10;:

Authors: Adnan A, Basu S

Abstract
Neuroendocrine tumours (NETs) of the skin or soft tissue are rare tumors (mostly described as site of metastasis), while primary soft tissue neuroendocrine tumours are extremely rare; they are usually diagnosed at advanced stages with distant metastases due to their indolent nature. We herein describe our experience with two such cases. In the first case, the NET originated in the retroperitoneal soft tissue and the second patient was a middle aged lady with NET arising from soft tissue in the pelvis. Both patients were treated with 177Lu-DOTATATE in view of SSTR expressing metastatic lesions, demonstrating excellent outcome reflected by complete metabolic response and near-complete anatomical response to the administered PRRT. The noteworthy factors of the reported cases were: (i) unusual sites of primary tumour and (ii) near-complete to complete symptomatic, anatomical and metabolic resolution of the recurrent primary tumour and metastatic lesions with PRRT alone. NETs arising from the rare anatomical locations are usually non-functioning with good clinical outcomes and 177Lu-DOTATATE PRRT can be considered a promising therapeutic modality in patients with metastatic or advanced disease.

PMID: 31401619 [PubMed - as supplied by publisher]

Resolution of necrolytic migratory erythema with somatostatin analogue in a patient diagnosed with pancreatic glucagonoma.

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

Resolution of necrolytic migratory erythema with somatostatin analogue in a patient diagnosed with pancreatic glucagonoma.

BMJ Case Rep. 2019 Aug 10;12(8):

Authors: Saavedra C, Lamarca A, Hubner RA

Abstract
A 70-year-old man reported progressive weight loss, fatigue and a generalised rash. The rash was consistent with necrolytic migratory erythema, further investigations were performed and the patient was diagnosed with a mass in the tail of the pancreas, in keeping with a localised glucagonoma. Somatostatin analogue therapy was started for symptom control, leading to complete resolution of the skin rash and an improvement in constitutional symptoms. Subsequently, the pancreatic lesion was excised, and pathology assessment confirmed the diagnosis of well-differentiated neuroendocrine tumour with high expression of glucagon compatible with glucagonoma.

PMID: 31401568 [PubMed - in process]

Permalink for 'Letter to the Editor: "The conundrum of < 2-cm pancreatic neuroendocrine tumors: A preoperative risk score to predict lymph node metastases and guide surgical management".'

Letter to the Editor: "The conundrum of < 2-cm pancreatic neuroendocrine tumors: A preoperative risk score to predict lymph node metastases and guide surgical management".

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

Letter to the Editor: "The conundrum of < 2-cm pancreatic neuroendocrine tumors: A preoperative risk score to predict lymph node metastases and guide surgical management".

Surgery. 2019 Aug 06;:

Authors: Mattoo S, Mahalakshmi V, Dhanda M, Mayilvaganan S, Agarwal A

PMID: 31399215 [PubMed - as supplied by publisher]

Permalink for 'Distribution of Neuroendocrine Marker-Positive Cells in Colorectal Cancer Tissue and Normal Mucosal Tissue: Consideration of Histogenesis of Neuroendocrine Cancer.'

Distribution of Neuroendocrine Marker-Positive Cells in Colorectal Cancer Tissue and Normal Mucosal Tissue: Consideration of Histogenesis of Neuroendocrine Cancer.

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

Distribution of Neuroendocrine Marker-Positive Cells in Colorectal Cancer Tissue and Normal Mucosal Tissue: Consideration of Histogenesis of Neuroendocrine Cancer.

Oncology. 2019 Aug 07;:1-7

Authors: Ogimi T, Sadahiro S, Kamei Y, Chan LF, Miyakita H, Saito G, Okada K, Suzuki T, Kajiwara H

Abstract
BACKGROUND: Colorectal neuroendocrine carcinoma (NEC) is a rare disease, and mixed cases with colorectal adenocarcinoma also exist. The histogenesis of this disease remains unclear. We studied the numbers of neuroendocrine marker-positive cells in adenocarcinoma tissue and in normal -mucosal tissue to investigate the relation between adenocarcinoma and NEC and to discuss the histogenesis of NEC.
METHODS: We studied a total of 354 curatively resected cases of stage II or III colon cancer and 36 cases of rectal cancer treated at the Tokai University Hospital between 2007 and 2012. Adenocarcinoma tissue and normal mucosal tissue were immunohistochemically stained with chromogranin A, synaptophysin, and CD56. Cases in which neuroendocrine marker-positive cells were found in cancer tissue were defined as positive. In normal mucosa, the numbers of positive cells per 15 high-power fields (HPF) were counted.
RESULTS: Among the 390 cases, 181 cases had right sided colon cancer, 173 cases had left sided colon cancer, and 36 cases had rectal cancer. The rates of positive staining for chromogranin A, synaptophysin, and CD56 were significantly higher in the right sided colon than in the left sided colon, consistent with the preferred sites of NEC as reported previously. Cells positive for chromogranin A and synaptophysin in normal mucosa were significantly more common in the rectum and the left sided colon than in the right sided colon. No site-specific differences were found for CD56.
CONCLUSIONS: Neuroendocrine marker-positive cells in colorectal cancer tissue are more common in the right sided colon, whereas neuroendocrine marker-positive cells in normal mucosa are more common in the rectum. These results suggest that NEC may arise from preceding adenocarcinomas.

PMID: 31390635 [PubMed - as supplied by publisher]

Permalink for 'Prediction of Progression-Free Survival in Patients With Advanced, Well-Differentiated, Neuroendocrine Tumors Being Treated With a Somatostatin Analog: The GETNE-TRASGU Study.'

Prediction of Progression-Free Survival in Patients With Advanced, Well-Differentiated, Neuroendocrine Tumors Being Treated With a Somatostatin Analog: The GETNE-TRASGU Study.

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

Prediction of Progression-Free Survival in Patients With Advanced, Well-Differentiated, Neuroendocrine Tumors Being Treated With a Somatostatin Analog: The GETNE-TRASGU Study.

J Clin Oncol. 2019 Aug 07;:JCO1900980

Authors: Carmona-Bayonas A, Jiménez-Fonseca P, Lamarca Á, Barriuso J, Castaño Á, Benavent M, Alonso V, Riesco-Martínez MDC, Alonso-Gordoa T, Custodio A, Sánchez Cánovas M, Hernando Cubero J, López C, Lacasta A, Fernández Montes A, Marazuela M, Crespo G, Escudero P, Diaz JÁ, Feliciangeli E, Gallego J, Llanos M, Segura Á, Vilardell F, Percovich JC, Grande E, Capdevila J, Valle JW, García-Carbonero R

Abstract
PURPOSE: Somatostatin analogs (SSAs) are recommended for the first-line treatment of most patients with well-differentiated, gastroenteropancreatic (GEP) neuroendocrine tumors; however, benefit from treatment is heterogeneous. The aim of the current study was to develop and validate a progression-free survival (PFS) prediction model in SSA-treated patients.
PATIENTS AND METHODS: We extracted data from the Spanish Group of Neuroendocrine and Endocrine Tumors Registry (R-GETNE). Patient eligibility criteria included GEP primary, Ki-67 of 20% or less, and first-line SSA monotherapy for advanced disease. An accelerated failure time model was developed to predict PFS, which was represented as a nomogram and an online calculator. The nomogram was externally validated in an independent series of consecutive eligible patients (The Christie NHS Foundation Trust, Manchester, United Kingdom).
RESULTS: We recruited 535 patients (R-GETNE, n = 438; Manchester, n = 97). Median PFS and overall survival in the derivation cohort were 28.7 (95% CI, 23.8 to 31.1) and 85.9 months (95% CI, 71.5 to 96.7 months), respectively. Nine covariates significantly associated with PFS were primary tumor location, Ki-67 percentage, neutrophil-to-lymphocyte ratio, alkaline phosphatase, extent of liver involvement, presence of bone and peritoneal metastases, documented progression status, and the presence of symptoms when initiating SSA. The GETNE-TRASGU (Treated With Analog of Somatostatin in Gastroenteropancreatic and Unknown Primary NETs) model demonstrated suitable calibration, as well as fair discrimination ability with a C-index value of 0.714 (95% CI, 0.680 to 0.747) and 0.732 (95% CI, 0.658 to 0.806) in the derivation and validation series, respectively.
CONCLUSION: The GETNE-TRASGU evidence-based prognostic tool stratifies patients with GEP neuroendocrine tumors receiving SSA treatment according to their estimated PFS. This nomogram may be useful when stratifying patients with neuroendocrine tumors in future trials. Furthermore, it could be a valuable tool for making treatment decisions in daily clinical practice.

PMID: 31390276 [PubMed - as supplied by publisher]

Totally robotic right hemicolectomy with the hanging technique for carcinoid tumor.

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

Totally robotic right hemicolectomy with the hanging technique for carcinoid tumor.

Colorectal Dis. 2019 Aug 06;:

Authors: Kudsi OY, Gokcal F

Abstract
Carcinoid tumors are rare neuroendocrine tumors (NETs) found mostly in the gastrointestinal system. The occurrence of NETs in the large intestine according to the location of origin distribute as follows; 54% in the rectum, 20% in the cecum, 7.5% in the sigmoid colon, 5.5% in the rectosigmoid colon and 5% in the ascending colon [1]. A complete cure is usually possible in cases diagnosed and treated early. Extensive lymph node dissection is crucial for colon cancer surgery [2]. To this end, various techniques have been proposed to achieve better oncological results. This article is protected by copyright. All rights reserved.

PMID: 31389115 [PubMed - as supplied by publisher]

Safety and Feasibility of Robotic Reduced-Port Distal Pancreatectomy: a Multicenter Experience of a Novel Technique.

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

Safety and Feasibility of Robotic Reduced-Port Distal Pancreatectomy: a Multicenter Experience of a Novel Technique.

J Gastrointest Surg. 2019 Aug 06;:

Authors: Park G, Choi SH, Lee JH, Lim JH, Lee H, Lee JH, Kang CM

Abstract
BACKGROUND: A reduced-port approach including single-site surgery has been used for distal pancreatectomy. However, triangulation is difficult in reduced-port laparoscopic distal pancreatectomy, and instrument crowding, and collision may occur, so this approach has not been widely used. Recently, an innovative technique for distal pancreatectomy using a robotic single-site surgical system was introduced. Herein, we evaluate the safety and feasibility of this technique.
METHODS: Twenty-seven patients with a pancreatic tail mass underwent robotic single-site plus one-port distal pancreatectomy at six centers. We collected clinicopathologic data and evaluated the short-term perioperative outcomes of robotic single-site plus one-port distal pancreatectomy.
RESULTS: We evaluated 26 patients who underwent robotic single-site plus one-port distal pancreatectomy excluding one patient who needed more ports because of fatty abdomen. The mean age and body mass index were 47.3 years (range 21-74) and 22.6 kg/m2 (range 15.8-28.8), respectively. The most common pathologic diagnosis was solid papillary neoplasm followed by a neuroendocrine tumor. The mean operating time was 201 min. The mean length of hospital stay after surgery was 7 days (range 4-10). The rate of spleen preservation was 34.6% (9/26). Six patients had postoperative pancreatic fistula (POPF) grade A, and no patients had POPF grade B or C. Only one patient had class II morbidity.
CONCLUSION: Robotic single-site plus one-port distal pancreatectomy is safe and feasible in terms of short-term outcomes. This technique could be performed in select cases to expand the surgical boundaries of the robotic single-site platform. Further studies are needed with more cases to investigate long-term outcomes.

PMID: 31388883 [PubMed - as supplied by publisher]

Large cell neuroendocrine carcinoma of the submandibular gland: a case report and literature review.

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

Large cell neuroendocrine carcinoma of the submandibular gland: a case report and literature review.

Pathologica. 2019 Jun;111(2):70-75

Authors: Mascitti M, Luconi E, Togni L, Rubini C

Abstract
Neuroendocrine tumors (NET) are a heterogeneous group of malignancies with a broad spectrum of histomorphologies, tissue origins, and clinical outcomes, which arise from neural crest cells with neuroendocrine differentiation. Salivary gland tumors account for 3-6% of all head and neck neoplasms, while large cell neuroendocrine carcinomas (LCNEC) of the salivary gland are extremely rare, with few cases reported in literature, and only 5 cases involving submandibular gland. The rarity of these tumors in salivary glands is probably related to the scarcity of neuroendocrine cells in this tissue, whose presence is still a matter of debate. Regardless of their low frequency, it is imperative to differentiate these tumors from the much more common squamous cell carcinomas and metastatic NETs, due to different therapeutic approach and prognosis. In this paper, we report the case of a 21-year-old man, with a LCNEC involving a submandibular gland followed by several recurrences over the years. In addition, we include a comprehensive review of the available literature on this topic.

PMID: 31388199 [PubMed - in process]

Corrigendum to "Cystic pancreatic neuroendocrine tumors: A more favorable lesion?" [Pancreatology 19 (2) (March 2019) 372-376].

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

Corrigendum to "Cystic pancreatic neuroendocrine tumors: A more favorable lesion?" [Pancreatology 19 (2) (March 2019) 372-376].

Pancreatology. 2019 Aug 03;:

Authors: Carr RA, Bletsis P, Roch AM, House MG, Zyromski NJ, Nakeeb A, Schmidt CM, Ceppa EP

PMID: 31387834 [PubMed - as supplied by publisher]

MiRNAs as Potential Prognostic Biomarkers for Metastasis in Thin and Thick Primary Cutaneous Melanomas.

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

MiRNAs as Potential Prognostic Biomarkers for Metastasis in Thin and Thick Primary Cutaneous Melanomas.

Anticancer Res. 2019 Aug;39(8):4085-4093

Authors: Valentini V, Zelli V, Gaggiano E, Silvestri V, Rizzolo P, Bucalo A, Calvieri S, Grassi S, Frascione P, Donati P, Soda G, Ottini L, Richetta AG

Abstract
BACKGROUND/AIM: The identification of novel prognostic biomarkers for melanoma metastasis is essential to improve patient outcomes. To this aim, we characterized miRNA expression profiles in relation to metastasis in melanoma and correlated miRNAs expression with clinical-pathological factors.
MATERIALS AND METHODS: MiR-145-5p, miR-150-5p, miR-182-5p, miR-203-3p, miR-205-5p and miR-211-5p expression levels were analyzed in primary cutaneous melanomas, including thin and thick melanomas, and in melanoma metastases by quantitative Real-Time PCR.
RESULTS: A significantly lower miR-205-5p expression was found in metastases compared to primary melanomas. Furthermore, a progressive down-regulation of miR-205-5p expression was observed from loco-regional to distant metastasis. Significantly lower miR-145-5p and miR-203-3p expression levels were found in cases with Breslow thickness >1 mm, high Clark level, ulceration and mitotic rate ≥1/mm2 Conclusion: Our findings point to miR-205-5p as potential biomarker of distant metastases and to miR-145-5p and miR-203-3p as markers of aggressiveness in melanoma.

PMID: 31366492 [PubMed - indexed for MEDLINE]

[Ectopic adrenocorticotrophin syndrome caused by silent pheochromocytoma: a case report].

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

[Ectopic adrenocorticotrophin syndrome caused by silent pheochromocytoma: a case report].

Zhonghua Nei Ke Za Zhi. 2019 07 01;58(7):533-536

Authors: Song XX, Zhang HW, Guo YY, Wang XL, Ma Yi Nu Er, Zhang J, Zhao HL, Nu Rong Gu Li, Ha Ni Ke Zi

PMID: 31269572 [PubMed - indexed for MEDLINE]

Shikimoyl-ligand decorated gold nanoparticles for use in ex vivo engineered dendritic cell based DNA vaccination.

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

Shikimoyl-ligand decorated gold nanoparticles for use in ex vivo engineered dendritic cell based DNA vaccination.

Nanoscale. 2019 Apr 23;11(16):7931-7943

Authors: Meka RR, Mukherjee S, Patra CR, Chaudhuri A

Abstract
Since mannose receptors (MRs) are expressed on the surfaces of dendritic cells (DCs), the most professional antigen presenting cells in our body, DNA vaccine carriers containing either covalently grafted mannosyl- or mannose-mimicking shikimoyl-ligands are being increasingly used in ex vivo DC-transfection based DNA vaccination. To this end, we have recently demonstrated that ex vivo immunization of mice with liposomes of shikimoylated cationic amphiphiles containing a 6-amino hexanoic acid spacer group in the head-group region in complexation with melanoma antigen (MART1) encoded DNA vaccine (pCMV-MART1) induces long lasting anti-melanoma immune responses (C. Voshavar, et al., J. Med. Chem., 2017, 60, 1605-1610). This finding prompted us to examine, in the present investigation, the efficacies of gold nanoparticles conjugated to the mannose-mimicking shikimoyl ligand (SL) via a 6-amino hexane thiol spacer (AuNPs-SL) for use in ex vivo DC-transfection based genetic immunization. Herein, we report on the design, synthesis, physico-chemical characterization and bioactivities of AuNPs-SL. Dynamic light scattering and transmission electron microscopy studies revealed the hydrodynamic diameters of theAuNPs-SL nanoconjugates to be within the range of 23-44 nm and their surface potentials within the range of 9-28 mV. MTT-assay showed the non-cytotoxic nature of AuNPs-SL and the findings in the electrophoretic gel retardation assays revealed strong DNA binding properties of the AuNPs-SL. Importantly, subcutaneous immunization of C57BL/6J mice with DCs ex vivo transfected with an electrostatic complex of AuNPs-SL & melanoma antigen (MART1) encoded DNA vaccine (p-CMV-MART1) induced a long lasting (100 days) anti-tumor immune response in immunized mice upon subsequent challenge with a lethal dose of melanoma. Notably, mice immunized with either autologous mbmDCs ex vivo pre-transfected with nanoplexes of shikimoylated AuNPs-SL & an irrelevant pCMV-SPORT-β-gal plasmid (without having encoded melanoma antigen) or untransfected DCs showed no lasting protection against subsequent tumor challenge. The presently described shikimoyl-decorated gold nanoparticles (AuNPs-SL) are expected to find future use in ex vivo DC-transfection based genetic immunization against cancer and other infectious diseases.

PMID: 30964937 [PubMed - indexed for MEDLINE]

Axillary sentinel node biopsy in prone position for melanomas on the upper back or nape.

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

Axillary sentinel node biopsy in prone position for melanomas on the upper back or nape.

J Plast Surg Hand Surg. 2019 Aug;53(4):221-226

Authors: Kretschmer L, Hellriegel S, Cevik N, Hartmann F, Thoms KM, Schön MP

Abstract
In patients with melanomas on the upper back or nape, axillary sentinel lymph node (SLN) biopsy (SLNB), when performed in the traditional supine position, is often disturbed by scattered radiation emitted from the primary tumor site. The results from the present study suggestthat axillary SLNB performed in the prone position can solve this problem. We compared two consecutive groups of patients with melanomas of the dorsal trunk or nape who received axillary SLNB performed either in the supine (n = 119) or in the prone position (n = 130). The number of SLNs detected and excised was significantly higher in prone position group (2.4 ± 1.5 SLNs versus 1.9 ± 0.95 SLNs, p = 0.002). Using the prone position, intra-operative repositioning of the patient for excision of a primary site of the upper back or neck was not necessary. The SLN identification rates and the SLN-positivity rates did not differ significantly between the two types of intraoperative patient positioning. There were no significant differences in survival outcomes or false-negative rates. In conclusion, axillary SLNB in prone position yields a higher number of excised SLNs in patients with melanomas of the upper back or nape. Axillary SLNB in prone position is easy to perform and reliable. Intraoperative repositioning of the patient is not necessary, which saves time and resources.

PMID: 30848977 [PubMed - indexed for MEDLINE]

Management and surveillance of non-functional pancreatic neuroendocrine tumours: Retrospective review.

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

Management and surveillance of non-functional pancreatic neuroendocrine tumours: Retrospective review.

Pancreatology. 2019 Mar;19(2):360-366

Authors: Yohanathan L, Dossa F, St Germain AT, Golbafian F, Moulton CA, McGilvray ID, Greig PD, Serra S, Wei AC, Jhaveri KS, Gallinger S, Cleary SP

Abstract
BACKGROUND: /Objective. To determine the outcomes of a non-operative management approach for sporadic, small, non-functional pancreatic neuroendocrine tumours.
METHODS: A retrospective chart review of patients with non-functional pancreatic neuroendocrine tumours initially managed non-operatively at a single institution was performed. Patients were identified through a search of radiologic reports, and individuals with ≥2 cross-sectional imaging studies performed >6 months apart from Jan. 1, 2000 to Dec. 31, 2013 were included. Data on tumour size, radiologic characteristics at diagnosis, interval radiologic growth, and surgical outcomes were recorded.
RESULTS: Over the thirteen-year study period, 95 patients met inclusion criteria and were followed radiologically for a median of 36 months (18-69 months). Median initial tumour size on first imaging was 14.0 mm (IQR 10-19 mm). Median overall tumour growth rate was 0.03 mm/month (IQR: 0.00-0.14 mm/month). There was no significant relationship between initial tumour size and growth rate for tumours ≤ 2 cm or for lesions between 2 and 4 cm. Thirteen (14%) patients initially managed non-operatively underwent resection during the follow-up period. Reasons for surgery included interval tumour growth, patient anxiety or preference, or diagnostic uncertainty. Median time to surgery was 14 months (IQR 8-19 months). No patients progressed beyond resectability or developed metastatic disease during the observation period.
CONCLUSION: For patients with sporadic, small, non-functional pancreatic neuroendocrine tumours, radiologic surveillance appears to be a safe initial approach to management.

PMID: 30803874 [PubMed - indexed for MEDLINE]

Can we predict recurrence in WHO G1-G2 pancreatic neuroendocrine neoplasms? Results from a multi-institutional Spanish study.

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

Can we predict recurrence in WHO G1-G2 pancreatic neuroendocrine neoplasms? Results from a multi-institutional Spanish study.

Pancreatology. 2019 Mar;19(2):367-371

Authors: Ausania F, Senra Del Rio P, Gomez-Bravo MA, Martin-Perez E, Pérez-Daga JA, Dorcaratto D, González-Nicolás T, Sanchez-Cabus S, Tardio-Baiges A

Abstract
INTRODUCTION: Pancreatic neuroendocrine neoplasms (PNEN) are rare tumours and well differentiated PNEN are associated with relatively indolent physiological behaviour. For this reason, only few studies have investigated those factors associated with recurrence in this group of patients. The aim of this study is to analyse whether it is possible to predict tumour recurrence in World Health Organization (WHO) 2017 G1-G2 PNEN patients.
METHODS: This is a retrospective multi-institutional study. Patients submitted to pancreatic resection from 7 Spanish centres were reviewed. Only patients with WHO G1-G2 PNEN were included. Demographic and clinicopathological variables were analysed.
RESULTS: Data from 137 patients were reviewed. Median age was 59.2 (25-84) years. Recurrence of disease occurred in 19 (13.9%) patients. Median DFS was 55 months. At multivariate analysis, tumour size >20 mm, lymphnode metastasis and a new tumour grade 2 incorporating Ki-67 labelling index (LI) > 5% and mitotic index (MI) > 2 were independently associated with recurrence. We developed a risk score model with these three factors. High-risk patients had a significantly lower 5-year disease-specific survival compared to low-risk patients (70% vs 100%).
CONCLUSION: We propose a novel risk score for recurrence based on lymphnode metastasis, tumour size > 20 mm and a new grade 2 based on Ki-67 LI >5% and MI > 2. If 2 factors are present, patients have a higher risk for recurrence and a significantly poorer DSS, and therefore they should be closely monitored during follow-up. The role of adjuvant chemotherapy in these patients needs to be evaluated in clinical trials.

PMID: 30683515 [PubMed - indexed for MEDLINE]

Permalink for 'Updated Recommendations on the Diagnosis, Management, and Clinical Trial Eligibility Criteria for Patients With Renal Medullary Carcinoma.'

Updated Recommendations on the Diagnosis, Management, and Clinical Trial Eligibility Criteria for Patients With Renal Medullary Carcinoma.

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

Updated Recommendations on the Diagnosis, Management, and Clinical Trial Eligibility Criteria for Patients With Renal Medullary Carcinoma.

Clin Genitourin Cancer. 2019 02;17(1):1-6

Authors: Msaouel P, Hong AL, Mullen EA, Atkins MB, Walker CL, Lee CH, Carden MA, Genovese G, Linehan WM, Rao P, Merino MJ, Grodman H, Dome JS, Fernandez CV, Geller JI, Apolo AB, Daw NC, Hodges HC, Moxey-Mims M, Wei D, Bottaro DP, Staehler M, Karam JA, Rathmell WK, Tannir NM

Abstract
Renal medullary carcinoma (RMC) is one of the most aggressive renal cell carcinomas. It predominantly afflicts young adults and adolescents with sickle cell trait and other sickle hemoglobinopathies, and is refractory to targeted and antiangiogenic therapies used in patients with clear-cell renal cell carcinoma. Platinum-based cytotoxic chemotherapy is the mainstay for RMC treatment. On the basis of recent advances in the diagnosis, management, and clinical trial development for RMC, a panel of experts met in October 2017 and developed updated consensus recommendations to inform clinicians, researchers, and patients. Because RMC often aggressively recurs while patients are still recovering from nephrectomy, upfront chemotherapy should be considered for most patients, including those with localized disease. After safety and dosing information has been established in adults, phase II and III trials enrolling patients with RMC should allow patients aged 12 years and older to be accrued. Patients with the very rare unclassified renal cell carcinoma with medullary phenotype variant should be included in RMC trials. Medical providers should be aware that RMC can afflict subjects of all races, and not only those of African descent, and that the presence of sickle cell trait, or of other sickle hemoglobinopathies, can affect drug responses and toxicity.

PMID: 30287223 [PubMed - indexed for MEDLINE]

A Potential Therapy Using Engineered Stem Cells Prevented Malignant Melanoma in Cellular and Xenograft Mouse Models.

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

A Potential Therapy Using Engineered Stem Cells Prevented Malignant Melanoma in Cellular and Xenograft Mouse Models.

Cancer Res Treat. 2019 Apr;51(2):797-811

Authors: Heo JR, Hwang KA, Kim SU, Choi KC

Abstract
PURPOSE: In the present study, human neural stem cells (hNSCs) with tumor-tropic behavior were used as drug delivery vehicle to selectively target melanoma. A hNSC line (HB1.F3) was transduced into two types: one expressed only the cytosine deaminase (CD) gene (HB1.F3. CD) and the other expressed both CD and human interferon-β (IFN-β) genes (HB1.F3.CD. IFN-β).
Materials and Methods: This study verified the tumor-tropic migratory competence of engineered hNSCs on melanoma (A375SM) using a modified Boyden chamber assay in vitro and CM-DiI staining in vivo. The antitumor effect of HB1.F3.CD and HB1.F3.CD.IFN-β on melanoma was also confirmed using an MTT assay in vitro and xenograft mouse models.
RESULTS: A secreted form of IFN-β from the HB1.F3.CD.IFN-β cells modified the epithelial-mesenchymal transition (EMT) process and metastasis of melanoma. 5-Fluorouracil treatment also accelerated the expression of the pro-apoptotic protein BAX and decelerated the expression of the anti-apoptotic protein Bcl-xL on melanoma cell line.
CONCLUSION: Our results illustrate that engineered hNSCs prevented malignant melanoma cells from proliferating in the presence of the prodrug, and the form that secreted IFN-β intervened in the EMT process and melanoma metastasis. Hence, neural stem cell-directed enzyme/prodrug therapy is a plausible treatment for malignant melanoma.

PMID: 30213181 [PubMed - indexed for MEDLINE]

From validity to clinical utility: the influence of circulating tumor DNA on melanoma patient management in a real-world setting.

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

From validity to clinical utility: the influence of circulating tumor DNA on melanoma patient management in a real-world setting.

Mol Oncol. 2018 10;12(10):1661-1672

Authors: Rowe SP, Luber B, Makell M, Brothers P, Santmyer J, Schollenberger MD, Quinn H, Edelstein DL, Jones FS, Bleich KB, Sharfman WH, Lipson EJ

Abstract
Melanoma currently lacks a reliable blood-based biomarker of disease activity, although circulating tumor DNA (ctDNA) may fill this role. We investigated the clinical utility (i.e., impact on clinical outcomes and interpretation of radiographic data) of measuring ctDNA in patients with metastatic or high-risk resected melanoma. Patients were prospectively accrued into ≥ 1 of three cohorts, as follows. Cohort A: patients with radiographically measurable metastatic melanoma who underwent comparison of ctDNA measured by a BEAMing digital PCR assay to tissue mutational status and total tumor burden; when appropriate, determinations about initiation of targeted therapy were based on ctDNA data. Cohorts B and C: patients with BRAF- or NRAS-mutant melanoma who had either undergone surgical resection of high-risk disease (cohort B) or were receiving or had received medical therapy for advanced disease (cohort C). Patients were followed longitudinally with serial ctDNA measurements with contemporaneous radiographic imaging to ascertain times to detection of disease activity and progressive disease, respectively. The sensitivity and specificity of the ctDNA assay were 86.8% and 100%, respectively. Higher tumor burden and visceral metastases were found to be associated with detectable ctDNA. In two patients in cohort A, ctDNA test results revealed a targetable mutation where tumor testing had not; both patients experienced a partial response to targeted therapy. In four of 30 patients with advanced melanoma, ctDNA assessments indicated evidence of melanoma activity that predicted radiographic evidence of disease progression by 8, 14, 25, and 38 weeks, respectively. CtDNA was detectable in three of these four patients coincident with radiographic evaluations that alone were interpreted as showing no evidence of neoplastic disease. Our findings provide evidence for the clinical utility of integrating ctDNA data in managing patients with melanoma in a real-world setting.

PMID: 30113761 [PubMed - indexed for MEDLINE]

Predictors of sentinel lymph node status of cutaneous melanoma in Serbian patients.

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

Predictors of sentinel lymph node status of cutaneous melanoma in Serbian patients.

J BUON. 2018 Mar-Apr;23(2):468-474

Authors: Jokic S, Markovic I, Bukumiric Z, Jokic V, Rakovic M, Tripkovic J, Stojiljkovic D, Spurnic I, Jevric M, Matic M, Dobrosavljevic D

Abstract
PURPOSE: Presence of metastasis in sentinel lymph node (SLN) is considered to be the most important factor in terms of patient survival. The main aim of this study was to identify predictors of positive SLN in Serbian patients with melanoma.
METHODS: This retrospective study was conducted on 147 patients. Univariate chi-square and univariate logistic regression analyses were used to identify the association between prognostic factors and positive SLN. Receiver Operating Characteristics (ROC) was conducted to find the Breslow thickness cutoff point at which to perform SLN biopsy (SLNB). Kaplan-Meier analysis was used to evaluate disease-free survival (DFS), and log rank test was applied to compare differences between groups.
RESULTS: Breslow thickness and Clark level (p≤0.05), presence of ulceration and a high mitotic rate (>6 mitoses/mm2) (p<0.001) were significant independent predictors of SLN metastasis. ROC curve showed that Breslow thickness of 2.8 mm was the most suitable cutoff point for SLN positivity (sensitivity 86%, specificity 67%). Furthermore, Breslow thickness and presence of ulceration were found to be associated with DFS (p<0.05).
CONCLUSIONS: Patients with Breslow thickness ≥2.8 mm, ulceration, and high mitotic rate are at higher risk for SLN metastasis. In addition, high Breslow thickness and presence of ulceration are associated with decreased DFS. These results indicate that multiple selection criteria should be used when performing and predicting SLN metastasis and disease recurrence.

PMID: 29745094 [PubMed - indexed for MEDLINE]

Permalink for 'Integrative analysis of competing endogenous RNA network focusing on long noncoding RNA associated with progression of cutaneous melanoma.'

Integrative analysis of competing endogenous RNA network focusing on long noncoding RNA associated with progression of cutaneous melanoma.

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

Integrative analysis of competing endogenous RNA network focusing on long noncoding RNA associated with progression of cutaneous melanoma.

Cancer Med. 2018 04;7(4):1019-1029

Authors: Xu S, Sui J, Yang S, Liu Y, Wang Y, Liang G

Abstract
Cutaneous melanoma (CM) is the most malignant tumor of skin cancers because of its rapid development and high mortality rate. Long noncoding RNAs (lncRNAs), which play essential roles in the tumorigenesis and metastasis of CM and interplay with microRNAs (miRNAs) and mRNAs, are hopefully considered to be efficient biomarkers to detect deterioration during the progression of CM to improve the prognosis. Bioinformatics analysis was fully applied to predict the vital lncRNAs and the associated miRNAs and mRNAs, which eventually constructed the competing endogenous RNA (ceRNA) network to explain the RNA expression patterns in the progression of CM. Further statistical analysis emphasized the importance of these key genes, which were statistically significantly related to one or few clinical features from the ceRNA network. The results showed the lncRNAs MGC12926 and LINC00937 were verified to be strongly connected with the prognosis of CM patients.

PMID: 29522273 [PubMed - indexed for MEDLINE]

Higher than reported adolescent and young adult clinical trial enrollment during the "Golden Age" of melanoma clinical trials.

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

Higher than reported adolescent and young adult clinical trial enrollment during the "Golden Age" of melanoma clinical trials.

Cancer Med. 2018 04;7(4):991-996

Authors: Sreeraman Kumar R, Thapa R, Kim Y, Khushalani NI, Sondak VK, Reed DR

Abstract
Clinical trial enrollments in adolescents and young adults (AYA) with cancer have historically been lower than those in pediatric and older adult populations. We sought to examine therapeutic trial enrollment rates at our cancer center. We performed a retrospective evaluation of AYA patients treated before and after the first checkpoint inhibitor trial opened at our cancer center in 2007. We examined gender, stage at presentation and insurance status in terms of trial enrollment. We compared the trial participation rate of AYA patients with that of older adults. In this adult facility, 12.7% (1,831) of total patients were between age 15 and 39. Overall therapeutic clinical trial rate was 17.6% which increased to 19.8% since 2007. Both nodal disease or metastatic disease at presentation was associated with increasing odds of trial enrollment (OR = 5.36 and P < 0.001 for nodal disease and OR = 7.96 and P < 0.001 for metastatic disease). There was a nonstatistically significant trend toward improved 3-year overall survival in the AYA patients with advanced presentation that enrolled on clinical trials compared with those not enrolled on trials since 2007. AYA clinical trial enrollment at a comprehensive care center melanoma program was higher than reported in the literature overall for AYA patients. This 1,831 patient cohort may provide a foundation for more detailed investigation toward quantifying the effects of clinical trial enrollment in terms of age-specific benefits and toxicities for AYA patients with malignancies that have their peak incidence in older adults.

PMID: 29478277 [PubMed - indexed for MEDLINE]

Permalink for 'Expanded Transcanal Transpromontorial Approach: A Novel Surgical Technique for Cerebellopontine Angle Vestibular Schwannoma Removal.'

Expanded Transcanal Transpromontorial Approach: A Novel Surgical Technique for Cerebellopontine Angle Vestibular Schwannoma Removal.

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

Expanded Transcanal Transpromontorial Approach: A Novel Surgical Technique for Cerebellopontine Angle Vestibular Schwannoma Removal.

Otolaryngol Head Neck Surg. 2018 04;158(4):710-715

Authors: Marchioni D, Carner M, Soloperto D, Bianconi L, Sacchetto A, Sacchetto L, Masotto B, Presutti L

Abstract
Objective Vestibular schwannoma (VS) is a benign tumor of the lateral skull base. Different microscopic surgical techniques are described in literature: the retrosigmoid and translabyrinthine approaches are used to treat big tumors located in the cerebellopontine angle, and the middle cranial fossa approach is utilized for small tumors with good hearing preservation. The expanded transcanal transpromontorial (ExpTT) approach is a combined microscopic-endoscopic technique previously indicated for Koos stage I and II VS and now proposed for larger VS, up to 3 cm in diameter, with linear progression into the cerebellopontine angle and touching the brainstem. Study Design The study was a retrospective case series of patients who underwent ExpTT surgery for VS in our ear, nose, and throat department. Setting We reviewed the surgical videos and electrophysiologic data recorded during the surgical operations. Subjects and Methods From January 2015 to January 2017, 20 patients affected by Koos stage II and III VS underwent surgery in our department with the ExpTT approach. This novel technique is described step by step, with a focus on the surgical procedure and anatomic landmarks; outcomes are detailed in terms of early and late complications. The mean follow-up was 15 months. Results The ExpTT approach permitted, in all patients, gross total resection of the tumor without any complication and with preservation of facial nerve function. All patients had a good postoperative recovery. Conclusion The ExpTT technique is a new approach that combines the advantages of a microscopic technique with the ones offered by the endoscope in removal of VS.

PMID: 29405836 [PubMed - indexed for MEDLINE]

Permalink for 'Erratum to "Characteristics of 252 patients with bronchopulmonary neuroendocrine tumours treated at the Copenhagen NET Centre of Excellence" [Lung Cancer 132 (June) (2019) 141-149].'

Erratum to "Characteristics of 252 patients with bronchopulmonary neuroendocrine tumours treated at the Copenhagen NET Centre of Excellence" [Lung Cancer 132 (June) (2019) 141-149].

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

Erratum to "Characteristics of 252 patients with bronchopulmonary neuroendocrine tumours treated at the Copenhagen NET Centre of Excellence" [Lung Cancer 132 (June) (2019) 141-149].

Lung Cancer. 2019 Jul 31;:

Authors: Grøndahl V, Binderup T, Langer SW, Petersen RH, Nielsen K, Kjaer A, Federspiel B, Knigge U

PMID: 31377004 [PubMed - as supplied by publisher]

Radiological and histological findings of an asymptomatic ever-increasing neoplasm: The small bowel neuroendocrine tumor (NET).

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

Radiological and histological findings of an asymptomatic ever-increasing neoplasm: The small bowel neuroendocrine tumor (NET).

Curr Probl Cancer. 2019 Jul 26;:

Authors: Picchia S, Terlizzo M, Bali MA

Abstract
The small bowel neuroendocrine tumor is a rare but ever-increasing tumor, most of the time asymptomatic and found incidentally. An early diagnosis can consistently change the prognosis.

PMID: 31376987 [PubMed - as supplied by publisher]

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Endocrine/Neuroendocrine (528 unread)

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