Rare Cancer News & Clinical Trials » Endocrine/Neuroendocrine

Endocrine/Neuroendocrine (527 unread)

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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]

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

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

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

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

Int J Cancer. 2019 Mar 15;:

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

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

PMID: 30873613 [PubMed - as supplied by publisher]

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

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

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

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

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

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

PMID: 30640835 [PubMed - indexed for MEDLINE]

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

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

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

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

Authors: Veness M

PMID: 28804895 [PubMed - indexed for MEDLINE]

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

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

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

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

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

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

PMID: 30865403 [PubMed - in process]

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

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

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

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

Authors: Kobrinski DA, Choudhury AM, Shah RP

Abstract

PMID: 30325324 [PubMed - indexed for MEDLINE]

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

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

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

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

Authors: Siref A, Hendifar A, Balzer B

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

PMID: 29894357 [PubMed - indexed for MEDLINE]

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

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

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

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

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

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

PMID: 30598450 [PubMed - indexed for MEDLINE]

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

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

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

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

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

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

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

PMID: 30315594 [PubMed - indexed for MEDLINE]

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

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

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

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

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

PMID: 30852509 [PubMed - in process]

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

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

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

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

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

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

PMID: 30099776 [PubMed - indexed for MEDLINE]

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

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

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

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

Authors: Yom SS

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

PMID: 30827456 [PubMed - in process]

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

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

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

Icon for Silverchair Information Systems

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

JAMA Dermatol. 2019 Mar 02;:

Authors: Cheraghlou S, Agogo GO, Girardi M

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

PMID: 30825411 [PubMed - as supplied by publisher]

Merkel Cell Carcinoma: Therapeutic Update and Emerging Therapies.

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

Merkel Cell Carcinoma: Therapeutic Update and Emerging Therapies.

Dermatol Ther (Heidelb). 2019 Feb 28;:

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

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

PMID: 30820877 [PubMed - as supplied by publisher]

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

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

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

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

Clin Cancer Res. 2019 Feb 26;:

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

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

PMID: 30808776 [PubMed - as supplied by publisher]

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

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

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

Eur J Surg Oncol. 2019 Feb 16;:

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

PMID: 30808525 [PubMed - as supplied by publisher]

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

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

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

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

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

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

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

PMID: 29808366 [PubMed - indexed for MEDLINE]

Merkel Cell Polyomavirus Infection and Detection.

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

Merkel Cell Polyomavirus Infection and Detection.

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

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

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

PMID: 30799855 [PubMed - in process]

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

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

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

Neoplasia. 2019 03;21(3):322-330

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

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

PMID: 30797188 [PubMed - indexed for MEDLINE]

Unknown primary Merkel cell carcinoma with cutaneous spread.

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

Unknown primary Merkel cell carcinoma with cutaneous spread.

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

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

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

PMID: 30796073 [PubMed - in process]

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

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

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

Elife. 2019 Feb 22;8:

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

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

PMID: 30794158 [PubMed - in process]

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

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

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

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

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

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

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

PMID: 30788731 [PubMed - as supplied by publisher]

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

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

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

Am J Clin Dermatol. 2019 Feb 19;:

Authors: Samimi M

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

PMID: 30784027 [PubMed - as supplied by publisher]

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

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

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

Exp Dermatol. 2019 Feb 13;:

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

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

PMID: 30758073 [PubMed - as supplied by publisher]

Immunotherapy for skin cancer.

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

Immunotherapy for skin cancer.

Int Immunol. 2019 Feb 08;:

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

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

PMID: 30753483 [PubMed - as supplied by publisher]

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

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

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

Virchows Arch. 2019 Feb 12;:

Authors: Ottaviano M, De Placido S, Ascierto PA

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

PMID: 30747264 [PubMed - as supplied by publisher]

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

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

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

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

Front Oncol. 2019;9:20

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

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

PMID: 30733932 [PubMed]

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

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

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

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

J Clin Oncol. 2019 Feb 06;:JCO1801896

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

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

PMID: 30726175 [PubMed - as supplied by publisher]

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

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

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

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

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

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

PMID: 27655121 [PubMed - indexed for MEDLINE]

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

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

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

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

Cancer Immunol Immunother. 2019 Feb 05;:

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

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

PMID: 30721341 [PubMed - as supplied by publisher]

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

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

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

Icon for Scientific Electronic Library Online

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

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

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

PMID: 27166275 [PubMed - indexed for MEDLINE]

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

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

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

Oncoimmunology. 2019;8(2):e1546544

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

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

PMID: 30713808 [PubMed]

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

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

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

Br J Haematol. 2019 Jan 31;:

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

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

PMID: 30706458 [PubMed - as supplied by publisher]

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

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

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

J Am Acad Dermatol. 2019 Jan 28;:

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

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

PMID: 30703452 [PubMed - as supplied by publisher]

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

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

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

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

Br J Dermatol. 2019 Jan 31;:

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

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

PMID: 30703276 [PubMed - as supplied by publisher]

[Merkel cell carcinoma].

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

[Merkel cell carcinoma].

Hautarzt. 2019 Jan 30;:

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

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

PMID: 30701288 [PubMed - as supplied by publisher]

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

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

Conditions: Advanced Digestive System Neuroendocrine Neoplasm; Digestive System Neuroendocrine Tumor; Foregut Carcinoid Tumor; Hindgut Carcinoid Tumor; Locally Advanced Unresectable Digestive System Neuroendocrine Neoplasm; Metastatic Digestive System Neuroendocrine Neoplasm; Midgut Carcinoid Tumor; Pancreatic Neuroendocrine Tumor; Refractory Digestive System Neuroendocrine Neoplasm
Intervention: Drug: Abemaciclib
Sponsors: University of Washington; National Cancer Institute (NCI)
Not yet recruiting

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

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

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

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

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

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

Conditions: Carcinoma, Non-Small-Cell Lung; Melanoma; Nasopharyngeal Carcinoma; Microsatellite Stable Colorectal Cancer; Triple Negative Breast Cancer
Interventions: Drug: DKY709; Drug: PDR001
Sponsor: Novartis Pharmaceuticals
Not yet recruiting

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

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

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

Survivin Long Peptide Vaccine in Treating Patients With Metastatic Neuroendocrine Tumors

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

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

DEBOXA for Inoperable NET Liver Metastases

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

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

68Ga-DOTATATE PET for Management of Neuroendocrine Tumors

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

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

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

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

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

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

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

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

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

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

Conditions: Bladder Adenocarcinoma; Bladder Mixed Adenocarcinoma; Bladder Small Cell Carcinoma; Bladder Squamous Cell Carcinoma; 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
Not yet recruiting

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

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

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

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

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

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

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

pDNA Intralesional Cancer Vaccine for Cutaneous Melanoma

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

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

A Safety and Tolerability Study of INCAGN02390 in Select Advanced Malignancies

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

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

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

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

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

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

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

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

Molecular-Guided Surgery for Pancreatic and GI Neuroendocrine Cancers

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

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

Denosumab + PD-1 in Subjects With Stage III/ IV Melanoma

Posted: August 8th, 2018, 2:00pm GMT

Conditions: Melanoma Stage Iii; Melanoma Stage Iv; Melanoma; Melanoma (Skin); Cutaneous Melanoma
Interventions: Drug: Denosumab; Drug: Pembrolizumab; Drug: Nivolumab
Sponsors: UNC Lineberger Comprehensive Cancer Center; Amgen
Recruiting

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Whole Body Dynamic 68Ga-DOTATOC PET/CT in Neuroendocrine Tumors

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

Condition: Neuroendocrine Tumors
Intervention: Device: Whole Body Dynamic 68Ga-DOTATOC PET/CT
Sponsor: University Hospital, Brest
Recruiting

Olaparib Before Surgery in Treating Participants With Localized Prostate Cancer

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

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

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

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

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

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

Lymph Node Identification in Skin Malignancy Using ICG Transcutaneously Study

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

Adaptive BRAF-MEK Inhibitor Therapy for Advanced BRAF Mutant Melanoma

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

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

Targeted Imaging of Glutamate Carboxypeptidase II With DCFPyL-PET

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

Conditions: Schwannomas; Malignant Tumors
Intervention: Drug: 18F-DCFPyL Injection
Sponsors: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; National Cancer Institute (NCI)
Recruiting

A Safety and Tolerability Study of INCAGN02385 in Select Advanced Malignancies

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

A Pilot Study Using Short-Term Cultured Anti-Tumor Autologous Lymphocytes

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

Condition: Metastatic Melanoma
Interventions: Drug: Tumor Infiltrating Lymphocytes; Drug: Nivolumab and Ipilimumab
Sponsor: Yale University
Recruiting

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

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

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

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

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

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

A Phase I/II Study of Regorafenib Plus Avelumab in Solid Tumors

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

Conditions: Colorectal Cancer Not MSI-H or MMR-deficient; GIST; Oesophageal or Gastric Carcinoma; Biliary Tract Cancer; Hepatocellular Carcinoma; Soft-tissue Sarcoma; Thyroid Cancer; Gastro-enteropancreatic Neuroendocrine Tumor
Interventions: Drug: Phase 1 : Regorafenib; Drug: Phase 1 : Avelumab; Drug: Phase 2 : Regorafenib; Drug: Phase 2 : Avelumab
Sponsors: Institut Bergonié; Bayer; Merck KGaA, Darmstadt, Germany
Recruiting

Permalink for 'Inhibition of CArbonic Anhydrase in Combination With Platinum and Etoposide-based Radiochemotherapy in Patients With Localized Small Cell Lung Cancer'

Inhibition of CArbonic Anhydrase in Combination With Platinum and Etoposide-based Radiochemotherapy in Patients With Localized Small Cell Lung Cancer

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

Condition: Small Cell Lung Cancer
Intervention: Drug: acetazolamide in combination with platinum and etoposide-based radiochemotherapy
Sponsor: Centre Antoine Lacassagne
Not yet recruiting

Clinicopathological characteristics and molecular abnormalities of primary grade 2 neuroendocrine tumors of the cervix.

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

Clinicopathological characteristics and molecular abnormalities of primary grade 2 neuroendocrine tumors of the cervix.

Diagn Pathol. 2019 Jun 22;14(1):64

Authors: Zhu R, Wu H, Chen B, Pang J, Huo Z

Abstract
BACKGROUND: Primary grade 2 neuroendocrine tumors of the cervix in female patients are rare and have a highly aggressive clinical course. This study is aimed to analyse the diagnosis, genetic changes, management and prognosis of these tumors and investigate whether the genetic alterations could provide more useful information to guide the molecular characterization and potential individualized treatment of grade 2 cervical neuroendocrine tumors.
METHODS: The clinical records of all three patients diagnosed as primary grade 2 neuroendocrine tumors of the cervix in Peking Union Medical College Hospital (PUMCH) from 2011 to 2018 were reviewed retrospectively. We investigated the morphology, immunophenotype and molecular abnormalities of all the cases. The follow-up data were also collected.
RESULTS: The age of the patients ranged from 46 to 69 years. All cases were in stage II and treated with surgery. The microscopic examination showed that the tumors took the form of nest-like, trabecular, sheet-like, "single file" strands or rosette-like structures. The mitotic figures ranged from 2 to 5 in every 10 high-power fields, and necrotic foci were observed in one case. Immunohistochemically, the tumor cells were positive for AE1/AE3, Cg A, Syn, CD56, P16, CAM5.2, and PGP9.5 and negative for ER, PR, P63, P40, CK7, and CK20. The expression of P53 showed as normal/wild-type pattern, and the proliferation index of Ki-67 ranged from 2 to 7%. A total of 560 genes were sequenced by next-generation sequencing for each patient, and nonsynonymous somatic mutations were identified in the three cases. Non-frameshift insertions of the MAGI1 and SLC45A were both observed in case 1, while we only observed the non-frameshift insertion of the MAGI1 in case 2 and the non-frameshift insertion of the SLC45A in case 3. Case 1 was treated with chemoradiotherapy before and after surgery. Cases 2 and 3 were treated with chemotherapy before and after surgery. The follow-up time ranged from 27 to 74 months. Cases 2 and 3 survived, while case 1 died.
CONCLUSION: Cervical grade 2 neuroendocrine tumors are extremely rare. We presented the first mutation profile revealed by whole exome sequencing in a series of grade 2 cervical NETs along with their clinicopathological characteristics. Their genetic changes are different from those that take place in the gastrointestinal tract, pancreas and lung, which have gene changes in VEGF, RTKs or the mTOR signalling pathway. While changes in MAGI1 and SLC45L3 were observed in two of our cases and the case who had the gene changes of both MAGI1 and SLC45L3 died because of metastases to the liver and bone. The genetic alterations may provide more useful information to guide the molecular characterization and potential individualized treatment of grade 2 cervical neuroendocrine tumors.

PMID: 31228945 [PubMed - in process]

Permalink for 'Histopathological diagnosis of appendiceal neuroendocrine neoplasms: when to perform a right hemicolectomy? A systematic review and meta-analysis.'

Histopathological diagnosis of appendiceal neuroendocrine neoplasms: when to perform a right hemicolectomy? A systematic review and meta-analysis.

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

Histopathological diagnosis of appendiceal neuroendocrine neoplasms: when to perform a right hemicolectomy? A systematic review and meta-analysis.

Endocrine. 2019 Jun 21;:

Authors: Ricci C, Ingaldi C, Alberici L, Brighi N, Santini D, Mosconi C, Ambrosini V, Campana D, Minni F, Casadei R

Abstract
PURPOSE: The European Neuroendocrine Tumor Society (ENETS) guidelines advocate a right hemicolectomy (RHC) only in patients with appendiceal neuroendocrine neoplasms (aNENs) at risk for N+(node positive). The risk is defined using site, size, and grading of tumor as well as mesoappendiceal or lymphovascular invasion.
METHODS: A systematic review and meta-analysis was carried out. The data were reported using risk difference (RD) to define the risk of N+. The number needed to treat/harm (NNT/NNH) and the likelihood of being helped or harmed (LHH) were calculated using RD. Two strategies were considered: "to treat all" versus "to treat only patients having aNENs with risk stigmata". The aim was to evaluate the harm/benefit ratio related to the use of the ENETS lymph-nodal metastases (N+) risk factors.
RESULTS: Six studies were included involving a total of 261 patients. The RD (-0.30; P < 0.001) of N+ was significantly lower in aNENs ≤ 20 mm as compared to those >20 mm. One unnecessary RHC every five patients (NNT = 5) could be avoided while 1 patient with N+ every six patients (NNH = 6) remained untreated. The risk was lower than the benefits (LHH = 1.2). The RD NNT, NNH, and LHH values suggested that only a 15 mm cutoff and the presence of lymphovascular invasion could be considered useful.
CONCLUSIONS: An RHC should be performed in patients with aNENs >20 mm. The use of a 15 mm cutoff criterion had a similar outcome to that of a 20 mm cutoff. Lymphovascular invasion should only be considered a minor criterion. Selection based on other parameters should be avoided.

PMID: 31227991 [PubMed - as supplied by publisher]

CT radiomics may predict the grade of pancreatic neuroendocrine tumors: a multicenter study.

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

CT radiomics may predict the grade of pancreatic neuroendocrine tumors: a multicenter study.

Eur Radiol. 2019 Jun 21;:

Authors: Gu D, Hu Y, Ding H, Wei J, Chen K, Liu H, Zeng M, Tian J

Abstract
OBJECTIVE: To develop and validate a radiomics-based nomogram for preoperatively predicting grade 1 and grade 2/3 tumors in patients with pancreatic neuroendocrine tumors (PNETs).
METHODS: One hundred thirty-eight patients derived from two institutions with pathologically confirmed PNETs (104 in the training cohort and 34 in the validation cohort) were included in this retrospective study. A total of 853 radiomic features were extracted from arterial and portal venous phase CT images respectively. Minimum redundancy maximum relevance and random forest methods were adopted for the significant radiomic feature selection and radiomic signature construction. A fusion radiomic signature was generated by combining both the single-phase signatures. The nomogram based on a comprehensive model incorporating the clinical risk factors and the fusion radiomic signature was established, and decision curve analysis was applied for clinical use.
RESULTS: The fusion radiomic signature has significant association with histologic grade (p < 0.001). The nomogram integrating independent clinical risk factor tumor margin and fusion radiomic signature showed strong discrimination with an area under the curve (AUC) of 0.974 (95% CI 0.950-0.998) in the training cohort and 0.902 (95% CI 0.798-1.000) in the validation cohort with good calibration. Decision curve analysis verified the clinical usefulness of the predictive nomogram.
CONCLUSION: We proposed a comprehensive nomogram consisting of tumor margin and fusion radiomic signature as a powerful tool to predict grade 1 and grade 2/3 PNET preoperatively and assist the clinical decision-making for PNET patients.
KEY POINTS: • Radiomic signature has strong discriminatory ability for the histologic grade of PNETs. • Arterial and portal venous phase CT imaging are complementary for the prediction of PNET grading. • The comprehensive nomogram outperformed clinical factors in assisting therapy strategy in PNET patients.

PMID: 31227882 [PubMed - as supplied by publisher]

Primary small cell neuroendocrine carcinoma of adrenal gland.

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

Primary small cell neuroendocrine carcinoma of adrenal gland.

Int Cancer Conf J. 2019 Jul;8(3):122-125

Authors: Ogawa K, Shimizu Y, Uketa S, Utsunomiya N, Kida K, Ishihara M, Hashimoto K, Kanamaru S

Abstract
Neuroendocrine tumors are an extremely rare form of retroperitoneum tumor. A 79-year-old man presented with abdominal pain. Computed tomography and magnetic resonance imaging revealed a 51 × 36 mm mass in the left adrenal gland. Gastrofiberscopy, colonfiberscopy and positron emission tomography were performed and showed no lesions or other malignancies. Endocrine tests were normal. Two months later, the mass had grown to 68 × 52 mm. Suspecting a malignant tumor, we performed laparoscopic adrenalectomy. Histopathological diagnosis revealed the tumor was small cell neuroendocrine carcinoma. No other malignancies were revealed, so we diagnosed primary small cell neuroendocrine carcinoma of adrenal gland. To our knowledge, this is only the third report in English of primary small cell neuroendocrine carcinoma of the adrenal gland and the first report that is confined to the adrenal gland. Adrenal masses are often misdiagnosed as adenoma; however, we need to raise awareness of the potential for malignant adrenal tumors such as the rarer small cell neuroendocrine carcinoma.

PMID: 31218188 [PubMed]

Cost-of-illness of melanoma in Europe - a modelling approach.

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

Cost-of-illness of melanoma in Europe - a modelling approach.

J Eur Acad Dermatol Venereol. 2019 Mar;33 Suppl 2:34-45

Authors: Krensel M, Schäfer I, Augustin M

Abstract
BACKGROUND: Malignant melanoma is accounting for the vast majority of skin cancer death. The treatment and productivity loss due to morbidity or premature mortality are associated with costs for society. There are few cost-of-illness (COI) studies on malignant melanoma in European countries from societal perspective and currently there is no publication analysing the COI in all European countries.
OBJECTIVES: The objective of the present study was to comparatively estimate COI of malignant melanoma in the European countries based on an identical approach.
METHODS: Cost information was obtained from results of a systematic literature research. For countries with no available cost information, a model for imputation of cost data was developed. Country-specific costs were modelled on the national gross domestic product, health expenditures, gross national income and epidemiological data. The adjustment for purchasing power parity allowed a comparison across countries.
RESULTS: Crude national costs of malignant melanoma ranged between € 1.1 million in Iceland and € 543.8 million in Germany and resulted in € 2.7 billion for all EU/EFTA states. Estimated crude costs per patient were lowest in Bulgaria (€ 6422) and highest in Luxembourg (€ 50 734). The share of direct costs varied from 3% to 26% across countries. After adjustment for the purchasing power parity costs per patient ranged between € 14 420 in Bulgaria and € 50 961 in Cyprus. Treatment expenses and morbidity costs were markedly lower for countries that entered the EU since 2004. By contrast, mortality costs were lower in countries with a high gross domestic product per capita.
CONCLUSION: In this first estimation, malignant melanoma induces relevant COI in Europe. There was large variation in the costs per patient due to different health care systems and expenses. Beyond decreasing patient burden, early intervention and prevention of melanoma could have a relevant potential to save costs across Europe.

PMID: 30811699 [PubMed - indexed for MEDLINE]

Permalink for 'Prevalence and determinants of sunbed use in thirty European countries: data from the Euromelanoma skin cancer prevention campaign.'

Prevalence and determinants of sunbed use in thirty European countries: data from the Euromelanoma skin cancer prevention campaign.

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

Prevalence and determinants of sunbed use in thirty European countries: data from the Euromelanoma skin cancer prevention campaign.

J Eur Acad Dermatol Venereol. 2019 Mar;33 Suppl 2:13-27

Authors: Suppa M, Gandini S, Njimi H, Bulliard JL, Correia O, Duarte AF, Peris K, Stratigos AJ, Nagore E, Longo MI, Bylaite-Bucinskiene M, Karls R, Helppikangas H, Euromelanoma Working Group,, Del Marmol V

Abstract
BACKGROUND: Although considered as a first-group carcinogen, indoor tanning is a common practice in Europe. Euromelanoma is a pan-European skin cancer prevention campaign.
OBJECTIVES: To compare several European countries in terms of the prevalence and determinants of sunbed use.
METHODS: Participants in the Euromelanoma campaigns filled in questionnaires containing demographics and risk factors, including type/duration of sunbed use. Multivariate analyses adjusted for age, gender, education, skin type and year of survey were employed to assess factors independently associated with sunbed use in each country.
RESULTS: In total, 227 888 individuals (67.4% females, median age 44, 63.4% highly educated, 71.9% skin types III-VI) from 30 countries participated. Overall, the prevalence of sunbed ever use was 10.6% (≤19-year-olds: 5.9%; 20 to 35-year-olds: 17.0%; >35-year-olds: 8.3%). Females displayed a higher prevalence than males in all countries. Balkan countries displayed the highest female/male ratios (≥4). Sunbed use was significantly more prevalent among skin type III-VI (14/30 countries) and highly educated participants (11/30 countries). Significant correlations were found between sunbed use prevalence and countries' latitude (P < 0.001) and sunshine (P = 0.002); Italy and Spain represented exceptions towards excessive exposure. Very different prevalence rates were found for Spain (19.3%) and Portugal (2.0%). Scandinavian countries ranked highest in sunbed use among ≤19-year-olds, Baltic countries among 20 to 35-year-olds.
CONCLUSIONS: Sunbed use prevalence was higher in northern, sun-deprived countries, with the exception of Italy and Spain. The main determinants of sunbed use were age (young adults) and gender (females), whereas education and skin type had a less relevant effect. Geographic particularities were found in four regions: Iberian (prevalence ten times higher in Spain than Portugal), Balkan (prevalence disproportionately higher among women), Baltic (highest prevalence among young adults) and Scandinavian (highest prevalence among adolescents). These data have public health relevance for future interventions aimed at reducing sunbed use in Europe.

PMID: 30811698 [PubMed - indexed for MEDLINE]

Ultraviolet radiation exposure among Belgrade high school students: analysis of knowledge, attitudes and behaviour.

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

Ultraviolet radiation exposure among Belgrade high school students: analysis of knowledge, attitudes and behaviour.

J Eur Acad Dermatol Venereol. 2019 Mar;33 Suppl 2:63-75

Authors: Skiljevic D, Sreckovic L

Abstract
BACKGROUND: The incidence of melanoma has been increasing worldwide. Extended UV exposure during childhood or adolescence significantly increases the probability of skin cancer in adulthood.
OBJECTIVE: The objective of this study was to analyse knowledge, attitudes and behaviour regarding exposure to natural and artificial UV radiation among Belgrade high school students.
METHODS: The study was conducted using a questionnaire among 549 students of 3rd and 4th grade (17 and 18 years of age) in four Belgrade high schools. The questionnaire had 32 questions: questions about gender, date and month of birth and parents' education, nine questions regarding sunbed use, nine questions regarding behaviour in the sun during summer months, four questions regarding personal and family history and skin phototype and seven questions regarding attitude and general knowledge about effects of UV radiation. Assessment of frequency rate and relative numbers was used as methods of descriptive statistics.
RESULTS: As many as 39% of participants had used a sunbed at least once, 38% plan on using it in the future. One quarter spends more than 3 hours in the sun on the beach during summer without any protection, and only one-third of participants had not experienced sunburn during last summer. Only one-half of students know what melanoma is, while 37% stated that they do not know.
CONCLUSION: General awareness of risk factors regarding sun exposure as well as general knowledge about melanoma is not on a high level among Belgrade high school students. Therefore, besides legislative measures, it is extremely important to conduct adequate education programmes in high schools.

PMID: 30811695 [PubMed - indexed for MEDLINE]

Modelling first-year cost-of-illness of melanoma attributable to sunbed use in Europe.

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

Modelling first-year cost-of-illness of melanoma attributable to sunbed use in Europe.

J Eur Acad Dermatol Venereol. 2019 Mar;33 Suppl 2:46-56

Authors: Krensel M, Schäfer I, Augustin M

Abstract
BACKGROUND: Melanoma is a life-threatening disease of the skin with an increasing incidence of approximately 87 000 new cases treated per year in the European Union and the European Free Trade Association states resulting in considerable costs for the society. Since the use of sunbeds is known to be a risk factor, which can be easily avoided, costs of malignant melanoma attributable to sunbed use are modelled in the present study.
METHODS: Costs-of-illness of melanoma were calculated and compared for all member states of the European Union and the European Free Trade Association states using an established modelling approach. Calculations were based on a systematic literature research. For countries with no available information on cost-of-illness the gross domestic product, health expenditures and gross national income served as a basis for extrapolation of costs. International comparison was enabled by adjusting costs by the national purchasing power parity.
RESULTS: After adjusting melanoma treatment costs for the purchasing power parity, direct costs per patient vary between € 1056 in Romania and € 10 215 in Luxembourg. Costs due to morbidity range from € 102 per patient in Sweden and € 5178 in the UK resulting in total costs of € 1751-€ 12 611 per patient. Average weighted total costs per patient amount for € 6861-€ 6967 annually. In total, in 2012 approximately 4450 new cases of melanoma have been induced by sunbed use in the 31 included countries, which corresponds to 5.1% of all incident melanoma cases. National attributable melanoma costs range from € 1570 in Malta to € 11.1 million in Germany and sum up to an amount of € 32.5-€ 33.4 million for all countries.
CONCLUSION: This article provides a first estimation on costs of melanoma in Europe. It illustrates the contribution of exposure to artificial ultraviolet light in the economic burden of malignant melanoma.

PMID: 30811692 [PubMed - indexed for MEDLINE]

Epidemiological evidence of carcinogenicity of sunbed use and of efficacy of preventive measures.

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

Epidemiological evidence of carcinogenicity of sunbed use and of efficacy of preventive measures.

J Eur Acad Dermatol Venereol. 2019 Mar;33 Suppl 2:57-62

Authors: Gandini S, Doré JF, Autier P, Greinert R, Boniol M

Abstract
The International Agency for Research on Cancer classified, in July 2009, exposure to artificial tanning devices (sunbeds) as carcinogenic to humans. This classification was based on evidence from epidemiological and experimental animal studies. The present chapter will review these epidemiological evidences. The summary risk estimates from 27 epidemiological studies obtained through a meta-analysis showed an increased risk of melanoma: summary relative risk (SRR) = 1.20 [95% confidence interval (CI) 1.08-1.34]. The risk was higher when exposure took place at younger age (SRR = 1.59; 95% CI 1.36-1.85). The risk was independent of skin sensitivity or population and a dose response was evident. A meta-analysis of 12 studies was conducted for non-melanoma skin cancers and showed a significantly increased risk for basal cell carcinoma (SRR = 1.29; 95% CI 1.08-1.53) and for squamous cell carcinoma (SRR = 1.67; 95% CI 1.29-2.17). As for melanoma, the risk for other skin cancers increased for first exposures at young age. Epidemiological studies have gradually strengthened the evidence for a causal relationship between indoor tanning and skin cancer and they fit with prior knowledge on relationship between UV exposure and skin cancer. Additionally, several case-control studies provided consistent evidence of a positive association between use of sunbed and ocular melanoma, also with greater risk for first exposures at younger age. Preventive measures based on information on risk or by requiring parental authorization for young users proved to be inefficient in several studies. The significant impact of strong actions or total ban, such as performed in Iceland, or a total ban of sunbed use, as in Brazil or Australian states, needs to be further assessed.

PMID: 30811691 [PubMed - indexed for MEDLINE]

Sunbeds and carcinogenesis: the need for new regulations and restrictions in Europe from the Euromelanoma perspective.

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

Sunbeds and carcinogenesis: the need for new regulations and restrictions in Europe from the Euromelanoma perspective.

J Eur Acad Dermatol Venereol. 2019 Mar;33 Suppl 2:104-109

Authors: Calzavara-Pinton PG, Arisi M, Wolf P

Abstract
Experimental investigations have definitely assessed that ultraviolet A (UVA) as well as ultraviolet B (UVB) radiation induce mutagenic DNA photoproducts and other cell damages with a carcinogenic potential. Artificial tanning increases significantly the lifetime risk for basal cell carcinoma, squamous cell carcinoma and melanoma particularly in subjects with fair skin type, subjects with a history of skin cancer or frequent childhood sunburn or if exposures took place at an age younger than 18 years. In addition, experimental and clinical evidence indicate that UVA exposure promotes skin photoageing. Therefore we are dealing with a recreational activity (for customers) and a profitable business (for the tanning industry) with human costs, i.e. an increase in morbidity and mortality by skin cancer, and health and social costs leading to an increased expenditure by the European national health systems. In a few European countries, legislation has recently prohibited the use of sunbeds for minors, pregnant women, people with skin cancer or a history of skin cancer and individuals who do not tan or who burn easily from sun exposure. However, this legislation seems to be insufficient from a photobiological perspective, and importantly, it is largely disregarded by consumers and tanning industry. Therefore the Euromelanoma group proposes a new, more stringent regulation for the tanning industry and restrictions for customers, particularly for those individuals with constitutional and anamnestic risk factors. Finally, we ask for an enhanced commitment to increase the awareness of the general population on the risk of artificial tanning.

PMID: 30811688 [PubMed - indexed for MEDLINE]

[Cytotoxic Effect of Low-Intensity Infrared Laser Irradiation on Human Melanoma Cells].

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

[Cytotoxic Effect of Low-Intensity Infrared Laser Irradiation on Human Melanoma Cells].

Mol Biol (Mosk). 2018 Nov-Dec;52(6):1014-1028

Authors: Andreeva NV, Zotov KV, Yegorov YY, Kandarakov OF, Yusupov VI, Belyavsky AV

Abstract
Continuous low-intensity laser irradiation (LILI) affects the state of cells in culture, including their proliferation rate. Data collected with various cell models vary significantly, but most studies have reported positive effects of LILI on cell proliferation. The effects of continuous infrared LILI (835 nm) was studied using three independent different melanoma cell lines. The LILI effect was shown to strongly depend on the irradiation dose. Higher doses (230 kJ/m^(2)) significantly suppressed the cell growth. A further increase in LILI dose led to a significant cytotoxic effect, which increased disproportionately quickly with the increasing light intensity. Human mesenchymal stem cells (MSCs) were found to be significantly more resistant to the cytotoxic effect of higher-dose LILI. Importantly, the effects were not due to the difference in culture conditions. Control experiments showed that 15 non-melanoma tumor cell lines were more resistant to LILI than melanoma cells. Selective sensitivity of melanoma cells to LILI in vitro was assumed to provide a basis for LILI-based approaches to melanoma treatment.

PMID: 30633244 [PubMed - indexed for MEDLINE]

[Multiplex Assay to Evaluate the Genetic Risk of Developing Human Melanoma].

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

[Multiplex Assay to Evaluate the Genetic Risk of Developing Human Melanoma].

Mol Biol (Mosk). 2018 Nov-Dec;52(6):997-1005

Authors: Fesenko DO, Abramov IS, Shershov VE, Kuznetsova VE, Surzhikov SA, Grechishnikova IV, Barsky VE, Chudinov AV, Nasedkina TV

Abstract
A genotyping procedure based on single-step PCR and subsequent allele-specific hybridization on a hydrogel biochip was developed to address the polymorphisms of HERC2, OCA2, SLC24A4, SLC45A2, TYR, IRF4, MC1R,MITF, PIGU, MYH7B, NCOA6, and CDK10. Amplified gene fragments were fluorescently labeled in PCR, and fluorescent signals from biochip cells were detected to evaluate how efficiently the PCR product formed a perfect duplex with an immobilized probe. The analytical characteristics of hybridization analysis were estimated for several fluorophores with different optical spectra. Cyanine dyes fluorescing in the range of Cy5 and Cy7 were synthesized for the purpose and used as 5'-tags of universal primers in single-step PCR. A Cy7 analog fluorescing in the near infrared range was found to increase the sensitivity of hybridization analysis by producing a lower background signal in the cases where target gene amplification was low.

PMID: 30633242 [PubMed - indexed for MEDLINE]

Permalink for 'Enhanced effect of checkpoint inhibitors when given after or together with IMM-101: significant responses in four advanced melanoma patients with no additional major toxicity.'

Enhanced effect of checkpoint inhibitors when given after or together with IMM-101: significant responses in four advanced melanoma patients with no additional major toxicity.

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

Enhanced effect of checkpoint inhibitors when given after or together with IMM-101: significant responses in four advanced melanoma patients with no additional major toxicity.

J Transl Med. 2018 08 14;16(1):227

Authors: Dalgleish AG, Mudan S, Fusi A

Abstract
BACKGROUND: The use of checkpoint inhibitors (ipilimumab, pembrolizumab, nivolumab) has revolutionised the treatment of metastatic melanoma. However still more than the half the patients do not respond to single-agent immunotherapy. This has led to the development of combining these agents in an attempt to enhance the anti-cancer activity. More than 300 different studies with 15 different drug doses are currently ongoing. Combining different checkpoint inhibitors (CPIs) does indeed lead to an increase in response rate, but this is associated with significant toxicity. IMM-101 is a heat killed Mycobacterium preparation which induces marked immune modulation and little systemic toxicity. It has been reported as having activity in melanoma as single agent and in pancreatic cancer in combination with gemcitabine, the latter in a randomised study.
METHODS: Here we report the effect of adding CPIs to 3 patients who had previously been on IMM-101, either as a trial or a named patient programme and a patient who received the IMM-101 together with nivolumab.
RESULTS: All 4 patients had rapid and very good responses, three of them maintained over 18 months with no significant additional toxicity.
CONCLUSIONS: The rapid and complete clinical responses seen in these patients may suggest that IMM-101 is activating a complementary pathway which is synergistic with CPI treatment.

PMID: 30107850 [PubMed - indexed for MEDLINE]

Effect of Low-Field High-Frequency nsPEFs on the Biological Behaviors of Human A375 Melanoma Cells.

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

Icon for IEEE Engineering in Medicine and Biology Society

Effect of Low-Field High-Frequency nsPEFs on the Biological Behaviors of Human A375 Melanoma Cells.

IEEE Trans Biomed Eng. 2018 09;65(9):2093-2100

Authors: Zhang B, Kuang D, Tang X, Mi Y, Luo Q, Song G

Abstract
OBJECTIVE: To evaluate the effect of low-field high-frequency nanosecond pulsed electric fields (nsPEFs) on multiple biological behaviors of human A375 melanoma cells and to optimize suitable parameters for further study and clinical use.
METHODS: An nsPEF generator was developed to generate appropriate pulses. Cell apoptosis and the cell cycle were evaluated by flow cytometry. The CCK-8 assay was performed to explore the effect of nsPEFs on the viability of A375 melanoma cells. Cell migration was assessed using a Transwell Boyden Chamber. The proliferation of A375 melanoma cells was determined by the cloning efficacy test. Furthermore, the nude mouse tumorigenicity assay was used to detect the effectiveness of nsPEFs in vivo.
RESULTS: The nsPEFs with our tested parameters failed to induce apoptosis of A375 melanoma cells, though nsPEFs with high pulse duration (500 ns) induced necrosis. However, the viability and migration of A375 melanoma cells were significantly inhibited by nsPEFs. nsPEFs also suppressed the proliferation of A375 melanoma cells by restricting cells in G0/G1 phase. Moreover, animal experiments demonstrated that nsPEFs inhibited the growth of melanoma in vivo.
CONCLUSION: Low-field high-frequency nsPEFs failed to induce apoptosis but effectively inhibited the growth of melanoma via affecting other biological behaviors of melanoma cells, such as cell viability, proliferation, and migration.
SIGNIFICANCE: This study investigated the influence of low-field high-frequency nsPEFs on melanoma through evaluating their effects on multiple biological behaviors and is helpful in the treatment of melanoma and other tumors.

PMID: 29989943 [PubMed - indexed for MEDLINE]

Antitumor effect of antibiotic resistance gene-free plasmids encoding interleukin-12 in canine melanoma model.

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

Antitumor effect of antibiotic resistance gene-free plasmids encoding interleukin-12 in canine melanoma model.

Cancer Gene Ther. 2018 10;25(9-10):260-273

Authors: Lampreht Tratar U, Kos S, Kamensek U, Ota M, Tozon N, Sersa G, Cemazar M

Abstract
The electrotransfer of interleukin-12 (IL-12) has been demonstrated as an efficient and safe treatment for tumors in veterinary oncology. However, the plasmids used encode human or feline IL-12 and harbor the gene for antibiotic resistance. Therefore, our aim was to construct plasmids encoding canine IL-12 without the antibiotic resistance genes driven by two different promoters: constitutive and fibroblast-specific. The results obtained in vitro in different cell lines showed that following gene electrotransfer, the newly constructed plasmids had cytotoxicity and expression profiles comparable to plasmids with antibiotic resistance genes. Additionally, in vivo studies showed a statistically significant prolonged tumor growth delay of CMeC-1 tumors compared to control vehicle-treated mice after intratumoral gene electrotransfer. Besides the higher gene expression obtained by plasmids with constitutive promoters, the main difference between both plasmids was in the distribution of the transgene expression. Namely, after gene electrotransfer, plasmids with constitutive promoters showed an increase of serum IL-12, whereas the gene expression of IL-12, encoded by plasmids with fibroblast-specific promoters, was restricted to the tumor. Furthermore, after the gene electrotransfer of plasmids with constitutive promoters, granzyme B-positive cells were detected in the tumor and spleen, indicating a systemic effect of the therapy. Therefore, plasmids with different promoters present valuable tools for focused therapy with local or systemic effects. The results of the present study demonstrated that plasmids encoding canine IL-12 under constitutive and fibroblast-specific promoters without the gene for antibiotic resistance provide feasible tools for controlled gene delivery that could be used for the treatment of client-owned dogs.

PMID: 29593358 [PubMed - indexed for MEDLINE]

Item 299 – UE 9 Tumeurs cutanées épithéliales et mélaniques.

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

Item 299 – UE 9 Tumeurs cutanées épithéliales et mélaniques.

Ann Dermatol Venereol. 2018 Mar;145 Suppl 1:S165-S185

Authors: CEDEF

PMID: 29475619 [PubMed - indexed for MEDLINE]

Variations in Hospice Utilization and Length of Stay for Medicare Patients With Melanoma.

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

Variations in Hospice Utilization and Length of Stay for Medicare Patients With Melanoma.

J Pain Symptom Manage. 2018 04;55(4):1165-1172.e5

Authors: Hutchinson RN, Lucas FL, Becker M, Wierman HR, Fairfield KM

Abstract
CONTEXT: Timely hospice referral is an indicator of high-quality end-of-life care for cancer patients. Variations in patient characteristics associated with hospice utilization and length of stay have been demonstrated in studies of other malignancies but not melanoma.
OBJECTIVES: We sought to understand hospice utilization and patient characteristics associated with variability in use for the older melanoma population.
METHODS: We used the Surveillance, Epidemiology, and End Results-Medicare database to identify 13,393 melanoma patients aged 65+ years at time of diagnosis between 2000 and 2009, who died by 12/31/10. The primary outcome was enrollment in hospice with secondary outcome of hospice duration. Patient characteristics associated with variations in hospice enrollment were examined.
RESULTS: Among 13,393 patients who died with melanoma, 5298 (40%) received hospice care. Of these, 17% were enrolled in hospice for three days or less, while 13% had ≥90 days of hospice care. Despite improvements over time in the proportion of patients who received hospice and those who received at least 90 days of hospice care, late hospice enrollments did not change. Multivariable analysis revealed that patients of older age, with distant disease at time of diagnosis, and residing in rural areas or in census tracts with higher rates of high school completion were more likely to enroll in hospice.
CONCLUSION: Rates of hospice enrollment increased over time but remained under accepted quality benchmarks with variations evident in those who receive hospice services. Efforts to increase access to earlier hospice care for all patients dying with melanoma are essential.

PMID: 29247755 [PubMed - indexed for MEDLINE]

Letter: When Less is More: Dexamethasone Dosing for Brain Tumors.

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

Letter: When Less is More: Dexamethasone Dosing for Brain Tumors.

Neurosurgery. 2019 Jun 19;:

Authors: Lim-Fat MJ, Bi WL, Lo J, Lee EQ, Ahluwalia MS, Batchelor TT, Chang SM, Chiocca EA, Chukwueke U, Cloughesy TF, Colman H, Deangelis LM, Galanis E, Gilbert MR, De Groot JF, Lassman AB, Liau LM, Mason W, McFaline-Figueroa JR, Mehta MP, Mellinghoff IK, Nabors LB, Nayak L, Reardon DA, Wen PY

PMID: 31215634 [PubMed - as supplied by publisher]

DLL3: an emerging target in small cell lung cancer.

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

DLL3: an emerging target in small cell lung cancer.

J Hematol Oncol. 2019 Jun 18;12(1):61

Authors: Owen DH, Giffin MJ, Bailis JM, Smit MD, Carbone DP, He K

Abstract
Small cell lung cancer (SCLC) accounts for approximately 15% of all lung cancers. Despite high rates of response to first-line chemotherapy and radiotherapy, patients with extensive-stage disease eventually relapse, and very few patients survive more than 5 years from diagnosis. Treatment options for recurrent or refractory disease are limited, and the treatments that do exist are associated with significant treatment-related toxicities. Delta-like ligand 3 (DLL3) is an inhibitory Notch ligand that is highly expressed in SCLC and other neuroendocrine tumors but minimally expressed in normal tissues. It is therefore being explored as a potential therapeutic target in SCLC. Here, we review the preclinical and clinical evidence for targeting DLL3 in SCLC and discuss several DLL3-specific therapies being developed for the treatment of SCLC: the antibody-drug conjugate rovalpituzumab tesirine, the bispecific T cell engager immuno-oncology therapy AMG 757, and the chimeric antigen receptor T cell therapy AMG 119.

PMID: 31215500 [PubMed - in process]

Permalink for 'Limited role of carbidopa-assisted 18F-FDOPA PET/CT in patients with sporadic non-functional gastroduodenal neuroendocrine neoplasms.'

Limited role of carbidopa-assisted 18F-FDOPA PET/CT in patients with sporadic non-functional gastroduodenal neuroendocrine neoplasms.

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

Limited role of carbidopa-assisted 18F-FDOPA PET/CT in patients with sporadic non-functional gastroduodenal neuroendocrine neoplasms.

Ann Nucl Med. 2019 Jun 15;:

Authors: Imperiale A, Averous G, Helali M, Taieb D, Pessaux P, Goichot B, Addeo P, Bachellier P

Abstract
OBJECTIVE: To evaluate 18F-fluorodihydroxyphenylalanine (18F-FDOPA) positron emission tomography/computed tomography (PET/CT) after carbidopa premedication to localize sporadic, well-differentiated, nonfunctioning gastroduodenal neuroendocrine neoplasms (NENs).
METHODS: Ten patients undergoing staging carbidopa-assisted 18F-FDOPA PET/CT before endoscopic or surgical resection of gastroduodenal NENs were retrospectively selected. Preoperative imaging work up also included CT, magnetic resonance imaging (MRI), and somatostatin receptor scintigraphy (SRS) single-photon emission computed tomography/computed tomography (SPECT/CT) in ten, six, and eight patients, respectively. Histopathological diagnosis of primary NEN was the diagnostic standard of truth. Metastatic spread was defined as the presence of histologically proven nodal, visceral, and/or bone metastases.
RESULTS: Tumors were located in the duodenal bulb in five patients, in descending duodenum in three, and in the gastric fundus in two. Three patients presented with both lymph nodes and distant metastases, and two with exclusive lymphatic spread. CT and MRI detected primary tumor in one out of ten and three out of six patients, respectively. SRS failed to detect intestinal NEN in all cases. 18F-FDOPA PET/CT detected four primary NENs (one gastric and three duodenal tumors) and was false negative in six patients. NENs missed by 18F-FDOPA PET/CT were smaller than 10 mm in two cases and measured about 30 mm in three patients. The remaining tumor was detected only on blind endoscopic biopsy. Among patients who underwent both 18F-FDOPA PET/CT and SRS, three presented discordant results for primary tumor detection (PET/CT positive/SRS negative) and five showed concordant negative studies. 18F-FDOPA PET/CT correctly identified all three patients with both nodal and visceral metastatic disease and failed to detect lymph node metastases in both N+ M0 patients.
CONCLUSIONS: 18F-FDOPA PET/CT is not sufficiently accurate for localization of primary well-differentiated nonfunctioning sporadic gastroduodenal NENs. 18F-FDOPA PET/CT's value for the assessment of visceral and lymph node metastases needs to be clarified in multicenter trials including a larger number of patients.

PMID: 31214959 [PubMed - as supplied by publisher]

The Relationship Between Neuroimmunity and Bipolar Disorder: Mechanism and Translational Application.

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

The Relationship Between Neuroimmunity and Bipolar Disorder: Mechanism and Translational Application.

Neurosci Bull. 2019 Jun 18;:

Authors: Niu Z, Yang L, Wu X, Zhu Y, Chen J, Fang Y

Abstract
Neuroimmune system may be involved in the pathological process of bipolar disorder (BD), but the essential association is not fully understood. Accumulating evidence has shown that BD involves the activation of immune cells and the release of inflammatory substances in the central nerve system (CNS). Meanwhile, neuroimmune responses also interact with other hypothesis of the etiology of BD that are widely recognized, such as neurotransmitter systems, neuroendocrine systems, neurotrophic factors, and oxidative stress. Simultaneously, related genes and immune changes in peripheral blood vary with it. Overall, neuroimmunity may play an important role in the pathogenesis of BD, and the inflammatory cytokines, especially interleukin-6 and tumor necrosis factor-alpha, have potential value for the clinical diagnosis and prognosis of BD, as well as predicting the therapeutic effects of drugs. Large-scale studies are needed to extend the evidence on neuroimmunity in BD, and to examine its clinical value for applications such as early prediction and treatment.

PMID: 31214924 [PubMed - as supplied by publisher]

Optimizing Genetic Workup in Pheochromocytoma and Paraganglioma by Integrating Diagnostic and Research Approaches.

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

Optimizing Genetic Workup in Pheochromocytoma and Paraganglioma by Integrating Diagnostic and Research Approaches.

Cancers (Basel). 2019 Jun 11;11(6):

Authors: Gieldon L, William D, Hackmann K, Jahn W, Jahn A, Wagner J, Rump A, Bechmann N, Nölting S, Knösel T, Gudziol V, Constantinescu G, Masjkur J, Beuschlein F, Timmers HJ, Canu L, Pacak K, Robledo M, Aust D, Schröck E, Eisenhofer G, Richter S, Klink B

Abstract
Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors with a strong hereditary background and a large genetic heterogeneity. Identification of the underlying genetic cause is crucial for the management of patients and their families as it aids differentiation between hereditary and sporadic cases. To improve diagnostics and clinical management we tailored an enrichment based comprehensive multi-gene next generation sequencing panel applicable to both analyses of tumor tissue and blood samples. We applied this panel to tumor samples and compared its performance to our current routine diagnostic approach. Routine diagnostic sequencing of 11 PPGL susceptibility genes was applied to blood samples of 65 unselected PPGL patients at a single center in Dresden, Germany. Predisposing germline mutations were identified in 19 (29.2%) patients. Analyses of 28 PPGL tumor tissues using the dedicated PPGL panel revealed pathogenic or likely pathogenic variants in known PPGL susceptibility genes in 21 (75%) cases, including mutations in IDH2, ATRX and HRAS. These mutations suggest sporadic tumor development. Our results imply a diagnostic benefit from extended molecular tumor testing of PPGLs and consequent improvement of patient management. The approach is promising for determination of prognostic biomarkers that support therapeutic decision-making.

PMID: 31212687 [PubMed]

Immune checkpoint inhibitor-related acral vasculitis.

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

Immune checkpoint inhibitor-related acral vasculitis.

J Immunother Cancer. 2018 11 16;6(1):120

Authors: Comont T, Sibaud V, Mourey L, Cougoul P, Beyne-Rauzy O

Abstract
Commentary on « Ipilimumab induced vasculitis » by Padda A. et al., J Immunother Cancer. 2018;6:12. The authors diagnosed a small vessel vasculitis following treatment with anti-CTLA-4 (ipilimumab) for a resected stage III B/C melanoma. We report a similar case of acral vasculitis occurring with a combination of anti-CTLA-4 (tremelimumab) and anti-PD-L1 (durvalumab) prescribed for the management of a metastatic urothelial bladder cancer. In contrast to Padda A. et al., we observed a significant improvement with oral corticosteroids.

PMID: 30446009 [PubMed - indexed for MEDLINE]

[Modulation of Luciferase Production in Melanoma Cells in vitro].

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

[Modulation of Luciferase Production in Melanoma Cells in vitro].

Mol Biol (Mosk). 2018 Sep-Oct;52(5):826-835

Authors: Kandarakov OF, Bruter AV, Belyavsky AV

Abstract
Reporter proteins find increasing application in biomedical studies in vitro and in vivo. However, to correctly interpret the results based on their use, it is important to understand whether reporter protein production is modulated in model cells and in what conditions such modulation may occur. Reporter activity was studied in Mel IL melanoma cells transiently transfected with a pCpG vector-based plasmid construct expressing firefly luciferase. Luciferase expression quickly dropped during the first two culture passages, which were followed by a quasi-stable period, when luciferase expression relatively slightly decreased with time. Phases of maximal and minimal luciferase production, which corresponded to the exponential and stationary growth phases, respectively, were observed during batch culture. When the medium was changed, luciferase production was stimulated in the stationary, but not exponential, cell growth phase. Severe hypoxia (0.1% O2) decreased the luciferase amount, suggesting substantial modulation of cell metabolism in total and luciferase production in particular. The targeted drug vemurafenib suppressed the luciferase production in Mel IL cells, whereas DMSO, which is often used as a drug solvent in experiments with cells, stimulated the luciferase production. Based on the results, it was hypothesized that modulation of reporter protein production in mammalian cells reflects the adaptation of intracellular metabolism to external conditions and may be a source of incorrect interpretations of experiments using reporter proteins.

PMID: 30363058 [PubMed - indexed for MEDLINE]

Permalink for 'Prognostic correlation between vitamin D serological levels, Body Mass Index and clinical-pathological features in melanoma patients.'

Prognostic correlation between vitamin D serological levels, Body Mass Index and clinical-pathological features in melanoma patients.

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

Prognostic correlation between vitamin D serological levels, Body Mass Index and clinical-pathological features in melanoma patients.

G Ital Dermatol Venereol. 2018 Oct;153(5):732-733

Authors: Moliterni E, Paolino G, Veronese N, Bottoni U, Corsetti P, Cardone M, Didona D, Lopez T, Calvieri S

PMID: 30246955 [PubMed - indexed for MEDLINE]

The age of enlightenment in melanoma immunotherapy.

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

The age of enlightenment in melanoma immunotherapy.

J Immunother Cancer. 2018 08 22;6(1):80

Authors: Albertini MR

Abstract
An updated survival analysis by Callahan et al. published in the February 1, 2018 issue of the Journal of Clinical Oncology reported a 3-year overall survival (OS) rate of 63% for 94 patients with previously treated or untreated advanced melanoma who received ipilimumab and nivolumab as concurrent therapy in a phase 1 dose escalation study CA209-004 (n = 53) or in an expansion cohort with the dose and schedule of concurrent ipilimumab and nivolumab now approved for patients with unresectable or metastatic melanoma (n = 41). While this 3-year OS rate of 63% in patients with measurable, unresectable stage III or IV melanoma is an impressive accomplishment that compares very favorably with historical metastatic melanoma survival rates, findings from larger phase 3 studies are needed to determine whether combination immunotherapy significantly improves survival more than single agent immunotherapy with PD-1 blockade. This Commentary discusses the transition from the dark ages to the age of enlightenment in melanoma immunotherapy and provides a roadmap for a better tomorrow for patients with metastatic melanoma.

PMID: 30134977 [PubMed - indexed for MEDLINE]

Perspectives in melanoma: Meeting report from the Melanoma Bridge (30 November-2 December, 2017, Naples, Italy).

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

Perspectives in melanoma: Meeting report from the Melanoma Bridge (30 November-2 December, 2017, Naples, Italy).

J Transl Med. 2018 07 21;16(1):207

Authors: Ascierto PA, Puzanov I, Agarwala SS, Bifulco C, Botti G, Caracò C, Ciliberto G, Davies MA, Dummer R, Ferrone S, Gajewski TF, Garbe C, Luke JJ, Marincola FM, Masucci G, Mehnert JM, Mozzillo N, Palmieri G, Postow MA, Schoenberger SP, Wang E, Thurin M

Abstract
Metastatic melanoma represents a challenging clinical situation and, until relatively recently, there was an absence of effective treatment options. However, in 2011, the advanced melanoma treatment landscape was revolutionised with the approval of the anti-cytotoxic T-lymphocyte-associated protein-4 checkpoint inhibitor ipilimumab and the selective BRAF kinase inhibitor vemurafenib, both of which significantly improved overall survival. Since then, availability of new immunotherapies, especially the anti-programmed death-1 checkpoint inhibitors, as well as other targeted therapies, have further improved outcomes for patients with advanced melanoma. Seven years on from the first approval of these novel therapies, evidence for the use of various immune-based and targeted approaches is continuing to increase at a rapid rate. Improved understanding of the tumour microenvironment and tumour immuno-evasion strategies has resulted in different approaches to target and harness the immune response. These new immune-based approaches offer the opportunity for various approaches with distinct modes of action being used in combination with one another, as well as combined with other treatment modalities such as targeted therapy, electrochemotherapy and surgery. The increasing number of treatment options that are now available has resulted in a growing need to identify which patients will derive most benefit from which treatments. Much research is now focused on the identification of biomarkers that can be utilised to help select patients for treatment. These and other recent advances in the management of melanoma were the focus of discussions at the third Melanoma Bridge meeting (30 November-2 December, 2017, Naples, Italy), which is summarised in this report.

PMID: 30031393 [PubMed - indexed for MEDLINE]

The Great Debate at "Melanoma Bridge", Napoli, December 2nd, 2017.

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

The Great Debate at "Melanoma Bridge", Napoli, December 2nd, 2017.

J Transl Med. 2018 04 17;16(1):101

Authors: Ascierto PA, Caracò C, Gershenwald JE, Hamid O, Ross M, Sullivan RJ, Puzanov I

Abstract
As part of the 2017 Melanoma Bridge congress (November 30-December 2, 2017, Napoli, Italy), the great debate session featured counterpoint views from leading experts on three contemporary controversial clinical issues in the care of the melanoma patient. These were: (1) whether complete lymph node dissection should be routinely offered to all melanoma patients with sentinel lymph node-positive disease; (2) whether first-line treatment of BRAF-mutated melanoma should consist of BRAF-targeted therapy or immunotherapy with checkpoint inhibitors; and (3) whether combined or sequential administration of treatments should be the preferred option in the management of patients with advanced melanoma. Discussion of these three important issues and audience responses are reported here.

PMID: 29665799 [PubMed - indexed for MEDLINE]

Predictors of anxiety and depression 2 years following treatment in uveal melanoma survivors.

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

Predictors of anxiety and depression 2 years following treatment in uveal melanoma survivors.

Psychooncology. 2018 07;27(7):1727-1734

Authors: Brown SL, Hope-Stone L, Heimann H, Damato B, Salmon P

Abstract
OBJECTIVE: We examined the role of posttreatment symptoms and functional problems and of worry about recurrent disease (WREC) in predicting probable anxiety and depression cases 24 months after diagnosis in survivors of posterior uveal melanoma. We examined whether WREC mediates links between symptoms, functional problems, and probable anxiety and depression cases.
METHODS: Prospective cohort study of 261 treated uveal melanoma survivors 6, 12, and 24 months after diagnosis. Hierarchical logistic regression analyses predicting anxiety and depression 24 months after diagnosis identified by Hospital Anxiety and Depression Scale cutoff scores. Symptoms, functional problems, and WREC 6-month posttreatment were entered into the analyses as predictors, then the same variables at 12 months. We controlled anxiety or depression at 6 and 12 months and chromosome 3 status, which accurately predicts 10-year survival. Mediation of links between 6-month symptoms and functional problems and 24-month anxiety and depression by 12-month WREC was tested.
RESULTS: Anxiety caseness at 24 months was predicted by 6-month ocular irritation, headache, and functional problems and 12-month WREC. Depression caseness at 24 months was predicted by 6-month headache and functional problems. Worry about recurrent disease at 12 months mediated prediction of anxiety caseness by 6-month symptoms and functional problems. Chromosome 3 status predicted neither anxiety nor depression.
CONCLUSIONS: Survivors reporting symptoms, functional problems, and WREC should be monitored for anxiety and depression. Appropriate reassurance that symptoms do not signify future disease might help prevent anxiety.

PMID: 29601654 [PubMed - indexed for MEDLINE]

4-1BB costimulation induces T cell mitochondrial function and biogenesis enabling cancer immunotherapeutic responses.

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

4-1BB costimulation induces T cell mitochondrial function and biogenesis enabling cancer immunotherapeutic responses.

J Exp Med. 2018 04 02;215(4):1091-1100

Authors: Menk AV, Scharping NE, Rivadeneira DB, Calderon MJ, Watson MJ, Dunstane D, Watkins SC, Delgoffe GM

Abstract
Despite remarkable responses to cancer immunotherapy in a subset of patients, many patients remain resistant to these therapies. The tumor microenvironment can impose metabolic restrictions on T cell function, creating a resistance mechanism to immunotherapy. We have previously shown tumor-infiltrating T cells succumb to progressive loss of metabolic sufficiency, characterized by repression of mitochondrial activity that cannot be rescued by PD-1 blockade. 4-1BB, a costimulatory molecule highly expressed on exhausted T cells, has been shown to influence metabolic function. We hypothesized that 4-1BB signaling might provide metabolic support to tumor-infiltrating T cells. 4-1BB costimulation of CD8+ T cells results in enhanced mitochondrial capacity (suggestive of fusion) and engages PGC1α-mediated pathways via activation of p38-MAPK. 4-1BB treatment of mice improves metabolic sufficiency in endogenous and adoptive therapeutic CD8+ T cells. 4-1BB stimulation combined with PD-1 blockade results in robust antitumor immunity. Sequenced studies revealed the metabolic support afforded by 4-1BB agonism need not be continuous and that a short course of anti-4-1BB pretreatment was sufficient to provide a synergistic response. Our studies highlight metabolic reprogramming as the dominant effect of 4-1BB therapy and suggest that combinatorial strategies using 4-1BB agonism may help overcome the immunosuppressive metabolic landscape of the tumor microenvironment.

PMID: 29511066 [PubMed - indexed for MEDLINE]

Unveiling skin macrophage dynamics explains both tattoo persistence and strenuous removal.

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

Unveiling skin macrophage dynamics explains both tattoo persistence and strenuous removal.

J Exp Med. 2018 04 02;215(4):1115-1133

Authors: Baranska A, Shawket A, Jouve M, Baratin M, Malosse C, Voluzan O, Vu Manh TP, Fiore F, Bajénoff M, Benaroch P, Dalod M, Malissen M, Henri S, Malissen B

Abstract
Here we describe a new mouse model that exploits the pattern of expression of the high-affinity IgG receptor (CD64) and allows diphtheria toxin (DT)-mediated ablation of tissue-resident macrophages and monocyte-derived cells. We found that the myeloid cells of the ear skin dermis are dominated by DT-sensitive, melanin-laden cells that have been missed in previous studies and correspond to macrophages that have ingested melanosomes from neighboring melanocytes. Those cells have been referred to as melanophages in humans. We also identified melanophages in melanocytic melanoma. Benefiting of our knowledge on melanophage dynamics, we determined the identity, origin, and dynamics of the skin myeloid cells that capture and retain tattoo pigment particles. We showed that they are exclusively made of dermal macrophages. Using the possibility to delete them, we further demonstrated that tattoo pigment particles can undergo successive cycles of capture-release-recapture without any tattoo vanishing. Therefore, congruent with dermal macrophage dynamics, long-term tattoo persistence likely relies on macrophage renewal rather than on macrophage longevity.

PMID: 29511065 [PubMed - indexed for MEDLINE]

In-vitro study of the influence of octocrylene on a selected metastatic melanoma cell line.

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

In-vitro study of the influence of octocrylene on a selected metastatic melanoma cell line.

G Ital Dermatol Venereol. 2019 Apr;154(2):197-204

Authors: Prunk Zdravković T, Zdravković B, Zdravković M, Dariš B, Lunder M, Ferk P

Abstract
BACKGROUND: Octocrylene (OCT) is one of the most widespread chemical UV filters used in sunscreens and cosmetic products. Despite the use of sunscreens and personal care products over decades, melanoma as the most serious and aggressive form of skin cancer is still a cause of concern. Hence the aim of this study was to investigate any potential influence of OCT on metabolic activity, cytotoxicity and ABCB5 mRNA expression in melanoma cells. The ABCB5 transmembrane protein was tested due to its well-known role in the initiation, invasion and metastatic spread of various cancers, including melanoma.
METHODS: Metastatic melanoma cell line WM-266-4 (ATCC) was incubated with selected concentrations of OCT and for different time intervals. The MTT and LDH assays to measure the cells' metabolic activity and cytotoxicity were used respectively. Target gene (ABCB5) expression was detected by quantitative real-time PCR (qRT-PCR), using TaqMan® chemistry.
RESULTS: Our results suggest decreased metastatic melanoma cells' metabolic activity, increased cytotoxicity and increased ABCB5 mRNA expression (P<0.05) with longer time of exposure to OCT as compared to control cells. Accordingly, we suspect that the surviving cells are more invasive and aggressive, which might explain their microscopically observed cannibalistic activity.
CONCLUSIONS: With this study, we elucidate a new promising field for further research to contribute to etiology and prevention of melanoma.

PMID: 28704989 [PubMed - indexed for MEDLINE]

Sequential monitoring of pigmented lesions during dabrafenib treatment: a prospective study and a literature overview.

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

Sequential monitoring of pigmented lesions during dabrafenib treatment: a prospective study and a literature overview.

G Ital Dermatol Venereol. 2019 Apr;154(2):170-176

Authors: Dika E, Lambertini M, Fanti PA, Piraccini BM, Gurioli C, Ravaioli GM, Chessa MA, Traniello Gradassi A, Melotti B, Sperandi F, Patrizi A

Abstract
BACKGROUND: Targeted therapies in melanoma have shown clinical benefit in incrementing the overall survival of metastatic patients. However, cutaneous adverse events have been frequently associated with these drugs.
METHODS: We report our experience in the management of patients treated with dabrafenib for metastatic melanoma, focusing on the monitoring of pigmented lesions. Dermatologic evaluation was performed during the first visit, at the start of each treatment and subsequently after every four weeks. Global nevi count, videodermoscopy of suspected lesions, and surgical excisions when necessary were performed at the beginning of the treatment and every fourth week. All other cutaneous adverse events (cAEs) were noted and documented. Eleven patients were included.
RESULTS: The most important cAEs included palmo-plantar hyperkeratosis, diffuse xerosis and pigmented lesion changes. Regarding the latter, in 6 patients, especially in the first months of treatment, we observed hyperpigmentation and hyperkeratosis of the nevi, of the pigmented mucosae and, in one patient, hyperkeratotic changes on a cutaneous metastasis. Histopathology of the excised lesions showed one ex novo melanoma occurrence and benign changes to pre-existing nevi.
CONCLUSIONS: The awareness of the importance of sequential monitoring of pigmented lesions, with particular attention to the lesions of new onset, is crucial for the best management of these complex patients.

PMID: 28290623 [PubMed - indexed for MEDLINE]

Resected thymic large cell neuroendocrine carcinoma: A case report and review of the literature.

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

Resected thymic large cell neuroendocrine carcinoma: A case report and review of the literature.

Int J Surg Case Rep. 2019 Jun 08;60:53-57

Authors: Ogata S, Maeda R, Tomita M, Sato Y, Ayabe T, Nakamura K

Abstract
INTRODUCTION: Large cell neuroendocrine carcinoma (LCNEC) of the thymus is an extremely rare neoplasm.
PRESENTATION OF CASE: We report a rare case of LCNEC of the thymus in a 55-year-old woman. Her chest roentgenogram during a routine checkup revealed an abnormal shadow in the mediastinal left upper lung field. Chest computed tomography showed an anterior mediastinal mass measuring 4.8 × 4.0 cm. Positron emission tomography with 18F-fluorodeoxyglucose (FDG) showed high FDG accumulation at the lesion. To obtain a definitive diagnosis and achieve complete resection, a surgery was performed. The postoperative diagnosis was thymic LCNEC; it was classified as a Masaoka stage III tumor due to the invasion of tumor cells into the left lung. Postoperatively, the patient received adjuvant chemotherapy and survived without any signs of recurrence for 30 months after surgery.
DISCUSSION/CONCLUSION: The detailed clinical features of thymic LCNEC remain unknown because of its rarity. In total, 20 cases of resection for LCNEC, including the present case, have been reported in the English language literature; we have presented a review of these cases and discussed the optimal therapy for this rare and virulent tumor of the thymus.

PMID: 31202999 [PubMed - as supplied by publisher]

Permalink for 'Clear cell renal cell carcinoma with Paneth-like cells: Clinicopathologic, morphologic, immunohistochemical, ultrastructural, and molecular analysis of 13 cases.'

Clear cell renal cell carcinoma with Paneth-like cells: Clinicopathologic, morphologic, immunohistochemical, ultrastructural, and molecular analysis of 13 cases.

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

Clear cell renal cell carcinoma with Paneth-like cells: Clinicopathologic, morphologic, immunohistochemical, ultrastructural, and molecular analysis of 13 cases.

Ann Diagn Pathol. 2019 Jun 03;41:96-101

Authors: Kojima F, Bulimbasic S, Alaghehbandan R, Martinek P, Vanecek T, Michalova K, Pivovarcikova K, Michal M, Hora M, Murata SI, Sugawara E, Rogala J, Limani R, Hes O

Abstract
Clear cell renal cell carcinoma (CRCC) is well known for its intratumoral heterogeneity. Paneth-like cells (PLC) have been reported in variable organs (i.e., hepatobiliary, genitourinary, and female genital tract). In genitourinary system, it is possible to find PLCs in epididymis, urinary bladder and prostate. The objective of this study was to assess PLC in CRCCs 13 CRCCs with prominent PLC (CRCCPLC) were selected out of 1378 CRCCs in our registry. The tumors were analyzed using morphologic, immunohistochemical, ultrastructural, and molecular genetic methods. CRCCPLCs were mostly of low histologic grade (12/13). Immunohistochemical profile was compatible with classic CRCC. PLC constituted 10 to-70% of the tumor volume (mean 17.7%, median 10%). PLCs did not express neuroendocrine markers (chromogranin, synaptophysin, CD56, INSM-1). Ultrastructurally, PLCs were filled by membrane bounded vesicles of various sizes and were compatible with secretory type of cells. VHL mutation was found in 9/9 cases, and LOH3p was found in 6/8 analyzable cases. Conclusions: PLC morphology can variably be present in "classic" CRCC, even in a substantial proportion. Ultrastructurally, PLCs have all attributes of secretory cells. Preliminary follow up data showed that these tumors may not be associated with aggressive clinical behavior.

PMID: 31202196 [PubMed - as supplied by publisher]

Spread through air spaces (STAS) is a predictor of poor outcome in atypical carcinoids of the lung.

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

Spread through air spaces (STAS) is a predictor of poor outcome in atypical carcinoids of the lung.

Virchows Arch. 2019 Jun 15;:

Authors: Altinay S, Metovic J, Massa F, Gatti G, Cassoni P, Scagliotti GV, Volante M, Papotti M

Abstract
Spread through air spaces (STAS) have been recently recognized as a prognostic factor for adenocarcinoma and squamous cell carcinoma of the lung. Pulmonary neuroendocrine neoplasms (NENs) include tumors with different morphology and a heterogeneous clinical behavior. Among atypical carcinoids (ACs), new prognostic factors able to refine prognosis are needed. In the present study, a retrospective series of 91 surgically resected ACs was investigated, in parallel with 191 control cases of typical carcinoids (TCs) and of high-grade small- and large-cell neuroendocrine carcinomas, to assess the presence and potential prognostic role of STAS. STAS was defined by the presence of neoplastic nests or single cells in air spaces beyond the tumor edge. Clinicopathological parameters and survival were correlated by univariate and multivariate analyses. STAS was identified in 48% of ACs (44/91) compared to 20.5% of TCs and 71-88% of high-grade large- and small-cell carcinomas in the control group. In the carcinoid group, presence of STAS was significantly correlated with unfavorable parameters, such as high tumor stage, positive nodal status, high Ki-67 index, presence of angioinvasion, and with adverse disease outcome, shorter overall survival, and time to progression. In conclusion, the presence of STAS is an additional relevant adverse prognostic factor in pulmonary AC that currently has the most unpredictable outcome and the most controversial treatment strategy.

PMID: 31201506 [PubMed - as supplied by publisher]

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;:

PMID: 31201352 [PubMed - as supplied by publisher]

Permalink for 'Paraneoplastic pemphigus and myasthenia gravis as the first manifestations of a rare case of pancreatic follicular dendritic cell sarcoma: CT findings and review of literature.'

Paraneoplastic pemphigus and myasthenia gravis as the first manifestations of a rare case of pancreatic follicular dendritic cell sarcoma: CT findings and review of literature.

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

Paraneoplastic pemphigus and myasthenia gravis as the first manifestations of a rare case of pancreatic follicular dendritic cell sarcoma: CT findings and review of literature.

BMC Gastroenterol. 2019 Jun 14;19(1):92

Authors: Lu T, Song B, Pu H, Li X, Chen Q, Yang C

Abstract
BACKGROUND: Follicular dendritic cell sarcoma (FDCS) is a rare neoplasm that originates from follicular dendritic cells in lymphoid tissue while paraneoplastic pemphigus (PNP) is an autoimmune blistering disease associated with neoplasms. Pancreatic FDCS associated with PNP and myasthenia gravis (MG) is even rarer and highly malignant. We present the clinical data, pathological materials and computed tomography (CT) features of a rare case of this disease.
CASE PRESENTATION: A 49-year-old woman presented with repeated ptosis of both eyelids, oral ulcers and erosions. Her laboratory results showed a slight elevation of CA125 and positivity of some autoimmune antibodies. CT revealed a round solid mass with central necrosis in the pancreatic tail. The solid component of the mass showed slight enhancement and serpentine feeding arteries in the arterial phase, moderate enhancement with a draining vein around the tumor in the portal venous phase and persistent enhancement in the delayed phase. Surgical resection was performed, and the pathological diagnosis was FDCS. However, the patient died of inability to excrete sputum and occlusion of the respiratory tract.
CONCLUSIONS: Pancreatic FDCS manifested as PNP and MG is very rare. Its CT features are not specific, and the disease should be differentiated from neuroendocrine tumors, solid pseudopapillary neoplasms and acinar cell carcinoma.

PMID: 31200650 [PubMed - in process]

Serous Cystadenoma of the Pancreas With Complex Florid Papillary Architecture: A Case Report and Review of the Literature.

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

Serous Cystadenoma of the Pancreas With Complex Florid Papillary Architecture: A Case Report and Review of the Literature.

Int J Surg Pathol. 2019 Jun 12;:1066896919854544

Authors: Tracht J, Reid MD, Hissong E, Sekhar A, Sarmiento J, Krasinskas A, Xue Y

Abstract
Serous cystadenoma (SCA) is a relatively rare benign pancreatic neoplasm. It has a very distinctive gross and microscopic appearance including pure and mixed microcystic and macrocystic patterns as well as rare solid architectural pattern. In this article, we present a rare case of SCA with a complex florid papillary architecture. A 40-year-old man was diagnosed with a 3.5 cm SCA of the uncinate process of the pancreas based on abdominal computed tomography scan. The tumor was monitored radiographically until recent magnetic resonance imaging showed a new 1.0-cm eccentric mural nodule within the tumor with multiple arterial enhancing septations and features suspicious for a neuroendocrine tumor. A pylorus-preserving Whipple procedure was subsequently performed and the mass was resected. Gross examination confirmed the radiological findings of a well-demarcated, 3.5 cm multicystic pancreatic lesion with a 1.0 cm circumscribed, tan solid nodule at its periphery. Microscopic evaluation revealed a predominantly microcystic pattern classical of SCA with occasional macrocysts. The 1.0 cm discrete nodule was also a SCA, but showed unusually exuberant complex papillary growth. To our knowledge, this is the first reported case describing this morphologic variant. Recognition of this rare and unusual pattern is important to avoid misdiagnosis, especially on small biopsy specimens.

PMID: 31187681 [PubMed - as supplied by publisher]

ACTH-producing thymic neuroendocrine tumor initially presenting as psychosis: A case report and literature review.

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

ACTH-producing thymic neuroendocrine tumor initially presenting as psychosis: A case report and literature review.

Thorac Cancer. 2019 Jun 11;:

Authors: Okumura T, Takayama S, Nishio SI, Miyakoshi T, Noguchi T, Kobayashi T, Fukushima T, Sekiguchi N, Otsuki T, Komatsu M, Koizumi T

Abstract
A 32-year-old woman was referred to our hospital because of severe psychosis and was found to have an ectopic ACTH-producing thymic neuroendocrine tumor. Laboratory data revealed an elevated serum cortisol and plasma ACTH level, hypokalemia, and metabolic alkalosis. Chest computed tomography (CT) revealed an anterior mediastinal mass and multiple pulmonary nodules. As the patient was unable to communicate because of her consciousness disturbance, she was managed with artificial ventilation and deep sedation. Metyrapone and potassium supplementation were administered, and steroid psychosis gradually improved. Thoracic surgery was performed and the histopathological diagnosis was thymic neuroendocrine tumor with positive anti-ACTH immunohistochemical staining. Here we present details of the case and review the literature.

PMID: 31187563 [PubMed - as supplied by publisher]

Permalink for 'Characteristics and outcomes of therapy-related myeloid neoplasms after peptide receptor radionuclide/chemoradionuclide therapy (PRRT/PRCRT) for metastatic neuroendocrine neoplasia: a single-institution series.'

Characteristics and outcomes of therapy-related myeloid neoplasms after peptide receptor radionuclide/chemoradionuclide therapy (PRRT/PRCRT) for metastatic neuroendocrine neoplasia: a single-institution series.

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

Characteristics and outcomes of therapy-related myeloid neoplasms after peptide receptor radionuclide/chemoradionuclide therapy (PRRT/PRCRT) for metastatic neuroendocrine neoplasia: a single-institution series.

Eur J Nucl Med Mol Imaging. 2019 Jun 11;:

Authors: Goncalves I, Burbury K, Michael M, Iravani A, Ravi Kumar AS, Akhurst T, Tiong IS, Blombery P, Hofman MS, Westerman D, Hicks RJ, Kong G

Abstract
PURPOSE: Peptide receptor radionuclide/chemoradionuclide therapy (PRRT/PRCRT) is an effective therapy for metastatic neuroendocrine neoplasia (NEN), but therapy-related myeloid neoplasms (t-MN) remain of concern. The study reviewed the clinicopathological features and outcomes of patients who developed t-MN.
METHODS: Retrospective analysis of all patients diagnosed with t-MN by 2016 WHO classification, from a cohort of 521 patients who received PRRT/PRCRT over a 12-year period. Molecular next-generation sequencing using an in-house 26-gene panel was performed.
RESULTS: Twenty-five of 521 (4.8%) patients were diagnosed with t-MN, including six acute myeloid leukaemia (AML) and 19 myelodysplastic syndrome (MDS). The median time from first cycle PRRT/PRCRT to diagnosis of t-MN was 26 months (range 4-91). Twenty-two of 25 (88%) patients had grade 1-2 pancreatic or small bowel NEN with moderate metastatic liver burden. Six patients (24%) had prior chemotherapy. Median number of PRRT cycles = 5 (22/25 (88%) with concomitant radiosensitising chemotherapy). All 25 patients achieved disease stabilisation (68%) or partial response (32%) on RECIST 1.1 at 3 months post-PRRT. At t-MN diagnosis, all patients presented with thrombocytopenia (median nadir 33 × 109/L, range 3-75) and 17 (68%) remained NEN progression-free. Marrow genetic analysis revealed unfavourable karyotype in 16/25 (66%) patients with tumour protein 53 (TP53) mutation in nine (36%). Azacitidine therapy was utilised in ten eligible patients, while four received induction chemotherapy for AML. The median overall survival from first PRRT was 62 months (19-94), but from t-MN diagnosis was only 13 months (1-56), with death due primarily to haematological disease progression.
CONCLUSIONS: The diagnosis of t-MN after PRRT/PRCRT is an infrequent but serious complication with poor overall survival. Most patients present with thrombocytopenia; unfavourable genetic mutations have a poor response to t-MN treatment. Prospective data are needed to explore potential pre-existing genetic factors and predictive biomarkers to minimise the risk of t-MN.

PMID: 31187162 [PubMed - as supplied by publisher]

Pancreatic Neuroendocrine Tumor in a Young Child With Tuberous Sclerosis Complex 1.

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

Pancreatic Neuroendocrine Tumor in a Young Child With Tuberous Sclerosis Complex 1.

J Endocr Soc. 2019 Jun 01;3(6):1201-1206

Authors: Mehta S, Rusyn L, Ginsburg H, Hajdu C, Kohn B

Abstract
Pancreatic neuroendocrine tumors (PNETs) occur in the context of tuberous sclerosis complex (TSC). To date, PNETs in association with TSC have been described almost exclusively in adults and in the context of TSC2. We present the evaluation of a PNET in a young child with TSC1. A 3-year, 6-month-old boy with TSC1 was found on surveillance to have a small pancreatic lesion measuring 0.4 cm on magnetic resonance imaging (MRI). The lesion showed interval enlargement to 1 cm on serial MRI studies during the ensuing 16 weeks. Endocrine laboratory tests did not reveal a functional tumor. The patient underwent enucleation of the pancreatic lesion. Microscopic examination defined a well-differentiated PNET, grade II/intermediate grade with a mitotic rate of two mitotic figures per 10 high-powered field and Ki-67 proliferation index of ∼15%. The tumor was positive for the TSC1 gene mutation. The patient was free of tumor recurrence at the 5-year follow-up examination, as determined by endocrine surveillance and annual MRI of the abdomen. In the reported data, PNET in patients with TSC has been primarily reported in association with TSC2. Our case demonstrates that patients with TSC1 can develop PNETs, even at an early age. The international TSC consensus group 2012 recommendation was to obtain MRI of the abdomen every 1 to 3 years for surveillance of renal angiomyolipomas and renal cystic disease. It might be beneficial to add a pancreatic protocol to the surveillance guidelines to evaluate for PNET.

PMID: 31187078 [PubMed]

Prognostic Factors and Survival Time in Patients with Small Bowel Tumors: A Retrospective Observational Study.

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

Prognostic Factors and Survival Time in Patients with Small Bowel Tumors: A Retrospective Observational Study.

Int J Surg Oncol. 2019;2019:2912361

Authors: Taghipour Zahir S, Heidarymeybodi Z, AleSaeidi S

Abstract
This study examines survival time in patients with small bowel tumors and determines its contributing factors. In this retrospective analytical study, the medical records of 106 patients with small bowel cancer (from 2006 to 2011) were investigated. The patients' data were extracted, including age, gender, clinical presentation, location of tumor, histological type, grade of tumor, site of metastasis, and type of treatment. The Kaplan-Meier test was used to estimate the overall survival time and the Log-rank test to compare the survival curves. The Cox regression was also used to evaluate the effect of the confounding variables on survival time. This study was conducted on 106 patients with a median age of 60 years (Min: 7, Max: 87). The tumor types included adenocarcinoma (n=78, 73.6%), MALToma (n=22, 20.8%), neuroendocrine tumors (n=4, 3.8%), and sarcoma (n=2. 1.8%). Grade 3 adenocarcinomas had a significantly lower survival time (HR: 1.48, 95% CI: 0.46-2.86; P=.001). Combined therapy (chemotherapy and surgery) vs. single-therapy (only surgery) had no significant effects on the survival of the patients with MALToma (5 vs. 3 months, 95% CI: 1.89-5.26; P=.06). There were no significant differences between the survival time in adenocarcinoma and MALToma (12 vs. 20 months, 95% CI: 6.24-24.76; P=.49). Tumor grade was the only independent prognostic factor that affected survival in adenocarcinoma. The patients diagnosed with MALToma in the study also had a poor prognosis, and the type of treatment had no significant effect on their survival.

PMID: 31186956 [PubMed - in process]

DNA methylation-based classification of sinonasal undifferentiated carcinoma.

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

DNA methylation-based classification of sinonasal undifferentiated carcinoma.

Mod Pathol. 2019 Jun 11;:

Authors: Dogan S, Vasudevaraja V, Xu B, Serrano J, Ptashkin RN, Jung HJ, Chiang S, Jungbluth AA, Cohen MA, Ganly I, Berger MF, Momeni Boroujeni A, Ghossein RA, Ladanyi M, Chute DJ, Snuderl M

Abstract
Sinonasal undifferentiated carcinoma (SNUC) is an aggressive malignancy harboring IDH2 R172 mutations in >80% cases. We explored the potential of genome-wide DNA methylation profiling to elucidate tumor biology and improve the diagnosis of sinonasal undifferentiated carcinoma and its histologic mimics. Forty-two cases, including sinonasal undifferentiated, large cell neuroendocrine, small cell neuroendocrine, and SMARCB1-deficient carcinomas and olfactory neuroblastoma, were profiled by Illumina Infinium Methylation EPIC array interrogating >850,000 CpG sites. The data were analyzed using a custom bioinformatics pipeline. IDH2 mutation status was determined by the targeted exome sequencing (MSK-IMPACTTM) in most cases. H3K27 methylation level was assessed by the immunohistochemistry-based H-score. DNA methylation-based semi-supervised hierarchical clustering analysis segregated IDH2 mutants, mostly sinonasal undifferentiated (n = 10) and large cell neuroendocrine carcinomas (n = 4), from other sinonasal tumors, and formed a single cluster irrespective of the histologic type. t-distributed stochastic neighbor embedding dimensionality reduction analysis showed no overlap between IDH2 mutants, SMARCB1-deficient carcinoma and olfactory neuroblastoma. IDH2 mutants demonstrated a global methylation phenotype and an increase in repressive trimethylation of H3K27 in comparison to IDH2 wild-type tumors (p < 0.001). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed no difference in pathway activation between IDH2-mutated sinonasal undifferentiated and large cell neuroendocrine carcinomas. In comparison to SMARCB1-deficient, IDH2-mutated carcinomas were associated with better disease-free survival (p = 0.034) and lower propensity for lung metastasis (p = 0.002). ARID1A mutations were common in small cell neuroendocrine carcinoma but not among IDH2 mutants (3/3 versus 0/18 and p < 0.001). IDH2 mutations in sinonasal carcinomas induce a hypermethylator phenotype and define a molecular subgroup of tumors arising in this location. IDH2-mutated sinonasal undifferentiated carcinoma and large cell neuroendocrine carcinoma likely represent a phenotypic spectrum of the same entity, which is distinct from small cell neuroendocrine and SMARCB1-deficient sinonasal carcinomas. DNA methylation-based analysis of the sinonasal tumors has potential to improve the diagnostic accuracy and classification of tumors arising in this location.

PMID: 31186531 [PubMed - as supplied by publisher]

Incidence of Neuroendocrine Tumors in the United States from 2001-2015: A United States Cancer Statistics Analysis of 50 States.

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

Incidence of Neuroendocrine Tumors in the United States from 2001-2015: A United States Cancer Statistics Analysis of 50 States.

Cureus. 2019 Mar 26;11(3):e4322

Authors: Patel N, Benipal B

Abstract
Introduction Neuroendocrine tumors (NETs), once considered a rare malignancy, has started to become a more common cancer within the United States (US). Given the limited data available on the incidence of NETs in the entire US population, our goal in this study was to investigate the incidence of NETs in at-risk populations in all 50 states. Methods The United States Cancer Statistics (USCS) was used to obtain data for NETs from 2001 to 2015. An incidence analysis was done for sex, race, stage, primary location within the gastrointestinal (GI) tract, and US regional location. Results The overall incidence of NETs from 2001 to 2015 was 2.89 per 100,000 people per year. The overall incidence rates were the greatest for each stratification of males, blacks, localized disease, primary location in the small intestine, and in the Northeast. The incidence in males between 2013 and 2015 increased with an annual percent change (APC) of 8.44. Between 2006 and 2015, the incidence in blacks increased with an APC of 1.89. Between 2013 and 2015, the incidence of localized disease and a primary location in the small intestine increased with an APC of 16.89 and 14.37, respectively. In the Northeast, between 2013 and 2015, the incidence increased with an APC of 11.09. Conclusion In this study, we investigated the incidence of NETs using data obtained from the USCS database, which covers all 50 states. We found that there is a rising incidence in most subpopulations possibly related to improved compliance with surveillance colonoscopies and improved endoscopic and radiographic techniques. Further studies are needed to ultimately determine the exact causes of our findings. However, our study will serve as an important first step to determine the exact etiology for the rising incidence of NETs in all 50 states.

PMID: 31183301 [PubMed]

Carcinoid Tumor Arising from the Sphenoid Sinus Treated with Definitive Intensity-modulated Radiation Therapy: A Case Report.

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

Carcinoid Tumor Arising from the Sphenoid Sinus Treated with Definitive Intensity-modulated Radiation Therapy: A Case Report.

Cureus. 2019 Mar 21;11(3):e4288

Authors: Hilal L, Jammal M, Khalifeh I, Tfayli A, Youssef B

Abstract
Head and neck neuroendocrine tumors (NET) are a rare type of cancer. NET can be classified according to the histopathological features. The typical carcinoid tumor is a well-differentiated tumor that is the least common among other types. Owing to its indolent behavior and variable radiological and pathological features, treatment of carcinoid tumors remains a challenge. We report a case of a 54-year-old man presenting with a non-operable carcinoid tumor arising in the sphenoid sinuses treated with radiotherapy with stable disease control after three years follow-up.

PMID: 31183269 [PubMed]

Permalink for 'Octreotide Use in a Patient with MEN-1 Syndrome and Multifocal Pancreatic Neuroendocrine Tumors: A Case Report and Review of the Literature.'

Octreotide Use in a Patient with MEN-1 Syndrome and Multifocal Pancreatic Neuroendocrine Tumors: A Case Report and Review of the Literature.

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

Octreotide Use in a Patient with MEN-1 Syndrome and Multifocal Pancreatic Neuroendocrine Tumors: A Case Report and Review of the Literature.

Case Rep Gastrointest Med. 2019;2019:9462942

Authors: Kemm MH, Manly CD, Hoang TD, Mai VQ, Shakir MKM

Abstract
We report a patient with multiple endocrine neoplasia type 1 with pancreatic polypeptide (PP) secreting subcentimeter pancreatic neuroendocrine tumors (pNETs) treated with octreotide and review the current literature that pertains to the management of these patients. Clinical data, laboratory results, and imaging were reviewed. A literature search was performed in PUBMED using combinations of the terms "multiple endocrine neoplasia type 1," "somatostatin," octreotide," "pancreatic polypeptide," and "pancreatic tumor." Relevant references were selected and reviewed. A 43-year-old male with a history of MEN1 and multiple subcentimeter neuroendocrine tumors with elevation of PP was treated with octreotide therapy leading to a reduction and normalization of PP levels. The patient tolerated octreotide therapy but self-discontinued octreotide after 24 months with a rise in PP levels off therapy. Tumors remained stable in size through 40 months of imaging follow-up. In patients with MEN1 and subcentimeter pNETs, octreotide therapy is well tolerated and can lead to a significant drop in PP levels with no change in lesion size. There is insufficient data to suggest long-term benefit with octreotide therapy but it may be considered versus standard conservative management.

PMID: 31183223 [PubMed]

Metastatic retroperitoneal paraganglioma: Case report and review of the literature.

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

Metastatic retroperitoneal paraganglioma: Case report and review of the literature.

Clin Oncol (Belmont). 2019 Mar;4:

Authors: Tabakin AL, Weintraub MA, Radadia KD, Salazar CG, Sadimin E, Singer EA

Abstract
Paragangliomas are rare neuroendocrine tumors with 500 to 1600 new cases in the United States each year (1). The clinical presentation may range from asymptomatic to the classic triad of episodic diaphoresis, headache, and palpitations. Surgery is the hallmark of treatment when tumors are amenable to resection. When patients are found to have metastases, systemic therapies may be employed. In this case report, we present a patient found to have a large retroperitoneal paraganglioma with nodal metastases.

PMID: 31179416 [PubMed]

Permalink for 'Efficacy of perioperative chemotherapy for pulmonary high-grade neuroendocrine carcinomas: a propensity score matching analysis.'

Efficacy of perioperative chemotherapy for pulmonary high-grade neuroendocrine carcinomas: a propensity score matching analysis.

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

Efficacy of perioperative chemotherapy for pulmonary high-grade neuroendocrine carcinomas: a propensity score matching analysis.

J Thorac Dis. 2019 Apr;11(4):1145-1154

Authors: Ogawa H, Tanaka Y, Kitamura Y, Shimizu N, Doi T, Hokka D, Tane S, Nishio W, Yoshimura M, Maniwa Y

Abstract
Background: Large-cell neuroendocrine carcinoma (LCNEC) and small cell lung cancer (SCLC) are categorized as high-grade neuroendocrine carcinoma (HGNEC). We analyzed the efficacy of perioperative chemotherapy for HGNEC and the prognostic factors.
Methods: We retrospectively reviewed the medical records of patients who underwent tumor resection and were diagnosed with HGNEC between January 2001 and December 2014. The overall survival (OS) was estimated by the Kaplan-Meier method. Propensity score matching was performed to compare the OS between the treatment groups. Multivariate analyses using a Cox proportional hazards model were performed to search for prognostic factors for HGNEC.
Results: We analyzed 146 HGNEC patients (LCNEC n=92, SCLC n=54) without synchronous multiple cancers, who underwent complete resection. Seventy patients (LCNEC n=31, SCLC n=32) received perioperative chemotherapy and all of them received a platinum-based anticancer drug. Perioperative chemotherapy significantly improved the 5-year OS rates of HGNEC patients (all stages: 74.5% vs. 34.7%, P<0.01, stage I: 88.5% vs. 40.0%, P<0.01). The efficacy of perioperative chemotherapy was similar between LCNEC and SCLC patients [LCNEC all stages: hazard ratio (HR) 0.27, P<0.01, LCNEC stage I: HR 0.27, P=0.01; SCLC all stages: HR 0.38, P=0.02, SCLC stage I: HR 0.34, P=0.06]. The survival benefit of perioperative chemotherapy for HGNEC patients was confirmed by propensity score matching analysis (HR 0.31, P<0.01). The multivariate analysis revealed that perioperative chemotherapy (HR 0.29, P<0.01), sublobar resection (HR 2.11, P=0.04), and lymph node metastasis (HR 3.34, P<0.01) were independently associated with survival.
Conclusions: Surgical resection combined with perioperative chemotherapy was considered to be effective even for stage I HGNEC patients. Sublobar resection might increase the risk of death in HGNEC patients.

PMID: 31179056 [PubMed]

[Diagnosis of pancreatic neuroendocrine tumor led to diagnosis of multiple endocrine neoplasia type 1:a report of two cases].

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

[Diagnosis of pancreatic neuroendocrine tumor led to diagnosis of multiple endocrine neoplasia type 1:a report of two cases].

Nihon Shokakibyo Gakkai Zasshi. 2019;116(6):531-539

Authors: Toriyama K, Hijioka S, Oseto K, Mizuno N, Tanaka T, Ishihara M, Tajika M, Shimizu Y, Hara K, Niwa Y

Abstract
Two cases of multiple endocrine neoplasia type 1 are reported. In both cases, computed tomography (CT) showed hypervascular lesions of the pancreas. Endoscopic ultrasound showed multiple lesions in the pancreas, and each case was diagnosed as pancreatic neuroendocrine tumor by EUS-FNA. In addition to a pancreatic neuroendocrine tumor, case 1 had hyperparathyroidism and case 2 had a history of parathyroid tumor. Furthermore, case 1 had a family history of pancreatic tumor and case 2 had a family history of pancreatic tumor and parathyroid resection. From these indications, multiple endocrine neoplasia type 1 was diagnosed by genetic testing. As demonstrated in these two cases, it is important to consider multiple endocrine neoplasia type 1 when diagnosing pancreatic neuroendocrine tumor.

PMID: 31178583 [PubMed - in process]

Neuroendocrine Tumor Treated with Arterial Chemoembolization Using DEB-TACE.

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

Neuroendocrine Tumor Treated with Arterial Chemoembolization Using DEB-TACE.

Intern Med. 2019 Jun 07;:

Authors: Suzuki K, Yoneda M, Kobayashi N, Nakajima A

PMID: 31178516 [PubMed - as supplied by publisher]

Permalink for 'Synchronous Early Gastric Cancer/Neuroendocrine Tumor Associated with Autoimmune Gastritis Completely Resected with Endoscopic Submucosal Dissection: A Case Report.'

Synchronous Early Gastric Cancer/Neuroendocrine Tumor Associated with Autoimmune Gastritis Completely Resected with Endoscopic Submucosal Dissection: A Case Report.

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

Synchronous Early Gastric Cancer/Neuroendocrine Tumor Associated with Autoimmune Gastritis Completely Resected with Endoscopic Submucosal Dissection: A Case Report.

Intern Med. 2019 Jun 07;:

Authors: Kubo K, Kimura N, Matsuda S, Mabe K, Kato M

Abstract
Synchronous early gastric cancer/neuroendocrine tumor (NET) associated with autoimmune gastritis is rare, and its endoscopic and pathological features remain poorly described. Screening esophagogastroduodenoscopy (EGD) performed on a 71-year-old man revealed a whitish, superficial elevated lesion and a submucosal tumor with redness that appeared slightly centrally depressed. Endoscopic submucosal dissection allowed these lesions to be resected with negative margins, and they were diagnosed as tubular adenocarcinoma, well-differentiated type (tub1), pT1a (M) and NET G1, pT1b (SM). To our knowledge, this is the first report describing the endoscopic and pathological findings of synchronous early gastric cancer/NET that was amenable to complete resection with ESD.

PMID: 31178500 [PubMed - as supplied by publisher]

A case of pedunculated duodenal neuroendocrine tumor.

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

A case of pedunculated duodenal neuroendocrine tumor.

Dig Endosc. 2019 Jun 08;:

Authors: Katsurahara M, Miura H, Horiki N

Abstract
A 68-year-old man with a medical history of chronic pancreatitis underwent computed tomography (CT) at our hospital for a detailed examination of his pancreas. Incidentally, the CT revealed an enhanced mass in the third portion of duodenum. An upper endoscopy analysis found a pedunculated polyp in the third portion of duodenum, the long stalk of which arose from the wall of the second portion (Fig. 1(a) (b)). The polyp head was slightly lobulated and the surface was completely covered with normal duodenal mucosa, suggesting a submucosal tumor (Fig. 1(c)). We performed endoscopy with magnifying narrow-band imaging (NBI) and found neither abnormal vessels nor irregular structures. This article is protected by copyright. All rights reserved.

PMID: 31177568 [PubMed - as supplied by publisher]

Ca2+ channels toolkit in Neuroendocrine tumors.

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

Ca2+ channels toolkit in Neuroendocrine tumors.

Neuroendocrinology. 2019 Jun 10;:

Authors: Fiorio Pla A, Gkika D

Abstract
Neuroendocrine tumors (NET) constitute an heterogenous group of malignancies with various clinical presentations and growth rates but all rising from neuroendocrine cells located all over the body. NET present a relatively low frequency disease being mostly represented by gastroenteropancreatic (GEP) and bronchopulmonary tumors (pNET); on the other hand an increasing frequency and prevalence has been associated to NET. Beside the great effort of the latest years, management of NET is still a critical unmet point due to the lack in the knowledge of the biology of the disease, lack of adequate biomarkers, late presentation, the relative insensitivity of imaging modalities and a paucity of predictably effective treatment options. In this context Ca2+ signals, being pivotal molecular devices in sensing and integrating signals from the microenvironment, are emerging to be particularly relevant in cancer, where they mediate interactions between tumor cells and the tumor microenvironment to drive different aspects of neoplastic progression (e.g. cell proliferation and survival, cell invasiveness and pro-angiogenetic programs). Indeed, ion channels represent good potential pharmacological targets due to their location on the plasma membrane, where they can be easily accessed by drugs. The present review aims to provide a critical and up to date overview on NET development integrating Ca2+ signals involvement. In this perspective, we first give an introduction to NET and Ca2+ channels and then describe the different families of Ca2+ channels implicated in NET, namely ionotropic receptors, voltage-dependent Ca2+ channels, Transient Receptor Potential channels as well as intracellular Ca2+ channels and their signaling molecules.

PMID: 31177261 [PubMed - as supplied by publisher]

DEPTOR inhibits cell proliferation and confers sensitivity to dopamine agonist in pituitary adenoma.

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

DEPTOR inhibits cell proliferation and confers sensitivity to dopamine agonist in pituitary adenoma.

Cancer Lett. 2019 Jun 06;:

Authors: Yao H, Tang H, Zhang Y, Zhang QF, Liu XY, Liu YT, Gu WT, Zheng YZ, Shang HB, Wang Y, Huang JY, Wei YX, Zhang X, Zhang J, Wu ZB

Abstract
DEP domain-containing mechanistic target of rapamycin (mTOR)-interacting protein (DEPTOR) is an important modulator of mTOR, a highly conserved kinase, whose hyperactivation is critically involved in a variety of human tumors. However, the role of DEPTOR playing in pituitary adenoma (PA) is largely unknown. Here, we reported that DEPTOR was downregulated in PA tissues, especially dopamine-resistant prolactinomas. Consistently, overexpression of DEPTOR inhibited pituitary tumor GH3 and MMQ cells proliferation in vitro and in vivo, and sensitized GH3 and MMQ cells to cabergoline (CAB), a dopamine agonist (DA). Conversely, knockdown of DEPTOR promoted GH3 and MMQ cells proliferation, and conferred cells resistance to CAB. Mechanistically, DEPTOR inhibited both mTOR Complex 1 (mTORC1) and 2 (mTORC2) activities in PA cells. In addition, DEPTOR expression level was increased to suppress mTOR kinase activity via decreasing E3 ubiquitin ligase, βTrCP1, in response to CAB. Furthermore, DEPTOR enhanced autophagy-dependent cell death to confer cells sensitivity to CAB. Taken together, our results suggest that DEPTOR may be a potential target for the treatment of PAs.

PMID: 31176743 [PubMed - as supplied by publisher]

[Clinical features and surgical treatment of neurilemmoma versus carotid body tumors at bifurcation of carotid artery].

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

[Clinical features and surgical treatment of neurilemmoma versus carotid body tumors at bifurcation of carotid artery].

Zhejiang Da Xue Xue Bao Yi Xue Ban. 2018 Dec 25;47(6):583-587

Authors: Shao H, Liu F, Zhang W, Wang L, Chen B, Jiang J, Dong Z, Shi Y, Guo D, Fu W

Abstract
OBJECTIVE: To analyze clinical features, surgical treatment and outcomes of neurilemmoma and carotid body tumors in bifurcation of carotid artery.
METHODS: The clinical data of 17 patients with neurilemmomas and 76 patients with carotid body tumors at the bifurcation of carotid artery, who were surgically treated in Zhongshan Hospital of Fudan University from March 2012 to November 2016, were retrospectively analyzed. The clinicopathological characteristics, surgical procedures and outcomes were compared between two groups.
RESULTS: No difference of preoperative clinical demographic data was found between two groups. Operation time of the neurilemmoma group was significantly shorter than that of the carotid body tumor group[(93.9±30.8) min vs. (159.3±52.9) min, P<0.01]. The neurilemmoma group had lower volume of intra-operative blood loss[(110±96) mL vs. (356±239) mL, P<0.01] and lower rate of external carotid artery resection (11.8% vs. 68.4%, P<0.01) than the carotid body tumor group. In the neurilemmoma group, 17 tumors were completely resected and no malignant disease was found. In the carotid body tumor group, 76 patients underwent complete surgical resection for the tumor, of which 5 (6.6%) were malignant. Tumor size of the neurilemmoma group was larger than that of the carotid body tumor group[(4.5±1.4) cm vs. (3.1±1.0) cm, P<0.01]. There was no significant difference in the incidence of peri-operative complications and length of hospital stay between two groups (P>0.05).
CONCLUSIONS: The clinical manifestations of neurilemmoma and carotid body tumors at carotid artery bifurcation are similar. The carotid body tumor group has a longer operating time, larger intra-operative blood loss, higher external carotid resection rate and relative higher incidence of malignancy. More cautions should be given when carotid body tumors at carotid artery bifurcation are treated.

PMID: 30900834 [PubMed - indexed for MEDLINE]

Resveratrol as a Multifunctional Topical Hypopigmenting Agent.

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

Resveratrol as a Multifunctional Topical Hypopigmenting Agent.

Int J Mol Sci. 2019 Feb 22;20(4):

Authors: Na JI, Shin JW, Choi HR, Kwon SH, Park KC

Abstract
Melanin is produced in melanocytes and stored in melanosomes, after which it is transferred to keratinocytes and, thus, determines skin color. Despite its beneficial sun-protective effects, abnormal accumulation of melanin results in esthetic problems. A range of topical hypopigmenting agents have been evaluated for their use in the treatment of pigmentary disorders with varying degrees of success. Hydroquinone (HQ), which competes with tyrosine, is the main ingredient in topical pharmacological agents. However, frequent occurrence of adverse reactions is an important factor that limits its use. Thus, efforts to discover effective topical hypopigmenting agents with less adverse effects continue. Here, we describe the potential of resveratrol to function as an effective hypopigmenting agent based on its mechanism of action. Resveratrol is not only a direct tyrosinase inhibitor but an indirect inhibitor as well. Additionally, it can affect keratinocytes, which regulate the function of melanocytes. Resveratrol regulates the inflammatory process of keratinocytes and protects them from oxidative damage. In this way, it prevents keratinocyte-induced melanocyte stimulation. Furthermore, it has a rescuing effect on the stemness of interfollicular epidermal cells that can repair signs of photoaging in the melasma, a typical pigmentary skin disorder. Overall, resveratrol is a promising potent hypopigmenting agent.

PMID: 30813264 [PubMed - indexed for MEDLINE]

Amelanotic primary vaginal melanoma: A case report with cyto-histological correlations.

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

Amelanotic primary vaginal melanoma: A case report with cyto-histological correlations.

Diagn Cytopathol. 2019 Mar;47(3):230-233

Authors: Boggio F, Lopez G, Del Gobbo A, Scarfone G, Marchini M, Cribiù FM

Abstract
Vaginal mucosa represents a rare site for primary melanoma. These neoplasms more commonly occur in the postmenopausal period, usually presenting with vaginal discharge, bleeding, or palpable mass. We report a case of an 89-year-old woman presenting with vaginal bleeding and a non-pigmented lesion in the lower third of the vagina at the gynaecological examination. A PAP smear and tissue incisional biopsy were concurrently performed. The cytological sample showed a subpopulation of non-cohesive, atypical epithelioid cells suggestive for malignancy. The histological examination showed the same morphological characteristics in the neoplastic population widely underlying the vaginal epithelium, with scattered intraepithelial nests and single elements. In both samples, there was no evidence of melanin pigment within the malignant cells. Immunohistochemical analysis performed on the tissue biopsy demonstrated a strong and diffuse positivity for melanocytic markers (HMB-45, S-100, Melan-A), confirming the diagnosis of primary amelanotic vaginal melanoma.

PMID: 30478998 [PubMed - indexed for MEDLINE]

Suicide Risk in Melanoma: What Do We Know?

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

Suicide Risk in Melanoma: What Do We Know?

Am Surg. 2017 Nov 01;83(11):e435-e437

Authors: Komic A, Taludker A, Walsh N, Jones A, Lawson A, Bateson B, Kruse EJ

PMID: 30454229 [PubMed - indexed for MEDLINE]

Permalink for 'Certainty within uncertainty: a qualitative study of the experience of metastatic melanoma patients undergoing pembrolizumab immunotherapy.'

Certainty within uncertainty: a qualitative study of the experience of metastatic melanoma patients undergoing pembrolizumab immunotherapy.

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

Certainty within uncertainty: a qualitative study of the experience of metastatic melanoma patients undergoing pembrolizumab immunotherapy.

Support Care Cancer. 2019 May;27(5):1845-1852

Authors: Levy D, Dhillon HM, Lomax A, Marthick M, McNeil C, Kao S, Lacey J

Abstract
OBJECTIVE: Little is known about the lived experiences of patients with metastatic melanoma undergoing checkpoint inhibitor treatment. We conducted a feasibility study of a supportive care intervention for melanoma patients being treated with pembrolizumab. Here, we report a secondary objective of the study, which was to explore the lived experience of being on pembrolizumab treatment for advanced melanoma.
METHODS: Twenty-eight participants with metastatic melanoma were recruited across two cohorts, all receiving 3-weekly immunotherapy treatment. Semi-structured interviews were conducted with 26 participants once at 9 weeks. Thematic analysis using interpretative phenomenological analysis (IPA) was performed with multiple iterations of data review to achieve consensus.
RESULTS: Three overarching themes were identified; here, we report the first and most dominant theme: how metastatic melanoma patients live within uncertain spaces. Although immunotherapy increases overall survival, metastatic melanoma patients live within an uncertain spectrum. They confront uncertainty related to immunotherapy treatment, their disease trajectory, family relationships, and decision-making. Melanoma patients attempt to normalize their lives, engaging in their usual activities. Uncertainty increases prior to active treatment and intensifies during investigation phases.
CONCLUSIONS: Despite progress in melanoma patient treatment and outcomes, these patients face sustained uncertainty about their disease trajectory.

PMID: 30178142 [PubMed - indexed for MEDLINE]

Exome analysis of carotid body tumor.

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

Exome analysis of carotid body tumor.

BMC Med Genomics. 2018 02 13;11(Suppl 1):17

Authors: Snezhkina AV, Lukyanova EN, Kalinin DV, Pokrovsky AV, Dmitriev AA, Koroban NV, Pudova EA, Fedorova MS, Volchenko NN, Stepanov OA, Zhevelyuk EA, Kharitonov SL, Lipatova AV, Abramov IS, Golovyuk AV, Yegorov YE, Vishnyakova KS, Moskalev AA, Krasnov GS, Melnikova NV, Shcherbo DS, Kiseleva MV, Kaprin AD, Alekseev BY, Zaretsky AR, Kudryavtseva AV

Abstract
BACKGROUND: Carotid body tumor (CBT) is a form of head and neck paragangliomas (HNPGLs) arising at the bifurcation of carotid arteries. Paragangliomas are commonly associated with germline and somatic mutations involving at least one of more than thirty causative genes. However, the specific functionality of a number of these genes involved in the formation of paragangliomas has not yet been fully investigated.
METHODS: Exome library preparation was carried out using Nextera® Rapid Capture Exome Kit (Illumina, USA). Sequencing was performed on NextSeq 500 System (Illumina).
RESULTS: Exome analysis of 52 CBTs revealed potential driver mutations (PDMs) in 21 genes: ARNT, BAP1, BRAF, BRCA1, BRCA2, CDKN2A, CSDE1, FGFR3, IDH1, KIF1B, KMT2D, MEN1, RET, SDHA, SDHB, SDHC, SDHD, SETD2, TP53BP1, TP53BP2, and TP53I13. In many samples, more than one PDM was identified. There are also 41% of samples in which we did not identify any PDM; in these cases, the formation of CBT was probably caused by the cumulative effect of several not highly pathogenic mutations. Estimation of average mutation load demonstrated 6-8 mutations per megabase (Mb). Genes with the highest mutation rate were identified.
CONCLUSIONS: Exome analysis of 52 CBTs for the first time revealed the average mutation load for these tumors and also identified potential driver mutations as well as their frequencies and co-occurrence with the other PDMs.

PMID: 29504908 [PubMed - indexed for MEDLINE]

Acute autoimmune myocarditis and hepatitis due to ipilimumab monotherapy for malignant melanoma.

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

Acute autoimmune myocarditis and hepatitis due to ipilimumab monotherapy for malignant melanoma.

J Oncol Pharm Pract. 2019 Jun;25(4):966-968

Authors: Samara Y, Yu CL, Dasanu CA

Abstract
An important agent in melanoma therapy, ipilimumab is associated with autoimmune toxicity. Two cases of autoimmune pericarditis and large pericardial effusion have been documented with its use. Reports of myocardial toxicity have surfaced with this agent, mainly when used in combination with PD1 blockade. We present herein a case of autoimmune myocarditis leading to biventricular failure after four doses of IV ipilimumab 3 mg/kg as a single agent. Furthermore, this toxic effect may be anticipated with PD1 inhibitors. Increased clinical suspicion, prompt diagnosis, and steroid therapy are crucial to ensure a favorable clinical outcome.

PMID: 29444608 [PubMed - indexed for MEDLINE]

Melanoma of the Sinonasal Tract: Value of a Septate Pattern on Precontrast T1-Weighted MR Imaging.

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

Melanoma of the Sinonasal Tract: Value of a Septate Pattern on Precontrast T1-Weighted MR Imaging.

AJNR Am J Neuroradiol. 2018 Apr;39(4):762-767

Authors: Kim YK, Choi JW, Kim HJ, Kim HY, Park GM, Ko YH, Cha J, Kim ST

Abstract
BACKGROUND AND PURPOSE: Various tumors of the sinonasal tract can exhibit high signal intensity on T1WI. The purpose of this study was to determine the value of a septate pattern on precontrast T1WI for diagnosing sinonasal melanoma.
MATERIALS AND METHODS: Retrospectively, 3 observers independently reviewed MR images of 31 histologically proved sinonasal melanomas with special attention to the presence or absence of a septate pattern on precontrast T1WI, defined as alternating hyperintense and hypointense striations on precontrast T1WI. For comparison, we evaluated the prevalence of a septate pattern on precontrast T1WI in 106 nonmelanomatous sinonasal malignant tumors with 16 different histologic types. We also tried to identify the histopathologic features responsible for the septate pattern on precontrast T1WI.
RESULTS: Twenty-seven (87.1%) of 31 sinonasal melanomas showed hyperintense foci on T1WI, among which a septate pattern on precontrast T1WI was seen in 23 (74.2%), while 22 (20.8%) of 106 nonmelanomatous malignant tumors demonstrated hyperintense foci on T1WI, among which only 3 (2.8%) showed a septate pattern on precontrast T1WI. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of a septate pattern on precontrast T1WI for the diagnosis of sinonasal melanoma were 74%, 97%, 88%, 93%, and 92%, respectively. Although limited due to the retrospective nature, 4 of 23 histologically reviewed sinonasal melanomas revealed an uneven distribution of melanin with alternating melanin and fibrous bands within the tumors.
CONCLUSIONS: A septate pattern on precontrast T1WI might be an adjunctive imaging finding for the diagnosis of sinonasal melanoma. This might be attributed histologically to an uneven distribution of melanin and hemorrhage within the tumors.

PMID: 29371259 [PubMed - indexed for MEDLINE]

Permalink for 'Combination Ipilimumab and Nivolumab for Metastatic Melanoma Associated With Ciliochoroidal Effusion and Exudative Retinal Detachment.'

Combination Ipilimumab and Nivolumab for Metastatic Melanoma Associated With Ciliochoroidal Effusion and Exudative Retinal Detachment.

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

Combination Ipilimumab and Nivolumab for Metastatic Melanoma Associated With Ciliochoroidal Effusion and Exudative Retinal Detachment.

JAMA Ophthalmol. 2017 Dec 01;135(12):1455-1457

Authors: Tsui E, Madu A, Belinsky I, Yannuzzi LA, Freund KB, Modi YS

PMID: 29145556 [PubMed - indexed for MEDLINE]

Molecular Characteristics of Conjunctival Melanoma Using Whole-Exome Sequencing.

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

Molecular Characteristics of Conjunctival Melanoma Using Whole-Exome Sequencing.

JAMA Ophthalmol. 2017 12 01;135(12):1434-1437

Authors: Swaminathan SS, Field MG, Sant D, Wang G, Galor A, Dubovy SR, Harbour JW, Karp CL

Abstract
Importance: Conjunctival melanoma (CM) is a highly aggressive ocular cancer for which treatment options are limited; the molecular pathogenesis is poorly understood.
Objective: To identify the molecular characteristics of CM using next-generation whole-exome sequencing (WES).
Design, Setting, and Participants: Whole-exome sequencing was performed on tumor DNA extracted from the archived specimens of 5 patients with CM who had been treated with surgical excision between 2006 and 2011. These samples were analyzed at a tertiary academic ocular oncology referral center using a customized bioinformatic pipeline.
Main Outcomes and Measures: Sample analyses were designed to detect driver mutations, chromosome copy number aberrations, and mutation signatures.
Results: The study’s 5 patients ranged in age from 51 to 77 years. Four of the 5 were female, and all were white. Mutations were detected in known oncogenes, including BRAF, NRAS, NF1, EGFR, ALK, TERT, and APC. None of the mutations associated with uveal melanoma were found. All samples demonstrated a C→T mutation signature typical of UV-induced DNA damage. The most common CNA was a gain in chromosome 6p.
Conclusions and Relevance: In these 5 patients, WES allowed identification of mutations that can be targeted with therapy and supported the role of UV light in CM pathogenesis. These findings indicate a need for larger studies to evaluate the diagnostic, prognostic, and therapeutic value of WES for CM.

PMID: 29121185 [PubMed - indexed for MEDLINE]

Continuous Petri Nets and microRNA Analysis in Melanoma.

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

Continuous Petri Nets and microRNA Analysis in Melanoma.

IEEE/ACM Trans Comput Biol Bioinform. 2018 Sep-Oct;15(5):1492-1499

Authors: Russo G, Pennisi M, Boscarino R, Pappalardo F

Abstract
Personalized target therapies represent one of the possible treatment strategies to fight the ongoing battle against cancer. New treatment interventions are still needed for an effective and successful cancer therapy. In this scenario, we simulated and analyzed the dynamics of BRAF V600E melanoma patients treated with BRAF inhibitors in order to find potentially interesting targets that may make standard treatments more effective in particularly aggressive tumors that may not respond to selective inhibitor drugs. To this aim, we developed a continuous Petri Net model that simulates fundamental signalling cascades involved in melanoma development, such as MAPK and PI3K/AKT, in order to deeply analyze these complex kinase cascades and predict new crucial nodes involved in melanomagenesis. The model pointed out that some microRNAs, like hsa-mir-132, downregulates expression levels of p120RasGAP: under high concentrations of p120RasGAP, MAPK pathway activation is significantly decreased and consequently also PI3K/PDK1/AKT activation. Furthermore, our analysis carried out through the Genomic Data Commons (GDC) Data Portal shows the evidence that hsa-mir-132 is significantly associated with clinical outcome in melanoma cancer genomic data sets of BRAF-mutated patients. In conclusion, targeting miRNAs through antisense oligonucleotides technology may suggest the way to enhance the action of BRAF-inhibitors.

PMID: 28767374 [PubMed - indexed for MEDLINE]

Regression of Iris Metastasis After Systemic Treatment With Melanoma-Targeted Therapy.

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

Regression of Iris Metastasis After Systemic Treatment With Melanoma-Targeted Therapy.

JAMA Ophthalmol. 2017 Feb 09;135(2):e165462

Authors: Fonseca C, Fernandes J, Proença R

PMID: 28196206 [PubMed - indexed for MEDLINE]

Biological Activities of Extracts from Different Parts of Cryptomeria japonica.

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

Biological Activities of Extracts from Different Parts of Cryptomeria japonica.

Nat Prod Commun. 2016 Sep;11(9):1337-1342

Authors: Horiba H, Nakagawa T, Zhu Q, Ashour A, Watanabe A, Shimizu K

Abstract
Cryptomeria japonica is one of the most important forest tree species in Japan. To increase the demand for domestic timber, broad uses related to the functional attributes of C. japonica must be developed. Several studies have examined the usefulness of C. japonica in terms of its biological activities, but a comprehensive study subjecting all parts of the C. japonica plant to the same solvent for extraction has not been done. Here, methanol extractions from the leaves, branches, bearing branches, male flowers, female flowers, cones, bark, heartwood, sapwood, pith, rhizomes, roots, and pollen were subjected to several in vitro assays of their biological activities such as antioxidant activity, anti-lipase activity, antibacterial activity and melanin-biosynthesis-inhibition activity. Their total phenolic content was also determined. The methanol extracts from each part of C. japonica except for pollen showed strong activities in the bioactivity assays. Furthermore, the methanol extracts were analyzed by GC/MS. The phytochemical profile varied among extracts from various parts of C. japonica. Our results suggest the great potential of C. japonica for use as a functional ingredient in health-related products.

PMID: 30807038 [PubMed - indexed for MEDLINE]

Permalink for 'Activity and Safety of Standard and Prolonged Capecitabine/Temozolomide Administration in Patients with Advanced Neuroendocrine Neoplasms.'

Activity and Safety of Standard and Prolonged Capecitabine/Temozolomide Administration in Patients with Advanced Neuroendocrine Neoplasms.

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

Activity and Safety of Standard and Prolonged Capecitabine/Temozolomide Administration in Patients with Advanced Neuroendocrine Neoplasms.

Neuroendocrinology. 2019 Jun 03;:

Authors: Chatzellis E, Angelousi A, Daskalakis K, Tsoli M, Alexandraki KI, Wachuła E, Meirovitz A, Maimon O, Grozinsky-Glasberg S, Gross D, Kos-Kudła B, Koumarianou A, Kaltsas G

Abstract
BACKGROUND: Capecitabine and temozolomide combination (CAPTEM) is associated with high response rates in patients with advanced neuroendocrine neoplasms (NENs). We evaluated the real-world activity and safety of CAPTEM from 3 NEN centers.
METHODS: Clinicopathological characteristics and outcome

Rare Cancer News & Clinical Trials » Endocrine/Neuroendocrine

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Endocrine/Neuroendocrine (527 unread)

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