Rare Cancer News & Clinical Trials » Endocrine/Neuroendocrine

Endocrine/Neuroendocrine (533 unread)

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

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

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

Int J Surg Pathol. 2019 Oct 10;:1066896919880260

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

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

PMID: 31601140 [PubMed - as supplied by publisher]

Rapidly Growing Eyelid Mass in an Elderly Man.

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

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Rapidly Growing Eyelid Mass in an Elderly Man.

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

Authors: Messenger WB, Liu CY, Aakalu VK

PMID: 29543951 [PubMed - indexed for MEDLINE]

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

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

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

Microb Pathog. 2019 Oct 07;:103778

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

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

PMID: 31600537 [PubMed - as supplied by publisher]

[Head & Neck Merkel Cell Carcinoma].

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

[Head & Neck Merkel Cell Carcinoma].

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

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

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

PMID: 30005427 [PubMed - indexed for MEDLINE]

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

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

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

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

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

PMID: 31495098 [PubMed - indexed for MEDLINE]

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

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

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

Int J Gynecol Pathol. 2019 Oct 03;:

Authors: Harkness R, Kelly PJ, McCluggage WG

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

PMID: 31584482 [PubMed - as supplied by publisher]

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

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

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

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

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

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

PMID: 31582892 [PubMed]

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

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

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

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

Clin Cancer Res. 2019 Oct 03;:

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

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

PMID: 31582519 [PubMed - as supplied by publisher]

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

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

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

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

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

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

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

PMID: 31570452 [PubMed - in process]

Merkel Cell Carcinoma: A Case Series

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

Merkel Cell Carcinoma: A Case Series

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

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

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

PMID: 30556674 [PubMed - indexed for MEDLINE]

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

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

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

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

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

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

PMID: 29616562 [PubMed - indexed for MEDLINE]

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

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

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

Book. 2019 03 20

Authors: Ho C, Argáez C

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

PMID: 31553552

Merkel cell carcinoma: A series of seven cases.

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

Merkel cell carcinoma: A series of seven cases.

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

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

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

PMID: 31550749 [PubMed]

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

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

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

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

Authors: Tun Min S, Nordman IIC, Tran HA

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

PMID: 31543781 [PubMed]

Possible immunotherapies of skin cancers

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

Possible immunotherapies of skin cancers

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

Authors: Lengyel LZS, Gyulai GYR

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

PMID: 31538441 [PubMed - in process]

Cabozantinib in Patients with Advanced Merkel Cell Carcinoma.

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

Cabozantinib in Patients with Advanced Merkel Cell Carcinoma.

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

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

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

PMID: 29445030 [PubMed - indexed for MEDLINE]

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

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

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

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

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

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

PMID: 30073632 [PubMed - indexed for MEDLINE]

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

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

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

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

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

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

PMID: 31527246 [PubMed - as supplied by publisher]

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

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

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

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

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

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

PMID: 31522944 [PubMed - as supplied by publisher]

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

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

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

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

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

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

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

PMID: 30454872 [PubMed - indexed for MEDLINE]

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

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

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

Semin Oncol Nurs. 2019 Sep 09;:150924

Authors: Rubin KM, Hoffner B, Bullock AC

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

PMID: 31514991 [PubMed - as supplied by publisher]

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

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

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

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

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

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

PMID: 29777657 [PubMed - indexed for MEDLINE]

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

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

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

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

Authors: Perez MC, Zager JS

Abstract

PMID: 30151562 [PubMed - indexed for MEDLINE]

Immune checkpoint inhibitors of PD-L1 as cancer therapeutics.

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

Immune checkpoint inhibitors of PD-L1 as cancer therapeutics.

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

Authors: Akinleye A, Rasool Z

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

PMID: 31488176 [PubMed - in process]

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

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

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

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

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

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

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

PMID: 29409030 [PubMed - indexed for MEDLINE]

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

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

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

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

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

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

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

PMID: 31274613 [PubMed - indexed for MEDLINE]

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

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

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

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

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

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

PMID: 30407150 [PubMed - indexed for MEDLINE]

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

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

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

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

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

Authors: Pincus J

PMID: 30152112 [PubMed - indexed for MEDLINE]

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

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

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

J Am Acad Dermatol. 2019 Aug 29;:

Authors: Cheraghlou S, Agogo GO, Girardi M

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

PMID: 31473294 [PubMed - as supplied by publisher]

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

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

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

Cell Immunol. 2019 Aug 01;:103961

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

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

PMID: 31472938 [PubMed - as supplied by publisher]

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

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

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

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

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

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

PMID: 31471421 [PubMed - in process]

[Immune checkpoint inhibition in Merkel cell carcinoma].

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

[Immune checkpoint inhibition in Merkel cell carcinoma].

Hautarzt. 2019 Aug 29;:

Authors: Terheyden P, Mohr A, Langan EA

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

PMID: 31468071 [PubMed - as supplied by publisher]

Updates on Merkel Cell Carcinoma.

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

Updates on Merkel Cell Carcinoma.

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

Authors: Emge DA, Cardones AR

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

PMID: 31466589 [PubMed - in process]

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

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

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

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

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

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

PMID: 31466237 [PubMed]

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

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

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

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

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

PMID: 29265481 [PubMed - indexed for MEDLINE]

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

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

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

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

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

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

PMID: 30865131 [PubMed - indexed for MEDLINE]

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

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

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

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

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

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

PMID: 29377285 [PubMed - indexed for MEDLINE]

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

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

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

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

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

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

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

PMID: 30809835 [PubMed - indexed for MEDLINE]

Distant recurrence of Merkel cell carcinoma after spontaneous regression.

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

Distant recurrence of Merkel cell carcinoma after spontaneous regression.

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

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

PMID: 30230579 [PubMed - indexed for MEDLINE]

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

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

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

Front Oncol. 2019;9:711

Authors: Del Valle L, Piña-Oviedo S

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

PMID: 31440465 [PubMed]

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

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

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

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

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

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

PMID: 31439556 [PubMed - in process]

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

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

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

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

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

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

PMID: 30588655 [PubMed - indexed for MEDLINE]

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

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

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

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

Cancer Immunol Res. 2019 Aug 12;:

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

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

PMID: 31405946 [PubMed - as supplied by publisher]

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

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

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

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

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

Authors: Goto K

PMID: 28841242 [PubMed - indexed for MEDLINE]

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

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

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

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

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

PMID: 28256019 [PubMed - indexed for MEDLINE]

Merkel Cell Polyomavirus Small T Antigen Induces DNA Damage Response.

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

Merkel Cell Polyomavirus Small T Antigen Induces DNA Damage Response.

Intervirology. 2019 Aug 09;:1-5

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

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

PMID: 31401636 [PubMed - as supplied by publisher]

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

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

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

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

Clin Cancer Res. 2019 Aug 09;:

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

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

PMID: 31399473 [PubMed - as supplied by publisher]

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

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

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

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

Cells. 2019 Jul 31;8(8):

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

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

PMID: 31370278 [PubMed - in process]

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

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

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

Front Med (Lausanne). 2019;6:160

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

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

PMID: 31355203 [PubMed]

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

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

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

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

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

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

PMID: 30255436 [PubMed - indexed for MEDLINE]

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

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

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

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

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

PMID: 29797735 [PubMed - indexed for MEDLINE]

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

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

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

Oral Maxillofac Surg. 2019 Jul 24;:

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

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

PMID: 31342210 [PubMed - as supplied by publisher]

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

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

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

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

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

PMID: 30148734 [PubMed - indexed for MEDLINE]

Incidental Merkel Cell Carcinoma Encountered During Mohs Surgery.

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

Incidental Merkel Cell Carcinoma Encountered During Mohs Surgery.

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

Authors: Mafee M, Bennett DD, Swanson AM

PMID: 29933296 [PubMed - indexed for MEDLINE]

BK polyomavirus is a cause of bladder cancer.

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

BK polyomavirus is a cause of bladder cancer.

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

Authors: Starrett GJ, Buck CB

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

PMID: 31336246 [PubMed - as supplied by publisher]

Iatrogenic solid tumors following immunosuppressive therapy.

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

Iatrogenic solid tumors following immunosuppressive therapy.

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

Authors: Dantey K, Pantanowitz L

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

PMID: 29066044 [PubMed - indexed for MEDLINE]

Skin ultrasound features of Merkel cell carcinoma.

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

Skin ultrasound features of Merkel cell carcinoma.

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

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

PMID: 28045198 [PubMed - indexed for MEDLINE]

Endoscopic ultrasound diagnosis of Merkel cell carcinoma metastasising to pancreas.

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

Endoscopic ultrasound diagnosis of Merkel cell carcinoma metastasising to pancreas.

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

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

PMID: 29665210 [PubMed - indexed for MEDLINE]

Merkel cell carcinoma: morphologic aspects on reflectance confocal microscopy.

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

Merkel cell carcinoma: morphologic aspects on reflectance confocal microscopy.

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

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

PMID: 28502121 [PubMed - indexed for MEDLINE]

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

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

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

J Geriatr Oncol. 2019 Jul 11;:

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

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

PMID: 31303463 [PubMed - as supplied by publisher]

What's new in HIV dermatology?

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

What's new in HIV dermatology?

F1000Res. 2019;8:

Authors: Coates SJ, Leslie KS

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

PMID: 31297183 [PubMed - in process]

Atypical case of Merkel cell carcinoma difficult to diagnose clinically.

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

Atypical case of Merkel cell carcinoma difficult to diagnose clinically.

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

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

PMID: 28328104 [PubMed - indexed for MEDLINE]

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

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

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

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

J Invest Dermatol. 2019 Jul 06;:

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

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

PMID: 31288011 [PubMed - as supplied by publisher]

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

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

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

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

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

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

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

PMID: 31287031 [PubMed - in process]

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

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

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

J Invest Dermatol. 2019 Jul 05;:

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

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

PMID: 31283928 [PubMed - as supplied by publisher]

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

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

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

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

J Eur Acad Dermatol Venereol. 2019 Jul 07;:

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

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

PMID: 31281986 [PubMed - as supplied by publisher]

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

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

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

Oral Oncol. 2019 Jul 02;:

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

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

PMID: 31277904 [PubMed - as supplied by publisher]

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

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

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

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

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

PMID: 28859738 [PubMed - indexed for MEDLINE]

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

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

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

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

Authors: Kini JR, Tapadia R, Shenoy S

PMID: 27377389 [PubMed - indexed for MEDLINE]

In Response.

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

In Response.

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

Authors: Peña Zúñiga EB

PMID: 30299274 [PubMed - indexed for MEDLINE]

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

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

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

Appl Health Econ Health Policy. 2019 Jun 28;:

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

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

PMID: 31250217 [PubMed - as supplied by publisher]

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

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

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

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

Ann Oncol. 2019 Jun 10;:

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

PMID: 31250007 [PubMed - as supplied by publisher]

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

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

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

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

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

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

PMID: 31234633 [PubMed - indexed for MEDLINE]

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

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

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

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

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

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

PMID: 29992788 [PubMed - indexed for MEDLINE]

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

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

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

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

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

PMID: 29631722 [PubMed - indexed for MEDLINE]

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

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

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

Am J Clin Oncol. 2019 Jun 24;:

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

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

PMID: 31246585 [PubMed - as supplied by publisher]

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

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

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

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

Histopathology. 2019 Jun 24;:

Authors: Bellizzi AM

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

PMID: 31233624 [PubMed - as supplied by publisher]

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

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

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

J Cutan Pathol. 2019 Jun 20;:

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

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

PMID: 31218705 [PubMed - as supplied by publisher]

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

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

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

Br J Dermatol. 2019 Jun 17;:

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

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

PMID: 31206594 [PubMed - as supplied by publisher]

Application of PD-1 Blockade in Cancer Immunotherapy.

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

Application of PD-1 Blockade in Cancer Immunotherapy.

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

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

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

PMID: 31205619 [PubMed]

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

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

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

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

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

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

PMID: 30238578 [PubMed - indexed for MEDLINE]

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

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

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

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

Mod Pathol. 2019 Jun 14;:

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

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

PMID: 31201352 [PubMed - as supplied by publisher]

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

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

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

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

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

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

PMID: 31198464 [PubMed]

[What's new in oncodermatology?]

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

[What's new in oncodermatology?]

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

Authors: Robert C

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

PMID: 30583756 [PubMed - indexed for MEDLINE]

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

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

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

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

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

Authors: Lamb EP, Shaw FR, Fleming MD

PMID: 30454322 [PubMed - indexed for MEDLINE]

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

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

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

Int J Cancer. 2019 Jun 10;:

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

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

PMID: 31180579 [PubMed - as supplied by publisher]

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

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

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

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

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

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

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

PMID: 31164102 [PubMed - in process]

Unusual Merkel cell carcinoma: the great pretender.

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

Unusual Merkel cell carcinoma: the great pretender.

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

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

PMID: 28121080 [PubMed - indexed for MEDLINE]

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

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

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

J Am Acad Dermatol. 2019 Jun 01;:

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

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

PMID: 31163235 [PubMed - as supplied by publisher]

Dermoscopy improves diagnostic accuracy for clinically amelanotic nodules.

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

Dermoscopy improves diagnostic accuracy for clinically amelanotic nodules.

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

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

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

PMID: 30123971 [PubMed - indexed for MEDLINE]

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

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

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

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

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

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

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

PMID: 31143109 [PubMed]

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

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

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

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

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

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

PMID: 31142383 [PubMed - in process]

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

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

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

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

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

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

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

PMID: 30565285 [PubMed - indexed for MEDLINE]

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

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

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

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

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

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

PMID: 31128428 [PubMed - as supplied by publisher]

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

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

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

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

Authors: Kim DK

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

PMID: 31127879 [PubMed - in process]

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

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

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

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

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

Abstract

PMID: 30685912 [PubMed - indexed for MEDLINE]

Merkel cells in extraocular sebaceous carcinoma.

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

Merkel cells in extraocular sebaceous carcinoma.

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

Authors: Fernandez-Flores A, Cassarino DS

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

PMID: 30362151 [PubMed - indexed for MEDLINE]

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

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

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

Mol Carcinog. 2019 May 22;:

Authors: Cohen L, Tsai KY

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

PMID: 31116890 [PubMed - as supplied by publisher]

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

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

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

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

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

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

PMID: 30311164 [PubMed - indexed for MEDLINE]

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

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

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

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

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

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

PMID: 30556118 [PubMed - indexed for MEDLINE]

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

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

Conditions: Melanoma; Breast Cancer; Merkel Cell Carcinoma; Squamous Cell Cancer; Non Small Cell Lung Cancer; Cervical Cancer; Urothelial Carcinoma; Ovarian Cancer; Hepatocellular Carcinoma; Small-cell Lung Cancer; Microsatellite Instability High; Gastric Cancer; Esophageal Cancer
Interventions: Device: Echopulse; Drug: Imiquimod; Drug: Standard of Care PD-1 Therapy
Sponsors: Craig L Slingluff, Jr; Theraclion
Not yet recruiting

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

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

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

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

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

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

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

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

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

Adoptive Transfer of Tumor Infiltrating Lymphocytes for Advanced Solid Cancers

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

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

High-Risk Skin Cancers With Atezolizumab Plus NT-I7

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

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

AMPLIFYing NEOepitope-specific VACcine Responses in Progressive Diffuse Glioma

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

A Safety and Tolerability Study of INCAGN02390 in Select Advanced Malignancies

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

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

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

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

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

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

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

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

A Study of INCMGA00012 in Metastatic Merkel Cell Carcinoma

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

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

Lymph Node Identification in Skin Malignancy Using ICG Transcutaneously Study

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

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

A Safety and Tolerability Study of INCAGN02385 in Select Advanced Malignancies

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

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

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

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

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

How Microbes and Metabolism May Predict Skin Cancer Immunotherapy Outcomes

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Studies of Dermatologic Diseases Biospecimen Acquisition Protocol

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

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

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

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

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

Isolated Limb Perfusion of Melphalan for Melanoma and Sarcoma Treatment

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

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

Tamoxifen for Well Differentiated Neurodendocrine Tumors and Hormone Receptor Positive Expression

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

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

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

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

Conditions: Clinical Stage IV Cutaneous Melanoma AJCC v8 (American Joint Committee on Cancer ); IL13RA2 Positive; Metastatic Melanoma; Pathologic Stage IIIC Cutaneous Melanoma AJCC v8; Pathologic Stage IV Cutaneous Melanoma AJCC v8
Interventions: Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Biological: IL13Ralpha2-specific Hinge-optimized 4-1BB-co-stimulatory CAR/Truncated CD19-expressing Autologous TN/MEM Cells; Drug: Recombinant Interleukin-2
Sponsors: Jonsson Comprehensive Cancer Center; National Cancer Institute (NCI)
Not yet recruiting

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Registry of Subjects at Risk of Pancreatic Cancer

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

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

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

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

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

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

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

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

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

Image-Enhanced Endoscopy in the Gastrointestinal Tract

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

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

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

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

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

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

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

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

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

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

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

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

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

Conditions: Metastatic Large Cell Neuroendocrine Carcinoma; Metastatic Neuroendocrine Carcinoma; Metastatic Neuroendocrine Neoplasm; Metastatic Small Cell Carcinoma
Interventions: Drug: Cabozantinib; Drug: Cabozantinib S-malate; Biological: Ipilimumab; Biological: Nivolumab
Sponsor: National Cancer Institute (NCI)
Not yet recruiting

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

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

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

Study of ARRY-614 Plus Either Nivolumab or Ipilimumab

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

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

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

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

Conditions: VHL Pancreatic Neuroendocrine Tumors; Von Hippel-Lindau Disease; Neuroendocrine Tumors
Intervention:
Sponsor: National Cancer Institute (NCI)
Not yet recruiting

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

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

Conditions: Neuroendocrine Tumor; Carcinoid Syndrome
Interventions: Dietary Supplement: Enterade®; Other: Functional Assessment of Chronic Illness Therapy for Patients with Diarrhea (version 4.0)
Sponsors: Vanderbilt-Ingram Cancer Center; Entrinsic Health Solutions, Inc.
Not yet recruiting

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

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

Condition: Melanoma (Skin)
Interventions: Drug: Peptide; Drug: Anti-PD-1; Drug: rhGM-CSF; Drug: Imiquimod 5% Topical Cream
Sponsor: Xiangya Hospital of Central South University
Not yet recruiting

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

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

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

Conditions: Advanced Renal Cell Carcinoma; Chromophobe Renal Cell Carcinoma; Clear Cell Renal Cell Carcinoma; Collecting Duct Carcinoma; Kidney Medullary Carcinoma; Metastatic Malignant Neoplasm in the Bone; Papillary Renal Cell Carcinoma; Stage IV Renal Cell Cancer AJCC v8; Unclassified Renal Cell Carcinoma
Interventions: Drug: Cabozantinib; Drug: Cabozantinib S-malate; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Radiation: Radium Ra 223 Dichloride
Sponsor: National Cancer Institute (NCI)
Not yet recruiting

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

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

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

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

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

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

Resection of Metastatic Pancreatic Neuroendocrine Tumors After Induction System Treatment

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

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

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

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

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

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

Intra-Peritoneal Local Anaesthetics in Ovarian Cancer

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

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

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

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

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

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

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

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

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

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

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

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

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

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

TAS-102 in Extrapulmonary Neuroendocrine Carcinoma

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

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

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

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

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

A Study of SGN-CD228A in Advanced Solid Tumors

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

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

68Ga-DOTATATE PET/CT in Neuroendocrine Tumor

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

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

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

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

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

Improving Skin Cancer Management With Artificial Intelligence (04.17 SMARTI)

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

Conditions: Skin Cancer; Melanoma (Skin)
Intervention: Device: Molemap Skin Cancer Triage Artificial Intelligence Device
Sponsors: Melanoma and Skin Cancer Trials Limited; Molemap Australia Pty Ltd; Monash University, Melbourne
Recruiting

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

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

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

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

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

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

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

The Master Registry of Oncology Outcomes Associated With Testing and Treatment

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

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

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

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

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

Dynamic Whole Body Positron Emission Tomography/Computed Tomography Imaging

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

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

Sonidegib and Pembrolizumab in Treating Patients With Advanced Solid Tumors

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

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

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

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

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

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

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

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

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

3TMPO (Triple-Tracer Strategy Against Metastatic Prostate Cancer

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

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

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

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

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

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

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

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

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

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

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

Cryoablation of Bone Metastases From Endocrine Tumors

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

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

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

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

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

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

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

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

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

PDR001 + Panobinostat for Melanoma and NSCLC

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

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

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

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

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

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

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

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

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

CT Radiomic Features of Pancreatic Neuroendocrine Neoplasms

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

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

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

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

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

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

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

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

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

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

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

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

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

Condition: Pancreatic Neuroendocrine Tumor
Intervention:
Sponsor: Ipsen
Recruiting

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

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

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

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

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

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

Adoptive Transfer of Tumor Infiltrating Lymphocytes for Advanced Solid Cancers

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

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

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

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

Dosimetry Guided PRRT With 177Lu-DOTATATE in Children

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Conditions: Neuroendocrine Carcinoma; Large Cell Neuroendocrine Carcinoma of the Lung; High Grade Neuroendocrine Carcinoma, Any Site
Intervention: Drug: Pembrolizumab
Sponsors: Ochsner Health System; Merck Sharp & Dohme Corp.
Not yet recruiting

High-Risk Skin Cancers With Atezolizumab Plus NT-I7

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Posted: March 27th, 2019, 2:00pm GMT

Conditions: Carcinoma, Non-Small-Cell Lung; Melanoma; Nasopharyngeal Carcinoma; Microsatellite Stable Colorectal Cancer; Triple Negative Breast Cancer
Interventions: Drug: DKY709; Drug: PDR001
Sponsor: Novartis Pharmaceuticals
Recruiting

Al18F-NOTA-octreotide PET Imaging of the Somatostatin Receptor in Neuroendocrine Tumors

Posted: March 21st, 2019, 2:00pm GMT

Condition: Neuroendocrine Tumors
Interventions: Drug: Al18F-NOTA-octreotide; Device: PET/CT; Other: Venous blood samples
Sponsor: Universitaire Ziekenhuizen Leuven
Recruiting

Survivin Long Peptide Vaccine in Treating Patients With Metastatic Neuroendocrine Tumors

Posted: March 19th, 2019, 2:00pm GMT

Conditions: Lung Atypical Carcinoid Tumor; Lung Typical Carcinoid Tumor; Metastatic Pancreatic Neuroendocrine Tumor
Interventions: Biological: Incomplete Freund's Adjuvant; Drug: Octreotide Acetate; Biological: Sargramostim; Biological: SVN53-67/M57-KLH Peptide Vaccine
Sponsors: Roswell Park Cancer Institute; NeuroEndocrine Tumor Research Foundation (NETRF); National Cancer Institute (NCI)
Recruiting

DEBOXA for Inoperable NET Liver Metastases

Posted: March 19th, 2019, 2:00pm GMT

Conditions: Neuroendocrine Tumors; Neoplasm Metastasis; Liver
Intervention: Procedure: D-TACE using CalliSpheres and Oxaliplatin
Sponsor: Xiangya Hospital of Central South University
Recruiting

68Ga-DOTATATE PET for Management of Neuroendocrine Tumors

Posted: March 14th, 2019, 2:00pm GMT

Condition: Neuroendocrine Tumors
Intervention: Diagnostic Test: 68Ga -DOTATATE PET scans
Sponsor: University Health Network, Toronto
Recruiting

Low Dose Ipilimumab With Pembrolizumab in Treating Patients With Melanoma That Has Spread to the Brain

Posted: March 13th, 2019, 2:00pm GMT

Conditions: Clinical Stage IV Cutaneous Melanoma AJCC v8; Metastatic Malignant Neoplasm in the Brain; Metastatic Melanoma; Pathologic Stage IV Cutaneous Melanoma AJCC v8
Interventions: Biological: Ipilimumab; Biological: Pembrolizumab
Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI)
Recruiting

Study of Tamoxifen in Well Differentiated Neuroendocrine Tumors and Hormone Receptor Positive Expression

Posted: March 12th, 2019, 2:00pm GMT

Conditions: Neuroendocrine Tumors; Progesterone Receptor Positive Tumor; Estrogen Receptor Positive Tumor
Intervention: Drug: Tamoxifen
Sponsor: AC Camargo Cancer Center
Recruiting

Cabozantinib S-Malate, Nivolumab, and Ipilimumab in Treating Patients With Metastatic Genitourinary Tumors

Posted: March 7th, 2019, 3:00pm GMT

Conditions: Bladder Adenocarcinoma; Bladder Mixed Adenocarcinoma; Bladder Small Cell Carcinoma; Bladder Squamous Cell Carcinoma; 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; Non-small Cell Lung Carcinoma; Small Cell Lung Carcinoma; Gastric or Gastroesophageal Junction Adenocarcinoma; Advanced or Metastatic Solid Tumors; Prostate Carcinoma; MSI-H; Mismatch Repair Deficiency; Epithelial Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Carcinoma; Intrahepatic Cholangiocarcinoma
Interventions: Biological: XmAb®22841; Biological: Pembrolizumab (Keytruda®)
Sponsors: Xencor, Inc.; ICON Clinical Research
Recruiting

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

Is There a Role for Surgery in Patients with Neuroendocrine Tumors of the Esophagus? A Contemporary View from the NCDB.

Fetched: October 14th, 2019, 5:01am GMT

Is There a Role for Surgery in Patients with Neuroendocrine Tumors of the Esophagus? A Contemporary View from the NCDB.

Ann Surg Oncol. 2019 Oct 11;:

Authors: Erdem S, Troxler E, Warschkow R, Tsai C, Yerokun B, Schmied B, Stettler C, Blazer DG, Hartwig M, Worni M, Gloor B

Abstract
BACKGROUND: Esophageal neuroendocrine tumors (eNETs) are exceedingly rare, aggressive and have a poor prognosis. Treatment guidelines are ill-defined and mainly based on evidence from case reports and analogous experiences drawn from similar disease sites.
METHODS: The NCDB was reviewed for histologically confirmed stage I-III, primary eNETs from 2006 to 2014. Patients were grouped into whether or not they underwent primary tumor resection. Univariate, multivariable, and full bipartite propensity score (PS) adjusted Cox regression analyses were used to assess overall and relative survival differences.
RESULTS: A total of 250 patients were identified. Mean age was 65.0 (standard deviation [SD] 11.9) years, and 174 (69.6%) patients were male. Most patients had stage III disease (n = 136, 54.4%), and the most common type of NET was small cell eNET (n = 111, 44.4%). Chemotherapy was used in 186 (74.4%), radiation therapy in 178 (71.2%), and oncological resection was performed in 69 (27.6%) patients. Crude 2-year survival rates were higher in the operated (57.3%) compared with the nonoperated group (35.2%; p < 0.001). The survival benefit held true after multivariable adjustment (hazard ratio [HR] 0.47, 95% confidence interval [CI] 0.32-0.69, p < 0.001). After full bipartite PS adjustment analysis, survival was longer for patients who received a surgical resection compared with those who did not (HR 0.48, 95% CI 0.31-0.75, p = 0.003) with a corresponding 2-year overall survival rate of 63.3% (95% CI 52.0-77.2) versus 38.8% (95% CI 30.9-48.8), respectively.
CONCLUSIONS: Multimodal treatment that includes surgery is associated with better overall survival for eNETs. Additional research is needed to more definitively identify patients who benefit from esophagectomy and to establish an appropriate treatment algorithm.

PMID: 31605338 [PubMed - as supplied by publisher]

Outcomes of Lymph Node Dissection for Nonmetastatic Pancreatic Neuroendocrine Tumors: To Dissect or Not To Dissect.

Fetched: October 14th, 2019, 5:01am GMT

Outcomes of Lymph Node Dissection for Nonmetastatic Pancreatic Neuroendocrine Tumors: To Dissect or Not To Dissect.

Ann Surg Oncol. 2019 Oct 11;:

Authors: Hua J, Shi S, Yu X

PMID: 31605334 [PubMed - as supplied by publisher]

Permalink for 'Epidemiological Data and Treatment of Gastroenteropancreatic Neuroendocrine Neoplasms: Insights From Tertiary Referral Hospitals in Latvia.'

Epidemiological Data and Treatment of Gastroenteropancreatic Neuroendocrine Neoplasms: Insights From Tertiary Referral Hospitals in Latvia.

Fetched: October 14th, 2019, 5:01am GMT

Epidemiological Data and Treatment of Gastroenteropancreatic Neuroendocrine Neoplasms: Insights From Tertiary Referral Hospitals in Latvia.

World J Surg. 2019 Oct 11;:

Authors: Ptasnuka M, Ozolins A, Narbuts Z, Truskovs A, Sperga M, Plaudis H

Abstract
BACKGROUND: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) are rare, heterogeneous group which tend to rise in incidence. Epidemiological profile and outcomes of GEP-NEN may vary among countries. The aim of study was to provide baseline clinical and histopathological features of patients with GEP-NEN from tertiary referral hospitals in Latvia.
METHODS: A retrospective study of patients with histologically confirmed diagnosis of GEP-NEN treated between 2006 and 2018. Joinpoint regression modeling was used to estimate annual percentage change (APC) for incidence trends. Overall survival (OS) rate was obtained by Kaplan-Meier method.
RESULTS: In total, 205 patients were included. The median age at diagnosis was 61.0 (IQR 52.0-70.5) years, 69.3% were females. The age-adjusted incidence per 100 000 inhabitants increased from 0.03 in 2006 to 0.67 in 2018 with APC of 24.1%, p < 0.005. The most common primary tumor site was pancreas (30.7%), followed by stomach (24.9%) and small intestine (20.5%). Non-functional tumors are present in 83.4%, while carcinoid syndrome in 7.8%. Stage IV metastatic disease was present in 27.8% tumors. The majority of patients (82%) received an operation with radical or palliative intent. The 1- and 3-year OS rate were 88.0% (95% CI 83.3-92.7) and 77.1% (95% CI 70.4-83.8), respectively. Increasing tumor grade, stage and the presence of distant metastases were associated with significantly worse OS.
CONCLUSION: Our study highlights increasing incidence of GEP-NEN in Latvia. The most common primary site was pancreas and surgery considered as main modality of treatment. Registry and long-term data collection are necessary to develop GEP-NEN management concept in Latvia.

PMID: 31605174 [PubMed - as supplied by publisher]

Permalink for 'Prognostic Assessment of Non-functioning Neuroendocrine Pancreatic Neoplasms as a Basis for Risk-Adapted Resection Strategies.'

Prognostic Assessment of Non-functioning Neuroendocrine Pancreatic Neoplasms as a Basis for Risk-Adapted Resection Strategies.

Fetched: October 14th, 2019, 5:01am GMT

Prognostic Assessment of Non-functioning Neuroendocrine Pancreatic Neoplasms as a Basis for Risk-Adapted Resection Strategies.

World J Surg. 2019 Oct 11;:

Authors: Watzka FM, Meyer F, Staubitz JI, Fottner C, Schad A, Lang H, Musholt TJ

Abstract
BACKGROUND: In contrast to exocrine pancreatic carcinomas, prognosis and treatment of pancreatic neuroendocrine neoplasms (PNEN) are significantly different. The variable growth pattern and associated clinical situation of functioning and non-functioning PNEN demand an individualized surgical approach. However, due to the scarce evidence associated with the rare disease, guidelines lack detailed recommendations for indication and for the required extent of surgical resection.
METHODS: In a retrospective single-center study from 1990 to 2018, 239 patients with PNEN were identified. Clinical data were collected in the MaDoc database of the University Medical Center Mainz. A total of 155 non-functional PNEN were selected for further analysis.
RESULTS: According to the classification of NET by the WHO in 2017, 28.8% (n = 40) of the tumors were G1, 61.9% (n = 86) G2, and 9.4% (n = 13) G3. In 73 patients, hepatic metastases were present. Sixty patients had lymph node metastasis. An R0 resection was achieved in 98 cases, an R1 situation in 10 cases. Five times, a tumor debulking was carried out (R2) and 5 times the operation was aborted without any resection because of the advanced tumor stage. A relapse occurred in 29 patients. Different prognostic factors (grade, tumor size, age) were analyzed. Grade-dependent 10-year overall survival rates were 79.5% (grade 1) and 60.1% (grade 2), respectively. The survival rate of grade 3 patients was limited to 66.7% after 13 months.
CONCLUSION: In our study, patients with non-functioning PNEN had a longer overall survival after successful R0 resection. The risk analysis confirmed a Ki-67 cutoff value of 5%, which divided a high- and low-risk group. Patients with a PNEC G3 (Ki-67 index > 50%) had a very poor prognosis.

PMID: 31605171 [PubMed - as supplied by publisher]

Radiation Exposure to the Nuclear Medicine personnel during preparation and handling of 213Bi- radiopharmaceuticals.

Fetched: October 14th, 2019, 5:01am GMT

Radiation Exposure to the Nuclear Medicine personnel during preparation and handling of 213Bi- radiopharmaceuticals.

J Nucl Med Technol. 2019 Oct 11;:

Authors: Thakral P, Sen I, Simecek J, Marx S, Kumari J, Kumar S, Tandon P, Dureja S, Pant V

Abstract
Background: Due to excellent ability of α-particles to transfer the high amount of energy over a short tissue range, targeted α-therapy (TAT) has been attracting rising number of nuclear medicine centers. In this study, we estimated the radiation exposure to the occupational worker with pocket dosimeter during the handling of α-emitter: Bi-213, used for targeted α-therapy (TAT) of neuroendocrine tumors (NET) and castration resistant prostate cancer (CRPC) patients. The dose rates from the patients at different distances and at different time points after therapeutic injection were also evaluated. Materials and Methods: This prospective study was done in the Department of Nuclear Medicine at Fortis Memorial Research Institute, Gurgaon, India. A total of twelve patients with NET or CRPC were enrolled for 213Bi-DOTATOC or 213Bi-PSMA therapy, respectively. Each patient received 2-3 intravenous injections of 213Bi-peptide, 266 - 362MBq (7.2 - 9.8mCi) in a single cycle over 2-3 days. Radiation exposure to nuclear medicine personnel at chest and extremity levels were assessed for different tasks such as elution, dispensing, injecting and, collecting blood samples etc. Radiation levels were measured at a distance of 1cm and at 1m from the patients immediately after, and at 1, 2, and 4h after the administration of 213Bi-peptide. Results: The effective external doses incurred by a radiopharmacist during synthesis, by physicians during injection, by technologists during imaging and nurses during sample collection at the chest level were measured using the pocket dosimeter and were found to be in the range of 2-7 µSv/procedure. The extremity doses were in the range of 1-14 µSv/procedure. The dose rate at 1m from 213Bi-radiopharmaceutical injected patients immediately after therapy was in the range of 0.02-0.03µSv/MBq.h. Conclusion: The study shows that the use of 213Bi-PSMA/DOTATOC for the therapy of CRPC and NET, respectively, has been convenient, safe and straightforward. The external radiation doses to the occupational workers involved in different procedures were far below the dose limits prescribed by the Regulatory Authority (20mSv/yr). The dose rates from the treated patients showed no detrimental effect on public and environment.

PMID: 31604889 [PubMed - as supplied by publisher]

Pediatric intramedullary schwannoma with syringomyelia: a case report and literature review.

Fetched: October 13th, 2019, 5:01am GMT

Pediatric intramedullary schwannoma with syringomyelia: a case report and literature review.

BMC Pediatr. 2018 11 28;18(1):374

Authors: Wang K, Zhao J, Zhang Y, Su Y

Abstract
BACKGROUND: Intramedullary schwannomas without neurofibromatosis are exceedingly rare. They are rarer in children with only 8 cases reported so far. The association of intramedullary schwannomas with syringomyelia is also rare. Here, we present a case of intramedullary schwannoma with syringomyelia treated surgically in an 9-year-old boy.
CASE PRESENTATION: We reviewed the clinical course of a 9-year-old boy, who presented with both lower extremity weakness of 6-month duration. Neurophysical examination revealed a decreased sensation below the T10 dermatome. Magnetic resonance imaging (MRI) showed an well-demarcated intramedullary lesion located at the level of T8 vertebra with isointensity on T2WI and hypointensity on T1WI, which was homogeneous enhanced after gadolinium injection. There was associated syringomyelia extending from T7 down to the level of T10. A mild scoliotic deformity was also observed. The lesion was totally resected after an T7-T8 laminoplasty. Histopathological findings were consistent with schwannoma. Postoperative MRI did not reveal the presence of a residual tumor with syringomyelia reducted. By 2 weeks after treatment, the patient had experienced nearly complete recovery. Management with external bracing was performed on this patient for 3 months after surgery to prevent spinal deformity. However, mild spinal kyphosis occurred 5 months after surgery, and a progressive postoperative spinal kyphosis was observed during these 3 years of follow-up. Continued conservative management with observation was performed as there is no association with functional decline and impairment in health-related quality-of-life measures.
CONCLUSION: Although extremely rare and uncommonly associated with syringomyelia, schwannomas need to be considered in the preoperative diagnosis of solitary intramedullary tumors in children as total resection can be achieved improving surgical outcome; Pediatric patients should be monitored closely for the development of spinal deformity following resection of intramedullary schwannoma, particularly possessing preoperative scoliotic deformity and/or tumor-associated syringomyelia.

PMID: 30486806 [PubMed - indexed for MEDLINE]

Cardiac CT Angiography in Carcinoid Heart Disease.

Fetched: October 13th, 2019, 5:01am GMT

Cardiac CT Angiography in Carcinoid Heart Disease.

Radiology. 2019 01;290(1):32

Authors: Alsaad AA, Rojas CA

PMID: 30375927 [PubMed - indexed for MEDLINE]

Permalink for 'Carbohydrate-based adjuvants activate tumor-specific Th1 and CD8+ T-cell responses and reduce the immunosuppressive activity of MDSCs.'

Carbohydrate-based adjuvants activate tumor-specific Th1 and CD8+ T-cell responses and reduce the immunosuppressive activity of MDSCs.

Fetched: October 13th, 2019, 5:01am GMT

Carbohydrate-based adjuvants activate tumor-specific Th1 and CD8+ T-cell responses and reduce the immunosuppressive activity of MDSCs.

Cancer Lett. 2019 01;440-441:94-105

Authors: Xu X, Jin Z, Liu Y, Gong H, Sun Q, Zhang W, Zhao L

Abstract
Toll-like receptors (TLRs) and C-type lectin receptors (CLRs) contribute to antigen capture, uptake, presentation and activation of immune responses. We recently developed a new and lymph node (LN) targeting adjuvant (D-CpG) by chemical conjugation type B CpG DNA with FDA-approved dextran polymer for lymph node imaging. To elucidate the possible antitumor mechanisms of this adjuvant, prophylaxis and therapeutic models of melanoma were used in this study. Our results showed that D-CpG was an efficient adjuvant of protein-based tumor vaccine in both prophylaxis and therapeutic models. It enhanced the tumor-specific Th1 and CTL responses. It also facilitated the tumor infiltration of the T cells and promoted IFNγ and TNFα production of both CD4+ and CD8+ T cells. In therapeutic model, D-CpG included tumor vaccine decreased the percentage of CD11b+Gr1low+ MDSCs in spleen and inhibited their infiltration in tumor microenvironments. Administration of the D-CpG included vaccine significantly inhibited lung metastasis of the tumor through similar mechanisms. In conclusion, D-CpG used as tumor vaccine adjuvant can enhance both Th1 and CTL responses and inhibit CD11b+Gr1low MDSCs, which may have general applicability to the development of vaccines against tumors.

PMID: 30352261 [PubMed - indexed for MEDLINE]

Chemoprevention agents for melanoma: A path forward into phase 3 clinical trials.

Fetched: October 13th, 2019, 5:01am GMT

Chemoprevention agents for melanoma: A path forward into phase 3 clinical trials.

Cancer. 2019 01 01;125(1):18-44

Authors: Jeter JM, Bowles TL, Curiel-Lewandrowski C, Swetter SM, Filipp FV, Abdel-Malek ZA, Geskin LJ, Brewer JD, Arbiser JL, Gershenwald JE, Chu EY, Kirkwood JM, Box NF, Funchain P, Fisher DE, Kendra KL, Marghoob AA, Chen SC, Ming ME, Albertini MR, Vetto JT, Margolin KA, Pagoto SL, Hay JL, Grossman D, Ellis DL, Kashani-Sabet M, Mangold AR, Markovic SN, Nelson KC, Powers JG, Robinson JK, Sahni D, Sekulic A, Sondak VK, Wei ML, Zager JS, Dellavalle RP, Thompson JA, Weinstock MA, Leachman SA, Cassidy PB

Abstract
Recent progress in the treatment of advanced melanoma has led to unprecedented improvements in overall survival and, as these new melanoma treatments have been developed and deployed in the clinic, much has been learned about the natural history of the disease. Now is the time to apply that knowledge toward the design and clinical evaluation of new chemoprevention agents. Melanoma chemoprevention has the potential to reduce dramatically both the morbidity and the high costs associated with treating patients who have metastatic disease. In this work, scientific and clinical melanoma experts from the national Melanoma Prevention Working Group, composed of National Cancer Trials Network investigators, discuss research aimed at discovering and developing (or repurposing) drugs and natural products for the prevention of melanoma and propose an updated pipeline for translating the most promising agents into the clinic. The mechanism of action, preclinical data, epidemiological evidence, and results from available clinical trials are discussed for each class of compounds. Selected keratinocyte carcinoma chemoprevention studies also are considered, and a rationale for their inclusion is presented. These data are summarized in a table that lists the type and level of evidence available for each class of agents. Also included in the discussion is an assessment of additional research necessary and the likelihood that a given compound may be a suitable candidate for a phase 3 clinical trial within the next 5 years.

PMID: 30281145 [PubMed - indexed for MEDLINE]

Post-surgical outcome and prognostic factors in canine malignant melanomas of the haired skin: 87 cases (2003-2015).

Fetched: October 13th, 2019, 5:01am GMT

Post-surgical outcome and prognostic factors in canine malignant melanomas of the haired skin: 87 cases (2003-2015).

Can Vet J. 2018 09;59(9):981-987

Authors: Laver T, Feldhaeusser BR, Robat CS, Baez JL, Cronin KL, Buracco P, Annoni M, Regan RC, McMillan SK, Curran KM, Selmic LE, Shiu KB, Clark K, Fagan E, Thamm DH

Abstract
The medical records of 87 dogs treated with surgery for cutaneous malignant melanoma (CMM) of the haired skin were retrospectively reviewed for overall survival time (OST), progression-free survival time (PFS), and prognostic factors. The post-surgery median PFS and median OST were 1282 days and 1363 days, respectively. The post-surgery metastatic rate was 21.8% with a local recurrence rate of 8%. Increasing mitotic index (MI) was predictive of a significantly decreased OST and PFS on multivariable analysis [hazard ratio (HR): 1.05, 95% confidence interval (CI): 1.02 to 1.07 and HR: 1.04, 95% CI: 1.02 to 1.06, respectively]. Increasing age was likewise predictive of a significantly decreased OST and PFS on multivariable analysis (HR: 1.39, 95% CI: 1.17 to 1.65 and HR: 1.33, 95% CI: 1.14 to 1.54, respectively). These results confirm clinical impressions that long survival times are likely in dogs diagnosed with malignant melanoma of the haired skin when treated with surgery alone.

PMID: 30197441 [PubMed - indexed for MEDLINE]

Diagnosis and Management of Acral Lentiginous Melanoma.

Fetched: October 13th, 2019, 5:01am GMT

Diagnosis and Management of Acral Lentiginous Melanoma.

Curr Treat Options Oncol. 2018 06 27;19(8):42

Authors: Nakamura Y, Fujisawa Y

Abstract
OPINION STATEMENT: Melanoma is one of the most aggressive malignant skin tumors and its incidence has been increasing worldwide in recent decades. Among the four subtypes, acral lentiginous melanoma (ALM) shows the highest incidence in Asian countries, whereas ALM comprises only 1% of all melanomas in white populations. Early clinical diagnosis of ALM is essential, but early ALM lesions are often difficult to diagnose because the pigmentation of the lesions sometimes follows the skin marking of the palms and soles, resulting in an asymmetrical appearance and an irregular border in both ALM and benign melanocytic nevus. To overcome this difficulty, dermoscopy was introduced, and determination of the patterns by this method is essential for accurate clinical diagnosis of ALM. Although recent clinical trials have demonstrated that immune checkpoint inhibitors and BRAF/MEK inhibitors showed significantly improved overall survival of patients with advanced melanoma, ALM may be less susceptible to immune checkpoint inhibitors because of the poor immune response to the tumor. Therefore, strategies for enhancing the immune response to the tumor cells may be required when we apply immune checkpoint inhibitors in advanced ALM. In this context, imiquimod, dacarbazine, or interferon are possible therapies that may enhance the effectiveness of the immune checkpoint inhibitors. In addition to being known to have poor immunogenicity, ALM is also known to have infrequent BRAF mutation. Therefore, the majority of ALM patients may not benefit from therapy with BRAF/MEK inhibitors. However, some ALMs have mutations such as KIT and NRAS mutations, and therefore, targeted therapies may improve the survival of ALM patients in the future.

PMID: 29951919 [PubMed - indexed for MEDLINE]

Permalink for 'Angio-3, a 10-residue peptide derived from human plasminogen kringle 3, suppresses tumor growth in mice via impeding both angiogenesis and vascular permeability.'

Angio-3, a 10-residue peptide derived from human plasminogen kringle 3, suppresses tumor growth in mice via impeding both angiogenesis and vascular permeability.

Fetched: October 13th, 2019, 5:01am GMT

Angio-3, a 10-residue peptide derived from human plasminogen kringle 3, suppresses tumor growth in mice via impeding both angiogenesis and vascular permeability.

Angiogenesis. 2018 08;21(3):653-665

Authors: Venugopal S, Kao C, Chandna R, Sulochana KN, Subramanian V, Chen M, Kini RM, Ge R

Abstract
Anti-angiogenesis therapy is an established therapeutic strategy for cancer. The endogenous angiogenic inhibitor angiostatin contains the first 3-4 kringle domains of plasminogen and inhibits both angiogenesis and vascular permeability. We present here a 10-residue peptide, Angio-3, derived from plasminogen kringle 3, which retains the functions of angiostatin in inhibiting both angiogenesis and vascular permeability. NMR studies indicate that Angio-3 holds a solution structure similar to the corresponding region of kringle 3. Mechanistically, Angio-3 inhibited both VEGF- and bFGF-induced angiogenesis by inhibiting EC proliferation and migration while inducing apoptosis. Inhibition of VEGF-induced vascular permeability results from its ability to impede VEGF-induced dissociation of adherens junction and tight junction proteins as well as the formation of actin stress fibers. When administered intravenously, Angio-3 inhibited subcutaneous breast cancer and melanoma growth by suppressing both tumor angiogenesis and intra-tumor vascular permeability. Hence, Angio-3 is a novel dual inhibitor of angiogenesis and vascular permeability. It is valuable as a lead peptide that can be further developed as therapeutics for diseases involving excessive angiogenesis and/or vascular permeability.

PMID: 29691683 [PubMed - indexed for MEDLINE]

Rapidly Growing Eyelid Mass in an Elderly Man.

Fetched: October 13th, 2019, 5:01am GMT

Rapidly Growing Eyelid Mass in an Elderly Man.

JAMA Ophthalmol. 2018 06 01;136(6):710-711

Authors: Messenger WB, Liu CY, Aakalu VK

PMID: 29543951 [PubMed - indexed for MEDLINE]

Interrater reliability of a method to assess hypothalamic involvement in pediatric adamantinomatous craniopharyngioma.

Fetched: October 13th, 2019, 5:01am GMT

Interrater reliability of a method to assess hypothalamic involvement in pediatric adamantinomatous craniopharyngioma.

J Neurosurg Pediatr. 2019 Oct 11;:1-6

Authors: Whelan R, Prince E, Mirsky DM, Naftel R, Bhatia A, Pettorini B, Avula S, Staulcup S, Alexander AL, Meier M, Hankinson TC

Abstract
OBJECTIVE: Pediatric adamantinomatous craniopharyngiomas (ACPs) are histologically benign brain tumors that confer significant neuroendocrine morbidity. Previous studies have demonstrated that injury to the hypothalamus is associated with worsened quality of life and a shorter lifespan. This insight helps many surgeons define the goals of surgery for patients with ACP. Puget and colleagues proposed a 3-tiered preoperative and postoperative grading system based on the degree of hypothalamic involvement identified on MRI. In a prospective cohort from their institution, the authors found that use of the system to guide operative goals was associated with decreased morbidity. To date, however, the Puget system has not been externally validated. Here, the authors present an interrater reliability study that assesses the generalizability of this system for surgeons planning initial operative intervention for children with craniopharyngiomas.
METHODS: A panel of 6 experts, consisting of pediatric neurosurgeons and pediatric neuroradiologists, graded 30 preoperative and postoperative MRI scans according to the Puget system. Interrater reliability was calculated using Fleiss' κ and Krippendorff's α statistics.
RESULTS: Interrater reliability in the preoperative context demonstrated moderate agreement (κ = 0.50, α = 0.51). Interrater reliability in the postoperative context was 0.27 for both methods of statistical evaluation.
CONCLUSIONS: Interrater reliability for the system as defined is moderate. Slight refinements of the Puget MRI grading system, such as collapsing the 3 grades into 2, may improve its reliability, making the system more generalizable.

PMID: 31604324 [PubMed - as supplied by publisher]

A case of gastric small cell carcinoma with metastases to bone and liver.

Fetched: October 13th, 2019, 5:01am GMT

A case of gastric small cell carcinoma with metastases to bone and liver.

J Gastrointest Oncol. 2019 Oct;10(5):1027-1031

Authors: Rajasekaran Rathnakumar G, Gupta A, John F, Liu Y, Shakil S, Guevara E

Abstract
Gastric small cell carcinoma (GSCC) is a rare entity in the western hemisphere. GSCC's typically arise in the upper one-third of the stomach and have histologic features similar to those of small-cell lung carcinoma (SCLC). They have an aggressive natural history that is characterized by early and widespread metastases. Prognosis is dismal with an overall survival of less than 12 months. We present the case of a 79-year-old African-American woman who presented with two weeks of progressive dysphagia associated with nausea, vomiting and a foreign body sensation in the throat. Computed tomography (CT) imaging showed multiple hepatic and lymph node lesions but revealed no gastric thickening. Endoscopy revealed a large ulcer on the lesser curvature of the stomach. Biopsy proved the diagnosis of pure-type GSCC. Bone scan identified multiple focal bony lesions at the thoracolumbar vertebrae, ribcage, bilateral scapulae, pelvic bones and right proximal femur. Treatment was started with cisplatin and etoposide. To our knowledge, this is the one of the first reported cases of gastric small cell cancer with bone metastases in the western hemisphere. Our report shows the importance of doing a full metastatic workup in these patients to identify sites of metastases.

PMID: 31602342 [PubMed]

Permalink for 'Does the addition of adjuvant intraoperative tumor bed chemotherapy during midgut neuroendocrine tumor debulking procedures benefit patients?'

Does the addition of adjuvant intraoperative tumor bed chemotherapy during midgut neuroendocrine tumor debulking procedures benefit patients?

Fetched: October 13th, 2019, 5:01am GMT

Does the addition of adjuvant intraoperative tumor bed chemotherapy during midgut neuroendocrine tumor debulking procedures benefit patients?

J Gastrointest Oncol. 2019 Oct;10(5):928-934

Authors: Wang YZ, Chauhan A, Ramirez RA, Beyer DT, Stevens MA, Woltering EA, Boudreaux JP, Anthony L

Abstract
Background: Midgut neuroendocrine tumor (NET) patients are often diagnosed at advanced stages with extensive mesenteric nodal and hepatic metastasis. The only potentially curative treatment is surgical tumor eradication. Despite an aggressive resection, macro and microscopic residual disease still may remain in the resection bed. We hypothesize that the application of 5-fluorouracil (5-FU) within the tumor bed will help eliminate microscopic residual disease.
Methods: Records of 189 patients who underwent extensive cytoreductive surgeries during 2003-2012 for advanced, midgut NETs with extensive mesenteric lymphadenopathy were reviewed. Eighty-six patients (46%) who had 5-FU saturated gel foam strips secured into their mesenteric resection sites served as the study group and a matching 103 patients (54%) who did not have such an intra-operative chemotherapy served as controls. Survival from the time of diagnosis and post-operative complications between the two groups were compared.
Results: Mortality rates at 30, 60 and 90 days post-operatively were 4%, 0%, 0% versus 2%, 0%, 2% for study and control groups, respectively. Major complications (Grades III & IV) at the same intervals were 0, 0, 1 versus 2, 3, 2 for study and control groups, respectively. Median survival was 236 months versus 148 months for the study and control groups, respectively 24 (P=0.15).
Conclusions: Intraoperative tumor resection bed chemotherapy is a safe adjuvant without discernible toxicity. This procedure may provide survival benefits to midgut NET patients with extensive mesenteric lymphadenopathy undergoing extensive cytoreductive surgery. Further study in prospective trials must be conducted to determine definitive benefit to the NET patient.

PMID: 31602331 [PubMed]

Survival trends of metastatic small intestinal neuroendocrine tumor: a population-based analysis of SEER database.

Fetched: October 13th, 2019, 5:01am GMT

Survival trends of metastatic small intestinal neuroendocrine tumor: a population-based analysis of SEER database.

J Gastrointest Oncol. 2019 Oct;10(5):869-877

Authors: Shah CP, Mramba LK, Bishnoi R, Unnikrishnan A, Duff JM, Chandana SR

Abstract
Background: Incidence of small intestinal neuroendocrine tumors (SNETs) is increasing and they now comprise the most common types of small intestinal cancer. SNETs frequently present with distant metastasis. Significant uncertainty prevails with regards to the surgical management strategies in metastatic SNETs. Therefore, we aim to analyze survival trends in metastatic SNET patients stratified by type of surgical treatment.
Methods: We analyzed the data from the SEER database: Incidence - SEER 18 Regs Research Data + Hurricane Katrina Impacted Louisiana Cases, Nov 2016 Sub (1973-2014 varying). Relative survival rates (RSRs) and hazard ratios (HRs) were measured for patients diagnosed with metastatic SNET between 2000 and 2014. Treatment received was divided into two broad categories; surgical resection and no surgery and further subcategorized into local resection (LR) (surgery of the primary tumor only) and radical resection (RR) (surgery for primary tumor and metastasectomy).
Results: We identified 1,138 metastatic SNET cases. Median age was 61 years. Median survival was 41 months and 5 year RSR was 72%. Age >50 years (HR 2.10, P<0.001), poorly differentiated histology (HR 3.50, P<0.001) and tumor size >2 cm (HR 1.27, P=0.07), showed poor outcome. The group which did not receive any tumor directed surgery showed the worst survival (5 years RSR 45.30% vs. 76%, respectively for no surgery vs. surgery group, P<0.001). We found no significant difference in survival between LR and RR (HR 1.01, 95% CI: 0.73-1.40, P=0.92). Upon further stratification, surgery significantly improved survival on patients who were >50 years (HR 0.37), and for primary tumor location in the duodenum (HR 0.13).
Conclusions: Surgery for the primary tumor (LR or RR) significantly improved 5-year survival even in the presence of distant metastasis irrespective of primary tumor size, grade, or histology. Poor prognostic factors include, age >50 years, duodenal primary, tumor size >2 cm, and poorly differentiated histology.

PMID: 31602324 [PubMed]

Large-Cell Neuroendocrine Carcinoma of the Lung: A Population-Based Study.

Fetched: October 13th, 2019, 5:01am GMT

Large-Cell Neuroendocrine Carcinoma of the Lung: A Population-Based Study.

Clin Lung Cancer. 2019 Aug 03;:

Authors: Kinslow CJ, May MS, Saqi A, Shu CA, Chaudhary KR, Wang TJC, Cheng SK

Abstract
INTRODUCTION: Large-cell neuroendocrine carcinoma (LCNEC) accounts for approximately 3% of lung malignancies. There are limited data on the epidemiology and best treatment practices for this malignancy. This study aimed to be the largest cohort with the most up-to-date analysis of the epidemiology of LCNEC.
PATIENTS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried to identify cases of LCNEC diagnosed from 2010 through 2015, reflecting years the American Joint Committee on Cancer 7th edition staging system was in use. Using these data, we compared the epidemiology, demographics, clinical characteristics, and survival times of LCNEC with small-cell lung carcinoma (SCLC) and non-SCLC (NSCLC). Trends in incidence and mortality were recorded from 2004 to 2015.
RESULTS: A total of 195,148 cases of lung cancer, including 1681 (0.9%) cases of LCNEC, were analyzed. LCNEC was more common among male subjects, and disease usually presented at stage IV (55%). Brain metastasis occurred more frequently in LCNEC (19.2%) than SCLC (16.7%, P < .001) or NSCLC (13%, P < .001). Incidence increased by 0.011 people per 100,000 per year, primarily of stage IV disease. Annual mortality from LCNEC doubled over the time period studied. Survival in patients with stage I-III LCNEC mirrored survival trends of patients with NSCLC, whereas stage IV LCNEC behaved similarly to SCLC.
CONCLUSION: LCNEC generally presents at more advanced stages than NSCLC but earlier than SCLC. Stage I-III LCNEC behaves similarly to NSCLC, whereas stage IV is more akin to SCLC. LCNEC incidence is increasing. Despite this, it remains poorly studied and did not demonstrate an improved prognosis in our cohort.

PMID: 31601526 [PubMed - as supplied by publisher]

RADIATION MACULOPATHY AFTER ONE-DAY SESSION STEREOTACTIC RADIOSURGERY IN PATIENTS WITH CILIARY BODY AND CHOROIDAL MELANOMA.

Fetched: October 13th, 2019, 5:01am GMT

RADIATION MACULOPATHY AFTER ONE-DAY SESSION STEREOTACTIC RADIOSURGERY IN PATIENTS WITH CILIARY BODY AND CHOROIDAL MELANOMA.

Cesk Slov Oftalmol. 2019;75(1):3-10

Authors: Zahorjanová P, Furdová A, Waczulíková I, Šramka M, Králik G, Štubňa M

Abstract
INTRODUCTION: Nowadays radiotherapy is the standard treatment care for patients with uveal melanoma. In Slovakia the only one option is a one-day session stereotactic radiosurgery at linear accelerator LINAC. Irradiation of surrounding tissues of the eye and orbit causes radiation complications. One of the most serious and vision-threatening is the radiation retinopathy, which divides into maculopathy and peripheric retinopathy. The clinical signs include microanerysms, teleangiectases, hard exsudates, cotton wool spots and macular edema, neovascularisation, and vitreous hemorrhage. Radiation macular edema can be classified by optical coherence tomography into cystoid or noncystoid edema. On fluorescein angiography macular edema is divided into non-ischemic and ischemic, while the latter means usually irreversible loss of the visual acuity. This paper is focused on risk factors of radiation retinopathy although it strongly influences functional result of radiotherapy and preservation of the visual acuity.
PURPOSE: By means of bivariate and multivariate analysis to determine the association of radiation dose and other variables with the development of radiation maculopathy.
MATERIAL AND METHODS: The retrospective analysis of 168 patients with ciliary body or choroidal melanoma who performed one-day session stereotactic radiosurgery on a linear accelerator LINAC in a period 2007-2016.
RESULTS: The prevalence of the radiation maculopathy was 29% with the median time from the irradiation to maculopathy 16 months. Median radiation dose on the macula was 37 Gy. Variables statistically significantly associated with the maculopathy were: radiation dose (p = 0.0016), postequatorial location of the tumor (p = 0.0271) and better visual acuity before treatment (p = 0.0007). The tumor touch of the macula was strongly associated with the visual acuity in the bivariate analysis (p = 0.0006), thus it could be omitted from the final model.
DISCUSSION: The radiation dose on a macula is the key determinant for radiation-induced maculopathy, according to other authors and our study approvingly. Other variables were related to proximity of the tumor to the macula, so the radiation dose on the macula was higher indirectly. Better visual acuity before treatment as a risk factor for maculopathy can be a consequence of: a) earlier diagnostics of tumor with proximity to the posterior pole, b) lower enucleation rate; frequency of the enucleation was 1.6 higher in patients without maculopathy. Naturally, on enucleated eyes maculopathy was not diagnosed. Five patients underwent intravitreal application of the bevacizumab as a treatment of the radiation maculopathy, without improvement of the visual acuity.
CONCLUSION: Radiation complications can be vision and eye threatening. Radiation maculopathy is a consequence of higher radiation dose on the macula. The treatment modalities of radiation maculopathy are rather ineffective.

PMID: 31382751 [PubMed - indexed for MEDLINE]

Delta-like 3 localizes to neuroendocrine cells and plays a pivotal role in gastrointestinal neuroendocrine malignancy.

Fetched: October 13th, 2019, 5:01am GMT

Delta-like 3 localizes to neuroendocrine cells and plays a pivotal role in gastrointestinal neuroendocrine malignancy.

Cancer Sci. 2019 Oct;110(10):3122-3131

Authors: Matsuo K, Taniguchi K, Hamamoto H, Ito Y, Futaki S, Inomata Y, Shima T, Asakuma M, Lee SW, Tanaka K, Okuda J, Kondo Y, Uchiyama K

Abstract
Delta-like 3 (DLL3) is a member of the Delta/Serrate/Lag2 (DSL) group of Notch receptor ligands. Five DSL ligands are known in mammals, among which DLL3 has a unique structure. In the last few years, DLL3 has attracted attention as a novel molecular targeting gene in neuroendocrine carcinoma of the lung due to its high expression. However, the expression pattern and functions of DLL3 in the gastrointestinal tract and gastrointestinal neuroendocrine carcinoma remain unclear. In this study, we examined the expression and role of DLL3 in the gastrointestinal tract, as well as in gastrointestinal neuroendocrine carcinoma. Immunohistochemical staining of the human normal gastrointestinal tract revealed that DLL3 localized in neuroendocrine cells. DLL3 showed intense staining in chromogranin A-positive gastric cancer specimens. Real-time quantitative RT-PCR and western blotting analyses showed considerable upregulation of DLL3 in gastrointestinal neuroendocrine carcinoma cell lines. Immuno-electron microscopy demonstrated abundant expression of DLL3 in neurosecretory granules in these cells. Furthermore, gene silencing of DLL3 caused significant growth inhibition through the induction of intrinsic apoptosis. Our findings suggest that DLL3 is expressed in neuroendocrine cells of the gastrointestinal tract and that it has a pivotal role in gastrointestinal neuroendocrine carcinoma cells. Based on these findings, further investigations are required to achieve a breakthrough in developing therapeutic strategies for gastrointestinal neuroendocrine carcinoma.

PMID: 31369178 [PubMed - indexed for MEDLINE]

Treatment Options for Melanoma of Gray Horses.

Fetched: October 13th, 2019, 5:01am GMT

Treatment Options for Melanoma of Gray Horses.

Vet Clin North Am Equine Pract. 2019 Aug;35(2):311-325

Authors: MacKay RJ

Abstract
All gray horses inherited a single gene mutation, STX17G, that unbalances melanocyte behavior to cause graying and propensities to develop vitiligo and melanoma. The coat color genes ASIPa and MC1RE add risk such that relative likelihood of melanoma based on pregraying coat color is black > bay > chestnut. Melanomas begin at about 4 years. Locoregional control of melanoma masses depends on surgical removal and/or intralesional chemotherapy (possibly with adjunctive hyperthermia or electroporation). Systemic treatment is not evidence based but immunomodulators (cimetidine, levamisole) and vaccines can be tried.

PMID: 31279435 [PubMed - indexed for MEDLINE]

Extracellular vesicle-dependent effect of RNA-binding protein IGF2BP1 on melanoma metastasis.

Fetched: October 13th, 2019, 5:01am GMT

Extracellular vesicle-dependent effect of RNA-binding protein IGF2BP1 on melanoma metastasis.

Oncogene. 2019 05;38(21):4182-4196

Authors: Ghoshal A, Rodrigues LC, Gowda CP, Elcheva IA, Liu Z, Abraham T, Spiegelman VS

Abstract
Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) is a multifunctional RNA-binding protein with an oncofetal pattern of expression shown to be implicated in the development of a variety of malignancies. In this study, we explored the role and mechanisms of IGF2BP1 in melanoma development and progression. In two different in vivo models, we showed that although genetic deletion or shRNA-mediated suppression of IGF2BP1 did not affect primary tumor formation, it drastically suppressed lung metastasis. Here we demonstrated that extracellular vesicles (EVs) secreted by melanoma cells mediate the effects of IGF2BP1 on metastasis: EVs from the IGF2BP1 knockdown melanoma cells failed to promote metastasis, whereas EVs isolated from IGF2BP1-overexpressed melanoma cells further accelerated EV-induced metastasis. Moreover, the EVs from IGF2BP1 knockdown melanoma cells inhibited fibronectin deposition and accumulation of CD45+ cells in the lungs compared with control EVs, thus blocking the pre-metastatic niche formation potential of EVs. IGF2BP1 knockdown did not affect size, number, or protein/RNA concentration of secreted EVs or their uptake by recipient cells in vitro or in vivo. However, RNA-sequencing and proteomics analysis of the EVs revealed differential expression in a number of mRNA, proteins, and miRNAs. This suggested that IGF2BP1 is intimately involved in the regulation of the cargo of EVs, thereby affecting the pro-metastatic function of melanoma-derived EVs. To the best of our knowledge, this is the first study that demonstrates the role of RNA-binding protein IGF2BP1 in EV-mediated promotion of melanoma metastasis and may provide novel avenues for the development of metastatic inhibitors.

PMID: 30936459 [PubMed - indexed for MEDLINE]

An actionable axis linking NFATc2 to EZH2 controls the EMT-like program of melanoma cells.

Fetched: October 13th, 2019, 5:01am GMT

An actionable axis linking NFATc2 to EZH2 controls the EMT-like program of melanoma cells.

Oncogene. 2019 05;38(22):4384-4396

Authors: Perotti V, Baldassari P, Molla A, Nicolini G, Bersani I, Grazia G, Benigni F, Maurichi A, Santinami M, Anichini A, Mortarini R

Abstract
Discovery of new actionable targets and functional networks in melanoma is an urgent need as only a fraction of metastatic patients achieves durable clinical benefit by targeted therapy or immunotherapy approaches. Here we show that NFATc2 expression is associated with an EMT-like transcriptional program and with an invasive melanoma phenotype, as shown by analysis of melanoma cell lines at the mRNA and protein levels, interrogation of the TCGA melanoma dataset and characterization of melanoma lesions by immunohistochemistry. Gene silencing or pharmacological inhibition of NFATc2 downregulated EMT-related genes and AXL, and suppressed c-Myc, FOXM1, and EZH2. Targeting of c-Myc suppressed FOXM1 and EZH2, while targeting of FOXM1 suppressed EZH2. Inhibition of c-Myc, or FOXM1, or EZH2 downregulated EMT-related gene expression, upregulated MITF and suppressed migratory and invasive activity of neoplastic cells. Stable silencing of NFATc2 impaired melanoma cell proliferation in vitro and tumor growth in vivo in SCID mice. In NFATc2+ EZH2+ melanoma cell lines pharmacological co-targeting of NFATc2 and EZH2 exerted strong anti-proliferative and pro-apoptotic activity, irrespective of BRAF or NRAS mutations and of BRAF inhibitor resistance. These results provide preclinical evidence for a role of NFATc2 in shaping the EMT-like melanoma phenotype and reveal a targetable vulnerability associated with NFATc2 and EZH2 expression in melanoma cells belonging to different mutational subsets.

PMID: 30710146 [PubMed - indexed for MEDLINE]

MEK inhibition enhances oncolytic virus immunotherapy through increased tumor cell killing and T cell activation.

Fetched: October 13th, 2019, 5:01am GMT

MEK inhibition enhances oncolytic virus immunotherapy through increased tumor cell killing and T cell activation.

Sci Transl Med. 2018 12 12;10(471):

Authors: Bommareddy PK, Aspromonte S, Zloza A, Rabkin SD, Kaufman HL

Abstract
Melanoma is an aggressive cutaneous malignancy, but advances over the past decade have resulted in multiple new therapeutic options, including molecularly targeted therapy, immunotherapy, and oncolytic virus therapy. Talimogene laherparepvec (T-VEC) is a herpes simplex type 1 oncolytic virus, and trametinib is a MEK inhibitor approved for treatment of melanoma. Therapeutic responses with T-VEC are often limited, and BRAF/MEK inhibition is complicated by drug resistance. We observed that the combination of T-VEC and trametinib resulted in enhanced melanoma cell death in vitro. Further, combination treatment resulted in delayed tumor growth and improved survival in mouse models. Tumor regression was dependent on activated CD8+ T cells and Batf3+ dendritic cells. We also observed antigen spreading and induction of an inflammatory gene signature, including increased expression of PD-L1. Triple therapy with the combination of T-VEC, MEK inhibition, and anti-PD-1 antibody further augmented responses. These data support clinical development of combination oncolytic viruses, MEK inhibitors, and checkpoint blockade in patients with melanoma.

PMID: 30541787 [PubMed - indexed for MEDLINE]

Permalink for 'Endoscopic Ultrasound Features Associated with Malignancy and Aggressiveness of Nonhypovascular Solid Pancreatic Lesions: Results from a Prospective Observational Study.'

Endoscopic Ultrasound Features Associated with Malignancy and Aggressiveness of Nonhypovascular Solid Pancreatic Lesions: Results from a Prospective Observational Study.

Fetched: October 11th, 2019, 5:01am GMT

Endoscopic Ultrasound Features Associated with Malignancy and Aggressiveness of Nonhypovascular Solid Pancreatic Lesions: Results from a Prospective Observational Study.

Ultraschall Med. 2019 Oct 09;:

Authors: Crinó SF, Brandolese A, Vieceli F, Paiella S, Conti Bellocchi MC, Manfrin E, Bernardoni L, Sina S, D'Onofrio M, Marchegiani G, Larghi A, Frulloni L, Landoni L, Gabbrielli A

Abstract
BACKGROUND AND STUDY AIMS: On contrast-enhanced imaging studies, nonhypovascular (i. e., isovascular and hypervascular) patterns can be observed in solid pancreatic lesions (SPLs) of different nature, prognosis, and management. We aimed to identify endoscopic ultrasound (EUS) features of nonhypovascular SPLs associated with malignancy/aggressiveness. The secondary aims were EUS tissue acquisition (EUS-TA) outcome and safety in this setting of patients.
PATIENTS AND METHODS: This prospective observational study included patients with nonhypovascular SPLs detected on cross-sectional imaging and referred for EUS-TA. Lesion features (size, site, margins, echotexture, vascular pattern, and upstream dilation of the main pancreatic duct) were recorded. Malignancy/aggressiveness was determined by evidence of carcinoma at biopsy/surgical pathology, signs of aggressiveness (perineural invasion, lymphovascular invasion, and/or microscopic tumor extension/infiltration or evidence of metastatic lymph nodes) in the surgical specimen, radiologic detection of lymph nodes or distant metastases, and/or tumor growth > 5 mm/6 months. Uni- and multivariate analyses were performed to assess the primary aim.
RESULTS: A total of 154 patients with 161 SPLs were enrolled. 40 (24.8 %) lesions were defined as malignant/aggressive. Irregular margins and size > 20 mm were independent factors associated with malignancy/aggressiveness (p < 0.001, OR = 5.2 and p = 0.003, OR = 2.1, respectively). However, size > 20 mm was not significant in the subgroup of other-than-neuroendocrine tumor (NET) lesions. The EUS-TA accuracy was 92 %, and the rate of adverse events was 4 %.
CONCLUSION: Irregular margins on EUS are associated with malignancy/aggressiveness of nonhypovascular SPLs. Size > 20 mm should be considered a malignancy-related feature only in NET patients. EUS-TA is safe and highly accurate for differential diagnosis in this group of patients.

PMID: 31597179 [PubMed - as supplied by publisher]

177Lu-DOTATATE peptide receptor radionuclide therapy: dose response in small intestinal neuroendocrine tumors.

Fetched: October 11th, 2019, 5:01am GMT

177Lu-DOTATATE peptide receptor radionuclide therapy: dose response in small intestinal neuroendocrine tumors.

Neuroendocrinology. 2019 Oct 10;:

Authors: Jahn U, Ilan E, Sandström M, Garske-Román U, Lubberink M, Sundin A

Abstract
INTRODUCTION: Peptide receptor radionuclide therapy (PRRT) has during the last few years become frequently used in patients with progressive, disseminating well differentiated neuroendocrine tumors (NETs).
OBJECTIVE: To study whether the absorbed dose (AD) in small intestinal NET (SI-NET) metastases from PRRT with 177Lu-DOTATATE is related to tumor shrinkage.
MATERIALS AND METHODS: Dosimetry for one tumor was performed in each of 25 SI-NET patients based on sequential SPECT/CT at 1, 4 and 7 days after 177Lu-DOTATATE infusion. The SPECT data were corrected for the partial volume effect based on previous phantom measurements, and the unit density sphere model from OLINDA was used for absorbed dose calculations. Morphological therapy response was assessed by CT/MRI regarding tumor diameter, tumor volume, total liver tumor volume, liver volume and overall tumor response according to RECIST 1.1. Plasma chromogranin A and urinary 5-hydroxy-indole-acetic-acid were measured during PRRT and follow-up to assess biochemical response.
RESULTS: At the time of best response (BR) for tumor diameter and volume shrinkage the median absorbed dose was 128.6 Gy (range 28.4-326.9), and 140 Gy (range 50.9- 487.4), respectively. All metrics regarding tumor shrinkage and biochemical response were unrelated to the absorbed dose. A correlation was, however, found between the administered activity and the tumor volume shrinkage (p=0.01) and between the administered activity and RECIST 1.1 response (p=0.01).
CONCLUSIONS: It was not possible to demonstrate a tumor dose-response relationship in SI-NET metastases, with the applied dosimetry method, contrary to what was previously shown for pancreatic NETs.

PMID: 31597134 [PubMed - as supplied by publisher]

Permalink for 'Elevating SOX2 in prostate tumor cells upregulates expression of neuroendocrine genes, but does not reduce the inhibitory effects of enzalutamide.'

Elevating SOX2 in prostate tumor cells upregulates expression of neuroendocrine genes, but does not reduce the inhibitory effects of enzalutamide.

Fetched: October 8th, 2019, 5:01am GMT

Elevating SOX2 in prostate tumor cells upregulates expression of neuroendocrine genes, but does not reduce the inhibitory effects of enzalutamide.

J Cell Physiol. 2019 Oct 06;:

Authors: Metz EP, Wilder PJ, Dong J, Datta K, Rizzino A

Abstract
Prostate cancer (PCa) is one of the leading causes of cancer deaths in men. In this cancer, the stem cell transcription factor SOX2 increases during tumor progression, especially as the cancer progresses to the highly aggressive neuroendocrine-like phenotype. Other studies have shown that knockdown of RB1 and TP53 increases the expression of neuroendocrine markers, decreases the sensitivity to enzalutamide, and increases the expression of SOX2. Importantly, knockdown of SOX2 in the context of RB1 and TP53 depletion restored sensitivity to enzalutamide and reduced the expression of neuroendocrine markers. In this study, we examined whether elevating SOX2 is not only necessary, but also sufficient on its own to promote the expression of neuroendocrine markers and confer enzalutamide resistance. For this purpose, we engineered LNCaP cells for inducible overexpression of SOX2 (i-SOX2-LNCaP). As shown previously for other tumor cell types, inducible elevation of SOX2 in i-SOX2-LNCaP inhibited cell proliferation. SOX2 elevation also increased the expression of several neuroendocrine markers, including several neuropeptides and synaptophysin. However, SOX2 elevation did not decrease the sensitivity of i-SOX2-LNCaP cells to enzalutamide, which indicates that elevating SOX2 on its own is not sufficient to confer enzalutamide resistance. Furthermore, knocking down SOX2 in C4-2B cells, a derivative of LNCaP cells which is far less sensitive to enzalutamide and which expresses much higher levels of SOX2 than LNCaP cells, did not alter the growth response to this antiandrogen. Thus, our studies indicate that NE marker expression can increase independently of the sensitivity to enzalutamide.

PMID: 31587305 [PubMed - as supplied by publisher]

Detection of Nonhematologic Neoplasms by Routine Flow Cytometry Analysis.

Fetched: October 8th, 2019, 5:01am GMT

Detection of Nonhematologic Neoplasms by Routine Flow Cytometry Analysis.

Am J Clin Pathol. 2019 Oct 06;:

Authors: Annunziata J, Miller ML, Park DC, Vlad G, Bhagat G, Alobeid B

Abstract
OBJECTIVES: We investigated the ability of routine flow cytometry (FC) to detect nonhematologic neoplasms (non-HN) using antibody panels routinely used for the diagnosis of hematologic neoplasms.
METHODS: FC analyses of 4,000 various diagnostic samples were retrospectively reviewed to identify cases in which an aberrant, viable CD45-negative, nonhematologic neoplastic population was detected by FC panels designed to evaluate hematologic neoplasms.
RESULTS: A total of 57 (1.4%) diverse non-HNs were identified, representing neuroendocrine tumors (33/57) and carcinomas (9/57), as well as other malignancies (15/57) such as sarcoma and melanoma. The majority of neoplasms were positive for at least one antibody, typically CD56 (43/51, 84.3%), followed by CD117 (15/34, 44.1%) and CD138 (6/33, 18.2%).
CONCLUSIONS: Our findings highlight the importance of carefully inspecting CD45-negative events to identify non-HNs by routine FC analysis. This can help expedite further downstream immunophenotypic analysis of specimens and triage samples for appropriate genetic and molecular studies.

PMID: 31587038 [PubMed - as supplied by publisher]

Elderly patients with metastatic neuroendocrine tumors are undertreated and have shorter survival: The LyREMeNET study.

Fetched: October 8th, 2019, 5:01am GMT

Icon for S. Karger AG, Basel, Switzerland

Elderly patients with metastatic neuroendocrine tumors are undertreated and have shorter survival: The LyREMeNET study.

Neuroendocrinology. 2019 Oct 07;:

Authors: Lemelin A, Maucort-Boulch D, Castel-Kremer E, Forestier J, Hervieu V, Lorcet M, Boutitie F, Theillaumas A, Robinson P, Duclos A, Lombard-Bohas C, Walter T

Abstract
INTRODUCTION: The incidence of neuroendocrine tumors (NETs) is rising, especially in elderly patients. The elderly cancer population present considerable challenges, yet little is known about the characteristics, treatment pattern, and outcomes of metastatic NET patients.
METHODS: The Lyon Real-life Evidence in Metastatic NeuroEndocrine Tumors study (LyREMeNET, NCT03863106) included consecutive metastatic NET patients (mNETs), diagnosed between January 1990 and December 2017. The exclusion criteria were non-metastatic NET, poorly differentiated neuroendocrine carcinoma, and mixed neuroendocrine-nonneuroendocrine neoplasms. We aim to compare patients ≥70 years old (yo) to patients <70 yo.
RESULTS: A total of 866 patients were included, 198 (23%) were ≥70 yo. There was no significant difference in characteristics except that elderly patients had more frequently synchronous metastasis. Elderly patients received significantly fewer treatments (median of 2.0 lines vs. 3.0 respectively, p<0.0001), were significantly less frequently treated by chemotherapy (32% vs. 54%), targeted therapy (16% vs. 30%), peptide receptor radionuclide therapy (5% vs. 16%), and they underwent significantly less frequently locoregional intervention. Median overall survival was significantly shorter in elderly patients (5.2 years vs. 9.6 years). The most frequent cause of death was related to disease progression (71%). Multivariate analysis found that, after adjustment for tumor location, tumor grade and number of metastatic sites, age remained significantly associated with overall survival (HR: 1.66, 95%CI [1.26; 2.18]); indicating a poorer survival in patients ≥70 yo in comparison with younger, p=0.0003).
CONCLUSION: Patients ≥70 yo have a worse survival, die frequently from their disease, and are undertreated compared to younger patients.

PMID: 31586998 [PubMed - as supplied by publisher]

Perioperative and long-term outcomes of laparoscopic liver resections for non-colorectal liver metastases.

Fetched: October 7th, 2019, 5:01am GMT

Perioperative and long-term outcomes of laparoscopic liver resections for non-colorectal liver metastases.

Surg Endosc. 2019 Oct 04;:

Authors: Triantafyllidis I, Gayet B, Tsiakyroudi S, Tabchouri N, Beaussier M, Bennamoun M, Sarran A, Lefevre M, Louvet C, Fuks D

Abstract
BACKGROUND: Liver is a common metastatic site not only of colorectal but of non-colorectal neoplasms, as well. However, resection of non-colorectal liver metastases (NCRLMs) remains controversial. The aim of this retrospective study was to analyze the short- and long-term outcomes of patients undergoing laparoscopic liver resection (LLR) for NCRLMs.
METHODS: From a prospectively maintained database between 2000 and 2018, patients undergoing LLR for colorectal liver metastases (CRLMs) and NCRLMs were selected. Clinicopathologic, operative, short- and long-term outcome data were collected, analyzed, and compared among patients with CRLMs and NCRLMs.
RESULTS: The primary tumor was colorectal in 354 (82.1%), neuroendocrine in 21 (4.9%), and non-colorectal, non-neuroendocrine in the remaining 56 (13%) patients. Major postoperative morbidities were 12.7%, 19%, and 3.6%, respectively (p = 0.001), whereas the mortality was 0.6% for patients with CRLMs and zero for patients with NCRLMs. The rate of R1 surgical margin was comparable (p = 0.432) among groups. According to the survival analysis, 3- and 5-year recurrence-free survival (RFS) rates were 76.1% and 64.3% in the CRLM group, 57.1% and 42.3% in the neuroendocrine liver metastase (NELM) group, 33% and 20.8% in the non-colorectal, non-neuroendocrine liver metastase (NCRNNELM) group (p = 0.001), respectively. Three- and 5-year overall survival (OS) rates were 88.3% and 82.7% in the CRLM group, 85.7% and 70.6% in the NELM group, 71.4% and 52.9% in the NCRNNELM group (p = 0.001), respectively. In total, 113 out of 354 (31.9%) patients with CRLMs, 2 out of 21(9.5%) with NELMs, and 8 out of 56 (14.3%) patients with NCRNNELMs underwent repeat LLR for recurrent metastatic tumors.
CONCLUSION: LLR is safe and feasible in the context of a multimodal management where an aggressive surgical approach, necessitating even complex procedures for bilobar multifocal metastases and repeat hepatectomy for recurrences, is the mainstay and may be of benefit in the long-term survival, in selected patients with NCRNNELMs.

PMID: 31586246 [PubMed - as supplied by publisher]

Lanreotide therapy vs active surveillance in MEN1-related pancreatic neuroendocrine tumors

Fetched: October 7th, 2019, 5:01am GMT

Lanreotide therapy vs active surveillance in MEN1-related pancreatic neuroendocrine tumors <2 cm.

J Clin Endocrinol Metab. 2019 Oct 05;:

Authors: Faggiano A, Modica R, Lo Calzo F, Camera L, Napolitano V, Altieri B, de Cicco F, Bottiglieri F, Sesti F, Badalamenti G, Isidori AM, Colao A

Abstract
PURPOSE: Pancreatic neuroendocrine tumors (pNETs) are frequent in MEN1 syndrome. They are usually not surged unless a size >1-2 cm or a growth rate >0.5 cm per year. Somatostatin analogues represent one of the main therapeutic option in pNETs, but they have never been prospectively investigated in MEN1-related pNETs. The aim of this study was to prospectively evaluate the effectiveness of lanreotide in patients with MEN1-related pNETs <2 cm.
METHODS: MEN1 patients with one or more pNETs <2 cm of maximal diameter were considered. Study design was prospective observational, with comparison of patients treated with lanreotide autogel 120 mg every 28 days (LAN group) and patients in active surveillance, not receiving any therapy (AS group).
RESULTS: Forty-two patients were enrolled: 23 in LAN and 19 in AS group. Median follow-up was 73 months. As a whole, 91 pNETs were identified at initial imaging. The median PFS was significantly longer in LAN than in AS group (median not reached vs 40 months, p<0.001). In the LAN group, 4 patients had an objective tumor response, 15 patients had stable disease, while 4 had tumor progression. In the AS group, 13 patients had pNET progression, while 6 were stable.
CONCLUSIONS: This is the first prospective study evaluating the efficacy of somatostatin analogues in MEN1-related pNETs. These findings highlight that lanreotide autogel is effective as anti-proliferative therapy in MEN1-related pNETs <2cm, suggesting the use of these compounds to arrest the development of tumor lesions as well as to delay or avoid pancreatic surgery.

PMID: 31586182 [PubMed - as supplied by publisher]

Permalink for 'Lymphovascular invasion as a prognostic value in small rectal neuroendocrine tumor treated by local excision: A systematic review and meta-analysis.'

Lymphovascular invasion as a prognostic value in small rectal neuroendocrine tumor treated by local excision: A systematic review and meta-analysis.

Fetched: October 7th, 2019, 5:01am GMT

Lymphovascular invasion as a prognostic value in small rectal neuroendocrine tumor treated by local excision: A systematic review and meta-analysis.

Pathol Res Pract. 2019 Sep 21;:152642

Authors: Kang HS, Kwon MJ, Kim TH, Han J, Ju YS

Abstract
Because rectal neuroendocrine tumors (NETs) are usually small-sized despite of malignant potential, endoscopic resection techniques are recommended. It is unclear whether the lymphovascular invasion (LVI) in the endoscopic resected specimens of small rectal NETs should be indicated for completion surgery. We performed a systematic review and meta-analysis for the incidence of LVI in small rectal NETs (≤20 mm) treated by endoscopic resection and its prognostic impacts. We searched the relevant literature published before January 2019. A total of 21 publications including 1816 patients were enrolled. Overall prevalence of LVI in small rectal NETs was 21.8%. Immunohistochemical method significantly increased the detection rate of LVI up to 35.8% compared than H&E staining only (13.2%). Tumor size more than 5 mm was a risk factor for LVI in small rectal NET, whereas tumor grade did not influence the risk. The LVI in the endoscopic resected specimens was a risk factor for subsequent lymph node metastasis. Separately analyzed in detail, the vascular invasion had a stronger impact on lymph node metastasis than the lymphatic invasion. The prognosis of endoscopically treated rectal NET with LVI was excellent with only 0.3% of recurrence rate during the 5-year follow-up period. LVI is highly prevalent and a risk factor for lymph node metastasis in the small rectal NETs. Endoscopically treated small rectal NETs had excellent short-term prognoses despite of LVI. Immediate completion radical surgery is not absolutely necessary for the LVI-positive small rectal NETs. However, long-term follow-up is recommended for any delayed recurrence.

PMID: 31585816 [PubMed - as supplied by publisher]

Small-cell carcinoma-associated ovarian mucinous carcinoma: A case report and literature review.

Fetched: October 7th, 2019, 5:01am GMT

Small-cell carcinoma-associated ovarian mucinous carcinoma: A case report and literature review.

Pathol Res Pract. 2019 Aug 27;:152619

Authors: Wei J, Wang Y, Li P, Fan L, Li M, Wang Z

Abstract
Neuroendocrine neoplasm-associated ovarian mucinous carcinoma occurs extremely rarely. Here, we report an ovarian composite tumor consisting of small-cell carcinoma and mucinous carcinoma in a 51-year-old woman presented with abdominal distention. Ultrasonography revealed the presence of a complex irregular cystic solid mass. Microscopic findings showed pulmonary-type small-cell carcinoma-associated, intestinal-type ovarian mucinous carcinoma-with positive results for several neuroendocrine markers (chromogranin, CD56) and the thyroid transcription factor-1. The patient underwent total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and six cycles of adjuvant chemotherapy but died eight months after the surgery due to disease progression. Few reports are available in China on this clinicopathological feature in this composite tumor type. The timely identification of ovarian small-cell carcinoma among other ovarian tumors is critically important to the accurate and prompt determination of the therapy due to its high invasiveness and metastatic potential.

PMID: 31585810 [PubMed - as supplied by publisher]

Rare Pulmonary Neuroendocrine Cells Are Stem Cells Regulated by Rb, p53, and Notch.

Fetched: October 6th, 2019, 5:01am GMT

Rare Pulmonary Neuroendocrine Cells Are Stem Cells Regulated by Rb, p53, and Notch.

Cell. 2019 Oct 03;179(2):403-416.e23

Authors: Ouadah Y, Rojas ER, Riordan DP, Capostagno S, Kuo CS, Krasnow MA

Abstract
Pulmonary neuroendocrine (NE) cells are neurosensory cells sparsely distributed throughout the bronchial epithelium, many in innervated clusters of 20-30 cells. Following lung injury, NE cells proliferate and generate other cell types to promote epithelial repair. Here, we show that only rare NE cells, typically 2-4 per cluster, function as stem cells. These fully differentiated cells display features of classical stem cells. Most proliferate (self-renew) following injury, and some migrate into the injured area. A week later, individual cells, often just one per cluster, lose NE identity (deprogram), transit amplify, and reprogram to other fates, creating large clonal repair patches. Small cell lung cancer (SCLC) tumor suppressors regulate the stem cells: Rb and p53 suppress self-renewal, whereas Notch marks the stem cells and initiates deprogramming and transit amplification. We propose that NE stem cells give rise to SCLC, and transformation results from constitutive activation of stem cell renewal and inhibition of deprogramming.

PMID: 31585080 [PubMed - in process]

Permalink for 'The usefulness of lymphoid enhancer-binding factor 1 and androgen receptor in diagnosing solid pseudopapillary neoplasm of the pancreas on cytopathology.'

The usefulness of lymphoid enhancer-binding factor 1 and androgen receptor in diagnosing solid pseudopapillary neoplasm of the pancreas on cytopathology.

Fetched: October 6th, 2019, 5:01am GMT

The usefulness of lymphoid enhancer-binding factor 1 and androgen receptor in diagnosing solid pseudopapillary neoplasm of the pancreas on cytopathology.

Cancer Cytopathol. 2019 Oct 04;:

Authors: McHugh KE, Stelow EB, Harrison GP, Policarpio-Nicolas MLC

Abstract
BACKGROUND: Solid pseudopapillary neoplasm (SPN) is an uncommon tumor that is challenging to diagnose on cytology due to morphologic overlap with other pancreatic neoplasms. Recently, putative diagnostic markers for SPN have been reported in the surgical pathology literature, with nuclear positivity for lymphoid enhancer-binding factor 1 (LEF1) and androgen receptor (AR) identified in >90% and >80% of cases, respectively. In the current study, the authors sought to evaluate the sensitivity and specificity of LEF1 and AR on SPN cytology specimens and available corresponding surgical resection specimens.
METHODS: Immunohistochemistry was performed using monoclonal antibodies against LEF1 and AR on 19 SPN cytology cases and 15 corresponding follow-up surgical resection specimens from 2 institutions. To evaluate specificity, the authors stained 23 non-SPN tumors diagnosed on cytology with corresponding surgical specimens (4 acinar cell carcinomas, 9 pancreatic neuroendocrine tumors, and 10 ductal adenocarcinomas). Positivity for LEF1 and AR was defined as any nuclear staining within neoplastic nuclei.
RESULTS: LEF1 was found to be positive in 18 of 19 cytology cases (94.7%) and 15 of 15 corresponding surgical resection specimens (100%). AR was positive in 4 of 16 cytology cases (25.0%) and 4 of 15 corresponding surgical resection specimens (26.7%). Among non-SPN tumors, LEF1 demonstrated a specificity of 87% whereas the specificity for AR was 100%.
CONCLUSIONS: LEF1 for SPN on cytology material was found to demonstrate a sensitivity of 94.7% and a specificity of 87%. Although AR was found to have a specificity of 100%, its sensitivity was lower (25%). LEF1 could be a valuable immunostain on cytology cell block material for the diagnosis of SPN. However, the same may not hold true for AR.

PMID: 31584754 [PubMed - as supplied by publisher]

Permalink for 'Excellent Response to 177Lu-DOTATATE Peptide Receptor Radionuclide Therapy in a Patient With Progressive Metastatic Castration-Resistant Prostate Cancer With Neuroendocrine Differentiation After 177Lu-PSMA Therapy.'

Excellent Response to 177Lu-DOTATATE Peptide Receptor Radionuclide Therapy in a Patient With Progressive Metastatic Castration-Resistant Prostate Cancer With Neuroendocrine Differentiation After 177Lu-PSMA Therapy.

Fetched: October 6th, 2019, 5:01am GMT

Excellent Response to 177Lu-DOTATATE Peptide Receptor Radionuclide Therapy in a Patient With Progressive Metastatic Castration-Resistant Prostate Cancer With Neuroendocrine Differentiation After 177Lu-PSMA Therapy.

Clin Nucl Med. 2019 Oct 03;:

Authors: Liu C, Liu T, Zhang J, Baum RP, Yang Z

Abstract
Prostate cancer with neuroendocrine differentiation is associated with a poor prognosis, rapid disease progression, and treatment resistance, and constitutes a diagnostic and therapeutic dilemma. We present images of Lu-DOTATATE scan and Ga-DOTATATE PET/CT scan conducted on a 65-year-old man with prostate cancer with neuroendocrine differentiation, whose disease progressed despite conventional treatment and Lu-PSMA radioligand therapy; however, an extraordinary radiographic tumor remission, biochemical response, and improvement of clinical symptoms were observed after the patient underwent Lu-DOTATATE peptide receptor radionuclide therapy.

PMID: 31584494 [PubMed - as supplied by publisher]

Primary Ovarian High-grade Neuroendocrine Carcinoma With Merkel Cell-like Immunophenotype Arising in a Teratoma.

Fetched: October 6th, 2019, 5:01am GMT

Primary Ovarian High-grade Neuroendocrine Carcinoma With Merkel Cell-like Immunophenotype Arising in a Teratoma.

Int J Gynecol Pathol. 2019 Oct 03;:

Authors: Harkness R, Kelly PJ, McCluggage WG

PMID: 31584482 [PubMed - as supplied by publisher]

Permalink for 'Carcinoid heart failure in a duodenal neuroendocrine tumor: role of cardiac surgery in a challenging patient and brief review of the literature.'

Carcinoid heart failure in a duodenal neuroendocrine tumor: role of cardiac surgery in a challenging patient and brief review of the literature.

Fetched: October 6th, 2019, 5:01am GMT

Carcinoid heart failure in a duodenal neuroendocrine tumor: role of cardiac surgery in a challenging patient and brief review of the literature.

Acta Oncol. 2019 Oct 04;:1-5

Authors: La Salvia A, Brizzi MP, Trevisi E, Parisi F, Muratori L, Atzeni F, Di Maio M, Scagliotti GV

PMID: 31583924 [PubMed - as supplied by publisher]

Neuroendocrine marker staining pattern categorization of small-sized pulmonary large cell neuroendocrine carcinoma.

Fetched: October 6th, 2019, 5:01am GMT

Neuroendocrine marker staining pattern categorization of small-sized pulmonary large cell neuroendocrine carcinoma.

Thorac Cancer. 2019 Oct 03;:

Authors: Minami K, Tanaka Y, Ogawa H, Jimbo N, Nishio W, Yoshimura M, Itoh T, Maniwa Y

Abstract
BACKGROUND: The aim of this study was to identify subgroups with good or bad prognosis in patients with pulmonary large cell neuroendocrine carcinoma (LCNEC) based on immunostaining patterns with neuroendocrine markers and compare them with small cell lung carcinoma (SCLC).
METHODS: From January 2001 to December 2017, of all patients with resected LCNEC and SCLC, we selected patients whose pathological tumor sizes were ≤30 mm in diameter (defined as small-sized tumors) and who underwent complete resection with lymphadenectomy. We classified patients with small-sized LCNEC (sLCNEC) into two subgroups based on immunostaining patterns with three neuroendocrine markers (chromogranin A, synaptophysin, and NCAM) and compared them to small-sized SCLC (sSCLC).
RESULTS: A total of 48 patients with sLCNEC and 39 patients with sSCLC were enrolled. Of 48 patients with sLCNEC, 21 were categorized as the small-sized triple-positive group (sTP), whose patients were positive for the three neuroendocrine markers, and 27 patients were categorized as the small-sized nontriple-positive group (sNTP), whose patients were not positive for all three neuroendocrine markers. The percentage of lymph node metastasis was significantly lower in sNTP than in sTP and sSCLC. There was no significant difference in overall survival, but recurrence-free survival (RFS) and tumor-specific survival (TSS) were significantly poorer in sTP and sSCLC than in sNTP. Multivariate analysis revealed sTP and sSCLC were independent prognostic factors for poorer RFS and TSS than those of sNTP.
CONCLUSIONS: The sNTP subgroup had a good prognosis and the sTP subgroup a poor prognosis. There were some similarities in clinicopathological features between sTP and sSCLC.

PMID: 31583856 [PubMed - as supplied by publisher]

Synchronous bilateral adrenalectomy in ACTH-dependent hypercortisolism: predictors, biomarkers and outcomes.

Fetched: October 6th, 2019, 5:01am GMT

Synchronous bilateral adrenalectomy in ACTH-dependent hypercortisolism: predictors, biomarkers and outcomes.

Endocrine. 2019 Oct 03;:

Authors: Chiloiro S, Giampietro A, Raffaelli M, D'Amato G, Bima C, Lauretti L, Anile C, Lombardi CP, Rindi G, Bellantone R, De Marinis L, Pontecorvi A, Bianchi A

Abstract
INTRODUCTION: Hypercortisolism requires a prompt therapeutic management to reduce the risk of development of a potential fatal emergency. A synchronous bilateral adrenalectomy (SBA) is effective in recovering hypercortisolism. However, specific indications for an SBA are not available. We aimed to evaluate the outcome of patients who underwent an SBA and to identify biomarkers able to predict the requirements of an SBA.
PATIENTS AND METHODS: A mono-centric and longitudinal study was conducted on 19 consecutive patients who underwent SBA for ACTH-dependent hypercortisolism between December 2003 and December 2017. This study population was compared to two control groups composed of patients cured after the resection of the ACTH secreting pituitary adenoma (Group A: 44 patients) and of the ACTH-secreting neuroendocrine tumours (Group B: 8 patients).
RESULTS: Short- or long-term SBA complications or the recurrence of hypercortisolism did not occur. A single patient experienced Nelson syndrome. Clinical features after SBA showed improvement in the glico-metabolic assessment, hypertension, bone metabolism and the occurrence of hypokalaemia and infections. The younger the age at the time of Cushing's disease diagnosis, the longer the duration of active hypercortisolism, higher values of plasmatic ACTH and Cortisol (1 month after pituitary neurosurgery) and higher values of Ki67 in pituitary adenomas were detected in this study population as compared to Group A.
CONCLUSIONS: SBA is an effective and safe treatment for patients with unmanageable ACTH-dependent hypercortisolism. A multidisciplinary team in a referral centre with a high volume of patients is strongly recommended for the management of these patients and the identification of patients, for better surgical timing.

PMID: 31583577 [PubMed - as supplied by publisher]

Permalink for '68Ga-DOTATOC PET/CT in detecting neuroendocrine tumours responsible for initial or recurrent paraneoplastic Cushing's syndrome.'

68Ga-DOTATOC PET/CT in detecting neuroendocrine tumours responsible for initial or recurrent paraneoplastic Cushing's syndrome.

Fetched: October 6th, 2019, 5:01am GMT

68Ga-DOTATOC PET/CT in detecting neuroendocrine tumours responsible for initial or recurrent paraneoplastic Cushing's syndrome.

Endocrine. 2019 Oct 03;:

Authors: Bélissant Benesty O, Nataf V, Ohnona J, Michaud L, Zhang-Yin J, Bertherat J, Chanson P, Reznik Y, Talbot JN, Montravers F

Abstract
PURPOSE: Paraneoplastic Cushing's syndrome (PCS) is frequently caused by neuroendocrine tumours (NETs). Approximately 20% of tumours are still occult years later. Gallium-68 somatostatin receptor-PET/CT is promising for the detection of the causal primary NET, but its role in case of recurrent PCS is rarely reported. We report our experience with DOTATOC PET/CT in localising the causal NET in cases of initial but also recurrent PCS, and its clinical impact.
METHODS: A retrospective review of all DOTATOC PET/CTs performed in consecutive patients referred for PCS to our centre, between January 2011 and June 2017, was done. Nineteen patients underwent 26 PET/CTs, 13 for detection of a primary NET, seven for persistent or recurrent PCS after resection, and six for surveillance after resection of NETs previously detected on a DOTATOC PET/CT in our centre.
RESULTS: Among the 13 PET/CTs performed to search for primary NET, five were positive: four carcinoid lung tumours were confirmed after resection and one lung focus was not confirmed since surgery would have carried a high risk. Clinical impact was 23% (3/13). Among the seven PET/CTs performed for persistent or recurrent PCS, six were true-positive, with confirmation of metastatic lymph nodes after resection. Clinical impact was 57% (4/7). All PET/CTs performed for surveillance were true-negative.
CONCLUSIONS: DOTATOC PET/CT seems to be a valuable tool for detection of the NET responsible for persistent or recurrent PCS after surgery. In this context, DOTATOC PET/CT was more effective than for the detection of the causal tumour in initial PCS.

PMID: 31583575 [PubMed - as supplied by publisher]

Brain metastasis of Merkel cell carcinoma - A rare case report.

Fetched: October 6th, 2019, 5:01am GMT

Brain metastasis of Merkel cell carcinoma - A rare case report.

Surg Neurol Int. 2019;10:172

Authors: Caramanti RL, Chaddad Neto FE, Meguins LC, Rocha CE, de Moraes DF, Góes MJ

Abstract
Background: Merkel cell carcinoma (MCC) is a rare neuroendocrine skin tumor. In our knowledge, only 30 cases of brain metastasis were reported in literature. The authors report a case of 57-year-old male with elevated intracranial pressure signs, which a frontal mass with pathological diagnosis of MCC.
Case Description: A 57-year-old male was admitted with a 3-month history of progressive headache, associated with nausea and dizziness. The magnetic resonance imaging showed a left frontal lobe, parasagittal, and nodular lesion with perilesional edema. The patient underwent complete surgical resection with success. The adjuvant treatment was radiotherapy and chemotherapy.
Conclusion: In our knowledge, there is a little number of cases of MCC reported in literature. Surgical management is considered in cases with intracranial hypertension or focal signs. The adjuvant treatment options are immunotherapy and radiotherapy.

PMID: 31583169 [PubMed]

Targeting Wnt/EZH2/microRNA-708 signaling pathway inhibits neuroendocrine differentiation in prostate cancer.

Fetched: October 6th, 2019, 5:01am GMT

Targeting Wnt/EZH2/microRNA-708 signaling pathway inhibits neuroendocrine differentiation in prostate cancer.

Cell Death Discov. 2019;5:139

Authors: Shan J, Al-Muftah MA, Al-Kowari MK, Abuaqel SWJ, Al-Rumaihi K, Al-Bozom I, Li P, Chouchane L

Abstract
Prostate cancer (PC) castration resistance has been linked to the differentiation of PC luminal cells into hormone-refractory neuroendocrine (NE) cells. However, the molecular mechanisms controlling the emergence of lethal NE prostate cancer (NEPC) remain unclear. The present study aimed to investigate the mechanisms underlying the transition from prostate adenocarcinoma to NEPC. The microRNA miR-708 was involved in NE differentiation and was downregulated in NEPC cells and tumor specimens. miR-708 targeted Sestrin-3 to inhibit Forkhead Box O1 (FOXO1) phosphorylation, resulting in apoptosis of prostate adenocarcinoma cells and AKT-inactivated NEPC cells, the latter of which was consistent with the progression of tumor xenografts in mice under miR-708 treatment. In silico analysis of PC and NEPC tumor specimens suggested that the polycomb repressive complex subunit Enhancer of zeste homolog 2 (EZH2) was particularly overexpressed in NEPC. Notably, EZH2 bound to the miR-708 promoter and induced its silencing in NEPC. Inhibition of EZH2 prevented NE differentiation of PC cells. EZH2 expression was regulated by both Cyclin Dependent Kinase 1 (CDK1) and Wnt signaling. Silencing transcription factor 4 (TCF4), as a key protein in Wnt signaling, prevented NEPC formation. These results provide a molecular basis for the roles of miR-708 and EZH2 in NE differentiation in PC and highlight a new paradigm in NEPC formation and survival.

PMID: 31583122 [PubMed]

Nodal Merkel Cell Carcinoma in Head and Neck Lesions with an Unknown Primary: A Case Report in Light of the Literature.

Fetched: October 6th, 2019, 5:01am GMT

Nodal Merkel Cell Carcinoma in Head and Neck Lesions with an Unknown Primary: A Case Report in Light of the Literature.

Yonago Acta Med. 2019 Sep;62(3):258-262

Authors: Ikeda R, Ohta N, Fukaya S, Shoji F, Suzuki T, Noguchi N, Kakuta R, Hayashi K, Kiba T, Murakami K, Nakamura Y

PMID: 31582892 [PubMed]

Long-term analgesic pharmacotherapy in addiction to intranasal fentanyl.

Fetched: October 6th, 2019, 5:01am GMT

Long-term analgesic pharmacotherapy in addiction to intranasal fentanyl.

BMJ Support Palliat Care. 2019 Oct 03;:

Authors: Olczak B, Zaforemska A, Cialkowska-Rysz A

Abstract
OBJECTIVE: The risk of inappropriate use of opioid drugs increases, especially the short-acting ones. The risk of addiction in patients with cancer with a relatively good prognosis is a challenge. The aim of the study is to evaluate the decision to continue therapy with a short-acting fentanyl.
METHODS: The study concerns a 49-year-old male patient with an advanced neuroendocrine tumour in the pre-sacral region. The research method includes the medical history and physical examination, an analysis of the patient's medical record and a self-designed questionnaire to assess the degree of dependence on opioid drugs.
RESULTS: The analysis of the results of the survey confirmed the patient's dependence on opioid drugs. He gave positive answers to 16 out of 19 questions in the survey.
CONCLUSION: Despite an addiction, the improvement of life quality is of the utmost importance. Therefore, decision to continue the intranasal fentanyl therapy is justified because of toleration and a high satisfactory effect.

PMID: 31582384 [PubMed - as supplied by publisher]

Tailoring a rapid autopsy protocol to explore cancer evolution: a patient collaboration.

Fetched: October 5th, 2019, 5:00am GMT

Tailoring a rapid autopsy protocol to explore cancer evolution: a patient collaboration.

N Z Med J. 2019 Oct 04;132(1503):83-92

Authors: Blenkiron C, Robb T, Parker K, Kramer N, Stables S, Tse R, Modahl L, Coats E, Print C, Lawrence B

Abstract
Genomic analysis of tissues from rapid autopsy programmes has transformed our understanding of cancer. However, these programmes are not yet established in New Zealand. Our neuroendocrine tumour research group, NETwork!, received a request from a patient wishing to donate tumour tissues post-mortem. This viewpoint article summarises the ethical, logistical and social process undertaken to accept this patient's generous donation, and highlights the scientific and educational value of such a gift.

PMID: 31581185 [PubMed - in process]

Permalink for 'The efficacy and safety of scheduled early endoscopic ultrasonography-guided ethanol reinjection for patients with pancreatic neuroendocrine tumors: A prospective pilot study.'

The efficacy and safety of scheduled early endoscopic ultrasonography-guided ethanol reinjection for patients with pancreatic neuroendocrine tumors: A prospective pilot study.

Fetched: October 5th, 2019, 5:00am GMT

The efficacy and safety of scheduled early endoscopic ultrasonography-guided ethanol reinjection for patients with pancreatic neuroendocrine tumors: A prospective pilot study.

Dig Endosc. 2019 Oct 03;:

Authors: Matsumoto K, Kato H, Kawano S, Fujiwara H, Nishida K, Harada R, Fujii M, Yoshida R, Umeda Y, Hinotsu S, Yagi T, Okada H

Abstract
Endoscopic ultrasonography (EUS)-guided ethanol injection was recently proposed for the treatment of patients with small pancreatic neuroendocrine tumors (p-NETs); however, tips on how to perform safe and effective procedures are unclear. We launched a pilot study for scheduled early EUS-guided ethanol reinjection for small p-NETs. The major eligibility criteria were the presence of a pathologically diagnosed grade (G) 1 or G2, a tumor size of ≤2 cm and being a poor or rejected candidate for surgery. For the treatment, we used a 25-gauge needle and pure ethanol. Contrast-enhanced computed tomography (CE-CT) was performed on postoperative day 3, and if enhanced areas of the tumor were still apparent, an additional session was scheduled during the same hospitalization period. The primary endpoint was the complete ablation rate at one month after treatment, and the secondary endpoint was the procedure-related adverse events. A total of five patients were treated. The median size of the tumor was 10 (range: 7-14) mm. Of the five patients, three underwent an additional session. The median volume of ethanol injection per session was 0.8 (range: 0.3-1.0) mL, and the total was 1.0 (0.9-1.8) mL. Complete ablation was achieved in 4 of the 5 tumors (80%) with no adverse events. During one year of follow-up, none of the patients reported any procedure-related adverse events, and no recurrence of tumor. Scheduled early EUS-guided ethanol reinjection appears to be safe and effective for treating small p-NETs (UMIN number: 000018834).

PMID: 31580507 [PubMed - as supplied by publisher]

Permalink for 'Endoscopic ultrasound-guided fine-needle biopsy is superior to fine-needle aspiration in assessing pancreatic neuroendocrine tumors.'

Endoscopic ultrasound-guided fine-needle biopsy is superior to fine-needle aspiration in assessing pancreatic neuroendocrine tumors.

Fetched: October 5th, 2019, 5:00am GMT

Endoscopic ultrasound-guided fine-needle biopsy is superior to fine-needle aspiration in assessing pancreatic neuroendocrine tumors.

Endosc Int Open. 2019 Oct;7(10):E1281-E1287

Authors: Leeds JS, Nayar MK, Bekkali NLH, Wilson CH, Johnson SJ, Haugk B, Darne A, Oppong KW

Abstract
Background and study aims Pancreatic neuroendocrine tumors (PanNETs) outcomes are dependent upon grading by Ki67. This study compared endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) to fine-needle aspiration (FNA) in assessing PanNETs. Patients and methods All pancreatic histology for PanNET between January 2009 and June 2017 was included if EUS sampling was performed prior to surgical resection. Ki67 and grade from FNA and FNB samples was compared to surgical histology using correlation coefficient and kappa values. Subgroup analysis was performed for purely solid lesions, lesions < 2 cm and FNB needle type. Results One hundred sixity-four patients had PanNET of which 57 underwent surgical resection. Thirty-five lesions underwent FNA and 26 FNB (4 had both) confirming PanNET. 23/ of 35 FNA samples reported Ki67/grading compared to all 26 FNB samples ( P = 0.0006). Compared to surgical histology, Ki67 on FNA correlated poorly overall (r = -0.08), in solid lesions (r = -0.102) and lesions < 2 cm (r = -0.149) whereas FNB correlated moderately overall (r = 0.65), in solid lesions (r = 0.64) and lesions < 2 cm (r = 0.61). Tumor grade showed poor agreement (kappa) with FNA overall (0.026), in solid lesions (0.044) and lesions < 2 cm (0.00) whereas FNB showed moderate-good agreement overall (0.474), in solid lesions (0.58) and lesions < 2 cm (0.745). Fork-tip FNB needles Ki67 showed strong correlation with surgical histology (r = 0.788) compared to reverse bevel FNB needles (r = 0.521). Both FNB needles showed moderate agreement with tumor grade. Conclusion FNB samples were significantly more likely than FNA to provide adequate material for Ki67/grading and showed a closer match to surgical histology. FNB needle types require prospective investigation.

PMID: 31579710 [PubMed]

[Un- and dedifferentiated endometrial carcinoma : A rare entity with a wide range of differential diagnosis].

Fetched: October 5th, 2019, 5:00am GMT

[Un- and dedifferentiated endometrial carcinoma : A rare entity with a wide range of differential diagnosis].

Pathologe. 2019 Oct 02;:

Authors: Höhn AK, Brambs CE, Opitz S, Erber R, Hartmann A, Horn LC

Abstract
Dedifferentiated endometrial carcinomas (ECs) are composed of undifferentiated EC and a FIGO grade 1 or 2 endometrioid carcinoma. The undifferentiated component represents a malignant epithelial neoplasm with no obvious differentiation and immunohistochemical loss of PAX8, E‑cadherin and focal expression of EMA and/or CK18 and the predominant presence of nuclear staining for INI1 (SMARCB1) and BRG1 (SMARCA4). The main differential diagnoses include poorly differentiated endometrioid EC, neuroendocrine carcinoma, lymphoma, plasmocytoma, high-grade endometrial stromal sarcomas, undifferentiated uterine sarcomas (UUS), carcinosarcomas, and metastases to the endometrium. The histogenesis is not yet fully understood and molecular data are still limited. Some tumors represent a loss of MHL1 and PMS2 staining due to MLH1-promotor methylation. Rare cases are associated with Lynch syndrome or POLE mutation. The un- or dedifferentiated EC represents a high-grade endometrial carcinoma that requires extended surgery and indicates a poor prognosis. In cases with mismatch repair protein deficiency or POLE mutation, immuno-oncological treatment with checkpoint inhibitors are a therapeutic option.

PMID: 31578630 [PubMed - as supplied by publisher]

Permalink for 'A standardised diagnostic approach to pituitary neuroendocrine tumours (PitNETs): a European Pituitary Pathology Group (EPPG) proposal.'

A standardised diagnostic approach to pituitary neuroendocrine tumours (PitNETs): a European Pituitary Pathology Group (EPPG) proposal.

Fetched: October 5th, 2019, 5:00am GMT

A standardised diagnostic approach to pituitary neuroendocrine tumours (PitNETs): a European Pituitary Pathology Group (EPPG) proposal.

Virchows Arch. 2019 Oct 02;:

Authors: Villa C, Vasiljevic A, Jaffrain-Rea ML, Ansorge O, Asioli S, Barresi V, Chinezu L, Gardiman MP, Lania A, Lapshina AM, Poliani L, Reiniger L, Righi A, Saeger W, Soukup J, Theodoropoulou M, Uccella S, Trouillas J, Roncaroli F

Abstract
The 2017 World Health Organization (WHO) classification proposes to type and subtype primary adenohypophyseal tumours according to their cell lineages with the aim to establish more uniform tumour groups. The definition of atypical adenoma was removed in favour of high-risk adenoma, and the assessment of proliferative activity and invasion was recommended to diagnose aggressive tumours. Recently, the International Pituitary Pathology Club proposed to replace adenoma with the term of pituitary neuroendocrine tumour (PitNET) to better reflect the similarities between adenohypophyseal and neuroendocrine tumours of other organs. The European Pituitary Pathology Group (EPPG) endorses this terminology and develops practical recommendations for standardised reports of PitNETs that are addressed to histo- and neuropathologists. This brief report presents the results of EPPG's consensus for the reporting of PitNETs and proposes a diagnostic algorithm.

PMID: 31578606 [PubMed - as supplied by publisher]

Permalink for 'Surgery Versus Surveillance for Well-Differentiated, Nonfunctional Pancreatic Neuroendocrine Tumors: An 11-Year Analysis of the National Cancer Database.'

Surgery Versus Surveillance for Well-Differentiated, Nonfunctional Pancreatic Neuroendocrine Tumors: An 11-Year Analysis of the National Cancer Database.

Fetched: October 5th, 2019, 5:00am GMT

Surgery Versus Surveillance for Well-Differentiated, Nonfunctional Pancreatic Neuroendocrine Tumors: An 11-Year Analysis of the National Cancer Database.

Oncologist. 2019 Oct 02;:

Authors: Assi HA, Mukherjee S, Kunz PL, Machiorlatti M, Vesely S, Pareek V, Hatoum H

Abstract
BACKGROUND: Pancreatic neuroendocrine tumors (panNETs) are a rare group of tumors that make up 2%-3% of pancreatic tumors. Recommended treatment for panNETs generally consists of resection for symptomatic or large asymptomatic tumors; however, optimal management for localized disease is still controversial, with conflicting recommendations in established guidelines. Our study aim is to compare surgical intervention versus active surveillance in nonmetastatic panNETs by size of primary tumor.
MATERIALS AND METHODS: Using the National Cancer Database, we identified 2,004 patients diagnosed with localized well-differentiated, nonfunctional panNETs (NF-panNETs) between 2004 and 2015. Patients' clinicopathologic characteristics, treatment modalities, and overall survival (OS) were analyzed using frequency statistics, chi-square, and Kaplan-Meier curves. The objective of the study is to assess the outcome of surgical resection versus nonoperative management in patients with panNETs with different tumor sizes.
RESULTS: Tumor sizes were divided into three categories: <1 cm, 1-2 cm, and >2 cm. The number of patients with tumor size <1 cm, 1-2 cm, and >2 cm was 220 (11%), 794 (39.6%), and 990 (49.4%), respectively. Overall, 1,781 underwent surgical resection, whereas 223 patients did not. Median follow-up was 25.9 months. After adjusting for covariates, surgical resection was associated with improved OS in patients with tumor size 1-2 cm (hazard ratio [HR] = 0.37) and >2c m (HR = 0.30) but not <1 cm (HR = 2.81). Independent prognostic factors were age at diagnosis, Charlson-Deyo comorbidity score, stage, tumor location, and surgical resection. Higher tumor grade was not associated with worse OS.
CONCLUSION: Our findings suggest that active surveillance is potentially a safe approach for NF-panNETs <1 cm. Larger tumors likely need active intervention. Intermediate-grade tumors did not result in worse survival outcome compared with low-grade tumors. Future studies might consider prospective randomized clinical trials to validate our findings.
IMPLICATIONS FOR PRACTICE: The present study seeks to address the discrepancy in treatment recommendations in the management of nonfunctional pancreatic neuroendocrine tumors (NF-panNETs) by evaluating whether surgical resection is associated with improved overall survival in different tumor size groups as well as elucidating independent prognostic factors in patients with NF-panNETs. Data from the National Cancer Database were reviewed. This study's findings suggest that active surveillance is potentially a safe approach for NF-panNETs <1 cm. Larger tumors likely need active intervention. Independent prognostic factors include age at diagnosis, Charlson-Deyo comorbidity score, stage, tumor location, and surgical resection. These findings will help guide medical and surgical oncologists when formulating treatment plans for patients with small NF-panNETs.

PMID: 31578277 [PubMed - as supplied by publisher]

Permalink for 'Pancreatoblastoma: Cytologic and histologic analysis of 12 adult cases reveals helpful criteria in their diagnosis and distinction from common mimics.'

Pancreatoblastoma: Cytologic and histologic analysis of 12 adult cases reveals helpful criteria in their diagnosis and distinction from common mimics.

Fetched: October 5th, 2019, 5:00am GMT

Pancreatoblastoma: Cytologic and histologic analysis of 12 adult cases reveals helpful criteria in their diagnosis and distinction from common mimics.

Cancer Cytopathol. 2019 Oct 03;:

Authors: Reid MD, Bhattarai S, Graham RP, Pehlivanoglu B, Sigel CS, Shi J, Saqi A, Shirazi M, Xue Y, Basturk O, Adsay V

Abstract
BACKGROUND: Pancreatoblastoma (PBL) is a rare malignant pancreatic tumor seen predominantly in childhood, and its cytologic diagnosis remains challenging.
METHODS: Twelve fine-needle-aspirations from 11 adults were analyzed.
RESULTS: In total, 6 men and 5 women (median age, 45 years; age range, 32-60 years) had tumors measuring a median 5.6 cm (range, 2.5-12 cm) located in the pancreatic head (n = 7) or tail (n = 4), including 3 with familial adenomatous polyposis (FAP)/FAP-related syndromes and 4 with metastasis at diagnosis. The median follow-up was 39.8 months (range, 0.8-348 months), and 5 patients died of disease. The original cytology diagnoses were: PBL (n = 2), neuroendocrine neoplasm (n = 2), poorly differentiated neuroendocrine carcinoma (n = 2), well differentiated neuroendocrine tumor (n = 1), poorly differentiated carcinoma (n = 2), "positive for malignancy" (n = 1), acinar cell carcinoma (n = 1), and epithelioid neoplasm with endocrine and acinar differentiation versus PBL (n = 1). Universal cytopathologic findings included hypercellularity; 3-dimensional clusters; and single, monotonous, blast-like cells that were from 1.5 to 2.0 times the size of red blood cells with high nuclear-to-cytoplasmic ratio, fine chromatin, small, distinct nucleoli, and a resemblance to well differentiated neuroendocrine tumor and poorly differentiated neuroendocrine carcinoma. Branching pseudopapillae (n = 7) and grooved nuclei (n = 3) raised the differential diagnosis of solid-pseudopapillary neoplasm, but with more atypia. Uncommon features included pleomorphism (n = 4) and numerous mitoses (n = 1). Squamoid morules were seen on smears (n = 5) or cell blocks (n = 6) in 70% of patients and were characterized by epithelioid cells with elongated, streaming nuclei, fine chromatin, absent nucleoli, and positive nuclear β-catenin (n = 6 of 8). The median Ki-67 index was 21% (range, 2%-70%), and neuroendocrine marker expression was common (100%), but acinar markers were variable (63%).
CONCLUSIONS: A combination of cytologic findings in PBL, including a predominant population of primitive blast-like cells, subtle squamoid morules, frequent neuroendocrine and variable acinar phenotype, should facilitate accurate cytologic diagnosis and distinction from common mimics.

PMID: 31581358 [PubMed - as supplied by publisher]

Permalink for 'Prospective study of chromogranin A as a predictor of progression in patients with pancreatic, small intestinal and unknown primary neuroendocrine tumors.'

Prospective study of chromogranin A as a predictor of progression in patients with pancreatic, small intestinal and unknown primary neuroendocrine tumors.

Fetched: October 4th, 2019, 5:01am GMT

Prospective study of chromogranin A as a predictor of progression in patients with pancreatic, small intestinal and unknown primary neuroendocrine tumors.

Neuroendocrinology. 2019 Oct 02;:

Authors: Dam G, Grønbæk H, Sorbye H, Thiis Evensen E, Paulsson B, Sundin A, Jensen C, Ebbesen D, Knigge U, Tiensuu Janson E

Abstract
Background Retrospective studies are conflicting but most report that an increase in plasma chromogranin A (CgA) predicts tumor progression in neuroendocrine tumor (NET) patients. Prospectively we investigated if changes in plasma CgA was associated with tumor burden changes in NET patients with disseminated disease. Methods We included 239 patients from five NET centers between 2010-2013. CgA was measured within six weeks of a CT or an MRI in a patient undergoing at least two scan examinations performed with 1-24 months interval. In a post-hoc analysis, CgA measured 3-6 month prior to the CT/MRI was analyzed. Changes in tumor size were evaluated by RECIST1.1. A 25% change in CgA was chosen to discriminate between increased, decreased or unchanged levels. Results In 671 events (2 CT/MRI scans and 2 corresponding CgA measurements) we found a weak positive correlation between the RECIST 1.1 responses and change in plasma CgA from baseline (Spearman's rank correlation coefficient: 0.15; p<0.05). Of 304 events in the post-hoc analysis, 58 showed progression, 228 stable disease, and 18 regression with a median change in CgA +19%(IQR:57-(-20)), -12%(+23-(-38)) and -73%(-55-(-83)), respectively. The correlation coefficients for all sites were 0.17(p=0.003); and 0.16(p=0.07), 0.18(p=0.04); and 0.20(p=0.21) for small intestinal (n=137), pancreatic (n=123) and unknown primary NET (n=40), respectively. In the 58 events showing tumor progression, sensitivity and specificity of an increased CgA concentration were 36% and 82% with positive and negative predictive values of 32% and 85%. Conclusions In this prospective study of GEP-NET patients we observed only a weak association between change in plasma CgA and change in tumor burden. CgA as a single biomarker was thus inadequate to predict tumor progression.

PMID: 31578011 [PubMed - as supplied by publisher]

Should 68Ga-DOTATATE PET/CT be Performed Routinely in Patients with Neuroendocrine Tumors Before Surgical Resection?

Fetched: October 4th, 2019, 5:01am GMT

Should 68Ga-DOTATATE PET/CT be Performed Routinely in Patients with Neuroendocrine Tumors Before Surgical Resection?

World J Surg. 2019 Oct 01;:

Authors: Babazadeh NT, Schlund DJ, Cornelius T, Singh JS, Tierney JF, Chen M, Keutgen XM

Abstract
BACKGROUND: The only potential cure for neuroendocrine tumors (NETs) is operative resection, which may also offer a survival benefit for advanced disease. We aimed to assess the role of 68Ga-DOTATATE PET/CT in preoperative planning and compared its performance to CT with IV contrast and MRI with Eovist®, for abdominal NETs.
METHODS: Records of patients who underwent 68Ga-DOTATATE PET/CT in addition to MRI with Eovist® and/or CT with IV contrast were retrospectively evaluated. The effect of imaging findings on surgical management and characteristics of detected lesions were analyzed. Descriptive statistics were used.
RESULTS: Of 21 patients who underwent 68Ga-DOTATATE PET/CT prior to surgical resection, five (24%) had a change in surgical management due to findings. In three patients, 68Ga-DOTATATE PET/CT identified the primary tumor. In two patients, 68Ga-DOTATATE PET/CT helped clarify equivocal hepatic lesions seen on MRI with Eovist®. MRI with Eovist® had the highest number of lesions found (median 13, versus 9 on CT and 9.5 on 68Ga-DOTATATE PET/CT). DOTATATE-avid lesions were on average larger than lesions seen only on MRI with Eovist® (1.6 cm versus 0.6 cm, p = 0.0002). The optimal cutoff point for detection by 68Ga-DOTATATE PET/CT was a size of 0.95 cm, with a sensitivity of 56% and specificity of 98%.
CONCLUSIONS: Preoperative 68Ga-DOTATATE PET/CT is useful only in a subset of patients undergoing surgical resection for NETs. MRI with Eovist® is superior at identifying liver metastases when compared to 68Ga-DOTATATE PET/CT and should therefore be used routinely before hepatic cytoreduction of NETs.

PMID: 31576440 [PubMed - as supplied by publisher]

Pancreatectomies for Pediatric Pancreatic Tumors: A Single Institute Experience from 2007 to 2018.

Fetched: October 4th, 2019, 5:01am GMT

Pancreatectomies for Pediatric Pancreatic Tumors: A Single Institute Experience from 2007 to 2018.

J Pediatr Surg. 2019 Sep 04;:

Authors: Cheng H, Yang S, Ren Q, Yang W, Han W, Chang X, Zhu Z, Qin H, Wang H

Abstract
BACKGROUND: To investigate the safety, feasibility, and complications of pancreatectomies for pediatric pancreatic tumors.
METHODS: The medical records of pancreatectomy patients from January 2007 to January 2018 were retrospectively analyzed for perioperative factors and complications. Patients were divided into pancreatic head (n = 43), body (n = 18) and tail (n = 43) groups.
RESULTS: Seventy-two girls and 32 boys (median age 10 years at diagnosis, range: 0-15 years) were enrolled and had solid pseudopapillary tumors (n = 73), pancreatoblastoma (n = 19), neuroendocrine tumors (n = 9), and others. Primary surgical procedures included pylorus-preserving pancreaticoduodenectomy (n = 10) and distal pancreatectomy with splenectomy (n = 4), and organ-sparing resection procedures included duodenum-preserving pancreas head resection (n = 25), middle segmental pancreatic resection (n = 15), spleen-preserving distal pancreatectomy (n = 37) and local enucleation (n = 13), with a median blood loss of 20 cm3 (range: 10-300 cm3). Short-term complications included pancreatic fistula (35.6%), bile leakage (2.9%), intraabdominal infection (21.2%), delayed gastric emptying (23.1%), and postpancreatectomy hemorrhage (5.8%). After a median follow-up of 38 months (range: 3-143 months), 94 patients (90.4%) were alive without tumor recurrence, 2 were alive after tumor recurrence, 1 pancreatoblastoma patient died from tumor recurrence, and 7 were lost to follow-up. Only 14 patients (14/96, 14.6%) had long-term complications at the outpatient follow-up.
CONCLUSIONS: Surgical resection was the main treatment for pancreatic tumors. Organ-sparing resection procedures led to good long-term results for pediatric pancreatic tumors, even if these procedures could cause a relatively high incidence of short-term complications (especially pancreatic fistula and postpancreatectomy hemorrhage).
LEVEL OF EVIDENCE: Level IV.

PMID: 31575410 [PubMed - as supplied by publisher]

Surgical treatment of malignant paraganglioma with spinal invasion in a juvenile patient: A case report.

Fetched: October 4th, 2019, 5:01am GMT

Surgical treatment of malignant paraganglioma with spinal invasion in a juvenile patient: A case report.

Medicine (Baltimore). 2019 Sep;98(39):e17145

Authors: Liu S, Zhou X, Song A, Huo Z, Li WA, Rastogi R, Wang Y, Liu Y

Abstract
RATIONALE: Paragangliomas are rare neuroendocrine tumors that originate in specialized cells derived from the neural crest with metastasis to the thoracic spine being among the rarest forms. Here, we are presenting a detailed analysis of a case of malignant paraganglioma in the thoracic spinal region in a 14-year-old boy. Our focus is to emphasize the importance of considering malignant paraganglioma as a diagnosis and guiding the perioperative management upon surgical treatment. The management of these unique cases has yet to be well-documented.
PATIENT CONCERNS: A 14-year-old boy presented with a 5-month history of continuous and progressive elevated blood pressure and back pain. The patient, who had been diagnosed of malignant paraganglioma in the left posterior mediastinum for 3 months, received surgical resection of paraganglioma in the left posterior mediastinum, which had involved the left intervertebral foramen of T4. However, the tumor was not completely resected during the first operation.
DIAGNOSES: Magnetic resonance imaging of spine and positron emission tomography-computed tomography showed spinal cord compression secondary to the epidural component of the T4 mass, with increased marrow infiltration of the left T4 intervertebral foramen, which was difficult to be removed. Postoperative pathology confirmed the diagnosis of spinal involvement of malignant paraganglioma.
INTERVENTIONS: The patient underwent biopsy and percutaneous vertebroplasty of T4 and paravertebral lesions, and needle-track cement augmentation via a posterior approach.
OUTCOMES: The patient's neurological deficits improved significantly after the surgery, and the postoperative period was uneventful at the 10-month follow-up visit. There were no other complications associated with the operation during the follow-up period.
LESSONS: Combined efforts of specialists from orthopedics, neurosurgery, thoracic surgery, and medical oncology led to the successful diagnosis and management of this patient. Malignant paraganglioma of thoracic spine, although rare, should be part of the differential diagnosis when the patient has a history of paraganglioma and presents with back pain and radiculopathy. We recommend the posterior approach for spinal decompression of the malignant paraganglioma when the tumor has caused neurological deficits. Osteoplasty by cement augmentation is also a good choice for surgical treatment. However, we need to take the potential risk of complications in bone cement applications into full consideration.

PMID: 31574816 [PubMed - in process]

[Large cell neuroendocrine carcinoma with foci of well-differentiated adenocarcinoma of the gallbladder: report of a case].

Fetched: October 4th, 2019, 5:01am GMT

[Large cell neuroendocrine carcinoma with foci of well-differentiated adenocarcinoma of the gallbladder: report of a case].

Zhonghua Bing Li Xue Za Zhi. 2019 09 08;48(9):723-725

Authors: Xu MX, Zhao M, Ma J, He XL

PMID: 31495096 [PubMed - indexed for MEDLINE]

Immunotherapy with ipilimumab plus nivolumab in a stage IV melanoma patient during pregnancy.

Fetched: October 4th, 2019, 5:01am GMT

Immunotherapy with ipilimumab plus nivolumab in a stage IV melanoma patient during pregnancy.

Eur J Cancer. 2018 11;104:239-242

Authors: Menzer C, Beedgen B, Rom J, Duffert CM, Volckmar AL, Sedlaczek O, Richtig E, Enk A, Jäger D, Hassel JC

PMID: 30454709 [PubMed - indexed for MEDLINE]

Permalink for 'Access to innovative medicines for metastatic melanoma worldwide: Melanoma World Society and European Association of Dermato-oncology survey in 34 countries.'

Access to innovative medicines for metastatic melanoma worldwide: Melanoma World Society and European Association of Dermato-oncology survey in 34 countries.

Fetched: October 4th, 2019, 5:01am GMT

Access to innovative medicines for metastatic melanoma worldwide: Melanoma World Society and European Association of Dermato-oncology survey in 34 countries.

Eur J Cancer. 2018 11;104:201-209

Authors: Kandolf Sekulovic L, Guo J, Agarwala S, Hauschild A, McArthur G, Cinat G, Wainstein A, Caglevic C, Lorigan P, Gogas H, Alvarez M, Duncombe R, Lebbe C, Peris K, Rutkowski P, Stratigos A, Forsea AM, De La Cruz Merino L, Kukushkina M, Dummer R, Hoeller C, Gorry C, Bastholt L, Herceg D, Neyns B, Vieira R, Arenberger P, Bylaite-Bucinskiene M, Babovic N, Banjin M, Putnik K, Todorovic V, Kirov K, Ocvirk J, Zhukavets A, Ymeri A, Stojkovski I, Garbe C

Abstract
According to data from recent studies from Europe, a large percentage of patients have restricted access to innovative medicines for metastatic melanoma. Melanoma World Society and European Association of Dermato-oncology conducted a Web-based survey on access to first-line recommended treatments for metastatic melanoma by current guidelines (National Comprehensive Center Network, European Society for Medical Oncology [ESMO] and European Organization for Research and Treatment of Cancer/European Association of Dermato-oncology/European dermatology Forum) among melanoma experts from 27 European countries, USA, China, Australia, Argentina, Brazil, Chile and Mexico from September 1st, 2017 to July 1st, 2018. Data on licencing and reimbursement of medicines and the number of patient treated were correlated with the data on health expenditure per capita (HEPC), Mackenbach score of health policy performance, health technology assessment (HTA), ASCO and ESMO Magnitude of clinical benefit scale (ESMO MCBS) scores of clinical benefit and market price of medicines. Regression analysis for evaluation of correlation between the parameters was carried out using SPSS software. The estimated number of patients without access in surveyed countries was 13768. The recommended BRAFi + MEKi combination and anti-PD1 immunotherapy were fully reimbursed/covered in 19 of 34 (55.8%) and 17 of 34 (50%) countries, and combination anti-CTLA4+anti-PD1 in was fully covered in 6 of 34 (17.6%) countries. Median delay in reimbursement was 991 days, and it was in significant correlation with ESMO MCBS (p = 0.02), median market price (p = 0.001), HEPC and Mackenbach scores (p < 0.01). Price negotiations or managed entry agreements (MEAs) with national authorities were necessary for reimbursement. In conclusion, great discrepancy exists in metastatic melanoma treatment globally. Access to innovative medicines is in correlation with economic parameters as well as with healthcare system performance parameters. Patient-oriented drug development, market access and reimbursement pathways must be urgently found.

PMID: 30388700 [PubMed - indexed for MEDLINE]

[Dermoscopy of cutaneous metastases].

Fetched: October 4th, 2019, 5:01am GMT

[Dermoscopy of cutaneous metastases].

Hautarzt. 2019 Feb;70(2):142-144

Authors: Deinlein T, Haenssle HA, Fink C, Hofmann-Wellenhof R, Blum A

Abstract

PMID: 30377718 [PubMed - indexed for MEDLINE]

Permalink for 'Interpreting European Organisation for Research and Treatment for Cancer Quality of life Questionnaire core 30 scores as minimally importantly different for patients with malignant melanoma.'

Interpreting European Organisation for Research and Treatment for Cancer Quality of life Questionnaire core 30 scores as minimally importantly different for patients with malignant melanoma.

Fetched: October 4th, 2019, 5:01am GMT

Interpreting European Organisation for Research and Treatment for Cancer Quality of life Questionnaire core 30 scores as minimally importantly different for patients with malignant melanoma.

Eur J Cancer. 2018 11;104:169-181

Authors: Musoro JZ, Bottomley A, Coens C, Eggermont AM, King MT, Cocks K, Sprangers MA, Groenvold M, Velikova G, Flechtner HH, Brandberg Y, EORTC Melanoma Group and EORTC Quality of Life Group

Abstract
INTRODUCTION: Health-related quality of life (HRQOL) is increasingly recognised as an important end-point in cancer clinical trials. The concept of minimally important difference (MID) enables interpreting differences and changes in HRQOL scores in terms of clinical meaningfulness. We aimed to estimate MIDs for interpreting group-level change of European Organisation for Research and Treatment for Cancer Quality of life Questionnaire core 30 (EORTC QLQ-C30) scores in patients with malignant melanoma.
METHODS: Data were pooled from three published melanoma phase III trials. Anchors relying on clinician's ratings, e.g. performance status, were selected using correlation strength and clinical plausibility of associating the anchor/EORTC QLQ-C30 scale pair. HRQOL change was evaluated between time periods that were common to all trials: start of treatment to end of treatment and end of treatment to end of follow-up. Three change status groups were formed: deteriorated by one anchor category, improved by one anchor category and no change. Patients with greater anchor change were excluded. The mean change method and linear regression were used to estimate MIDs for change in HRQOL scores within the group and between the groups of patients, respectively.
RESULTS: MIDs varied according to QLQ-C30 scale, direction (improvement versus deterioration), anchor and period. MIDs for within-group change ranged from 4 to 18 points (improvement) and -16 to -4 points (deterioration), and MIDs for between-group change ranged from 3 to 16 points and from -16 to -3 points. MIDs for most of QLQ-C30 scales ranged from 5 to 10 points in absolute values.
CONCLUSIONS: These results are useful for interpreting changes in EORTC QLQ-C30 scores over time and for performing more accurate sample size calculations in adjuvant melanoma settings.

PMID: 30359910 [PubMed - indexed for MEDLINE]

Anti-PD-1/PD-L1 immunotherapy in patients with solid organ transplant, HIV or hepatitis B/C infection.

Fetched: October 4th, 2019, 5:01am GMT

Anti-PD-1/PD-L1 immunotherapy in patients with solid organ transplant, HIV or hepatitis B/C infection.

Eur J Cancer. 2018 11;104:137-144

Authors: Tio M, Rai R, Ezeoke OM, McQuade JL, Zimmer L, Khoo C, Park JJ, Spain L, Turajlic S, Ardolino L, Yip D, Goldinger SM, Cohen JV, Millward M, Atkinson V, Kane AY, Ascierto PA, Garbe C, Gutzmer R, Johnson DB, Rizvi HA, Joshua AM, Hellmann MD, Long GV, Menzies AM

Abstract
BACKGROUND: Anti-programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1) immunotherapy is now routinely used to treat several cancers. Clinical trials have excluded several populations, including patients with solid organ transplant, HIV infection and hepatitis B/C infection. We examined the safety outcomes of these populations treated with anti-PD-1/PD-L1 treatment in a multicentre retrospective study.
METHODS: Patients from 16 centres with advanced cancer and solid organ transplant, HIV infection or hepatitis B/C infection were included. Demographic, tumour, treatment, toxicity and outcome data were recorded.
RESULTS: Forty-six patients were included for analysis, with a median age of 60 years, and the majority of patients diagnosed with melanoma (72%). Among six patients with solid organ transplants, two graft rejections occurred, with one resulting in death, whereas two patients achieved partial responses. There were four responses in 12 patients with HIV infection. In 14 patients with hepatitis B, there were three responses, and similarly, there were three responses in 14 patients with hepatitis C. There was no unexpected toxicity in any viral infection group or an increase in viral load.
CONCLUSION: Patients with HIV or hepatitis B/C infections treated with anti-PD-1/PD-L1 immunotherapy may respond to treatment without increased toxicity. Given the risk of graft rejection in solid organ transplant patients and also the potential for response, the role of anti-PD-1/PD-L1 immunotherapy needs to be carefully considered.

PMID: 30347289 [PubMed - indexed for MEDLINE]

Pembrolizumab-induced dermatomyositis in a patient with metastatic melanoma.

Fetched: October 4th, 2019, 5:01am GMT

Pembrolizumab-induced dermatomyositis in a patient with metastatic melanoma.

Eur J Cancer. 2018 11;104:227-230

Authors: Berger M, Legeay AL, Souci S, Streichenberger N, Thomas L, Dalle S

PMID: 30322679 [PubMed - indexed for MEDLINE]

Permalink for 'Proof of concept studies for siRNA delivery by nonionic surfactant vesicles: in vitro and in vivo evaluation of protein knockdown.'

Proof of concept studies for siRNA delivery by nonionic surfactant vesicles: in vitro and in vivo evaluation of protein knockdown.

Fetched: October 4th, 2019, 5:01am GMT

Proof of concept studies for siRNA delivery by nonionic surfactant vesicles: in vitro and in vivo evaluation of protein knockdown.

J Liposome Res. 2019 Sep;29(3):229-238

Authors: Obeid MA, Dufès C, Somani S, Mullen AB, Tate RJ, Ferro VA

Abstract
RNA interference is an effective and naturally occurring post-transcriptional gene regulatory mechanism. This mechanism involves the degradation of a target messenger RNA (mRNA) through the introduction of short interfering RNA (siRNA) that is complementary to the target mRNA. The application of siRNA-based therapeutics is limited by the development of an effective delivery system, as naked siRNA is unstable and cannot penetrate the cell membrane. In this study, we investigated the use of cationic niosomes (CN) prepared by microfluidic mixing for siRNA delivery. In an in vitro model, these vesicles were able to deliver anti-luciferase siRNA and effectively suppress luciferase expression in B16-F10 mouse melanoma cells. More importantly, in an in vivo mouse model, intratumoral administration of CN-carrying anti-luciferase siRNA led to significant suppression of luciferase expression compared with naked siRNA. Thus, we have established a novel and effective system for the delivery of siRNA both in vitro and in vivo, which shows high potential for future application of gene therapeutics.

PMID: 30296860 [PubMed - indexed for MEDLINE]

Permalink for 'The College of Nuclear Physicians of South Africa Practice Guidelines on Peptide Receptor Radionuclide Therapy in Neuroendocrine Tumours.'

The College of Nuclear Physicians of South Africa Practice Guidelines on Peptide Receptor Radionuclide Therapy in Neuroendocrine Tumours.

Fetched: October 4th, 2019, 5:01am GMT

The College of Nuclear Physicians of South Africa Practice Guidelines on Peptide Receptor Radionuclide Therapy in Neuroendocrine Tumours.

S Afr J Surg. 2018 Sep;56(3):55-64

Authors: Lawal I, Louw L, Warwick J, Nyakale N, Steyn R, Lengana T, Lengana T, Ellmann A, Kotze T, Vangu M, Vorster M, Sathekge M

Abstract
BACKGROUND: Peptide receptor radionuclide therapy (PRRT) for metastatic or inoperable neuroendocrine tumours (NETs) is a systemic therapy which targets somatostatin receptors overexpressed by differentiated NETs for endoradiotherapy. This guideline has been compiled by the College of Nuclear Physicians of the Colleges of Medicine of South Africa, with endorsement by the South African Society of Nuclear Medicine and the Association of Nuclear Physicians to guide Nuclear Medicine Physicians in its application during the management of these patients.
RECOMMENDATIONS: Patients with well- to moderately-differentiated NETs should be comprehensively worked-up to determine their suitability for PRRT. Treatment should be administered by a Nuclear Medicine Physician in a licensed, appropriately equipped and fully staffed facility. Patient monitoring is mandatory during and after each therapy cycle to identify and treat therapy-related adverse events. Patients should also be followed-up after completion of therapy cycles for monitoring of long-term toxicities and response assessment.
CONCLUSION: PRRT is a safe and effective therapy option in patients with differentiated NETs. Its use in appropriate patients is associated with a survival benefit.

PMID: 30264945 [PubMed - indexed for MEDLINE]

Radiosurgery of Glomus Tumors of Temporal Bone: a Meta-analysis.

Fetched: October 4th, 2019, 5:01am GMT

Radiosurgery of Glomus Tumors of Temporal Bone: a Meta-analysis.

Otol Neurotol. 2018 04;39(4):488-493

Authors: Sahyouni R, Mahboubi H, Moshtaghi O, Goshtasbi K, Sahyouni S, Lin HW, Djalilian HR

Abstract
OBJECTIVE: 1) Perform a meta-analysis of the available data on the outcomes of stereotactic radiosurgery (SRS) for the treatment of temporal bone glomus tumors (GT), and 2) evaluate the collective outcomes of SRS treatment with respect to tumor control.
DATA SOURCES: A thorough literature search of the published English-language literature from 2011 to 2016 was performed in PubMed, Ovid, and Cochrane databases using the keywords ("Gamma Knife" or "CyberKnife" or "linear accelerator" or "radiosurgery") and ("glomus jugulare" or "jugular paraganglioma" or "glomus tympanicum").
STUDY SELECTION: Studies reporting outcomes of SRS for temporal bone GT were included.
DATA EXTRACTION: Of 45 articles found, 15 studies met our inclusion and exclusion criteria and were selected for qualitative and quantitative analyses totaling 511 patients.
DATA SYNTHESIS: Average margin dose, modality, isodose line, volume decrease, follow-up duration, and tumor control rate data were extracted and analyzed.
CONCLUSION: Gamma Knife was the most commonly implemented radiosurgery modality and was used in eight studies. The mean marginal dose varied between 13.2 and 20 Gy. The pooled tumor control rate was 95.4% (95% CI: 93.6-97.2%) over a median follow-up duration ranging between 27.4 and 148 months. Clinical data on outcomes of SRS for the treatment of GTs are sparse and primarily limited to single institutional analyses, with considerable variation in tumor volume and follow-up duration. This meta-analysis provides an in-depth analysis of the available data in the literature and reviews the reported outcomes. Future studies on SRS for GT should include data on tumor growth before radiation as well as follow-up periods sufficiently long to identify true tumor control.

PMID: 29533338 [PubMed - indexed for MEDLINE]

Localized pretibial bullous pemphigoid arising in a patient on pembrolizumab for metastatic melanoma.

Fetched: October 4th, 2019, 5:01am GMT

Localized pretibial bullous pemphigoid arising in a patient on pembrolizumab for metastatic melanoma.

J Dtsch Dermatol Ges. 2018 Feb;16(2):196-198

Authors: Amber KT, Valdebran M, Lu Y, De Feraudy S, Linden KG

PMID: 29389067 [PubMed - indexed for MEDLINE]

Does Hospital Volume Affect Outcomes in Patients Undergoing Vestibular Schwannoma Surgery?

Fetched: October 4th, 2019, 5:01am GMT

Does Hospital Volume Affect Outcomes in Patients Undergoing Vestibular Schwannoma Surgery?

Otol Neurotol. 2018 04;39(4):481-487

Authors: Hatch JL, Bauschard MJ, Nguyen SA, Lambert PR, Meyer TA, McRackan TR

Abstract
OBJECTIVE: To determine the effect of hospital surgical case volume on the outcomes of vestibular schwannoma surgery.
STUDY DESIGN: Retrospective case review.
SETTING: University HealthSystem Consortium member hospitals (includes nearly every US academic medical center).
PATIENTS: Three thousand six hundred ninety-seven patients who underwent vestibular schwannoma resection over a 3-year timespan (2012-2015) grouped by race, age, comorbidities, payer, and sex.
INTERVENTION: Surgical resection of vestibular schwannoma.
MAIN OUTCOME MEASURES: Morbidity and mortality following vestibular schwannoma excision are compared by hospital volume (low, medium, and high) including deciles.
RESULTS: There was significantly longer length of stay (p ≤ 0.005) among groups with low-volume hospitals followed by medium-volume hospitals and high-volume hospitals. Low-volume hospitals had a significantly higher rate of complications including stroke, aspiration, and respiratory failure (p ≤ 0.0175). Patient characteristics of age, sex, sex, and baseline comorbidities were similar between hospital groups. However, patients at high-volume hospitals were more likely to be Caucasian (83.1%, p = 0.0001) and have private insurance (76.7%, p < 0.0001). There was a strong negative correlation between complication rates and hospital volume (r = -0.8164, p = 0.0040).
CONCLUSION: The volume of vestibular schwannoma surgeries performed at a hospital impacts length of stay and rates of postoperative complications. Demographics among hospital groups were similar though high-volume hospitals had significantly more patients who were privately insured and Caucasian.

PMID: 29342051 [PubMed - indexed for MEDLINE]

Permalink for 'Prospective comparison of whole-body MRI with diffusion-weighted and conventional imaging for the follow-up of neuroendocrine tumors.'

Prospective comparison of whole-body MRI with diffusion-weighted and conventional imaging for the follow-up of neuroendocrine tumors.

Fetched: October 1st, 2019, 5:01am GMT

Prospective comparison of whole-body MRI with diffusion-weighted and conventional imaging for the follow-up of neuroendocrine tumors.

Endocrine. 2019 Sep 28;:

Authors: Minon M, Soriano C, Morland D, Walter T, Lepage C, Tabarin A, Deblock M, Rousset P, Barbe C, Hoeffel C, Cadiot G

Abstract
AIM: To determine whether whole-body magnetic resonance imaging is valuable in staging of neuroendocrine tumors by comparison with the conventional imaging defined by the combination of computed tomography and somatostatin receptor scintigraphy.
METHODS: This study concerned the patients included in the multicenter prospective study NCT02786303 with the following inclusion criteria: well-differentiated gastroenteropancreatic neuroendocrine tumors or of unknown primary, and computed tomography, whole-body magnetic resonance imaging and somatostatin receptor scintigraphy performed within 6 weeks. Results of the conventional imaging were compared with those of magnetic resonance imaging. Discrepancies between the conventional imaging and magnetic resonance imaging were evaluated by reviewing medical records.
RESULTS: Thirty-one patients (17 men and 14 women) were prospectively included. Complete concordance between the magnetic resonance imaging and the conventional imaging results was observed in 25 patients and discrepancies in 6. Whole-body magnetic resonance imaging detected more liver lesions than the conventional imaging did but standard imaging set was more effective in the detection of bone and peritoneum lesions than magnetic resonance imaging. Detecting more lesions had no impact on therapeutic management.
CONCLUSIONS: Whole-body magnetic resonance imaging including diffusion weighted may be a valuable alternative to computed tomography and somatostatin receptor scintigraphy. Further studies should compare whole-body MRI to the 68Ga PET/CT.

PMID: 31564038 [PubMed - as supplied by publisher]

Mesenteric Castleman's disease mimicking neuroendocrine tumour.

Fetched: October 1st, 2019, 5:01am GMT

Mesenteric Castleman's disease mimicking neuroendocrine tumour.

Int J Surg Case Rep. 2019 Sep 18;63:56-58

Authors: Bhogal RH, Wotherspoon A, Khan AK

Abstract
INTRODUCTION: Castleman's disease is a rare entity and is a benign hyperplastic enlargement of lymph nodes. It can occur anywhere within the body but only approximately 50 cases of mesenteric Castleman's disease have been reported within the literature.
CASE PRESENTATION: We report a female patient who was thought to have developed a neuroendocrine tumour within the small bowel and a large nodal mass within the mesentery based on nuclear scintigraphy imaging. Following surgical resection the nodal mass found confirmed to be Castleman's disease.
DISCUSSION: Although rare complete resection of mesenteric Castleman's disease offer excellent long term outcome although the diagnosis may only be made after surgery.
CONCLUSION: The diagnosis of mesenteric Castleman's disease is often made post-operatively but complete surgical resection offers excellent long-term survival.

PMID: 31563665 [PubMed - as supplied by publisher]

A Consensus Molecular Classification of Muscle-invasive Bladder Cancer.

Fetched: October 1st, 2019, 5:01am GMT

A Consensus Molecular Classification of Muscle-invasive Bladder Cancer.

Eur Urol. 2019 Sep 25;:

Authors: Kamoun A, Reyniès A, Allory Y, Sjödahl G, Gordon Robertson A, Seiler R, Hoadley KA, Groeneveld CS, Al-Ahmadie H, Choi W, Castro MAA, Fontugne J, Eriksson P, Mo Q, Kardos J, Zlotta A, Hartmann A, Dinney CP, Bellmunt J, Powles T, Malats N, Chan KS, Kim WY, McConkey DJ, Black PC, Dyrskjøt L, Höglund M, Lerner SP, Real FX, Radvanyi F, Bladder Cancer Molecular Taxonomy Group

Abstract
BACKGROUND: Muscle-invasive bladder cancer (MIBC) is a molecularly diverse disease with heterogeneous clinical outcomes. Several molecular classifications have been proposed, but the diversity of their subtype sets impedes their clinical application.
OBJECTIVE: To achieve an international consensus on MIBC molecular subtypes that reconciles the published classification schemes.
DESIGN, SETTING, AND PARTICIPANTS: We used 1750 MIBC transcriptomic profiles from 16 published datasets and two additional cohorts.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We performed a network-based analysis of six independent MIBC classification systems to identify a consensus set of molecular classes. Association with survival was assessed using multivariable Cox models.
RESULTS AND LIMITATIONS: We report the results of an international effort to reach a consensus on MIBC molecular subtypes. We identified a consensus set of six molecular classes: luminal papillary (24%), luminal nonspecified (8%), luminal unstable (15%), stroma-rich (15%), basal/squamous (35%), and neuroendocrine-like (3%). These consensus classes differ regarding underlying oncogenic mechanisms, infiltration by immune and stromal cells, and histological and clinical characteristics, including outcomes. We provide a single-sample classifier that assigns a consensus class label to a tumor sample's transcriptome. Limitations of the work are retrospective clinical data collection and a lack of complete information regarding patient treatment.
CONCLUSIONS: This consensus system offers a robust framework that will enable testing and validation of predictive biomarkers in future prospective clinical trials.
PATIENT SUMMARY: Bladder cancers are heterogeneous at the molecular level, and scientists have proposed several classifications into sets of molecular classes. While these classifications may be useful to stratify patients for prognosis or response to treatment, a consensus classification would facilitate the clinical use of molecular classes. Conducted by multidisciplinary expert teams in the field, this study proposes such a consensus and provides a tool for applying the consensus classification in the clinical setting.

PMID: 31563503 [PubMed - as supplied by publisher]

Merkel cell carcinoma: A series of seven cases.

Fetched: September 26th, 2019, 5:01am GMT

Merkel cell carcinoma: A series of seven cases.

Arch Plast Surg. 2019 Sep;46(5):441-448

Authors: Lee YW, Bae YC, Nam SB, Bae SH, Kim HS

PMID: 31550749 [PubMed]

High-Grade Neuroendocrine Carcinoma of the Head and Neck: Human Papillomavirus Status and PD-L1 Expression.

Fetched: September 26th, 2019, 5:01am GMT

High-Grade Neuroendocrine Carcinoma of the Head and Neck: Human Papillomavirus Status and PD-L1 Expression.

ORL J Otorhinolaryngol Relat Spec. 2019 Sep 24;:1-8

Authors: Bahr K, Zimmer S, Springer E, Fottner C, Becker S, Ernst BP, Matthias C, Künzel J

Abstract
BACKGROUND: Human papillomavirus (HPV)-related head and neck squamous cell carcinoma represents an important subgroup of head and neck cancer, but HPV occurs also in the less common neuroendocrine carcinomas (NEC). The PD-1/PD-L1 pathway appears to be activated in pulmonary NEC and correlates with a higher mutation burden, but the potential of NEC to respond to checkpoint inhibitors is unknown to a large extent.
OBJECTIVES: To determine the HPV status of NEC of the head and neck region and to investigate the expression of PD-1 and its ligands PD-L1 and PD-L2.
METHODS: Surgical tumor samples from 2006 to 2017 were analyzed. HPV status was determined by p16 immunohistochemistry (IHC) and multiplex PCR. IHC using the Cologne Score was performed for PD-1, PD-L1, and PD-L2.
RESULTS: Seven NEC tumor samples were analyzed, three of them showed HPV type 18. Expression of PD-1 and PD-L1 differed widely and showed no correlation to HPV status. IHC showed an overexpression of PD-L2 in most of the patients.
CONCLUSIONS AND SIGNIFICANCE: A multicentric analysis of NEC is needed to further evaluate the role of HPV as well as immunocheckpoints with regard to inflammatory immune response in genesis and clinical course of this rare tumor entity. Biomarkers for selection of novel treatment regimens, including immunotherapeutic approaches, are warranted.

PMID: 31550725 [PubMed - as supplied by publisher]

Permalink for 'Diagnosis of intrapancreatic accessory spleen by endoscopic ultrasound-guided fine-needle aspiration mimicking a pancreatic neoplasm: a case report and review of literature.'

Diagnosis of intrapancreatic accessory spleen by endoscopic ultrasound-guided fine-needle aspiration mimicking a pancreatic neoplasm: a case report and review of literature.

Fetched: September 26th, 2019, 5:01am GMT

Diagnosis of intrapancreatic accessory spleen by endoscopic ultrasound-guided fine-needle aspiration mimicking a pancreatic neoplasm: a case report and review of literature.

Clin J Gastroenterol. 2019 Sep 23;:

Authors: Renno A, Hill M, Abdel-Aziz Y, Meawad H, Lenhard A, Nawras A

Abstract
Accessory spleen (AS) is a benign condition, where ectopic spleen tissue can be found elsewhere in the abdomen and pelvis, with approximately 20% of cases located at or in the tail of the pancreas. When discovered on imaging, it can be mistaken for conditions that do require surgical removal, including neuroendocrine tumor, and so accurate diagnosis of AS can prevent unnecessary surgery. Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) is a commonly performed diagnostic modality that can lead to a confirmatory diagnosis of AS. We present a case of AS diagnosed at our institution by EUS-FNA and review the literature for all reported cases of AS that have been confirmed by EUS-FNA.

PMID: 31549337 [PubMed - as supplied by publisher]

[Risk factors for lymph node metastases of neuroendocrine tumors of the appendix].

Fetched: September 26th, 2019, 5:01am GMT

[Risk factors for lymph node metastases of neuroendocrine tumors of the appendix].

Chirurg. 2019 Sep 23;:

Authors: Dralle H

PMID: 31549195 [PubMed - as supplied by publisher]

$Permalink for 'Brainstem Tumor Resection via Occipital Interhemispheric Transtentorial Infracollicular Approach: 2-Dimensional Operative Video.'$

Brainstem Tumor Resection via Occipital Interhemispheric Transtentorial Infracollicular Approach: 2-Dimensional Operative Video.

Fetched: September 26th, 2019, 5:01am GMT

Brainstem Tumor Resection via Occipital Interhemispheric Transtentorial Infracollicular Approach: 2-Dimensional Operative Video.

Oper Neurosurg (Hagerstown). 2019 Sep 23;:

Authors: Song J, Zhao X, Li P, Zhang X, Fan Z, Pan Z, Zhu W

Abstract
A brainstem tumor located at the upper pons or pontomesencephalic region is surgically challenging because of the deep-seated location and difficulty to approach, especially if the lesion is intra-axial and extends anteriorly without appearing on the pia surface. In our experience, the infracollicular entry point is feasible for such lesions and can be approached by an occipital interhemispheric transtentorial corridor through a straightforward trajectory, which ensures surgical ergonomics. Herein, we present a case of a 55-yr-old woman with a pontomesencephalic lesion removed via an occipital interhemispheric transtentorial infracollicular approach. Informed consent was obtained from the patient. Her preoperative medical course and radiological findings strongly indicated the lesion as a brainstem cavernous malformation. Although the overlying brainstem parenchyma was thin, the lesion did not appear on the pial surface. The lesion was removed via an occipital interhemispheric transtentorial infracollicular approach. During the operation, the lesion was observed to have an old hemorrhagic component and an obvious gliotic boundary, resembling the typical macropathology of a brainstem cavernous malformation. We easily dissected the lesion circumferentially off the brainstem parenchyma after thorough debulking, and a gross total resection was performed en bloc. However, postoperative pathology confirmed a diagnosis of a metastatic neuroendocrine tumor, and further systematic examination revealed cancerous lesions in the lungs. The patient experienced slight hypophrasia but recovered within 3 d postoperatively and then was discharged for further treatment. This case demonstrates the safety and efficacy of an occipital interhemispheric transtentorial infracollicular approach for brainstem tumor resection.

PMID: 31549174 [PubMed - as supplied by publisher]

Consensus-Derived Quality Performance Indicators for Neuroendocrine Tumour Care.

Fetched: September 26th, 2019, 5:01am GMT

Consensus-Derived Quality Performance Indicators for Neuroendocrine Tumour Care.

J Clin Med. 2019 Sep 12;8(9):

Authors: Woodhouse B, Pattison S, Segelov E, Singh S, Parker K, Kong G, Macdonald W, Wyld D, Meyer-Rochow G, Pavlakis N, Conroy S, Gordon V, Koea J, Kramer N, Michael M, Wakelin K, Asif T, Lo D, Price T, Lawrence B, Commonwealth Neuroendocrine Tumour Collaboration (CommNETs)

Abstract
Quality performance indicators (QPIs) are used to monitor the delivery of cancer care. Neuroendocrine tumours (NETs) are a family of individually uncommon cancers that derive from neuroendocrine cells or their precursors, and can occur in most organs. There are currently no QPIs available for NETs and their heterogeneity makes QPI development difficult. CommNETs is a collaboration between NET clinicians, researchers and advocates in Canada, Australia and New Zealand. We created QPIs for NETs using a three-step consensus process. First, a multidisciplinary team used the nominal group technique to create candidates (n = 133) which were then curated into appropriateness statements (62 statements, 44 sub-statements). A two-stage modified RAND/UCLA Delphi consensus process was conducted: an online survey rated the statement appropriateness then the top-ranked statements (n = 20) were assessed in a face-to-face meeting. Finally, 10 QPIs met consensus criteria; documentation of primary site, proliferative index, differentiation, tumour board review, use of a structured pathology report, presence of distant metastasis, 5- and 10-year disease-free and overall survival. These NET QPIs will be trialed as a method to monitor and improve care for people with NETs and to facilitate international comparison.

PMID: 31547431 [PubMed]

Neuroendocrine Differentiation of Prostate Cancer-An Intriguing Example of Tumor Evolution at Play.

Fetched: September 26th, 2019, 5:01am GMT

Neuroendocrine Differentiation of Prostate Cancer-An Intriguing Example of Tumor Evolution at Play.

Cancers (Basel). 2019 Sep 20;11(10):

Authors: Patel GK, Chugh N, Tripathi M

Abstract
Our understanding of neuroendocrine prostate cancer (NEPC) has assumed a new perspective in light of the recent advances in research. Although classical NEPC is rarely seen in the clinic, focal neuroendocrine trans-differentiation of prostate adenocarcinoma occurs in about 30% of advanced prostate cancer (PCa) cases, and represents a therapeutic challenge. Even though our knowledge of the mechanisms that mediate neuroendocrine differentiation (NED) is still evolving, the role of androgen deprivation therapy (ADT) as a key driver of this phenomenon is increasingly becoming evident. In this review, we discuss the molecular, cellular, and therapeutic mediators of NED, and emphasize the role of the tumor microenvironment (TME) in orchestrating the phenotype. Understanding the role of the TME in mediating NED could provide us with valuable insights into the plasticity associated with the phenotype, and reveal potential therapeutic targets against this aggressive form of PCa.

PMID: 31547070 [PubMed]

Permalink for 'Should platinum-based chemotherapy be preferred for germline BReast CAncer genes (BRCA) 1 and 2-mutated pancreatic ductal adenocarcinoma (PDAC) patients? A systematic review and meta-analysis.'

Should platinum-based chemotherapy be preferred for germline BReast CAncer genes (BRCA) 1 and 2-mutated pancreatic ductal adenocarcinoma (PDAC) patients? A systematic review and meta-analysis.

Fetched: September 24th, 2019, 5:01am GMT

Should platinum-based chemotherapy be preferred for germline BReast CAncer genes (BRCA) 1 and 2-mutated pancreatic ductal adenocarcinoma (PDAC) patients? A systematic review and meta-analysis.

Cancer Treat Rev. 2019 Sep 06;80:101895

Authors: Rebelatto TF, Falavigna M, Pozzari M, Spada F, Cella CA, Laffi A, Pellicori S, Fazio N

Abstract
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers worldwide. Recent studies have shown that 4-20% of patients with PDAC have a germline BReast CAncer (gBRCA) genes 1 and 2 mutation (m). Because homologous recombination is impaired in patients with gBRCAm, some reports suggested that these tumors may be more sensitive to platinum compounds. Therefore, this systematic review and meta-analysis focused on benefit of patients with gBRCAm receiving a platinum-based chemotherapy (PtCh) compared with those treated with a non-platinum-based chemotherapy (NPtCh).
MATERIAL AND METHODS: The following electronic databases were searched from inception to May 12, 2018: PubMed (MEDLINE), EMBASE, and Cochrane Library. Abstracts from conferences were also reviewed for inclusion. Cohort, case-control and randomized studies of patients with PDAC and gBRCAm were eligible for inclusion if they provided data to compare patients receiving PtCh vs NPtCh. The primary endpoint was overall survival (OS) in the PtCh group vs the NPtCh group in patients with clinical stage III (locally advanced) or IV (metastatic) (CS III-IV) PDAC.
RESULTS: Of 112 studies identified, 6 were included (total of 108 patients); of these, 4 provided sufficient data for meta-analysis. Half of the patients were males, with a mean age ranging from 58 to 63 years. The OS in the 85 patients with CS III-IV PDAC was higher in the PtCh group (23.7 vs 12.2 months; mean difference of 10.21 months, 95% confidence interval [CI] 5.05-15.37; P < 0.001; very low quality of evidence). PtCh was associated with a lower mortality (62.3 vs 87.5%; relative risk of 0.80, 95%CI 0.66-0.97; P = 0.021; very low quality of evidence).
CONCLUSION: Our study confirmed the hypothesis that patients with CS III-IV gBRCAm preferably benefit from a PtCh compared with NPtCh. However the very low quality of evidence should induce to be careful about the risk of potential biases. The generated hypothesis should be prospectively investigated in homogenous clinical settings.

PMID: 31542591 [PubMed - as supplied by publisher]

Spread of hyperplastic pulmonary neuroendocrine cells into air spaces (S.H.I.P.M.E.N.T.S): A proof for artifact.

Fetched: September 24th, 2019, 5:01am GMT

Spread of hyperplastic pulmonary neuroendocrine cells into air spaces (S.H.I.P.M.E.N.T.S): A proof for artifact.

Lung Cancer. 2019 Sep 13;137:43-47

Authors: Pelosi G, Nesa F, Taietti D, Servillo SP, Papanikolaou N, Zompatori M, Meroni A, Harari S, Incarbone M

Abstract
OBJECTIVES: Spread through air spaces (STAS) is a recently proposed invasion way of lung cancer, including neuroendocrine (NE) neoplasms. However, if this phenomenon is a real one or an artifact while manipulating lung specimens, it is still matter of debate.
MATERIAL AND METHODS: Three consecutive patients with newly diagnosed diffuse idiopathic pulmonary NE cell hyperplasia (DIPNECH) were reviewed for STAS.
RESULTS: In well-fixed lung specimens, DIPNECH was seen to coexist with atypical carcinoid, bifocal typical carcinoid and adenocarcinoma in the three patients, respectively. While STAS was not observed at the growing edges of tumors, a few freely-floating aggregates of hyperplastic NE cells within air spaces were noticed to emanate from foci of NE hype

Rare Cancer News & Clinical Trials » Endocrine/Neuroendocrine

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Endocrine/Neuroendocrine (533 unread)

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