Rare Cancer News & Clinical Trials » Endocrine/Neuroendocrine

Endocrine/Neuroendocrine (303 unread)

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

Fetched: October 14th, 2018, 5:00am GMT

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

Ann Surg Oncol. 2018 Oct 11;:

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 - as supplied by publisher]

Merkel cell carcinoma: An update and review: Current and future therapy.

Fetched: October 14th, 2018, 5:00am GMT

Merkel cell carcinoma: An update and review: Current and future therapy.

J Am Acad Dermatol. 2018 03;78(3):445-454

Authors: Tello TL, Coggshall K, Yom SS, Yu SS

Abstract
Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin associated with a high risk of local recurrence and distant metastases. It most commonly occurs on sun-exposed areas of white patients >65 years of age. The Merkel cell polyomavirus (MCV) is thought to be responsible for malignant transformation in approximately 80% of cases in the northern hemisphere, while ultraviolet radiation-induced DNA damage is implicated in MCV-negative tumors. The overall incidence of MCC is low, with approximately 1600 cases diagnosed annually in the United States. The rate is much higher in patients with lymphoproliferative malignancies, solid organ transplants, and HIV infection. The low overall incidence of this tumor makes it challenging to conduct prospective clinical trials with sufficient power. As a result, most management recommendations are based on case series, retrospective reviews, and expert opinion. The pathogenesis, diagnosis, and staging of MCC was discussed in the first article in this continuing medical education series. This article focuses on current management guidelines and promising new therapies in development. Because of the complexity, aggressive nature, and individuality of each case, MCC is best treated by a multidisciplinary team.

PMID: 29229573 [PubMed - indexed for MEDLINE]

A monoclonal antibody against SV40 large T antigen (PAb416) does not label Merkel cell carcinoma.

Fetched: October 13th, 2018, 5:00am GMT

A monoclonal antibody against SV40 large T antigen (PAb416) does not label Merkel cell carcinoma.

Histopathology. 2018 Jul;73(1):162-166

Authors: Pelletier DJ, Czeczok TW, Bellizzi AM

Abstract
AIMS: Merkel cell carcinoma represents poorly differentiated neuroendocrine carcinoma of cutaneous origin. In most studies, the vast majority of Merkel cell carcinomas are Merkel cell polyomavirus (MCPyV)-associated. SV40 polyomavirus immunohistochemistry is typically used in the diagnosis of other polyomavirus-associated diseases, including tubulointerstitial nephritis and progressive multifocal leukoencephalopathy, given cross-reactivity with BK and JC polyomaviruses. MCPyV-specific immunohistochemistry is commercially available, but, if antibodies against SV40 also cross-reacted with MCPyV, that would be advantageous from a resource-utilisation perspective.
METHODS AND RESULTS: Tissue microarrays were constructed from 39 Merkel cell carcinomas, 24 small-cell lung carcinomas, and 18 extrapulmonary visceral small-cell carcinomas. SV40 large T antigen immunohistochemistry (clone PAb416) was performed; MCPyV large T antigen immunohistochemistry (clone CM2B4) had been previously performed. UniProt was used to compare the amino acid sequences of the SV40, BK, JC and MCPyV large T antigens, focusing on areas recognised by the PAb416 and CM2B4 clones. SV40 immunohistochemistry was negative in all tumours; MCPyV immunohistochemistry was positive in 38% of Merkel cell carcinomas and in 0% of non-cutaneous poorly differentiated neuroendocrine carcinomas. UniProt analysis revealed a high degree of similarity between SV40, BK, and JC viruses in the region recognised by PAb416. There was less homology between SV40 and MCPyV in this region, which was also interrupted by two long stretches of amino acids unique to MCPyV. The CM2B4 clone recognises a unique epitope in one of these stretches.
CONCLUSIONS: The PAb416 antibody against the SV40 large T antigen does not cross-react with MCPyV large T antigen, and thus does not label Merkel cell carcinoma.

PMID: 29430700 [PubMed - indexed for MEDLINE]

Analysis of cutaneous Merkel Cell Carcinoma outcomes after different surgical interventions.

Fetched: October 10th, 2018, 5:00am GMT

Analysis of cutaneous Merkel Cell Carcinoma outcomes after different surgical interventions.

J Am Acad Dermatol. 2018 Oct 05;:

Authors: Yan L, Sun L, Guan Z, Wei S, Wang Y, Li P

Abstract
BACKGROUND: Current guidelines recommend local excision margin (EM) with 1 to 2cm on primary merkel cell carcinoma (MCC) site.
OBJECTIVE: We compared survival outcomes of MCC patients treated with different surgical interventions.
METHODS: A retrospective analysis of MCC cases in the SEER database was performed by Kaplan-Meier, competing risk and Cox proportional hazards regression model analyses. Influence of age, T stage, AJCC stage, adjuvant radiotherapy and other subgroups were also analyzed by pair-wise log-rank test.
RESULTS: Our results indicated significant association between local destruction method and inferior survival, while EM>2cm showed significantly higher overall survival (OS). In addition, competing risk analysis depicted similar trend as Kaplan-Meier analysis, and considerably reduced estimated cumulative incidence. Further subgroup pair-wise analysis demonstrated that EM>2cm method had better survival in patients younger than 60 years, having smaller tumor diameters (T1 and T2) or undergone adjuvant radiotherapy (p<0.05). In contrast, different EMs did not show any significant association with survival rate in patients older than 75 years or stage III tumors.
LIMITATIONS: This study was not prospectively randomized without relapse data.
CONCLUSIONS: It is challenging to make optimal EM recommendations, as surgical options may depend on individual case situations. Further prospective randomized studies are warranted.

PMID: 30296537 [PubMed - as supplied by publisher]

The biology and treatment of Merkel cell carcinoma: current understanding and research priorities.

Fetched: October 7th, 2018, 5:00am GMT

The biology and treatment of Merkel cell carcinoma: current understanding and research priorities.

Nat Rev Clin Oncol. 2018 Oct 04;:

Authors: Harms PW, Harms KL, Moore PS, DeCaprio JA, Nghiem P, Wong MKK, Brownell I, International Workshop on Merkel Cell Carcinoma Research (IWMCC) Working Group

Abstract
Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer associated with advanced age and immunosuppression. Over the past decade, an association has been discovered between MCC and either integration of the Merkel cell polyomavirus, which likely drives tumorigenesis, or somatic mutations owing to ultraviolet-induced DNA damage. Both virus-positive and virus-negative MCCs are immunogenic, and inhibition of the programmed cell death protein 1 (PD-1)-programmed cell death 1 ligand 1 (PD-L1) immune checkpoint has proved to be highly effective in treating patients with metastatic MCC; however, not all patients have a durable response to immunotherapy. Despite these rapid advances in the understanding and management of patients with MCC, many basic, translational and clinical research questions remain unanswered. In March 2018, an International Workshop on Merkel Cell Carcinoma Research was held at the US National Cancer Institute, at which academic, government and industry experts met to identify the highest-priority research questions. Here, we review the biology and treatment of MCC and report the consensus-based recommendations agreed upon during the workshop.

PMID: 30287935 [PubMed - as supplied by publisher]

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

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

Fetched: October 6th, 2018, 5:00am GMT

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

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

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

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

PMID: 30285852 [PubMed - in process]

Paraneoplastic neuronal intermediate filament autoimmunity.

Fetched: October 6th, 2018, 5:00am GMT

Paraneoplastic neuronal intermediate filament autoimmunity.

Neurology. 2018 Oct 03;:

Authors: Basal E, Zalewski N, Kryzer TJ, Hinson SR, Guo Y, Dubey D, Benarroch EE, Lucchinetti CF, Pittock SJ, Lennon VA, McKeon A

Abstract
OBJECTIVE: To describe paraneoplastic neuronal intermediate filament (NIF) autoimmunity.
METHODS: Archived patient and control serum and CSF specimens were evaluated by tissue-based indirect immunofluorescence assay (IFA). Autoantigens were identified by Western blot and mass spectrometry. NIF specificity was confirmed by dual tissue section staining and 5 recombinant NIF-specific HEK293 cell-based assays (CBAs, for α-internexin, neurofilament light [NfL], neurofilament medium, or neurofilament heavy chain, and peripherin). NIF-immunoglobulin Gs (IgGs) were correlated with neurologic syndromes and cancers.
RESULTS: Among 65 patients, NIF-IgG-positive by IFA and CBAs, 33 were female (51%). Median symptom onset age was 62 years (range 18-88). Patients fell into 2 groups, defined by the presence of NfL-IgG (21 patients, who mostly had ≥4 NIF-IgGs detected) or its absence (44 patients, who mostly had ≤2 NIF-IgGs detected). Among NfL-IgG-positive patients, 19/21 had ≥1 subacute onset CNS disorders: cerebellar ataxia (11), encephalopathy (11), or myelopathy (2). Cancers were detected in 16 of 21 patients (77%): carcinomas of neuroendocrine lineage (10) being most common (small cell [5], Merkel cell [3], other neuroendocrine [2]). Two of 257 controls (0.8%, both with small cell carcinoma) were positive by both IFA and CBA. Five of 7 patients with immunotherapy data improved. By comparison, the 44 NfL-IgG-negative patients had findings of unclear significance: diverse nervous system disorders (p = 0.006), as well as limited (p = 0.003) and more diverse (p < 0.0001) cancer accompaniments.
CONCLUSIONS: NIF-IgG detection by IFA, with confirmatory CBA testing that yields a profile including NfL-IgG, defines a paraneoplastic CNS disorder (usually ataxia or encephalopathy) accompanying neuroendocrine lineage neoplasia.

PMID: 30282771 [PubMed - as supplied by publisher]

Spontaneous regression of Merkel cell carcinoma.

Fetched: October 5th, 2018, 5:00am GMT

Spontaneous regression of Merkel cell carcinoma.

Cutis. 2018 Apr;101(4):301-305

Authors: Branch S, Maloney K, Purcell SM

Abstract
A 96-year-old woman presented with a rapidly enlarging lesion overlying the suprasternal notch. The lesion originated as a small, erythematous, scaly macule that rapidly increased in size over 8 weeks and became an ulcerated nodule measuring 5 cm in diameter and 4.5 cm in thickness. A 4-mm punch biopsy showed a poorly differentiated tumor with cells that were positive for CAM 5.2 and cytokeratin 20 in a dotlike paranuclear pattern and negative for cytokeratin 5/6, human melanoma black 45, and leukocyte common antigen. Two weeks after the punch biopsy, the lesion noticeably decreased in size, and within 8 weeks of the biopsy the tumor had completely resolved with no further intervention. Regression of Merkel cell carcinoma (MCC) is a very rare event, with as few as 30 cases reported. The mechanism of this phenomenon remains unclear; however, T-cell-mediated immunity and apoptosis appear to play a major role.

PMID: 29763480 [PubMed - indexed for MEDLINE]

Mechanisms of persistence by small DNA tumor viruses.

Fetched: October 4th, 2018, 5:00am GMT

Mechanisms of persistence by small DNA tumor viruses.

Curr Opin Virol. 2018 Sep 29;32:71-79

Authors: Krump NA, Liu W, You J

Abstract
Virus infection contributes to nearly 15% of human cancers worldwide. Many of the oncogenic viruses tend to cause cancer in immunosuppressed individuals, but maintain asymptomatic, persistent infection for decades in the general population. In this review, we discuss the tactics employed by two small DNA tumor viruses, Human papillomavirus (HPV) and Merkel cell polyomavirus (MCPyV), to establish persistent infection. We will also highlight recent key findings as well as outstanding questions regarding the mechanisms by which HPV and MCPyV evade host immune control to promote their survival. Since persistent infection enables virus-induced tumorigenesis, identifying the mechanisms by which small DNA tumor viruses achieve latent infection may inform new approaches for preventing and treating their respective human cancers.

PMID: 30278284 [PubMed - as supplied by publisher]

Primary cutaneous ganglioneuroma: anatomico-clinical study of 4 cases with focus on Merkel cells.

Fetched: October 4th, 2018, 5:00am GMT

Primary cutaneous ganglioneuroma: anatomico-clinical study of 4 cases with focus on Merkel cells.

J Cutan Pathol. 2018 Jun;45(6):403-411

Authors: Romero-Pérez D, Jegou MH, Lecointre C, Penchet I, Cribier B

Abstract
Cutaneous ganglioneuromas (CGNs) are exceptional. We aim to describe the anatomico-clinical profile of primary CGN and report 4 cases. Patients were 2 men and 2 women aged 53 to 76 years, who had flesh-colored nodules on the back, associated with adjacent keratotic changes, that is, epidermal nevus (1 case) or seborrheic keratosis (3 cases). Histopathology showed ganglion cells within a proliferation of Schwann cells. The epidermis was acanthotic, associated with sebaceous induction in 2 cases, with follicular hyperplasia as in fibroepithelial tumors (1 case) or with tricholemmoma (2 cases). Cytokeratin-20 immunostaining showed Merkel cells in the epidermis. A higher density of Merkel cells was observed in BerEP4+ follicular structures. Along with 16 published cases, our study indicates that a nodule associated with seborrheic keratosis on the back may represent a CGN, a complex mesenchymal and epidermal/follicular lesion of neuroectodermal lineage, associating neuronal proliferation and Merkel cell hyperplasia with follicular induction.

PMID: 29569258 [PubMed - indexed for MEDLINE]

Permalink for '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.'

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.

Fetched: October 3rd, 2018, 5:00am GMT

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.

J Med Imaging Radiat Oncol. 2018 Jun;62(3):412-419

Authors: Poulsen M, Macfarlane D, Veness M, Estall V, Hruby G, Kumar M, Pullar A, Tripcony L, Rischin D

Abstract
INTRODUCTION: TROG 09.03 prospectively studied the utility of Fluorine-18 Fluorodeoxyglucose (18-FDG) PET in the management of Merkel cell carcinoma of skin.
METHODS: Following consent and registration, a pre-treatment FDG-PET/CT was performed. Sites of avid disease were confirmed by cytology where practicable. Following surgery, patients with AJCCv7 Stages IIA-IIIB disease were treated with chemo-radiotherapy and reassessed with a post-treatment PET.
RESULTS: Fifty-eight subjects (45 males and 13 females, median age 68 years) were enrolled between 2011 and 2015, 43 patients of whom went on to receive chemo-radiotherapy. An occult primary was present in 22 (37.9%), T1 in 22 (37.9%) and T2 disease in 14 (24.1%). Nodal disease was present in 69% of cases. Fifty per cent of subjects had gross residual disease at the primary site and/or nodal site at the time of registration. 18-FDG PET/CT had a sensitivity of 94.74% (95% CI 82-99.3%) and a specificity of 88.24% (95% CI 63.56-98.54). The positive predictive value was 94.74% (83.01-98.51) and the negative predictive value was 88.24% (95% CI 65.81-96.69). The pre-treatment PET influenced a treatment decision in 27.6% of cases. Upstaging occurred in 15 (25.9%), with no down staging. Other diseases were identified in 4 (6.9%) patients. Univariate analysis failed to demonstrate that pre-treatment SUV levels or a negative post-treatment PET had any impact on overall survival. PET staged patients had 89% 3-year in-field loco-regional control and 76% 3-year overall survival.
CONCLUSION: Staging 18-FDG-PET significantly influenced treatment decisions in approximately one-third of cases of MCC and should be considered in the routine pre-treatment work-up. Post-treatment PET was not found to be prognostic. Funding through the Medicare Benefits Schedule needs to be considered for high risk MCC.

PMID: 29405630 [PubMed - indexed for MEDLINE]

Merkel cell carcinoma arising on a pre-existing Bowen's disease: is it just by chance?

Fetched: October 3rd, 2018, 5:00am GMT

Merkel cell carcinoma arising on a pre-existing Bowen's disease: is it just by chance?

G Ital Dermatol Venereol. 2018 Apr;153(2):273-275

Authors: Casari A, Argenziano G, Piana S, Lallas A, Moscarella E, Lombardi M, Raucci M, Pellacani G, Longo C

Abstract
Merkel cell carcinoma (MCC) is a cutaneous carcinoma with neuroendocrine differentiation. It arises typically on sun-exposed areas of elderly men as an asymptomatic, rapidly growing, red nodule. Although it is usually found as a solitary nodule, in almost one third of cases MCC may be associated with other malignancies such as basal cell or squamous cell carcinomas. Merkel cell carcinoma should be considered as differential diagnosis every time we have a rapidly growing, red nodule, arising in an elderly patient with signs of sun-damage. We report a case of MCC developing in association with a pre-existing Bowen's disease. The association between MCC and Bowen's disease is quite common and their area of occurrence is usually a sun-exposed area. Ultraviolet radiation contributes to the etiology of both the malignancies.

PMID: 26222729 [PubMed - indexed for MEDLINE]

Computed tomography accelerates staging in patients with Merkel cell carcinoma.

Fetched: October 1st, 2018, 5:00am GMT

Computed tomography accelerates staging in patients with Merkel cell carcinoma.

Eur Arch Otorhinolaryngol. 2018 Sep 28;:

Authors: Foki E, Fochtmann-Frana A, Haymerle G, Nemec S, Loader B, Perisanidis C, Erovic BM

Abstract
PURPOSE: No imaging algorithms for diagnostic imaging in patients suffering from Merkel cell carcinoma (MCC) have been established so far and thus staging work-up is challenging. Long presentation-to-treatment intervals determine further treatment course and, consequently, have an impact on clinical outcome in patients with MCC.
METHODS: In this retrospective study, diagnostic imaging of 37 MCC patients was analyzed. CT, ultrasound, and PET/PET-CT imaging for primary staging work-up with time frames from patients´ initial presentation and imaging until completion of tumor staging were analyzed.
RESULTS: Tumor staging could be completed earlier when (1) less examinations (35 vs. 42 days) were carried out or (2) computed tomography was used as the initial imaging modality (28 vs. 35 days). Furthermore, CT imaging, when used as the initial imaging study, was linked to less follow-up imaging (3 vs. 6).
CONCLUSION: Computed tomography as the first-staging imaging technique in MCC patients leads to less follow-up studies and fastest completion of tumor staging.

PMID: 30267216 [PubMed - as supplied by publisher]

Complete remission of metastatic Merkel cell carcinoma in a patient with severe psoriasis.

Fetched: September 29th, 2018, 5:00am GMT

Complete remission of metastatic Merkel cell carcinoma in a patient with severe psoriasis.

Cutis. 2018 01;101(1):E24-E27

Authors: Yousif J, Yousif B, Kuriata MA

PMID: 29529118 [PubMed - indexed for MEDLINE]

Merkel Cell Carcinoma of the Buccal Mucosa and Lower Lip.

Fetched: September 29th, 2018, 5:00am GMT

Merkel Cell Carcinoma of the Buccal Mucosa and Lower Lip.

Head Neck Pathol. 2018 Jun;12(2):279-285

Authors: Islam MN, Chehal H, Smith MH, Islam S, Bhattacharyya I

Abstract
Merkel cell carcinoma (MCC) is an uncommon relatively aggressive neuroendocrine dermal neoplasm first described in 1972 as a tumor of the sun exposed skin. Although most MCC affect the skin of the head and neck, rare primarily oral mucosal cases have been documented. Merkel cells are nondendritic neuroendocrine cells that are found not only in the skin but also the oral mucosa and give rise to MCC. Neuroendocrine cells may be found as aggregates in organs or as diffuse or isolated cells within organs and their epithelial lining. They contain peptide hormones and biogenic amines and occur in two forms: dendritic, which are not associated with nerve fibers and non-dendritic, which are associated with nerve fibers. Merkel cells as well as MCC express simple epithelium-type Cytokeratins (8, 18, 19, 20), neurosecretory substances; chromogranin A, synaptophysin, neuron-specific enolase (NSE), adhesion molecules, and villin (intermediate filament). Though weakly, they also express neural markers such as S-100 protein. Cytokeratin 20, and Cluster of differentiation 56, are the two key diagnostic markers for Merkel cells and MCC. Etiology includes UV radiation, the recently described Merkel cell polyomavirus, and long term systemic immunosuppression. The cutaneous and mucosal variants of MCC are considered aggressive tumors with a high risk for local recurrence and metastasis and should be considered in the differential diagnosis of head and neck mucosal lesions. We present two cases of primary Merkel cell carcinoma, one on the buccal mucosa and the other on the lower lip, and discuss the salient histologic, immunohistochemical and clinical features.

PMID: 28980225 [PubMed - indexed for MEDLINE]

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

Fetched: September 28th, 2018, 5:00am GMT

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

Updates Surg. 2018 Sep 25;:

Authors: Vennarecci G, Ferraro D, Tudisco A, Sandri GBL, 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 - as supplied by publisher]

Acquired cancer resistance to combination immunotherapy from transcriptional loss of class I HLA.

Fetched: September 27th, 2018, 5:00am GMT

Acquired cancer resistance to combination immunotherapy from transcriptional loss of class I HLA.

Nat Commun. 2018 Sep 24;9(1):3868

Authors: Paulson KG, Voillet V, McAfee MS, Hunter DS, Wagener FD, Perdicchio M, Valente WJ, Koelle SJ, Church CD, Vandeven N, Thomas H, Colunga AG, Iyer JG, Yee C, Kulikauskas R, Koelle DM, Pierce RH, Bielas JH, Greenberg PD, Bhatia S, Gottardo R, Nghiem P, Chapuis AG

Abstract
Understanding mechanisms of late/acquired cancer immunotherapy resistance is critical to improve outcomes; cellular immunotherapy trials offer a means to probe complex tumor-immune interfaces through defined T cell/antigen interactions. We treated two patients with metastatic Merkel cell carcinoma with autologous Merkel cell polyomavirus specific CD8+ T cells and immune-checkpoint inhibitors. In both cases, dramatic remissions were associated with dense infiltration of activated CD8+s into the regressing tumors. However, late relapses developed at 22 and 18 months, respectively. Here we report single cell RNA sequencing identified dynamic transcriptional suppression of the specific HLA genes presenting the targeted viral epitope in the resistant tumor as a consequence of intense CD8-mediated immunologic pressure; this is distinguished from genetic HLA-loss by its reversibility with drugs. Transcriptional suppression of Class I loci may underlie resistance to other immunotherapies, including checkpoint inhibitors, and have implications for the design of improved immunotherapy treatments.

PMID: 30250229 [PubMed - in process]

Permalink for 'Expression of the IDO1/TDO2-AhR pathway in tumor cells or the tumor microenvironment is associated with MCPyV status and prognosis in Merkel cell carcinoma.'

Expression of the IDO1/TDO2-AhR pathway in tumor cells or the tumor microenvironment is associated with MCPyV status and prognosis in Merkel cell carcinoma.

Fetched: September 23rd, 2018, 5:00am GMT

Expression of the IDO1/TDO2-AhR pathway in tumor cells or the tumor microenvironment is associated with MCPyV status and prognosis in Merkel cell carcinoma.

Hum Pathol. 2018 Sep 18;:

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

Abstract
Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer, with approximately 80% of cases related to Merkel cell polyomavirus (MCPyV). Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase 2 (TDO2) are the key rate-limiting enzymes of the tryptophan to kynurenine (KYN) metabolic pathway. With aryl hydrocarbon receptor (AhR), an intracellular transcription factor, they play a role in escaping the immunosurveillance process in several cancers. IDO1/TDO2/AhR expression associated with the MCPyV status and prognosis in MCC was investigated. Samples included 24 MCPyV-positive MCCs, 12 MCPyV-negative MCCs with squamous cell carcinoma, and seven MCPyV-negative pure MCCs. They were stained immunohistochemically with IDO1, TDO2, and AhR antibodies and analyzed. Higher IDO1 expression in MCC tumor cells was found in MCPyV-negative than in MCPyV-positive MCC (P < .001). The tumor microenvironment (TME) in MCPyV-negative MCC expressed higher TDO2 than MCPyV-positive MCC (P < .001). Kaplan-Meier and log-rank tests showed that MCC with lower IDO1 expression in tumor cells and with lower TDO2 and AhR expressions in TME had better overall survival than otherwise (P = .043, .008, and .035, respectively); lower TDO2 expression in TME was also associated with longer disease-specific survival (P = .016). This suggests that IDO1, TDO2, and AhR express differentially in tumor cells or TME and play different roles in tumorigenesis between MCPyV-positive and -negative MCC that may affect the MCC biology. Evaluating IDO1/TDO2/AhR expression is important for selecting the most likely patients with MCC for immunotherapies targeting the IDO1/TDO2-AhR pathway.

PMID: 30240768 [PubMed - as supplied by publisher]

Immunotherapy for Merkel Cell Carcinoma.

Fetched: September 23rd, 2018, 5:00am GMT

Immunotherapy for Merkel Cell Carcinoma.

Curr Treat Options Oncol. 2018 Sep 20;19(11):57

Authors: Nagase K, Narisawa Y

Abstract
OPINION STATEMENT: Merkel cell carcinoma (MCC) is a rare but highly aggressive neuroendocrine carcinoma of the skin, with frequent recurrences, metastasis, and a high mortality rate. For primary or locoregional MCC, a wide local excision followed by radiation therapy is the basic treatment modality for preventing recurrence at the primary site and involved lymph nodes. Cytotoxic chemotherapy has been commonly used to treat patients with metastatic MCC, but not as an adjuvant therapy for high-risk resected MCC. Although MCC is often chemotherapy-sensitive in the first-line setting, responses are rarely durable and most patients subsequently relapse and develop metastasis. Treatment with checkpoint inhibitors (CPIs) has shown a major advancement in the treatment of advanced MCC. Systemic therapy against programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) is associated with a high objective response rate (ORR), prolonged durable responses, and good tolerability in advanced-stage MCC. CPIs are now included in the National Comprehensive Cancer Network (NCCN) guidelines for the treatment of patients with metastatic MCC. Multiple clinical trials of CPIs administered as monotherapy or in combination with other agents or modalities, including the adjuvant setting, are ongoing. Immunotherapy offers a promising future for patients with MCC. In this review, we present an overview of emerging data on immunotherapy, especially CPIs of the PD-1/PD-L1 pathway, for patients with advanced MCC.

PMID: 30238195 [PubMed - in process]

Virus-related Merkel cell carcinoma complicating fingolimod treatment for multiple sclerosis.

Fetched: September 23rd, 2018, 5:00am GMT

Virus-related Merkel cell carcinoma complicating fingolimod treatment for multiple sclerosis.

Neurology. 2016 12 13;87(24):2595-2597

Authors: Beadnall HN, Gill AJ, Riminton S, Barnett MH

PMID: 27856777 [PubMed - indexed for MEDLINE]

Permalink for 'Differential Outcomes Among Immunosuppressed Patients With Merkel Cell Carcinoma: Impact of Immunosuppression Type on Cancer-specific and Overall Survival.'

Differential Outcomes Among Immunosuppressed Patients With Merkel Cell Carcinoma: Impact of Immunosuppression Type on Cancer-specific and Overall Survival.

Fetched: September 15th, 2018, 5:00am GMT

Differential Outcomes Among Immunosuppressed Patients With Merkel Cell Carcinoma: Impact of Immunosuppression Type on Cancer-specific and Overall Survival.

Am J Clin Oncol. 2018 Sep 11;:

Authors: Cook M, Baker K, Redman M, Lachance K, Nguyen MH, Parvathaneni U, Bhatia S, Nghiem P, Tseng YD

Abstract
OBJECTIVES: Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer with higher incidence among whites, elderly, and immunosuppressed patients. Although immunosuppressed MCC patients are at higher risk of recurrence and MCC-related death, it is unknown whether immunosuppression type is associated with differential outcomes.
MATERIALS AND METHODS: We retrospectively evaluated 89 nonmetastatic MCC patients with a diagnosis of chronic immunosuppression. Immunosuppression was categorized as chronic lymphocytic leukemia (31% of cohort), other hematologic malignancies (18%), solid organ transplant (21%), autoimmune disease (21%), and human immunodeficiency virus acquired deficiency syndrome (8%). Progression-free survival (PFS) and MCC-specific survival (MSS) were estimated with the cumulative incidence function. Overall survival (OS) was estimated by the Kaplan-Meier method.
RESULTS: With a median follow-up of 52 months, 53 deaths occurred (42 from MCC, 7 unknown, and 4 non-MCC). Two-year PFS, MSS, and OS were 30%, 55%, and 52%, respectively. Human immunodeficiency virus/acquired deficiency syndrome and solid organ transplant patients were diagnosed with MCC at a younger age (median 55 and 59 y, respectively) and with more advanced stage disease compared with other immunosuppressed subgroups. PFS did not significantly differ among the 5 immunosuppression subgroups (P=0.30), but significant differences were observed in MSS and OS (both P=0.01). Controlling for potential confounders for OS, including age and stage, immunosuppression type was still significantly associated with risk of death (P=0.01).
CONCLUSIONS: Among immunosuppressed MCC patients, recurrent MCC is the major cause of mortality. The risk of death from MCC differs among immunosuppression types, suggesting important biological differences in host-tumor immune interactions.

PMID: 30211723 [PubMed - as supplied by publisher]

PDQ Cancer Information Summaries

Fetched: September 13th, 2018, 5:00am GMT

PDQ Cancer Information Summaries

Book. 2002

Authors:

PMID: 26389158

Venous thromboembolism leading to diagnosis of de novo malignancy in an organ transplant recipient.

Fetched: September 11th, 2018, 5:00am GMT

Venous thromboembolism leading to diagnosis of de novo malignancy in an organ transplant recipient.

BMJ Case Rep. 2018 Sep 08;2018:

Authors: Mitchell N, Connell A, Kurth B

Abstract
We report the case of a patient with remote orthotopic liver transplant who was ultimately diagnosed with Merkel cell carcinoma following admission for initial venous thromboembolism. Additionally, we review pertinent literature related to the risk of skin cancer in solid organ transplant recipients and discuss the importance of yearly skin exams in this patient population.

PMID: 30196255 [PubMed - in process]

Epidemiology of Merkel Cell Carcinoma. A population-based study from 1985 to 2013, in Northeastern of France.

Fetched: September 10th, 2018, 5:00am GMT

Epidemiology of Merkel Cell Carcinoma. A population-based study from 1985 to 2013, in Northeastern of France.

Int J Cancer. 2018 Sep 08;:

Authors: Kieny A, Cribier B, Meyer N, Velten M, Jégu J, Lipsker D

Abstract
Merkel Cell Carcinoma (MCC) is an aggressive skin cancer with an increasing incidence. Population-based epidemiologic data about MCC in France are rare. This study aims to describe the epidemiology of MCC in Bas-Rhin, Northeastern of France, between 1985 and 2013. Data were collected from the Bas-Rhin Cancer Registry. We measured age-adjusted incidence rates (per 100,000 person-years) and effect of age, sex and period of diagnosis on survival. The world age-standardized incidence rate was 0.17 and it quadrupled between 1985 and 2013. Cases (n=111) occurred mostly in women (60%) and in persons ≥ 70 years of age (74%). Incidence rates was close for men (0.18) and women (0.16) and was 25-time higher in people ≥ 70 years of age but incidence rate similarly increased between 1985 and 2013 in persons older and younger than 70 years. Net five-year survival was 48.5 %; female sex and younger age were positive predictors of survival. Given the low number of cases, incidence and survival data should be interpreted with caution. Incidence of MCC in Bas-Rhin quadrupled between 1985 and 2013. The highest incidence rate was observed in people ≥ 70 years. Better survival was associated with female sex and younger age. We hypothesize that MCC will still increase and be diagnosed in increasingly younger patients in next generations. This article is protected by copyright. All rights reserved.

PMID: 30194728 [PubMed - as supplied by publisher]

Permalink for 'Effect of Patient Immune Status on the Efficacy of Radiation Therapy and Recurrence-Free Survival Among 805 Patients With Merkel Cell Carcinoma.'

Effect of Patient Immune Status on the Efficacy of Radiation Therapy and Recurrence-Free Survival Among 805 Patients With Merkel Cell Carcinoma.

Fetched: September 9th, 2018, 5:00am GMT

Effect of Patient Immune Status on the Efficacy of Radiation Therapy and Recurrence-Free Survival Among 805 Patients With Merkel Cell Carcinoma.

Int J Radiat Oncol Biol Phys. 2018 Oct 01;102(2):330-339

Authors: Tseng YD, Nguyen MH, Baker K, Cook M, Redman M, Lachance K, Bhatia S, Liao JJ, Apisarnthanarax S, Nghiem PT, Parvathaneni U

Abstract
PURPOSE: Patients with Merkel cell carcinoma (MCC) with chronic immunosuppression (IS) have worse outcomes, but the mechanisms are not well understood. We hypothesized that these differences may be mediated in part by differential response to treatment, and we evaluated whether radiation therapy (RT) efficacy is altered among IS compared with immune-competent (IC) patients with MCC.
METHODS AND MATERIALS: Among 805 patients with MCC, recurrence-free survival (RFS) and patterns of first recurrence were compared between 89 IS and 716 IC patients with stage I to III MCC treated with curative intent. We used a Fine and Gray's competing risk multivariable analysis to estimate associations with RFS.
RESULTS: IS and IC patients with MCC had similar demographic and disease characteristics. Most (77% IC, 86% IS) were irradiated (median, 50.4 Gy IC, 50.3 Gy IS), although more IS patients were irradiated to the primary site (97% vs 81%). With a median follow-up of 54.4 months, IS patients had inferior RFS (2-year: 30% vs 57%; P < .0001) and higher rates of local recurrence as the first site of relapse (25% vs 12%; P = .0002). The association between RT and RFS differed by immune status (interaction P = .01). Although RT was associated with significantly improved RFS among IC patients (hazard ratio 0.56, 95% confidence interval 0.44-0.72), no difference in RFS was observed with RT among IS patients (hazard ratio 1.49, 95% confidence interval 0.70-3.17).
CONCLUSIONS: Radiation therapy efficacy at current standard RT doses for MCC is impaired among immunosuppressed patients with MCC. Although a strong link between durability of RT response and immune function does not appear to be evident in most cancers, our results may reflect an especially dynamic interaction between immune status and RT efficacy in MCC.

PMID: 30191867 [PubMed - in process]

Permalink for 'Morphological and immunocytochemical features of Merkel cell carcinoma metastatic to the pancreas diagnosed by endoscopic ultrasound-guided fine-needle aspiration.'

Morphological and immunocytochemical features of Merkel cell carcinoma metastatic to the pancreas diagnosed by endoscopic ultrasound-guided fine-needle aspiration.

Fetched: September 9th, 2018, 5:00am GMT

Morphological and immunocytochemical features of Merkel cell carcinoma metastatic to the pancreas diagnosed by endoscopic ultrasound-guided fine-needle aspiration.

Diagn Cytopathol. 2017 Jul;45(7):629-630

Authors: Lucci R, D' Anna M, Marano A, Vigliar E, Avellino M, Napolitano V, Troncone G, Bellevicine C

PMID: 28387053 [PubMed - indexed for MEDLINE]

Permalink for 'Cellular sheddases are induced by Merkel cell polyomavirus small tumour antigen to mediate cell dissociation and invasiveness.'

Cellular sheddases are induced by Merkel cell polyomavirus small tumour antigen to mediate cell dissociation and invasiveness.

Fetched: September 8th, 2018, 5:00am GMT

Cellular sheddases are induced by Merkel cell polyomavirus small tumour antigen to mediate cell dissociation and invasiveness.

PLoS Pathog. 2018 Sep 06;14(9):e1007276

Authors: Nwogu N, Boyne JR, Dobson SJ, Poterlowicz K, Blair GE, Macdonald A, Mankouri J, Whitehouse A

Abstract
Merkel cell carcinoma (MCC) is an aggressive skin cancer with a high propensity for recurrence and metastasis. Merkel cell polyomavirus (MCPyV) is recognised as the causative factor in the majority of MCC cases. The MCPyV small tumour antigen (ST) is considered to be the main viral transforming factor, however potential mechanisms linking ST expression to the highly metastatic nature of MCC are yet to be fully elucidated. Metastasis is a complex process, with several discrete steps required for the formation of secondary tumour sites. One essential trait that underpins the ability of cancer cells to metastasise is how they interact with adjoining tumour cells and the surrounding extracellular matrix. Here we demonstrate that MCPyV ST expression disrupts the integrity of cell-cell junctions, thereby enhancing cell dissociation and implicate the cellular sheddases, A disintegrin and metalloproteinase (ADAM) 10 and 17 proteins in this process. Inhibition of ADAM 10 and 17 activity reduced MCPyV ST-induced cell dissociation and motility, attributing their function as critical to the MCPyV-induced metastatic processes. Consistent with these data, we confirm that ADAM 10 and 17 are upregulated in MCPyV-positive primary MCC tumours. These novel findings implicate cellular sheddases as key host cell factors contributing to virus-mediated cellular transformation and metastasis. Notably, ADAM protein expression may be a novel biomarker of MCC prognosis and given the current interest in cellular sheddase inhibitors for cancer therapeutics, it highlights ADAM 10 and 17 activity as a novel opportunity for targeted interventions for disseminated MCC.

PMID: 30188954 [PubMed - as supplied by publisher]

Onset of Kaposi sarcoma and Merkel cell carcinoma during low-dose steroid therapy for rheumatic polymyalgia.

Fetched: September 7th, 2018, 5:00am GMT

Onset of Kaposi sarcoma and Merkel cell carcinoma during low-dose steroid therapy for rheumatic polymyalgia.

Clin Exp Dermatol. 2017 Aug;42(6):702-704

Authors: Brambilla L, Esposito L, Nazzaro G, Tourlaki A

PMID: 28598021 [PubMed - indexed for MEDLINE]

Sentinel lymph node biopsy in Merkel cell carcinoma: The Mayo Clinic experience of 150 patients.

Fetched: September 6th, 2018, 5:00am GMT

Sentinel lymph node biopsy in Merkel cell carcinoma: The Mayo Clinic experience of 150 patients.

Surg Oncol. 2018 Mar;27(1):11-17

Authors: Sims JR, Grotz TE, Pockaj BA, Joseph RW, Foote RL, Otley CC, Weaver AL, Jakub JW, Price DL

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) is a rare cutaneous malignancy of neuroendocrine origin with a high propensity for lymph node metastasis. Sentinel lymph node (SLN) status is important for accurate staging; however, the optimal treatment following SLN biopsy, regardless of nodal status, remains unclear.
METHODS: 150 patients with MCC who underwent SLN biopsy from 1995 to 2011 at 3 Mayo Clinic sites were reviewed.
RESULTS: Of 150 patients with MCC who underwent SLN biopsy, 39 (26%) were positive and 111 (74%) were negative. There was no significant difference between the sex, age, tumor location, or size of primary in the positive and negative SLN groups. While there was no difference in the cumulative incidence of any regional recurrence between SLN groups, the rate of in-transit recurrences was significantly higher in patients with a positive SLN (p = 0.022). The disease-specific survival for MCC was 97.0%, 82.4%, and 82.4% at 1, 3, and 5 years with a positive SLN and 99.0%, 94.9%, and 86.8% with a negative SLN (p = 0.31). Among those alive at last follow up, the median follow up was 3.8 years (IQR, 2.1-8.4) and 2.9 years (IQR, 1.8-6.1) for positive and negative SLN cohorts respectively.
CONCLUSIONS: Occult nodal metastasis is common in MCC(26%). No tumor or patient characteristics were identified to predict SLN positivity. Patients with a positive SLN have a higher risk of in-transit recurrence and may benefit from adjuvant radiation with inclusion of the in-transit field in amenable cases. When patients with a positive SLN receive additional treatment to the at-risk nodal basin, both OS and DSS are similar to patients with a negative SLN.

PMID: 29549898 [PubMed - indexed for MEDLINE]

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

Fetched: September 3rd, 2018, 5:00am GMT

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

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

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

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

PMID: 30170630 [PubMed - in process]

Permalink for 'Proceedings of the NASHNP Companion Meeting, March 18th, 2018, Vancouver, BC, Canada: Salivary Neuroendocrine Carcinoma-An Overview of a Rare Disease with an Emphasis on Determining Tumor Origin.'

Proceedings of the NASHNP Companion Meeting, March 18th, 2018, Vancouver, BC, Canada: Salivary Neuroendocrine Carcinoma-An Overview of a Rare Disease with an Emphasis on Determining Tumor Origin.

Fetched: September 2nd, 2018, 5:00am GMT

Proceedings of the NASHNP Companion Meeting, March 18th, 2018, Vancouver, BC, Canada: Salivary Neuroendocrine Carcinoma-An Overview of a Rare Disease with an Emphasis on Determining Tumor Origin.

Head Neck Pathol. 2018 Mar;12(1):13-21

Authors: Chernock RD, Duncavage EJ

Abstract
Salivary neuroendocrine carcinomas are rare and the overwhelming majority is high-grade. The parotid gland is the most commonly involved site followed by the submandibular gland. Most arise de novo but rare examples occurring as a high-grade transformation of another type of salivary gland neoplasm exist. There is significant morphologic and immunophenotypic overlap with neuroendocrine carcinomas of other sites, especially the skin. Like cutaneous neuroendocrine (or Merkel cell) carcinomas, approximately three-fourths are cytokeratin 20 positive. Cytokeratin 20 positive salivary neuroendocrine carcinomas are often referred to as being of the 'Merkel cell type' since most other non-cutaneous neuroendocrine carcinomas are cytokeratin 20 negative. Salivary neuroendocrine carcinomas may be challenging to separate from Merkel cell carcinomas of the head and neck on pathologic grounds because the latter often metastasize to the parotid gland. Clinical history is often relied upon to separate primary salivary tumors from cutaneous metastases but may not be helpful in all cases. Here we review the clinical, pathologic and molecular features of salivary neuroendocrine carcinomas focusing on high-grade major salivary gland tumors. The difficulty in separating salivary tumors from metastatic Merkel cell carcinoma will be highlighted.

PMID: 29556963 [PubMed - indexed for MEDLINE]

Color Doppler Sonography of Merkel Cell Carcinoma.

Fetched: September 2nd, 2018, 5:00am GMT

Color Doppler Sonography of Merkel Cell Carcinoma.

J Ultrasound Med. 2018 Jan;37(1):285-292

Authors: Catalano O, Alfageme Roldán F, Scotto di Santolo M, Solivetti FM, Wortsman X

Abstract
We illustrate the color Doppler sonographic findings in primary cutaneous Merkel cell carcinoma. Eight cases (4 female and 4 male; mean age, 75.4 years) were collected. The most common affected regions were the face (63%) and the hip/buttock (25%). The mean transverse diameter and thickness were 21 and 14 mm, respectively. Fifty percent were oval, and 50% were dome shaped. All lesions were hypoechoic, with variable degrees of heterogeneity. All but 2 lesions were poorly defined. An acoustic reinforcement artifact was present in 3 and epidermal thickening in 2. All tumors had prominent and chaotic hypervascularity with arterial vessels (mean peak velocity, 11 cm/s; mean resistive index, 0.57).

PMID: 28726278 [PubMed - indexed for MEDLINE]

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

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

Fetched: September 1st, 2018, 5:00am GMT

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

J Am Acad Dermatol. 2018 Aug 27;:

Authors: Paulson KG, Nghiem P

PMID: 30165170 [PubMed - as supplied by publisher]

Do cancer registries play a role in determining the incidence of non-melanoma skin cancers?

Fetched: September 1st, 2018, 5:00am GMT

Do cancer registries play a role in determining the incidence of non-melanoma skin cancers?

Eur J Dermatol. 2018 Apr 01;28(2):169-176

Authors: Anselmo Lima C, Sampaio Lima M, Maria Da Silva A, Prado Nunes MA, Macedo Lima MM, Oliveira Santos M, Lyra D, Kleber Alves C

Abstract
Non-melanoma skin cancers have the highest incidence of all malignancies worldwide. However, cancer registries rarely include data on non-melanoma skin cancers because they tend to be under-reported. To determine incidence rates and changes over time for non-melanoma skin cancers in a mid-sized Brazilian population. We calculated age-standardized rates, adjusted to the world population using the direct method, from 1996-2012 in the Aracaju Cancer Registry and then calculated incidence trends using the Joinpoint Regression Program. We analysed 11,476 cases (5,695 men and 5,781 women) of non-melanoma skin cancer collected during the study period. The histological subtypes in men were 84.5% basal cell carcinoma, 14.5% squamous cell carcinoma, and 1% other histological subtypes, whereas the corresponding percentages in women were 89.1%, 10%, and 0.9%, respectively. Average incidence age-standardized rates were 228.6 (95% CI: 221.6; 235.6) per 100,000 men and 145.4 (95% CI: 141.0; 149.9) per 100,000 women. The incidence mostly increased in the first years for the series and then stabilized. The under-reporting of non-melanoma skin cancers, due to removal of lesions without histopathological confirmation, decisions to keep skin lesions under observation instead of excising them, and deferring medical examination, is a potential pitfall of this study. Age-standardized incidence of non-melanoma skin cancer was high during the study period, but tended to stabilise in the latter years of the study.

PMID: 29619990 [PubMed - indexed for MEDLINE]

Permalink for 'Definitive radiotherapy for a head and neck Merkel cell carcinoma and comprehensive nodal volumes: a case for using a computer-designed variable-thickness compensator to reduce risk and severity of mucositis.'

Definitive radiotherapy for a head and neck Merkel cell carcinoma and comprehensive nodal volumes: a case for using a computer-designed variable-thickness compensator to reduce risk and severity of mucositis.

Fetched: September 1st, 2018, 5:00am GMT

Definitive radiotherapy for a head and neck Merkel cell carcinoma and comprehensive nodal volumes: a case for using a computer-designed variable-thickness compensator to reduce risk and severity of mucositis.

Med Dosim. 2018 Spring;43(1):69-73

Authors: Ahamad A, Weed DT, Pruett DD, Saulpaugh D, Neeranjun W, Fernandez E

Abstract
When contemplating how to treat head and neck primary cancers and regional lymph nodes with radiotherapy, we often select the contemporary intensity-modulated radiotherapy (IMRT) without much consideration of older methods that may give fewer side effects and be more cost-effective. For an 87-year-old female with a 1.5-cm Merkel cell carcinoma (MCC) located 1.5 cm lateral to the orbital rim, we were challenged to deliver 50 Gy to comprehensive elective nodal regions and 70 Gy to the primary. We were particularly concerned about the potential adverse acute effects of radiotherapy to mucosal structures in this elderly female. Acute mucositis could impair nutrition, quality of life, and treatment intensity especially given her age. We compared 3 techniques that are appropriate for this target: step-and-shoot IMRT, matched electron fields (MEF), and electron conformal therapy (BolusECT™). We selected and treated her with BolusECT™ because of better sparing of larynx, pharynx, oral cavity and lips, and shortest treatment time. This is a reasonable option for treating ipsilateral head and neck target volumes at centers where only these 3 techniques are available.

PMID: 29031904 [PubMed - indexed for MEDLINE]

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

Fetched: August 30th, 2018, 5:00am GMT

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

Ann Surg Oncol. 2018 Aug 27;:

Authors: Perez MC, Zager JS

PMID: 30151562 [PubMed - as supplied by publisher]

Merkel-cell carcinoma of the upper limb.

Fetched: August 30th, 2018, 5:00am GMT

Icon for Silverchair Information Systems

Merkel-cell carcinoma of the upper limb.

J Surg Case Rep. 2018 Aug;2018(8):rjy190

Authors: M Rojoa D, Katsogridakis E, Madan M, Rao M

Abstract
Merkel-cell carcinoma is a rare form of aggressive cutaneous cancer that is associated with a poor prognosis. Despite significant advances, its pathogenesis is still poorly understood, and treatment remains controversial. Timely diagnosis and early management is essential in improving survival rate. We present a case of a 63-year-old patient with a rapidly growing upper limb Merkel-cell carcinoma. It was treated with wide-local excision and adjuvant radiotherapy.

PMID: 30151102 [PubMed]

Image Gallery: Merkel cell carcinoma under the rainbow.

Fetched: August 30th, 2018, 5:00am GMT

Image Gallery: Merkel cell carcinoma under the rainbow.

Br J Dermatol. 2017 10;177(4):e166

Authors: di Meo N, Vernoni S, Longone M, Trevisan G

PMID: 29052882 [PubMed - indexed for MEDLINE]

Coincident Metastatic Melanoma and Merkel Cell Carcinoma with Complete Remission on Treatment with Pembrolizumab.

Fetched: August 29th, 2018, 5:00am GMT

Coincident Metastatic Melanoma and Merkel Cell Carcinoma with Complete Remission on Treatment with Pembrolizumab.

Acta Derm Venereol. 2017 Nov 15;97(10):1252-1254

Authors: Thiem A, Kneitz H, Schummer P, Herz S, Schrama D, Houben R, Goebeler M, Schilling B, Gesierich A

PMID: 28761962 [PubMed - indexed for MEDLINE]

CCL17/TARC and CCR4 expression in Merkel cell carcinoma.

Fetched: August 26th, 2018, 5:00am GMT

CCL17/TARC and CCR4 expression in Merkel cell carcinoma.

Oncotarget. 2018 Jul 31;9(59):31432-31447

Authors: Rasheed K, Abdulsalam I, Fismen S, Grimstad Ø, Sveinbjørnsson B, Moens U

Abstract
Merkel cell carcinoma (MCC) is a rare, highly aggressive neuroendocrine skin cancer. In more than 80% of the cases, Merkel cell polyomavirus (MCPyV) is a causal factor. The oncogenic potential of MCPyV is mediated through its viral oncoproteins, large T antigen (LT) and small t antigen (sT). To investigate the role of cytokines in MCC, a PCR array analysis for genes encoding inflammatory cytokines and receptors was performed on MCPyV-negative and MCPyV-positive MCC cell lines, respectively. We detected an increased expression of CCL17/TARC in the MCPyV-positive MKL2 cell line compared to the MCPyV-negative MCC13 cell line. Transfection studies in MCC13 cells with LT expression plasmid, and a luciferase reporter plasmid containing the CCL17/TARC promoter, exhibited stimulated promoter activity. Interestingly, the ectopic expression of CCL17/TARC upregulated MCPyV early and late promoter activities in MCC13 cells. Furthermore, recombinant CCL17/TARC activated both the mitogen-activated protein kinase and the NF-κB pathways. Finally, immunohistochemical staining on human MCC tissues showed a strong staining of CCL17/TARC and its receptor CCR4 in both LT-positive and -negative MCC. Taken together, CCL17/TARC and CCR4 may be a potential target in MCC therapy providing MCC patients with a better overall survival outcome.

PMID: 30140381 [PubMed]

$Permalink for 'Favorable Response to Treatment with Avelumab in an HIV-Positive Patient with Advanced Merkel Cell Carcinoma Previously Refractory to Chemotherapy.'$

Favorable Response to Treatment with Avelumab in an HIV-Positive Patient with Advanced Merkel Cell Carcinoma Previously Refractory to Chemotherapy.

Fetched: August 26th, 2018, 5:00am GMT

Favorable Response to Treatment with Avelumab in an HIV-Positive Patient with Advanced Merkel Cell Carcinoma Previously Refractory to Chemotherapy.

Case Rep Oncol. 2018 May-Aug;11(2):467-475

Authors: Al Homsi MU, Mostafa M, Fahim K

Abstract
Avelumab is indicated for the management of Merkel cell carcinoma, a rare and aggressive neuroendocrine skin cancer. Its regulatory approval followed the positive outcome of a Phase 2 trial on 88 patients with stage IV disease, which excluded patients with immunodeficiency due to HIV, a risk factor for this cancer type. We report a positive and sustained response to avelumab in an HIV-positive patient with stage IV Merkel cell carcinoma refractory to previous chemotherapy (cisplatin/etoposide) and radiotherapy. Five cycles of avelumab 10 mg/m2 resulted in the resolution of tumor activity visualized using PET-CT scanning in all affected lymph nodes. The only major side effect associated with avelumab was thyroiditis and mild hypothyroidism, a known adverse effect of this treatment, which was well controlled by L-thyroxine treatment. Treatment is ongoing and the positive response has been sustained during 5 further cycles of treatment up to date. This apparently durable response is consistent with the earlier clinical trial experience with avelumab, but seen here in a patient with HIV-associated immunodeficiency as a predisposing factor (an exclusion criterion from the previous trial). Further clinical trials with avelumab in a broader patient population with Merkel cell carcinoma are warranted.

PMID: 30140209 [PubMed]

Merkel cell polyomavirus and Langerhans cell neoplasm.

Fetched: August 25th, 2018, 5:00am GMT

Merkel cell polyomavirus and Langerhans cell neoplasm.

Cell Commun Signal. 2018 Aug 22;16(1):49

Authors: Murakami I, Wada N, Nakashima J, Iguchi M, Toi M, Hashida Y, Higuchi T, Daibata M, Matsushita M, Iwasaki T, Kuwamoto S, Horie Y, Nagata K, Hayashi K, Oka T, Yoshino T, Imamura T, Morimoto A, Imashuku S, Gogusev J, Jaubert F

Abstract
BACKGROUND: The relationship between various external agents such as pollen, food, and infectious agents and human sensitivity exists and is variable depending upon individual's health conditions. For example, we believe that the pathogenetic potential of the Merkel cell polyomavirus (MCPyV), the resident virus in skin, is variable and depends from the degree of individual's reactivity. MCPyV as well as Epstein-Barr virus, which are normally connected with humans under the form of subclinical infection, are thought to be involved at various degrees in several neoplastic and inflammatory diseases. In this review, we cover two types of Langerhans cell neoplasms, the Langerhans cell sarcoma (LCS) and Langerhans cell histiocytosis (LCH), represented as either neoplastic or inflammatory diseases caused by MCPyV.
METHODS: We meta-analyzed both our previous analyses, composed of quantitative PCR for MCPyV-DNA, proteomics, immunohistochemistry which construct IL-17 endocrine model and interleukin-1 (IL-1) activation loop model, and other groups' data.
RESULTS: We have shown that there were subgroups associated with the MCPyV as a causal agent in these two different neoplasms. Comparatively, LCS, distinct from the LCH, is a neoplastic lesion (or sarcoma) without presence of inflammatory granuloma frequently observed in the elderly. LCH is a proliferative disease of Langerhans-like abnormal cells which carry mutations of genes involved in the RAS/MAPK signaling pathway. We found that MCPyV may be involved in the development of LCH.
CONCLUSION: We hypothesized that a subgroup of LCS developed according the same mechanism involved in Merkel cell carcinoma pathogenesis. We proposed LCH developed from an inflammatory process that was sustained due to gene mutations. We hypothesized that MCPyV infection triggered an IL-1 activation loop that lies beneath the pathogenesis of LCH and propose a new triple-factor model.

PMID: 30134914 [PubMed - in process]

Merkel Cell Carcinoma in a Steer.

Fetched: August 23rd, 2018, 5:00am GMT

Merkel Cell Carcinoma in a Steer.

J Comp Pathol. 2018 Jan;158:17-21

Authors: Teh APP, Izzati UZ, Diep NV, Hirai T, Yamaguchi R

Abstract
Merkel cell carcinoma is a rare and aggressive cutaneous neuroendocrine tumour reported only in man, dogs and cats. A 20-month-old Japanese black fattening steer was presented with necrotic protruding skin masses over the left thoracic area and a 20 × 25 cm subcutaneous mass in the left abdominal area. Microscopical evaluation of the masses revealed cords of small to medium-sized round tumour cells with marked anisocytosis and anisokaryosis and clear and vacuolated cytoplasm, which were separated by a delicate fibrovascular stroma and arranged in a trabecular and nested pattern. Necropsy examination revealed multiple solid white nodular masses in the lungs. Immunohistochemistry (IHC) for cytokeratin (CK) 20 and CKAE1/3 revealed focal perinuclear labelling of tumour cells. IHC for the neuroendocrine markers chromogranin A and neuron specific enolase, the neuroepithelial stem cell marker nestin and the hormonal markers adrenocorticotropic hormone and calcitonin revealed diffuse cytoplasmic labelling of all tumour cells. Ultrastructurally, the tumour cells contained few neurosecretory granules and abundant glycogen pools. The tumours were diagnosed as Merkel cell carcinoma with pulmonary metastases and this case represents the first such diagnosis in cattle.

PMID: 29422311 [PubMed - indexed for MEDLINE]

Hedgehog Signaling Inhibitors Fail to Reduce Merkel Cell Carcinoma Viability.

Fetched: August 22nd, 2018, 5:00am GMT

Hedgehog Signaling Inhibitors Fail to Reduce Merkel Cell Carcinoma Viability.

J Invest Dermatol. 2017 05;137(5):1187-1190

Authors: Carroll TM, Williams JS, Daily K, Rogers T, Gelb T, Coxon A, Wang SQ, Crago AM, Busam KJ, Brownell I

PMID: 28130073 [PubMed - indexed for MEDLINE]

Comparative effectiveness of avelumab versus chemotherapy in Merkel cell carcinoma: innovative use of patient insights.

Fetched: August 17th, 2018, 5:00am GMT

Comparative effectiveness of avelumab versus chemotherapy in Merkel cell carcinoma: innovative use of patient insights.

J Comp Eff Res. 2018 Aug 15;:

Authors: Bharmal M, Marrel A, Hennessy M, Fofana F, Lambert J, Arnould B

Abstract
AIM: To assess patient experience with chemotherapy and avelumab in metastatic Merkel cell carcinoma (mMCC).
METHODS: In the JAVELIN Merkel 200 trial, chemotherapy-refractory mMCC patients could participate in optional qualitative interviews at baseline documenting recollection of previous chemotherapy experience, and at weeks 13/25 documenting current experience with avelumab. Functional Assessment of Cancer Therapy subscale for melanoma questionnaire (FACT-M) was administered in parallel.
RESULTS: In our sample, chemotherapy was associated with an unpleasant experience. On selected FACT-M items addressing chemotherapy-impacted concepts, most patients receiving avelumab were improved or stable; few worsened. In addition, a few patients spontaneously reported experiencing less toxicity with avelumab than experienced during previous chemotherapy.
CONCLUSION: This approach merging qualitative and quantitative data suggests that mMCC patients report a better experience with avelumab than with chemotherapy.

PMID: 30107762 [PubMed - as supplied by publisher]

Management of cutaneous Merkel cell carcinoma.

Fetched: August 17th, 2018, 5:00am GMT

Management of cutaneous Merkel cell carcinoma.

Acta Oncol. 2018 Mar;57(3):320-323

Authors: Mendenhall WM, Morris CG, Kirwan JM, Amdur RJ, Shaw C, Dziegielewski PT

Abstract
PURPOSE: To report the outcomes of patients with previously untreated cutaneous Merkel cell carcinoma (MCC) managed with curative intent.
MATERIAL AND METHODS: Between December 1984 and August 2015, 59 patients with previously untreated cutaneous MCC were managed with curative intent with surgery and adjuvant radiotherapy (54 patients) or radiotherapy alone (5 patients) at the University of Florida. Primary sites included head and neck (45 patients), extremities (11 patients) and trunk (3 patients). Adjuvant chemotherapy was employed in 14 patients. Patients were staged according to the AJCC staging system: stage I, 25 patients; stage IIA, 7 patients; and, stage III, 27 patients. No patients had distant metastases. Median follow-up for all patients was 3.2 years (range, 0.3-20.9 years). Median follow-up for survivors was 6.7 years (range, 1.6-20.9 years).
RESULTS: The 5-year outcomes were as follows: local control, 91%; regional control, 79%; local-regional control, 77%; disease metastasis-free survival, 60%; cause-specific survival, 53%; and overall survival, 39%. The 5-year outcomes for patients with stage I-IIA versus stage-III disease were the following: local-regional control, 90% versus 57% (p = .0115); distant metastasis-free survival, 78% versus 36% (p = .0002); cause-specific survival, 68% versus 35% (p = .0050); and overall survival, 48% versus 27% (p = .0377). Local-regional recurrences occurred in 12 patients; no patients were successfully salvaged. Severe late complications were observed in four patients.
CONCLUSIONS: Although radiotherapy alone or combined with surgery results in a relatively high likelihood of local-regional control, the majority of recurrences are distant and approximately half of patients are cured. Patients with regional disease at diagnosis have significantly worse outcomes.

PMID: 28712323 [PubMed - indexed for MEDLINE]

Merkel cell carcinoma: new insights into pathogenesis.

Fetched: August 17th, 2018, 5:00am GMT

Merkel cell carcinoma: new insights into pathogenesis.

Eur J Dermatol. 2017 06 01;27(3):307-309

Authors: Curzio G, Paolini F, Cota C, Donati P, Di Mattia C, Mariani L, Migliano E, Venuti A

PMID: 28382918 [PubMed - indexed for MEDLINE]

Skin cancer management-updates on Merkel cell carcinoma.

Fetched: August 16th, 2018, 5:00am GMT

Skin cancer management-updates on Merkel cell carcinoma.

Ann Transl Med. 2018 Jul;6(14):282

Authors: Tai P, Au J

Abstract
There are many different types of skin tumors in the World Health Organization (WHO) classification. The natural course and treatment varies according to the histological type. This review summarizes clinical experience for treatment decision. Contemporary radiotherapy and systemic therapy are improving. Landmark studies for basal cell and Merkel cell carcinomas (MCC) trigger further research and impetus for improving treatment outcome. Avelumab, nivolumab, pembrolizumab, ipilimumab appear to be promising for treatment of advanced MCCs and adjuvant trials are underway.

PMID: 30105232 [PubMed]

Real-world treatment outcomes in patients with metastatic Merkel cell carcinoma treated with chemotherapy in the USA.

Fetched: August 16th, 2018, 5:00am GMT

Real-world treatment outcomes in patients with metastatic Merkel cell carcinoma treated with chemotherapy in the USA.

Future Oncol. 2017 Aug;13(19):1699-1710

Authors: Cowey CL, Mahnke L, Espirito J, Helwig C, Oksen D, Bharmal M

Abstract
AIM: This retrospective study of patients in the USA with metastatic Merkel cell carcinoma (mMCC) aimed to assess patient responses to second-line and later (2L+) and first-line (1L) chemotherapy.
PATIENTS & METHODS: Out of 686 patients with MCC identified in The US Oncology Network, 20 and 67 patients with mMCC qualified for the 2L+ and 1L study, respectively; the primary analysis population was restricted to immunocompetent patients.
RESULTS: In the 2L+ primary analysis population, objective response rate (ORR) was 28.6%, median duration of response (DOR) was 1.7 months and median progression-free survival was 2.2 months. In the 1L primary analysis population, ORR was 29.4%, median DOR was 6.7 months and median progression-free survival was 4.6 months.
CONCLUSION: The low ORR and brief DOR underscore the need for novel therapies.

PMID: 28605939 [PubMed - indexed for MEDLINE]

Importance of Sentinel Lymph Node Biopsy in Merkel Cell Carcinoma.

Fetched: August 15th, 2018, 5:00am GMT

Importance of Sentinel Lymph Node Biopsy in Merkel Cell Carcinoma.

J Oncol Pract. 2016 07;12(7):647-8

Authors: Angeles CV, Wong SL

PMID: 27407161 [PubMed - indexed for MEDLINE]

Permalink for 'Phase I, open-label study of pasireotide in patients with BRAF-wild type and NRAS-wild type, unresectable and/or metastatic melanoma.'

Phase I, open-label study of pasireotide in patients with BRAF-wild type and NRAS-wild type, unresectable and/or metastatic melanoma.

Fetched: August 12th, 2018, 5:00am GMT

Phase I, open-label study of pasireotide in patients with BRAF-wild type and NRAS-wild type, unresectable and/or metastatic melanoma.

ESMO Open. 2018;3(5):e000388

Authors: Dummer R, Michielin O, Nägeli MC, M Goldinger S, Campigotto F, Kriemler-Krahn U, Schmid H, Pedroncelli A, Micaletto S, Schadendorf D

Abstract
Introduction: Somatostatin analogues exert antitumour activity via direct and indirect mechanisms. The present study was designed to assess the safety and efficacy of pasireotide in patients with BRAF-wild type (WT) and NRAS-WT metastatic melanoma.
Patients and methods: Patients with unresectable and/or metastatic melanoma or Merkel cell carcinoma were eligible. Pasireotide was administered at different doses for ≤8 weeks in dose-escalation phase, followed by long-acting pasireotide 80 mg or lower dose in case of toxicity in follow-up phase up to six additional months. Primary endpoint was safety in the first 8 weeks of dose-escalation phase.
Results: The study was terminated early due to slow recruitment. Of the 10 patients with metastatic melanoma enrolled, only four reached the high dose level: two patients reached 3600 µg in dose-escalation and follow-up phases and two patients reached 3600 µg in dose-escalation and long-acting pasireotide 80 mg in follow-up phases and were stable for >5 months. Most common adverse events (AEs) during dose-escalation phase in ≥2 patients (20%) were: diarrhoea (50%), nausea (50%), fatigue (20%), hyperglycaemia (20%), hypophosphatemia (20%), chills (20%) and tumour pain (20%). Grade 3 or 4 study drug-related AEs were diarrhoea and nausea, reported in one patient. Partial response was documented in one patient and stable disease in another.
Conclusions: Pasireotide was well tolerated, and safety results were similar to those previously reported in other indications. Further studies are needed to evaluate its antitumour activity alone and in combination with other drugs in melanoma.

PMID: 30094073 [PubMed]

Permalink for 'Intratumoral G100, a TLR4 agonist, induces anti-tumor immune responses and tumor regression in patients with Merkel cell carcinoma.'

Intratumoral G100, a TLR4 agonist, induces anti-tumor immune responses and tumor regression in patients with Merkel cell carcinoma.

Fetched: August 12th, 2018, 5:00am GMT

Intratumoral G100, a TLR4 agonist, induces anti-tumor immune responses and tumor regression in patients with Merkel cell carcinoma.

Clin Cancer Res. 2018 Aug 09;:

Authors: Bhatia S, Miller NJ, Lu H, Vandeven NV, Ibrani D, Shinohara M, Byrd D, Parvathaneni U, Kulikauskas RM, Ter Meulen J, Hsu FJ, Koelle DM, Nghiem P

Abstract
PURPOSE: G100 is a toll-like receptor 4 (TLR4) agonist that triggers innate and adaptive anti-tumor immune responses in preclinical models. This pilot study assessed the safety, efficacy, and immunologic activity of intratumoral (IT) administration of G100 in patients with Merkel cell carcinoma (MCC).
EXPERIMENTAL DESIGN: Patients with loco-regional MCC (n=3; Cohort A) received neoadjuvant IT G100 (2 weekly doses at 5 μg/dose) followed by surgery and radiotherapy; patients with metastatic MCC (n=7; Cohort B) received 3 doses in a 6-week cycle and could receive additional cycles with/without radiotherapy.
RESULTS: IT G100 was safe and feasible in both neoadjuvant and metastatic settings. Treatment-related adverse events were mostly grade 1 or 2 injection site reactions. IT G100 led to increased inflammation in the injected tumors with infiltration of CD8+and CD4+T cells and activation of immune-related genes. These pro-inflammatory changes were associated with local tumor regression and appeared to promote systemic immunity. All 3 Cohort A patients successfully completed therapy; 2 patients remain recurrence-free at 44+ and 41+ months, including one with a pathologic complete response after G100 alone. In Cohort B, 2 patients achieved sustained partial responses, both lasting 33+ months after 2 cycles of therapy.
CONCLUSIONS: In this first-in-human study, IT G100 induced anti-tumor immune responses, demonstrated acceptable safety, and showed encouraging clinical activity.

PMID: 30093453 [PubMed - as supplied by publisher]

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

Fetched: August 11th, 2018, 5:00am GMT

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

J Glob Oncol. 2018 Jul;(4):1-11

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

PMID: 30085832 [PubMed - in process]

Permalink for 'INSM1 is More Sensitive and Interpretable than Conventional Immunohistochemical Stains Used to Diagnose Merkel Cell Carcinoma.'

INSM1 is More Sensitive and Interpretable than Conventional Immunohistochemical Stains Used to Diagnose Merkel Cell Carcinoma.

Fetched: August 11th, 2018, 5:00am GMT

INSM1 is More Sensitive and Interpretable than Conventional Immunohistochemical Stains Used to Diagnose Merkel Cell Carcinoma.

Am J Surg Pathol. 2018 Aug 04;:

Authors: Lilo MT, Chen Y, LeBlanc RE

Abstract
Merkel cell carcinoma (MCC) is an extremely aggressive skin cancer that must be distinguished from other basaloid cutaneous neoplasms that have different treatments and prognoses. This is sometimes challenging in small shave specimens, crushed samples, lymph nodes, and core needle biopsies. Insulinoma-associated protein 1 (INSM1) immunohistochemistry is a sensitive nuclear marker of neuroendocrine differentiation. INSM1 staining was performed on 56 MCC (47 primary tumors, 9 nodal metastases), 50 skin control cases that included basal cell carcinomas, basaloid squamous cell carcinomas, Bowen disease, sebaceous neoplasms, melanoma, and B-cell lymphomas, and 28 lymph node control cases that included metastatic neuroendocrine neoplasms, melanomas, squamous cell carcinomas, lymphomas, and adenocarcinomas. Percent of staining nuclei (0, <25%, 25% to 50%, 50% to 75%, >75%) and intensity (weak, moderate, strong) were recorded for each sample. All 56 MCC expressed INSM1. By comparison, synaptophysin, CK20, and chromogranin were expressed in 96%, 92%, and 32% of MCC, respectively. While the 3 conventional markers showed significant variability in staining intensity and distribution, INSM1 stained >75% tumor nuclei in 89% of MCC and 50% to 75% of tumor nuclei in 11%. Staining intensity was strong in 85% and moderate in 15%. None of the 50 cutaneous basaloid non-MCC neoplasms in the control group stained with INSM1, and among the lymph node controls 5 of 5 neuroendocrine neoplasms expressed INSM1, confirming that INSM1 staining cannot distinguish MCC from metastatic extracutaneous neuroendocrine carcinoma. INSM1 holds promise as a neuroendocrine marker that can distinguish MCC from its mimickers in the skin and improve detection of sentinel lymph node metastases.

PMID: 30080705 [PubMed - as supplied by publisher]

18F-FDG PET/CT for Monitoring Response of Merkel Cell Carcinoma to the Novel Programmed Cell Death Ligand 1 Inhibitor Avelumab.

Fetched: August 11th, 2018, 5:00am GMT

18F-FDG PET/CT for Monitoring Response of Merkel Cell Carcinoma to the Novel Programmed Cell Death Ligand 1 Inhibitor Avelumab.

Clin Nucl Med. 2018 May;43(5):e142-e144

Authors: Eshghi N, Lundeen TF, MacKinnon L, Avery R, Kuo PH

Abstract
An 85-year-old man with stage IIIA Merkel cell carcinoma of the left arm was initially treated with local excision and axillary node dissection followed by radiation therapy. Eight months after surgery, whole-body FDG PET/CT demonstrated intensely hypermetabolic hepatic metastases and abdominal lymphadenopathy. Given his age and comorbidities, he was considered a poor candidate for chemotherapy, and therefore the novel programmed cell death ligand 1 inhibitor avelumab was initiated. FDG PET/CT after 4 cycles showed complete resolution of hepatic and nodal metastases. Whole-body FDG PET/CT can be used for monitoring response of multisystem metastases from Merkel cell carcinoma to active immunotherapy.

PMID: 29538029 [PubMed - indexed for MEDLINE]

Insulinoma-associated 1: A novel nuclear marker in Merkel cell carcinoma (cutaneous neuroendocrine carcinoma).

Fetched: August 11th, 2018, 5:00am GMT

Insulinoma-associated 1: A novel nuclear marker in Merkel cell carcinoma (cutaneous neuroendocrine carcinoma).

J Cutan Pathol. 2018 Feb;45(2):129-135

Authors: Rush PS, Rosenbaum JN, Roy M, Baus RM, Bennett DD, Lloyd RV

Abstract
Merkel cell carcinoma (MCC) is a rare, clinically aggressive, cutaneous neuroendocrine (NE) neoplasm. As a tumor with small, round, blue cells, the histologic differential diagnosis for MCC can include melanoma, metastatic small cell carcinoma (SCC), nodular hematopoietic tumors, basal cell carcinoma (BCC), atypical variants of squamous carcinoma and the uncommon occurrence of primary cutaneous Ewing sarcoma. In cases with atypical histology or without the classic immunophenotype, the diagnosis can be challenging. Ultimately, immunohistochemistry (IHC) is essential to the definitive diagnosis of MCC and in difficult cases, the diagnosis may hinge entirely on the immunophenotype of the tumor cells. Insulinoma-associated 1 (INSM1) is a transcription factor expressed in tissues undergoing terminal NE differentiation. As a nuclear protein tied to both differentiation and the cell cycle, INSM1 may offer additional utility in comparison to traditional, cytoplasmic markers of NE differentiation.

PMID: 29148079 [PubMed - indexed for MEDLINE]

Permalink for 'Systematic literature review of efficacy, safety and tolerability outcomes of chemotherapy regimens in patients with metastatic Merkel cell carcinoma.'

Systematic literature review of efficacy, safety and tolerability outcomes of chemotherapy regimens in patients with metastatic Merkel cell carcinoma.

Fetched: August 11th, 2018, 5:00am GMT

Systematic literature review of efficacy, safety and tolerability outcomes of chemotherapy regimens in patients with metastatic Merkel cell carcinoma.

Future Oncol. 2017 Jun;13(14):1263-1279

Authors: Nghiem P, Kaufman HL, Bharmal M, Mahnke L, Phatak H, Becker JC

Abstract
AIM: Merkel cell carcinoma (MCC) is a rare neuroendocrine, cutaneous malignancy with poor prognosis once metastasized. The aim of this study was to conduct a systematic literature review to assess clinical outcomes associated with chemotherapy regimens in metastatic MCC.
MATERIALS & METHODS: Embase®, MEDLINE®, MEDLINE®-In-Process and CENTRAL were searched for studies published in January 2016.
RESULTS & CONCLUSION: Overall, the literature on chemotherapy in patients with metastatic MCC is sparse, with most studies being case series/reports. Across all studies, response rates ranged from 20 to 61%, with higher response rates in first-line setting (53-61%) versus second-line setting (23-45%). Among responders, duration of response was short (≤8 months) in both first- and second-line settings. There is a need for novel agents that can induce durable responses in metastatic MCC.

PMID: 28350180 [PubMed - indexed for MEDLINE]

Resection Margins in Merkel Cell Carcinoma: Is a 1-cm Margin Wide Enough?

Fetched: August 5th, 2018, 5:00am GMT

Resection Margins in Merkel Cell Carcinoma: Is a 1-cm Margin Wide Enough?

Ann Surg Oncol. 2018 Aug 02;:

Authors: Perez MC, de Pinho FR, Holstein A, Oliver DE, Naqvi SMH, Kim Y, Messina JL, Burke E, Gonzalez RJ, Sarnaik AA, Cruse CW, Wuthrick EJ, Harrison LB, Sondak VK, Zager JS

Abstract
BACKGROUND: Guidelines regarding specific resection margins for primary Merkel cell carcinoma (MCC) are not well established. The current National Comprehensive Cancer Network (NCCN) guidelines recommend 1- to 2-cm resection margins. This study aimed to determine the impact of margin width on local recurrence (LR), disease-specific survival (DSS), overall survival (OS), and type of wound closure.
METHODS: All patients who underwent resection of primary MCC at a single institution from 2000 to 2015 were reviewed. Patient demographics, clinicopathologic characteristics, treatments, and outcomes were reviewed.
RESULTS: A total of 240 patients underwent resection of primary MCC with resection margin width identified in the operative report. The median age was 76 years, and 65.8% of the patients were men. Of the 240 patients, 85 (35.4%) had head and neck primaries, 140 (58.3%) had extremity primaries, and 15 (6.3%) had trunk primaries. In terms of margins, 69 patients (28.8%) had a margin of 1 cm, 36 patients (15%) had a margin of 1.1-1.9 cm, and 135 patients (56.2%) had a margin of 2 cm or more. The median follow-up period was 21 months. The LR rate was 2.9% for a margin of 1 cm, 2.8% for a margin of 1.1-1.9 cm, and 5.2% for a margin of 2 cm or more (p = 0.80). The 5-year OS was 63.6% for a margin of 1 cm, 59.7% for a margin of 1.1-1.9, and 70.7% for a margin of 2 cm or more (p = 0.66). The 5-year DSS was 80.3% for a margin of 1 cm, 66.2% for a margin of 1.1-1.9 cm, and 91.8% for a margin of 2 cm or more (p = 0.28). For wound closure, 43.5, 50, and 65.9% of the patients respectively required a flap or graft with a margin of 1, 1.1-1.9, and 2 cm or more (p = 0.006).
CONCLUSIONS: A 1-cm resection margins did not increase the risk of LR. Margin width did not make a significant difference in DSS or OS. Larger resection margins increase the need for a graft or flap closure.

PMID: 30073600 [PubMed - as supplied by publisher]

Predictors of survival in neurometastatic Merkel cell carcinoma.

Fetched: August 4th, 2018, 5:00am GMT

Predictors of survival in neurometastatic Merkel cell carcinoma.

Eur J Cancer. 2018 Jul 30;101:152-159

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

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

PMID: 30071443 [PubMed - as supplied by publisher]

Circulating cell-free miR-375 as surrogate marker of tumor burden in Merkel cell carcinoma.

Fetched: August 2nd, 2018, 5:00am GMT

Circulating cell-free miR-375 as surrogate marker of tumor burden in Merkel cell carcinoma.

Clin Cancer Res. 2018 Jul 30;:

Authors: Fan K, Ritter C, Nghiem P, Blom A, Verhaegen ME, Dlugosz A, Odum N, Woetmann A, Tothill RW, Hicks RJ, Sand M, Schrama D, Schadendorf D, Ugurel S, Becker JC

Abstract
PURPOSE: Merkel cell carcinoma (MCC) is an aggressive skin cancer with neuroendocrine differentiation. There is an unmet need for MCC-specific blood-based surrogate biomarkers of tumor burden; circulating cell-free micro(mi)RNA may serve this purpose.
EXPERIMENTAL DESIGN: Expression of miR-375 was quantified in 24 MCC and 23 non-MCC cell lines, 67 MCC and 58 non-MCC tumor tissues, sera of two preclinical MCC models, sera of 109 MCC patients and 30 healthy controls by nCounter®human-v2-miRNA expression or miR-375 specific real-time PCR assays. The patients' sera consisted of two retrospective (discovery and training) and two prospective (validation) cohorts.
RESULTS: miR-375 expression was high in MCC cell lines and tissues compared to non-MCCs. It was readily detected in MCC conditioned medium and sera of preclinical models bearing MCC xenografts. miR-375 levels were higher in sera from tumor-bearing MCC patients than in tumor-free patients or healthy controls (p<0.0005). Moreover, miR-375 serum levels correlated with tumor stage in tumor-bearing (p=0.037) but not in tumor-free (p=0.372) MCC patients. miR-375 serum level showed high diagnostic accuracy to discriminate tumor-bearing and tumor-free MCC patients as demonstrated by receiver operating characteristic curve analysis in the retrospective cohorts (AUC=0.954 and 0.800) as well as in the prospective cohorts (AUC=0.929 and 0.959). miR-375 serum level reflected dynamic changes in tumor burden of MCC patients during therapeutic interventions.
CONCLUSIONS: Circulating cell-free miR-375 proved as a surrogate marker for tumor burden in MCC without restriction to polyomavirus positivity, it thus appears to be useful for therapy monitoring and the follow-up of MCC patients.

PMID: 30061360 [PubMed - as supplied by publisher]

Merkel Cell Carcinoma of the Head and Neck: Recommendations for Diagnostics and Treatment.

Fetched: August 2nd, 2018, 5:00am GMT

Merkel Cell Carcinoma of the Head and Neck: Recommendations for Diagnostics and Treatment.

Ann Surg Oncol. 2017 Oct;24(11):3430-3437

Authors: Müller-Richter UDA, Gesierich A, Kübler AC, Hartmann S, Brands RC

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive tumor that often occurs in the head and neck region. Because of these features, the classifications and diagnostic and treatment regimens are frequently modified. Especially in the anatomically complex head and neck region, it is crucial to be aware of the current recommendations for diagnostics and treatment of MCC to ensure appropriate treatment. This overview aims to summarize the currently available literature.
METHODS: The authors reviewed the relevant literature and international guidelines for MCC from 2012 to 2017 with respect to epidemiology and prognosis, diagnostic procedures and imaging, surgery, radiation, systemic treatment, and aftercare. These results were compared with existing guidelines, some of them current, and recommendations were derived.
RESULTS: Marked developments in imaging have resulted in an increased use of functional imaging. The surgical concepts have changed regarding safety margins and the use of sentinel node biopsies. In systemic treatment, a move from conventional agents toward immuno-oncology can be observed.
CONCLUSIONS: For staging, it is important to be as exact as possible using functional imaging (e.g., positron emission tomography/computed tomography scan), especially in the head and neck area with its complex lymph drainage. This often plays an especially important role in early stages of the tumor, when the resection margin can be reduced to preserve the organ. Aftercare also should include functional imaging. In an advanced, metastatic stage, immuno-oncology (PD-1, PD-L1, CTLA-4) is superior to the previous methods of systemic treatment.

PMID: 28762116 [PubMed - indexed for MEDLINE]

Endoscopic surgery reduces operation time for auditory neoplasm - Korea Biomedical Review

Posted: October 11th, 2018, 4:13am GMT

Korea Biomedical Review

Endoscopic surgery reduces operation time for auditory neoplasm
Korea Biomedical Review
Neuroendocrine tumors are benign tumors that originate inside the vestibular snail nerves, which are responsible for equilibrium sensation and hearing. The symptom mainly occurs in patients in their 40s to 50s. The diseases can accompany hearing loss, ...

Surveillance Appears Reasonable for Small pNETs - MedPage Today

Posted: October 8th, 2018, 6:45pm GMT

MedPage Today

Surveillance Appears Reasonable for Small pNETs
MedPage Today
SEATTLE -- Patients with small (<1 cm) pancreatic neuroendocrine tumors (pNETs) had a 5-year survival of 100% with surveillance, data from a large retrospective study showed. Surgery for small pNETs was associated with worse survival, though the ...

An Update on Lung NET Guidelines - AJMC.com Managed Markets Network

Posted: October 7th, 2018, 11:21am GMT

An Update on Lung NET Guidelines
AJMC.com Managed Markets Network
Despite lung neuroendocrine tumors (NETs) being the most common single organ site of NETs and increasing in both incidence and prevalence, there is limited lung NET-specific data to guide diagnosis and management. As a result, there are challenges ...

Surgery Improves Survival for most pNETs - MedPage Today

Posted: October 6th, 2018, 3:49pm GMT

MedPage Today

Surgery Improves Survival for most pNETs
MedPage Today
SEATTLE -- Surgery for pancreatic neuroendocrine tumors (pNETs) significantly improved survival for all patients except those with the earliest-stage disease, a retrospective review of 4,700 patients showed. Among patients with stages II-IV pNETs ...

Cancer origins—genetics rules the day - Science Magazine

Posted: October 4th, 2018, 3:59pm GMT

Cancer origins—genetics rules the day
Science Magazine
(2) investigate the mechanisms of development of neuro endocrine cancer in the lung and the prostate using human epithelial cells in culture. They find that these neuroendocrine tumors can arise from non-neuroendocrine epithelial cells, which converge ...

Reprogramming normal human epithelial tissues to a common, lethal neuroendocrine cancer lineage - Science Magazine

Posted: October 4th, 2018, 3:59pm GMT

Reprogramming normal human epithelial tissues to a common, lethal neuroendocrine cancer lineage
Science Magazine
Epithelial cancers develop resistance to targeted therapies in a number of different ways. Several cancer types do so by undergoing phenotypic conversion to a highly aggressive cancer called small cell neuroendocrine carcinoma (SCNC). Whether distinct ...

Permalink for 'Quality of Life in Patients with Metastatic Gastroenteropancreatic Neuroendocrine Tumors Receiving Peptide Receptor ... - Journal of Nuclear Medicine'

Quality of Life in Patients with Metastatic Gastroenteropancreatic Neuroendocrine Tumors Receiving Peptide Receptor ... - Journal of Nuclear Medicine

Posted: October 1st, 2018, 11:23am GMT

Quality of Life in Patients with Metastatic Gastroenteropancreatic Neuroendocrine Tumors Receiving Peptide Receptor ...
Journal of Nuclear Medicine
Gastroenteropancreatic neuroendocrine tumors (GEPNETs) are considered a relatively rare disease, although incidence rates have almost doubled over the past 3 decades (1,2). They may be asymptomatic for years and are often diagnosed at an advanced ...

Quality of Life in Patients with Metastatic Gastroenteropancreatic Neuroendocrine Tumors Receiving Peptide Receptor ... - Journal of Nuclear Medicine

Posted: October 1st, 2018, 11:23am GMT

Quality of Life in Patients with Metastatic Gastroenteropancreatic Neuroendocrine Tumors Receiving Peptide Receptor ...
Journal of Nuclear Medicine
Abstract. In patients with metastatic gastroenteropancreatic neuroendocrine tumors (NETs), we evaluated health-related quality of life (HRQoL) from the first peptide receptor radionuclide therapy (PRRT) to the first restaging and compared the scores ...

This Month in JNM - Journal of Nuclear Medicine

Posted: October 1st, 2018, 11:09am GMT

This Month in JNM
Journal of Nuclear Medicine
QoL and PRRT for NETs: Martini and colleagues evaluate quality-of-life factors in patients with gastroenteropancreatic neuroendocrine tumors from first peptide-receptor radionuclide therapy to first restaging and compare resulting scores with general ...

Pazopanib Shows Promise in Rare Cancer Syndrome - Medscape

Posted: October 1st, 2018, 9:24am GMT

Medscape

Pazopanib Shows Promise in Rare Cancer Syndrome
Medscape
Patients with VHL disease develop retinal, cerebellar, and spinal hemangioblastomas, renal cysts, clear cell renal cell carcinomas, pancreatic cysts, pancreatic neuroendocrine tumors, pheochromocytomas, endolymphatic sac tumors of the middle ear, and ...

Rozella “Rosie” Ritchison - Seymour Tribune

Posted: September 15th, 2018, 10:04pm GMT

Seymour Tribune

Rozella “Rosie” Ritchison
Seymour Tribune
She was preceded in death by her parents, Merlin L. and Irma Williams Sears, and brother, Tim. After having symptoms since shortly after her retirement in 2009, she was finally diagnosed with carcinoid cancer, a form of neuroendocrine tumor cancer ...

Neuroendocrine Tumors (NETs) Market Insights, Epidemiology and Market Forecast-2027 - Digital Journal

Posted: September 13th, 2018, 9:00pm GMT

Neuroendocrine Tumors (NETs) Market Insights, Epidemiology and Market Forecast-2027
Digital Journal
Albany, NY -- (SBWIRE) -- 09/13/2018 -- Neuroendocrine tumors (NETs) consists of complex group of tumors that develop predominantly in the digestive or respiratory tracts, but can occur in many areas of the body. These tumors arise from cells called ...

This RSS feed URL is deprecated

Posted: August 30th, 2018, 5:00am GMT

This RSS feed URL is deprecated, please update. New URLs can be found in the footers at [https:]

Permalink for 'Gastroenteropancreatic Neuroendocrine Tumor Therapeutics Market: Rise in Prevalence of Colorectal Cancer Drive ... - Digital Journal'

Gastroenteropancreatic Neuroendocrine Tumor Therapeutics Market: Rise in Prevalence of Colorectal Cancer Drive ... - Digital Journal

Posted: August 24th, 2018, 4:35pm GMT

Gastroenteropancreatic Neuroendocrine Tumor Therapeutics Market: Rise in Prevalence of Colorectal Cancer Drive ...
Digital Journal
This press release was orginally distributed by SBWire. Albany, NY -- (SBWIRE) -- 08/24/2018 -- Gastroenteropancreatic neuroendocrine tumors are a large and differing group of uncommon and complex neoplasms. Most gastroenteropancreatic ...

Two for One - HSC Newsbeat

Posted: August 16th, 2018, 11:14am GMT

HSC Newsbeat

Two for One
HSC Newsbeat
Neuroendocrine cancer is rare and hard to diagnose – and it can be difficult to treat and to survive. Its tumors can disrupt the body's hormones and food transit through the bowels, causing an array of nonspecific symptoms that may not be diagnosed ...

and more »

New targeted radiation therapy increases survival for neuroendocrine tumors - DOTmed.com

Posted: August 8th, 2018, 1:09pm GMT

New targeted radiation therapy increases survival for neuroendocrine tumors
DOTmed.com
The University of Kansas Cancer Center is one of the first in the region to offer patients Lutathera®, approved by the FDA earlier this year. Lutathera provides advanced, targeted nuclear medicine radiation therapy to cancer patients with primary ...

CTEP Protocol NCI Trials for August - The Cancer Letter Publications

Posted: August 3rd, 2018, 3:17pm GMT

The Cancer Letter Publications

CTEP Protocol NCI Trials for August
The Cancer Letter Publications
Randomized, Double-Blinded Phase III Study of CABozantinib Versus Placebo IN Patients with Advanced NEuroendocrine Tumors After Progression on Everolimus (CABINET). Alliance for Clinical Trials in Oncology. Chan, Jennifer Ang. (617) 632-6315.

Molecular mechanisms of late cancer relapse - Fred Hutch News Service

Posted: October 15th, 2018, 11:30pm GMT

Fred Hutch News Service

Molecular mechanisms of late cancer relapse
Fred Hutch News Service
Merkel cell carcinoma is an aggressive skin cancer associated with infection by Merkel cell polyomavirus (MCPγV). The two patients were treated with a combination of adoptive T cell therapy and immune checkpoint inhibitor antibodies. In the first ...

A Look Back at FDA News from September 2018 - Targeted Oncology

Posted: October 2nd, 2018, 5:31pm GMT

A Look Back at FDA News from September 2018
Targeted Oncology
On September 4, an sBLA for pembrolizumab was granted a priority review for the treatment of pediatric and adult patients with recurrent locally advanced or metastatic Merkel cell carcinoma. The decision was based on findings from KEYNOTE-017, a phase ...

How to tell the difference between psoriasis and skin cancer - Medical News Today

Posted: October 2nd, 2018, 3:05pm GMT

Medical News Today

How to tell the difference between psoriasis and skin cancer
Medical News Today
People are unlikely to confuse melanoma and Merkel cell carcinoma with psoriasis. A change in a mole can be an early symptom of melanoma. The American Academy of Dermatology encourages people to monitor their moles for any changes, using the ...

and more »

BAVENCIO® (avelumab) Plus INLYTA® (axitinib) Significantly Improved Progression-Free Survival in Previously ... - ACROFAN USA

Posted: September 11th, 2018, 11:49am GMT

BAVENCIO® (avelumab) Plus INLYTA® (axitinib) Significantly Improved Progression-Free Survival in Previously ...
ACROFAN USA
The FDA granted accelerated approval for BAVENCIO for the treatment of (i) adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (mMCC) and (ii) patients with locally advanced or metastatic urothelial carcinoma (mUC ...

and more »

Permalink for 'Checkmate Pharmaceuticals Announces Strategic Collaboration with Merck KGaA, Darmstadt, Germany and Pfizer to ... - Digital Journal'

Checkmate Pharmaceuticals Announces Strategic Collaboration with Merck KGaA, Darmstadt, Germany and Pfizer to ... - Digital Journal

Posted: September 5th, 2018, 9:05am GMT

Checkmate Pharmaceuticals Announces Strategic Collaboration with Merck KGaA, Darmstadt, Germany and Pfizer to ...
Digital Journal
Avelumab has received accelerated approval** by the US Food and Drug Administration (FDA) for the treatment of patients with metastatic Merkel cell carcinoma (MCC) and previously treated patients with locally advanced or metastatic urothelial carcinoma ...

CURE's Top 5 Stories: August 2018 - Curetoday.com

Posted: September 4th, 2018, 12:52pm GMT

CURE's Top 5 Stories: August 2018
Curetoday.com
The Food and Drug Administration (FDA) granted priority review to a new supplemental biologics license application for Keytruda (pembrolizumab) to treat adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma, ...

This RSS feed URL is deprecated

Posted: August 30th, 2018, 5:00am GMT

This RSS feed URL is deprecated, please update. New URLs can be found in the footers at [https:]

Permalink for 'Cytotoxic T Lymphocyte Protein 4 - Pipeline Review, H2 2018 Market Report; Launched via MarketResearchReports.com - Digital Journal'

Cytotoxic T Lymphocyte Protein 4 - Pipeline Review, H2 2018 Market Report; Launched via MarketResearchReports.com - Digital Journal

Posted: August 21st, 2018, 2:22pm GMT

Cytotoxic T Lymphocyte Protein 4 - Pipeline Review, H2 2018 Market Report; Launched via MarketResearchReports.com
Digital Journal
... Endometrial Cancer, Epithelial Ovarian Cancer, Fallopian Tube Cancer, Germ Cell Tumors, Hematological Tumor, Hodgkin Lymphoma (B-Cell Hodgkin Lymphoma), Malignant Pleural Mesothelioma, Merkel Cell Carcinoma, Metastatic Colorectal Cancer, ...

Roger “David” Bond - Gulf Coast News Today

Posted: August 6th, 2018, 1:03pm GMT

Gulf Coast News Today

Roger “David” Bond
Gulf Coast News Today
On Saturday, Aug. 4, 2018, Roger "David" Bond, husband, father, brother and PaPaw, passed away after a long and valiant fight with Merkel cell cancer. David, a resident of Foley, Alabama, formerly of South Carolina, went to be with his Lord and Savior, ...

A Phase 1b/2 Study of AST-008 Combined With Pembrolizumab in Patients With Advanced Solid Tumors

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

Conditions: Advanced or Metastatic Solid Tumors; Advanced or Metastatic Melanoma; Advanced or Metastatic Head and Neck Squamous Cell Carcinoma; Advanced or Metastatic Cutaneous Squamous Cell Carcinoma; Advanced or Metastatic Merkel Cell Carcinoma
Interventions: Drug: AST-008; Biological: Pembrolizumab
Sponsor: Exicure, Inc.
Not yet 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 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 to Evaluate the Safety and Tolerability of Immunotherapy Combinations in Participants With Advanced Malignancies

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

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

A Study of INCMGA00012 in Metastatic Merkel Cell Carcinoma

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

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

A Safety and Tolerability Study of INCAGN02385 in Select Advanced Malignancies

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

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

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

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

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

Permalink for 'Pembrolizumab With or Without Stereotactic Body Radiation Therapy in Treating Patients With Advanced or Metastatic Merkel Cell Cancer'

Pembrolizumab With or Without Stereotactic Body Radiation Therapy in Treating Patients With Advanced or Metastatic Merkel Cell Cancer

Posted: October 9th, 2017, 2:00pm GMT

Conditions: Stage III Merkel Cell Carcinoma AJCC v7; Stage IIIA Merkel Cell Carcinoma AJCC v7; Stage IIIB Merkel Cell Carcinoma AJCC v7; Stage IV Merkel Cell Carcinoma AJCC v7
Interventions: Biological: Pembrolizumab; Radiation: Stereotactic Body Radiation Therapy
Sponsor: National Cancer Institute (NCI)
Recruiting

French National Database of Rare Dermatological Cancers

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

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

Expanded Access to Avelumab for Treatment of Metastatic Merkel Cell Carcinoma (mMCC)

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

Condition: Metastatic Merkel Cell Carcinoma
Intervention: Drug: Avelumab
Sponsors: Merck KGaA; Pfizer
Available

Atezolizumab and Bevacizumab in Rare Solid Tumors

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

Conditions: Malignant Neoplasms of Digestive Organs; Malignant Neoplasms of Lip Oral Cavity and Pharynx; Malignant Neoplasms of Mesothelial and Soft Tissue; Malignant Neoplasms of Respiratory and Intrathoracic Organs
Interventions: Drug: Atezolizumab; Drug: Bevacizumab; Behavioral: Phone Call
Sponsors: M.D. Anderson Cancer Center; Genentech, Inc.
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

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

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

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

$Permalink for 'Talimogene Laherparepvec and Nivolumab in Treating Patients With Refractory Lymphomas or Advanced or Refractory Non-melanoma Skin Cancers'$

Talimogene Laherparepvec and Nivolumab in Treating Patients With Refractory Lymphomas or Advanced or Refractory Non-melanoma Skin Cancers

Posted: December 1st, 2016, 3:00pm GMT

Conditions: Adenoid Cystic Carcinoma; Adnexal Carcinoma; Apocrine Carcinoma; Eccrine Porocarcinoma; Extraocular Cutaneous Sebaceous Carcinoma; Hidradenocarcinoma; Keratoacanthoma; Malignant Sweat Gland Neoplasm; Merkel Cell Carcinoma; Microcystic Adnexal Carcinoma; NK-Cell Lymphoma, Unclassifiable; Non-Melanomatous Lesion; Paget Disease; Papillary Adenocarcinoma; Primary Cutaneous Mucinous Carcinoma; Refractory Anaplastic Large Cell Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Refractory Mycosis Fungoides; Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory T-Cell Non-Hodgkin Lymphoma; Sezary Syndrome; Signet Ring Cell Carcinoma; Skin Basal Cell Carcinoma; Skin Basosquamous Cell Carcinoma; Skin Squamous Cell Carcinoma; Spiradenocarcinoma; Squamous Cell Carcinoma of Unknown Primary Origin; Stage III Skin Cancer; Stage IV Skin Cancer; Sweat Gland Carcinoma; Trichilemmocarcinoma; Vulvar Squamous Cell Carcinoma
Interventions: Other: Laboratory Biomarker Analysis; Biological: Nivolumab; Biological: Talimogene Laherparepvec
Sponsor: National Cancer Institute (NCI)
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
Interventions: Drug: Durvalumab; Drug: Tremelimumab; Drug: Poly ICLC
Sponsors: Ludwig Institute for Cancer Research; MedImmune LLC; Cancer Research Institute, New York City
Recruiting

Studies of Dermatologic Diseases Biospecimen Acquisition Protocol

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

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

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

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

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

Selective Treatment According to Molecular Subtype of Prostate Cancer

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

Conditions: Castration-resistant Prostate Cancer; Prostate Cancer Metastatic
Interventions: Drug: Luminal type-1; Drug: Luminal type-2; Drug: Neuroendocrine type-1; Drug: Neuroendocrine type-2; Drug: Atypical type-1; Drug: Atypical type-2
Sponsor: Tianjin Medical University Second Hospital
Recruiting

A Study of IMMray™ PanCan-d Test for Early Detection of Pancreatic Cancer in High-risk Groups

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

Conditions: Pancreatic Ductal Adenocarcinoma; Familial Pancreatic Cancer; FAMMM - Familial Atypical Mole Malignant Melanoma Syndrome
Intervention:
Sponsor: Immunovia, Inc.
Recruiting

Post-Authorization Long-Term Safety Study of LUTATHERA

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

Condition: Neuroendocrine Tumors
Intervention: Drug: LUTATHERA
Sponsor: Advanced Accelerator Applications
Not yet recruiting

Evaluation of Melatonin Application of Immediate Dental Implant

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

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

Arginase-1 Peptide Vaccine in Patients With Metastatic Solid Tumors

Posted: September 28th, 2018, 2:00pm GMT

Conditions: Non Small Cell Lung Cancer; Urothelial Carcinoma; Malignant Melanoma; Ovarian Cancer; Colorectal Cancer; Breast Cancer; Squamous Cell Carcinoma of the Head and Neck; Metastatic Cancer
Intervention: Biological: ARG1-18,19,20
Sponsor: Inge Marie Svane
Not yet recruiting

A Phase 1b/2 Study of AST-008 Combined With Pembrolizumab in Patients With Advanced Solid Tumors

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

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

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

Conditions: Metastatic Non-small Cell Lung Cancer; Locally Advanced Urothelial Cancer; Metastatic Urothelial Cancer; Unresectable Melanoma; Metastatic Melanoma; Locally Advanced Renal Cell Carcinoma; Metastatic Clear-Cell Renal Cell Carcinoma
Intervention: Drug: INCMGA00012
Sponsor: Incyte Corporation
Not yet recruiting

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

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

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

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

Imaging of Patients With Known or Suspected Somatostatin Receptor Positive Neuroendocrine Tumors Using Cu64-DOTATATE

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

Condition: Neuroendocrine Tumors
Intervention: Drug: 64Cu-DOTATATE
Sponsor: Radiomedix, Inc.
Recruiting

Elderly Cancer PatIents, Safety and qualiTy of Life Under immunOtheraPies

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

Conditions: Advanced or Metastatic Melanoma; Advanced or Metastatic NSCLC
Intervention: Drug: immune-checkpoint inhibitors therapies
Sponsors: Institut Paoli-Calmettes; Société Francophone d'Onco-Gériatrie
Not yet recruiting

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

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

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

Condition: Neuroendocrine Tumors
Intervention: Drug: ABI-009
Sponsors: Robert Ramirez; Aadi, LLC
Not yet recruiting

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

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

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

Vegetative Monitoring During Brainstem-associated Surgery

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

Conditions: Brain Tumor, Recurrent; Vestibular Schwannoma; Brainstem Neoplasm; Brainstem Glioma
Intervention: Procedure: Intraoperative Monitoring during resection of brain tumor
Sponsor: University Hospital Tuebingen
Recruiting

Effects of Epidural Block on the Prognosis in Patients With Pancreatic Cancer Undergoing Distal Pancreatectomy

Posted: September 6th, 2018, 2:00pm GMT

Condition: Cancer of Pancreas
Interventions: Other: GEA; Other: PCEA; Other: GA; Other: PCIA
Sponsors: Fudan University; Washington University School of Medicine
Not yet recruiting

pDNA Intralesional Cancer Vaccine for Cutaneous Melanoma

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

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

High Intensity Interval Training (HIIT) for Patients With Cancer-related Lymphedema in the Lower Limbs

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

Conditions: Lymphedema of Leg; Cancer of Cervix; Cancer, Ovarian; Cancer, Endometrial; Cancer of the Prostate; Malignant Melanoma
Interventions: Other: First exercise session + compression; Other: First exercise session - compression
Sponsors: Herlev and Gentofte Hospital; University of Copenhagen
Recruiting

A Safety and Tolerability Study of INCAGN02390 in Select Advanced Malignancies

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

177Lu-PP-F11N in Combination With Sacubitril for Receptor Targeted Therapy and Imaging of Metastatic Thyroid Cancer

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

Condition: Thyroid Cancer, Medullary
Interventions: Drug: 177Lu-PP-F11N; Drug: Sacuitril
Sponsors: University Hospital, Basel, Switzerland; Krebsforschung Schweiz, Bern, Switzerland; Center for Proton Therapy, Paul Scherrer Institute, Villigen,Switzerland; University Hospital, Zürich; University Hospital Freiburg
Not yet recruiting

[68Ga]DOTATATE-PET/MRI in Hepatocellular Carcinoma

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

Condition: Hepatocellular Carcinoma
Intervention: Diagnostic Test: [68Ga]DOTATATE-PET/MRI
Sponsor: University of Alabama at Birmingham
Not yet recruiting

18F-Fluorocholine PET/CT in Medullary Thyroid Cancer

Posted: August 22nd, 2018, 2:00pm GMT

Condition: Medullary Thyroid Cancer
Intervention: Diagnostic Test: 18F-fluorocholine PET/CT
Sponsors: University Medical Centre Ljubljana; Institute of Oncology Ljubljana
Recruiting

Safety, Tolerability, Immunogenicity, and Antitumor Activity of GEN-009 Adjuvanted Vaccine

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

Conditions: Cutaneous Melanoma; Non-small Cell Lung Cancer; Squamous Cell Carcinoma of the Head and Neck; Urothelial Carcinoma; Renal Cell Carcinoma
Interventions: Biological: GEN-009 Adjuvanted Vaccine; Drug: Nivolumab
Sponsor: Genocea Biosciences, Inc.
Recruiting

Treatment of Neuroendocrine Tumors (NETs) With Combination of Everolimus and Radiolabeled Somatostatin Analogue

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

Condition: Neuroendocrine Tumors
Intervention: Drug: Everolimus
Sponsor: King Faisal Specialist Hospital & Research Center
Recruiting

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

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

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

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

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

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

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

Molecular-Guided Surgery for Pancreatic and GI Neuroendocrine Cancers

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

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

Permalink for 'Clinic, Pathologic and Genetic Characterization of Patients With Familial Carcinoid Tumors (Study From the GTE, Groupe d'étude Des Tumeurs Endocrines)'

Clinic, Pathologic and Genetic Characterization of Patients With Familial Carcinoid Tumors (Study From the GTE, Groupe d'étude Des Tumeurs Endocrines)

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

Condition: Small Intestinal Carcinoid Tumors
Intervention: Genetic: Research of constitutional genetic alterations
Sponsor: CHU de Reims
Recruiting

Denosumab + Pembrolizumab in Patients With Stage IV Melanoma

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

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

CMP-001 in Combo With Nivolumab in Stage IIIB/C/D Melanoma Patients With Clinically Apparent Lymph Node Disease

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

Conditions: Melanoma; Lymph Node Cancer
Interventions: Drug: CMP-001; Biological: Nivolumab
Sponsors: Diwakar Davar; Checkmate Pharmaceuticals
Recruiting

Pancreatic Cancer Dietary Assessment Study

Posted: August 6th, 2018, 2:00pm GMT

Conditions: Pancreatic Neoplasm; Pancreas Adenocarcinoma; Well-Differentiated Neuroendocrine Carcinoma; Malignant Neoplasm of Pancreas
Intervention: Diagnostic Test: Pancreo-KIT breath test
Sponsors: The Christie NHS Foundation Trust; Pancreatic Cancer UK
Recruiting

A Study of APG-115 in Combination With Pembrolizumab in Patients With Metastatic Melanomas or Advanced Solid Tumors

Posted: August 2nd, 2018, 2:00pm GMT

Condition: Unresectable or Metastatic Melanoma or Advanced Solid Tumors
Intervention: Drug: APG-115+Pembrolizumab
Sponsor: Ascentage Pharma Group Inc.
Not yet recruiting

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

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

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

Permalink for 'A Phase 1b Dose Escalation/Expansion Study of Abexinostat in Combination With Pembrolizumab in Patients With Advanced Solid Tumor Malignancies'

A Phase 1b Dose Escalation/Expansion Study of Abexinostat in Combination With Pembrolizumab in Patients With Advanced Solid Tumor Malignancies

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

Conditions: Stage III Cutaneous Melanoma; Stage IV Cutaneous Melanoma; Locally Advanced Melanoma; Locally Advanced Solid Neoplasm; Metastatic Head and Neck Squamous Cell Carcinoma; Metastatic Malignant Solid Neoplasm; Metastatic Melanoma; Metastatic Urothelial Carcinoma; Non-Small Cell Lung Carcinoma; Stage IB Lung Cancer AJCC v7; Stage III Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8; Stage III Lung Cancer AJCC v8; Stage III Ureter Cancer AJCC v8; Stage IIIA Lung Cancer AJCC v8; Stage IIIB Lung Cancer AJCC v8; Stage IIIC Lung Cancer AJCC v8; Stage IV Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8; Stage IV Lung Cancer AJCC v8; Stage IV Ureter Cancer AJCC v8; Stage IVA Lung Cancer AJCC v8; Stage IVB Lung Cancer AJCC v8
Interventions: Drug: Abexinostat; Biological: Pembrolizumab
Sponsors: Rahul Aggarwal; Xynomic Pharmaceuticals, Inc.
Recruiting

Trial of Ixazomib Combined With Gemcitabine and Doxorubicin in Patients With Renal Medullary Carcinoma

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

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

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

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

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

Conditions: Bladder Small Cell Neuroendocrine Carcinoma; Castration-Resistant Prostate Carcinoma; Metastatic Bladder Urothelial Carcinoma; Metastatic Urethral Urothelial Carcinoma; Prostate Carcinoma Metastatic in the Bone; Prostate Neuroendocrine Neoplasm; Prostate Small Cell Carcinoma; Stage III Bladder Cancer AJCC v8; Stage III Prostate Cancer AJCC v8; Stage III Urethral Cancer AJCC v8; Stage IV Bladder Cancer AJCC v8; Stage IV Prostate Cancer AJCC v8; Stage IV Urethral Cancer AJCC v8; Stage IVA Bladder Cancer AJCC v8; Stage IVB Bladder Cancer AJCC v8; Ureter Small Cell Carcinoma; Urothelial Carcinoma
Interventions: Drug: Carboplatin; Drug: Cisplatin; Drug: Docetaxel; Drug: Etoposide; Biological: Pembrolizumab
Sponsors: Jonsson Comprehensive Cancer Center; National Cancer Institute (NCI)
Not yet recruiting

Perception of Information and Quality of Life in Neuroendocrine Tumour on Lanreotide Autogel

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

Condition: Neuroendocrine Tumors
Intervention: Other: Data collection
Sponsor: Ipsen
Recruiting

Adaptive BRAF-MEK Inhibitor Therapy for Advanced BRAF Mutant Melanoma

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

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

A Safety and Tolerability Study of INCAGN02385 in Select Advanced Malignancies

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

Analysis of the Modulation of the Tumor Microenvironment by MK-3475 (Pembrolizumab) Using a Systems Biology Approach (PEMSYS)

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

Condition: Metastatic Melanoma Naive to Immune Therapy in Metastatic Setting
Interventions: Drug: Pembrolizumab; Drug: Pembrolizumab - additional treatment
Sponsor: Centre Hospitalier Universitaire Vaudois
Recruiting

Permalink for 'Methylphenidate and Physical Activity in Reducing Cancer-Related Fatigue in Participants With Metastatic Melanoma Who Receive Anti-PD1 Immunotherapy'

Methylphenidate and Physical Activity in Reducing Cancer-Related Fatigue in Participants With Metastatic Melanoma Who Receive Anti-PD1 Immunotherapy

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

Condition: Metastatic Melanoma
Interventions: Other: Laboratory Biomarker Analysis; Drug: Methylphenidate; Other: Physical Activity; Other: Placebo; Other: Quality-of-Life Assessment; Other: Questionnaire Administration
Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI)
Recruiting

A Study of Anlotinib in Patients With Gastroenteropancreatic Neuroendocrine Tumor G3

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

Condition: Gastroenteropancreatic Neuroendocrine Tumor G3
Intervention: Drug: Anlotinib
Sponsor: Jiangsu Chia-tai Tianqing Pharmaceutical Co.,Ltd
Recruiting

Permalink for 'SARC031: MEK Inhibitor Selumetinib (AZD6244) in Combination With the mTOR Inhibitor Sirolimus for Patients With Malignant Peripheral Nerve Sheath Tumors'

SARC031: MEK Inhibitor Selumetinib (AZD6244) in Combination With the mTOR Inhibitor Sirolimus for Patients With Malignant Peripheral Nerve Sheath Tumors

Posted: February 14th, 2018, 3:00pm GMT

Conditions: Malignant Peripheral Nerve Sheath Tumors; Neurofibromatosis 1
Interventions: Drug: Selumetinib; Drug: Sirolimus
Sponsors: Sarcoma Alliance for Research through Collaboration; United States Department of Defense; AstraZeneca
Not yet recruiting

Treating Patients With Melanoma and ALK Alterations With Ensartinib

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

Condition: Melanoma
Interventions: Drug: Ensartinib; Diagnostic Test: ALKATI by Customized Nanostring Assay
Sponsors: Memorial Sloan Kettering Cancer Center; Xcovery Holding Company, LLC
Recruiting

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

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

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

Permalink for 'Cabozantinib S-malate in Treating Patients With Neuroendocrine Tumors Previously Treated With Everolimus That Are Locally Advanced, Metastatic, or Cannot Be Removed by Surgery'

Cabozantinib S-malate in Treating Patients With Neuroendocrine Tumors Previously Treated With Everolimus That Are Locally Advanced, Metastatic, or Cannot Be Removed by Surgery

Posted: December 18th, 2017, 3:00pm GMT

Conditions: Atypical Carcinoid Tumor; Carcinoid Tumor; Digestive System Neuroendocrine Neoplasm; Enterochromaffin Cell Serotonin-Producing Pancreatic Neuroendocrine Tumor; Functional Pancreatic Neuroendocrine Tumor; Intermediate Grade Lung Neuroendocrine Neoplasm; Low Grade Lung Neuroendocrine Neoplasm; Lung Atypical Carcinoid Tumor; Lung Carcinoid Tumor; Metastatic Digestive System Neuroendocrine Tumor G1; Neuroendocrine Neoplasm; Nonfunctional Pancreatic Neuroendocrine Tumor; Pancreatic Neuroendocrine Tumor; Stage IIIA Digestive System Neuroendocrine Tumor AJCC v7; Stage IIIB Digestive System Neuroendocrine Tumor AJCC v7; Stage IV Digestive System Neuroendocrine Tumor AJCC v7
Interventions: Drug: Cabozantinib S-malate; Other: Laboratory Biomarker Analysis; Other: Placebo; Other: Quality-of-Life Assessment
Sponsor: National Cancer Institute (NCI)
Recruiting

Pembrolizumab With or Without Stereotactic Body Radiation Therapy in Treating Patients With Advanced or Metastatic Merkel Cell Cancer

Posted: October 9th, 2017, 2:00pm GMT

Permalink for 'Ability of a Dendritic Cell Vaccine to Immunize Melanoma or Epithelial Cancer Patients Against Defined Mutated Neoantigens Expressed by the Autologous Cancer'

Ability of a Dendritic Cell Vaccine to Immunize Melanoma or Epithelial Cancer Patients Against Defined Mutated Neoantigens Expressed by the Autologous Cancer

Posted: October 4th, 2017, 2:00pm GMT

Conditions: Melanoma; Gastrointestinal Cancer; Breast Cancer; Ovarian Cancer; Pancreatic Cancer
Intervention: Biological: Peptide loaded dendritic cell vaccine
Sponsor: National Cancer Institute (NCI)
Recruiting

A Study of PLX2853 in Advanced Malignancies.

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

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

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

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

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

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

Pembrolizumab in Advanced Poorly Differentiated and/or High Grade Neuroendocrine Tumors/Carcinomas

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

Conditions: Neuroendocrine Tumors; Neuroendocrine Carcinoma; Neuroendocrine Cancer
Intervention: Drug: Pembrolizumab
Sponsors: H. Lee Moffitt Cancer Center and Research Institute; Merck Sharp & Dohme Corp.
Recruiting

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

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

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

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

Avelumab in G2-3 NET

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

Condition: Neuroendocrine Tumors
Intervention: Drug: Avelumab
Sponsors: Sunnybrook Health Sciences Centre; Merck KGaA
Recruiting

Nivolumab Plus Ipilimumab in Patients With Renal Medullary Carcinoma

Posted: September 6th, 2017, 2:00pm GMT

Conditions: Renal Medullary Carcinoma; Other Disorders of Kidney and Ureter
Interventions: Drug: Nivolumab; Drug: Ipilimumab
Sponsors: M.D. Anderson Cancer Center; Bristol-Myers Squibb
Recruiting

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

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

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

Condition: Gastro-Enteropancreatic Neuroendocrine Tumor
Intervention: Drug: 68Ga-OPS202
Sponsor: Ipsen
Recruiting

French National Database of Rare Dermatological Cancers

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

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

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

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

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

A Trial of Niraparib in BAP1 and Other DNA Damage Response (DDR) Deficient Neoplasms (UF-STO-ETI-001)

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

Conditions: Mesothelioma; Uveal Melanoma; Renal Cell Carcinoma; Cholangiocarcinoma
Intervention: Drug: Niraparib
Sponsors: University of Florida; Tesaro, Inc.
Recruiting

Tissue Predictors of Abiraterone Benefit

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

Condition: Metastatic Castration-resistant Prostate Cancer
Intervention:
Sponsors: Tianjin Medical University Second Hospital; Tianjin Medical University General Hospital; Tianjin Medical University Cancer Institute and Hospital; Beijing Chao Yang Hospital; The Second Hospital of Hebei Medical University; Affiliated Hospital of Hebei University
Recruiting

Study of Cabozantinib in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors

Posted: May 31st, 2017, 2:00pm GMT

Conditions: Urothelial Carcinoma; Renal Cell Carcinoma; Non-Small Cell Lung Cancer; Castration-resistant Prostate Cancer
Interventions: Drug: cabozantinib; Drug: atezolizumab
Sponsor: Exelixis
Recruiting

Permalink for 'Study to Compare Irinotecan Combined With Cisplatin (IP) Versus Etoposide Combined With Cisplatin (EP) in Advanced and Metastatic Gastrointestinal Pancreatic and Esophageal Neuroendocrine Carcinoma'

Study to Compare Irinotecan Combined With Cisplatin (IP) Versus Etoposide Combined With Cisplatin (EP) in Advanced and Metastatic Gastrointestinal Pancreatic and Esophageal Neuroendocrine Carcinoma

Posted: May 30th, 2017, 2:00pm GMT

Condition: Neuroendocrine Carcinoma
Interventions: Drug: irinotecan cisplatin; Drug: Etoposide cisplatin
Sponsor: Peking University
Recruiting

Study of JS001 in Patients With Advanced Neuroendocrine Tumors

Posted: May 30th, 2017, 2:00pm GMT

Condition: Neuroendocrine Tumors
Intervention: Biological: humanized anti-PD-1 monoclonal antibody
Sponsors: Peking University; Shanghai Junshi Biosciencee Co.,Ltd
Recruiting

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

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

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

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

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

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

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

Phase 1/2 Study of LOXO-292 in Patients With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer

Posted: May 17th, 2017, 2:00pm GMT

Conditions: Non-Small Cell Lung Cancer; Medullary Thyroid Cancer; Colon Cancer; Solid Tumor
Intervention: Drug: LOXO-292
Sponsor: Loxo Oncology, Inc.
Recruiting

Health Care Coach Support in Reducing Acute Care Use and Cost in Patients With Cancer

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

Conditions: Acute Myeloid Leukemia; Brain Glioblastoma; Estrogen Receptor Negative; Extensive Stage Small Cell Lung Carcinoma; Head and Neck Carcinoma; HER2/Neu Negative; Hormone-Resistant Prostate Cancer; Limited Stage Small Cell Lung Carcinoma; Myelodysplastic Syndrome; Progesterone Receptor Negative; Progressive Disease; Recurrent Carcinoma; Stage II Pancreatic Cancer; Stage II Rectal Cancer; Stage IIA Pancreatic Cancer; Stage IIA Rectal Cancer; Stage IIB Pancreatic Cancer; Stage IIB Rectal Cancer; Stage IIC Rectal Cancer; Stage III Colon Cancer; Stage III Esophageal Cancer; Stage III Gastric Cancer; Stage III Non-Small Cell Lung Cancer; Stage III Ovarian Cancer; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Skin Melanoma; Stage IIIA Colon Cancer; Stage IIIA Esophageal Cancer; Stage IIIA Gastric Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Rectal Cancer; Stage IIIA Skin Melanoma; Stage IIIB Colon Cancer; Stage IIIB Esophageal Cancer; Stage IIIB Gastric Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Rectal Cancer; Stage IIIB Skin Melanoma; Stage IIIC Colon Cancer; Stage IIIC Esophageal Cancer; Stage IIIC Gastric Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Rectal Cancer; Stage IIIC Skin Melanoma; Stage IV Bladder Cancer; Stage IV Bone Sarcoma; Stage IV Breast Cancer; Stage IV Colon Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Ovarian Cancer; Stage IV Pancreatic Cancer; Stage IV Rectal Cancer; Stage IV Renal Cell Cancer; Stage IV Skin Melanoma; Stage IV Soft Tissue Sarcoma; Stage IVA Bone Sarcoma; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Bone Sarcoma; Stage IVB Colon Cancer; Stage IVB Rectal Cancer; Triple-Negative Breast Carcinoma
Interventions: Other: Best Practice; Other: Laboratory Biomarker Analysis; Procedure: Supportive Care; Other: Survey Administration
Sponsor: Stanford University
Recruiting

Permalink for 'A Study to Evaluate a New Way to Identify/Diagnose Tumours With Somatostatin Receptors Using [68]Ga-HA-DOTATATE and to Ensure it is Safe to Use'

A Study to Evaluate a New Way to Identify/Diagnose Tumours With Somatostatin Receptors Using [68]Ga-HA-DOTATATE and to Ensure it is Safe to Use

Posted: May 9th, 2017, 2:00pm GMT

Condition: Neuroendocrine Tumors
Intervention: Drug: [68]Ga-HA-DOTATATE
Sponsor: Alexander McEwan
Not yet recruiting

DIVIT Study Diet and Vitamin Supplementation in Patients With a Neuroendocrine Tumor

Posted: May 8th, 2017, 2:00pm GMT

Condition: Neuroendocrine Tumor
Interventions: Dietary Supplement: Vitamin supplement;; Other: Diet advice
Sponsor: University Medical Center Groningen
Recruiting

Multi-Institutional Registry for Malignant Peripheral Nerve Sheath Tumors

Posted: May 4th, 2017, 2:00pm GMT

Condition: Malignant Peripheral Nerve Sheath Tumors
Intervention:
Sponsor: Washington University School of Medicine
Recruiting

Permalink for 'A Study of a CD122-Biased Cytokine (NKTR-214) in Combination With Anti-PD-1 (Pembrolizumab) and of NKTR-214 in Combination With Anti-PD-L1 (Atezolizumab) in Patients With Select Advanced or Metastatic Solid Tumors'

A Study of a CD122-Biased Cytokine (NKTR-214) in Combination With Anti-PD-1 (Pembrolizumab) and of NKTR-214 in Combination With Anti-PD-L1 (Atezolizumab) in Patients With Select Advanced or Metastatic Solid Tumors

Posted: May 3rd, 2017, 2:00pm GMT

Conditions: Non-Small Cell Lung Cancer; Urinary Bladder Neoplasms; Neoplasm Metastasis; Melanoma
Interventions: Drug: NKTR-214; Drug: Pembrolizumab; Drug: Atezolizumab
Sponsor: Nektar Therapeutics
Recruiting

Atezolizumab and Bevacizumab in Rare Solid Tumors

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

A Study of LEE011 With Everolimus in Patients With Advanced Neuroendocrine Tumors

Posted: March 3rd, 2017, 3:00pm GMT

Condition: Neuroendocrine Tumors
Interventions: Drug: LEE011; Drug: everolimus
Sponsors: Memorial Sloan Kettering Cancer Center; Novartis; Dana-Farber Cancer Institute; M.D. Anderson Cancer Center
Recruiting

A Pilot Study Of Ga-68-DOTA-TOC Imaging In Participants With Small Bowel Carcinoid Tumors

Posted: February 20th, 2017, 3:00pm GMT

Condition: Small Bowel Carcinoid Tumor
Interventions: Drug: Ga-68-DOTA-TOC; Device: Siemens PET/MR scanner; Other: Standard Siemens Software; Drug: LAR Octreotide
Sponsor: Massachusetts General Hospital
Recruiting

Permalink for 'Efficacy and Safety of Treatment With Alpelisib Plus Endocrine Therapy in Patients With HR+, HER2-negative aBC, With PIK3CA Mutations, Whose Disease Has Progressed on or After CDK 4/6 Treatment With an Aromatase Inhibitor (AI) or Fulvestrant'

Efficacy and Safety of Treatment With Alpelisib Plus Endocrine Therapy in Patients With HR+, HER2-negative aBC, With PIK3CA Mutations, Whose Disease Has Progressed on or After CDK 4/6 Treatment With an Aromatase Inhibitor (AI) or Fulvestrant

Posted: February 17th, 2017, 3:00pm GMT

Condition: Breast Cancer
Interventions: Drug: alpelisib; Drug: fulvestrant; Drug: letrozole
Sponsor: Novartis Pharmaceuticals
Recruiting

Efficacy and Safety of 177Lu-edotreotide PRRT in GEP-NET Patients

Posted: February 9th, 2017, 3:00pm GMT

Condition: Neuroendocrine Tumors
Interventions: Drug: 177Lu-edotreotide PRRT; Drug: Everolimus; Other: Amino-Acid Solution
Sponsors: ITM Solucin GmbH; ABX CRO
Recruiting

Permalink for 'Phase 1 Study of the Highly-selective RET Inhibitor BLU-667 in Patients With Thyroid Cancer, Non-Small Cell Lung Cancer, and Other Advanced Solid Tumors'

Phase 1 Study of the Highly-selective RET Inhibitor BLU-667 in Patients With Thyroid Cancer, Non-Small Cell Lung Cancer, and Other Advanced Solid Tumors

Posted: January 31st, 2017, 3:00pm GMT

Conditions: RET-altered Non Small Cell Lung Cancer; Medullary Thyroid Cancer; RET-altered Papillary Thyroid Cancer; RET-altered Colon Cancer; RET-altered Solid Tumors
Intervention: Drug: BLU-667
Sponsor: Blueprint Medicines Corporation
Recruiting

Intravenous and Intrathecal Nivolumab in Treating Participants With Leptomeningeal Disease

Posted: January 19th, 2017, 3:00pm GMT

Conditions: Acral Lentiginous Melanoma; Clinical Stage IV Cutaneous Melanoma AJCC v8; Leptomeningeal Neoplasm; Metastatic Melanoma; Metastatic Uveal Melanoma; Mucosal Melanoma; Pathologic Stage IV Cutaneous Melanoma AJCC v8
Intervention: Biological: Nivolumab
Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI)
Recruiting

Permalink for 'An Exploratory Tumor Biopsy-driven Study to Understand the Relationship Between Biomarkers and Clinical Response in Melanoma Patients Receiving REGN2810 (Anti-PD-1)'

An Exploratory Tumor Biopsy-driven Study to Understand the Relationship Between Biomarkers and Clinical Response in Melanoma Patients Receiving REGN2810 (Anti-PD-1)

Posted: December 23rd, 2016, 3:00pm GMT

Condition: Melanoma
Intervention: Drug: REGN2810
Sponsors: Regeneron Pharmaceuticals; Sanofi
Recruiting

MAGE-A10ᶜ⁷⁹⁶T for Urothelial Cancer, Melanoma or Head and Neck Cancers

Posted: December 12th, 2016, 3:00pm GMT

Conditions: Urinary Bladder Cancer; Head and Neck Cancer; Melanoma
Intervention: Genetic: Autologous genetically modified MAGE A10ᶜ⁷⁹⁶T cells
Sponsor: Adaptimmune
Recruiting

$Permalink for 'Talimogene Laherparepvec and Nivolumab in Treating Patients With Refractory Lymphomas or Advanced or Refractory Non-melanoma Skin Cancers'$

Talimogene Laherparepvec and Nivolumab in Treating Patients With Refractory Lymphomas or Advanced or Refractory Non-melanoma Skin Cancers

Posted: December 1st, 2016, 3:00pm GMT

Circulating Tumor Cells and Tumor DNA in HCC and NET

Posted: November 25th, 2016, 3:00pm GMT

Conditions: Carcinoma, Hepatocellular; Neuroendocrine Tumors
Interventions: Drug: Sorafenib; Procedure: Radiofrequency ablation (RFA) or surgery; Drug: Everolimus; Drug: Lanreotide
Sponsors: University of Aarhus; Aarhus University Hospital
Recruiting

Talimogene Laherparepvec and Pembrolizumab in Treating Patients With Stage III-IV Melanoma

Posted: November 17th, 2016, 3:00pm GMT

Conditions: Recurrent Melanoma; Stage III Cutaneous Melanoma AJCC v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7
Interventions: Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Biological: Talimogene Laherparepvec
Sponsor: National Cancer Institute (NCI)
Recruiting

Permalink for 'Study of Efficacy and Safety of PDR001 in Patients With Advanced or Metastatic, Well-differentiated, Non-functional Neuroendocrine Tumors of Pancreatic, Gastrointestinal (GI), or Thoracic Origin or Poorly-differentiated Gastroenteropancreatic Neuroendocr'

Study of Efficacy and Safety of PDR001 in Patients With Advanced or Metastatic, Well-differentiated, Non-functional Neuroendocrine Tumors of Pancreatic, Gastrointestinal (GI), or Thoracic Origin or Poorly-differentiated Gastroenteropancreatic Neuroendocr

Posted: November 4th, 2016, 2:00pm GMT

Conditions: Well-differentiated Non-functional NET of Thoracic Origin; Well-differentiated Non-functional NET of Gastrointestinal Origin; Well-differentiated Non-functional NET of Pancreatic Origin; Poorly-differentiated Gastroenteropancreatic Neuroendocrine Carcinoma
Intervention: Drug: PDR001
Sponsor: Novartis Pharmaceuticals
Recruiting

Clinical Utility Assay as a Biomarker for Gastroenteropancreatic and Lung Neuroendocrine Tumors

Posted: October 31st, 2016, 2:00pm GMT

Conditions: Gastroenteropancreatic Neuroendocrine Tumor; Lung Neuroendocrine Neoplasm
Intervention: Procedure: NETest
Sponsor: H. Lee Moffitt Cancer Center and Research Institute
Recruiting

A Study of Pembrolizumab in Patients With Neuroendocrine Tumors

Posted: October 20th, 2016, 2:00pm GMT

Condition: Neuroendocrine Tumors
Intervention: Drug: Pembrolizumab
Sponsors: Fox Chase Cancer Center; Merck Sharp & Dohme Corp.
Recruiting

Circulating Tumor Material in Colorectal Cancer and Melanoma

Posted: September 20th, 2016, 2:00pm GMT

Condition: Colorectal Cancer and Melanoma
Intervention: Other: blood collection
Sponsor: Abramson Cancer Center of the University of Pennsylvania
Recruiting

$Permalink for 'Sapanisertib in Treating Patients With Metastatic or Refractory Pancreatic Neuroendocrine Tumor That Cannot Be Removed by Surgery'$

Sapanisertib in Treating Patients With Metastatic or Refractory Pancreatic Neuroendocrine Tumor That Cannot Be Removed by Surgery

Posted: September 9th, 2016, 2:00pm GMT

Conditions: Pancreatic Neuroendocrine Tumor G1; Pancreatic Neuroendocrine Tumor G2; Refractory Pancreatic Neuroendocrine Carcinoma
Intervention: Drug: Sapanisertib
Sponsor: National Cancer Institute (NCI)
Recruiting

Olaparib With or Without Cediranib in Treating Patients With Metastatic Castration-Resistant Prostate Cancer

Posted: September 9th, 2016, 2:00pm GMT

Conditions: Castration Levels of Testosterone; Castration-Resistant Prostate Carcinoma; Metastatic Prostate Carcinoma; Prostate Adenocarcinoma With Focal Neuroendocrine Differentiation; Prostate Carcinoma Metastatic in the Bone; Prostate Small Cell Carcinoma; PSA Progression; Stage IV Prostate Adenocarcinoma AJCC v7
Interventions: Drug: Cediranib; Other: Laboratory Biomarker Analysis; Drug: Olaparib
Sponsor: National Cancer Institute (NCI)
Recruiting

$Permalink for 'A Safety and Efficacy Study of CC-90011 in Subjects With Relapsed and/or Refractory Solid Tumors and Non-Hodgkin's Lymphomas'$

A Safety and Efficacy Study of CC-90011 in Subjects With Relapsed and/or Refractory Solid Tumors and Non-Hodgkin's Lymphomas

Posted: August 23rd, 2016, 2:00pm GMT

Conditions: Lymphoma, Non-Hodgkin; Neoplasms
Intervention: Drug: CC-90011
Sponsor: Celgene
Recruiting

$Permalink for 'Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors'$

Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors

Posted: August 16th, 2016, 2:00pm GMT

Conditions: Adrenal Cortex Carcinoma; Alveolar Soft Part Sarcoma; Central Nervous System Neoplasm; Childhood Clear Cell Sarcoma of Soft Parts; Clear Cell Sarcoma of Soft Tissue; Ewing Sarcoma; Hepatoblastoma; Hepatocellular Carcinoma; MITF Positive; Osteosarcoma; Recurrent Adrenal Cortex Carcinoma; Recurrent Alveolar Soft Part Sarcoma; Recurrent Ewing Sarcoma; Recurrent Hepatoblastoma; Recurrent Hepatocellular Carcinoma; Recurrent Malignant Central Nervous System Neoplasm; Recurrent Malignant Solid Neoplasm; Recurrent Osteosarcoma; Recurrent Renal Cell Carcinoma; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Recurrent Soft Tissue Sarcoma, Excluding Rhabdomyosarcoma; Recurrent Thyroid Gland Medullary Carcinoma; Refractory Ewing Sarcoma; Refractory Malignant Central Nervous System Neoplasm; Refractory Malignant Solid Neoplasm; Refractory Osteosarcoma; Refractory Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma; Refractory Soft Tissue Sarcoma, Excluding Rhabdomyosarcoma; Renal Cell Carcinoma; Rhabdomyosarcoma; Soft Tissue Sarcoma, Excluding Rhabdomyosarcoma; Solid Neoplasm; Thyroid Gland Medullary Carcinoma; Wilms Tumor
Interventions: Drug: Cabozantinib S-malate; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study
Sponsor: National Cancer Institute (NCI)
Recruiting

Pembrolizumab and Stereotactic Radiosurgery for Melanoma or Non-Small Cell Lung Cancer Brain Metastases

Posted: August 8th, 2016, 2:00pm GMT

Conditions: Metastatic Malignant Neoplasm in the Brain; Metastatic Melanoma; Mucosal Melanoma; Ocular Melanoma; Stage IV Non-Small Cell Lung Cancer; Stage IV Skin Melanoma
Interventions: Biological: Pembrolizumab; Radiation: Stereotactic Radiosurgery
Sponsors: Emory University; Merck Sharp & Dohme Corp.
Recruiting

Nivolumab and Ipilimumab in Treating Patients With Rare Tumors

Posted: July 15th, 2016, 2:00pm GMT

Conditions: Acinar Cell Carcinoma; Adenoid Cystic Carcinoma; Adrenal Cortex Carcinoma; Adrenal Gland Pheochromocytoma; Anal Canal Neuroendocrine Carcinoma; Anal Canal Undifferentiated Carcinoma; Appendix Mucinous Adenocarcinoma; Bartholin Gland Transitional Cell Carcinoma; Bladder Adenocarcinoma; Cervical Adenocarcinoma; Cholangiocarcinoma; Chordoma; Colorectal Squamous Cell Carcinoma; Desmoid-Type Fibromatosis; Endometrial Transitional Cell Carcinoma; Endometrioid Adenocarcinoma; Esophageal Neuroendocrine Carcinoma; Esophageal Undifferentiated Carcinoma; Extrahepatic Bile Duct Carcinoma; Fallopian Tube Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Fibromyxoid Tumor; Gastric Neuroendocrine Carcinoma; Gastric Squamous Cell Carcinoma; Gastric Undifferentiated Carcinoma; Gastrointestinal Stromal Tumor; Giant Cell Carcinoma; Intestinal Neuroendocrine Carcinoma; Intrahepatic Cholangiocarcinoma; Lung Carcinoid Tumor; Lung Sarcomatoid Carcinoma; Major Salivary Gland Carcinoma; Malignant Odontogenic Neoplasm; Malignant Peripheral Nerve Sheath Tumor; Malignant Testicular Sex Cord-Stromal Tumor; Metaplastic Breast Carcinoma; Metastatic Malignant Neoplasm of Unknown Primary Origin; Minimally Invasive Lung Adenocarcinoma; Mixed Mesodermal (Mullerian) Tumor; Mucinous Adenocarcinoma; Mucinous Cystadenocarcinoma; Nasal Cavity Adenocarcinoma; Nasal Cavity Carcinoma; Nasopharyngeal Carcinoma; Nasopharyngeal Papillary Adenocarcinoma; Nasopharyngeal Undifferentiated Carcinoma; Oral Cavity Carcinoma; Oropharyngeal Undifferentiated Carcinoma; Ovarian Adenocarcinoma; Ovarian Germ Cell Tumor; Ovarian Mucinous Adenocarcinoma; Ovarian Squamous Cell Carcinoma; Ovarian Transitional Cell Carcinoma; Pancreatic Acinar Cell Carcinoma; Pancreatic Neuroendocrine Carcinoma; Paraganglioma; Paranasal Sinus Adenocarcinoma; Paranasal Sinus Carcinoma; Parathyroid Gland Carcinoma; Pituitary Gland Carcinoma; Placental Choriocarcinoma; Placental-Site Gestational Trophoblastic Tumor; Primary Peritoneal High Grade Serous Adenocarcinoma; Pseudomyxoma Peritonei; Rare Disorder; Scrotal Squamous Cell Carcinoma; Seminal Vesicle Adenocarcinoma; Seminoma; Serous Cystadenocarcinoma; Small Intestinal Adenocarcinoma; Small Intestinal Squamous Cell Carcinoma; Spindle Cell Neoplasm; Squamous Cell Carcinoma of the Penis; Teratoma With Malignant Transformation; Testicular Non-Seminomatous Germ Cell Tumor; Thyroid Gland Carcinoma; Tracheal Carcinoma; Transitional Cell Carcinoma; Ureter Adenocarcinoma; Ureter Squamous Cell Carcinoma; Urethral Adenocarcinoma; Urethral Squamous Cell Carcinoma; Vaginal Adenocarcinoma; Vaginal Squamous Cell Carcinoma, Not Otherwise Specified; Vulvar Carcinoma
Interventions: Procedure: Biospecimen Collection; Biological: Ipilimumab; Biological: Nivolumab
Sponsor: National Cancer Institute (NCI)
Recruiting

Bio-marker Analysis Using Circulating Tumor Cells in Patients With Melanoma

Posted: July 11th, 2016, 2:00pm GMT

Condition: Melanoma
Intervention: Other: Specimen Collection
Sponsor: Abramson Cancer Center of the University of Pennsylvania
Recruiting

Phase Ib/II Study of MCS110 in Combination With PDR001 in Patients With Advanced Malignancies

Posted: June 21st, 2016, 2:00pm GMT

Conditions: Triple Negative Breast Cancer; Pancreatic Carcinoma; Melanoma; Endometrial Carcinoma
Interventions: Drug: MCS110; Drug: PDR001
Sponsor: Novartis Pharmaceuticals
Recruiting

Pembrolizumab in Treating Patients With Desmoplastic Melanoma That Can or Cannot Be Removed by Surgery

Posted: May 18th, 2016, 2:00pm GMT

Condition: Desmoplastic Melanoma
Interventions: Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Procedure: Therapeutic Conventional Surgery
Sponsor: National Cancer Institute (NCI)
Recruiting

Pembrolizumab-PET Imaging

Posted: May 3rd, 2016, 2:00pm GMT

Conditions: Melanoma; Non-small Cell Lung Cancer
Interventions: Drug: 89Zr-Pembrolizumab; Device: 89Zr-Pembrolizumab PET
Sponsor: University Medical Center Groningen
Recruiting

Aldesleukin and Pembrolizumab in Treating Patients With Stage III-IV Melanoma

Posted: April 22nd, 2016, 2:00pm GMT

Conditions: Metastatic Melanoma; Stage III Mucosal Melanoma of the Head and Neck; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma; Stage IVA Mucosal Melanoma of the Head and Neck; Stage IVB Mucosal Melanoma of the Head and Neck; Stage IVC Mucosal Melanoma of the Head and Neck
Interventions: Biological: Aldesleukin; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab
Sponsors: Rutgers, The State University of New Jersey; National Cancer Institute (NCI)
Recruiting

Study of Recombinant Adenovirus AdVince in Patients With Neuroendocrine Tumors; Safety and Efficacy

Posted: April 22nd, 2016, 2:00pm GMT

Condition: Neuroendocrine Tumors
Intervention: Drug: AdVince
Sponsor: Uppsala University
Recruiting

Lu-DOTATATE Treatment in Patients With 68Ga-DOTATATE Somatostatin Receptor Positive Neuroendocrine Tumors

Posted: April 19th, 2016, 2:00pm GMT

Condition: Neuroendocrine Tumors
Intervention: Drug: Lutetium-177 Octreotate
Sponsors: University Health Network, Toronto; Ozmosis Research Inc.; Cancer Care Ontario; Canadian Molecular Imaging Probe Consortium
Recruiting

Permalink for 'Assessment of Response to Pembrolizumab in Metastatic Melanoma: Computed Tomography (CT) Texture Analysis as a Predictive Biomarker'

Assessment of Response to Pembrolizumab in Metastatic Melanoma: Computed Tomography (CT) Texture Analysis as a Predictive Biomarker

Posted: April 15th, 2016, 2:00pm GMT

Condition: Metastatic Melanoma
Interventions: Drug: Pembrolizumab; Procedure: CT Scan
Sponsors: Canadian Cancer Trials Group; Merck Sharp & Dohme Corp.
Recruiting

Cross-Sectional Imaging and Thoracoscopic Resection of Functional Intrathoracic Paraganglioma of the Aortic Body.

Fetched: October 16th, 2018, 5:00am GMT

Cross-Sectional Imaging and Thoracoscopic Resection of Functional Intrathoracic Paraganglioma of the Aortic Body.

Curr Probl Diagn Radiol. 2018 Sep 11;:

Authors: Cleveland NC, Nguyen DN, Goel K, Tran CD, Mueller JS

Abstract
Paragangliomas are extra-adrenal tumors that are derived from neuroendocrine chromaffin cells. The rare disease has a variable presentation depending upon its anatomic location and functionality. We describe the case of a 56-year-old female patient who had an incidental mass found on imaging. The patient underwent biochemical testing and a mediastinal biopsy due to the nonspecific imaging findings. The mediastinal mass was resected through hemisternotomy and found to be a functional paraganglioma. This case highlights the importance of radiologists to consider the prospect of paragangliomas in the differential diagnosis of an intra-thoracic mass.

PMID: 30316617 [PubMed - as supplied by publisher]

Permalink for 'Clinical characteristics and surgical outcome in USP8-mutated human adrenocorticotropic hormone-secreting pituitary adenomas.'

Clinical characteristics and surgical outcome in USP8-mutated human adrenocorticotropic hormone-secreting pituitary adenomas.

Fetched: October 15th, 2018, 5:00am GMT

Clinical characteristics and surgical outcome in USP8-mutated human adrenocorticotropic hormone-secreting pituitary adenomas.

Endocrine. 2018 Oct 12;:

Authors: Losa M, Mortini P, Pagnano A, Detomas M, Cassarino MF, Pecori Giraldi F

Abstract
PURPOSE: somatic mutations in the ubiquitin-specific protease 8 (USP8) gene have recently been described in patients with Cushing's disease (CD). The aim of the study is to verify whether USP8 mutation may predict early and late outcome of pituitary surgery in patients with CD operated at a single institution.
METHODS: We performed a retrospective genetic analysis of 92 adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas. Specimens were screened for USP8 hotspot mutations in the exon 14 with Sanger sequencing. Hormonal and surgical data were compared between USP8 variant carriers and wild-type tumors.
RESULTS: USP8 variants were detected in 22 adenomas (23.9%) with higher prevalence in women (28.9% vs. 5.3% in men; p < 0.05). No significant difference in hormonal levels and tumoral features in relation to USP8 status was observed. Interestingly, USP8-variant carriers were more likely to achieve surgical remission than wild-type adenomas (100% vs. 75.7%; p = 0.01). Conversely, recurrence of CD occurred in 23% of USP8-mutated patients and in 13% of patients with wild-type adenoma. The recurrence-free survival did not differ significantly between the two groups (p = 0.42).
CONCLUSIONS: ACTH-secreting pituitary adenomas carrying somatic USP8 mutations are associated with a greater likelihood of surgical remission in patients operated by a single neurosurgeon. Recurrence rates are not related with USP8-variant status.

PMID: 30315484 [PubMed - as supplied by publisher]

ATRX, DAXX or MEN1 mutant pancreatic neuroendocrine tumors are a distinct alpha-cell signature subgroup.

Fetched: October 15th, 2018, 5:00am GMT

ATRX, DAXX or MEN1 mutant pancreatic neuroendocrine tumors are a distinct alpha-cell signature subgroup.

Nat Commun. 2018 Oct 12;9(1):4158

Authors: Chan CS, Laddha SV, Lewis PW, Koletsky MS, Robzyk K, Da Silva E, Torres PJ, Untch BR, Li J, Bose P, Chan TA, Klimstra DS, Allis CD, Tang LH

Abstract
The commonly mutated genes in pancreatic neuroendocrine tumors (PanNETs) are ATRX, DAXX, and MEN1. We genotyped 64 PanNETs and found 58% carry ATRX, DAXX, and MEN1 mutations (A-D-M mutant PanNETs) and this correlates with a worse clinical outcome than tumors carrying the wild-type alleles of all three genes (A-D-M WT PanNETs). We performed RNA sequencing and DNA-methylation analysis to reveal two distinct subgroups with one consisting entirely of A-D-M mutant PanNETs. Two genes differentiating A-D-M mutant from A-D-M WT PanNETs were high ARX and low PDX1 gene expression with PDX1 promoter hyper-methylation in the A-D-M mutant PanNETs. Moreover, A-D-M mutant PanNETs had a gene expression signature related to that of alpha-cells (FDR q-value < 0.009) of pancreatic islets including increased expression of HNF1A and its transcriptional target genes. This gene expression profile suggests that A-D-M mutant PanNETs originate from or transdifferentiate into a distinct cell type similar to alpha cells.

PMID: 30315258 [PubMed - in process]

Permalink for 'Biliary stone disease in patients receiving somatostatin analogs for neuroendocrine neoplasms. A retrospective observational study.'

Biliary stone disease in patients receiving somatostatin analogs for neuroendocrine neoplasms. A retrospective observational study.

Fetched: October 15th, 2018, 5:00am GMT

Biliary stone disease in patients receiving somatostatin analogs for neuroendocrine neoplasms. A retrospective observational study.

Dig Liver Dis. 2018 Sep 24;:

Authors: Brighi N, Lamberti G, Maggio I, Manuzzi L, Ricci C, Casadei R, Santini D, Mosconi C, Lisotti A, Ambrosini V, Pantaleo MA, Campana D

Abstract
BACKGROUND: Somatostatin analogs are the backbone of neuroendocrine neoplasms treatment. Biliary stone disease is a potentially severe adverse event of somatostatin analogs: an increased incidence has been reported in somatostatin analogs-treated acromegalic patients, but studies on patients with neuroendocrine neoplasms are lacking.
AIMS: To evaluate biliary stone disease incidence and associated factors in a large series of patients treated with somatostatin analogs for neuroendocrine neoplasms.
METHODS: A prospectively-collected database of patients with a diagnosis of neuroendocrine neoplasms of any grade and site, treated with somatostatin analogs at our Institution between 1995 and 2017, was retrospectively analyzed. Patients' demographics and disease characteristics were analyzed to evaluate the incidence and the factors related to biliary stone disease.
RESULTS: Three-hundred patients were included; 101 (33.7%) patients underwent cholecystectomy before starting somatostatin analogs. Among 164 patients with gallbladder in situ and no history of stone disease, 60 (36.6%) developed gallstones after a mean of 36.7 months (range 1-239) from treatment start with a mean yearly incidence of 8.73%. Previous cholecystectomy was associated with a lower rate of development of gallstones (p < 0.001) or related complications (p = 0.017).
CONCLUSION: We observed a high incidence of biliary stone disease in patients treated with somatostatin analogs-treated for neuroendocrine neoplams. Previous cholecystectomy was the only factor associated with a lower occurrence of biliary stone disease.

PMID: 30314949 [PubMed - as supplied by publisher]

ACTH-Secreting Neuroendocrine Carcinoma of the Cecum: Case Report and Review of the Literature.

Fetched: October 15th, 2018, 5:00am GMT

ACTH-Secreting Neuroendocrine Carcinoma of the Cecum: Case Report and Review of the Literature.

Clin Colorectal Cancer. 2018 Aug 11;:

Authors: Mokhtar A, Arnason T, Gaston D, Huang WY, MacKenzie H, Al-Hazmi R, Vaninetti N, Tugwell B, Rayson D

Abstract
BACKGROUND: Approximately 30% of neuroendocrine tumors (NETs) present with secretory syndromes or develop one during the course of the disease. Cushing syndrome caused by a gastrointestinal tract NET is rare, with limited published information. We describe a patient with florid Cushing syndrome due to ectopic adrenocorticotropic hormone (ACTH) from a NET of colonic origin. A literature review was conducted to describe the spectrum of this clinical and pathologic entity as reported in the scientific literature.
PATIENT AND METHODS: Next-generation sequencing and microsatellite instability testing was carried out on the tumor from our case. A preliminary PubMed search was conducted using the following terms under the publication type "Case Reports": "Cushing" AND "colon," "neuroendocrine" AND "colon" and "neuroendocrine AND Cushing AND "colon." A manual search was performed to review all references for inclusion and relevant clinical, biochemical and pathologic data was abstracted.
RESULTS: Mutations in BRAF V600E and TP53 were detected in our case. We retrieved 18 previously reported cases of Cushing syndrome associated with a NET of colonic origin, none of which had next-generation sequencing performed. Median age at diagnosis was 54.5 years (range, 24-74 years), with equal gender distribution. ACTH was detected by immunohistochemistry in the primary tumor and/or metastatic lesion in 61.5%. Review of the reports suggested that ectopic ACTH secretion from a colonic tumor might be more common in mixed glandular and NETs, including mixed adenocarcinoma-neuroendocrine carcinoma. Among studies reporting outcomes, the unadjusted mortality rate was 77.7%, with median overall survival from presentation of 63 days (range, 17-380 days).
CONCLUSION: Cushing syndrome associated with ectopic ACTH from tumors of colonic origin is a rare phenomenon with poor outcomes and can be associated with pure NETs, adenocarcinomas, and mixed-phenotype tumors, including mixed adenocarcinoma-neuroendocrine carcinoma.

PMID: 30314823 [PubMed - as supplied by publisher]

Permalink for 'Clinical features and outcomes of gastric neuroendocrine tumors after endoscopic diagnosis and treatment: A digestive endoscopy society of Tawian (DEST): Erratum.'

Clinical features and outcomes of gastric neuroendocrine tumors after endoscopic diagnosis and treatment: A digestive endoscopy society of Tawian (DEST): Erratum.

Fetched: October 15th, 2018, 5:00am GMT

Clinical features and outcomes of gastric neuroendocrine tumors after endoscopic diagnosis and treatment: A digestive endoscopy society of Tawian (DEST): Erratum.

Medicine (Baltimore). 2018 Oct;97(41):e12850

Authors:

PMID: 30313124 [PubMed - in process]

Permalink for 'Metastatic esophageal carcinosarcoma comprising neuroendocrine carcinoma, squamous cell carcinoma, and sarcoma: A case report.'

Metastatic esophageal carcinosarcoma comprising neuroendocrine carcinoma, squamous cell carcinoma, and sarcoma: A case report.

Fetched: October 15th, 2018, 5:00am GMT

Metastatic esophageal carcinosarcoma comprising neuroendocrine carcinoma, squamous cell carcinoma, and sarcoma: A case report.

Medicine (Baltimore). 2018 Oct;97(41):e12796

Authors: Tsuchihashi K, Arita S, Fujiwara M, Iwasaki K, Hirano A, Yoshihiro T, Nio K, Koga Y, Esaki M, Ariyama H, Kusaba H, Moriyama T, Ohuchida K, Nagai E, Nakamura M, Oda Y, Akashi K, Baba E

Abstract
RATIONALE: Esophageal carcinosarcoma generally comprises 2 histological components: squamous cell carcinoma (SqCC) and sarcoma. Esophageal carcinosarcoma comprising 3 components is extremely rare and no reports have described therapeutic effects for this disease with metastasis.
PATIENT CONCERNS: A 76-year-old man with dysphagia presented to a local clinic. Gastrointestinal endoscopy revealed a polypoid tumor in the middle esophagus and he was referred to our hospital.
DIAGNOSIS AND INTERVENTIONS: Thoracoscopic esophagectomy with super-extended (D3) nodal dissection and gastric tube reconstitution was performed, which resulted in carcinosarcoma comprising neuroendocrine carcinoma (NEC), SqCC, and sarcoma. Pathological stage was T1bN1M0 stage IIB according to the TNM Classification of Malignant Tumors-7th edition. The NEC component was observed in lymph node. At 47 days after surgery, lymph nodes, liver, and bone metastasis appeared, and tumor markers such as ProGRP and NSE were elevated. Combination chemotherapy with cisplatin and etoposide (EP) adapted to NEC was performed.
OUTCOMES: The patient showed complete response within 4 cycles of chemotherapy. However, the disease recurred 5.5 months after the final course of EP chemotherapy.
LESSONS: A therapeutic strategy based on assessment of which component caused metastasis might be important for metastatic carcinosarcoma comprising 3 components, although more accumulation of data about the efficacy of chemotherapy is necessary. Moreover, elucidation of the mechanisms underlying generation of carcinosarcoma is expected in the future.

PMID: 30313107 [PubMed - in process]

Permalink for 'Safety and efficacy of combining capecitabine and temozolomide (CAPTEM) to treat advanced neuroendocrine neoplasms: A meta-analysis.'

Safety and efficacy of combining capecitabine and temozolomide (CAPTEM) to treat advanced neuroendocrine neoplasms: A meta-analysis.

Fetched: October 15th, 2018, 5:00am GMT

Safety and efficacy of combining capecitabine and temozolomide (CAPTEM) to treat advanced neuroendocrine neoplasms: A meta-analysis.

Medicine (Baltimore). 2018 Oct;97(41):e12784

Authors: Lu Y, Zhao Z, Wang J, Lv W, Lu L, Fu W, Li W

Abstract
Retrospective studies have suggested that capecitabine combined with temozolomide (CAPTEM) is effective for treating patients with advanced neuroendocrine neoplasms (NENs); however, the efficacy and safety of this regimen needs to be verified by high-quality evidence or results of randomized controlled trials.We carried out a meta-analysis to evaluate the safety and effectiveness of a CAPTEM protocol for patients with advanced NENs. Systematic electronic literature searches were conducted using PubMed, EMBASE, and the Cochrane Library, and among meeting abstracts of the American Society of Clinical Oncology, European Society for Medical Oncology, European Neuroendocrine Tumor Society, and North American Neuroendocrine Tumor Society, up to June 30, 2017. We selected studies describing CAPTEM regimens for treating advanced NENs and reported on tumor response and/or toxicities according to clear World Health Organization (WHO) grading of patients. Three reviewers independently and repeatedly identified studies, extracted data, and assessed the quality of the literature. A single-proportion meta-analysis was applied to included articles.Fifteen studies with a total of 384 individuals were included. Medium overall survival in most studies was more than 12 months, whereas medium progression-free survival was similar or slightly higher than that in studies using other treatment regimes. Disease control rate of CAPTEM administration for patients with NENs was 72.89% (95% confidence interval, 64.04-81.73%; I = 82.4%; P < .01). WHO grade 3 to 4 toxicities, such as thrombocytopenia (3.36%), neutropenia (0.69%), lymphopenia (0.65%), anemia (0.59%), mucositis (0.57%), fatigue (0.54%), diarrhea (0.49%), nausea (0.39%), and transaminase elevation (0.13%) were reported in the trials included.CAPTEM is effective and relatively safe for treating patients with advanced NENs.

PMID: 30313101 [PubMed - in process]

Androgen deprivation-induced ZBTB46-PTGS1 signaling promotes neuroendocrine differentiation of prostate cancer.

Fetched: October 14th, 2018, 5:00am GMT

Androgen deprivation-induced ZBTB46-PTGS1 signaling promotes neuroendocrine differentiation of prostate cancer.

Cancer Lett. 2018 Oct 09;:

Authors: Chen WY, Zeng T, Wen YC, Yeh HL, Jiang KC, Chen WH, Zhang Q, Huang J, Liu YN

Abstract
Androgen receptor (AR) targeting is an important therapeutic strategy for treating prostate cancer. Most tumors progress to castration-resistant prostate cancer (CRPC) and develop the neuroendocrine (NE) phenotype under androgen deprivation therapy (ADT). The molecular basis for NE transdifferentiation after ADT remains incompletely understood. Herein, we show that an immunocyte expression protein, ZBTB46, induces inflammatory response gene expression and contributes to NE differentiation of prostate cancer cells. We demonstrated a molecular mechanism whereby ZBTB46 can be regulated by the androgen-responsive gene, SPDEF, and is associated with NE prostate cancer (NEPC) differentiation. In addition, ZBTB46 acts as a transcriptional coactivator that binds to the promoter of prostaglandin-endoperoxide synthase 1 (PTGS1) and transcriptionally regulated PTGS1 levels. Overexpression of ZBTB46 decreases the sensitivity of the combination of enzalutamide and a PTGS1 inhibitor; however, knockdown of ZBTB46 sensitizes the PTGS1 inhibitor and reduces tumor malignancy. ZBTB46 is inversely correlated with SPDEF and is increased in higher tumor grades and small-cell NE prostate cancer (SCNC) patients, which are positively associated with PTGS1. Our findings suggest that the induction of ZBTB46 results in increased PTGS1 expression, which is associated with NEPC progression and linked to the dysregulation of the AR-SPDEF pathway.

PMID: 30312731 [PubMed - as supplied by publisher]

Predictors of Metastases in Rectal Neuroendocrine Tumors: Results of a National Cohort Study.

Fetched: October 14th, 2018, 5:00am GMT

Predictors of Metastases in Rectal Neuroendocrine Tumors: Results of a National Cohort Study.

Dis Colon Rectum. 2018 Oct 11;:

Authors: Concors SJ, Sinnamon AJ, Folkert IW, Mahmoud NN, Fraker DL, Paulson EC, Roses RE

Abstract
BACKGROUND: Rectal neuroendocrine tumors are often found incidentally. Local excision alone has been advocated for lesions ≤2 cm; however, the evidence base for this approach is limited.
OBJECTIVE: Associations among tumor size, degree of differentiation, and presence of distant metastatic disease were examined.
DESIGN: This was a retrospective cohort study.
SETTINGS: This study was conducted using a nationwide cohort.
PATIENTS: A total of 4893 patients with rectal neuroendocrine tumors were identified in the National Cancer Database (2006-2015).
MAIN OUTCOME MEASURES: Logistic regression analyses were used to evaluate associations among tumor size, degree of differentiation, and presence of regional and distant metastatic disease. Cut point analysis was performed to identify an optimal size threshold predictive of distant metastatic disease.
RESULTS: Of patients included for analysis, 3880 (79.3%) had well-differentiated tumors, 540 (11.0%) had moderately differentiated tumors, and 473 (9.7%) had poorly differentiated tumors. On logistic regression, increasing size was associated with a higher likelihood of pathologically confirmed lymph node involvement (among patients undergoing proctectomy), and both size and degree of differentiation were independently associated with a higher likelihood of distant metastatic disease. The association between tumor size and distant metastatic disease was stronger for well-differentiated and moderately differentiated tumors (OR = 1.4; p < 0.001 for both) than for poorly differentiated tumors (OR = 1.1; p = 0.010). For well-differentiated tumors, the optimal cut point for the presence of distant metastatic disease was 1.15 cm (area under the curve = 0.88; 88% sensitive and 88% specific). Tumors ≥1.15 cm in diameter were associated with a substantially increased incidence of distant metastatic disease (72/449 (13.8%)). For moderately differentiated tumors, the optimal cut point was also 1.15 cm (area under the curve = 0.87, 100% sensitive and 75% specific).
LIMITATIONS: This study was limited by its retrospective design.
CONCLUSIONS: Tumor size and degree of differentiation are predictive of regional and distant metastatic disease in rectal neuroendocrine tumors. Patients with tumors >1.15 cm are at substantial risk of distant metastasis and should be staged and managed accordingly. See Video Abstract at [links.lww.com]

PMID: 30312223 [PubMed - as supplied by publisher]

Permalink for 'Reply to Letter: "Current Management and Predictive Factors of Lymph Node Metastasis of Appendix Neuroendocrine Tumors: A National Study from the French Group of Endocrine Tumors (GTE)".'

Reply to Letter: "Current Management and Predictive Factors of Lymph Node Metastasis of Appendix Neuroendocrine Tumors: A National Study from the French Group of Endocrine Tumors (GTE)".

Fetched: October 14th, 2018, 5:00am GMT

Reply to Letter: "Current Management and Predictive Factors of Lymph Node Metastasis of Appendix Neuroendocrine Tumors: A National Study from the French Group of Endocrine Tumors (GTE)".

Ann Surg. 2018 Oct 11;:

Authors: Walter PT, Rault-Petit B, Scoazec PJ

PMID: 30312203 [PubMed - as supplied by publisher]

Permalink for 'Current Management and Predictive Factors of Lymph Node Metastasis of Appendix Neuroendocrine Tumors: A National Study From the French Group of Endocrine Tumors (GTE).'

Current Management and Predictive Factors of Lymph Node Metastasis of Appendix Neuroendocrine Tumors: A National Study From the French Group of Endocrine Tumors (GTE).

Fetched: October 14th, 2018, 5:00am GMT

Current Management and Predictive Factors of Lymph Node Metastasis of Appendix Neuroendocrine Tumors: A National Study From the French Group of Endocrine Tumors (GTE).

Ann Surg. 2018 Oct 11;:

Authors: Lamberti G, Brighi N, Campana D

PMID: 30312201 [PubMed - as supplied by publisher]

Outcomes of 1639 hepatectomies for non-colorectal non-neuroendocrine liver metastases: a multicenter analysis.

Fetched: October 14th, 2018, 5:00am GMT

Outcomes of 1639 hepatectomies for non-colorectal non-neuroendocrine liver metastases: a multicenter analysis.

J Hepatobiliary Pancreat Sci. 2018 Oct 12;:

Authors: Sano K, Yamamoto M, Mimura T, Endo I, Nakamori S, Konishi M, Miyazaki M, Wakai T, Nagino M, Kubota K, Unno M, Sata N, Yamamoto J, Yamaue H, Takada T, Japanese Society of Hepato-Biliary-Pancreatic Surgery

Abstract
BACKGROUND: Whether non-colorectal non-neuroendocrine liver metastasis (NCNNLM) should be treated surgically remains unclear.
METHODS: Data regarding 1639 hepatectomies performed between 2001 and 2010 for 1539 patients with NCNNLM were collected from 124 institutions. Patient characteristics, types of primary tumor, characteristics of liver metastases, and post-hepatectomy outcomes were analyzed.
RESULTS: The 5 most frequent primary tumors were gastric carcinoma (540 patients [35%]), gastrointestinal stromal tumor (204 patients [13%]), biliary carcinoma (150 patients [10%]), ovarian cancer (107 patients [7%]), and pancreatic carcinoma (77 patients [5%]). R0/1 hepatectomy was achieved in 87% of patients, with 1.5% in-hospital mortality rate. Overall and disease-free survival rates of 1465 patients included in survival analysis were 41% and 21%, respectively, at 5 years, and 28% and 15%, respectively, at 10 years. Five-year survival associated with the 5 frequent primary tumors were 32%, 72%, 17%, 52%, and 31%, respectively, and factors predictive of a poor outcome differed by the primary tumor type.
CONCLUSIONS: Our data indicated that hepatectomy is safe for NCNNLM and that patient prognoses vary depending on the type of primary tumors. Indications for hepatectomy should be determined with reference to survival rates and risk factors specific to each of the various types of primary tumor. This article is protected by copyright. All rights reserved.

PMID: 30311741 [PubMed - as supplied by publisher]

Clinicopathological features and prognosis of patients with gastric neuroendocrine tumors: A population-based study.

Fetched: October 14th, 2018, 5:00am GMT

Clinicopathological features and prognosis of patients with gastric neuroendocrine tumors: A population-based study.

Cancer Med. 2018 Oct 11;:

Authors: Tian FX, Cai YQ, Zhuang LP, Chen MF, Xiu ZB, Zhang Y, Liu H, Liu ZH, Liu GP, Zeng C, Lin FL, Liu J, Huang ST, Zhang LZ, Lin HY

Abstract
BACKGROUND: Despite its rarity, studies have shown the incidence of gastric neuroendocrine tumors (G-NETs) is increasing. This study investigated the risk factors affecting the survival of G-NETs patients and their prognosis over time.
METHOD: A retrospective analysis of 506 G-NETs patients who underwent surgery for nonmetastatic disease from the Surveillance, Epidemiology and End Result database from 1988 to 2011 was conducted. Multivariate Cox regression analyses identified the prognostic factors affecting overall survival (OS) and disease-specific survival (DSS). Three-year conditional survival (COS3 and CDS3) estimates at "x" year after treatment were calculated as follows: COS3 = OS(x + 3)/OS(x) and CDS3 = DSS(x + 3)/DSS(x).
RESULTS: The 1-, 3-, and 5-year OS rates of all patients after surgery were 90.2%, 77.3%, and 68.8%, respectively. The 1-, 3-, and 5-year DSS rates after surgery were 93.9%, 84.5%, and 80.9%, respectively. In the multivariate analysis, age, tumor grade, and T stage were independent prognostic factors of OS and DSS (all P < 0.05). With 1-, 3-, and 5-year survivorship, the COS3 improved by +5.2 (82.2%), +7.2 (84.4%), and +8.5 (85.5%), respectively, and the CDS3 improved by +4.4 (89.4%), +9.1 (94.1%), and +12.5 (97.5%), respectively. Notably, the CDS3 improved dramatically among patients with advanced stage disease (eg, N0 stage: 93.0%-98.9%, Δ5.9% vs N1 stage: 52.0%-95.7%, Δ43.7%).
CONCLUSION: For G-NETs patients, age, tumor grade, T stage, and N stage were the clinicopathological factors significantly associated with prognosis. There were excellent outcomes for most G-NETs patients, with a CDS3 of greater than 90% across all independent prognostic factors after 5 years of survival.

PMID: 30311450 [PubMed - as supplied by publisher]

Clinical and in vitro studies of the correlation between MGMT and the effect of streptozocin in pancreatic NET.

Fetched: October 14th, 2018, 5:00am GMT

Clinical and in vitro studies of the correlation between MGMT and the effect of streptozocin in pancreatic NET.

Cancer Chemother Pharmacol. 2018 Oct 11;:

Authors: Hijioka S, Sakuma K, Aoki M, Mizuno N, Kuwahara T, Okuno N, Hara K, Yatabe Y

Abstract
PURPOSE: This study aimed to determine the correlation between DNA repair enzyme O6-methylguanine DNA methyltransferase (MGMT) status and the response to streptozocin in advanced well-differentiated pancreatic neuroendocrine tumors (WD panNETs).
METHODS: To test the hypothesis that MGMT deficiency was required for an alkylating drug response, we retrospectively reviewed the response of 13 patients with WD panNETs to alkylating agents in relation to MGMT status. We also studied MGMT expression in streptozocin resistance using panNET cell lines.
RESULTS: The cohort included 54% of patients with and 46% without MGMT expression. Among these, 83.3% (5/6) of MGMT-negative cases showed a partial response to streptozocin. In contrast, only 14.2% (1/7) of MGMT-positive cases showed a partial response (P = 0.013). Induced expression of MGMT in BON1 cells (a panNET cell line with undetectable endogenous MGMT) produced streptozocin resistance. Knockdown of MGMT in QGP1 cells, which express MGMT endogenously, did not alter the response to streptozocin.
CONCLUSIONS: We observed a relationship between MGMT status and streptozocin response in both patients and cell culture. Despite limited cases examined, high concordance of negative expression of MGMT and response to streptozocin treatment suggest that MGMT expression can be a potential biomarker for this treatment.

PMID: 30310970 [PubMed - as supplied by publisher]

Mortality after deferral of treatment or no treatment for choroidal melanoma.

Fetched: October 14th, 2018, 5:00am GMT

Mortality after deferral of treatment or no treatment for choroidal melanoma.

Indian J Ophthalmol. 2018 Oct;66(10):1395-1400

Authors: Straatsma BR, Diener-West M, Caldwell R, Engstrom RE, Collaborative Ocular Melanoma Study Group*

Abstract
Purpose: To report mortality of patients who were eligible for enrollment in the Collaborative Ocular Melanoma Study (COMS) clinical trials of medium-sized choroidal melanoma or large-sized choroidal melanoma but chose to defer treatment or receive no melanoma treatment.
Design: Prospective nonrandomized multicenter cohort study as an adjunct to COMS randomized clinical trials.
Methods: Patient follow-up procedures included examinations, correspondence, telephone contacts, and National Death Index searches. Primary outcome was patient death measured by all-cause mortality. Secondary outcomes were melanoma treatment and melanoma metastasis.
Results: Of 77 patients eligible for COMS clinical trials who chose to defer or receive no melanoma treatment, 61 were appropriate candidates and 45 (74%) enrolled in the natural history study (NHS). In all, 42 patients (42 eyes) had medium melanoma, and the median follow-up was 5.3 years (range, 4-10.7 years). In all, 22 patients (52%) had subsequent melanoma treatment, and 20 (48%) had no melanoma treatment. For the 42 patients, Kaplan-Meier estimate of 5-year mortality was approximately 30% [95% confidence interval (CI), 18%-47%]. For COMS medium melanoma trial, 5-year mortality was 18% (95% CI, 16%-20%), not statistically significantly different from the NHS patients. After adjusting for differences in age and longest basal diameter, the 5-year risk of death for NHS patients versus COMS trial patients was 1.54 (95% CI, 0.93-2.56). Three patients had large melanoma. Melanoma metastasis was confirmed or suspected in 8 (42%) of 19 deaths.
Conclusion: Greater mortality and higher risk of death for NHS patients are probative but not conclusive evidence of a beneficial, life-extending effect of medium melanoma treatment.

PMID: 30249822 [PubMed - indexed for MEDLINE]

Pilot trial of the hu14.18-IL2 immunocytokine in patients with completely resectable recurrent stage III or stage IV melanoma.

Fetched: October 14th, 2018, 5:00am GMT

Pilot trial of the hu14.18-IL2 immunocytokine in patients with completely resectable recurrent stage III or stage IV melanoma.

Cancer Immunol Immunother. 2018 Oct;67(10):1647-1658

Authors: Albertini MR, Yang RK, Ranheim EA, Hank JA, Zuleger CL, Weber S, Neuman H, Hartig G, Weigel T, Mahvi D, Henry MB, Quale R, McFarland T, Gan J, Carmichael L, Kim K, Loibner H, Gillies SD, Sondel PM

Abstract
Phase I testing of the hu14.18-IL2 immunocytokine (IC) in melanoma patients showed immune activation, reversible toxicities, and a maximal tolerated dose of 7.5 mg/m2/day. Preclinical data in IC-treated tumor-bearing mice with low tumor burden documented striking antitumor effects. Patients with completely resectable recurrent stage III or stage IV melanoma were scheduled to receive 3 courses of IC at 6 mg/m2/day i.v. on days 1, 2 and 3 of each 28-day course. Patients were randomized to complete surgical resection either following neoadjuvant (Group A) or prior to adjuvant (Group B) IC course 1. Primary objectives were to: (1) evaluate histological evidence of anti-tumor activity and (2) evaluate recurrence-free survival (RFS) and OS. Twenty melanoma patients were randomized to Group A (11 patients) or B (9 patients). Two Group B patients did not receive IC due to persistent disease following surgery. Six of 18 IC-treated patients remained free of recurrence, with a median RFS of 5.7 months (95% confidence interval (CI) 1.8-not reached). The 24-month RFS rate was 38.9% (95% CI 17.5-60.0%). The median follow-up of surviving patients was 50.0 months (range: 31.8-70.4). The 24-month OS rate was 65.0% (95% CI 40.3-81.5%). Toxicities were similar to those previously reported. Exploratory tumor-infiltrating lymphocyte (TIL) analyses suggest prognostic value of TILs from Group A patients. Prolonged tumor-free survival was seen in some melanoma patients at high risk for recurrence who were treated with IC.

PMID: 30073390 [PubMed - indexed for MEDLINE]

Permalink for 'Activation of central/effector memory T cells and T-helper 1 polarization in malignant melanoma patients treated with anti-programmed death-1 antibody.'

Activation of central/effector memory T cells and T-helper 1 polarization in malignant melanoma patients treated with anti-programmed death-1 antibody.

Fetched: October 14th, 2018, 5:00am GMT

Activation of central/effector memory T cells and T-helper 1 polarization in malignant melanoma patients treated with anti-programmed death-1 antibody.

Cancer Sci. 2018 Oct;109(10):3032-3042

Authors: Yamaguchi K, Mishima K, Ohmura H, Hanamura F, Ito M, Nakano M, Tsuchihashi K, Ota SI, Wada N, Uchi H, Ariyama H, Kusaba H, Niiro H, Akashi K, Baba E

Abstract
Human anti-programmed death-1 (PD-1) antibody possesses the capability to revitalize host T cells and has been an effective therapy for metastatic malignant melanoma (MM). The precise subsets of T cells predominantly activated by anti-PD-1, however, have not yet been clarified. In this study, peripheral blood mononuclear cells obtained from MM patients scheduled to receive anti-PD-1 (nivolumab) therapy, and healthy subjects (HS), were systematically examined on flow cytometry to identify changes in the proportion of immune cell subsets. Compared with HS, MM patients prior to therapy had an increased proportion of activated CD8+ T cells with effector memory phenotypes (Tem), and PD-1 positive subsets of CD4+ central memory T cells (Tcm) and T-helper (Th)17 cells. After a single course of anti-PD-1 therapy, MM patients had an increase in activated Tem and Tcm subsets of CD4+ and CD8+ T cells, and activated Th1 plus T-helper follicular 1 cells. There was no consistent change in the proportion of Tfh cells, B cells, natural killer cells, or dendritic cells. The observed activated phenotypes were attenuated during the course of therapy, but regulatory T cells belonging to the CD3+CD4+CD45RO+CD25high fraction increased at disease progression. Taken together, anti-PD-1 therapy modulates systemic immune reactions and exerts anti-tumor effects, not only by revitalizing Tem and Tcm of CD4+ and CD8+ T cells, but also via a shift to a Th1 phenotype.

PMID: 30066977 [PubMed - indexed for MEDLINE]

Permalink for 'Older melanoma patients aged 75 and above retain responsiveness to anti-PD1 therapy: results of a retrospective single-institution cohort study.'

Older melanoma patients aged 75 and above retain responsiveness to anti-PD1 therapy: results of a retrospective single-institution cohort study.

Fetched: October 14th, 2018, 5:00am GMT

Older melanoma patients aged 75 and above retain responsiveness to anti-PD1 therapy: results of a retrospective single-institution cohort study.

Cancer Immunol Immunother. 2018 Oct;67(10):1571-1578

Authors: Ibrahim T, Mateus C, Baz M, Robert C

Abstract
INTRODUCTION: The utility of immunotherapy in elderly melanoma patients is debated. We aimed in this study to evaluate the efficacy and tolerability of immunotherapy among elderly patients.
METHOD: This is a retrospective single-institution cohort study. Patients aged 75 years and above who had been treated with nivolumab, pembrolizumab or ipilimumab for advanced or metastatic melanoma, were included. Patients and disease characteristics were collected using electronic medical records. Objective response was determined according to the immune-related response criteria. Drug-related toxicities (DRT) were graded according to the CTCAE v4.03.
RESULTS: 99 patients were included with a mean age of 80 years (SD = 4). One patient received nivolumab and ipilimumab combination, but died because of drug-related diverticulitis. Median PFS on pembrolizumab, nivolumab or ipilimumab were equal to 11.9 (95% CI 5.4-18.4), 1.4 (95% CI 0.01-2.8), and 2.8 months (95% CI 2.6-3), respectively, while objective response rates were equal to 51.6, 12.5, and 17.3%, respectively. Median OS was not reached in patients who received only pembrolizumab, 8.7 months in the ipilimumab only group, and 23 months in patients receiving several immune therapies sequentially. Pembrolizumab, nivolumab, and ipilimumab grade 3-4 DRT rates were equal to 24.2, 62.5, and 32.7% respectively, while discontinuation rates were equal to 43.5, 62.5, and 28.8%, respectively.
CONCLUSIONS: Our study suggests that immunotherapy is effective and well tolerated in the elderly. The PFS on pembrolizumab was greater than expected, a finding that needs to be investigated further.

PMID: 30056599 [PubMed - indexed for MEDLINE]

Safety and immunogenicity of a potential checkpoint blockade vaccine for canine melanoma.

Fetched: October 14th, 2018, 5:00am GMT

Safety and immunogenicity of a potential checkpoint blockade vaccine for canine melanoma.

Cancer Immunol Immunother. 2018 Oct;67(10):1533-1544

Authors: Kurupati RK, Zhou X, Xiang Z, Keller LH, Ertl HCJ

Abstract
Human immunotherapy with checkpoint blockades has achieved significant breakthroughs in recent years. In this study, a checkpoint blockade vaccine for canine melanoma was tested for safety and immunogenicity. Five healthy adult dogs received a mixture of three replication-defective chimpanzee-derived adenoviral vectors, one expressing mouse fibroblast-associated protein (mFAP) and the others expressing canine melanoma-associated antigens Trp-1 or Trp-2 fused into Herpes Simplex-1 glycoprotein D, a checkpoint inhibitor of herpes virus entry mediator (HVEM) pathways. The vaccine mixture was shown to be well tolerated and increased frequencies of canineTrp-1-specific activated CD8+ and CD4+ T cells secreting interferon-(IFN)-γ, tumor necrosis factor (TNF)-α, or interleukin (IL)-2 alone or in combinations in four and five out of five dogs, respectively. To avoid excessive bleeds, responses to cTrp-2 were not analyzed. All dogs responded with increased frequencies of mFAP-specific activated CD8+ and CD4+ T cells. The results of this safety/immunogenicity trial invite further testing of this checkpoint blockade vaccine combination in dogs with melanoma.

PMID: 30051333 [PubMed - indexed for MEDLINE]

Permalink for 'LncNEN885 inhibits epithelial-mesenchymal transition by partially regulation of Wnt/β-catenin signalling in gastroenteropancreatic neuroendocrine neoplasms.'

LncNEN885 inhibits epithelial-mesenchymal transition by partially regulation of Wnt/β-catenin signalling in gastroenteropancreatic neuroendocrine neoplasms.

Fetched: October 14th, 2018, 5:00am GMT

LncNEN885 inhibits epithelial-mesenchymal transition by partially regulation of Wnt/β-catenin signalling in gastroenteropancreatic neuroendocrine neoplasms.

Cancer Sci. 2018 Oct;109(10):3139-3148

Authors: Wei YL, Hua J, Liu XY, Hua XM, Sun C, Bai JA, Tang QY

Abstract
It has been shown that long noncoding RNAs (lncRNAs) are involved in the carcinogenesis of multiple cancers. However, the roles of lncRNAs in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) remain elusive. In the present study, we found that lncNEN885 was markedly decreased in human gastric NEN samples compared to adjacent normal tissues by transcriptome sequencing. Functionally, silencing or overexpression of lncNEN885 could not obviously affect cell proliferation or apoptosis in BON-1 or LCC-18 cells but could affect cell migration and invasion as well as wound-healing rates. Furthermore, dysregulation of lncNEN885 affected these biological functions by activating epithelial-mesenchymal transition through increased expression of Snail, vimentin, and N-cadherin as well as decreased E-cadherin levels in BON-1 and LCC-18 cells. Silencing of lncNEN885 could dramatically increase the phosphorylation of glycogen synthase kinase-3β and decrease the expression of adenomatous polyposis coli and Axin, with the subsequent accumulation of β-catenin. Taken together, dysregulation of lncNEN885 can regulate cell migration and invasion by activating epithelial-mesenchymal transition process partially through canonical Wnt/β-catenin signaling in GEP-NEN cells, which may be a novel biomarker for the metastasis of GEP-NENs.

PMID: 30033597 [PubMed - indexed for MEDLINE]

Transanal minimally invasive surgery for local excision of early rectal tumor.

Fetched: October 14th, 2018, 5:00am GMT

Transanal minimally invasive surgery for local excision of early rectal tumor.

Asian J Endosc Surg. 2018 May;11(2):182-184

Authors: Yoshitomi M, Hasegawa S, Takahashi R, Hida K, Kawada K, Sakai Y

Abstract
INTRODUCTION: Local excision (LE) is used in early rectal cancer and other pathologies for diagnostic purposes and curative treatment, as well as for palliative surgery in patients who are medically unfit for radical resection. Recently, transanal minimally invasive surgery (TAMIS) has been increasingly accepted as a means for performing LE. Here, we present a TAMIS technique for LE to which endoscopic submucosal dissection was applied.
MATERIALS AND SURGICAL TECHNIQUE: We used conventional laparoscopic instruments, including a 10-mm 30° camera. A GelPOINT Path® was introduced into the anal canal to maintain stable pneumorectum and valve-free access. After injecting MucoUp® (SI-4404) into the submucosal layer at the edge of the tumor, we marked dots on the mucosa with cautery using the point of the monopolar diathermy L-hook; we then performed circumferential mucosal incision and submucosal dissection. The remaining defects do not always have to be sutured.
DISCUSSION: TAMIS for LE was performed for seven patients with no postoperative complication and mortality. One lesion required full-thickness resection, one lesion required partial full-thickness resection, and five lesions were dissected completely beneath the submucosal layer. Based on the pathological results, three patients underwent conventional radical resections. One patient had local recurrence at the 8-month follow-up and underwent endoscopic mucosal resection. TAMIS may be a promising option for LE that provides acceptable oncological outcomes and benefits to quality of life.

PMID: 29869844 [PubMed - indexed for MEDLINE]

Acoustic Neuroma Treated with Stereotactic Radiosurgery: Follow-up of 335 Patients.

Fetched: October 14th, 2018, 5:00am GMT

Acoustic Neuroma Treated with Stereotactic Radiosurgery: Follow-up of 335 Patients.

World Neurosurg. 2018 Aug;116:e194-e202

Authors: Rueß D, Pöhlmann L, Hellerbach A, Hamisch C, Hoevels M, Treuer H, Grau S, Jablonska K, Kocher M, Ruge MI

Abstract
OBJECTIVE: To determine the clinical and radiologic outcome of patients with acoustic neuroma (AN) treated with linear accelerator (LINAC) or CyberKnife-based stereotactic radiosurgery with respect to tumor control, preservation of serviceable hearing, and toxicity.
METHODS: A retrospective monocentric analysis including all patients who underwent single-fraction LINAC- or CyberKnife-based radiosurgery for AN between 1991 and 2015. Patient data were analyzed in terms of radiologic and clinical tumor control (no further intervention needed), treatment-related complications, preservation of serviceable hearing, and objectified hearing loss using pure tone average levels.
RESULTS: We included 335 patients (median age 58.2 years, treated either by LINAC-based [n = 270] or CyberKnife [n = 65] stereotactic radiosurgery). The median tumor volume was 1.1 mL (0.1-23.7 mL). The median radiation dose was 12 Gy (LINAC 12 Gy, 11-20 Gy; CyberKnife 13 Gy, 12-13 Gy) at an isodose level of 71.7% (LINAC 68.3%, 31.9%-86.2%; CyberKnife 80%, 65%-81%). The median follow-up was 30 months (LINAC 43 months, 2-224 months; CyberKnife 13 months, 4-37 months). Clinical tumor control was 98%, 89%, and 88% at 2, 5, and 10 years. The objective actuarial hearing preservation rate was 89%, 80%, and 55% at 1, 2, and 5 years. New symptoms were observed in 11.3% and classified as Common Terminology Criteria for Adverse Events grade 1/2, apart from 4 patients (1.2%), who developed Common Terminology Criteria for Adverse Events grade 3.
CONCLUSIONS: Our study shows that in AN, high tumor control and considerable hearing preservation rates can be achieved by single-dose radiosurgery at low toxicity rates, resulting in a positive impact on long-term clinical outcome.

PMID: 29715569 [PubMed - indexed for MEDLINE]

Selective cytotoxicity of the herbal substance acteoside against tumor cells and its mechanistic insights.

Fetched: October 14th, 2018, 5:00am GMT

Selective cytotoxicity of the herbal substance acteoside against tumor cells and its mechanistic insights.

Redox Biol. 2018 06;16:169-178

Authors: Cheimonidi C, Samara P, Polychronopoulos P, Tsakiri EN, Nikou T, Myrianthopoulos V, Sakellaropoulos T, Zoumpourlis V, Mikros E, Papassideri I, Argyropoulou A, Halabalaki M, Alexopoulos LG, Skaltsounis AL, Tsitsilonis OE, Aligiannis NN, Trougakos IP

Abstract
Natural products are characterized by extreme structural diversity and thus they offer a unique source for the identification of novel anti-tumor agents. Herein, we report that the herbal substance acteoside being isolated by advanced phytochemical methods from Lippia citriodora leaves showed enhanced cytotoxicity against metastatic tumor cells; acted in synergy with various cytotoxic agents and it sensitized chemoresistant cancer cells. Acteoside was not toxic in physiological cellular contexts, while it increased oxidative load, affected the activity of proteostatic modules and suppressed matrix metalloproteinases in tumor cell lines. Intraperitoneal or oral (via drinking water) administration of acteoside in a melanoma mouse model upregulated antioxidant responses in the tumors; yet, only intraperitoneal delivery suppressed tumor growth and induced anti-tumor-reactive immune responses. Mass-spectrometry identification/quantitation analyses revealed that intraperitoneal delivery of acteoside resulted in significantly higher, vs. oral administration, concentration of the compound in the plasma and tumors of treated mice, suggesting that its in vivo anti-tumor effect depends on the route of administration and the achieved concentration in the tumor. Finally, molecular modeling studies and enzymatic activity assays showed that acteoside inhibits protein kinase C. Conclusively, acteoside holds promise as a chemical scaffold for the development of novel anti-tumor agents.

PMID: 29505920 [PubMed - indexed for MEDLINE]

Merkel cell carcinoma: Current US incidence and projected increases based on changing demographics.

Fetched: October 14th, 2018, 5:00am GMT

Merkel cell carcinoma: Current US incidence and projected increases based on changing demographics.

J Am Acad Dermatol. 2018 03;78(3):457-463.e2

Authors: Paulson KG, Park SY, Vandeven NA, Lachance K, Thomas H, Chapuis AG, Harms KL, Thompson JA, Bhatia S, Stang A, Nghiem P

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) incidence rates are rising and strongly age-associated, relevant for an aging population.
OBJECTIVE: Determine MCC incidence in the United States and project incident cases through the year 2025.
METHODS: Registry data were obtained from the SEER-18 Database, containing 6600 MCC cases. Age- and sex-adjusted projections were generated using US census data.
RESULTS: During 2000-2013, the number of reported solid cancer cases increased 15%, melanoma cases increased 57%, and MCC cases increased 95%. In 2013, the MCC incidence rate was 0.7 cases/100,000 person-years in the United States, corresponding to 2488 cases/year. MCC incidence increased exponentially with age, from 0.1 to 1.0 to 9.8 (per 100,000 person-years) among age groups 40-44 years, 60-64 years, and ≥85 years, respectively. Due to aging of the Baby Boomer generation, US MCC incident cases are predicted to climb to 2835 cases/year in 2020 and 3284 cases/year in 2025.
LIMITATIONS: We assumed that the age-adjusted incidence rate would stabilize, and thus, the number of incident cases we projected might be an underestimate.
CONCLUSION: An aging population is driving brisk increases in the number of new MCC cases in the United States. This growing impact combined with the rapidly evolving therapeutic landscape warrants expanded awareness of MCC diagnosis and management.

PMID: 29102486 [PubMed - indexed for MEDLINE]

Permalink for 'Why we should improve current practice of diagnosing and treating pulmonary large cell neuroendocrine carcinomas in patients with advanced disease.'

Why we should improve current practice of diagnosing and treating pulmonary large cell neuroendocrine carcinomas in patients with advanced disease.

Fetched: October 14th, 2018, 5:00am GMT

Why we should improve current practice of diagnosing and treating pulmonary large cell neuroendocrine carcinomas in patients with advanced disease.

Eur Respir J. 2017 10;50(4):

Authors: Derks J, van Suylen RJ, Thunnissen E, den Bakker M, Groen H, Smit E, Damhuis R, van den Broek E, Speel EJ, Dingemans AC

PMID: 29074548 [PubMed - indexed for MEDLINE]

Large cell neuroendocrine carcinoma of the lung: chemotherapy regimen depends on how "large" your diagnostic criteria are.

Fetched: October 14th, 2018, 5:00am GMT

Large cell neuroendocrine carcinoma of the lung: chemotherapy regimen depends on how "large" your diagnostic criteria are.

Eur Respir J. 2017 10;50(4):

Authors: Rossi G, Longo L, Barbieri F, Bertolini F, Spagnolo P

PMID: 29074547 [PubMed - indexed for MEDLINE]

Nivolumab for the treatment of malignant melanoma in a patient with pre-existing myasthenia gravis.

Fetched: October 14th, 2018, 5:00am GMT

Nivolumab for the treatment of malignant melanoma in a patient with pre-existing myasthenia gravis.

Nagoya J Med Sci. 2016 02;78(1):119-22

Authors: Maeda O, Yokota K, Atsuta N, Katsuno M, Akiyama M, Ando Y

Abstract
A 79-year-old man with lymph node recurrence of malignant melanoma received nivolumab, an anti-programmed death 1 (PD-1) monoclonal antibody. He had pre-existing ocular myasthenia gravis (MG) and a continued small amount of corticosteroid. Grade 3 creatine phosphokinase elevation appeared after two doses of nivolumab, and the treatment was postponed until it improved to grade 1. After three doses of nivolumab, he experienced diplopia and facial muscle weakness which were consistent with an acute exacerbation of MG, and the symptoms relieved without additional treatment for MG. He achieved shrinkage of metastasis after ten doses of nivolumab. Although a case who died due to MG after administration of nivolumab was reported recently, pre-existing MG is considered not to be always a contraindication of nivolumab.

PMID: 27019533 [PubMed - indexed for MEDLINE]

Gastroenteropancreatic Neuroendocrine Tumors.

Fetched: October 10th, 2018, 5:00am GMT

Gastroenteropancreatic Neuroendocrine Tumors.

CA Cancer J Clin. 2018 Oct 08;:

Authors: Cives M, Strosberg JR

Abstract
Neuroendocrine tumors (NETs) are heterogeneous malignancies arising from the diffuse neuroendocrine system. They frequently originate in the gastroenteropancreatic (GEP) tract and the bronchopulmonary tree, and their incidence has steadily increased in the last 3 decades. Fundamental biologic and genomic differences underlie the clinical heterogeneity of NETs, and distinct molecular features characterize NETs of different grades and different primary sites. Although surgery remains the cornerstone of treatment for localized tumors, systemic treatment options for patients with metastatic NETs have expanded considerably. Somatostatin analogs have demonstrated both antisecretory and antitumor efficacy. Peptide receptor radionuclide therapy with lutetium-177 dotatate (177 Lu-DOTATATE) has been approved for advanced GEP-NETs. The antitumor activity of everolimus has been demonstrated across a wide spectrum of NETs, and the antiangiogenic agent sunitinib has been approved for pancreatic NETs (pNETs). Chemotherapy with temozolomide and capecitabine has recently demonstrated an unprecedented prolongation of progression-free survival in a randomized trial of pNETs. Multiple retrospective series have reported the efficacy of liver-directed therapies both for palliating symptoms of hormone excess and for controlling tumor growth. Telotristat, an oral inhibitor of tryptophan hydroxylase, has been shown to reduce diarrhea in patients with carcinoid syndrome. Defining the therapeutic algorithm and identifying biomarkers predictive of response to treatments are among the main priorities for the next decade of research in the NET field.

PMID: 30295930 [PubMed - as supplied by publisher]

Permalink for 'The first pediatric case of glucagon receptor defect due to biallelic mutations in GCGR is identified by newborn screening of elevated arginine.'

The first pediatric case of glucagon receptor defect due to biallelic mutations in GCGR is identified by newborn screening of elevated arginine.

Fetched: October 10th, 2018, 5:00am GMT

The first pediatric case of glucagon receptor defect due to biallelic mutations in GCGR is identified by newborn screening of elevated arginine.

Mol Genet Metab Rep. 2018 Dec;17:46-52

Authors: Li H, Zhao L, Singh R, Ham JN, Fadoju DO, Bean LJH, Zhang Y, Xu Y, Xu HE, Gambello MJ

Abstract
Glucagon receptor (GCGR) defect (Mahvash disease) is an autosomal recessive hereditary pancreatic neuroendocrine tumor (PNET) syndrome that has only been reported in adults with pancreatic α cell hyperplasia and PNETs. We describe a 7-year-old girl with persistent hyperaminoacidemia, notable for elevations of glutamine (normal ammonia), alanine (normal lactate), dibasic amino acids (arginine, lysine and ornithine), threonine and serine. She initially was brought to medical attention by an elevated arginine on newborn screening (NBS) and treated for presumed arginase deficiency with a low protein diet, essential amino acids formula and an ammonia scavenger drug. This treatment normalized plasma amino acids. She had intermittent emesis and anorexia, but was intellectually normal. Arginase enzyme assay and ARG1 sequencing and deletion/duplication analysis were normal. Treatments were stopped, but similar pattern of hyperaminoacidemia recurred. She also had hypercholesterolemia type IIa, with only elevated LDL cholesterol, despite an extremely lean body habitus. Exome sequencing was initially non-diagnostic. Through a literature search, we recognized the pattern of hyperaminoacidemia was strikingly similar to that reported in the Gcgr -/- knockout mice. Subsequently the patient was found to have an extremely elevated plasma glucagon and a novel, homozygous c.958_960del (p.Phe320del) variant in GCGR. Functional studies confirmed the pathogenicity of this variant. This case expands the clinical phenotype of GCGR defect in children and emphasizes the clinical utility of plasma amino acids in screening, diagnosis and monitoring glucagon signaling interruption. Early identification of a GCGR defect may provide an opportunity for potential beneficial treatment for an adult onset tumor predisposition disease.

PMID: 30294546 [PubMed]

Multilayered heterogeneity as an intrinsic hallmark of neuroendocrine tumors.

Fetched: October 9th, 2018, 5:00am GMT

Multilayered heterogeneity as an intrinsic hallmark of neuroendocrine tumors.

Rev Endocr Metab Disord. 2018 Oct 06;:

Authors: Pedraza-Arévalo S, Gahete MD, Alors-Pérez E, Luque RM, Castaño JP

Abstract
Neuroendocrine tumors (NETs) comprise a complex and highly heterogeneous group of neoplasms that can arise all over the body, originating from neuroendocrine cells. NETs are characterized by a general lack of symptoms until they are in advanced phase, and early biomarkers are not as available and useful as required. Heterogeneity is an intrinsic, pivotal feature of NETs that derives from diverse causes and ultimately shapes tumor fate. The different layers that conform NET heterogeneity include a wide range of distinct characteristics, from the mere location of the tumor to its clinical and functional features, and from its cellular properties, to the core signaling and (epi)genetic components defining the molecular signature of the tumor. The importance of this heterogeneity resides in that it translates into a high variability among tumors and, hence, patients, which hinders a more precise diagnosis and prognosis and more efficacious treatment of these diseases. In this review, we highlight the significance of this heterogeneity as an intrinsic hallmark of NETs, its repercussion on clinical approaches and tumor management, and some of the possible factors associated to such heterogeneity, including epigenetic and genetic elements, post-transcriptional regulation, or splicing alterations. Notwithstanding, heterogeneity can also represent a valuable and actionable feature, towards improving medical approaches based on personalized medicine. We conclude that NETs can no longer be viewed as a single disease entity and that their diagnosis, prognosis and treatment must reflect and incorporate this heterogeneity.

PMID: 30293213 [PubMed - as supplied by publisher]

Permalink for 'Differentiation of duodenal gastrointestinal stromal tumors from hypervascular pancreatic neuroendocrine tumors in the pancreatic head using contrast-enhanced computed tomography.'

Differentiation of duodenal gastrointestinal stromal tumors from hypervascular pancreatic neuroendocrine tumors in the pancreatic head using contrast-enhanced computed tomography.

Fetched: October 9th, 2018, 5:00am GMT

Differentiation of duodenal gastrointestinal stromal tumors from hypervascular pancreatic neuroendocrine tumors in the pancreatic head using contrast-enhanced computed tomography.

Abdom Radiol (NY). 2018 Oct 06;:

Authors: Ren S, Chen X, Wang J, Zhao R, Song L, Li H, Wang Z

Abstract
PURPOSE: To determine useful contrast-enhanced computed tomography (CE-CT) features in differentiating duodenal gastrointestinal stromal tumors (duodenal GISTs) from hypervascular pancreatic neuroendocrine tumors in the pancreatic head (pancreatic head NETs).
METHODS: Seventeen patients with pathologically confirmed duodenal GISTs and 25 with pancreatic NETs underwent preoperative CE-CT. CT image analysis included tumor size, morphology, and contrast enhancement. Receiver operating characteristic curves were performed, and cutoff values were calculated to determine CT findings with high sensitivity and specificity.
RESULTS: CT imaging showed duodenal GISTs with higher frequencies of tumor central location close to the duodenum and a predominantly solid tumor type when compared with pancreatic head NETs (p < 0.05 for both). Duodenal GISTs were larger than pancreatic head NETs (3.3 ± 0.9 cm vs. 2.5 ± 1.1 cm, p = 0.03). Duodenal GISTs had significantly lower CT attenuation values (112.9 ± 17.9HU vs. 137.4 ± 32.1HU, p < 0.01) at the arterial phase and higher CT attenuation values at the delayed phase (94.3 ± 7.9HU vs. 84.9 ± 10.4HU, p < 0.01) when compared with pancreatic head NETs. A CT attenuation value of ≤ 135 HU at the arterial phase (30 s) was 76% sensitive, 94.1% specific, and 83.3% accurate for the diagnosis of duodenal GISTs, while a CT attenuation value of ≥ 89.5 HU at the delayed phase (120 s) was 93.3% sensitive, 81.8% specific, and 76.2% accurate for the diagnosis of duodenal GISTs.
CONCLUSION: Tumor central location, size, texture, and contrast enhancement are valuable characteristics for the differentiation between duodenal GISTs and hypervascular pancreatic head NETs during preoperative examination.

PMID: 30293109 [PubMed - as supplied by publisher]

Cystic mixed adenoneuroendocrine carcinoma of the pancreas: A case report.

Fetched: October 8th, 2018, 5:00am GMT

Cystic mixed adenoneuroendocrine carcinoma of the pancreas: A case report.

Int J Surg Case Rep. 2018 Sep 23;52:1-4

Authors: Shimada N, Miwa S, Arai T, Kitagawa N, Akita S, Iinuma N, Ishii K

Abstract
INTRODUCTION: Pancreatic mixed adenoneuroendocrine carcinoma (MANEC) is a rare tumor. We report herein a case of pancreatic MANEC with cystic features.
PRESENTATION OF CASE: A 67-year-old woman presented with jaundice. A CT scan revealed an 18-mm mass at the pancreatic head that obstructed the common bile duct and another 35-mm cystic lesion containing a mural nodule in the pancreatic body, which was suspected to be an intraductal papillary mucinous carcinoma. A biopsy of the head mass led to the diagnosis of adenocarcinoma. The patient underwent pancreatoduodenectomy, and the body cyst was resected with the head mass. A histopathological analysis revealed that the body cyst had two components, ductal adenocarcinoma and neuroendocrine tumor. We diagnosed the cystic tumor as MANEC.
DISCUSSION: Cases of MANEC have been reported as originating from the stomach, small intestine, and colon, but pancreatic MANEC is rare. The histogenesis and the therapeutic strategy for pancreatic MANEC are controversial.
CONCLUSION: The clinicopathological features of pancreatic MANEC remain unclear; therefore, more reports of cases of pancreatic MANEC are necessary for a complete analysis.

PMID: 30292093 [PubMed - as supplied by publisher]

Efficacy and Safety of High-Specific-Activity I-131 MIBG Therapy in Patients with Advanced Pheochromocytoma or Paraganglioma.

Fetched: October 8th, 2018, 5:00am GMT

Efficacy and Safety of High-Specific-Activity I-131 MIBG Therapy in Patients with Advanced Pheochromocytoma or Paraganglioma.

J Nucl Med. 2018 Oct 05;:

Authors: Pryma DA, Chin BB, Noto RB, Dillon JS, Perkins S, Solnes L, Kostakoglu L, Serafini AN, Pampaloni MH, Jensen J, Armor T, Lin T, White T, Stambler N, Apfel S, DiPippo V, Mahmood S, Wong V, Jimenez C

Abstract
Patients with metastatic or unresectable (advanced) pheochromocytoma or paraganglioma (PPGL) have poor prognoses and few treatment options. This multicenter, phase 2 trial evaluated the efficacy and safety of high-specific-activity I-131 meta-iodobenzylguanidine (HSA I-131 MIBG) in patients with advanced PPGL. Methods: In this open-label, single-arm study, 81 PPGL patients were screened for enrollment, and 74 received a treatment-planning dose of HSA I-131 MIBG. 68 patients with advanced PPGL received at least one therapeutic dose (~18.5 GBq) of HSA I-131 MIBG intravenously. The primary endpoint was the proportion of patients with at least a 50% reduction in baseline antihypertensive medication use lasting at least 6 months. Secondary endpoints included objective tumor response as assessed by Response Evaluation Criteria in Solid Tumors version 1.0; biochemical tumor marker response; overall survival (OS); and safety. Results: Of the 68 patients who received at least one therapeutic dose of HSA I-131 MIBG, 17 (25%; 95% CI, 16-37%) had a durable reduction in baseline antihypertensive medication use. Among 64 patients with evaluable disease, 59 (92%) had a partial response or stable disease as the best objective response within 12 months. Decreases in elevated (≥1.5 times the upper limit of normal (ULN) at baseline) serum CgA levels were observed with confirmed complete and partial responses 12 months after treatment in 19 of 28 patients (68%). The median OS duration was 36.7 months (95% CI, 29.9-49.1 months). The most common treatment-emergent adverse events were nausea, myelosuppression, and fatigue. No patients had drug-related acute hypertensive events during or after the administration of HSA I-131 MIBG. Conclusion: HSA I-131 MIBG offers multiple benefits, including sustained blood pressure control and tumor response in PPGL patients.

PMID: 30291194 [PubMed - as supplied by publisher]

Esophageal neuroendocrine carcinoma complicated with unexpected hyperprocalcitonin: Case report and literature review.

Fetched: October 8th, 2018, 5:00am GMT

Esophageal neuroendocrine carcinoma complicated with unexpected hyperprocalcitonin: Case report and literature review.

Medicine (Baltimore). 2018 Oct;97(40):e12219

Authors: Hu Q, Jin P, Zhao X, Wu W, Huang B, Shao S, Que R, Liang T

Abstract
RATIONALE: Neuroendocrine tumors (NETs) with hyperprocalcitonin are relatively rare with a low incidence rate.
PATIENT CONCERNS: An afebrile 63-year-old male with persistent low back pain unexpectedly presented with an extreme hyperprocalcitonin. Radiological assessment revealed thickening of the esophageal wall with vertebral bone destruction and liver lesions. Endoscopy showed an irregular-shaped esophageal lesion which turned out to be poorly-differentiated NETs.
DIAGNOSIS: Esophageal NETs with multiple metastases.
INTERVENTIONS: The patient was treated with chemotherapies, and was evaluated by procalcitonin level and radiology within follow-up.
OUTCOME: The procalcitonin levels were altered in line with the therapeutic response and disease progression during the treatment course.
LESSONS: Increased procalcitonin occurs in several malignancies with neuroendocrine components, such as NETs of the digestive system.

PMID: 30290592 [PubMed - in process]

Cell-Free DNA and Neuromediators in Detecting Aggressive Variant Prostate Cancer.

Fetched: October 6th, 2018, 5:00am GMT

Icon for S. Karger AG, Basel, Switzerland

Cell-Free DNA and Neuromediators in Detecting Aggressive Variant Prostate Cancer.

Oncol Res Treat. 2018;41(10):627-633

Authors: von Hardenberg J, Worst TS, Westhoff N, Erben P, Fuxius S, Müller M, Bolenz C, Weiss C, Heinrich E

Abstract
BACKGROUND: Aggressive variant transformation in metastatic castration-resistant prostate cancer (mCRPC) represents an under-recognized phenomenon. There is an urgent need for non-invasive biomarkers to detect these variants and identify treatment alternatives.
METHODS: A prospective observational pilot study in mCRPC patients receiving treatment with cabazitaxel (CAB) was conducted. Neuromediators were sequentially evaluated and their impact on disease endpoints calculated. Targeted next-generation sequencing (NGS) of cell-free DNA (cfDNA) was also performed in a highly pretreated subset of patients.
RESULTS: 23 patients were included. Estimated effects indicate that neuron-specific enolase (NSE) levels at baseline may be correlated with overall survival (NSE unit 18.3 ng/ml: HR1.262 (95% confidence interval (CI) 0.985-1.616)) and that chromogranin A (CGA) may be correlated with progression-free survival (CGA unit 98.1 ng/ml: HR1.341 (95% CI 1.011-1.778)). cfDNA analysis revealed mutations annotated in prostate cancer (PCA) and small cell cancers (SCC). 1 patient showed elevated neuromediators along with annotated mutations in PCA and SCC, potentially indicating aggressive variant cancer. In 3 patients KIT mutations (e.g. pM541L, pV654A) known to be tissue-based biomarkers with level 1 evidence for the treatment with imatinib and sunitinib were found.
CONCLUSIONS: Sequential analysis of neuromediators and targeted NGS of cfDNA provide insight for the estimation of tumor heterogeneity under therapy with CAB.

PMID: 30286478 [PubMed - in process]

Adamantinoma-like Ewing Sarcoma of the Salivary Glands: A Newly Recognized Mimicker of Basaloid Salivary Carcinomas.

Fetched: October 6th, 2018, 5:00am GMT

Adamantinoma-like Ewing Sarcoma of the Salivary Glands: A Newly Recognized Mimicker of Basaloid Salivary Carcinomas.

Am J Surg Pathol. 2018 Oct 03;:

Authors: Rooper LM, Jo VY, Antonescu CR, Nose V, Westra WH, Seethala RR, Bishop JA

Abstract
Adamantinoma-like Ewing sarcoma (ALES) is a rare tumor that demonstrates the EWSR1-FLI1 translocation characteristic of Ewing sarcoma despite overt epithelial differentiation including diffuse expression of cytokeratins and p40. Most cases of ALES described to date have occurred in the head and neck where they can mimic a wide range of small round blue cell tumors. Because distinguishing ALES from basaloid salivary gland carcinomas can be particularly difficult, we analyzed a series of 10 ALESs that occurred in the salivary glands with the aim of identifying features that allow for better recognition of this entity. The salivary ALESs included 8 parotid gland and 2 submandibular gland tumors in patients ranging from 32 to 77 years (mean: 52 y). Nine were initially misclassified as various epithelial neoplasms. Although these tumors displayed the basaloid cytology, rosette formation, infiltrative growth, and nuclear monotony characteristic of ALES, peripheral palisading and overt keratinization were relatively rare in this site. Salivary ALESs not only displayed positivity for AE1/AE3, p40, and CD99, but also demonstrated a higher proportion of synaptophysin reactivity than has been reported for nonsalivary ALESs. These morphologic and immunohistochemical findings make ALES susceptible to misclassification as various other tumors including basal cell adenocarcinoma, adenoid cystic carcinoma, squamous cell carcinoma, NUT carcinoma, large cell neuroendocrine carcinoma and myoepithelial carcinoma. Nevertheless, monotonous cytology despite highly infiltrative growth and concomitant positivity for p40 and synaptophysin can provide important clues for consideration of ALES, and identification of the defining EWSR1-FLI1 translocations can confirm the diagnosis.

PMID: 30285997 [PubMed - as supplied by publisher]

Reduced menin expression impairs rapamycin effects as evidenced by an increase in mTORC2 signaling and cell migration.

Fetched: October 6th, 2018, 5:00am GMT

Reduced menin expression impairs rapamycin effects as evidenced by an increase in mTORC2 signaling and cell migration.

Cell Commun Signal. 2018 Oct 01;16(1):64

Authors: Razmara M, Monazzam A, Skogseid B

Abstract
BACKGROUND: Mammalian target of rapamycin (mTOR) is a master regulator of various cellular responses by forming two functional complexes, mTORC1 and mTORC2. mTOR signaling is frequently dysregulated in pancreatic neuroendocrine tumors (PNETs). mTOR inhibitors have been used in attempts to treat these lesions, and prolonged progression free survival has been recorded. If this holds true also for the multiple endocrine neoplasia type 1 (MEN1) associated PNETs is yet unclear. We investigated the relationship between expression of the MEN1 protein menin and mTOR signaling in the presence or absence of the mTOR inhibitor rapamycin.
METHODS: In addition to use of menin wild type and menin-null mouse embryonic fibroblasts (MEFs), menin was silenced by siRNA in pancreatic neuroendocrine tumor cell line BON-1. Panels of protein phosphorylation, as activation markers downstream of PI3k-mTOR-Akt pathways, as well as menin expression were evaluated by immunoblotting. The impact of menin expression in the presence and absence of rapamycin was determinate upon Wound healing, migration and proliferation in MEFs and BON1 cells.
RESULTS: PDGF-BB markedly increased phosphorylation of mTORC2 substrate Akt, at serine 473 (S473) and threonine 450 (T450) in menin-/- MEFs but did not alter phosphorylation of mTORC1 substrates ribosomal protein S6 or eIF4B. Acute rapamycin treatment by mTORC1-S6 inhibition caused a greater enhancement of Akt phosphorylation on S473 in menin-/- cells as compared to menin+/+ MEFs (116% vs 38%). Chronic rapamycin treatment, which inhibits both mTORC1and 2, reduced Akt phosphorylation of S473 to a lesser extent in menin-/- MEFs than menin+/+ MEFs (25% vs 75%). Silencing of menin expression in human PNET cell line (BON1) also enhanced Akt phosphorylation at S473, but not activation of mTORC1. Interestingly, silencing menin in BON1 cells elevated S473 phosphorylation of Akt in both acute and chronic treatments with rapamycin. Finally, we show that the inhibitory effect of rapamycin on serum mediated wound healing and cell migration is impaired in menin-/- MEFs, as well as in menin-silenced BON1 cells.
CONCLUSIONS: Menin is involved in regulatory mechanism between the two mTOR complexes, and its reduced expression is accompanied with increased mTORC2-Akt signaling, which consequently impairs anti-migratory effect of rapamycin.

PMID: 30285764 [PubMed - in process]

Immunohistochemical analysis of OTP and NKX6.1 in neuroendocrine tumors of the lung and pancreas.

Fetched: October 6th, 2018, 5:00am GMT

Immunohistochemical analysis of OTP and NKX6.1 in neuroendocrine tumors of the lung and pancreas.

Diagn Cytopathol. 2018 Oct 03;:

Authors: Yoxtheimer LM, Heymann JJ, Cohen C, Rao RA, Goyal A, Siddiqui MT

Abstract
BACKGROUND: Homeobox transcription factors have demonstrated utility in diagnosing neuroendocrine tumors. Orthopedia homeobox protein (OTP) has a well-defined role in embryonic neurodevelopment and has also been described as a prognostic marker in lung neuroendocrine tumors (NET). Additionally, NK6 homeobox-1 (NKX6.1) has been described to be necessary for the development of neuroendocrine cells in the pancreas. We evaluated immunohistochemical (IHC) expression of OTP and NKX6.1 to determine their utility in the diagnosis of NETs from lung and pancreas fine-needle aspirations (FNA).
METHODS: Our study examined 50 FNA specimens, including 30 primary pulmonary NETs (8 carcinoid tumors (CT), 6 atypical carcinoids (AC), 11 small-cell neuroendocrine carcinomas (SCNEC), 5 large-cell neuroendocrine carcinomas (LCNEC)) and 20 primary pancreatic NETs (17 well-differentiated pancreatic neuroendocrine tumors (PanNET) and 3 poorly differentiated pancreatic neuroendocrine carcinomas (PanNEC)). IHC expression of OTP, NKX6.1, and Ki-67 was evaluated on FNA cell blocks.
RESULTS: Half of the pulmonary TC tumors expressed OTP, while only 17% of AC and 20% of LCNEC expressed OTP. Neither SCNECs nor any pancreatic NET expressed OTP. In contrast, intermediate and high-grade tumors expressed NKX6.1 (LCNEC-80%, SCNEC-82%, and AC-83%) more often than low-grade tumors (TC-63%, PanNET-71%). All three PanNECs expressed NKX6.1.
CONCLUSIONS: OTP may be useful in diagnosing well-differentiated NETs of pulmonary origin. NKX6.1 may have utility in segregating high from low-grade NETs of both pulmonary and pancreatic origin, although other methods will be required to determine site of origin.

PMID: 30284410 [PubMed - as supplied by publisher]

Permalink for 'Pancreatic mixed acinar-neuroendocrine carcinoma, a unique diagnostic challenge on FNA cytology: A small series of two cases with literature review.'

Pancreatic mixed acinar-neuroendocrine carcinoma, a unique diagnostic challenge on FNA cytology: A small series of two cases with literature review.

Fetched: October 6th, 2018, 5:00am GMT

Pancreatic mixed acinar-neuroendocrine carcinoma, a unique diagnostic challenge on FNA cytology: A small series of two cases with literature review.

Diagn Cytopathol. 2018 Oct 03;:

Authors: Strait AM, Sharma N, Tsapakos MJ, Vaickus LJ, Liu X

Abstract
Mixed acinar-neuroendocrine carcinoma (MANEC) of the pancreas is a rare tumor. We present two cases of MANEC diagnosed on endoscopic ultrasound (EUS) guided fine-needle aspiration (FNA). The first patient is a 33-year-old male who had a 3.6 cm mass in the uncinate process and liver metastasis. The second patient is a 66-year-old male with a 10 cm mass in the pancreatic tail. The FNA smears from both cases were hypercellular with neoplastic cells in loosely cohesive clusters and many naked nuclei. In both cases, the tumor cells were positive for CKAE1/3, synaptophysin, chromogranin, and trypsin by immunohistochemistry. Final diagnoses of MANEC were rendered based on cytological features and immunohistochemical profiles. To date, 44 cases of MANEC have been reported in the English literature, only three of which were diagnosed on cytopathology specimens before surgical resection. Our report adds two more cases diagnosed on cytopathology alone. Herein, we discuss the various cytomorphologic and clinical features of MANEC and present a brief review of the literature. Diagn. Cytopathol. 2018. © 2018 Wiley Periodicals, Inc.

PMID: 30284406 [PubMed - as supplied by publisher]

Diagnosing microscopic pancreatic neuroendocrine tumor using 68-Ga-DOTATATE PET/CT: case series.

Fetched: October 6th, 2018, 5:00am GMT

Diagnosing microscopic pancreatic neuroendocrine tumor using 68-Ga-DOTATATE PET/CT: case series.

J Surg Case Rep. 2018 Sep;2018(9):rjy237

Authors: Barrio M, Ceppa EP

Abstract
Neuroendocrine tumors (NETs) are an uncommon diagnosis which often present asymptomatically or with vague symptoms. They can originate from many different organs such as the GI tract, lungs, pancreas and others. 68Gallium DOTATATE positron emission topography/computed topography has been shown to be an effective imaging modality for diagnosing NET and evaluating management options for patients. Here, we present two cases of positive findings in the distal pancreas on the DOTATATE PET/CT scans without any morphological lesion found to be NET in a healthy 48-year-old male and 68-year-old male.

PMID: 30283629 [PubMed]

Mixed Adenoneuroendocrine Carcinoma of the Esophagus: A Case Report and Review of the Literature.

Fetched: October 6th, 2018, 5:00am GMT

Mixed Adenoneuroendocrine Carcinoma of the Esophagus: A Case Report and Review of the Literature.

Niger J Surg. 2018 Jul-Dec;24(2):131-134

Authors: Mendoza-Moreno F, Díez-Gago MR, Mínguez-García J, Tallón-Iglesias B, Zarzosa-Hernández G, Fernández S, Solana-Maoño M, Argüello-De-Andrés JM

Abstract
The most frequent presentation of esophageal cancer is adenocarcinoma and squamous cell carcinoma. In recent years, the latter has decreased its incidence increasing the adenocarcinoma. Currently, another type of tumor with a much lower incidence has been described, which has a neuroendocrine component along with another exocrine glandular component and has been classified since 2010 as mixed adenoneuroendocrine carcinoma (MANEC). We present the case of a 68-year-old male with a history of dyspepsia and epigastric pain who after performing a gastroscopy, was diagnosed with a malignant neoplasm of the esophagus. The patient underwent a total esophagectomy with reconstruction by tubular gastroplasty with cervical anastomosis. The final result of the piece after immunohistochemistry revealed that the tumor was composed of one component of adenocarcinoma in 60% together with another component compatible with neuroendocrine in 40%. With these findings and according to the World Health Organization classification of 2010 was diagnosed as esophageal MANEC. MANECs are rare tumors, described in other locations of the digestive tract, the esophagus being an infrequent location. Its preoperative diagnosis is difficult, and it is not until the final analysis of the complete piece by means of specific immunohistochemical techniques when its diagnosis can be established. Its treatment is fundamentally surgical, whereas the adjuvant therapeutic schemes with chemotherapy are not well defined at present because of their low incidence.

PMID: 30283226 [PubMed]

Primary Merkel cell carcinoma of the earlobe in a young healthy man.

Fetched: October 6th, 2018, 5:00am GMT

Primary Merkel cell carcinoma of the earlobe in a young healthy man.

Arch Craniofac Surg. 2018 Sep;19(3):205-209

Authors: Ha NH, Kim SK, Shin YS, Kim SM

Abstract
Merkel cell carcinoma (MCC) is an uncommon neuroendocrine cutaneous tumor with poor prognosis. It has the high rate of recurrence, mortality, regional nodal involvement, and distant metastases. It is difficult to diagnose MCC because of its non-specific clinical findings. It usually occurs on sun-exposed areas of the skin, mostly at head and neck. There is a difference in the incidence and prognosis according to site in the head and neck. However, there is no consented site-specific diagnosis, treatment or follow-up protocol for MCC at the head and neck. We herein report a case of MCC arising in the right earlobe of an otherwise healthy young man who has been diagnosed early, thereby successfully treated. With our closed follow-up, there was no tumor recurrence or complication at 33 months after diagnosis.

PMID: 30282431 [PubMed]

[Primary small cell neuroendocrine carcinoma of the tonsil: a case report].

Fetched: October 6th, 2018, 5:00am GMT

[Primary small cell neuroendocrine carcinoma of the tonsil: a case report].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2018 Sep;32(17):1354-1356

Authors: Zeng W, Tian KQ, Pan YY

Abstract
Neuroendocrine carcinoma(NEC) of the tonsil is extremely rare that exhibits highly malignant and poorly prognosis. Only a few of case reports and the optial treatment is still uncertain. Here, the current study presents a case of 60-year-old male with neck mass rapidly growing for four months. It was diagnosed a primary tonsil neuroendocrine carcinoma. And he was treated by one cycle of cisplatin and etoposide. It had no effect and the tumor was rapidly progressed. With review of the literatures, the nomenclature, clinicopathological characteristics and treatment modalities of this rare tumor are discussed.

PMID: 30282194 [PubMed]

[One case report of laryngeal large cell neuroendocrine carcioma].

Fetched: October 6th, 2018, 5:00am GMT

[One case report of laryngeal large cell neuroendocrine carcioma].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2018 Aug 05;32(15):1192-1193

Authors: Zhou YL, Wang Y

Abstract
The clinical data of large cell neuroendcrine carcinoma were analyzed retrospectively．The patient was a middle-age male,complained of throat pain for 10 years, it was misdiagnosed as chronic pharyngitis. The patient received tracheotomy, vertical laryngeal resection and left cervical lymph node dissection. Half month after surgery, the patient was transferred to the oncology department and remains under follow-up. Large cell neuroendcrine carcinoma is a rare malignant tumor, which is easily misdiagnosed. To Mastering its clinical features is important for the diagnosis and treatment.

PMID: 30282156 [PubMed]

Is Collaborative Ocular Melanoma Study (COMS) still relevant?

Fetched: October 6th, 2018, 5:00am GMT

Is Collaborative Ocular Melanoma Study (COMS) still relevant?

Indian J Ophthalmol. 2018 10;66(10):1385-1387

Authors: Honavar SG

PMID: 30249817 [PubMed - indexed for MEDLINE]

Failure of Classical β-Blocker Carvedilol to Deactivate Brown Adipose Tissue in a Patient With Pheochromocytoma.

Fetched: October 6th, 2018, 5:00am GMT

Failure of Classical β-Blocker Carvedilol to Deactivate Brown Adipose Tissue in a Patient With Pheochromocytoma.

Clin Nucl Med. 2018 Aug;43(8):604-605

Authors: Tsechelidis I, El Darazi E, Muteganya R, Weyts K, Goldman S

Abstract
A 37-year-old woman with pheochromocytoma underwent presurgical FDG PET/CT. Despite her usual antiadrenergic medication consisting in 25 mg of carvedilol, PET/CT demonstrated intense and widespread FDG uptake in brown adipose tissue (BAT). No BAT FDG uptake was detectable on a repeated examination after specific preparation consisting in 40 mg propranolol and 5 mg diazepam. We therefore recommend this propranolol-diazepam preparation in patients with pheochromocytoma referred for PET/CT. Carvedilol-classically prescribed to alleviate effects of adrenergic overstimulation-seems ineffective on BAT. This observation questions the benefit of carvedilol to reduce β3-adrenoreceptor-mediated effects, not only in BAT, but also in other tissues.

PMID: 29916915 [PubMed - indexed for MEDLINE]

Permalink for 'Brain Metastasis of Medullary Thyroid Carcinoma Without Macroscopic Calcification Detected First on 68Ga-Dotatate and Then on 18F-Fluoride PET/CT.'

Brain Metastasis of Medullary Thyroid Carcinoma Without Macroscopic Calcification Detected First on 68Ga-Dotatate and Then on 18F-Fluoride PET/CT.

Fetched: October 6th, 2018, 5:00am GMT

Brain Metastasis of Medullary Thyroid Carcinoma Without Macroscopic Calcification Detected First on 68Ga-Dotatate and Then on 18F-Fluoride PET/CT.

Clin Nucl Med. 2018 Aug;43(8):623-624

Authors: Duarte PS, Marin JFG, De Carvalho JWA, Sapienza MT, Buchpiguel CA

Abstract
We report a case of a medullary thyroid carcinoma noncalcified brain metastasis characterized on Ga-dotatate PET/CT but not on an F-fluoride PET/CT performed 1 month later. Subsequent F-fluoride PET/CT studies performed 7 and 19 months after the Ga-dotatate PET/CT study demonstrated focal uptake in the metastasis. The CT images of the last PET/CT study also depicted a small focus of calcification beginning in the metastatic site.

PMID: 29894334 [PubMed - indexed for MEDLINE]

Temporary suppression the sequestrated function of host macrophages for better nanoparticles tumor delivery.

Fetched: October 6th, 2018, 5:00am GMT

Temporary suppression the sequestrated function of host macrophages for better nanoparticles tumor delivery.

Drug Deliv. 2018 Nov;25(1):1289-1301

Authors: Hao J, Han T, Wang M, Zhuang Q, Wang X, Liu J, Wang Y, Tang H

Abstract
Orchestration of nanoparticles to achieve targeting has become the mainstream for efficient delivery of antitumor drugs. However, the low delivery efficiency becomes the biggest barrier for clinical translation of cancer nanomedicines, as most of them are sequestrated in the liver where more macrophages located in are responsible for capture of systemic administrated nanoparticles. In this study, we found that the depletion of the liver macrophages could lead to a superior improvement in the nanoparticles delivery. Firstly, we developed clodronate-containing liposomes (clodrolip) to transiently suppress the phagocytic function of macrophages, the residual macrophages in liver only accounted for less than 1% when the mice were treated with clodrolip in advance. In addition, the pharmacokinetics results of treatment with paclitaxel-poly(lactic-co-glycolic acid) (PTX-PLGA) nanoparticles disclosed that the AUC of PTX in the macrophages depletion group increased 2.11-fold. These results meant that the removal of macrophages would decrease the nanoparticles accumulation in the liver and better the biodistribution and bioavailability of nanoparticles delivery systems. Moreover, treatment of mice with melanoma by the combination of clodrolip and PTX-PLGA nanoparticles resulted in an elevated anti-tumor efficacy, the tumor inhibition ratio was nearly reached to 80%. Furthermore, these combinatorial regimens have demonstrated negligible toxicity in incidence of adverse effects. In conclusion, the encouraging results from this study inspire the generation of a rational strategy to focus on microenvironmental priming for modulation of innate immunity and to improve delivery efficiency of nanoparticles.

PMID: 29869519 [PubMed - indexed for MEDLINE]

Stereotactic body radiation therapy for heart-base tumors in six dogs.

Fetched: October 6th, 2018, 5:00am GMT

Stereotactic body radiation therapy for heart-base tumors in six dogs.

J Vet Cardiol. 2018 Jun;20(3):186-197

Authors: Magestro LM, Gieger TL, Nolan MW

Abstract
INTRODUCTION: Heart-base tumors are increasingly treated with radiotherapy, yet safety and efficacy are incompletely understood. This case series describes outcomes after stereotactic body radiation therapy (SBRT) for presumed chemodectoma.
ANIMALS: Six pet dogs.
METHODS: A retrospective study was performed, including dogs with a clinical diagnosis of chemodectoma and treatment with three-fraction SBRT (30 Gy total).
RESULTS: Heart-base tumors, presumed or confirmed to be chemodectomas, were diagnosed via histopathology or imaging. Treatment was delivered with intensity modulation and cone-beam computed tomography-based image guidance, using a linear accelerator and robotic couchtop. Intrafraction respiratory motion was managed with either neuromuscular blockade and breath-holding (n = 3) or high-frequency jet ventilation (n = 3); mean total anesthesia times for each technique were 165 and 91 min per fraction, respectively. Four tumors were assessed after SBRT; tumor volume decreased by 30-76%. Possible treatment-related complications included cough, tachyarrhythmias, and congestive heart failure. Two dogs experienced sudden death 150 and 294 days after SBRT. Three dogs are alive 408-751 days after SBRT, and one dog died of unrelated disease 1,228 days after SBRT.
CONCLUSIONS: This SBRT protocol resulted in rapid tumor volume reduction, and jet ventilation effectively reduced treatment delivery times. However, cardiac arrhythmias (presumably tumor or treatment associated) and sudden death were common after SBRT. Therefore, SBRT is a potentially useful treatment but may not be appropriate for dogs with incidentally diagnosed, slowly growing tumors, which are not causing cardiovascular disturbances. Longer follow-up and larger case numbers are needed to more completely define safety and impact of treatment on long-term survivability.

PMID: 29724584 [PubMed - indexed for MEDLINE]

Gamma irradiation of ocular melanoma and lymphoma cells in the presence of gold nanoparticles: in vitro study.

Fetched: October 6th, 2018, 5:00am GMT

Gamma irradiation of ocular melanoma and lymphoma cells in the presence of gold nanoparticles: in vitro study.

J Appl Clin Med Phys. 2018 May;19(3):268-275

Authors: Kanavi MR, Asadi S, Balagholi S, Alikarami F, Nosrati H, Ahmadieh H

Abstract
The aim of this work was to determine whether conjugation of cultivated choroidal melanoma and Burkitt's lymphoma cells with gold nanoparticles (GNPs) is beneficial for these series of ocular cancer patients. GNPs are radiosensitizers and can sensitize tumors to radiotherapy.This application has been examined in several tumor types, but not in choroidal melanoma. This study shows the results of in vitro study on the choroidal melanoma and also Burkitt's lymphoma cells in the presence of GNPs during continuous gamma irradiation. Cytotoxicity of GNPs were assessed for five different concentrations then cultured melanoma and Burkitt's lymphoma cells were irradiated with a Gamma source in the presence and absence of NPs. Incubation of melanoma cells with GNP concentrations below 100 μg/ml, accompanied by gamma irradiation, increased cell death (P value = 0.016) . In the absence of irradiation, GNPs at these concentrations did not affect cultured melanoma cell metabolism. Reduced cell viability resulted from a significant increase in absorbed energy by the tumor. Moreover, GNP concentrations higher than 200 μg/ml induced cytotoxicity in melanoma cells. Cytotoxicity assay in GNPs-loaded Burkitt's lymphoma cells showed a slight decrease in cell viability at 50 μg/ml and clear cytotoxicity at concentrations higher than 100 μg/ml (P value = 0.035). Concentration and proper injection doses of GNPs in sensitive tissues such as the human eye are important variables yet to be determined.This is the first report of choroidal melanoma dosimetry performed in the presence of GNPs and provides valuable insights into future therapeutic approaches. Further in vitro study with more different sizes and concentrations is needed to determine the optimum size and concentration before any clinical research in this regard.

PMID: 29707895 [PubMed - indexed for MEDLINE]

Permalink for 'A promising combination: electrical impedance spectroscopy added at baseline visit to short-term sequential digital dermoscopy.'

A promising combination: electrical impedance spectroscopy added at baseline visit to short-term sequential digital dermoscopy.

Fetched: October 6th, 2018, 5:00am GMT

A promising combination: electrical impedance spectroscopy added at baseline visit to short-term sequential digital dermoscopy.

Br J Dermatol. 2017 11;177(5):1166-1167

Authors: Tromme I

PMID: 29192982 [PubMed - indexed for MEDLINE]

Very low expression of PD-L1 in medullary thyroid carcinoma.

Fetched: October 6th, 2018, 5:00am GMT

Very low expression of PD-L1 in medullary thyroid carcinoma.

Endocr Relat Cancer. 2017 06;24(6):L35-L38

Authors: Bongiovanni M, Rebecchini C, Saglietti C, Bulliard JL, Marino L, de Leval L, Sykiotis GP

PMID: 28420659 [PubMed - indexed for MEDLINE]

Pernicious Anaemia with Gastric Carcinoids.

Fetched: October 6th, 2018, 5:00am GMT

Pernicious Anaemia with Gastric Carcinoids.

J Assoc Physicians India. 2016 07;64(7):76-77

Authors: Basha SJ, Shetty NR, Devarbhavi H

Abstract
We report the case of a 42 year male with history of chronic anaemia who was found to have pernicious anaemia with beta thalassemia trait and had on esophago-gastric-duodenoscopy, gastric carcinoids with gastric atrophy. Pernicious anaemia and gastric carcinoids occurring simultaneously in a single individual is rare. Our case emphasises the need for esophago-gastric-duodenoscopy in cases of pernicious anaemia.

PMID: 27759350 [PubMed - indexed for MEDLINE]

Practice-based evidence for the clinical benefit of PET/CT-results of the first oncologic PET/CT registry in Germany.

Fetched: October 2nd, 2018, 5:00am GMT

Practice-based evidence for the clinical benefit of PET/CT-results of the first oncologic PET/CT registry in Germany.

Eur J Nucl Med Mol Imaging. 2018 Sep 29;:

Authors: Pfannenberg C, Gueckel B, Wang L, Gatidis S, Olthof SC, Vach W, Reimold M, la Fougere C, Nikolaou K, Martus P

Abstract
PURPOSE: The purpose of this study was to evaluate the impact of PET/CT on clinical management of cancer patients based on a prospective data registry. The study was developed to inform consultations with public health insurances on PET/CT coverage.
METHODS: We evaluated a prospective patient cohort having a clinically indicated PET/CT at a single German University Center from April 2013 to August 2016. The registry collected questionnaire data from requesting physicians on intended patient management before and after PET/CT. A total of 4,504 patients with 5,939 PET/CT examinations were enrolled in the registry, resulting in evaluable data from 3,724 patients receiving 4,754 scans. The impact of PET/CT on patient management was assessed across 22 tumor types, for different indications (diagnosis, staging, suspected recurrence) and different categories of management including treatment (curative or palliative) and non-treatment (watchful waiting, additional imaging, invasive tests).
RESULTS: The most frequent PET/CT indication was tumor staging (59.7%). Melanoma, lung cancer, lymphoma, neuroendocrine tumor and prostate cancer accounted for 70% of cases. Overall, the use of PET/CT resulted in a 37.1% change of clinical management (95% CI, 35.7-38.5), most frequently (30.6%) from an intended non-treatment strategy before PET/CT to active treatment after PET/CT. The frequency of changes ranged from 28.3% for head and neck cancers up to 46.0% for melanomas. The impact of PET/CT was greatest in reducing demands for additional imaging which decreased from 66.1% before PET/CT to 6.1% after PET/CT. Pre-PET/CT planned invasive tests could be avoided in 72.7% of cases. The treatment goal changed after PET/CT in 21.7% of cases, in twice as many cases from curative to palliative therapy than vice versa.
CONCLUSIONS: The data of this large prospective registry confirm that physicians often change their intended management on the basis of PET/CT by initiating treatment and reducing additional imaging as well as invasive tests. This applies to various cancer types and indications.

PMID: 30269155 [PubMed - as supplied by publisher]

Potential Novel Therapy Targets in Neuroendocrine Carcinomas of the Breast.

Fetched: October 2nd, 2018, 5:00am GMT

Potential Novel Therapy Targets in Neuroendocrine Carcinomas of the Breast.

Clin Breast Cancer. 2018 Sep 05;:

Authors: Vranic S, Palazzo J, Sanati S, Florento E, Contreras E, Xiu J, Swensen J, Gatalica Z

Abstract
INTRODUCTION: Neuroendocrine carcinoma (NEC) of the breast is a rare, special type of breast cancer, reportedly constituting 2% to 5% of all breast cancers. Although breast NEC does not have a specific targeted therapy, several new targeted therapies based on specific biomarkers were recently investigated in the NEC of lung and in other types of breast carcinoma, which may provide guidance to their feasibility in breast NEC.
MATERIALS AND METHODS: Twenty breast NECs were profiled for biomarkers of therapy including antibody-drug conjugates (DLL3, TROP-2, and FOLR1), histone deacetylase (H3K36Me3) inhibitors, tropomyosin receptor kinases (NTRK1/2/3 gene fusions) targeted inhibitors, alkylating agents (MGMT), and immune checkpoint inhibitors (PD-L1, TMB, and MSI) using immunohistochemistry and DNA/RNA next-generation sequencing assays.
RESULTS: Predictive expression of TROP-2, FOLR1, and H3K36Me3 were detected in different subsets of tumors and may pave the way for development of novel targeted therapies in some patients with breast NECs. There was no evidence of DLL3 expression, NTRK gene fusions, or MGMT hypermethylation. No biomarkers predictive of immune checkpoint inhibitor efficacy (programmed death-ligand 1 expression, tumor mutational burden, microsatellite instability) were identified. FGFR and CCND1 gene amplifications were detected in isolated cases.
CONCLUSIONS: This study identified several potential targets for novel therapies in breast NEC, including farletuzumab and mirvetuximab soravtansine (FOLR1), sacituzumab govitecan (TROP-2), and HDAC inhibitors (H3K36Me3). In some cases, CCND1 gene amplification may indicate the usefulness of investigational therapies. The reported results should serve as an early indication of potential clinical relevance in selected patients with breast NEC.

PMID: 30268765 [PubMed - as supplied by publisher]

[WSPÓŁCZESNA DIAGNOSTYKA NOWOTWORÓW NEUROENDOKRYNNYCH Current diagnostics of neuroendocrine tumors].

Fetched: October 1st, 2018, 5:00am GMT

[WSPÓŁCZESNA DIAGNOSTYKA NOWOTWORÓW NEUROENDOKRYNNYCH Current diagnostics of neuroendocrine tumors].

Wiad Lek. 2018;71(6):1267-1274

Authors: Bober B, Zaleska M, Kowalski Ł, Zaręba K, Saracyn M

Abstract
Neuroendocrine tumors (NEN) are rarely diagnosed neoplasms, which frequency is estimated on about 35 cases/100 000. During last 30 years the number of NEN's new diagnosis increased five-times and nowadays reaches 5,86/100 000/year. It is partially associated with increasing detectability of these tumors. Such diagnostic methods as capsule endoscopy and positron emission tomography are becoming increasingly widely accessible. Though, one should bear in mind that in case of patients diagnosed with NEN cooperation between specialists in different fields of medicine, such as endocrinology, nuclear medicine, oncology, radiology, internal medicine and surgery is needed.

PMID: 30267512 [PubMed - in process]

Permalink for 'Clinical outcomes of patients with G1/G2 neuroendocrine tumors arising from foregut or hindgut treated with somatostatin analogs: a retrospective study.'

Clinical outcomes of patients with G1/G2 neuroendocrine tumors arising from foregut or hindgut treated with somatostatin analogs: a retrospective study.

Fetched: October 1st, 2018, 5:00am GMT

Clinical outcomes of patients with G1/G2 neuroendocrine tumors arising from foregut or hindgut treated with somatostatin analogs: a retrospective study.

Invest New Drugs. 2018 Sep 28;:

Authors: Ida H, Honma Y, Hirano H, Shoji H, Iwasa S, Okita N, Takashima A, Kato K, Fukuda T, Boku N

Abstract
Neuroendocrine tumors (NET) are rare tumors for which somatostatin analogs (SSA) are used not only for symptom control due to a functioning tumor, but also for the disease control of unresectable NET. The efficacy of SSA for midgut NET has been verified by previous studies, but insufficient evidence exists for SSA treatment of NET in the foregut and hindgut (F/H-NET). The aim of this retrospective study was to evaluate the efficacy of SSA for unresectable F/H-NET. Patients with unresectable F/H-NET treated with SSA between February 2011 and August 2017 at our hospital were retrospectively reviewed. Parameters of efficacy were progression-free survival (PFS), overall survival, objective response rate (ORR), and adverse events. Twelve cases with unresectable F/H-NET were extracted from our database. With a median follow-up time of 25.9 months, the median PFS was 13.6 months. Two- and 3-year survival rates were 87.5 and 62.5%, respectively. The ORR was 8.3%, and the disease control rate was 75%. Serious adverse events were not observed. Subgroup analysis, including G1/G2, and hepatic tumor load, which is the volume of NET liver metastases, did not reveal a difference in PFS. The efficacy and safety of SSA for F/H-NET seemed similar to that found in the PROMID study, highlighting its relevance for the treatment of this disease.

PMID: 30267338 [PubMed - as supplied by publisher]

Nutrition and neuroendocrine tumors: An update of the literature.

Fetched: October 1st, 2018, 5:00am GMT

Nutrition and neuroendocrine tumors: An update of the literature.

Rev Endocr Metab Disord. 2018 Sep 29;:

Authors: Altieri B, Barrea L, Modica R, Muscogiuri G, Savastano S, Colao A, Faggiano A

Abstract
Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms with worldwide increasing incidence, high prevalence and survival. Both the tumor itself and the systemic therapy may have an impact on patients' nutrition. Malnutrition negatively impacts on outcome in NETs patients. Moreover, it has been demonstrated that body mass index was a risk factor for NET development and that metabolic syndrome was associated with worse prognosis in these patients. Of note, food could also interact with the metabolism of oral target therapy and antineoplastic agents used for the treatment of progressive NETs. Therefore, the nutritional assessment, based on body composition, and lifestyle modifications should be an integral component of management of the NET patients. The nutrition care plans are an integral part of the multidisciplinary management team for patients with NETs. Nutritionists with expertise in NETs can provide dietary approaches to improve the quality of life and nutritional status during various therapeutic modalities used in patients with NETs. The aim of this review is to critically discuss the importance of nutrition and body composition in patients with NETs.

PMID: 30267297 [PubMed - as supplied by publisher]

Permalink for 'Is endoscopic ultrasonography more sensitive than magnetic resonance imaging in detecting and localizing pancreatic neuroendocrine tumors?'

Is endoscopic ultrasonography more sensitive than magnetic resonance imaging in detecting and localizing pancreatic neuroendocrine tumors?

Fetched: October 1st, 2018, 5:00am GMT

Is endoscopic ultrasonography more sensitive than magnetic resonance imaging in detecting and localizing pancreatic neuroendocrine tumors?

Rev Endocr Metab Disord. 2018 Sep 29;:

Authors: Kann PH

Abstract
To compare endoscopic ultrasonography (EUS) and magnetic resonance imaging (MRI) in terms of their sensitivities to localize pancreatic neuroendocrine tumors (pNET) preoperatively. Systematic analysis of the literature; sensitivity of EUS and MRI in insulinomas and pancreaticoduodenal NETs in multiple endocrine neoplasia type 1 (MEN1) in series of at least 20 subjects referring to tumors confirmed by surgery and histopathology. Other imaging methods reported were also assessed. Eighteen publications on insulinomas (782 cases) could be analyzed, no study in MEN1 fulfilled the inclusion criteria and compared EUS to MRI. Data quality was moderate: all publications referred to case series. Mean correct detection / localization rates (sensitivity) were calculated: EUS 80%, MRI 66%, computed tomography 63%, angiography 52%, somatostatin receptor scintigraphy 42%, ultrasonography 23%; arterial calcium stimulation with hepatic venous sampling regionalized correctly in 80%. EUS seems to be more sensitive than MRI in localizing pancreatic neuroendocrine tumors. If a specialized endosonographist is available, EUS is the preferable imaging procedure. Otherwise, MRI is a suitable alternative.

PMID: 30267296 [PubMed - as supplied by publisher]

Permalink for 'Salvage peptide receptor radionuclide therapy with [177Lu-DOTA,Tyr3]octreotate in patients with bronchial and gastroenteropancreatic neuroendocrine tumours.'

Salvage peptide receptor radionuclide therapy with [177Lu-DOTA,Tyr3]octreotate in patients with bronchial and gastroenteropancreatic neuroendocrine tumours.

Fetched: October 1st, 2018, 5:00am GMT

Salvage peptide receptor radionuclide therapy with [177Lu-DOTA,Tyr3]octreotate in patients with bronchial and gastroenteropancreatic neuroendocrine tumours.

Eur J Nucl Med Mol Imaging. 2018 Sep 28;:

Authors: van der Zwan WA, Brabander T, Kam BLR, Teunissen JJM, Feelders RA, Hofland J, Krenning EP, de Herder WW

Abstract
PURPOSE: Therapy with [177Lu-DOTA,Tyr3]octreotate is effective in patients with grade I/II metastasized and/or inoperable bronchial neuroendocrine tumour (NET) or gastroenteropancreatic NET (GEP-NET). In this study, we investigated the efficacy and safety of salvage treatment with [177Lu-DOTA,Tyr3]octreotate.
METHODS: Patients with progressive bronchial NET or GEP-NET were selected for re-(re)treatment if they had benefited from initial peptide receptor radionuclide therapy (I-PRRT) with a minimal progression-free survival (PFS) of 18 months. Patients received an additional cumulative dose of 14.8 GBq of [177Lu-DOTA,Tyr3]octreotate over two cycles per retreatment with PRRT (R-PRRT) or re-retreatment with PRRT (RR-PRRT).
RESULTS: The safety and efficacy analyses included 181 patients and 168 patients, respectively, with bronchial NET or GEP-NET. Overall median follow-up was 88.6 months (95% CI 79.0-98.2). Median cumulative doses were 44.7 GBq (range 26.3-46.4 GBq) during R-PRRT (168 patients) and 59.7 GBq (range 55.2-≤60.5 GBq) during RR-PRRT (13 patients). Objective response and stable disease, as best response, were observed in 26 patients (15.5%) and 100 patients (59.5%) following R-PRRT, and in 5 patients (38.5%) and 7 patients (53.8%) following RR-PRRT, respectively. Median PFS was 14.6 months (95% CI 12.4-16.9) following R-PRRT and 14.2 months (95% CI 9.8-18.5) following RR-PRRT. Combined overall survival (OS) after I-PRRT plus R-PRRT and RR-PRRT was 80.8 months (95% CI 66.0-95.6). Grade III/IV bone marrow toxicity occurred in 6.6% and 7.7% of patients after R-PRRT and RR-PRRT, respectively. Salvage therapy resulted in a significantly longer OS in patients with bronchial NET, GEP-NET and midgut NET than in a nonrandomized control group. The total incidence of acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) was 2.2%. No PRRT-related grade III/IV nephrotoxicity was observed.
CONCLUSION: A cumulative dose of up to 60.5 GBq salvage PRRT with [177Lu-DOTA,Tyr3]octreotate is safe and effective in patients with progressive disease (relapse-PD) following I-PRRT with [177Lu-DOTA,Tyr3]octreotate. Safety appears similar to that of I-PRRT as no higher incidence of AML or MDS was observed. No grade III/IV renal toxicity occurred after retreatment.

PMID: 30267116 [PubMed - as supplied by publisher]

Radioguided Surgery With Gallium 68 Dotatate for Patients With Neuroendocrine Tumors.

Fetched: October 1st, 2018, 5:00am GMT

Radioguided Surgery With Gallium 68 Dotatate for Patients With Neuroendocrine Tumors.

JAMA Surg. 2018 Sep 26;:

Authors: El Lakis M, Gianakou A, Nockel P, Wiseman D, Tirosh A, Quezado MA, Patel D, Nilubol N, Pacak K, Sadowski SM, Kebebew E

Abstract
Importance: Neuroendocrine tumors (NETs) express somatostatin receptors, which can be targeted with radiolabeled peptides. In a variety of solid tumors, radioguided surgery (RGS) has been used to guide surgical resection. Gallium 68 (68Ga) dota peptides have been shown to be more accurate than other radioisotopes for detecting NETs. A pilot study previously demonstrated the feasibility and safety of 68Ga-dotatate RGS for patients with NETs.
Objective: To evaluate what intraoperative techniques and thresholds define positive lesions that warrant resection during 68Ga-dotatate RGS.
Design, Setting, and Participants: This prospective cohort study, conducted between October 23, 2013, and February 14, 2018, included 44 patients with NETs who underwent 68Ga-dotatate RGS.
Intervention: Gallium 68-dotatate RGS.
Main Outcomes and Measures: The in vivo and ex vivo tumor to background ratio (TBR) was assessed for resected lesions and correlated with the histopathologic findings.
Results: Forty-four patients (22 women and 22 men; mean [SD] age, 51.0 [13.7] years) had 133 lesions detected on preoperative imaging scans, with a diagnosis of a pancreatic NET (19 of 44 [43%]), gastrointestinal NET (22 of 44 [50%]), and pheochromocytoma or paraganglioma (3 of 44 [7%]). The TBR was obtained by normalizing to the omentum (106 of 133 [79.7%]) or other solid organs (27 of 133 [20.3%]). The omentum had a significantly lower mean (SD) count than other solid organs for background count activity 3 hours after injection (22.1 [17.0] vs 34.5 [39.0]; P < .001). The lesions containing NETs had a higher TBR than those that did not contain NETs (18.9 vs 4.4; P < .001). On a receiver operating characteristic curve analysis, a TBR of 2.5 had a sensitivity of 90% and a specificity of 25%, and a TBR of 16 had a sensitivity of 54% and a specificity of 81%.
Conclusions and Relevance: A TBR of 2.5 or greater is a highly sensitive threshold for indicating a lesion to be consistent with a NET on histologic findings and thus warranting surgical resection. The omentum should be used as the background count activity for 68Ga-dotatate RGS for patients with abdominal NETs.

PMID: 30267071 [PubMed - as supplied by publisher]

Radioguided Surgery With Gallium for Neuroendocrine Tumors.

Fetched: October 1st, 2018, 5:00am GMT

Radioguided Surgery With Gallium for Neuroendocrine Tumors.

JAMA Surg. 2018 Sep 26;:

Authors: Howe JR

PMID: 30267062 [PubMed - as supplied by publisher]

Aggressive resection of neuroendocrine tumor (NET) liver metastases: NET neutral or gain?

Fetched: October 1st, 2018, 5:00am GMT

Aggressive resection of neuroendocrine tumor (NET) liver metastases: NET neutral or gain?

Surgery. 2018 Sep 25;:

Authors: Cisco R, Lin D, Kebebew E

PMID: 30266442 [PubMed - as supplied by publisher]

Intratumoral Heterogeneity of Bladder Cancer by Molecular Subtypes and Histologic Variants.

Fetched: October 1st, 2018, 5:00am GMT

Intratumoral Heterogeneity of Bladder Cancer by Molecular Subtypes and Histologic Variants.

Eur Urol. 2018 Sep 25;:

Authors: Warrick JI, Sjödahl G, Kaag M, Raman JD, Merrill S, Shuman L, Chen G, Walter V, DeGraff DJ

Abstract
Molecular subtyping may inform on prognosis and treatment response in bladder cancer. However, intratumoral molecular heterogeneity is not well studied in this disease and could complicate efforts to use molecular subtyping to guide patient management. To investigate intratumoral heterogeneity in bladder cancer, we examined molecular subtypes in a consecutive, retrospective cystectomy series of histologic variant bladder cancers and conventional urothelial carcinomas co-occurring with them. Molecular subtypes were assigned as per the approach reported by Lund University, an approach that incorporates cell cycle alterations and markers of differentiation, to give the urothelial-like, genomically unstable, basal-squamous, mesenchymal-like, and neuroendocrine-like subtypes. The majority (93%) of tumors were classified as urothelial like, genomically unstable, or basal squamous. Among patients with more than one tumor histology, 39% demonstrated molecular heterogeneity among the different tumor histologies. This was greatest for the basal-squamous subtype, 78% of which co-occurred with either urothelial-like or genomically unstable carcinoma (among cases with multiple histologies). In contrast, there was no co-occurrence of urothelial-like and genomically unstable carcinoma in the same patient. The findings indicate that bladder cancer is often molecularly heterogeneous, particularly in the basal-squamous subtype. This raises the concern for sampling error in laboratory tests that guide therapy based on molecular subtyping. Patient summary: In this report, we investigated molecular diversity among different areas from the same tumor in patients with bladder cancer. We found that different areas from the same tumor are often molecularly different. We conclude that this biological diversity must be taken into account when interpreting clinical molecular tests performed on bladder cancer samples.

PMID: 30266310 [PubMed - as supplied by publisher]

Type 2 diabetes in neuroendocrine tumors: are biguanides and statins part of the solution?

Fetched: September 30th, 2018, 5:00am GMT

Type 2 diabetes in neuroendocrine tumors: are biguanides and statins part of the solution?

J Clin Endocrinol Metab. 2018 Sep 27;:

Authors: Herrera-Martínez AD, Pedraza-Arevalo S, L-López F, Gahete MD, Gálvez-Moreno MA, Castaño JP, Luque RM

Abstract
Background: Biguanides and statins have been reported to exert beneficial effects on various cancer types. However, their precise effects and underlying molecular mechanisms are still poorly understood.
Materials and Methods: We analyzed the relation between metabolic-syndrome, i.e., presence of type-2 diabetes (T2DM), hyperlipidemia and their treatment, with histological, epidemiological, and prognosis variables in two patient cohorts with neuroendocrine-tumors [NETs: lung-carcinoids (LCs; n=81) and gastro-entero-pancreatic (GEP-NET; n=100)]. Additionally, we investigated the antitumoral effects of different biguanides and statins by evaluating proliferation/migration/secretion/gene-expression and involved molecular pathways using BON1/QGP1-cell cultures.
Results: In T2DM patients, pleura invasion was higher (LCs group; p<0.05) and tumor diameter tended to be increased (GEP-NET group). mRNA levels of somatostatin and ghrelin systems were different in tumor tissue of T2DM patients with and without metformin. Biguanides (metformin/buformin/phenformin) decreased proliferation rate in BON1/QGP1-cells (24-72h). However, the effects of statins on proliferation-rate were dependent of the statin-type, cell-type, and time. Specifically, only simvastatin/atorvastatin decreased proliferation in BON1-cells (48/72h and 72h, respectively), while all statins decreased proliferation rate in QGP1-cells (48/72h). Remarkably, metformin and simvastatin decreased migration capacity in BON1-cells and biguanides decreased serotonin secretion in BON1-cells. Phenformin increased apoptosis in BON1/QGP1-cells, and simvastatin in QGP1-cells. These antitumor effects likely involved altered expression of key genes related to cancer aggressiveness (i.e. GLUT4, INSR). Altogether, our results reveal a clear inhibitory effect of biguanides and statins on NET-cell aggressiveness.
Conclusion: Given the demonstrated clinical safety of these drugs, our results invite to further explore their potential therapeutic role for the treatment of NET patients.
Precis: Clinical/molecular changes in patients with T2DM and NETs reversed in metformin treated patients. Biguanides/statins altered aggressiveness features (proliferation, apoptosis, etc.) in NET cells.

PMID: 30265346 [PubMed - as supplied by publisher]

Permalink for 'The incidence and survival of pancreatic cancer by histology, including rare subtypes: a nation-wide cancer registry-based study from Taiwan.'

The incidence and survival of pancreatic cancer by histology, including rare subtypes: a nation-wide cancer registry-based study from Taiwan.

Fetched: September 30th, 2018, 5:00am GMT

The incidence and survival of pancreatic cancer by histology, including rare subtypes: a nation-wide cancer registry-based study from Taiwan.

Cancer Med. 2018 Sep 27;:

Authors: Chang JS, Chen LT, Shan YS, Chu PY, Tsai CR, Tsai HJ

Abstract
Studies have indicated a significant rise in the incidence of pancreatic adenocarcinoma. However, the epidemiology of other rare histologic subtypes of pancreatic cancer is not well understood. This study analyzed the incidence and survival of pancreatic cancer in Taiwan by histologic subtype, sex, age group, and year of diagnosis. The incidence trends of pancreatic cancer in Taiwan from 2002 to 2013 were calculated using data from the Taiwan Cancer Registry. The survival of pancreatic cancer patients was assessed using the life-table method and Cox proportional hazards analysis. The incidence of pancreatic cancer increased from 4.62 per 100,000 in 2002 to 6.04 per 100,000 in 2013 in Taiwan. The most common histologic subtype of pancreatic cancer was adenocarcinoma followed by carcinoma and neuroendocrine tumors (NETs). Adenocarcinoma and NETs showed a rapid increase in incidence, while the incidences of other subtypes did not change significantly. Patients with adenocarcinoma showed a poor survival with a 5-year survival of 5.2%. Patients with endocrinomas, NETs, and lymphoma displayed a better survival than those with adenocarcinoma, with a 5-year survival ranging from 41.8% to 59.1%. The survival of adenocarcinoma, lymphoma, and NETs improved after the introduction of novel therapies. Understanding the risk factors and identifying the biomarkers for the early diagnosis of pancreatic cancer are important to prevent the development and improve the survival of pancreatic cancer.

PMID: 30264519 [PubMed - as supplied by publisher]

Prognostic factors for death after surgery for small intestinal neuroendocrine tumours.

Fetched: September 30th, 2018, 5:00am GMT

Prognostic factors for death after surgery for small intestinal neuroendocrine tumours.

BJS Open. 2018 Sep;2(5):345-352

Authors: Eriksson J, Garmo JEH, Ihre-Lundgren C, Hellman P

Abstract
Background: Neuroendocrine tumours of the small intestine (SI-NETs) are rare gastrointestinal neoplasms with an annual incidence of about one per 100 000. Patients with apparently similar tumours have variable outcomes. The aim of this study was to identify postoperative prognostic factors identifiable after initial surgery.
Methods: This was a nested case-control study of patients with SI-NETs who were treated between 1961 and 2001. Data were retrieved from the Swedish Cancer Registry. Patients who died from the SI-NET and corresponding controls (who outlived cases by at least 1 month), matched by age at diagnosis and calendar period, were included. Sex, postoperative symptoms, postoperative 5-hydroxyindoleacetic acid (5-HIAA) values, European Neuroendocrine Tumor Society (ENETS) stage, insufficiency of the tricuspid valve, radical secondary surgery and secondary malignancy were studied as potential prognostic factors.
Results: In total, 1122 patients were included (561 cases, 561 controls). Postoperative factors of prognostic importance included hormone-related symptoms, stage IV disease, raised levels of 5-HIAA, insufficiency of the tricuspid valve, secondary surgery not being macroscopically radical and a second malignancy.
Conclusion: Stage and symptomatic disease are important prognostic factors in SI-NET.

PMID: 30263986 [PubMed]

Permalink for 'Neuroendocrine differentiation contributes to radioresistance development and metastatic potential increase in non-small cell lung cancer.'

Neuroendocrine differentiation contributes to radioresistance development and metastatic potential increase in non-small cell lung cancer.

Fetched: September 30th, 2018, 5:00am GMT

Neuroendocrine differentiation contributes to radioresistance development and metastatic potential increase in non-small cell lung cancer.

Biochim Biophys Acta Mol Cell Res. 2018 Sep 15;1865(12):1878-1890

Authors: Zhu R, Yang X, Xue X, Shen M, Chen F, Chen X, Tsai Y, Keng PC, Chen Y, Lee SO, Chen Y

Abstract
Radiation treatment induces neuroendocrine differentiation (NED) in non-small cell lung cancer (NSCLC) A549 and H157 cells, so higher NE-like features in radioresistant A549 (A549R26-1) and H157 (H157R24-1) cells are observed than in parental cells. We detected higher NED marker expressions in A549R26-1 cell-derived tumors than in A549 cell-derived tumors. In mechanism studies, we found that NED induction in A549R26-1 and H157R24-1 cells was accompanied by increased intracellular cAMP and IL-6 levels. Treatment of radioresistant lung cancer cells with the inhibitor (SQ22536) of adenylate cyclase (AC) which is the enzyme responsible for the cAMP production, or the neutralizing antibody (Ab) of IL-6, resulted in decreased NE-like features in radioresistant lung cancer cells. In addition, we found MEK/Erk is the signaling pathway that triggers the cAMP- and IL-6-mediated NED induction in radioresistant lung cancer cells. Also, we found that MEK/Erk signaling pathway inhibition decreased NED in radioresistant cells. Radioresistant lung cancer cells exhibiting high NE-like features also showed higher radioresistance and higher metastatic potential than parental cells. When we inhibited cAMP-, or IL-6-mediated pathways, or the downstream MEK/Erk signaling pathway, radiosensitivity of radioresistant lung cancer cells was significantly increased and their metastatic potential was significantly reduced. In in vivo mouse studies, reducing NED by treating mice with the MEK/Erk inhibitor increased radiosensitivity. Immunohistochemical staining of tumor tissues lowered expressions of the NED/epithelial-mesenchymal transition (EMT)/metastatic markers when mice were treated with the MEK/Erk inhibitor.

PMID: 30262435 [PubMed - as supplied by publisher]

Permalink for 'Comparative study of phototoxicity of protoporphyrin IX synthetic and extracted from ssp Rattus novergicus albinus rats toward murine melanoma cells.'

Comparative study of phototoxicity of protoporphyrin IX synthetic and extracted from ssp Rattus novergicus albinus rats toward murine melanoma cells.

Fetched: September 27th, 2018, 5:00am GMT

Comparative study of phototoxicity of protoporphyrin IX synthetic and extracted from ssp Rattus novergicus albinus rats toward murine melanoma cells.

Eur Biophys J. 2018 Sep;47(6):601-609

Authors: Reis ER, Ferreira LP, Nicola EMD, Borissevitch I

Abstract
Protoporphyrin IX (PpIX) is a precursor of heme synthesis and is known to be an active photosensitizer and precursor of photosensitizers applied in photodynamic therapy (PDT) and photodynamic diagnostics (PDD). On irradiation with visible light, PpIX undergoes phototransformation, producing photoproducts which may also be phototoxic and increase its efficacy. The mechanism of PpIX phototransformation depends on environmental characteristics and can be different in vitro and in vivo. In this paper, we present a comparative study of the photoactivity of synthetic PpIX and PpIX extracted from the Harderian gland of ssp Rattus novergicus albinus rats, along with their photoproducts toward murine B16F-10 melanoma cells. It was observed that when irradiated with visible light the endogenous PpIX demonstrates photocytotoxicity ten times higher than the synthetic PpIX. The photoproduct of endogenous PpIX also possesses phototoxicity, though slightly lower than that of PpIX itself. The rate of cell internalization for both endogenous PpIX and its photoproduct was eightfold greater than that obtained for the synthetic porphyrin. This difference might result from a complexation of the native PpIX with some amphiphilic compounds during its synthesis within the Harderian glands, which facilitates the cell uptake of PpIX. Fluorescence microscopy images show that both endogenous and synthetic porphyrins are localized after uptake predominantly in the mitochondrial region of cells.

PMID: 29453611 [PubMed - indexed for MEDLINE]

Efficacy and safety of metyrosine in pheochromocytoma/paraganglioma: a multi-center trial in Japan.

Fetched: September 27th, 2018, 5:00am GMT

Efficacy and safety of metyrosine in pheochromocytoma/paraganglioma: a multi-center trial in Japan.

Endocr J. 2018 Mar 28;65(3):359-371

Authors: Naruse M, Satoh F, Tanabe A, Okamoto T, Ichihara A, Tsuiki M, Katabami T, Nomura M, Tanaka T, Matsuda T, Imai T, Yamada M, Harada T, Kawata N, Takekoshi K

Abstract
To assess the efficacy, safety, and pharmacokinetics of metyrosine (an inhibitor of catecholamine synthesis) in patients with pheochromocytoma/paraganglioma (PPGL), we conducted a prospective, multi-center, open-label study at 11 sites in Japan. We recruited PPGL patients aged ≥12 years requiring preoperative or chronic treatment, receiving α-blocker treatment, having baseline urinary metanephrine (uMN) or normetanephrine (uNMN) levels ≥3 times the upper limit of normal values, and having symptoms associated with excess catecholamine. Metyrosine treatment was started at 500 mg/day and modified according to dose-adjustment criteria up to 4,000 mg/day. The main outcome measure was the proportion of patients who achieved at least 50% reduction in uMN or uNMN levels from baseline. Sixteen patients (11 males/5 females) aged 12-86 years participated. After 12 weeks of treatment and at the last evaluation of efficacy, the primary endpoint was achieved in 31.3% of all patients, including 66.7% of those under preoperative treatment and 23.1% of those under chronic treatment. Sedation, anemia, and death were reported in 1 patient each as serious adverse drug reactions during the 24-week treatment. Metyrosine was shown to be tolerated and to relieve symptoms by reducing excess catecholamine in PPGL patients under both preoperative and chronic treatment.

PMID: 29353821 [PubMed - indexed for MEDLINE]

Paraganglioma as a risk factor for bone metastasis.

Fetched: September 27th, 2018, 5:00am GMT

Paraganglioma as a risk factor for bone metastasis.

Endocr J. 2018 Mar 28;65(3):253-260

Authors: Yokomoto-Umakoshi M, Umakoshi H, Tsuiki M, Ogasawara T, Hamanaka-Hiroshima K, Tanabe A, Tagami T, Shimatsu A, Naruse M

Abstract
Malignant pheochromocytoma (PHEO) and paraganglioma (PGL) (PHEO and PGL: PPGL) are frequently associated with bone metastasis. Bone metastasis requires long-term management and may lead to skeletal-related events (SREs) that remarkably reduce patients' quality of life (QOL). The aim of this study was to elucidate the risk factors for developing bone metastasis in patients with PPGL. The medical records of 40 consecutive adult patients with malignant PPGL at the National Hospital Organization Kyoto Medical Center between 2006 and 2016 were reviewed. SREs were defined as pathologic fracture, spinal cord compression, and the need for bone irradiation and/or surgery. PHEO (20/40) and PGL (20/40) were each present in 50% of the patients. Bone was the most frequent site of metastasis, detected in 60% (24/40). Bone metastasis was more frequent in patients with PGL (16/20, 80%) than in patients with PHEO (8/20, 40%) (p = 0.02). Half (12/24) of the patients with bone metastasis had at least one SRE. Extra-skeletal invasion of the spine, defined as local infiltration to the surrounding tissue beyond the cortical bone, was more frequently observed in patients with bone metastasis associated with SREs than without them (p = 0.001). Careful follow-up and management are warranted especially in patients with PGL as a risk factor for bone metastasis and with extra-skeletal invasion of the spine as risk factor of SREs.

PMID: 29187703 [PubMed - indexed for MEDLINE]

Expression signatures of early-stage and advanced medaka melanomas.

Fetched: September 27th, 2018, 5:00am GMT

Expression signatures of early-stage and advanced medaka melanomas.

Comp Biochem Physiol C Toxicol Pharmacol. 2018 Jun;208:20-28

Authors: Klotz B, Kneitz S, Regensburger M, Hahn L, Dannemann M, Kelso J, Nickel B, Lu Y, Boswell W, Postlethwait J, Warren W, Kunz M, Walter RB, Schartl M

Abstract
Melanoma is one of the most aggressive tumors with a very low survival rate once metastasized. The incidence of newly detected cases increases every year suggesting the necessity of development and application of innovative treatment strategies. Human melanoma develops from melanocytes localized in the epidermis of the skin to malignant tumors because of deregulated effectors influencing several molecular pathways. Despite many advances in describing the molecular changes accompanying melanoma formation, many critical and clinically relevant molecular features of the transformed pigment cells and the underlying mechanisms are largely unknown. To contribute to a better understanding of the molecular processes of melanoma formation, we use a transgenic medaka melanoma model that is well suited for the investigation of melanoma tumor development because fish and human melanocytes are both localized in the epidermis. The purpose of our study was to gain insights into melanoma development from the first steps of tumor formation up to melanoma progression and to identify gene expression patterns that will be useful for monitoring treatment effects in drug screening approaches. Comparing transcriptomes from juvenile fish at the tumor initiating stage with nevi and advanced melanoma of adults, we identified stage specific expression signatures and pathways that are characteristic for the development of medaka melanoma, and are also found in human malignancies.

PMID: 29162497 [PubMed - indexed for MEDLINE]

Schwannoma of the trochlear nerve-an illustrated case series and a systematic review of management.

Fetched: September 27th, 2018, 5:00am GMT

Schwannoma of the trochlear nerve-an illustrated case series and a systematic review of management.

Neurosurg Rev. 2018 Jul;41(3):699-711

Authors: Torun N, Laviv Y, Jazi KK, Mahadevan A, Bhadelia RA, Matthew A, Strominger M, Kasper EM

Abstract
Schwannomas of cranial nerves in the absence of systemic neurofibromatosis are relatively rare. Among these, schwannomas of the trochlear nerve are even less common. They can be found incidentally or when they cause diplopia or other significant neurological deficits. Treatment options include observation only, neuro-ophthalmological intervention, and/or neurosurgical management via resection or sterotactic radiosurgery (SRS). In recent years, the latter has become an attractive therapeutic tool for a number of benign skull base neoplasm including a small number of reports on its successful use for trochlear Schwannomas. However, no treatment algorithm for the management of these tumors has been proposed so far. The goal of this manuscript is to illustrate a case series of this rare entity and to suggest a rational treatment algorithm for trochlear schwannomas, based on our institutional experience of recent cases, and a pertinent review of the literature. Including our series of 5 cases, a total of 85 cases reporting on the management of trochlear schwannomas have been published. Of those reported, less than half (40 %) of patients underwent surgical resection, whereas the remainder were managed conservatively or with SRS. Seventy-six percent (65/85) of the entire cohort presented with diplopia, which was the solitary symptom in over half of the cases (n = 39). All patients who presented with symptoms other than diplopia or headaches as solitary symptoms underwent surgical resection. Patients in the non-surgical group were mostly male (M/F = 3.5:1), presented at an older age and had shorter mean diameter (4.6 vs. 30.4 mm, p < 0.0001) when compared to the surgical group. Twelve patients in the entire cohort were treated with SRS, none of whom had undergone surgical resection before or after radiation treatment. Trochlear schwannoma patients without systemic neurofibromatosis are rare and infrequently reported in the literature. Of those, patients harboring symptomatic trochlear Schwannomas do not form a single homogenous group, but fall into two rather distinct subgroups regarding demographics and clinical characteristics. Among those patients in need of intervention, open microsurgical resection as well as less invasive treatment options exist, which all aim at safe relief of symptoms and prevention of progression. Both open microsurgical removal as well as SRS can achieve good long-term local control. Consequently, a tailored multidisciplinary treatment algorithm, based on the individual presentation and tumor configuration, is proposed.

PMID: 27586875 [PubMed - indexed for MEDLINE]

Neurophysiological intraoperative monitoring during an optic nerve schwannoma removal.

Fetched: September 27th, 2018, 5:00am GMT

Neurophysiological intraoperative monitoring during an optic nerve schwannoma removal.

J Clin Monit Comput. 2017 Oct;31(5):1059-1064

Authors: San-Juan D, Escanio Cortés M, Tena-Suck M, Orozco Garduño AJ, López Pizano JA, Villanueva Domínguez J, Fernández Gónzalez-Aragón M, Gómez-Amador JL

Abstract
This paper reports the case of a patient with optic nerve schwannoma and the first use of neurophysiological intraoperative monitoring of visual evoked potentials during the removal of such tumor with no postoperative visual damage. Schwannomas are benign neoplasms of the peripheral nervous system arising from the neural crest-derived Schwann cells, these tumors are rarely located in the optic nerve and the treatment consists on surgical removal leading to high risk of damage to the visual pathway. Case report of a thirty-year-old woman with an optic nerve schwannoma. The patient underwent surgery for tumor removal on the left optic nerve through a left orbitozygomatic approach with intraoperative monitoring of left II and III cranial nerves. We used Nicolet Endeavour CR IOM (Carefusion, Middleton WI, USA) to performed visual evoked potentials stimulating binocularly with LED flash goggles with the patient´s eyes closed and direct epidural optic nerve stimulation delivering rostral to the tumor a rectangular current pulse. At follow up examinations 7 months later, the left eye visual acuity was 20/60; Ishihara score was 8/8 in both eyes; the right eye photomotor reflex was normal and left eye was mydriatic and arreflectic; optokinetic reflex and ocular conjugate movements were normal. In this case, the epidural direct electrical stimulation of optic nerve provided stable waveforms during optic nerve schwannoma resection without visual loss.

PMID: 27586244 [PubMed - indexed for MEDLINE]

StatPearls

Fetched: September 27th, 2018, 5:00am GMT

StatPearls

Book. 2018 01

Authors:

Abstract
The pancreas is an important organ in the digestive system that produces enzymes for digestion and releases important hormones into our circulation that help with metabolism. Pancreatic cysts are often detected in patients undergoing imaging with either CT or MRI for unrelated reasons due to a combination of an aging population and the overall increased use of imaging. Pancreatic cysts are identified in 2% to 20% of patients undergoing CT or MRI; however, these rates can be lower in those with no history of pancreatitis.[1],[2],[3] On the other hand, these rates can increase to nearly one-third of patients in high-risk populations with a family history of pancreatic cancer.[4],[5] These cysts can be either neoplastic or nonneoplastic. Neoplastic cysts include intraductal papillary mucinous neoplasms (IPMN), mucinous cystic neoplasm, solid pseudopapillary neoplasm, and cystic pancreatic neuroendocrine tumors. IPMNs can be subclassified as main duct IPMN, branch duct IPMN, and mixed IPMN. Nonneoplastic cysts include serous cystic adenoma, simple cysts, lymphoepithelial cysts, and mucinous nonneoplastic cysts. Correct diagnosis is important as management drastically changes if the cyst is neoplastic or nonneoplastic. Moreover, surgical resection is not always the best option for all pancreatic cysts as resection can be complicated and have many risks associated with it. Depending on the cyst type, growth pattern, and symptoms, surveillance can sometimes be the best option. Moreover, with the ever-growing concern about pancreatic cysts and their risk of malignancy, new advances, such as endoscopic ultrasound, have greatly improved surveillance and proper diagnosis to guide treatment options.

PMID: 30252235

YWHAE-NUTM2A/B Translocated High-grade Endometrial Stromal Sarcoma Commonly Expresses CD56 and CD99.

Fetched: September 27th, 2018, 5:00am GMT

YWHAE-NUTM2A/B Translocated High-grade Endometrial Stromal Sarcoma Commonly Expresses CD56 and CD99.

Int J Gynecol Pathol. 2018 Sep 24;:

Authors: McCluggage WG, Lee CH

Abstract
YWHAE-NUTM2A/B translocated high-grade endometrial stromal sarcoma is an uncommon and clinically aggressive uterine mesenchymal neoplasm which is sometimes associated with a low-grade fibromyxoid component. Although the diagnosis is confirmed using molecular techniques, it is possible to make the diagnosis based on the characteristic morphology and the immunophenotype; the latter typically includes diffuse positive staining of the high-grade component with cyclin D1 and CD117 and negative staining with CD10 and hormone receptors. Especially in a small biopsy specimen, in cases without a low-grade component or when presenting with extrauterine disease, the differential diagnosis may be wide and potentially include "small round cell tumors" such as a high-grade neuroendocrine carcinoma and a tumor in the Ewing family. In this study, we report consistent CD56 and CD99 immunoreactivity in YWHAE-NUTM2A/B translocated high-grade endometrial stromal sarcoma. We stained 20 of these neoplasms (10 molecularly confirmed and 10 where diagnosis was based on the morphology and immunophenotype) with CD56 and CD99; in one case, CD56 staining was not performed. Nineteen of 19 (100%) and 17 of 20 (85%) were positive with CD56 and CD99, respectively. Staining was usually diffuse with membranous and cytoplasmic immunoreactivity. Pathologists should be aware that YWHAE-NUTM2A/B translocated high-grade endometrial stromal sarcoma is commonly positive with CD56 and CD99; as well as potentially assisting in diagnosis, positivity with these markers may also result in consideration of other neoplasms in the differential diagnosis.

PMID: 30252726 [PubMed - as supplied by publisher]

Revisiting glucose metabolism in cancer: lessons from a PKM knock-in model.

Fetched: September 27th, 2018, 5:00am GMT

Revisiting glucose metabolism in cancer: lessons from a PKM knock-in model.

Mol Cell Oncol. 2018;5(4):e1472054

Authors: Sato T, Morita M, Nomura M, Tanuma N

Abstract
Isoform selection of pyruvate kinase M (PKM), a glycolytic enzyme, influences fates of glucose-derived carbons in cellular metabolic networks. We recently developed novel mouse lines to study PKM isoform function and identified PKM1 as a potential target in a subset of human lung cancers. This work provides new insight into cancer metabolism.

PMID: 30250920 [PubMed]

Current Standards and Recent Advances in Biomarkers of Major Endocrine Tumors.

Fetched: September 27th, 2018, 5:00am GMT

Current Standards and Recent Advances in Biomarkers of Major Endocrine Tumors.

Front Pharmacol. 2018;9:963

Authors: Luo Y, Zhu H, Tan T, He J

Abstract
The complexity of endocrine tumor diagnosis stems from its variable symptoms and presentation that may mimic many other disease states, or display asymptomatic properties for a prolonged amount of time. Early and accurate disease identification is needed for better patient prognosis. The key to this may be in using validated biomarkers with enhanced sensitivity and specificity. Several biomarkers are consistently used across various endocrine tumor types, possibly indicating a deeper pathophysiological mechanism behind endocrine cancer genesis and development. For example, carbohydrate antigen (CA) is measured in both pancreatic adenocarcinoma as well as ovarian cancer for diagnosis, surveillance, and risk stratification. The discovery of measuring miRNAs that are highly expressed in malignant tumors is also a novel strategy across multiple endocrine tumor types, and is propelling the future advancement of biomarker development. This review introduces currently utilized biomarkers in some of the commonly known endocrine tumors, including thyroid, adrenal, pituitary, pancreatic, and gonadal carcinoma, as well as future research directions.

PMID: 30250431 [PubMed]

Prognostic Factors in Merkel Cell Carcinoma: A Retrospective Single-Center Study in 90 Patients.

Fetched: September 27th, 2018, 5:00am GMT

Prognostic Factors in Merkel Cell Carcinoma: A Retrospective Single-Center Study in 90 Patients.

Cancers (Basel). 2018 Sep 24;10(10):

Authors: Rastrelli M, Ferrazzi B, Cavallin F, Chiarion Sileni V, Pigozzo J, Fabozzi A, Tropea S, Vecchiato A, Costa A, Parisi A, Rossi CR, Del Fiore P, Alaibac M

Abstract
Merkel Cell Carcinoma (MCC) is a rare but highly aggressive neuroendocrine neoplasm of the skin. This study aimed at describing characteristics, treatment, and prognosis of a series of consecutive cases of MCC patients, in order to contribute to the investigation of this rare malignancy and provide better patient care. This is a retrospective cohort study including all 90 patients diagnosed and/or treated for MCC between 1991 and 2018 at the Veneto Institute of Oncology in Padua (Italy). Patient and tumor characteristics, treatment, and immunohistochemical data were extracted from a prospectively collected local database. There were 68 primary (76%) and 22 non-primary (15 occult primary, three metastatic, four recurrence) tumors (24%). CK20 expression was associated with reduced overall (HR 2.92, 95% CI 1.04⁻8.16) and disease-specific (HR 4.62, 95% CI 1.31⁻16.28) survival. Immunomodulatory regimens for treatment of other comorbidities were associated with reduced disease-specific ((HR 2.15, 95% CI 1.06⁻4.36) and recurrence-free (HR 3.08, 95% CI 1.44⁻6.57) survival. Iatrogenic immunomodulation resulted as the main factor associated with impaired prognosis. Lack of CK20 expression was associated with better survival.

PMID: 30249978 [PubMed]

Primary large cell neuroendocrine carcinoma of the prostate in a hormone naive patient: A case report from Taiwan.

Fetched: September 27th, 2018, 5:00am GMT

Primary large cell neuroendocrine carcinoma of the prostate in a hormone naive patient: A case report from Taiwan.

J Cancer Res Ther. 2018 Sep;14(Supplement):S785-S788

Authors: Tzou KY, Cheng WH, Lee WH, Ho CH

Abstract
Large cell neuroendocrine carcinoma (LCNEC) of the prostate is extremely rare. Previously reported cases in the literature were almost exclusively developed in men receiving androgen deprivation therapy for prostate adenocarcinoma. We herein present a case of de novo LCNEC: A 66-year-old male was incidentally diagnosed as LCNEC after he underwent transurethral resection of prostate. The stage was T4N1M1. Therefore, the patient was treated with 6 cycles of cisplatin and etoposide in the following 6 months, which achieved a partial remission. He gave up the chance to eradicate the residual mass. Three months later, the tumor progressed rapidly. In conclusion, LCNEC is a rare prostate cancer. Our experience shows that chemotherapy with etoposide and cisplatin is effective to achieve a significant remission. However, LCNEC is highly malignant in nature, postchemotherapy surgery for the residual mass should be considered.

PMID: 30249904 [PubMed - in process]

Phase I trial of Lipovaxin-MM, a novel dendritic cell-targeted liposomal vaccine for malignant melanoma.

Fetched: September 27th, 2018, 5:00am GMT

Phase I trial of Lipovaxin-MM, a novel dendritic cell-targeted liposomal vaccine for malignant melanoma.

Cancer Immunol Immunother. 2018 Sep;67(9):1461-1472

Authors: Gargett T, Abbas MN, Rolan P, Price JD, Gosling KM, Ferrante A, Ruszkiewicz A, Atmosukarto IIC, Altin J, Parish CR, Brown MP

Abstract
INTRODUCTION: In this phase I study using a 3 + 3 dose escalation design, the safety, dose-limiting toxicity (DLT), immunogenicity and efficacy of intravenous Lipovaxin-MM-a multi-component dendritic cell-targeted liposomal vaccine against metastatic melanoma-was investigated.
METHODS: Twelve subjects with metastatic cutaneous melanoma were recruited in three cohorts. Patients in Cohort A (n = 3) and Cohort B (n = 3) received three doses of 0.1 and 1 mL of Lipovaxin-MM, respectively, every 4 weeks. Patients in Cohort C (n = 6) received four doses of 3 mL vaccine weekly. Immunologic assessments of peripheral blood were made at regular intervals and included leukocyte subsets, cytokine levels, and Lipovaxin-MM-specific T-cell and antibody reactivities. Tumor responses were assessed by RECIST v1.0 at screening, then 8 weekly in Cohorts A and B and 6 weekly in Cohort C.
RESULTS: Of a total of 94 adverse events (AEs) reported in ten subjects, 43 AEs in six subjects were considered to be possibly or probably vaccine-related. Most (95%) vaccine-related AEs were grade 1 or 2, two (5%) grade 3 vaccine-related AEs of anemia and lethargy were recorded, and higher grade AEs and DLTs were not observed. No consistent evidence of vaccine-specific humoral or cellular immune responses was found in post-immunization blood samples. One patient had a partial response, two patients had stable disease, and the remaining patients had progressive disease.
CONCLUSIONS: Lipovaxin-MM was well tolerated and without clinically significant toxicity. Immunogenicity of Lipovaxin-MM was not detected. Partial response and stable disease were observed in one and two patients, respectively.

PMID: 30014244 [PubMed - indexed for MEDLINE]

Antimelanogenesis and Anti-Inflammatory Activity of Selected Culinary-Medicinal Mushrooms.

Fetched: September 27th, 2018, 5:00am GMT

Antimelanogenesis and Anti-Inflammatory Activity of Selected Culinary-Medicinal Mushrooms.

Int J Med Mushrooms. 2018;20(2):141-153

Authors: Saad HM, Sim KS, Tan YS

Abstract
Five culinary-medicinal mushrooms are commonly available in the Malaysian market: Agaricus bisporus (white and brown), Ganoderma lucidum, Hypsizygus marmoreus, Pleurotus floridanus, and P. pulmonarius. These species were selected for use in the current study, the aim of which was to investigate the antimelanogenesis and anti-inflammatory activity of these mushrooms in an attempt to evaluate their potential use in cosmeceuticals. Mushroom fruiting bodies were extracted with hot water, and the extracts were freeze-dried before testing. The antimelanogenesis activity of the extracts was determined by cell viability assay, measurement of intracellular melanin content, and cellular tyrosinase assay with B16F10 melanoma cells. The anti-inflammatory activity of the mushroom extracts was tested by measuring the levels of nitric oxide (NO), tumor necrosis factor (TNF)-α, and interleukin-10 excreted by RAW264.7 macrophages. Brown A. bisporus reduced intracellular melanin content to the largest extent-up to 57.05 ± 3.90%-without a cytotoxic effect on B16F10 melanoma cells. This extract also reduced cellular tyrosinase activity to 17.93 ± 2.65%, performing better than kojic acid, the positive control. In parallel, the extract from brown A. bisporus, at the highest concentration tested, has appreciable anti-inflammatory activity through reductions of NO and TNF-α levels. The other 5 extracts showed moderate antimelanogenesis and anti-inflammatory activities. In summary, our findings show that A. bisporus (brown) extract has the potential to be used as an ingredient in whitening skincare products and to sooth the inflammatory response on the skin.

PMID: 29773006 [PubMed - indexed for MEDLINE]

Recommended parameters for pathology reporting of gastroenteropancreatic neuroendocrine tumours (GEP-NETs).

Fetched: September 27th, 2018, 5:00am GMT

Recommended parameters for pathology reporting of gastroenteropancreatic neuroendocrine tumours (GEP-NETs).

Malays J Pathol. 2018 Apr;40(1):79-82

Authors:

Abstract
No abstract available.

PMID: 29704389 [PubMed - indexed for MEDLINE]

Permalink for 'Nodal induced by hypoxia exposure contributes to dacarbazine resistance and the maintenance of stemness in melanoma cancer stem‑like cells.'

Nodal induced by hypoxia exposure contributes to dacarbazine resistance and the maintenance of stemness in melanoma cancer stem‑like cells.

Fetched: September 27th, 2018, 5:00am GMT

Nodal induced by hypoxia exposure contributes to dacarbazine resistance and the maintenance of stemness in melanoma cancer stem‑like cells.

Oncol Rep. 2018 Jun;39(6):2855-2864

Authors: Li H, Chen J, Wang X, He M, Zhang Z, Cen Y

Abstract
Nodal signaling has a critical role in the processes of embryogenesis and is necessary for maintaining cell stemness. However, its upregulation in melanoma is positively correlated with malignant potential, including cancer progression, metastasis and recurrence, and a recent report has revealed its role in promoting self‑renewal capacity in melanoma. Our study aimed to explore the effects of hypoxia exposure, which is one of the main causes of chemoresistance in melanoma, on the physiological processes of melanoma cancer stem‑like cells (CSCs) via regulating Nodal. A375 CSCs were enriched by culturing in serum‑free medium (SFM) and were analyzed for the expression levels of Nodal and its correlated proteins by semi‑quantitative western blotting. Lentiviral‑packaged Nodal coding sequence or short‑hairpin RNA (shRNA) was employed. After hypoxia exposure, the effects on glucose uptake, ATP production and O2 consumption were detected, and whether Nodal contributed to the proliferation, invasion, colony formation, self‑renewal capacity and chemoresistance was evaluated. We demonstrated that hypoxia exposure induced Nodal expression and activated the Smad2/3 pathway in A375 CSCs. Hypoxic‑induced Nodal partially promoted dacarbazine resistance, promoted invasion and self‑renewal capacity, but not proliferation which was further confirmed using Nodal knockdown. Blockage of Nodal signaling activity with the small‑molecule inhibitor SB431542 partially reversed Nodal‑induced chemoresistance. Nodal knockdown further sensitized A375 CSCs to dacarbazine after SB431542 pretreatment, indicating the involvement of proNodal in dacarbazine resistance. The introduction of mut‑proNodal induced chemoresistance further confirming the role of proNodal in this process. Taken together, our results demonstrated that Nodal induced by hypoxia exposure induced a malignant phenotype and chemoresistance in A375 CSCs, and proNodal also contributed to these processes, indicating that Nodal may be a potential therapeutic target for melanoma.

PMID: 29693169 [PubMed - indexed for MEDLINE]

Permalink for 'Structural characterization of polysaccharides from Saposhnikovia divaricata and their antagonistic effects against the immunosuppression by the culture supernatants of melanoma cells on RAW264.7 macrophages.'

Structural characterization of polysaccharides from Saposhnikovia divaricata and their antagonistic effects against the immunosuppression by the culture supernatants of melanoma cells on RAW264.7 macrophages.

Fetched: September 27th, 2018, 5:00am GMT

Structural characterization of polysaccharides from Saposhnikovia divaricata and their antagonistic effects against the immunosuppression by the culture supernatants of melanoma cells on RAW264.7 macrophages.

Int J Biol Macromol. 2018 Jul 01;113:748-756

Authors: Dong CX, Liu L, Wang CY, Fu Z, Zhang Y, Hou X, Peng C, Ran RX, Yao Z

Abstract
Two purified native polysaccharides, namely, SDNP-1 and SDNP-2 with apparent molecular weight of 67.9×103 and 5.2×103, separately, were isolated from the water extract of Saposhnikovia divaricata by combined ion-exchange and gel permeation chromatography. The structures of these polysaccharides were characterized by high-performance gel permeation chromatography, chemical derivative analysis, GC-MS, FT-IR spectroscopy, and NMR spectroscopy. Results showed that SDNP-1 and SDNP-2 were composed of arabinose and galactose with molar ratio of approximately 1:1. The polysaccharides were deduced to be AGII-type arabinogalactans with distinct molecular weights and backbone chains. The backbone chain of SDNP-2 mainly consisted of (1→3)-linked and (1→6)-linked Galp residues with an approximate molar ratio of 1:3. Approximately half of the (1→6)-linked Galp residues were substituted at O-3, and small amounts of (1→6)-linked Galp were substituted at O-3 and O-4 by branches that mainly consisted of terminal and (1→5)-linked Araf residues. Bioactivity tests showed that SDNP-2 exhibited significant antagonistic effect against immunosuppression as shown by the cell viability of the culture supernatants of melanoma cells on RAW264.7 macrophages. However, SDNP-1 showed no effect. Thus, molecular weight and backbone chain may be the key factors for the antagonistic effects against immunosuppression.

PMID: 29518443 [PubMed - indexed for MEDLINE]

Non-circumferential membranous resection of the trachea for paraganglioma: A case report.

Fetched: September 24th, 2018, 5:00am GMT

Non-circumferential membranous resection of the trachea for paraganglioma: A case report.

Int J Surg Case Rep. 2018 Sep 17;51:288-291

Authors: Wannaz L, Roumy A, Letovanec I, Lovis A, Beigelman C, Ris HB, Gonzalez M

Abstract
INTRODUCTION: Paraganglioma is a rare neuroendocrine tumor and may sometimes be located in the membranous part of the trachea.
PRESENTATION OF CASE: We report the case of a 52-year-old man presenting a paraganglioma just above the carina with obstructive symptoms. The patient successfully underwent a non-circumferential tracheal membranous resection, followed by latissimus dorsi muscle flap repair, under peripheral extra-corporeal membrane oxygenation (ECMO).
DISCUSSION: Complex carinal resection can be avoided for tracheal membranous tumors and replaced with non-circumferential resection and direct reconstruction with a muscle flap. In addition, ECMO support may be used for airway resection and reconstruction.
CONCLUSION: Tracheal membranous tumors can be managed without circumferential resection or direct anastomosis.

PMID: 30243261 [PubMed - as supplied by publisher]

Liver Resection for Neuroendocrine Tumor Liver Metastases Within Milan Criteria for Liver Transplantation.

Fetched: September 24th, 2018, 5:00am GMT

Liver Resection for Neuroendocrine Tumor Liver Metastases Within Milan Criteria for Liver Transplantation.

J Gastrointest Surg. 2018 Sep 21;:

Authors: Ruzzenente A, Bagante F, Bertuzzo F, Aldrighetti L, Campagnaro T, Ercolani G, Conci S, Giuliante F, Dore A, Ferrero A, Torzilli G, Grazi GL, Ratti F, Cucchetti A, De Rose AM, Russolillo N, Cimino M, Perri P, Guglielmi A, Iacono C

Abstract
BACKGROUND: The role of liver transplant (LT) for neuroendocrine liver metastasis (NELM) has not been completely defined. While international guidelines included LT as a potential treatment for highly selected patients with advanced NELM, recently, LT has been proposed as an alternative curative treatment for NELM for patients meeting restrictive criteria (Milan criteria).
METHODS: Using a multi-institutional cohort of patients undergoing liver resection for NELM, the long-term outcomes of patients meeting Milan criteria (resected NET drained by the portal system, stable disease/response to therapies for at least 6 months, metastatic diffusion to < 50% of the total liver volume, a confirmed histology of low-grade, and ≤ 60 years) were investigated.
RESULTS: Among the 238 patients included in the study, 28 (12%) patients met the Milan criteria for LT with a 5-year OS of 83%. Furthermore, among patients meeting Milan criteria, subsets of patients with favorable clinic-pathological characteristics had 5-year OS rates greater than 90% including G1 patients (5-year OS, 92%), patients undergoing minor liver resection (5-year OS, 94%), patients with low number of NELM (1-2 NELM), and small tumor size (< 3 cm) (for both groups of patients, 5-year OS, 100%).
CONCLUSIONS: In our series, only 12% of patients met Milan criteria, and the 5-year OS after liver resection for this small selected group of patients was comparable with that reported in the literature for patients undergoing LT for NELM within Milan criteria. While LT might be the optimal treatment for patients with unresectable NELM, surgical resection should be the first option for patients with resectable NELM.

PMID: 30242647 [PubMed - as supplied by publisher]

Unmet Needs in Appendiceal Neuroendocrine Neoplasms.

Fetched: September 22nd, 2018, 5:00am GMT

Unmet Needs in Appendiceal Neuroendocrine Neoplasms.

Neuroendocrinology. 2018 Sep 20;:

Authors: Toumpanakis C, Fazio N, Tiensuu Janson E, Hörsch D, Pascher A, Reed N, O'Toole D, Nieveen van Dijkum E, Partelli S, Rinke A, Kos-Kudla B, Costa F, Pape UF, Grozinsky-Glasberg S, Scoazec JY, ENETS 2016 Munich Advisory Board Participants

Abstract
Appendiceal neuroendocrine neoplasms (ANEN) are mostly discovered coincidentally during appendicectomy and usually have a benign clinical course, thus appendicectomy alone is considered as curative. However in some cases a malignant potential is suspected and therefore additional operations, such as completion right hemicolectomy, are considered. The existing European Neuroendocrine Tumour Society (ENETS) guidelines provide quite useful data about epidemiology and prognosis, as well as, practical recommendations with regards to the risk factors for a more aggressive disease course and the indications for a secondary operation. However, those guidelines are based on heterogeneous and retrospective studies. Therefore, the evidence does not seem to be robust and there are still unmet needs in terms of accurate epidemiology and overall prognosis, optimal diagnostic and follow-up strategy, and identified risk factors, which would indicate a more aggressive surgical approach at the beginning and a more intense follow-up. In this review, we are attempting a critical approach of ENETS guidelines and published series for ANEN, focusing on the above noted "grey areas".

PMID: 30235454 [PubMed - as supplied by publisher]

An Update on the Role of Immunohistochemistry in the Evaluation of Gastrointestinal Tract Disorders.

Fetched: September 22nd, 2018, 5:00am GMT

An Update on the Role of Immunohistochemistry in the Evaluation of Gastrointestinal Tract Disorders.

Adv Anat Pathol. 2018 Sep 18;:

Authors: Robertson S, Patil DT

Abstract
As in other organ systems, immunohistochemistry (IHC) serves as an ancillary diagnostic tool for a wide variety of neoplastic and non-neoplastic disorders, including infections, work-up of inflammatory conditions, and subtyping neoplasms of the gastrointestinal (GI) tract. In addition, IHC is also used to detect a variety of prognostic and predictive molecular biomarkers for carcinomas of the GI tract. The purpose of this review is to highlight the use of IHC in common diagnostic scenarios throughout the tubular GI tract. The clinical indication and guidelines for performing IHC for detecting Helicobacter pylori is discussed along with role of gastrin and neuroendocrine markers in the diagnosis of autoimmune metaplastic atrophic gastritis. The major portion of this review discusses the use of IHC in the diagnostic workup of malignant neoplasms of the GI tract, such as adenocarcinoma versus squamous cell carcinoma, workup of poorly differentiated malignant neoplasms, and evaluation of uncommon gastric neoplasms (alpha-feto protein-producing carcinomas) and switch/sucrose-nonfermenting complex-deficient carcinomas. Lastly, localization of neuroendocrine tumors of unknown origin to aid clinical management, as well as HPV-driven anal neoplasia and IHC in the workup of basaloid anal neoplasms are also reviewed.

PMID: 30234501 [PubMed - as supplied by publisher]

Permalink for 'A case of ectopic ACTH syndrome due to DDAVP-sensitive but V1b receptor-negative bronchial typical carcinoid with lymphatic metastasis and plasma ProGRP elevation.'

A case of ectopic ACTH syndrome due to DDAVP-sensitive but V1b receptor-negative bronchial typical carcinoid with lymphatic metastasis and plasma ProGRP elevation.

Fetched: September 22nd, 2018, 5:00am GMT

A case of ectopic ACTH syndrome due to DDAVP-sensitive but V1b receptor-negative bronchial typical carcinoid with lymphatic metastasis and plasma ProGRP elevation.

Endocr J. 2018 Sep 20;:

Authors: Yamamuro T, Inoue K, Nagai Y, Azuma D, Yamamoto A, Hara K, Kohara M, Iwata T, Nakatsuka S, Morii E, Yamamoto T

Abstract
Ectopic ACTH syndrome (EAS) is a potentially fatal endocrine disease that results from a variety of neuroendocrine tumors (NETs), such as small cell lung cancer (SCLC) and bronchial typical carcinoid. Typical carcinoid is usually slow growing, not associated with plasma progastrin releasing peptide (ProGRP) elevation. Here, we report a 47-year-old female smoker with progressive typical carcinoid and plasma ProGRP elevation. Several types of Cushingoid features were found on physical examination. In addition, laboratory examination showed elevated plasma ACTH and serum cortisol levels. These findings indicated ACTH-dependent Cushing's syndrome. Moreover, the serum cortisol level was not suppressed by overnight high-dose dexamethasone treatment, suggesting the presence of an extra-pituitary tumor. Contrast-enhanced brain MRI revealed no pituitary adenoma, which also supported the idea that EAS occurred in the present case. Strikingly, chest computed tomographic (CT) scan showed a single 18-mm peripheral nodule in the right middle lobe of the lung. Tumor marker analysis revealed an elevation in plasma ProGRP. These data suggested a possibility that SCLC secreted ACTH and caused EAS in this patient. Of note, the plasma ACTH level was increased (1.7 fold) in l-desamino-8-D-arginine vasopressin (DDAVP) test, also suggesting the specific clinical feature in this case. After additional imaging examinations, we performed surgical resection with the suspicion of limited SCLC. As a result, pathological examination revealed a vasopressin receptor Ib (V1b) receptor-negative bronchial typical carcinoid with ACTH production and mediastinal lymphatic metastasis. In summary, we present a case of EAS caused by progressive bronchial typical carcinoid with plasma ProGRP elevation. We propose a novel subtype of lung typical carcinoid.

PMID: 30232300 [PubMed - as supplied by publisher]

Permalink for 'A phase II trial of the aurora kinase A inhibitor alisertib for patients with castration resistant and neuroendocrine prostate cancer: efficacy and biomarkers.'

A phase II trial of the aurora kinase A inhibitor alisertib for patients with castration resistant and neuroendocrine prostate cancer: efficacy and biomarkers.

Fetched: September 22nd, 2018, 5:00am GMT

A phase II trial of the aurora kinase A inhibitor alisertib for patients with castration resistant and neuroendocrine prostate cancer: efficacy and biomarkers.

Clin Cancer Res. 2018 Sep 19;:

Authors: Beltran H, Oromendia C, Danila DC, Montgomery B, Hoimes C, Szmulewitz RZ, Vaishampayan U, Armstrong AJ, Stein M, Pinski J, Mosquera JM, Sailer V, Bareja R, Romanel A, Gumpeni N, Sboner A, Dardenne E, Puca L, Prandi D, Rubin MA, Scher HI, Rickman DS, Demichelis F, Nanus DM, Ballman KV, Tagawa ST

Abstract
BACKGROUND: Neuroendocrine prostate cancer (NEPC) is an aggressive variant of prostate cancer that may develop de novo or as a mechanism of treatment resistance. N-myc is capable of driving NEPC progression. Alisertib inhibits the interaction between N-myc and its stabilizing factor Aurora-A, inhibiting N-myc signaling, and suppressing tumor growth.
EXPERIMENTAL DESIGN: Sixty men were treated with alisertib50mg twice daily for 7 days every 21-days. Eligibility included metastatic prostate cancer and at least one: small cell neuroendocrine morphology; 50% neuroendocrine marker expression; new liver metastases without PSA progression; elevated serum neuroendocrine markers. The primary endpoint was six-month radiographic progression free survival (rPFS). Pre-treatment biopsies were evaluated by whole exome and RNA-seq and patient-derived organoids were developed.
RESULTS: Median PSA was 1.13 ng/ml (0.01-514.2), number of prior therapies was three, and 68% had visceral metastases. Genomic alterations involved RB1 (55%), TP53 (46%), PTEN (29%), BRCA2 (29%),AR (27%), and there was a range of androgen receptor signaling and NEPC marker expression. Six-month rPFS was 13.4% and median overall survival was 9.5 months (7.3-13). Four exceptional responders were identified, including complete resolution of liver metastases and prolonged stable disease, with tumors suggestive of N-myc and Aurora-A overactivity. Patient organoids exhibited concordant responses to alisertib and allowed for the dynamic testing of Aurora-N-myc complex disruption.
CONCLUSIONS: Although the study did not meet its primary endpoint, a subset of patients with advanced prostate cancer and molecular features supporting Aurora-A and N-myc activation achieved significant clinical benefit from single-agent alisertib.

PMID: 30232224 [PubMed - as supplied by publisher]

Permalink for 'International Union of Basic and Clinical Pharmacology. CV. Somatostatin Receptors: Structure, Function, Ligands, and New Nomenclature.'

International Union of Basic and Clinical Pharmacology. CV. Somatostatin Receptors: Structure, Function, Ligands, and New Nomenclature.

Fetched: September 22nd, 2018, 5:00am GMT

International Union of Basic and Clinical Pharmacology. CV. Somatostatin Receptors: Structure, Function, Ligands, and New Nomenclature.

Pharmacol Rev. 2018 Oct;70(4):763-835

Authors: Günther T, Tulipano G, Dournaud P, Bousquet C, Csaba Z, Kreienkamp HJ, Lupp A, Korbonits M, Castaño JP, Wester HJ, Culler M, Melmed S, Schulz S

Abstract
Somatostatin, also known as somatotropin-release inhibitory factor, is a cyclopeptide that exerts potent inhibitory actions on hormone secretion and neuronal excitability. Its physiologic functions are mediated by five G protein-coupled receptors (GPCRs) called somatostatin receptor (SST)1-5. These five receptors share common structural features and signaling mechanisms but differ in their cellular and subcellular localization and mode of regulation. SST2 and SST5 receptors have evolved as primary targets for pharmacological treatment of pituitary adenomas and neuroendocrine tumors. In addition, SST2 is a prototypical GPCR for the development of peptide-based radiopharmaceuticals for diagnostic and therapeutic interventions. This review article summarizes findings published in the last 25 years on the physiology, pharmacology, and clinical applications related to SSTs. We also discuss potential future developments and propose a new nomenclature.

PMID: 30232095 [PubMed - in process]

Biology and Systemic Treatment of Advanced Gastroenteropancreatic Neuroendocrine Tumors.

Fetched: September 22nd, 2018, 5:00am GMT

Icon for American Society of Clinical Oncology

Biology and Systemic Treatment of Advanced Gastroenteropancreatic Neuroendocrine Tumors.

Am Soc Clin Oncol Educ Book. 2018 May 23;(38):292-299

Authors: Raj N, Fazio N, Strosberg J

Abstract
In recent years, there have been important scientific advances in the biologic characterization of neuroendocrine neoplasms and in their treatment. This review will describe these scientific advances, the evolving systemic treatment approaches, and important topics to be addressed in future research.

PMID: 30231344 [PubMed - in process]

[Small cell neuroendocrine carcinoma of the bladder: Report of five cases and a review of the literature].

Fetched: September 22nd, 2018, 5:00am GMT

[Small cell neuroendocrine carcinoma of the bladder: Report of five cases and a review of the literature].

Cancer Radiother. 2018 Sep;22(5):417-422

Authors: Safini F, Jouhadi H, Marnissi F, Bouchbika Z, Benchakroun N, Tawfiq N, Sahraoui S, Benider A

Abstract
Neuroendocrine small cell carcinoma of the bladder is a rare and aggressive tumour, accounting for less than 1% of all bladder tumours. Given its rarity and the absence of randomized trials, the therapeutic management of these tumours remains difficult. By analogy with small cell lung cancer, multimodal treatment is often proposed. Radical cystectomy plus chemotherapy and chemoradiation therapy are associated with better survival compared to monotherapy. We report our experience in the management of these tumours with literature review.

PMID: 30049597 [PubMed - indexed for MEDLINE]

Human melanoma-derived ectosomes are enriched with specific glycan epitopes.

Fetched: September 22nd, 2018, 5:00am GMT

Human melanoma-derived ectosomes are enriched with specific glycan epitopes.

Life Sci. 2018 Aug 15;207:395-411

Authors: Surman M, Hoja-Łukowicz D, Szwed S, Drożdż A, Stępień E, Przybyło M

Abstract
AIMS: Numerous studies confirmed the involvement of extracellular vesicles in cancer development and progression. The present study was designed to investigate the glycan composition of ectosomes derived by human cutaneous melanoma (CM) cell lines with the use of lectins.
MAIN METHODS: Ectosomes released by primary (WM115, WM793) and metastatic (WM266-4, WM1205Lu) CM cells were isolated from conditioned media by sequential centrifugation. Proteins from ectosomes, the whole cell extracts and membrane fractions were probed with a panel of lectins using Western Blot and flow cytometry and compared in terms of disease stage and glycosignature.
KEY FINDINGS: Ectosomal proteins revealed enrichment (mainly with fucose and complex type N-glycans with bisecting GlcNAc) or depletion of specific glycoepitopes in comparison to the parental cell membranes. Moreover, similar lectin binding patterns were observed between related cell lines. It is the first study to characterize the glycosylation of ectosome proteins released by CM cells.
SIGNIFICANCE: Our data indirectly supports the findings that ectosomes derive from particular regions of the cell membrane contain a unique glycan composition, which could serve as a specific sorting signal. If proven correct, the hypothesis that glycan-based protein sorting is a major mechanism for protein incorporation into ectosomes may provide new means to control vesicular content and have possible clinical implications.

PMID: 29959030 [PubMed - indexed for MEDLINE]

Upregulation of UHRF1 promotes the progression of melanoma by inducing cell proliferation.

Fetched: September 22nd, 2018, 5:00am GMT

Upregulation of UHRF1 promotes the progression of melanoma by inducing cell proliferation.

Oncol Rep. 2018 Jun;39(6):2553-2562

Authors: Wei C, Lu N, Wang L, Zhang Y, Feng Z, Yang Y, Qi F, Gu J

Abstract
Melanoma is the most aggressive cutaneous cancer due to its propensity to metastasise and proliferate. Melanoma accounts for 80‑90% of skin‑cancer related deaths worldwide. Alhough numerous published studies have attempted to define the markers of diagnosis and prognosis of melanoma, a sensitive and specific biomarker for melanoma remains unknown. Recently, ubiquitin‑like with PHD and ring finger domains 1 (UHRF1) has attracted attention due to its role in cell proliferation and it has been deemed as a potential therapeutic target for cancer. The aim of the present study was to investigate the role and the clinical significance of UHRF1 in melanoma. Immunohistochemical analysis was performed with tissue microarray (TMA) to examine the expression of UHRF1 and Ki‑67, and the role of UHRF1 in cell proliferation was determined through CCK‑8, colony formation and flow cytometry by interfering with the expression of UHRF1. Subsequently, the relationship among the expression of UHRF1 and several major clinical characteristics of melanoma were analysed to evaluate the role of UHRF1 in the progression of melanoma. Finally, the clinical significance of UHRF1 was estimated in 56 melanoma patients. It was observed that the expression of UHRF1 was significantly upregulated in melanoma compared with benign nevi tissues (P<0.05). In addition, the downregulation of the expression of UHRF1 significantly decreased cell proliferation. Furthermore, the level of UHRF1 was positively correlated with the expression of Ki‑67 in melanoma cells, as well as in melanoma tissues. Clinically, a high level of UHRF1 was prone to be related to a high TNM classification (P=0.017) and Breslow's thickness (P=0.034) of melanoma. Furthermore, a high level of UHRF1 was positively associated with a shorter overall survival of melanoma patients. Importantly, the Cox regression model analysis demonstrated that the expression of UHRF1 was an independent prognostic factor for the overall survival of melanoma patients. In conclusion, the elevated expression of UHRF1 plays an important role in melanoma cell proliferation and progression, and it can be used as a prognostic biomarker for melanoma.

PMID: 29620240 [PubMed - indexed for MEDLINE]

68Ga-DOTATATE PET-CT imaging in carotid body paragangliomas.

Fetched: September 22nd, 2018, 5:00am GMT

68Ga-DOTATATE PET-CT imaging in carotid body paragangliomas.

Ann Nucl Med. 2018 May;32(4):297-301

Authors: Şimşek DH, Şanlı Y, Kuyumcu S, Başaran B, Mudun A

Abstract
OBJECTIVE: The aim of this study was to present our experience in the baseline evaluation of carotid body paragangliomas (CBP) with 68Ga-DOTATATE PET-CT.
METHODS: Five patients (4F, 1M; age 24-73 years) with CBPs who underwent 68Ga-DOTATATE PET-CT scan before the treatment were evaluated retrospectively. PET-CT images were analyzed visually as well as semiquantitatively, with measurement of maximum standardized uptake value (SUVmax).
RESULTS: All patients had unilateral CBP lesion, showed intense 68Ga-DOTATATE uptake in PET-CT. Additionally, 68Ga-DOTATATE avid lesions were found in two patients. One of them had focal intense uptake in thyroid gland and frontal cerebrum. The other one had intense uptake in bone and adrenal mass. Four patients were operated for unilateral primary CBP. Last patient was treated with peptide receptor radionuclide therapy (177Lu-DOTATATE) for both metastatic pheochromocytoma and CBP.
CONCLUSIONS: 68Ga-DOTATATE PET-CT is a valuable imaging modality for staging of CBPs, detecting unknown lesions and changing the management of patients. It is also useful in demonstrating expression of SSTRs for PRRT opportunity.

PMID: 29468487 [PubMed - indexed for MEDLINE]

Permalink for '[Severe ipilimumab-induced ulcerative colitis remitting after infliximab therapy and secondary switching with pembrolizumab].'

[Severe ipilimumab-induced ulcerative colitis remitting after infliximab therapy and secondary switching with pembrolizumab].

Fetched: September 22nd, 2018, 5:00am GMT

[Severe ipilimumab-induced ulcerative colitis remitting after infliximab therapy and secondary switching with pembrolizumab].

Therapie. 2018 May - Jun;73(3):291-293

Authors: Yelehe-Okouma M, Granel-Brocard F, Hudziak H, Schmutz JL, Gillet P

PMID: 29203065 [PubMed - indexed for MEDLINE]

Aneuploidy and Tetraploidy as Distinct Patterns During Melanomagenesis.

Fetched: September 22nd, 2018, 5:00am GMT

Aneuploidy and Tetraploidy as Distinct Patterns During Melanomagenesis.

Surg Technol Int. 2016 Oct 26;29:53-59

Authors: Escandon J, King L, Blobstein R, Eller MS, Aurich-Costa J

Abstract
Melanoma is characterized by a high degree of chromosome instability (CIN), the loss or gain of entire chromosomes or pieces of chromosomes. Also, CIN is likely to drive the progression of benign melanocytic lesions to malignant tumors, although very little is known about the acquisition of the mechanisms that promote CIN along this progression. Here, we describe the development of a model system to study the progression of melanomagenesis starting with normal human melanocytes followed by inactivation of the p53 and pRb tumor suppressors by addition of the E6/E7 proteins. The cells were then transduced with a growth-promoting, constitutionally-active mutant NRAS. The addition of E6/E7 and E6/E7 NRAS was found to give a growth advantage to the cells compared to normal melanocytes and a statistically significant gain of aneuploidy; aneuploidy was 24.7% in primary melanocytes, 33.8% in E6/E7 melanocytes, and 70.5% in E6/E7 NRAS melanocytes. Further, we found an increase in tetraploid cells in the cell model which was statistically significant between primary melanocytes and E6/E7, NRAS melanocytes. We also observed an increase in aneuploid cells between three population doublings in primary melanocytes, whereas this increase was not seen in the E6/E7 melanocytes. Together, these data demonstrate that this model system utilizing stepwise addition of genetic mutations driving melanomagenesis is a useful tool to study CIN and could even be used to study the mechanisms responsible for these alterations in genetic makeup.

PMID: 27466867 [PubMed - indexed for MEDLINE]

Rare Cancer News & Clinical Trials » Endocrine/Neuroendocrine

Feeds

Endocrine/Neuroendocrine (303 unread)

Fetched: October 14th, 2018, 5:00am GMT

Fetched: October 14th, 2018, 5:00am GMT

Fetched: October 13th, 2018, 5:00am GMT

Fetched: October 10th, 2018, 5:00am GMT

Fetched: October 7th, 2018, 5:00am GMT

Fetched: October 6th, 2018, 5:00am GMT

Fetched: October 6th, 2018, 5:00am GMT

Fetched: October 5th, 2018, 5:00am GMT

Fetched: October 4th, 2018, 5:00am GMT

Fetched: October 4th, 2018, 5:00am GMT

Fetched: October 3rd, 2018, 5:00am GMT

Fetched: October 3rd, 2018, 5:00am GMT

Fetched: October 1st, 2018, 5:00am GMT

Fetched: September 29th, 2018, 5:00am GMT

Fetched: September 29th, 2018, 5:00am GMT

Fetched: September 28th, 2018, 5:00am GMT

Fetched: September 27th, 2018, 5:00am GMT

Fetched: September 23rd, 2018, 5:00am GMT

Fetched: September 23rd, 2018, 5:00am GMT

Fetched: September 23rd, 2018, 5:00am GMT

Fetched: September 15th, 2018, 5:00am GMT

Fetched: September 13th, 2018, 5:00am GMT

Fetched: September 11th, 2018, 5:00am GMT

Fetched: September 10th, 2018, 5:00am GMT

Fetched: September 9th, 2018, 5:00am GMT

Fetched: September 9th, 2018, 5:00am GMT

Fetched: September 8th, 2018, 5:00am GMT

Fetched: September 7th, 2018, 5:00am GMT

Fetched: September 6th, 2018, 5:00am GMT

Fetched: September 3rd, 2018, 5:00am GMT

Fetched: September 2nd, 2018, 5:00am GMT

Fetched: September 2nd, 2018, 5:00am GMT

Fetched: September 1st, 2018, 5:00am GMT

Fetched: September 1st, 2018, 5:00am GMT

Fetched: September 1st, 2018, 5:00am GMT

Fetched: August 30th, 2018, 5:00am GMT

Fetched: August 30th, 2018, 5:00am GMT

Fetched: August 30th, 2018, 5:00am GMT

Fetched: August 29th, 2018, 5:00am GMT

Fetched: August 26th, 2018, 5:00am GMT

Fetched: August 26th, 2018, 5:00am GMT

Fetched: August 25th, 2018, 5:00am GMT

Fetched: August 23rd, 2018, 5:00am GMT

Fetched: August 22nd, 2018, 5:00am GMT

Fetched: August 17th, 2018, 5:00am GMT

Fetched: August 17th, 2018, 5:00am GMT

Fetched: August 17th, 2018, 5:00am GMT

Fetched: August 16th, 2018, 5:00am GMT

Fetched: August 16th, 2018, 5:00am GMT

Fetched: August 15th, 2018, 5:00am GMT

Fetched: August 12th, 2018, 5:00am GMT

Fetched: August 12th, 2018, 5:00am GMT

Fetched: August 11th, 2018, 5:00am GMT

Fetched: August 11th, 2018, 5:00am GMT

Fetched: August 11th, 2018, 5:00am GMT

Fetched: August 11th, 2018, 5:00am GMT

Fetched: August 11th, 2018, 5:00am GMT

Fetched: August 5th, 2018, 5:00am GMT

Fetched: August 4th, 2018, 5:00am GMT

Fetched: August 2nd, 2018, 5:00am GMT

Fetched: August 2nd, 2018, 5:00am GMT

Posted: October 11th, 2018, 4:13am GMT

Posted: October 8th, 2018, 6:45pm GMT

Posted: October 7th, 2018, 11:21am GMT

Posted: October 6th, 2018, 3:49pm GMT

Posted: October 4th, 2018, 3:59pm GMT

Posted: October 4th, 2018, 3:59pm GMT

Posted: October 1st, 2018, 11:23am GMT

Posted: October 1st, 2018, 11:23am GMT

Posted: October 1st, 2018, 11:09am GMT

Posted: October 1st, 2018, 9:24am GMT

Posted: September 15th, 2018, 10:04pm GMT