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https://www.readbyqxmd.com/read/28636555/overcoming-resistance-to-targeted-therapy-with-immunotherapy-and-combination-therapy-for-metastatic-melanoma
#1
REVIEW
Hilary R Keller, Xin Zhang, Li Li, Helmut Schaider, James W Wells
Resistance to targeted therapy is an ongoing problem for the successful treatment of Stage IV metastatic melanoma. For many patients, the use of targeted therapies, such as BRAF kinase inhibitors, were initially promising yet resistance inevitably occurred. Even after combining BRAF kinase inhibitors with MEK pathway inhibitors to offset re-activation of the MAP kinase pathway, resistance is still documented. Similarly, outcomes with immune checkpoint inhibitors as monotherapy were optimistic for some patients without relapse or progression, yet the majority of patients undergoing monotherapy have progressive disease...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636540/implementation-and-utilization-of-the-molecular-tumor-board-to-guide-precision-medicine
#2
REVIEW
Shuko Harada, Rebecca Arend, Qian Dai, Jessica A Levesque, Thomas S Winokur, Rongjun Guo, Martin J Heslin, Lisle Nabell, L Burt Nabors, Nita A Limdi, Kevin A Roth, Edward E Partridge, Gene P Siegal, Eddy S Yang
BACKGROUND: With rapid advances in genomic medicine, the complexity of delivering precision medicine to oncology patients across a university health system demanded the creation of a Molecular Tumor Board (MTB) for patient selection and assessment of treatment options. The objective of this report is to analyze our progress to date and discuss the importance of the MTB in the implementation of personalized medicine. MATERIALS AND METHODS: Patients were reviewed in the MTB for appropriateness for comprehensive next generation sequencing (NGS) cancer gene set testing based on set criteria that were in place...
June 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28630590/analysis-of-prognostic-factors-for-melanoma-patients
#3
Andrė Lideikaitė, Julija Mozūraitienė, Simona Letautienė
Introduction. Melanoma is the most dangerous form of skin cancer. Morbidity from melanoma is increasing every year. Previous studies have revealed that there are some demographic and clinical factors having effect on melanoma survival prognosis. Aim of the study. Purpose of our study was to assess melanoma survival depending on prognostic factors, such as age, sex, stage, depth, histology and anatomical site. Materials and methods. We investigated melanoma-specific survival up to 10 years in 85 primary cases of melanoma from diagnosis at the National Cancer Institute in 2006...
2017: Acta medica Lituanica
https://www.readbyqxmd.com/read/28628251/a-network-meta-analysis-of-short-and-long-term-efficacy-of-targeted-therapy-with-single-or-double-drug-regimens-in-the-treatment-of-stage-iii-iv-malignant-melanoma-based-on-16-randomized-controlled-trials
#4
Ting Xie, Chun-Yu Huang, Xu Kang, Jia-Sheng Luo, Xiao-Min Qin, Feng Han
For the treatment of stage III/IV malignant melanoma (MM), a network meta-analysis (NMA) was conducted to compare the short and long-term efficacy of targeted therapy with single or double-drug regimens. All conducted randomized controlled trials (RCTs) searched from PubMed and Cochrane Library were included in the study for direct and indirect comparison for MM. The odds ratio (OR) and surface under the cumulative ranking curves (SUCRA) value of the targeted therapy with single or double-drug regimens for treatment of stage III/IV MM were also analyzed...
June 19, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28616701/predictive-value-of-pd-l1-based-on-mrna-level-in-the-treatment-of-stage-iv-melanoma-with-ipilimumab
#5
C Brüggemann, M C Kirchberger, S M Goldinger, B Weide, A Konrad, M Erdmann, D Schadendorf, R S Croner, L Krähenbühl, K C Kähler, C Hafner, W Leisgang, F Kiesewetter, R Dummer, G Schuler, M Stürzl, L Heinzerling
INTRODUCTION: PD-L1 is established as a predictive marker for therapy of non-small cell lung cancer with pembrolizumab. Furthermore, PD-L1 positive melanoma has shown more favorable outcomes when treated with anti-PD1 antibodies and dacarbazine compared to PD-L1 negative melanoma. However, the role of PD-L1 expression with regard to response to checkpoint inhibition with anti-CTLA-4 is not clear, yet. In addition, the lack of standardization in the immunohistochemical assessment of PD-L1 makes the comparison of results difficult...
June 14, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28613357/optical-coherence-tomography-angiography-in-the-multimodal-imaging-evaluation-of-interferon-associated-retinopathy-a-case-report
#6
Leonardo Mastropasqua, Enrico Borrelli, Francesco Amodei, Agbeanda Aharrh-Gnama, Lisa Toto, Peter A Mattei, Rodolfo Mastropasqua
The authors present the case of a 59-year-old woman in treatment with interferon alfa-2b for stage IV melanoma and widespread metastases who presented with interferon-associated retinopathy. An ocular examination revealed multiple retinal cotton-wool spots and hard exudates. Interferon treatment was suspended. The patient was followed up for 5 months following the baseline visit by means of en face optical coherence tomography (OCT), spectral-domain OCT, and OCT angiography. Multimodal imaging was useful in the follow-up of this condition, permitting the characterization of all the lesions hallmarking the interferon-retinopathy and showing that this illness was related to a reduction of the retinal vascular perfusion...
June 1, 2017: Ophthalmic Surgery, Lasers & Imaging Retina
https://www.readbyqxmd.com/read/28607807/immunohistochemical-evaluation-of-vitamin-d-receptor-vdr-expression-in-cutaneous-melanoma-tissues-and-four-vdr-gene-polymorphisms
#7
Francesco La Marra, Giuseppe Stinco, Cinzia Buligan, Giovanni Chiriacò, Diego Serraino, Carla Di Loreto, Sabina Cauci
OBJECTIVE: : Vitamin D receptor (VDR) mediates vitamin D activity. We examined whether VDR expression in excised melanoma tissues is associated with VDR gene (VDR) polymorphisms. METHODS: : We evaluated VDR protein expression (by monoclonal antibody immunostaining), melanoma characteristics, and carriage of VDR-FokI-rs2228570 (C>T),VDR-BsmI-rs1544410 (G>A),VDR-ApaI-rs7975232 (T>G), andVDR-TaqI-rs731236 (T>C) polymorphisms (by restriction fragment length polymorphism)...
May 2017: Cancer Biology & Medicine
https://www.readbyqxmd.com/read/28601879/outcomes-in-melanoma-patients-treated-with-braf-mek-directed-therapy-or-immune-checkpoint-inhibition-stratified-by-clinical-trial-versus-standard-of-care
#8
Chloe Goldman, Jeremy Tchack, Eric M Robinson, Sung Won Han, Una Moran, David Polsky, Russell S Berman, Richard L Shapiro, Patrick A Ott, Iman Osman, Hua Zhong, Anna C Pavlick, Melissa Ann Wilson
OBJECTIVES: Since 2011, metastatic melanoma treatment has evolved with commercial approval of BRAF- and MEK-targeted therapy and CTLA-4- and PD-1-blocking antibodies (immune checkpoint inhibitors, ICI). While novel therapies have demonstrated improved prognosis in clinical trials, few studies have examined the evolution of prognosis and toxicity of these drugs among an unselected population. We assess whether survival and toxicity reported in trials, which typically exclude most patients with brain metastases and poor performance status, are recapitulated within a commercial access population...
June 10, 2017: Oncology
https://www.readbyqxmd.com/read/28583644/improved-detection-of-melanoma-metastases-by-iodine-maps-from-dual-energy-ct
#9
Monika Uhrig, David Simons, David Bonekamp, Heinz-Peter Schlemmer
OBJECTIVE: Metastatic disease in melanoma has an unpredictable nature with deposits in rare locations such as musculature. Dual energy CT (DECT) provides high contrast-visualization of enhancement by using spectral properties of iodine. Purpose of this study was to evaluate whether iodine maps from DECT improve lesion detection in staging examinations of melanoma patients. METHODS: This retrospective study was approved by IRB and written informed consent was obtained from all patients...
May 2017: European Journal of Radiology
https://www.readbyqxmd.com/read/28557366/radiosensitization-by-braf-inhibitors
#10
Sophia Boyoung Strobel, Sylvie Pätzold, Lisa Zimmer, Alexandra Jensen, Alexander Enk, Jessica Cecile Hassel
BACKGROUND: Increased skin toxicity during combination therapy with a BRAF inhibitor and radiation therapy has recently been reported. MATERIAL AND METHODS: We present seven melanoma patients with non-resectable stage III or IV disease and concomitant treatment with a BRAF inhibitor and radiation therapy. RESULTS: In all patients, combination therapy yielded a good local response. Only two patients, both on vemurafenib, showed severe radiation dermatitis (CTCAE grade 3/4) after one and two weeks, respectively, resulting in interruption of BRAF inhibitor treatment...
May 30, 2017: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
https://www.readbyqxmd.com/read/28557046/decisions-to-limit-or-withdraw-treatment-in-young-adults-with-melanoma
#11
Le Guern, L Touzet-Huffman, A Greliak, L Mortier
melanoma reaches the highest mortality rate by cancer among young men (ages 20-34) in France (1). A recent study suggests that age does not affect survival in patients with advanced disease (3). The prognosis of patients with metastatic or stage IV melanoma is grim, with a 1-year survival rate of 25% and a median overall survival of 6.2 months (2). This article is protected by copyright. All rights reserved.
May 30, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28551671/sarcoidosis-under-dendritic-cell-vaccination-immunotherapy-in-long-term-responding-patients-with-metastatic-melanoma
#12
Ugur Uslu, Michael Erdmann, Stefan Schliep, Jan Dörrie, Niels Schaft, Gerold Schuler, Beatrice Schuler-Thurner
Sarcoidosis, a chronic inflammatory disorder, results from increased immune responses. Its development can be triggered in patients under immunotherapy, as activation of the immune system in these patients is desired. Since 1997, 249 patients with metastasized cutaneous melanoma (stage III and IV, AJCC 2009) have been treated with dendritic cell (DC)-based vaccines at our hospital. Three out of these patients were diagnosed with sarcoidosis after or during long-term DC vaccination therapy (1.20%). Metastatic disease was initially suspected based on the radiographic manifestation of lung masses or bilateral hilar lymphadenopathy...
June 2017: Anticancer Research
https://www.readbyqxmd.com/read/28543700/interaction-of-molecular-alterations-with-immune-response-in-melanoma
#13
REVIEW
Robert A Szczepaniak Sloane, Vancheswaran Gopalakrishnan, Sangeetha M Reddy, Xue Zhang, Alexandre Reuben, Jennifer A Wargo
Major advances have been made in melanoma treatment with the use of molecularly targeted therapies and immunotherapies, and numerous regimens are now approved by the US Food and Drug Administration for patients with stage IV disease. However, therapeutic resistance remains an issue to both classes of agents, and reliable biomarkers of therapeutic response and resistance are lacking. Mechanistic insights are being gained through preclinical studies and translational research, offering potential strategies to enhance responses and survival in treated patients...
June 1, 2017: Cancer
https://www.readbyqxmd.com/read/28536308/immune-correlates-of-gm-csf-and-melanoma-peptide-vaccination-in-a-randomized-trial-for-the-adjuvant-therapy-of-resected-high-risk-melanoma-e4697
#14
Lisa H Butterfield, Fengmin Zhao, Sandra Lee, Ahmad A Tarhini, Kim A Margolin, Richard L White, Michael Atkins, Gary I Cohen, Theresa L Whiteside, John M Kirkwood, David H Lawson
Purpose: E4697 was a multi-center intergroup randomized placebo-controlled Phase III trial of adjuvant GM-CSF and/or a multi-epitope melanoma peptide vaccine for patients with completely resected, high-risk stage III/IV melanoma. <p>Experimental Design: 815 patients were enrolled from 12/99 to 10/06 into this 6-arm study. GM-CSF was chosen to promote the numbers and functions of dendritic cells (DC). The melanoma antigen peptide vaccine (Tyrosinase368-376 (370D), gp100209-217 (210M), MART-127-35) in Montanide was designed to promote melanoma specific CD8(+) T cell responses...
May 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28522460/soluble-pd-l1-as-a-biomarker-in-malignant-melanoma-treated-with-checkpoint-blockade
#15
Jun Zhou, Kathleen M Mahoney, Anita Giobbie-Hurder, Fengmin Zhao, Sandra Lee, Xiaoyun Liao, Scott Rodig, Jingjing Li, Xinqi Wu, Lisa H Butterfield, Matthias Piesche, Michael P Manos, Lauren M Eastman, Glenn Dranoff, Gordon J Freeman, F Stephen Hodi
Blockade of the pathway including programmed death-ligand 1 (PD-L1) and its receptor programmed cell death protein 1 (PD-1) has produced clinical benefits in patients with a variety of cancers. Elevated levels of soluble PD-L1 (sPD-L1) have been associated with worse prognosis in renal cell carcinoma and multiple myeloma. However, the regulatory roles and function of sPD-L1 particularly in connection with immune checkpoint blockade treatment are not fully understood. We identified four splice variants of PD-L1 in melanoma cells, and all of them are secreted...
June 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28512666/diagnostic-efficacy-of-digital-dermoscopy-and-clinical-findings-in-thin-melanoma-of-the-lower-limbs
#16
Emi Dika, Marco Adriano Chessa, Simone Ribero, Pier A Fanti, Carlotta Gurioli, Martina Lambertini, Carlotta Baraldi, Annalisa Patrizi
The introduction of dermoscopy has improved the accuracy of diagnosis of melanoma. However, early stage melanoma can be difficult to diagnose. Eighty-nine cases of thin melanoma with a Breslow thickness ≤1 mm located on the lower limb and diagnosed between 2008 and 2016 were assessed using 4 dermoscopic algorithms: (i) modified pattern analysis; (ii) ABCD rule of dermoscopy; (iii) 7-point checklist; and (iv) Menzies' method. Two groups of early stage melanomas of the legs were identified: "difficult to diagnose melanomas" (DDM) and "non-difficult to diagnose melanomas" (NDDM)...
May 17, 2017: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/28512174/dynamic-changes-in-pd-l1-expression-and-immune-infiltrates-early-during-treatment-predict-response-to-pd-1-blockade-in-melanoma
#17
Ricardo E Vilain, Alexander M Menzies, James S Wilmott, Hojabr Kakavand, Jason Madore, Alexander Guminski, Elizabeth Liniker, Ben Kong, Adam Cooper, Julie R Howle, Robyn P M Saw, Valerie Jakrot, Serigne Lo, John F Thompson, Matteo S Carlino, Richard F Kefford, Georgina V Long, Richard A Scolyer
Disruption of PD-L1/cytotoxic T-cell PD-1 signalling by immune-checkpoint inhibitors improves survival in cancer patients. This study sought to identify changes in tumoral PD-L1 expression and tumor-associated immune cell flux with anti-PD1 therapies in melanoma patients, particularly early during treatment, and correlate them with treatment response<br /><br />Experimental Design: Forty-six tumor biopsies from 23 unresectable AJCC Stage III/IV melanoma patients receiving pembrolizumab/nivolumab were analyzed...
May 16, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28509765/multicenter-real-life-experience-with-checkpoint-inhibitors-and-targeted-therapy-agents-in-advanced-melanoma-patients-in-switzerland
#18
Joanna Mangana, Phil F Cheng, Corina Kaufmann, Valerie C Amann, Anna L Frauchiger, Viola Stögner, Ulrike Held, Roger von Moos, Olivier Michielin, Ralph P Braun, Mitchell P Levesque, Simone M Goldinger, Reinhard Dummer
Metastatic melanoma is a highly aggressive disease. Recent progress in immunotherapy (IT) and targeted therapy (TT) has led to significant improvements in response and survival rates in metastatic melanoma patients. The current project aims to determine the benefit of the introduction of these new therapies in advanced melanoma across several regions of Switzerland. This is a retrospective multicenter analysis of 395 advanced melanoma patients treated with standard chemotherapy, checkpoint inhibitors, and kinase inhibitors from January 2008 until December 2014...
June 1, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28506536/checkpoint-inhibition-and-melanoma-considerations-in-treating-the-older-adult
#19
REVIEW
Claire F Friedman, Jedd D Wolchok
The incidence of melanoma and associated mortality rate from advanced disease in older adults is increasing over time. Checkpoint inhibitors have demonstrated a survival benefit for the treatment of stage IV or unresectable stage III disease and have become one of the standards of care. Data suggests that adults aged 65 and older benefit from treatment with checkpoint inhibitors without an increased incidence in adverse events. However, clinicians should be aware of the potential side effects of this class of medications and how to manage them in older adults...
May 11, 2017: Journal of Geriatric Oncology
https://www.readbyqxmd.com/read/28499411/paraneoplastic-acral-vascular-syndrome-in-a-patient-with-metastatic-melanoma-under-immune-checkpoint-blockade
#20
Thilo Gambichler, Stefanie Strutzmann, Andrea Tannapfel, Laura Susok
BACKGROUND: Paraneoplastic acral vascular syndrome (PAVS) is a rare phenomenon which is observed in patients with adenocarcinomas and other malignancies. Various potential pathogenic mechanisms such as tumour invasion of sympathetic nerves, hyperviscosity, hypercoagulability, vasoactive tumour-secreted substances, and immunological mechanisms have been suggested. CASE PRESENTATION: We report a 60-year-old Caucasian male attended our hospital with a bulky lymph node mass in the right axilla...
May 12, 2017: BMC Cancer
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