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https://www.readbyqxmd.com/read/28423700/hla-class-i-loss-in-metachronous-metastases-prevents-continuous-t-cell-recognition-of-mutated-neoantigens-in-a-human-melanoma-model
#1
Barbara Schrörs, Silke Lübcke, Volker Lennerz, Martina Fatho, Anne Bicker, Catherine Wölfel, Patrick Derigs, Thomas Hankeln, Dirk Schadendorf, Annette Paschen, Thomas Wölfel
T lymphocytes against tumor-specific mutated neoantigens can induce tumor regression. Also, the size of the immunogenic cancer mutanome is supposed to correlate with the clinical efficacy of checkpoint inhibition. Herein, we studied the susceptibility of tumor cell lines from lymph node metastases occurring in a melanoma patient over several years towards blood-derived, neoantigen-specific CD8+ T cells. In contrast to a cell line established during early stage III disease, all cell lines generated at later time points from stage IV metastases exhibited partial or complete loss of HLA class I expression...
March 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28401596/successful-retreatment-with-combined-braf-mek-inhibition-in-metastatic-brafv600-mutated-melanoma
#2
Valerie C Amann, Dorothée Hoffmann, Joanna Mangana, Reinhard Dummer, Simone M Goldinger
BACKGROUND: The combination treatment with BRAF- and MEK-inhibitors is amongst the current standard of care for stage IIIC/IV BRAF-mutated melanoma. However, therapeutic options are limited once patients have progressed upon both targeted and immunotherapy. OBJECTIVE: To investigate whether retreatment with BRAF- and MEK-inhibitor combination is an option for patients with metastatic BRAF-mutated melanoma upon previous progression on kinase inhibitors. METHODS: Two patients with metastatic BRAF-mutated melanoma were rechallenged with BRAF- and MEK-inhibitor combination after progression on targeted therapy and subsequent immunotherapy with anti-CTLA-4 and anti-PD-1 antibodies...
April 12, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28397821/t-cell-invigoration-to-tumour-burden-ratio-associated-with-anti-pd-1-response
#3
Alexander C Huang, Michael A Postow, Robert J Orlowski, Rosemarie Mick, Bertram Bengsch, Sasikanth Manne, Wei Xu, Shannon Harmon, Josephine R Giles, Brandon Wenz, Matthew Adamow, Deborah Kuk, Katherine S Panageas, Cristina Carrera, Phillip Wong, Felix Quagliarello, Bradley Wubbenhorst, Kurt D'Andrea, Kristen E Pauken, Ramin S Herati, Ryan P Staupe, Jason M Schenkel, Suzanne McGettigan, Shawn Kothari, Sangeeth M George, Robert H Vonderheide, Ravi K Amaravadi, Giorgos C Karakousis, Lynn M Schuchter, Xiaowei Xu, Katherine L Nathanson, Jedd D Wolchok, Tara C Gangadhar, E John Wherry
Despite the success of monotherapies based on blockade of programmed cell death 1 (PD-1) in human melanoma, most patients do not experience durable clinical benefit. Pre-existing T-cell infiltration and/or the presence of PD-L1 in tumours may be used as indicators of clinical response; however, blood-based profiling to understand the mechanisms of PD-1 blockade has not been widely explored. Here we use immune profiling of peripheral blood from patients with stage IV melanoma before and after treatment with the PD-1-targeting antibody pembrolizumab and identify pharmacodynamic changes in circulating exhausted-phenotype CD8 T cells (Tex cells)...
April 10, 2017: Nature
https://www.readbyqxmd.com/read/28389511/epigenetic-regulation-of-kpc1-ubiquitin-ligase-effects-the-nf-%C3%AE%C2%BAb-pathway-in-melanoma
#4
Yuuki Iida, Aaron Ciechanover, Diego M Marzese, Keisuke Hata, Matias Bustos, Shigeshi Ono, Jinhua Wang, Matthew P Salomon, Kevin Tran, Stella Lam, Sandy C Hsu, Nellie Nelson, Yelena Kravtsova-Ivantsiv, Gordon B Mills, Michael A Davies, Dave Sb Hoon
PURPOSE: Abnormal activation of the NF-κB pathway induces a more aggressive phenotype of cutaneous melanoma. Understanding the mechanisms involved in melanoma NF-κB activation may identify novel targets for this pathway. KPC1, an E3 ubiquitin ligase, is a regulator of NF-κB pathway. The objective of this study was to investigate the mechanisms regulating KPC1 expression and its clinical impact in melanoma. EXPERIMENTAL DESIGN: The clinical impact of KPC1 expression and its epigenetic regulation were assessed in large cohorts of clinically well-annotated melanoma tissues (tissue micro-arrays; n=137, JWCI cohort; n=40) and The Cancer Genome Atlas database (TCGA cohort, n=370)...
April 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28359784/ipilimumab-10-mg-kg-versus-ipilimumab-3-mg-kg-in-patients-with-unresectable-or-metastatic-melanoma-a-randomised-double-blind-multicentre-phase-3-trial
#5
Paolo A Ascierto, Michele Del Vecchio, Caroline Robert, Andrzej Mackiewicz, Vanna Chiarion-Sileni, Ana Arance, Céleste Lebbé, Lars Bastholt, Omid Hamid, Piotr Rutkowski, Catriona McNeil, Claus Garbe, Carmen Loquai, Brigitte Dreno, Luc Thomas, Jean-Jacques Grob, Gabriella Liszkay, Marta Nyakas, Ralf Gutzmer, Joanna Pikiel, Florent Grange, Christoph Hoeller, Virginia Ferraresi, Michael Smylie, Dirk Schadendorf, Laurent Mortier, Inge Marie Svane, Delphine Hennicken, Anila Qureshi, Michele Maio
BACKGROUND: A phase 2 trial suggested increased overall survival and increased incidence of treatment-related grade 3-4 adverse events with ipilimumab 10 mg/kg compared with ipilimumab 3 mg/kg in patients with advanced melanoma. We report a phase 3 trial comparing the benefit-risk profile of ipilimumab 10 mg/kg versus 3 mg/kg. METHODS: This randomised, double-blind, multicentre, phase 3 trial was done in 87 centres in 21 countries worldwide. Patients with untreated or previously treated unresectable stage III or IV melanoma, without previous treatment with BRAF inhibitors or immune checkpoint inhibitors, were randomly assigned (1:1) with an interactive voice response system by the permuted block method using block size 4 to ipilimumab 10 mg/kg or 3 mg/kg, administered by intravenous infusion for 90 min every 3 weeks for four doses...
March 27, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28356222/neutrophil-to-lymphocyte-ratio-is-associated-with-outcome-during-ipilimumab-treatment
#6
Michael R Cassidy, Rachel E Wolchok, Junting Zheng, Katherine S Panageas, Jedd D Wolchok, Daniel Coit, Michael A Postow, Charlotte Ariyan
BACKGROUND: Ipilimumab (IPI) and BRAF inhibitors (BRAFi) improve survival in melanoma, but not all patients will benefit and toxicity can be significant. Pretreatment neutrophil to lymphocyte ratio (NLR) has been associated with outcome in IPI-treated patients, but has not been studied during treatment or in BRAFi-treated patients. METHODS: Using a prospectively maintained database, patients with unresectable stage III or IV melanoma treated with IPI or a BRAFi (vemurafenib or dabrafenib as monotherapy) from 2006 to 2011 were identified...
March 24, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28342215/efficacy-and-safety-of-nivolumab-in-japanese-patients-with-previously-untreated-advanced-melanoma-a-phase-ii-study
#7
Naoya Yamazaki, Yoshio Kiyohara, Hisashi Uhara, Jiro Uehara, Manabu Fujimoto, Tatsuya Takenouchi, Masaki Otsuka, Hiroshi Uchi, Hironobu Ihn, Hironobu Minami
Treating advanced or recurrent melanoma remains a challenge. Cancer cells can evade the immune system by blocking T-cell activation via overexpression of the inhibitory receptor programmed death 1 (PD-1) ligands. The PD-1 inhibitor nivolumab blocks the inhibitory signal in T cells, thus overcoming the immune resistance of cancer cells. Nivolumab has demonstrated promising anti-cancer activity in various cancers. We conducted a single-arm, open-label, multicenter, phase II study to investigate the efficacy and safety of nivolumab in previously untreated Japanese patients with advanced melanoma...
March 25, 2017: Cancer Science
https://www.readbyqxmd.com/read/28334439/a-phase-2-trial-of-dasatinib-in-patients-with-locally-advanced-or-stage-iv-mucosal-acral-or-vulvovaginal-melanoma-a-trial-of-the-ecog-acrin-cancer-research-group-e2607
#8
Kevin Kalinsky, Sandra Lee, Krista M Rubin, Donald P Lawrence, Anthony J Iafrarte, Darell R Borger, Kim A Margolin, Mario M Leitao, Ahmad A Tarhini, Henry B Koon, Andrew L Pecora, Anthony J Jaslowski, Gary I Cohen, Timothy M Kuzel, Christopher D Lao, John M Kirkwood
BACKGROUND: KIT-directed tyrosine kinase inhibitors such as imatinib have demonstrated benefits in KIT-mutant (KIT+) mucosal, acral, vulvovaginal, and chronically sun-damaged (CSD) melanoma. Dasatinib has superior preclinical activity in comparison with other tyrosine kinase inhibitors against cells with the most common KIT mutation, exon 11(L576P) . The ECOG-ACRIN E2607 trial assessed dasatinib in patients with these melanoma subtypes. METHODS: Patients received 70 mg of oral dasatinib twice daily...
March 23, 2017: Cancer
https://www.readbyqxmd.com/read/28329597/melanoma-occurrence-under-long-term-etanercept-treatment-for-psoriasis-a-case-report
#9
Laura Atzori, Luca Pilloni, Severino Murgia, Cristina Mugheddu, Monica Pau, Franco Rongioletti
Melanoma occurrence during treatment with anti-tumor necrosis factor is considered an incidental event, although very recent studies suggest a risk. Etanercept is a fusion protein that binds the tumor necrosis factor receptor and is included among TNF inhibitors, approved for the treatment of several autoimmune diseases, such as psoriasis.We described a 79-year-old man with psoriasis, being treated with etanercept, who presented with a new brown to black macule on his right shoulder; this was immediately surgically excised...
October 15, 2016: Dermatology Online Journal
https://www.readbyqxmd.com/read/28323504/pembrolizumab-use-for-the-treatment-of-advanced-melanoma
#10
Pol Specenier
Until recently, overall long term survival in patients with stage IV melanoma was lower than 10 %. However, the treatment of melanoma has evolved rapidly over the last few years, with the advent of inhibitors of BRAF and MEK and of immunotherapeutic agents including ipilimumab, nivolumab, and pembrolizumab. Areas covered: This is a comprehensive review of the literature on the role of pembrolizumab in melanoma. Pembrolizumab is a Programmed Death Receptor 1 (PD-1) directed monoclonal antibody which is approved by FDA and EMA for the treatment of patients with metastatic melanoma...
March 21, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28316007/talimogene-laherparepvec-for-treating-metastatic-melanoma-an-evidence-review-group-perspective-of-a-nice-single-technology-appraisal
#11
REVIEW
Nigel Fleeman, Adrian Bagust, Angela Boland, Sophie Beale, Marty Richardson, Ashma Krishan, Angela Stainthorpe, Ahmed Abdulla, Eleanor Kotas, Lindsay Banks, Miranda Payne
The National Institute for Health and Care Excellence (NICE) invited the manufacturer (Amgen) of talimogene laherparepvec (T-VEC) to submit clinical and cost-effectiveness evidence for previously untreated advanced (unresectable or metastatic) melanoma as part of the Institute's Single Technology Appraisal process. The Liverpool Reviews and Implementation Group (LRiG) at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG). This article presents a summary of the company's submission of T-VEC, the ERG review and the resulting NICE guidance (TA410), issued in September 2016...
March 18, 2017: PharmacoEconomics
https://www.readbyqxmd.com/read/28315947/impact-of-18-f-fdg-pet-ct-on-surgical-management-in-patients-with-advanced-melanoma-an-outcome-based-analysis
#12
Andrea Forschner, Susann-Cathrin Olthof, Brigitte Gückel, Peter Martus, Werner Vach, Christian la Fougère, Konstantin Nikolaou, Ulrike Keim, Thomas Kurt Eigentler, Claus Garbe, Christina Pfannenberg
PURPOSE: To evaluate the influence of (18)F-FDG-PET/CT on clinical decision making and outcome in advanced melanoma patients planned for radical metastasectomy. METHODS AND MATERIALS: A cohort of 333 patients with mainly stage III/IV melanoma having a PET/CT for clinical reasons was prospectively enrolled in our oncologic PET/CT registry between 2013 and 2015. Referring physicians completed questionnaires regarding their intended management for each patient before and after PET/CT...
March 18, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28315636/pembrolizumab-for-metastatic-melanoma-in-a-renal-allograft-recipient-with-subsequent-graft-rejection-and-treatment-response-failure-a-case-report
#13
Vineet Kwatra, Narayan V Karanth, Kelum Priyadarshana, Michail Charakidis
BACKGROUND: Transplant patients were excluded from the pivotal phase III trials of checkpoint inhibitors in metastatic melanoma. The efficacy and toxicity profiles of checkpoint inhibitors in this cohort of patients are not well described. To the best of our knowledge, this is the first case report of a renal transplant patient with stage IV melanoma treated with a programmed cell death protein 1 checkpoint inhibitor that led to both treatment failure and renal graft rejection. CASE PRESENTATION: We present a case of a 58-year-old white man with a long-standing cadaveric renal transplant who was diagnosed with a B-Raf Proto-Oncogene, Serine/Threonine Kinase wild-type metastatic melanoma...
March 19, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/28314913/laser-and-light-based-therapy-for-cutaneous-and-soft-tissue-metastases-of-malignant-melanoma-a-systematic-review
#14
REVIEW
Evan Austin, Andrew Mamalis, Derek Ho, Jared Jagdeo
Invasive cutaneous melanoma is a growing health concern. Although surgical excision can effectively treat in situ tumors, use for metastatic melanoma is limited. Laser and light-based therapies may be a valuable palliative treatment option for patients with stage III and stage IV cutaneous metastatic melanoma. Our goal is to review the published literature and provide evidence-based recommendations on laser and light-based palliative therapies for metastatic melanoma. A search of the databases Pubmed, EMBASE, Web of Science, and CINAHL was performed on March 10, 2016...
May 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28303429/elevated-blood-neutrophil-to-lymphocyte-ratio-a-readily-available-biomarker-associated-with-death-due-to-disease-in-high-risk-nonmetastatic-melanoma
#15
Jeremy L Davis, Russell C Langan, Katherine S Panageas, Junting Zheng, Michael A Postow, Mary S Brady, Charlotte Ariyan, Daniel G Coit
BACKGROUND: Elevated peripheral blood neutrophil-to-lymphocyte ratio (NLR) is associated with poor oncologic outcomes in patients with stage IV melanoma and other solid tumors, but its impact has not been characterized for patients with high-risk, nonmetastatic melanoma. METHODS: Retrospective review of a melanoma database identified patients with high-risk melanoma who underwent operation with curative intent at a single institution. NLR was calculated from blood samples obtained within 2 weeks before operation...
March 16, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28296712/association-between-the-use-of-surveillance-pet-ct-and-the-detection-of-potentially-salvageable-occult-recurrences-among-patients-with-resected-high-risk-melanoma
#16
Roberto A Leon-Ferre, Lisa A Kottschade, Matthew S Block, Robert R McWilliams, Roxana S Dronca, Edward T Creagan, Jacob B Allred, Val J Lowe, Svetomir N Markovic
The optimal surveillance for patients with resected high-risk melanoma is controversial. Select locoregional or oligometastatic recurrences can be cured with salvage resection. Data on the ability of PET/CT to detect such recurrences are sparse. We evaluated whether surveillance PET/CT in patients with resected stage III-IV melanoma led to detection of clinically occult recurrences amenable to curative-intent salvage treatment. We retrospectively identified 1429 melanoma patients who underwent PET/CT between January 2008 and October 2012 at Mayo Clinic (Rochester, Minnesota)...
March 14, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28291064/scrotal-melanoma-a-systematic-review-of-presentation-treatment-and-outcomes
#17
Joseph Zikry, Lance W Chapman, Dorota Z Korta, Janellen Smith
BACKGROUND: Primary male genital melanomas are rare. Of these, scrotal melanoma is the least common, and is unfortunately often detected late in the disease course. OBJECTIVE: To assess the clinical presentation, treatment modalities, and outcome of scrotal melanoma to aid clinician management. METHODS: Systematic literature review of PubMed, yielding 23 cases, of which 20 met the inclusion criteria. RESULTS: Although previously thought to have the best outcome of genitourinary melanomas, scrotal melanomas are associated with high mortality and late presentation...
March 13, 2017: Dermatologic Surgery: Official Publication for American Society for Dermatologic Surgery [et Al.]
https://www.readbyqxmd.com/read/28290625/treatment-of-metastatic-melanoma-a-multi-disciplinary-approach
#18
Paolo Fava, Chiara Astrua, Martina Sanlorenzo, Simone Ribero, Matteo Brizio, Andrea R Filippi, Elena Marra, Franco Picciotto, Dario Sangiolo, Fabrizio Carnevale-Schianca, Massimo Aglietta, Sergio Sandrucci, Umberto Ricardi, Virginia Caliendo, Pietro Quaglino, Maria T Fierro
The prognosis of stage IV metastatic melanoma is poor. An overal 1-year survival of 25.5% and a median survival of 6.2 months were reported without any significant improvement during the last 30 years before the introduction of new drugs (immune check point inhibitors and targeted therapies) which completely modified the therapeutic approach and induced an overwhelming improvement on the survival rates of these patients. This review will analyse the therapeutic tools available for the treatment of patients with metastatic melanoma, including adjuvant interferon and loco-regional therapies (surgery, radiotherapy and electrochemotherapy) and will mainly focus on the presentation of results obtained by the new treatments (check point inhibitors and targeted therapies)...
March 14, 2017: Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Società Italiana di Dermatologia e Sifilografia
https://www.readbyqxmd.com/read/28284557/binimetinib-versus-dacarbazine-in-patients-with-advanced-nras-mutant-melanoma-nemo-a-multicentre-open-label-randomised-phase-3-trial
#19
Reinhard Dummer, Dirk Schadendorf, Paolo A Ascierto, Ana Arance, Caroline Dutriaux, Anna Maria Di Giacomo, Piotr Rutkowski, Michele Del Vecchio, Ralf Gutzmer, Mario Mandala, Luc Thomas, Lev Demidov, Claus Garbe, David Hogg, Gabriella Liszkay, Paola Queirolo, Ernesto Wasserman, James Ford, Marine Weill, L Andres Sirulnik, Valentine Jehl, Viviana Bozón, Georgina V Long, Keith Flaherty
BACKGROUND: There are no established therapies specific for NRAS-mutant melanoma despite the emergence of immunotherapy. We aimed to assess the efficacy and safety of the MEK inhibitor binimetinib versus that of dacarbazine in patients with advanced NRAS-mutant melanoma. METHODS: NEMO is an ongoing, randomised, open-label phase 3 study done at 118 hospitals in 26 countries. Patients with advanced, unresectable, American Joint Committee on Cancer stage IIIC or stage IV NRAS-mutant melanoma who were previously untreated or had progressed on or after previous immunotherapy were randomised (2:1) to receive either binimetinib 45 mg orally twice daily or dacarbazine 1000 mg/m(2) intravenously every 3 weeks...
April 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28272106/m1-and-m2-macrophages-clinicopathological-significance-in-cutaneous-melanoma
#20
Monica Falleni, Federica Savi, Delfina Tosi, Elena Agape, Amilcare Cerri, Laura Moneghini, Gaetano P Bulfamante
Skin malignant melanoma (MM) is an aggressive cancer with an increasing incidence with limited therapies in advanced stages. Tumor-associated macrophages (TAMs) are the major immune constituent of the MM microenvironment and contribute toward its prognosis. TAMs' characterization and localization in human cancer is important to understand cancer progression and to identify molecular personalized therapies. M2 TAMs in stage I-II MMs are associated with worse prognostic parameters. A comprehensive M1-macrophage and M2-macrophage intratumoral localization and quantification in all stages of skin MMs is documented here with its clinical significance...
March 7, 2017: Melanoma Research
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