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Melanoma: HELP
Articles from Washington
Based on 227 articles published since 2008
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These are the 227 published articles about Melanoma that originated from Washington during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8 · 9 · 10
1 Guideline Guidelines of care for the management of primary cutaneous melanoma. 2019

Swetter, Susan M / Tsao, Hensin / Bichakjian, Christopher K / Curiel-Lewandrowski, Clara / Elder, David E / Gershenwald, Jeffrey E / Guild, Valerie / Grant-Kels, Jane M / Halpern, Allan C / Johnson, Timothy M / Sober, Arthur J / Thompson, John A / Wisco, Oliver J / Wyatt, Samantha / Hu, Shasa / Lamina, Toyin. ·Department of Dermatology, Stanford University Medical Center and Cancer Institute, Stanford, California; Veterans Affairs Palo Alto Health Care System, Palo Alto, California. Electronic address: sswetter@stanford.edu. · Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Wellman Center for Photomedicine, Boston, Massachusetts. · Department of Dermatology, University of Michigan Health System, Ann Arbor, Michigan; Comprehensive Cancer Center, Ann Arbor, Michigan. · Division of Dermatology, University of Arizona, Tucson, Arizona; University of Arizona Cancer Center, Tucson, Arizona. · Department of Dermatology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania; Department of Pathology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. · Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas; Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas. · AIM at Melanoma Foundation, Plano, Texas. · Department of Dermatology, University of Connecticut Health Center, Farmington, Connecticut; Department of Pathology, University of Connecticut Health Center, Farmington, Connecticut; Department of Pediatrics, University of Connecticut Health Center, Farmington, Connecticut. · Department of Dermatology, Memorial Sloan-Kettering Cancer Center, New York, New York. · Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. · Division of Oncology, University of Washington, Seattle, Washington; Seattle Cancer Care Alliance, Seattle, Washington. · Department of Dermatology, Oregon Health and Science University, Portland, Oregon. · Decatur Dermatology, Decatur, Alabama. · Department of Dermatology, University of Miami Health System, Miami, Florida. · American Academy of Dermatology, Rosemont, Illinois. ·J Am Acad Dermatol · Pubmed #30392755.

ABSTRACT: The incidence of primary cutaneous melanoma continues to increase each year. Melanoma accounts for the majority of skin cancer-related deaths, but treatment is usually curative following early detection of disease. In this American Academy of Dermatology clinical practice guideline, updated treatment recommendations are provided for patients with primary cutaneous melanoma (American Joint Committee on Cancer stages 0-IIC and pathologic stage III by virtue of a positive sentinel lymph node biopsy). Biopsy techniques for a lesion that is clinically suggestive of melanoma are reviewed, as are recommendations for the histopathologic interpretation of cutaneous melanoma. The use of laboratory, molecular, and imaging tests is examined in the initial work-up of patients with newly diagnosed melanoma and for follow-up of asymptomatic patients. With regard to treatment of primary cutaneous melanoma, recommendations for surgical margins and the concepts of staged excision (including Mohs micrographic surgery) and nonsurgical treatments for melanoma in situ, lentigo maligna type (including topical imiquimod and radiation therapy), are updated. The role of sentinel lymph node biopsy as a staging technique for cutaneous melanoma is described, with recommendations for its use in clinical practice. Finally, current data regarding pregnancy and melanoma, genetic testing for familial melanoma, and management of dermatologic toxicities related to novel targeted agents and immunotherapies for patients with advanced disease are summarized.

2 Guideline Sentinel Lymph Node Biopsy and Management of Regional Lymph Nodes in Melanoma: American Society of Clinical Oncology and Society of Surgical Oncology Clinical Practice Guideline Update. 2018

Wong, Sandra L / Faries, Mark B / Kennedy, Erin B / Agarwala, Sanjiv S / Akhurst, Timothy J / Ariyan, Charlotte / Balch, Charles M / Berman, Barry S / Cochran, Alistair / Delman, Keith A / Gorman, Mark / Kirkwood, John M / Moncrieff, Marc D / Zager, Jonathan S / Lyman, Gary H. ·Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA. · The Angeles Clinic and Research Institute, Santa Monica, CA, USA. · American Society of Clinical Oncology, Alexandria, VA, USA. guidelines@asco.org. · St Luke's Cancer Center, Easton, PA, USA. · Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. · Memorial Sloan Kettering Cancer Center, New York, NY, USA. · MD Anderson Cancer Center, Houston, TX, USA. · Broward Health, Fort Lauderdale, FL, USA. · Los Angeles Center for Health Services, University of California, Los Angeles, CA, USA. · Emory University, Atlanta, GA, USA. · , Silver Spring, MD, USA. · University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA. · Norfolk and Norwich University Hospital, Norwich, UK. · H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. · Fred Hutchinson Cancer Research Center, Seattle, WA, USA. ·Ann Surg Oncol · Pubmed #29236202.

ABSTRACT: PURPOSE: To update the American Society of Clinical Oncology (ASCO)-Society of Surgical Oncology (SSO) guideline for sentinel lymph node (SLN) biopsy in melanoma. METHODS: An ASCO-SSO panel was formed, and a systematic review of the literature was conducted regarding SLN biopsy and completion lymph node dissection (CLND) after a positive sentinel node in patients with melanoma. RESULTS: Nine new observational studies, two systematic reviews and an updated randomized controlled trial (RCT) of SLN biopsy, as well as two randomized controlled trials of CLND after positive SLN biopsy, were included. RECOMMENDATIONS: Routine SLN biopsy is not recommended for patients with thin melanomas that are T1a (non-ulcerated lesions < 0.8 mm in Breslow thickness). SLN biopsy may be considered for thin melanomas that are T1b (0.8 to 1.0 mm Breslow thickness or <0.8 mm Breslow thickness with ulceration) after a thorough discussion with the patient of the potential benefits and risk of harms associated with the procedure. SLN biopsy is recommended for patients with intermediate-thickness melanomas (T2 or T3; Breslow thickness of >1.0 to 4.0 mm). SLN biopsy may be recommended for patients with thick melanomas (T4; > 4.0 mm in Breslow thickness), after a discussion of the potential benefits and risks of harm. In the case of a positive SLN biopsy, CLND or careful observation are options for patients with low-risk micrometastatic disease, with due consideration of clinicopathological factors. For higher risk patients, careful observation may be considered only after a thorough discussion with patients about the potential risks and benefits of foregoing CLND. Important qualifying statements outlining relevant clinicopathological factors, and details of the reference patient populations are included within the guideline.

3 Guideline NCCN Guidelines Insights: Melanoma, Version 3.2016. 2016

Coit, Daniel G / Thompson, John A / Algazi, Alain / Andtbacka, Robert / Bichakjian, Christopher K / Carson, William E / Daniels, Gregory A / DiMaio, Dominick / Fields, Ryan C / Fleming, Martin D / Gastman, Brian / Gonzalez, Rene / Guild, Valerie / Johnson, Douglas / Joseph, Richard W / Lange, Julie R / Martini, Mary C / Materin, Miguel A / Olszanski, Anthony J / Ott, Patrick / Gupta, Aparna Priyanath / Ross, Merrick I / Salama, April K / Skitzki, Joseph / Swetter, Susan M / Tanabe, Kenneth K / Torres-Roca, Javier F / Trisal, Vijay / Urist, Marshall M / McMillian, Nicole / Engh, Anita. ·From Memorial Sloan Kettering Cancer Center; Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance; UCSF Helen Diller Family Comprehensive Cancer Center; Huntsman Cancer Institute at the University of Utah; University of Michigan Comprehensive Cancer Center; The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute; UC San Diego Moores Cancer Center; Fred & Pamela Buffett Cancer Center; Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine; The University of Tennessee Health Science Center; Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute; University of Colorado Cancer Center; Aim at Melanoma; Vanderbilt-Ingram Cancer Center; Mayo Clinic Cancer Center; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Robert H. Lurie Comprehensive Cancer Center of Northwestern University; Yale Cancer Center/Smilow Cancer Hospital; Fox Chase Cancer Center; Dana-Farber/Brigham and Women's Cancer Center; The University of Texas MD Anderson Cancer Center; Duke Cancer Institute; Roswell Park Cancer Institute; Stanford Cancer Institute; Massachusetts General Hospital Cancer Center; Moffitt Cancer Center; City of Hope Comprehensive Cancer Center; University of Alabama at Birmingham Comprehensive Cancer Center; and National Comprehensive Cancer Network. ·J Natl Compr Canc Netw · Pubmed #27496110.

ABSTRACT: The NCCN Guidelines for Melanoma have been significantly revised over the past few years in response to emerging data on a number of novel agents and treatment regimens. These NCCN Guidelines Insights summarize the data and rationale supporting extensive changes to the recommendations for systemic therapy in patients with metastatic or unresectable melanoma.

4 Guideline Screening for Skin Cancer: US Preventive Services Task Force Recommendation Statement. 2016

Anonymous2770876 / Bibbins-Domingo, Kirsten / Grossman, David C / Curry, Susan J / Davidson, Karina W / Ebell, Mark / Epling, John W / García, Francisco A R / Gillman, Matthew W / Kemper, Alex R / Krist, Alex H / Kurth, Ann E / Landefeld, C Seth / Mangione, Carol M / Phillips, William R / Phipps, Maureen G / Pignone, Michael P / Siu, Albert L. ·University of California, San Francisco. · Group Health Research Institute, Seattle, Washington. · University of Iowa, Iowa City. · Columbia University, New York, New York. · University of Georgia, Athens. · State University of New York Upstate Medical University, Syracuse. · Pima County Department of Health, Tucson, Arizona. · Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts. · Duke University, Durham, North Carolina. · Fairfax Family Practice Residency, Fairfax, Virginia11Virginia Commonwealth University, Richmond. · Yale University, New Haven, Connecticut. · University of Alabama at Birmingham. · University of California, Los Angeles. · University of Washington, Seattle. · Brown University, Providence, Rhode Island. · University of Texas at Austin. · Mount Sinai School of Medicine, New York, New York19James J. Peters Veterans Affairs Medical Center, Bronx, New York. ·JAMA · Pubmed #27458948.

ABSTRACT: IMPORTANCE: Basal and squamous cell carcinoma are the most common types of cancer in the United States and represent the vast majority of all cases of skin cancer; however, they rarely result in death or substantial morbidity, whereas melanoma skin cancer has notably higher mortality rates. In 2016, an estimated 76,400 US men and women will develop melanoma and 10,100 will die from the disease. OBJECTIVE: To update the 2009 US Preventive Services Task Force (USPSTF) recommendation on screening for skin cancer. EVIDENCE REVIEW: The USPSTF reviewed the evidence on the effectiveness of screening for skin cancer with a clinical visual skin examination in reducing skin cancer morbidity and mortality and death from any cause; its potential harms, including any harms resulting from associated diagnostic follow-up; its test characteristics when performed by a primary care clinician vs a dermatologist; and whether its use leads to earlier detection of skin cancer compared with usual care. FINDINGS: Evidence to assess the net benefit of screening for skin cancer with a clinical visual skin examination is limited. Direct evidence on the effectiveness of screening in reducing melanoma morbidity and mortality is limited to a single fair-quality ecologic study with important methodological limitations. Information on harms is similarly sparse. The potential for harm clearly exists, including a high rate of unnecessary biopsies, possibly resulting in cosmetic or, more rarely, functional adverse effects, and the risk of overdiagnosis and overtreatment. CONCLUSIONS AND RECOMMENDATION: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of visual skin examination by a clinician to screen for skin cancer in adults (I statement).

5 Guideline Melanoma, version 4.2014. 2014

Coit, Daniel G / Thompson, John A / Andtbacka, Robert / Anker, Christopher J / Bichakjian, Christopher K / Carson, William E / Daniels, Gregory A / Daud, Adil / Dimaio, Dominick / Fleming, Martin D / Gonzalez, Rene / Guild, Valerie / Halpern, Allan C / Hodi, F Stephen / Kelley, Mark C / Khushalani, Nikhil I / Kudchadkar, Ragini R / Lange, Julie R / Martini, Mary C / Olszanski, Anthony J / Ross, Merrick I / Salama, April / Swetter, Susan M / Tanabe, Kenneth K / Trisal, Vijay / Urist, Marshall M / McMillian, Nicole R / Ho, Maria / Anonymous5170793. ·From 1Memorial Sloan-Kettering Cancer Center; 2Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance; 3Huntsman Cancer Institute at the University of Utah; 4University of Michigan Comprehensive Cancer Center; 5The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute; 6UC San Diego Moores Cancer Center; 7UCSF Helen Diller Family Comprehensive Cancer Center; 8Fred & Pamela Buffett Cancer Center at The Nebraska Medical Center; 9St. Jude Children's Research Hospital/The University of Tennessee Health Science Center; 10University of Colorado Cancer Center; 11Aim at Melanoma; 12Dana-Farber/Brigham and Women's Cancer Center; 13Vanderbilt-Ingram Cancer Center; 14Roswell Park Cancer Institute; 15Moffitt Cancer Center; 16The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; 17Robert H. Lurie Comprehensive Cancer Center of Northwestern University; 18Fox Chase Cancer Center; 19The University of Texas MD Anderson Cancer Center; 20Duke Cancer Institute; 21Stanford Cancer Institute; 22Massachusetts General Hospital Cancer Center; 23City of Hope Comprehensive Cancer Center; 24University of Alabama at Birmingham Comprehensive Cancer Center; and 25National Comprehensive Cancer Network. ·J Natl Compr Canc Netw · Pubmed #24812131.

ABSTRACT: The NCCN Guidelines for Melanoma provide multidisciplinary recommendations for the management of patients with melanoma. These NCCN Guidelines Insights highlight notable recent updates. Dabrafenib and trametinib, either as monotherapy (category 1) or combination therapy, have been added as systemic options for patients with unresectable metastatic melanoma harboring BRAF V600 mutations. Controversy continues regarding the value of adjuvant radiation for patients at high risk of nodal relapse. This is reflected in the category 2B designation to consider adjuvant radiation following lymphadenectomy for stage III melanoma with clinically positive nodes or recurrent disease.

6 Editorial Disparate clinical activity of PD-1 blockade in melanoma subtypes: Know thy enemy! 2016

Bhatia, Shailender / Margolin, Kim. ·Department of Medicine/Medical Oncology, University of Washington, Seattle, Washington. sbhatia@uw.edu. · Fred Hutchinson Cancer Research Center, Seattle, Washington. sbhatia@uw.edu. · Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, California. ·Cancer · Pubmed #27533794.

ABSTRACT: -- No abstract --

7 Editorial PD-1 Blockade in Melanoma: A Promising Start, but a Long Way to Go. 2016

Bhatia, Shailender / Thompson, John A. ·University of Washington, Seattle2Fred Hutchinson Cancer Research Center, Seattle, Washington. ·JAMA · Pubmed #27092829.

ABSTRACT: -- No abstract --

8 Editorial Agents make "preferred list" in metastatic melanoma. 2014

Thompson, John A. ·Presented by John A. Thompson, MD, Co-Director, Melanoma Clinic, Seattle Cancer Care Alliance, Seattle, Washington. ·J Natl Compr Canc Netw · Pubmed #24853217.

ABSTRACT: The 2014 version of the NCCN Guidelines for Melanoma lists 6 preferred regimens, most with a category 1 recommendation, and 8 "other active regimens." Effective new agents include ipilimumab, a monoclonal anti-CTLA4 antibody, and agents targeted against mutated BRAF and MEK. Researchers are now focused on the optimal way to combine or sequence these agents, while exploring other new classes.

9 Review Leptomeningeal metastasis. 2018

Taillibert, Sophie / Chamberlain, Marc C. ·Department of Neurology 2, Pitié-Salpétrière Hospital, Paris, France. · Departments of Neurology and Neurological Surgery, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, United States. Electronic address: marccchamberlain@gmail.com. ·Handb Clin Neurol · Pubmed #29307353.

ABSTRACT: Leptomeningeal metastasis (LM) results from dissemination of cancer cells to both the leptomeninges (pia and arachnoid) and cerebrospinal fluid (CSF) compartment. Breast cancer, lung cancer, and melanoma are the most common solid tumors that cause LM. Recent approval of more active anticancer therapies has resulted in improvement in survival that is partly responsible for an increased incidence of LM. Neurologic deficits, once manifest, are mostly irreversible, and often have a significant impact on patient quality of life. LM-directed therapy is based on symptom palliation, circumscribed use of neurosurgery, limited field radiotherapy, intra-CSF and systemic therapies. Novel methods of detecting LM include detection of CSF circulating tumor cells and tumor cell-free DNA. A recent international guideline for a standardization of response assessment in LM may improve cross-trial comparisons as well as within-trial evaluation of treatment. An increasing number of retrospective studies suggest that molecular-targeted therapy, such as EGFR and ALK inhibitors in lung cancer, trastuzumab in HER2+ breast cancer, and BRAF inhibitors in melanoma, may be effective as part of the multidisciplinary management of LM. Prospective randomized trials with standardized response assessment are needed to further validate these preliminary findings.

10 Review Interdisciplinary Perspectives on Sun Safety. 2018

Geller, Alan C / Jablonski, Nina G / Pagoto, Sherry L / Hay, Jennifer L / Hillhouse, Joel / Buller, David B / Kenney, W Larry / Robinson, June K / Weller, Richard B / Moreno, Megan A / Gilchrest, Barbara A / Sinclair, Craig / Arndt, Jamie / Taber, Jennifer M / Morris, Kasey L / Dwyer, Laura A / Perna, Frank M / Klein, William M P / Suls, Jerry. ·Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. · Department of Anthropology, The Pennsylvania State University, University Park. · Department of Medicine, University of Massachusetts Medical School, Worcester. · Department of Psychiatry & Behavioral Sciences, Memorial Sloan Kettering Cancer Center, New York, New York. · Community and Behavioral Health, East Tennessee State University, Johnson City. · Klein Buendel, Golden, Colorado. · Department of Kinesiology, The Pennsylvania State University. · Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois. · Chief Editor. · MRC Centre for Inflammation Research, Queens Medical Research Institute, University of Edinburgh, Edinburgh, Scotland. · Division of General Pediatrics, University of Washington, Seattle. · Department of Dermatology, Harvard Medical School and Massachusetts General Hospital, Boston. · Cancer Council Victoria, Melbourne, Australia. · Department of Psychological Sciences, University of Missouri, Columbia. · Department of Psychological Sciences, Kent State University, Kent, Ohio. · National Cancer Institute, Rockville, Maryland. ·JAMA Dermatol · Pubmed #29117315.

ABSTRACT: Overexposure to the sun is associated with an increased risk of melanoma and nonmelanoma skin cancer, but indications of improvements in sun protection behavior are poor. Attempts to identify emerging themes in skin cancer control have largely been driven by groups of experts from a single field. In December 2016, 19 experts from various disciplines convened for Interdisciplinary Perspectives on Skin Cancer, a 2-day meeting hosted by the National Academy of Sciences. The group discussed knowledge gaps, perspectives on sun exposure, implications for skin cancer risk and other health outcomes, and new directions. Five themes emerged from the discussion: (1) The definition of risk must be expanded, and categories for skin physiology must be refined to incorporate population diversities. (2) Risky sun exposure often co-occurs with other health-related behaviors. (3) Messages must be nuanced to target at-risk populations. (4) Persons at risk for tanning disorder must be recognized and treated. (5) Sun safety interventions must be scalable. Efficient use of technologies will be required to sharpen messages to specific populations and to integrate them within multilevel interventions. Further interdisciplinary research should address these emerging themes to build effective and sustainable approaches to large-scale behavior change.

11 Review Assessing Tumor-Infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method from the International Immuno-Oncology Biomarkers Working Group: Part 2: TILs in Melanoma, Gastrointestinal Tract Carcinomas, Non-Small Cell Lung Carcinoma and Mesothelioma, Endometrial and Ovarian Carcinomas, Squamous Cell Carcinoma of the Head and Neck, Genitourinary Carcinomas, and Primary Brain Tumors. 2017

Hendry, Shona / Salgado, Roberto / Gevaert, Thomas / Russell, Prudence A / John, Tom / Thapa, Bibhusal / Christie, Michael / van de Vijver, Koen / Estrada, M V / Gonzalez-Ericsson, Paula I / Sanders, Melinda / Solomon, Benjamin / Solinas, Cinzia / Van den Eynden, Gert G G M / Allory, Yves / Preusser, Matthias / Hainfellner, Johannes / Pruneri, Giancarlo / Vingiani, Andrea / Demaria, Sandra / Symmans, Fraser / Nuciforo, Paolo / Comerma, Laura / Thompson, E A / Lakhani, Sunil / Kim, Seong-Rim / Schnitt, Stuart / Colpaert, Cecile / Sotiriou, Christos / Scherer, Stefan J / Ignatiadis, Michail / Badve, Sunil / Pierce, Robert H / Viale, Giuseppe / Sirtaine, Nicolas / Penault-Llorca, Frederique / Sugie, Tomohagu / Fineberg, Susan / Paik, Soonmyung / Srinivasan, Ashok / Richardson, Andrea / Wang, Yihong / Chmielik, Ewa / Brock, Jane / Johnson, Douglas B / Balko, Justin / Wienert, Stephan / Bossuyt, Veerle / Michiels, Stefan / Ternes, Nils / Burchardi, Nicole / Luen, Stephen J / Savas, Peter / Klauschen, Frederick / Watson, Peter H / Nelson, Brad H / Criscitiello, Carmen / O'Toole, Sandra / Larsimont, Denis / de Wind, Roland / Curigliano, Giuseppe / André, Fabrice / Lacroix-Triki, Magali / van de Vijver, Mark / Rojo, Federico / Floris, Giuseppe / Bedri, Shahinaz / Sparano, Joseph / Rimm, David / Nielsen, Torsten / Kos, Zuzana / Hewitt, Stephen / Singh, Baljit / Farshid, Gelareh / Loibl, Sibylle / Allison, Kimberly H / Tung, Nadine / Adams, Sylvia / Willard-Gallo, Karen / Horlings, Hugo M / Gandhi, Leena / Moreira, Andre / Hirsch, Fred / Dieci, Maria V / Urbanowicz, Maria / Brcic, Iva / Korski, Konstanty / Gaire, Fabien / Koeppen, Hartmut / Lo, Amy / Giltnane, Jennifer / Rebelatto, Marlon C / Steele, Keith E / Zha, Jiping / Emancipator, Kenneth / Juco, Jonathan W / Denkert, Carsten / Reis-Filho, Jorge / Loi, Sherene / Fox, Stephen B. ·Departments of *Pathology §§§Medical Oncology, Peter MacCallum Cancer Centre, Melbourne †The Sir Peter MacCallum Department of Oncology Departments of **Pathology ∥∥Medicine, University of Melbourne ¶¶Department of Anatomical Pathology, Royal Melbourne Hospital, Parkville #Department of Anatomical Pathology, St Vincent's Hospital Melbourne, Fitzroy ††Department of Medical Oncology, Austin Health ‡‡Olivia Newton-John Cancer Research Institute, Heidelberg §§School of Cancer Medicine, La Trobe University, Bundoora §§§§§Centre for Clinical Research and School of Medicine, The University of Queensland ∥∥∥∥∥Pathology Queensland, Royal Brisbane and Women's Hospital, Brisbane §§§§§§§§§§The Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst ∥∥∥∥∥∥∥∥∥∥Australian Clinical Labs, Bella Vista ‡‡‡‡‡‡‡‡‡‡‡‡Directorate of Surgical Pathology, SA Pathology §§§§§§§§§§§§Discipline of Medicine, Adelaide University, Adelaide, Australia ***********Department of Surgical Oncology, Netherlands Cancer Institute †††††††††††††Department of Pathology ##Divisions of Diagnostic Oncology & Molecular Pathology, Netherlands Cancer Institute-Antoni van Leeuwenhoek, Amsterdam, The Netherlands ###Université Paris-Est ****INSERM, UMR 955 ††††Département de pathologie, APHP, Hôpital Henri-Mondor, Créteil ∥∥∥∥∥∥∥∥∥Service de Biostatistique et d'Epidémiologie, Gustave Roussy, CESP, Inserm U1018, Université-Paris Sud, Université Paris-Saclay ¶¶¶¶¶¶¶¶¶¶INSERM Unit U981, and Department of Medical Oncology, Gustave Roussy, Villejuif ##########Faculté de Médecine, Université Paris Sud, Kremlin-Bicêtre †††††††Department of Surgical Pathology and Biopathology, Jean Perrin Comprehensive Cancer Centre ‡‡‡‡‡‡‡University of Auvergne UMR1240, Clermont-Ferrand, France ‡‡‡‡Department of Medicine, Clinical Division of Oncology §§§§Institute of Neurology, Comprehensive Cancer Centre Vienna, Medical University of Vienna, Vienna ††††††††††††††Institute of Pathology, Medical University of Graz, Austria ∥∥∥∥European Institute of Oncology ¶¶¶¶School of Medicine ######Department of Pathology, Istituto Europeo di Oncologia, University of Milan, Milan ¶¶¶¶¶¶¶¶¶¶¶¶¶Department of Surgery, Oncology and Gastroenterology, University of Padova #############Medical Oncology 2, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy †††††Molecular Oncology Group, Vall d'Hebron Institute of Oncology, Barcelona †††††††††††Pathology Department, IIS-Fundacion Jimenez Diaz, UAM, Madrid, Spain §Department of Pathology and TCRU, GZA ¶¶¶Department of Pathology, GZA Ziekenhuizen, Antwerp ∥Laboratory of Experimental Urology, Department of Development and Regeneration, KU Leuven ‡‡‡‡‡‡‡‡‡‡‡Department of Pathology, University Hospital Leuven, Leuven, Belgium ¶Department of Pathology, AZ Klina, Brasschaat ††††††Department of Pathology, GZA Ziekenhuizen, Sint-Augustinus, Wilrijk ∥∥∥Molecular Immunology Unit ‡‡‡‡‡‡Department of Medical Oncology, Institut Jules Bordet, Université Libre de Bruxelles ‡Breast Cancer Translational Research Laboratory/Breast International Group, Institut Jules Bordet **************European Organisation for Research and Treatment of Cancer (EORTC) Headquarters *******Department of Pathology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium §§§§§§§Department of Surgery, Kansai Medical School, Hirakata, Japan #######Severance Biomedical Science Institute and Department of Medical Oncology, Yonsei University College of Medicine, Seoul, South Korea ∥∥∥∥∥∥∥∥Tumor Pathology Department, Maria Sklodowska-Curie Memorial Cancer Center ¶¶¶¶¶¶¶¶Institute of Oncology, Gliwice Branch, Gliwice, Poland ‡‡‡‡‡‡‡‡‡‡‡‡‡‡Pathology and Tissue Analytics, Roche Innovation Centre Munich, Penzberg †††††††††Institute of Pathology, Charité Universitätsmedizin Berlin ‡‡‡‡‡‡‡‡‡VMscope GmbH, Berlin ¶¶¶¶¶¶¶¶¶German Breast Group GmbH, Neu-Isenburg, Germany **********Trev & Joyce Deeley Research Centre, British Columbia Cancer Agency ††††††††††Department of Biochemistry and Microbiology, University of Victoria, Victoria Departments of ‡‡‡‡‡‡‡‡‡‡Medical Genetics #########Pathology and Laboratory Medicine ¶¶¶¶¶¶¶¶¶¶¶Department of Pathology and Laboratory Medicine, Genetic Pathology Evaluation Centre, University of British Columbia, Vancouver, BC ###########Department of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, Canada §§§§§§§§§§§Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Doha, Qatar ‡‡‡‡‡‡‡‡Department of Pathology and Laboratory Medicine, Rhode Island Hospital and Lifespan Medical Center §§§§§§§§Warren Alpert Medical School of Brown University, Providence ¶¶¶¶¶National Surgical Adjuvant Breast and Bowel Project Operations Center/NRG Oncology, Pittsburgh, PA †††Breast Cancer Research Program, Vanderbilt Ingram Cancer Center, Vanderbilt University Departments of ‡‡‡Pathology, Microbiology and Immunology ########Department of Medicine, Vanderbilt University Medical Centre *********Vanderbilt Ingram Cancer Center, Nashville §§§§§§§§§Department of Pathology, Yale University School of Medicine, New Haven ∥∥∥∥∥∥∥∥∥∥∥Department of Oncology, Montefiore Medical Centre, Albert Einstein College of Medicine ∥∥∥∥∥∥∥Montefiore Medical Center ¶¶¶¶¶¶¶The Albert Einstein College of Medicine, Bronx, NY ********Department of Pathology, Brigham and Women's Hospital #####Cancer Research Institute and Department of Pathology, Beth Israel Deaconess Cancer Center ******Harvard Medical School ¶¶¶¶¶¶¶¶¶¶¶¶Division of Hematology-Oncology, Beth Israel Deaconess Medical Center ††††††††Department of Cancer Biology ‡‡‡‡‡‡‡‡‡‡‡‡‡Dana-Farber Cancer Institute, Boston, MA ∥∥∥∥∥∥∥∥∥∥∥∥∥Department of Medicine, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO ‡‡‡‡‡Department of Cancer Biology, Mayo Clinic, Jacksonville, FL ∥∥∥∥∥∥Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis, IN ¶¶¶¶¶¶Cancer Immunotherapy Trials Network, Central Laboratory and Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, WA ††††††††††††Department of Pathology, New York University Langone Medical Centre ############New York University Medical School *************Perlmutter Cancer Center §§§§§§§§§§§§§Pulmonary Pathology, New York University Center for Biospecimen Research and Development, New York University ***************Department of Pathology, Memorial Sloan-Kettering Cancer Center ####Departments of Radiation Oncology and Pathology, Weill Cornell Medicine, New York, NY *****Department of Pathology, University of Texas M.D. Anderson Cancer Center, Houston, TX ∥∥∥∥∥∥∥∥∥∥∥∥Pathology Department, Stanford University Medical Centre, Stanford ∥∥∥∥∥∥∥∥∥∥∥∥∥∥Department of Pathology, Stanford University, Palo Alto ***Department of Pathology, School of Medicine, University of California, San Diego §§§§§§§§§§§§§§Research Pathology, Genentech Inc., South San Francisco, CA *************Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda ¶¶¶¶¶¶¶¶¶¶¶¶¶¶Translational Sciences, MedImmune, Gaithersberg, MD §§§§§§Academic Medical Innovation, Novartis Pharmaceuticals Corporation, East Hanover ##############Translational Medicine, Merck & Co. Inc., Kenilworth, NJ. ·Adv Anat Pathol · Pubmed #28777143.

ABSTRACT: Assessment of the immune response to tumors is growing in importance as the prognostic implications of this response are increasingly recognized, and as immunotherapies are evaluated and implemented in different tumor types. However, many different approaches can be used to assess and describe the immune response, which limits efforts at implementation as a routine clinical biomarker. In part 1 of this review, we have proposed a standardized methodology to assess tumor-infiltrating lymphocytes (TILs) in solid tumors, based on the International Immuno-Oncology Biomarkers Working Group guidelines for invasive breast carcinoma. In part 2 of this review, we discuss the available evidence for the prognostic and predictive value of TILs in common solid tumors, including carcinomas of the lung, gastrointestinal tract, genitourinary system, gynecologic system, and head and neck, as well as primary brain tumors, mesothelioma and melanoma. The particularities and different emphases in TIL assessment in different tumor types are discussed. The standardized methodology we propose can be adapted to different tumor types and may be used as a standard against which other approaches can be compared. Standardization of TIL assessment will help clinicians, researchers and pathologists to conclusively evaluate the utility of this simple biomarker in the current era of immunotherapy.

12 Review Insights from zebrafish on human pigment cell disease and treatment. 2017

Cooper, Cynthia D. ·School of Molecular Biosciences, Washington State University Vancouver, Vancouver, Washington. ·Dev Dyn · Pubmed #28710811.

ABSTRACT: Black pigment cells, melanocytes, arise early during development from multipotent neural crest cells. Melanocytes protect human skin from DNA damaging sunrays and provide color for hair, eyes, and skin. Several disorders and diseases originate from these cells, including the deadliest skin cell cancer, melanoma. Thus, melanocytes are critical for a healthy life and for protecting humans from disease. Due to the ease of visualizing pigment cells through transparent larvae skin and conserved roles for zebrafish melanophore genes to mammalian melanocyte genes, zebrafish larvae offer a biologically relevant model for understanding pigment cell development and disease in humans. This review discusses our current knowledge of melanophore biology and how zebrafish are contributing to improving how diseases of melanocytes are understood and treated in humans. Developmental Dynamics 246:889-896, 2017. © 2017 Wiley Periodicals, Inc.

13 Review Neoplastic Meningitis Due to Lung, Breast, and Melanoma Metastases. 2017

Le Rhun, Emilie / Taillibert, Sophie / Chamberlain, Marc C. ·Division of Neuro-Oncology in the Department of Neurosurgery, University Hospital and the Breast Unit in the Department of Medical Oncology, Oscar Lambret Center, Lille Cedex, France. · Division of Neuro-Oncology in the Departments of Neurology, and Radiation Oncology, Pitie-Salpetriere Hospital, and Assistance Publique des Hopitaux de Paris, Universite Pierre et Marie Curie, Paris, France. · Department of Neurology, Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance, and Division of Neuro-Oncology, Departments of Neurology and Neurological Surgery, University of Washington School of Medicine, Seattle, WA. marccchamberlain@gmail.com. ·Cancer Control · Pubmed #28178709.

ABSTRACT: BACKGROUND: Neoplastic meningitis, a central nervous system (CNS) complication of cancer metastatic to the meninges and cerebrospinal fluid (CSF), is relevant to oncologists due to the impact of the disease on patient quality of life and survival rates. METHODS: A review of the literature of articles published in English was conducted with regard to neoplastic meningitis. RESULTS: The incidence of neoplastic meningitis is increasing because patients with cancer are surviving longer in part because of the use of novel therapies with poor CNS penetration. Up to 5% of patients with solid tumors develop neoplastic meningitis during the disease course (breast cancer, lung cancer, and melanoma being the predominantly causative cancers). The rate of median survival in patients with untreated neoplastic meningitis is 1 to 2 months, although it can be as long as 5 months in some cases. Therapeutic options for the treatment of neoplastic meningitis include systemic therapy (cancer-specific, CNS-penetrating chemotherapy or targeted therapies), intra-CSF administration of chemotherapy (methotrexate, cytarabine, thiotepa) and CNS site-specific radiotherapy. Determining whom to treat with neoplastic meningitis remains challenging and, in part, relates to the extent of systemic disease, the neurological burden of disease, the available systemic therapies, and estimated rates of survival. CONCLUSIONS: The prognosis of neoplastic meningitis remains poor. The increasing use of novel, targeted therapies and immunotherapy in solid tumors and its impact on neoplastic meningitis remains to be determined and is an area of active research. Thus, well conducted trials are needed.

14 Review Systemic therapy of brain metastases: non-small cell lung cancer, breast cancer, and melanoma. 2017

Chamberlain, Marc C / Baik, Christina S / Gadi, Vijayakrishna K / Bhatia, Shailender / Chow, Laura Q M. ·Seattle Cancer Center Alliance, Seattle, Washington (M.C.C., C.S.B., V.K.G., S.B., L.Q.M.C.); Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington (C.S.B., V.K.G., L.Q.M.C.); Departments of Neurology and Neurological Surgery, University of Washington, Seattle, Washington (M.C.C.); Division of Medical Oncology, University of Washington, Seattle, Washington (C.S.B., V.K.G., S.B., L.Q.M.C) marccchamberlain@gmail.com. · Seattle Cancer Center Alliance, Seattle, Washington (M.C.C., C.S.B., V.K.G., S.B., L.Q.M.C.); Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington (C.S.B., V.K.G., L.Q.M.C.); Departments of Neurology and Neurological Surgery, University of Washington, Seattle, Washington (M.C.C.); Division of Medical Oncology, University of Washington, Seattle, Washington (C.S.B., V.K.G., S.B., L.Q.M.C). ·Neuro Oncol · Pubmed #28031389.

ABSTRACT: Brain metastases (BM) occur frequently in many cancers, particularly non-small cell lung cancer (NSCLC), breast cancer, and melanoma. The development of BM is associated with poor prognosis and has an adverse impact on survival and quality of life. Commonly used therapies for BM such as surgery or radiotherapy are associated with only modest benefits. However, recent advances in systemic therapy of many cancers have generated considerable interest in exploration of those therapies for treatment of intracranial metastases.This review discusses the epidemiology of BM from the aforementioned primary tumors and the challenges of using systemic therapies for metastatic disease located within the central nervous system. Cumulative data from several retrospective and small prospective studies suggest that molecularly targeted systemic therapies may be an effective option for the treatment of BM from NSCLC, breast cancer, and melanoma, either as monotherapy or in conjunction with other therapies. Larger prospective studies are warranted to further characterize the efficacy and safety profiles of these targeted agents for the treatment of BM.

15 Review Screening for Skin Cancer in Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. 2016

Wernli, Karen J / Henrikson, Nora B / Morrison, Caitlin C / Nguyen, Matthew / Pocobelli, Gaia / Blasi, Paula R. ·Group Health Research Institute, Kaiser Permanente Research Affiliates Evidence-based Practice Center, Seattle, Washington. ·JAMA · Pubmed #27458949.

ABSTRACT: IMPORTANCE: Skin cancer, primarily melanoma, is a leading cause of morbidity and mortality in the United States. OBJECTIVE: To provide an updated systematic review for the US Preventive Services Task Force regarding clinical skin cancer screening among adults. DATA SOURCES: MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials were searched for relevant studies published from January 1, 1995, through June 1, 2015, with surveillance through February 16, 2016. STUDY SELECTION: English-language studies conducted in asymptomatic populations 15 years and older at general risk for skin cancer. DATA EXTRACTION AND SYNTHESIS: Relevant data were abstracted, and study quality was rated. MAIN OUTCOMES AND MEASURES: Melanoma incidence and mortality, harms from cancer screening, diagnostic accuracy, and stage distribution. RESULTS: No randomized clinical trials were identified. There was limited evidence on the association between skin cancer screening and mortality. A German ecologic study (n = 360,288) found a decrease of 0.8 per 100,000 melanoma deaths in a region with population-based skin cancer screening compared with no change or slight increases in comparison regions. The number of excisions needed to detect 1 skin cancer from clinical visual skin examinations varied by age and sex; for example, 22 for women 65 years or older compared with 41 for women aged 20 to 34 years. In 2 studies of performing visual skin examination, sensitivity to detect melanoma was 40.2% and specificity was 86.1% when conducted by primary care physicians (n = 16,383). Sensitivity was 49.0% and specificity was 97.6% when skin examinations were performed by dermatologists (n = 7436). In a case-control study of melanoma (n = 7586), cases diagnosed with thicker lesions (>0.75 mm) had an odds ratio of 0.86 (95% CI, 0.75-0.98) for receipt of a physician skin examination in the prior 3 years compared with controls. Eight cohort studies (n = 236,485) demonstrated a statistically significant relationship between the degree of disease involvement at diagnosis and melanoma mortality, regardless of the characterization of the stage or lesion thickness. Tumor thickness greater than 4.0 mm was associated with increased melanoma mortality compared with thinner lesions, and late stage at diagnosis was associated with increased all-cause mortality. CONCLUSIONS AND RELEVANCE: Only limited evidence was identified for skin cancer screening, particularly regarding potential benefit of skin cancer screening on melanoma mortality. Future research on skin cancer screening should focus on evaluating the effectiveness of targeted screening in those considered to be at higher risk for skin cancer.

16 Review Expression of CD133 cancer stem cell marker in melanoma: a systematic review and meta-analysis. 2016

Madjd, Zahra / Erfani, Elham / Gheytanchi, Elmira / Moradi-Lakeh, Maziar / Shariftabrizi, Ahmad / Asadi-Lari, Mohsen. ·Oncopathology Research Center, Iran University of Medical Sciences, Tehran - Iran. · Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran - Iran. · Department of Community Medicine, Iran University of Medical Sciences and Health Services, Tehran - Iran. · Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA - USA. · Department of Nuclear Medicine and Molecular Imaging, State University of New York at Buffalo, Buffalo, NY - USA. · Department of Epidemiology, Iran University of Medical Sciences, Tehran - Iran. ·Int J Biol Markers · Pubmed #27102864.

ABSTRACT: BACKGROUND: CD133-positive melanoma cells are thought to be melanoma-initiating cells with cancer stem cell (CSC) characteristics. Some researchers have reported that CD133-negative subsets can also initiate tumors, so the clinical significance of a CD133-positive subpopulation of cells in melanoma remains controversial. This systematic review was designed to assess the value of CD133 as a CSC marker in melanomas. A meta-analysis was also performed to cumulatively analyze the data on CD133 expression levels in the selected studies. MATERIALS AND METHOD: Eligible studies were identified via an electronic search through various databases including PubMed, MEDLINE, Ovid MEDLINE, and Web of Science (from May 2005 through September 2014) using the following keywords: "CD133 or prominin-1", "cancer stem cells", and "melanoma". Only articles in which CD133 antigen was detected by immunohistochemistry (IHC) were included. A meta-analysis was performed to identify any association between CD133 expression and clinical outcomes. RESULTS: Two hundred and ninety-nine melanoma cases from 5 studies were evaluated for expression levels of CD133 using IHC. Large heterogeneity was observed among the results (p<0.001, I2 = 94%). Approximately 47.9% (95% CI 23.7%-72.1%) of the studied melanoma cases had high CD133 expression. The I2 value and Q-test p value for heterogeneity were 89.0% and <0.001, respectively, and the pooled estimate of CD133 expression was 61.7% (95% CI 25.1%-98.4%). CONCLUSIONS: Our findings suggest that CD133 is not yet proven to be an appropriate biomarker in identifying CSCs of melanoma. Thus, detection of CD133 in combination with other putative CSC markers may be more valuable for clinical application.

17 Review The Evolving Role of Immune Checkpoint Inhibitors in Cancer Treatment. 2015

Pennock, Gregory K / Chow, Laura Q M. ·Levine Cancer Institute, Charlotte, North Carolina, USA; University of Washington, Seattle, Washington, USA Gregory.K.Pennock@carolinashealthcare.org. · Levine Cancer Institute, Charlotte, North Carolina, USA; University of Washington, Seattle, Washington, USA. ·Oncologist · Pubmed #26069281.

ABSTRACT: IMPLICATIONS FOR PRACTICE: Immunotherapy is an evolving treatment approach based on the role of the immune system in eradicating cancer. An example of an immunotherapeutic is ipilimumab, an antibody that blocks cytotoxic T-lymphocyte antigen-4 (CTLA-4) to augment antitumor immune responses. Ipilimumab is approved for advanced melanoma and induced long-term survival in a proportion of patients. The programmed death-1 (PD-1) checkpoint inhibitors are promising immunotherapies with demonstrated sustained antitumor responses in several tumors. Because they harness the patient's own immune system, immunotherapies have the potential to be a powerful weapon against cancer.

18 Review Durable benefit and the potential for long-term survival with immunotherapy in advanced melanoma. 2014

McDermott, David / Lebbé, Celeste / Hodi, F Stephen / Maio, Michele / Weber, Jeffrey S / Wolchok, Jedd D / Thompson, John A / Balch, Charles M. ·Department of Hematology/Oncology, Beth Israel Deaconess Medical Center, 375 Longwood Ave, Mailstop: MASCO 428, Boston, MA 02215, USA. Electronic address: dmcdermo@bidmc.harvard.edu. · APHP Department of Dermatology, CIC, U976 Hôpital Saint-Louis University Paris Diderot, 1 Avenue Claude Vellefaux, Paris 75010, France. Electronic address: celeste.lebbe@sls.aphp.fr. · Center for Immuno-Oncology, Melanoma Center, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02215, USA. Electronic address: Stephen_Hodi@dfci.harvard.edu. · Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena, Siena 53100, Italy. Electronic address: mmaiocro@gmail.com. · Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA. Electronic address: jeffrey.weber@moffitt.org. · Ludwig Center for Cancer Immunotherapy, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA. Electronic address: wolchokj@mskcc.org. · Seattle Cancer Care Alliance, 825 Eastlake Ave E, G4-830, Seattle, WA 98109, USA. Electronic address: jat@uw.edu. · Department of Surgery, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA. Electronic address: charles.balch@utsouthwestern.edu. ·Cancer Treat Rev · Pubmed #25060490.

ABSTRACT: Historically, the median overall survival for patients with stage IV melanoma was less than 1 year and the 5-year survival rate was ∼10%. Recent advances in therapy have raised 5-year survival expectations to ∼20%. Notably, a subset of melanoma patients who receive immunotherapy with high-dose interleukin-2, and now ipilimumab, can achieve long-term survival of at least 5 years. A major goal in melanoma research is to increase the number of patients who experience this overall survival benefit. In this review, we discuss the attributes of immunotherapy and newer targeted agents, and consider how combination strategies might improve the chances of achieving durable benefit and long-term survival. We also discuss three areas that we believe will be critical to making further advances in melanoma treatment. To better understand the clinical profile of patients who achieve long-term survival with immunotherapy, we first present data from ipilimumab clinical trials in which a subset of patients experienced durable responses. Second, we discuss the limitations of traditional metrics used to evaluate the benefits of immunotherapies. Third, we consider emerging issues that clinicians are currently facing when making treatment decisions regarding immunotherapy. A better understanding of these novel treatments may improve survival outcomes in melanoma, increase the number of patients who experience this overall survival benefit, and inform the future use of these agents in the treatment of other cancer types.

19 Review Introduction to the role of the immune system in melanoma. 2014

Margolin, Kim. ·Medical Oncology, Seattle Cancer Care Alliance, University of Washington, 825 Eastlake Avenue E, Seattle, WA 98109, USA. Electronic address: kmargoli@seattlecca.org. ·Hematol Oncol Clin North Am · Pubmed #24880946.

ABSTRACT: The concept of immunosurveillance of cancer has been widely accepted for many years, but only recently have the precise mechanisms of tumor-host immune interactions been revealed. Inflammatory and immune reactions play a role in melanomagenesis, and may contribute to the eradication of tumor as well as potentiating its growth and proliferation. Studies of the role of tumor-immune system interactions are providing insights into the pathogenesis and opportunities for highly effective therapeutic strategies. Some patients, even with advanced disease, are now cured with immunotherapy, and increasing numbers of such cures are likely in future.

20 Review Multidisciplinary approach to brain metastasis from melanoma; local therapies for central nervous system metastases. 2013

Ramakrishna, Naren / Margolin, Kim A. ·From the MD Anderson Cancer Center Orlando, University of Central Florida College of Medicine, Orlando FL; University of Washington Fred Hutchinson Cancer Research Center, Seattle, WA. ·Am Soc Clin Oncol Educ Book · Pubmed #23714560.

ABSTRACT: The overall treatment paradigm for melanoma brain metastases continues to evolve and reflects the relative radioresistance of this histology, as well as the effect of emerging systemic therapies with central nervous system (CNS) activity. Local therapies, including surgery, whole brain radiotherapy (WBRT), and stereotactic radiosurgery (SRS), play an important role in the multidisciplinary management of melanoma brain metastases. Treatment selection for local therapies must consider many factors: (1) size, number, and location of lesions, (2) presence or absence of neurological symptoms, (3) extracranial disease status, expected survival, age, and performance status, (4) prior treatment history, (5) expected treatment toxicities, and (6) predicted response to systemic therapies. The choice of treatment modalities for brain metastases is among the most controversial areas in oncology. There has been a trend toward reduced use of WBRT and increased reliance on SRS and surgery for melanoma brain metastases. Although no prospective randomized data exist comparing local therapies for melanoma brain metastases, several large retrospective studies suggest aggressive local treatment with modalities including surgery and SRS are associated with favorable outcomes in select patients. Multidisciplinary collaboration is required to facilitate a treatment plan that balances reduction in risk of neurological death and symptomatic progression against the risk of treatment-related toxicity.

21 Review Multidisciplinary approach to brain metastasis from melanoma: the emerging role of systemic therapies. 2013

Long, Georgina V / Margolin, Kim A. ·From the Melanoma Institute Australia, The University of Sydney, Sydney, Australia; University of Washington/Fred Hutchinson Cancer Research Center, Seattle, WA. ·Am Soc Clin Oncol Educ Book · Pubmed #23714558.

ABSTRACT: Melanoma brain metastases are common, difficult to treat, and carry a poor prognosis. Until recently, systemic therapy was ineffective. Local therapy (including surgery, stereotactic radiotherapy, and whole brain radiotherapy) was considered the only option for a chance of disease control in the brain, and was highly dependent on the patient's performance status and age, number and size of brain metastases, and the presence of extracranial metastases. Since 2010, three drugs have demonstrated activity in progressing or "active" brain metastases including the anti-CTLA4 antibody ipilimumab (phase II study of 72 patients), and the BRAF inhibitors dabrafenib (phase II study of 172 patients, both previously treated and untreated brain metastases) and vemurafenib (a pilot study of 24 patients with heavily pretreated brain metastases). The challenge and unanswered question for clinicians is how to sequence all the available therapies, both local and systemic, to optimize the patient's quality of life and survival. This is an area of intense clinical research. The treatment of patients with melanoma brain metastases should be discussed by a multidisciplinary team of melanoma experts including a neurosurgeon, medical oncologist, and radiation oncologist. Important clinical features that help determine appropriate first line therapy include single compared with solitary brain metastasis, resectablity, BRAF mutation status of melanoma, rate of progression/performance status, and the presence of extracranial disease.

22 Review A concise review of the efficacy of stereotactic radiosurgery in the management of melanoma and renal cell carcinoma brain metastases. 2012

Hanson, Peter W / Elaimy, Ameer L / Lamoreaux, Wayne T / Demakas, John J / Fairbanks, Robert K / Mackay, Alexander R / Taylor, Blake / Cooke, Barton S / Thumma, Sudheer R / Lee, Christopher M. ·Gamma Knife of Spokane, 910 W 5th Ave, Suite 102, Spokane, WA, 99204, USA. ·World J Surg Oncol · Pubmed #22931379.

ABSTRACT: Melanoma and renal cell carcinoma have a well-documented tendency to develop metastases to the brain. Treating these lesions has traditionally been problematic, because chemotherapy has difficulty crossing the blood brain barrier and whole brain radiation therapy (WBRT) is a relatively ineffective treatment against these radioresistant tumor histologies. In recent years, stereotactic radiosurgery (SRS) has emerged as an effective and minimally-invasive treatment modality for irradiating either single or multiple intracranial structures in one clinical treatment setting. For this reason, we conducted a review of modern literature analyzing the efficacy of SRS in the management of patients with melanoma and renal cell carcinoma brain metastases. In our analysis we found SRS to be a safe, effective and attractive treatment modality for managing radioresistant brain metastases and highlighted the need for randomized trials comparing WBRT alone vs. SRS alone vs. WBRT plus SRS in treating patients with radioresistant brain metastases.

23 Review Tumor-infiltrating lymphocytes in melanoma. 2012

Lee, Sylvia / Margolin, Kim. ·Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA, 98195, USA. smlee@fhcrc.org ·Curr Oncol Rep · Pubmed #22878966.

ABSTRACT: Adoptive cell therapy using tumor-infiltrating lymphocytes (TIL) is arguably the most effective treatment for patients with metastatic melanoma. With higher response rates than ipilimumab or IL-2, and longer durations of response than vemurafenib, TIL therapy carries the potential to transform current outcomes in melanoma, while also defining the way cell-based immunotherapy gets incorporated into mainstream cancer treatment. This paper will review the current state of TIL therapy in melanoma, the strategies to improve its efficacy, the current obstacles, and future directions to expand the availability of TIL to the general patient population.

24 Review Systemic therapy for metastatic melanoma in 2012: dawn of a new era. 2012

Bhatia, Shailender / Thompson, John A. ·Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, Washington, USA. sbhatia@u.washington.edu ·J Natl Compr Canc Netw · Pubmed #22393198.

ABSTRACT: The 10-year survival rate for patients with metastatic melanoma is less than 10%. Although surgery and radiation therapy have a role in the treatment of metastatic disease, systemic therapy is the mainstay of treatment for these patients. After decades of failed attempts to improve treatment outcomes, recent successes with ipilimumab and vemurafenib have ushered in a new era in systemic therapy. Both ipilimumab and vemurafenib are associated with significant improvements in overall survival of patients in randomized phase III trials, an end point that had proven elusive so far. These breakthroughs not only provide more treatment options for patients with melanoma but also spur the investigation of a new generation of drugs for cancer therapy in general. This article reviews both the current systemic treatment options for metastatic melanoma and promising investigational approaches.

25 Review Brain metastasis in melanoma: clinical activity of CTLA-4 antibody therapy. 2010

Margolin, Kim A / Di Giacomo, Anna Maria / Maio, Michele. ·Medical Oncology, University of Washington, Seattle Cancer Care Alliance, Seattle, WA 98109-1023, USA. kmargoli@seattlecca.org ·Semin Oncol · Pubmed #21074062.

ABSTRACT: Melanoma metastasizes frequently to the brain, and brain metastases generally drive the prognosis of melanoma patients. Surgical and radiation therapy improve the outcome of selected melanoma patients with brain metastasis, while systemic treatment using cytotoxic agents still plays a limited role. Temozolomide and fotemustine are preferentially used in melanoma patients with brain metastases in the United States and in Europe, respectively, with modest clinical activity. However, the results obtained with either agent are still limited, and efforts are needed to improve the outcome of these patients who are generally excluded from clinical trials. Among therapeutic agents in development, antibodies that block the interaction of cytotoxic T-lymphocyte-associated antigen (CTLA-4) with its ligands B7.1 and B7.2 and thus enhance antitumor immune responses have shown clinical benefit in patients with metastatic melanoma, including durable control of brain metastases. This chapter reviews the current data and the rationale for ongoing and future trials of combination cytotoxic plus immunomodulatory therapy by US and Italian multicenter trial groups.

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