@article{3ffe94117f794c28a848a89b46ddd3de,
title = "Prognostic Gene Expression Profiling in Cutaneous Melanoma: Identifying the Knowledge Gaps and Assessing the Clinical Benefit",
abstract = "Importance: Use of prognostic gene expression profile (GEP) testing in cutaneous melanoma (CM) is rising despite a lack of endorsement as standard of care. Objective: To develop guidelines within the national Melanoma Prevention Working Group (MPWG) on integration of GEP testing into the management of patients with CM, including (1) review of published data using GEP tests, (2) definition of acceptable performance criteria, (3) current recommendations for use of GEP testing in clinical practice, and (4) considerations for future studies. Evidence Review: The MPWG members and other international melanoma specialists participated in 2 online surveys and then convened a summit meeting. Published data and meeting abstracts from 2015 to 2019 were reviewed. Findings: The MPWG members are optimistic about the future use of prognostic GEP testing to improve risk stratification and enhance clinical decision-making but acknowledge that current utility is limited by test performance in patients with stage I disease. Published studies of GEP testing have not evaluated results in the context of all relevant clinicopathologic factors or as predictors of regional nodal metastasis to replace sentinel lymph node biopsy (SLNB). The performance of GEP tests has generally been reported for small groups of patients representing particular tumor stages or in aggregate form, such that stage-specific performance cannot be ascertained, and without survival outcomes compared with data from the American Joint Committee on Cancer 8th edition melanoma staging system international database. There are significant challenges to performing clinical trials incorporating GEP testing with SLNB and adjuvant therapy. The MPWG members favor conducting retrospective studies that evaluate multiple GEP testing platforms on fully annotated archived samples before embarking on costly prospective studies and recommend avoiding routine use of GEP testing to direct patient management until prospective studies support their clinical utility. Conclusions and Relevance: More evidence is needed to support using GEP testing to inform recommendations regarding SLNB, intensity of follow-up or imaging surveillance, and postoperative adjuvant therapy. The MPWG recommends further research to assess the validity and clinical applicability of existing and emerging GEP tests. Decisions on performing GEP testing and patient management based on these results should only be made in the context of discussion of testing limitations with the patient or within a multidisciplinary group.",
author = "Douglas Grossman and Nwanneka Okwundu and Bartlett, {Edmund K.} and Marchetti, {Michael A.} and Megan Othus and Coit, {Daniel G.} and Hartman, {Rebecca I.} and Leachman, {Sancy A.} and Berry, {Elizabeth G.} and Larissa Korde and Lee, {Sandra J.} and Menashe Bar-Eli and Marianne Berwick and Tawnya Bowles and Buchbinder, {Elizabeth I.} and Burton, {Elizabeth M.} and Chu, {Emily Y.} and Clara Curiel-Lewandrowski and Curtis, {Julia A.} and Adil Daud and Deacon, {Dekker C.} and Ferris, {Laura K.} and Gershenwald, {Jeffrey E.} and Grossmann, {Kenneth F.} and Siwen Hu-Lieskovan and John Hyngstrom and Jeter, {Joanne M.} and Judson-Torres, {Robert L.} and Kendra, {Kari L.} and Kim, {Caroline C.} and Kirkwood, {John M.} and Lawson, {David H.} and Leming, {Philip D.} and Long, {Georgina V.} and Marghoob, {Ashfaq A.} and Mehnert, {Janice M.} and Ming, {Michael E.} and Nelson, {Kelly C.} and David Polsky and Scolyer, {Richard A.} and Smith, {Eric A.} and Sondak, {Vernon K.} and Stark, {Mitchell S.} and Stein, {Jennifer A.} and Thompson, {John A.} and Thompson, {John F.} and Venna, {Suraj S.} and Wei, {Maria L.} and Swetter, {Susan M.}",
note = "Funding Information: Funding/Support: This work was supported by the University of Utah Department of Dermatology (Drs Grossman and Okwundu), the Huntsman Cancer Foundation (Dr Grossman) at the University of Utah, the Melanoma Center at the Huntsman Cancer Institute (travel support for Dr Lee to attend summit meeting), the Hope Foundation (travel support for Dr Othus to attend summit meeting), the National Health and Medical Research Council of Australia (NHMRC) Program (Drs Long, Scolyer, and J. F. Thompson) and fellowship grants (Drs Long, Scolyer, and Stark), and grants from the American Skin Association (Dr Hartman) and the Sydney Medical School Foundation (Dr J. F. Thompson). This material is the result of work supported with resources and the use of facilities at the Veterans Affairs Palo Alto Health Care System in Palo Alto, California (Dr Swetter). The contents do not represent the views of the US Department of Veterans Affairs or the US Government. Funding Information: reported receiving personal fees from Orlucent outside the submitted work. Dr Othus reported receiving grants from the National Cancer Institute during the conduct of the study, and serving as a consultant for Merck, Daiichi Sankyo, and GlycoMimetics and on the Data Safety and Monitoring Boards of Celgene and GlycoMimetics outside the submitted work. Dr Hartman reported receiving grants from the American Skin Association outside the submitted work. Dr Leachman reported receiving nonfinancial support (early access program) from Castle Biosciences outside the submitted work, as well as having manuscripts and abstracts published using the test with company support of the assay—all publications were peer reviewed and no personal or institutional payment or compensation was received. Dr Berry reported receiving personal fees from Bristol-Myers Squibb outside the submitted work. Dr Lee reported serving as a consultant for the Data Safety Monitoring Board of Genentech/Roche outside the submitted work. Dr Buchbinder reported receiving personal fees from Novartis and Partners Therapeutics outside the submitted work. Dr Daud reported receiving grants from Novartis, GlaxoSmithKline, Bristol-Myers Squibb, Merck, Pfizer, Incyte, Xencor, and OncoSec Medical outside the submitted work. Dr Ferris reported receiving grants from Castle Biosciences and grants and personal fees from DermTech outside the submitted work. Dr Gershenwald reported receiving personal fees from Merck, Novartis, Bristol-Myers Squibb, Syndax, and Castle Biosciences outside the submitted work. Dr Hu-Lieskovan reported receiving grants from Vaccinex and Bristol-Myers Squibb and personal fees from Bristol-Myers Squibb, Xencor, and Genmab outside the submitted work. Dr Jeter reported receiving grants from Bristol-Myers Squibb and Merck and serving as a consultant for Array Biopharma outside the submitted work. Dr Long reported receiving personal fees from Aduro, Amgen, Bristol-Myers Squibb, Mass Avery, Merck, Merck Sharp & Dohme, Novartis, OncoSec Medical, Pierre-Fabre, Roche, and Sandoz outside the submitted work. Dr Mehnert reported receiving research grants from Amgen, AstraZeneca, Bristol-Myers Squibb, EMD Serono, Immunocore, Incyte, MacroGenics, Merck Sharp & Dohme, Novartis, Polynoma, and Sanofi; receiving personal fees for serving as a consultant for Amgen and Merck Sharp & Dohme; receiving honoraria from EMD Serono and Pfizer; and receiving personal fees for serving on advisory boards for Array BioPharma, Bristol-Myers Squibb, EMD Serono, and Sanofi/ Regeneron. Dr Polsky reported a research contract with Novartis and receiving personal fees from MolecularMD and Physician{\textquoteright}s Education Resource outside the submitted work. Dr Scolyer reported receiving a NHMRC Program Grant and NHMRC Fellowship Grant during the conduct of the study and personal fees from Merck Sharp & Dohme, GlaxoSmithKline Australia, Bristol-Myers Squibb, Novartis Pharmaceuticals Australia Pty Ltd, Myriad, NeraCare, and Amgen outside the submitted work; support from Melanoma Institute Australia, The University of Sydney, The Royal Prince Alfred Hospital and New South Wales Health Pathology, and The Ainsworth Foundation is also acknowledged. Dr Sondak reported receiving personal fees from Bristol-Myers Squibb, Merck, Polynoma, and Regeneron outside the submitted work. Dr Stein reported receiving other (compensation to department for diagnostic services) from MoleSafe USA outside the submitted work. Dr J. F. Thompson reported grants from Australian NHMRC and grants from Sydney Medical School Foundation, The University of Sydney, during the conduct of the study and receiving honoraria and travel support from GlaxoSmithKline and Provectus Inc and personal fees for serving on advisory boards for BMS Australia and MSD Australia outside the submitted work. Dr Wei reported serving as an investigator for Castle Biosciences (no personal financial compensation). No other disclosures were reported. Publisher Copyright: {\textcopyright} 2020 American Medical Association. All rights reserved.",
year = "2020",
month = sep,
doi = "10.1001/jamadermatol.2020.1729",
language = "English (US)",
volume = "156",
pages = "1004--1011",
journal = "JAMA Dermatology",
issn = "2168-6068",
publisher = "American Medical Association",
number = "9",
}