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Use of new molecular tests for melanoma by pigmented-lesion experts

2019; Elsevier BV; Volume: 82; Issue: 1 Linguagem: Inglês

10.1016/j.jaad.2019.08.022

1097-6787

Amir Varedi, Laura Gardner, Caroline C. Kim, Emily Y. Chu, Michael E. Ming, Sancy A. Leachman, Clara Curiel‐Lewandrowski, Susan M. Swetter, Douglas Grossman,

Skin Protection and Aging

To the Editor: Three commercial tests based on melanoma gene expression aim to improve diagnostic and/or prognostic accuracy for pigmented lesions. The myPath Melanoma test (Myriad, Salt Lake City, UT) is based on the expression of 23 genes from formalin-fixed material that may serve as an adjunct to histologic analysis to distinguish melanoma from nevi.1Ko J.S. Clarke L.E. Minca E.C. Brown K. Flake 2nd, D.D. Billings S.D. Correlation of melanoma gene expression score with clinical outcomes on a series of melanocytic lesions.Hum Pathol. 2019; 86: 213-221Crossref PubMed Scopus (10) Google Scholar The Pigmented Lesion Assay (DermTech, La Jolla, CA) is a noninvasive tape-stripping test based on the expression of 2 genes in the stratum corneum, intended to inform whether a lesion is concerning for melanoma.2Gerami P. Yao Z. Polsky D. et al.Development and validation of a noninvasive 2-gene molecular assay for cutaneous melanoma.J Am Acad Dermatol. 2017; 76: 114-120Abstract Full Text Full Text PDF PubMed Scopus (74) Google Scholar The Decision-Dx Melanoma test (Castle Biosciences, Friendswood, TX) is based on the expression of 31 genes (many derived from prior publicly available sources) from formalin-fixed material and provides a class 1 or class 2 result indicating a low or high risk, respectively, of melanoma recurrence and metastasis.3Gastman B.R. Gerami P. Kurley S.J. Cook R.W. Leachman S. Vetto J.T. Identification of patients at risk of metastasis using a prognostic 31-gene expression profile in subpopulations of melanoma patients with favorable outcomes by standard criteria.J Am Acad Dermatol. 2019; 80: 149-157Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar These tests are not endorsed outside of a clinical study by the National Comprehensive Cancer Network or American Academy of Dermatology,4Swetter S.M. Tsao H. Bichakjian C.K. et al.Guidelines of care for the management of primary cutaneous melanoma.J Am Acad Dermatol. 2019; 80: 208-250Abstract Full Text Full Text PDF PubMed Scopus (262) Google Scholar and it is unclear how they are currently used in clinical practice. We investigated the use of these tests by pigmented-lesion experts primarily in the United States using a survey platform (https://www.jotform.com) approved by the institutional review board at the University of Utah (no. 120210). The survey was disseminated by e-mail to 50 Pigmented Lesion Subcommittee members of the national Melanoma Prevention Working Group and additional pigmented-lesion clinic directors identified in a prior study.5Nelson K.C. Grossman D. Kim C.C. et al.Management strategies of academic pigmented lesion clinic directors in the United States.J Am Acad Dermatol. 2018; 79: 367-369Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar We queried for demographic information, whether each test was ordered, and how results affected patient treatment. There were 42 respondents (84% response rate) with a range of experience, most of whom manage pigmented lesions in a large percentage of their patients (Table I). The proportions who have ever ordered the myPath Melanoma, Pigmented Lesion Assay, and Decision-Dx tests were 21%, 21%, and 29%, respectively, and 63% of the respondents ordering these tests reported that results affected patient management (Table I). The tests were most commonly ordered less than once per month. There did not appear to be a correlation between test use and experience or percentage of practice devoted to pigmented lesions.Table IUse of molecular tests by pigmented-lesion expertsCharacteristicsn (%)Number using molecular testsmyPathPLADecisionDxPractice/faculty rank Private practice0 (0)000 Instructor1 (2)000 Assistant professor12 (29)333 Associate professor9 (21)133 Full professor20 (48)536Years in practice 2015 (36)314Percentage of practice focused on pigmented lesions 0-101 (2)100 11-251 (2)010 26-507 (17)022 51-10033 (79)8610Total participants using test, n (%)9/42 (21)9/42 (21)12/42 (29)Results affected management, n (%)4/9 (44)8/9 (89)7/12 (58)PLA, Pigmented Lesion Assay. Open table in a new tab PLA, Pigmented Lesion Assay. The survey results are presented in Table II. The most commonly cited reasons for not ordering a particular test were (1) lack of utility, (2) need for further validation, and (3) not advocated by guidelines. Unfamiliarity with the tests, institutional discouragement, and potential cost were also reasons for not ordering. myPath test results influenced decisions to re-excise or excision margin determination. Pigmented Lesion Assay test results were used both to avoid and justify biopsy of a lesion. DecisionDx test results were used to justify enhanced imaging surveillance to patients with early-stage melanoma and, in some cases, affected recommendations for sentinel lymph node biopsy and adjuvant therapy.Table IIExplanations for not using tests and effect on patient management∗Responses in each category are listed in descending order of frequency. Respondents were asked to identify all applicable selections for each test and were given the opportunity to fill in text boxes if they had responses not listed among the choices.ExplanationsNumber of responsesReasons for not ordering tests myPathDo not feel it would be useful in my practice16Unfamiliar with this test5Institution/hospital has discouraged ordering the test4Concern about the cost or insurance coverage4Prefer use of FISH, CGH, or other genetic test for indeterminate lesions3Defer to pathology for ordering3Feel that further validation studies are necessary1 PLAFeel that further validation studies are necessary20Do not feel it would be useful in my practice18Not feasible to delay biopsy decisions for several days waiting for results7Concern about the cost or insurance coverage2Unfamiliar with this test1Institution/hospital has discouraged ordering the test1Concern about time required to perform test1Concern that tape stripping might alter lesion architecture1 DecisionDxFeel that further validation studies are necessary25Test not recommended for routine care in guidelines22Do not feel test results would change patient management16Do not feel it would be useful in my practice12Concern about potential liability if results not used to change management1Concern about the cost or insurance coverage1Changes in patient management myPathRe-excision or more extensive surgery was recommended4Re-excision was not performed, or a less extensive surgery was recommended1 PLANegative test result led to avoidance of biopsy8Positive test result led to biopsy which would otherwise not been performed6 DecisionDx: melanomaStage I/II melanoma patient with class 2 result offered greater surveillance/imaging8Stage I/II melanoma patient with class 2 result offered immunotherapy2Stage IA melanoma patient with class 2 result offered SLNB2Stage IB melanoma patient with class 1 result not referred for SLNB2Stage IB/II melanoma patient with class 1 result not referred to oncology1Affected recommendations for adjuvant therapy in Stage IIIA melanoma patient1CGH, Comparative genomic hybridization; FISH, fluorescence in situ hybridization; PLA, Pigmented Lesion Assay; SLNB, Sentinel lymph node biopsy.∗ Responses in each category are listed in descending order of frequency. Respondents were asked to identify all applicable selections for each test and were given the opportunity to fill in text boxes if they had responses not listed among the choices. Open table in a new tab CGH, Comparative genomic hybridization; FISH, fluorescence in situ hybridization; PLA, Pigmented Lesion Assay; SLNB, Sentinel lymph node biopsy. Limitations include sampling error and potential biases of respondents. Notably, this survey study indicates that about a quarter of pigmented-lesion experts have ordered these new molecular tests and that for most of these individuals, the test results affected patient management. Given the lack of uniform use patterns and consensus in this group, it is likely that there also exists variation in practice among general dermatologists. Prospective clinical trials are needed to determine whether actions based on these different test results can improve patient outcomes.