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Molecular risk prediction in cutaneous melanoma: A meta-analysis of the 31-gene expression profile prognostic test in 1,479 patients - 19/08/20

Doi : 10.1016/j.jaad.2020.03.053 
Bradley N. Greenhaw, MD a, Kyle R. Covington, PhD b, Sarah J. Kurley, PhD b, Yildiray Yeniay, MD e, Nhat Anh Cao, BS f, Kristen M. Plasseraud, PhD b, Robert W. Cook, PhD b, Eddy C. Hsueh, MD c, Brian R. Gastman, MD d, Maria L. Wei, MD, PhD e, f,
a Dermatology Center of North Mississippi, Tupelo, Mississippi 
b Castle Biosciences, Inc, Friendswood, Texas 
c Saint Louis University, St Louis, Missouri 
d Cleveland Clinic Lerner Research Institute, Cleveland, Ohio 
e University of California–San Francisco, San Francisco, California 
f San Francisco Veterans Affairs Medical Center, San Francisco, California 

Correspondence to: Maria L. Wei, MD, PhD, 1701 Divisadero St, 4th Floor, San Francisco, CA 94115.1701 Divisadero St4th FloorSan FranciscoCA94115

Abstract

Background

Multiple studies have reported on the accuracy of the prognostic 31-gene expression profile test for cutaneous melanoma. Consistency of the test results across studies has not been systematically evaluated.

Objective

To assess the robustness of the prognostic value of the 31-gene expression profile.

Methods

Raw data were obtained from studies identified from systematic review. A meta-analysis was performed to determine overall effect of the 31-gene expression profile. Clinical outcome metrics for the 31-gene expression profile were compared with American Joint Committee on Cancer staging.

Results

Three studies met inclusion criteria; data from a novel cohort of 211 patients were included (n = 1,479). Five-year recurrence-free and distant metastasis-free survival rates were 91.4% and 94.1% for Class 1A patients and 43.6% and 55.5% for Class 2B patients (P < .0001). Meta-analysis results showed that Class 2 was significantly associated with recurrence (hazard ratio 2.90; P < .0001) and distant metastasis (hazard ratio 2.75; P < .0001). The 31-gene expression profile identified American Joint Committee on Cancer stage I to III patient subsets with high likelihood for recurrence and distant metastasis. Sensitivity was 76% (95% confidence interval 71%-80%) and 76% (95% confidence interval 70%-82%) for each end point, respectively. When 31-gene expression profile and sentinel lymph node biopsy results were considered together, sensitivity and negative predictive value for distant metastasis-free survival were both improved.

Conclusion

The 31-gene expression profile test consistently and accurately identifies melanoma patients at increased risk of metastasis, is independent of other clinicopathologic covariates, and augments current risk stratification by reclassifying patients for heightened surveillance who were previously designated as being at low risk.

Le texte complet de cet article est disponible en PDF.

Key words : genomics, melanoma, meta-analysis, metastasis, molecular classification, prognosis, recurrence, survival, 31-GEP

Abbreviation used : CI


Plan


 Funding sources: Supported by Castle Biosciences, Inc.
 Conflicts of interest: Drs Covington, Kurley, Plasseraud, and Cook are employees and options holders at Castle Biosciences, Inc. Drs Greenhaw, Gastman, and Hsueh serve on the speakers bureau for Castle Biosciences, Inc. Drs Yeniay, Hsueh, and Wei and Ms Cao have no conflicts of interest to declare.
 IRB approval status: All studies included in the meta-analysis were performed under IRB-approved protocols or received exemption from IRB review.
 Reprints not available from the authors.


© 2020  Publié par Elsevier Masson SAS.
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Vol 83 - N° 3

P. 745-753 - septembre 2020 Retour au numéro
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