Validation of a 40-gene expression profile test to predict metastatic risk in localized high-risk cutaneous squamous cell carcinoma - 03/09/20
Cet article a été publié dans un numéro de la revue, cliquez ici pour y accéder
Abstract |
Background |
Current staging systems for cutaneous squamous cell carcinoma (cSCC) have limited positive predictive value for identifying patients who will experience metastasis.
Objective |
To develop and validate a gene expression profile (GEP) test for predicting risk for metastasis in localized, high-risk cSCC with the goal of improving risk-directed patient management.
Methods |
Archival formalin-fixed paraffin-embedded primary cSCC tissue and clinicopathologic data (n = 586) were collected from 23 independent centers in a prospectively designed study. A GEP signature was developed using a discovery cohort (n = 202) and validated in a separate, nonoverlapping, independent cohort (n = 324).
Results |
A prognostic 40-GEP test was developed and validated, stratifying patients with high-risk cSCC into classes based on metastasis risk: class 1 (low risk), class 2A (high risk), and class 2B (highest risk). For the validation cohort, 3-year metastasis-free survival rates were 91.4%, 80.6%, and 44.0%, respectively. A positive predictive value of 60% was achieved for the highest-risk group (class 2B), an improvement over staging systems, and negative predictive value, sensitivity, and specificity were comparable to staging systems.
Limitations |
Potential understaging of cases could affect metastasis rate accuracy.
Conclusion |
The 40-GEP test is an independent predictor of metastatic risk that can complement current staging systems for patients with high-risk cSCC.
Le texte complet de cet article est disponible en PDF.Key words : cutaneous squamous cell carcinoma, gene expression profile, metastasis, prognostication, risk
Abbreviations used : AJCC, BWH, cSCC, GEP, HR, LR, MFS, NCCN, NPV, PPV
Plan
Drs Schmults and Arron are cosenior authors. |
|
Funding sources: Supported by Castle Biosciences, Inc, which provided funding for tissue and clinical data retrieval to contributing centers. |
|
Disclosure: Drs Wysong (steering committee), Newman (steering committee), Schmults (steering committee), Arron (steering committee), Ibrahim, Farberg, Bar, Cleaver, Somani, Brodland, Toyohara, Maher, Xia, Bibee, Griego, and Rigel are principal investigators for the study. Dr Wysong is an unpaid board member of the American College of Mohs Surgeons and World Congress of Dermatology. Drs Covington, Kurley, Meldi Plasseraud, Estrada, and Cook, and authors Scholl and Johnson are employees and options holders at Castle Biosciences. Dr Schmults is an investigator for Novartis, Genentech and Merck, a consultant for Sanofi and Regeneron (steering committee), and chair for the National Comprehensive Cancer Network. Dr Arron is an investigator for Pfizer, Regeneron and PellePharm, and a consultant for Enspectra Health, Rakuten Medical, and Gerson Lehrman Group. Drs Panther and Zitelli have no disclosures. |
|
Presented at the 2019 American Society for Dermatologic Surgery Annual Meeting, Chicago, IL, October 24-27, 2019. |
|
IRB approval status: Approved by IRBs before initiation. IRB granted a waiver of consent because of the nature of the disease under study. |
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?