Authors
Désirée Ratner, Gaurav Singh, Jason M Rizzo, Harrison Nguyen, Aaron S Farberg, Ally-Khan Somani, Jennifer J Siegel, Matthew S Goldberg, William Stebbins, Stanislav N Tolkachjov, Sarah T Arron
Published in
Journal of the American Academy of Dermatology. Aug 24, 2026. Epub Aug 24, 2026.
Abstract
Risk assessment in high-risk cutaneous squamous cell carcinoma (HRcSCC) uses several clinicopathologic staging system tools, yet under- and over-treatment often occur. Integration of tumor biology as an independent predictor via gene expression profile (GEP) may improve risk stratification and tailor adjuvant care.
Integrate clinicopathologic risk factors with 40-GEP testing to refine risk stratification.
Integrated 40-GEP (i40-GEP) combines optimized nested predictive models and five clinicopathologic features (immunosuppression, location, differentiation, tumor diameter, and perineural invasion) with the validated 40-GEP, and reports results: Class 1A (Low Risk), Class 1B (Moderate Risk), Class 2A (High Risk), and Class 2B (Highest Risk).
i40-GEP significantly stratifies metastatic and local recurrence (LR) risk (p<0.001) in a validation cohort (n=572), with >95% NPV for Class 1A across National Comprehensive Cancer Network subsets. The i40-GEP identified 12.9% of patients as Class 2B, with the lowest 3-year metastasis-free survival (66.2%) and a demonstrated benefit from adjuvant radiation treatment (ART). Multivariable analysis showed i40-GEP results significantly predict metastatic and LR risk more than individual clinicopathologic factors.
Retrospective study.
I40-GEP accurately stratifies metastatic and LR risk in patients with HRcSCC, leading to improved clinical decision-making. Class 2B i40-GEP identifies patients most likely to benefit from ART.
PMID:
42637048
Bibliographic data and abstract were imported from PubMed on 25 Aug 2026.
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