Association of a 40-Gene Expression Profile (40-GEP) with Risk of Metastatic Disease Progression of Cutaneous Squamous Cell Carcinoma (cSCC) and Benefit of Adjuvant Radiation Therapy (ART)

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Sarah Arron
Javier Cañueto
Jennifer Siegel
Alison Fitzgerald
Anesh Prasai
Shlomo Koyfman
Sue Yom


Adjuvant radiation therapy (ART), ART, 40-GEP, cSCC


Purpose: Adjuvant radiation therapy (ART) is recommended based on high-risk clinicopathologic features of cutaneous squamous cell carcinoma (cSCC), but these criteria are wide-ranging, encompassing a broad range of patients. The 40-gene expression profile (40-GEP) test is a prognostic tool which classifies cSCC tumors into low (Class 1), moderate (Class 2A), and high (Class 2B) risk of metastasis. This study determined if the metastatic risk as assessed by 40-GEP in high-risk cSCC patients predicts benefit from ART.

Study: Samples were obtained from 920 patients who were matched on clinical risk factors and stratified by ART status, to create 49 matched patient strata. Randomly sampled pairs of matched ART and non-ART patients comprising 10,000 resampled cohorts were each analyzed for 5-year metastasis-free survival (nodal and/or distant events; MFS) and predicted time to metastatic event (using a standard ‘life expectancy’ algorithm).

Results: Median 5-year MFS rates for the resampled cohorts demonstrated a 50% improvement, on average, for Class 2B ART-treated patient cohorts compared to Class 2B non-ART-treated patient cohorts. Class 2B ART-treated patient cohorts showed a 5-fold delay in predicted time to metastatic event and a deceleration of disease progression as compared to non-ART-treated patients (Kolmogorov-Smirnov test, p<0.01), that was not observed for Class 1 or 2A patients (p>0.05 for each). No risk factor or staging system combined with ART status was able to identify groups that would benefit from ART treatment as well as the 40-GEP test.

Conclusions: The 40-GEP test identifies patients at highest risk of nodal or distant metastasis who are most likely to benefit from ART, as well as lower-risk cohorts who benefit less from ART. These findings provide greater specificity than current clinicopathologic guidelines on which to base decisions for ART.


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