Clinical Summary

The decision to prescribe adjuvant radiation (ART) therapy for cutaneous squamous cell carcinoma (cSCC) is challenging. Recommendations are based on a number of wide-ranging clinicopathologic factors, which encompass a broad array of patients. These clinicopathologic factors have not been demonstrated to predict benefit from ART and have not been consistently used to guide ART decisions. DecisionDx-SCC (40-GEP) is a prognostic, gene expression profile test that classifies cSCC tumors into low (Class 1), higher (Class 2A), or highest (Class 2B) risk of nodal and/or distant metastasis.

To determine if the DecisionDx-SCC test could identify cSCC patients with one or more high-risk factors who benefit from ART in controlling metastatic disease progression from those who may not.

Samples were obtained from 920 patients who were matched on clinical risk factors and stratified by ART status. 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). Each sample was analyzed using survival methods and stratified by GEP result and ART status.

• 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).
• This benefit was not observed in Class 1 or Class 2A ART-treated patient cohorts (p>0.05 for each).
• No risk factor or staging system was able to identify patients who would benefit from ART treatment. Only patients with a DecisionDx-SCC Class 2B were independently identified as benefitting from reduced metastatic risk after ART treatment.
     

• DecisionDx-SCC identifies patients at highest risk of nodal/distant metastasis who may derive greatest benefit from ART, as well as patients who may have clinical indications for ART but are at low risk of metastasis or less likely to benefit.
• Compared to current guidelines, DecisionDx SCC can provide greater specificity in identifying individual patients who benefit from ART and improve riskaligned decision making for use of ART.