Predicting adjuvant radiation therapy benefit in cutaneous squamous cell carcinoma with the 40-gene expression profile
Creators: name: Ruiz, Emily S
name: Brito, Karina
name: Karn, Emily E
name: Vidimos, Allison T
name: Campbell, Shauna R
name: Wang, David M
name: Siegel, Jennifer J
name: Covington, Kyle R
name: Cook, Robert W
name: Goldberg, Matthew S
name: Koyfman, Shlomo A
Publisher: name: Taylor & Francis
Year: 2024
Subjects: subject: Medicine
subject: Cell Biology
subject: Genetics
subject: FOS: Biological sciences
subject: Immunology
subject: FOS: Clinical medicine
subject: Biological Sciences not elsewhere classified
subject: Mathematical Sciences not elsewhere classified
subject: Cancer
subject: Science Policy
subject: Hematology

description: <b>Aim:</b> To independently confirm that the 40-gene expression profile (40-GEP) test can identify patients with high-risk cutaneous squamous cell carcinoma who are more or less likely to benefit from adjuvant radiation therapy (ART). <b>Materials &amp; methods:</b> Primary cutaneous squamous cell carcinoma tumors from two academic centers received retrospective 40-GEP testing and were analyzed for 5-year metastasis-free survival and projected time to event. <b>Results:</b> Random sampling of matched patient pairs (<i>n</i> = 52 ART-treated; 371 no ART) showed a median 50% decrease in 5-year progression rate for ART-treated patients (vs no ART) with 40-GEP Class 2B. Class 2A was associated with a modest ART benefit, but not Class 1. <b>Conclusion:</b> The 40-GEP identified patients most likely to benefit from ART (Class 2B) and those that can consider deferring treatment (Class 1). Independent validation study: 40-GEP identifies patients with cutaneous squamous cell carcinoma who would be most likely to benefit from adjuvant radiation therapy. Select patients with completely resected high-risk squamous cell carcinoma are eligible for and undergo adjuvant radiation therapy (ART), but criteria for ART is heterogenous. Identifying patients with the highest risk of disease progression who would most benefit from ART is a clinical challenge. The 40-gene expression profile (40-GEP) test was recently reported to predict a benefit from ART for patients receiving a Class 2B result, and a low likelihood of benefit for a Class 1 result that together with low metastatic risk suggests these patients may consider deferring treatment. This validation study utilized an independent cohort of patients with high-risk cutaneous squamous cell carcinoma tumors matched on clinicopathological factors to compare disease progression rates and projected time to metastasis (using a “life expectancy” algorithm) for patients who received ART to those who did not. Patients with a 40-GEP Class 2B result showed a median ∼50% decrease in disease progression between ART-treated and untreated tumors and a significant deceleration in projected time to metastases. No differences were observed for Class 1 between ART treated and untreated tumors. The results validate the 40-GEP test as having predictive value in identifying patients benefitting from ART and those that can safely defer, and can guide difficult management decisions when patients and their physicians are considering the risks of side effects and benefit of ART. Previous work has shown that deferring ART in 40-GEP Class 1 patients can save $784 million annually in direct healthcare costs.