Association of Oxidative Stress Pathway Alterations with Risk of Treatment Failure in RTOG9512: A Randomized Trial of Hyperfractionation Versus Conventional Fractionation in T2 Squamous Cell Carcinoma of the Vocal Cord

Based on the growing body of retrospectively collected and heterogeneously treated clinical cohorts and preclinical models, we investigated the clinical importance of NRF2 pathway alteration in an independent set of patients treated uniformly in the large prospective phase III trial RTOG 9512. We tested the hypothesis that patients with T2 glottic squamous cell carcinoma (SCC) harboring NRF2 pathway mutations would show radioresistance and have more local failure (LF) and locoregional failure (LRF) compared to those who did not have these mutations, using patients who received radiotherapy alone, thus removing potentially confounding effects of other therapies, like surgery or chemotherapy.]]>
Two hundred fifty patients were enrolled in the RTOG 9512 trial, of whom 239 (95.6 percent) were eligible for primary analysis. Of these 239 patients, 153 had available pre-treatment paraffin embedded (FFPE) tissues, of which 119 were successfully sequenced using targeted high-throughput DNA sequencing and were included in our final analysis. We have submitted samples from all 153 subjects for whom a pre-treatment tissue sample was available. ]]>
Radiotherapy is the primary treatment for patients with T2N0 glottic squamous cell carcinoma (SCC). Approximately 30 percent of these patients experience locoregional relapse despite dose escalation. Mutations in the NFE2L2/KEAP1/CUL3 pathway have been linked to radioresistance preclinically and in small retrospective studies. We tested the hypothesis that patients with T2 glottic Squamous Cell Carcinoma (SCC) having these mutations would show radioresistance and more local (LF) and locoregional failures (LRF) when treated with RT compared to those without mutations, using samples from a phase III trial. ]]>