Association between time from surgery to radiation therapy and multimodality treatment outcomes in HPV+ head and neck cancer: a multi-institutional cohort experience.

PURPOSE Oropharyngeal squamous cell cancers (OPSCCs) are traditionally managed with surgery and, if indicated, adjuvant radiotherapy (RT) with or without chemotherapy. NCCN recommends keeping the time from surgery to the start of RT (TSRT) within 6 weeks to avoid possibly compromising patient outcomes. HPV+ OPSCCs behave more favorably than HPV- OPSCCs. We hypothesized that TSRT beyond 6 weeks may not portend poorer outcomes for the former. METHODS We identified non-metastatic, high-risk HPV+ OPSCCs treated with multimodal therapy at two institutions. Prolonged TSRT was defined as > 6 weeks and was evaluated for association with recurrence-free survival (RFS). Radiation treatment time (RTT; time from the first to the last day of RT), total treatment package time (TTPT; time from surgery to the end of adjuvant treatments), de-escalated RT (dose ≤56 Gy), concurrent chemotherapy, smoking history, and treatment institution were evaluated as possible confounders. RESULTS 96 patients were included. The median follow-up time was 62 months (4—123 months). 69 patients underwent transoral robotic surgeries. 27 received open surgeries. The median postoperative RT dose was 60 Gy (50—70.8 Gy). The median TSRT, RTT, and TTPT were 38 days (11—208), 43 days (26—56 days), and 81 days (40—255 days), respectively. 10 patients failed treatment at a median of 8 months (4—64 months). 2 locoregional and 4 distant failures occurred in the group without prolonged TSRT, while 2 locoregional and 2 distant failures were recorded in the prolonged TSRT group. Prolonged TTPT, de-escalated RT, chemotherapy, smoking history, and treatment institution were not associated with treatment failure. RTT was dropped from our analyses as no events appeared in the prolonged RTT group, and no reliable hazard ratio could be computed. CONCLUSIONS TSRT > 6 weeks was not significantly associated with inferior outcomes in the post-operative management of HPV+ OPSCCs. Longer TSRT may facilitate better recovery from surgical toxicity, as needed, without compromising oncologic outcomes. The TSRT goal for these cancers should be investigated in future studies.