Timely initiation of adjuvant therapy and survival in head and neck cancer: Post hoc analysis of the NDURE RCT.

182 Background: Initiation of postoperative radiation therapy (PORT) ≤ 6 weeks of surgery for head and neck squamous cell carcinoma (HNSCC) is a component of National Comprehensive Cancer Network Guidelines and a Commission on Cancer quality metric. Despite the radiobiologic principle of accelerated repopulation, the association between starting guideline-adherent PORT and oncologic outcomes have been derived primarily from retrospective studies, leading to uncertainty about the metric’s oncologic importance. Within the setting of the NDURE RCT, we hypothesize that initiation of timely, guideline-adherent PORT is associated with improved recurrence-free survival (RFS) among patients with HNSCC. Methods: Adults with HNSCC planning to undergo surgery and PORT were randomly assigned 1:1 to a multilevel, enhanced navigation-based intervention (NDURE) or usual care (UC) patient navigation. In this post-hoc analysis, patients were grouped according to guideline-adherence for time from surgery to PORT (≤ 6 weeks vs > 6 weeks) regardless of allocation to NDURE or UC. The primary endpoint was recurrence free survival (RFS). Secondary endpoints included overall survival (OS) and locoregional (LR) failure. Landmark (LM; surgery + 6 weeks) multivariable Cox proportional hazards (CPH) regression analysis evaluated the association of timely PORT with RFS and OS adjusted for age, race, Charlson Deyo Comorbidity score, ECOG performance status, HPV status, and AJCC pathologic stage. Locoregional failure (LRF) was analyzed using a univariate Fine and Gray competing risk LM regression approach with death as a competing event. Results: There were 143 patients who underwent surgery, had a pathologic indication for PORT, and were eligible for the RFS analysis (no RFS event prior to LM and still in follow-up at LM). Fifty nine percent of patients started PORT ≤6 weeks of surgery. For the RFS analysis, there were 27 events among those with timely PORT and 32 events among those without timely PORT with a median follow-up of 36 (IQR 20 to 46) months. Patients who started PORT ≤ 6 weeks of surgery had improved RFS relative to those who did not on adjusted CPH analysis (aHR 0.58; 95% CI 0.34 to 0.99; p = 0.048). The 2-year RFS was 74% (95% CI 65% to 84%) among those with timely PORT and 47% (95% CI 36% to 62%) among those without timely PORT. Patients who initiated PORT ≤ 6 weeks of surgery had improved OS relative to those who did not on adjusted CPH analysis (aHR 0.43; 95% CI 0.24 to 0.78; p = 0.005). The risk of LRF did not differ between those with and without timely PORT (LRF subdistribution HR = 0.79; 95% CI 0.31 to 2.06; Fine and Gray p = 0.63). Conclusions: Initiation of PORT ≤ 6 weeks of surgery was associated with improved RFS and OS but not LRF. These data support the oncologic benefit of timely, guideline-adherent PORT in this population and the therapeutic benefit of cancer care delivery interventions to improve initiation of timely PORT. Clinical trial information: NCT04030130 .