Survival Impact of Treatment Interval Delays in Head and Neck Cancer

Multidisciplinary head and neck cancer management must reconcile increasingly sophisticated subspecialty care with timeliness of care. Prior studies have examined the individual effects of prolonging diagnosis to treatment interval (DTI), postoperative interval, and radiation interval but not considered them collectively. We investigate the shared impact of these interwoven intervals on head and neck cancer patients completing definitive surgery with postoperative radiation. Head and neck cancer patients undergoing upfront surgical resection with adjuvant radiation were identified in the National Cancer Database between 2004 and 2013. Patients treated with curative intent who completed full-course radiation therapy were included. Diagnosis to treatment interval was defined as the time from diagnosis until surgery. Postoperative interval was defined as the time from surgery to the first day of radiation. Radiation interval was defined as the time from the first to the last day of radiation. Multivariable models were constructed to assess the association between treatment delays and overall survival. Overall, 15,177 patients were evaluated. Prolonged DTI, postoperative interval, and radiation interval all were associated with impaired survival in univariate analysis. After adjustment for covariates, only prolonged postoperative interval (P = .006) and radiation interval (P < .001) independently predicted for risk of death, while the association of DTI with overall survival disappeared. Using multivariable restricted cubic spline functions, mortality risk escalated continuously for postoperative interval with each additional day, plateauing at 74 days (cumulative HR 1.25, 95% CI 1.11-1.32, P < .001). Similarly, mortality risk increased continuously for radiation interval with each additional day, peaking at 56 days (cumulative HR 1.31, 95% CI 1.22-1.39, P < .001). Delays beyond these change points were not associated with additional survival decrements. Delays in postoperative interval and radiation interval are independently associated with mortality risk. The hazard conferred suggest that attention to these physician-modifiable covariates could considerably improve prognosis. Delays in initiating treatment conversely do not appear to impact survival when appraised in conjunction with the entire treatment course.