Association of Survival With Shorter Time to Radiation Therapy After Surgery for US Patients With Head and Neck Cancer

Abstract

Importance: Shortening the time from surgery to the start of radiation (TS-RT) is a consideration for physicians and patients. Although the National Comprehensive Cancer Network recommends radiation to start within 6 weeks, a survival benefit with this metric remains controversial.

Objective: To determine the association of delayed TS-RT with overall survival (OS) using a large cancer registry.

Design, setting, and participants: In this observational cohort study, 25 216 patients with nonmetastatic stages III to IV head and neck cancer were identified from the National Cancer Database (NCDB).

Exposures: Patients received definitive surgery followed by adjuvant radiation therapy, with an interval duration defined as TS-RT.

Main outcomes and measures: Overall survival as a function of TS-RT and the effect of clinicopathologic risk factors and accelerated fractionation.

Results: We identified 25 216 patients with nonmetastatic squamous cell carcinoma of the head and neck. There were 18 968 (75%) men and 6248 (25%) women and the mean (SD) age of the cohort was 59 (10.9) years. Of the 25 216 patients, 9765 (39%) had a 42-days or less TS-RT and 4735 (19%) had a 43- to 49-day TS-RT. Median OS was 10.5 years (95% CI, 10.0-11.1 years) for patients with a 42-days or less TS-RT, 8.2 years (95% CI, 7.4-8.6 years; absolute difference, -2.4 years, 95% CI, -1.5 to -3.2 years) for patients with a 43- to 49-day TS-RT, and 6.5 years (95% CI, 6.1-6.8 years; absolute difference, -4.1 years, 95% CI, -3.4 to -4.7 years) for those with a 50-days or more TS-RT. Multivariable analysis found that compared with a 42-days or less TS-RT, there was not a significant increase in mortality with a 43- to 49-day TS-RT (HR, 0.98; 95% CI, 0.93-1.04), although there was for a TS-RT of 50 days or more (HR, 1.07; 95% CI, 1.02-1.12). A significant interaction was identified between TS-RT and disease site. Subgroup effect modeling found that a delayed TS-RT of 7 days resulted in significantly worse OS for patients with tonsil tumors (HR, 1.22; 95% CI, 1.05-1.43) though not other tumor subtypes. Accelerated fractionation of 5.2 fractions or more per week was associated with improved survival (HR, 0.93; 95% CI, 0.87-0.99) compared with standard fractionation.

Conclusions and relevance: Delayed TS-RT of 50 days or more was associated with worse overall survival. The multidisciplinary care team should focus on shortening TS-RT to improve survival. Unavoidable delays may be an indication for accelerated fractionation or other dose intensification strategies.

Figure 1.. Association of Delay From Surgery to Radiation (T_S-RT) With Overall Survival

A, Kaplan-Meier estimates of overall survival according to a T_S-RT of 42 days or less, 43 to 49 days, or 50 days or more. The adjusted hazard ratio (HR) was determined from a Cox multivariable regression model with a T_S-RT of 42 days or less as the reference. B, Adjusted HR for mortality by T_S-RT modeled as a continuous variable with a restricted cubic spline with 3 knots. A 42-day T_S-RT was used as the reference. Shading indicates the 95% CI for HR estimates.

Figure 2.. Subgroup Effects of Covariates With Significant Interactions With T_S-RT

Adjusted hazard ratio for mortality according to a T_S-RT of 43 to 49 days or 50 days or more compared with 42 days or less varied by disease site. T_S-RT indicates time from surgery to the start of radiation.

Figure 3.. Association of Accelerated Fractionation With Overall Survival (OS)

Kaplan-Meier estimates of OS according to standard (<5.2 average fractions per week) or accelerated (≥5.2 average fractions per week) fractionation. The adjusted hazard ratio was determined from a Cox multivariable regression model with standard fractionation as the reference.