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Original Investigation
April 2018

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

Author Affiliations
  • 1Department of Radiation Oncology, Stanford University, Stanford, California
  • 2Palo Alto Veterans Affairs Health Care System, Palo Alto, California
  • 3Department of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, California
  • 4Department of Head and Neck Surgery, University of California San Diego, San Diego
JAMA Otolaryngol Head Neck Surg. 2018;144(4):349-359. doi:10.1001/jamaoto.2017.3406
Key Points

Question  Is there a survival benefit to a shorter time from surgery to the start of radiation (TS-RT) for patients with head and neck squamous cell carcinoma?

Finding  In this observational cohort study of 25 216 patients from the National Cancer Database, a TS-RT of 42 days or less was associated with improved survival compared with 50 days or longer; a delay of 1 week resulted in inferior outcomes for patients with tonsil tumors. Accelerated fractionation was associated with improved survival compared with standard fractionation.

Meaning  Efforts should be made to prevent delays in TS-RT, and there may be a role for intensifying therapy when delays are unavoidable.

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.

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