Effect of time to initiation of postoperative radiation therapy on survival in surgically managed head and neck cancer

Abstract

Background: The objective of this study was to determine the effects of National Comprehensive Cancer Network (NCCN) guideline-adherent initiation of postoperative radiation therapy (PORT) and different time-to-PORT intervals on the overall survival (OS) of patients with head and neck squamous cell carcinoma (HNSCC).

Methods: The National Cancer Data Base was reviewed for the period of 2006-2014, and patients with HNSCC undergoing surgery and PORT were identified. Kaplan-Meier survival estimates, Cox regression analysis, and propensity score matching were used to determine the effects of initiating PORT within 6 weeks of surgery and different time-to-PORT intervals on survival.

Results: This study included 41,291 patients. After adjustments for covariates, starting PORT >6 weeks postoperatively was associated with decreased OS (adjusted hazard ratio [aHR], 1.13; 99% confidence interval [CI], 1.08-1.19). This finding remained in the propensity score-matched subset (hazard ratio, 1.21; 99% CI, 1.15-1.28). In comparison with starting PORT 5 to 6 weeks postoperatively, initiating PORT earlier was not associated with improved survival (aHR for ≤ 4 weeks, 0.93; 99% CI, 0.85-1.02; aHR for 4-5 weeks, 0.92; 99% CI, 0.84-1.01). Increasing durations of delay beyond 7 weeks were associated with small, progressive survival decrements (aHR, 1.09, 1.10, and 1.12 for 7-8, 8-10, and >10 weeks, respectively).

Conclusions: Nonadherence to NCCN guidelines for initiating PORT within 6 weeks of surgery was associated with decreased survival. There was no survival benefit to initiating PORT earlier within the recommended 6-week timeframe. Increasing durations of delay beyond 7 weeks were associated with small, progressive survival decrements. Cancer 2017;123:4841-50. © 2017 American Cancer Society.

Keywords: National Cancer Data Base; National Comprehensive Cancer Network (NCCN) guidelines; head and neck cancer; postoperative radiation therapy; quality of care.

Figure 1

Legend: Kaplan-Meier estimates of overall survival (OS) demonstrating the effect of NCCN Guideline-adherent initiation of PORT within 6 weeks of surgery versus non-Guideline adherent care initiating PORT more than 6 weeks postoperatively (n=41,291). [Table: see text]

Figure 2

Legend: Kaplan-Meier estimates of overall survival (OS) in the propensity score matched subset analysis (n=29,910) demonstrating the effect of NCCN Guideline-adherent initiation of PORT within 6 weeks of surgery versus non-Guideline adherent care initiating PORT more than 6 weeks postoperatively. [Table: see text]

Figure 3

Legend: Kaplan-Meier estimates of overall survival (OS) demonstrating the impact of increasing time to initiation of PORT (n=41,291). Each PORT time interval is not inclusive of the lower bound and is inclusive of the upper bound. [Table: see text]

Figure 4

Legend: Effect of changing time to initiation of postoperative radiation therapy (PORT) on overall survival after multivariable Cox proportional hazards analysis compared to starting adjuvant therapy between 5–6 weeks after surgery (n=41,291). Estimated hazard ratios are shown by black circles; horizontal lines represent 99% confidence intervals. Each PORT time interval is not inclusive of the lower bound and is inclusive of the upper bound. Analyses are adjusted for age, race, sex, insurance, income, Charlson/Deyo comorbidity score, primary site, AJCC pathologic stage grouping, concurrent chemotherapy, radiation modality, radiation dose, and duration of radiation.