The Negative Impact of Longer Delays to Starting Radiation after Surgery for Head and Neck Cancer Patients in the United States

Abstract

For patients with head and neck cancer, the National Comprehensive Cancer Network recommends keeping the time from surgery to radiation (TS-RT) under 6 weeks when adjuvant therapy is given. However, an associated survival benefit remains controversial. We set out to explore the effect of a delayed TS-RT for patients in the US. Patients with squamous cell carcinoma of the oropharynx, oral cavity, hypopharynx, and larynx treated with definitive surgery followed by adjuvant radiation between 2004-2013 were identified from the National Cancer Database. Overall survival (OS) was compared according to a 6-week TS-RT cutoff. The effect of ≤42 day, 43-49 day, or ≥50 day TS-RT was tested using multivariate Cox regressions controlling for socioeconomic variables, comorbidity, clinicopathologic risk factors, type of facility, distance travelled, time from diagnosis to surgery, length of hospital stay, unplanned hospital readmissions, chemotherapy, radiation dose, and use of IMRT. The effect of accelerated fractionation (≥5.2 fractions/week) was tested according to length of TS-RT. We identified 42,740 patients. Median OS was greater for the 19,859 (46%) patients with a ≤6 week TS-RT (10.0 years vs 7.7 years, P < .0001). Compared to a ≤42 day TS-RT, there was no significant increase in mortality with a 43-49 day TS-RT (HR 1.03, P = .19), although there was for a ≥50 day TS-RT (HR 1.11, P <.0001). Compared to patients who had both surgery and radiation at an academic center, those who transferred care after surgery at an academic hospital (HR 1.12, P =.0001), or had all care at a Comprehensive Community Cancer Program (HR 1.06, P = .01) or all care at a community center (HR 1.08, P = .03) had inferior OS. For patients with a >6 week TS-RT, accelerated fractionation was associated with improved OS (HR 0.92, P = .02), and for those with a ≤6 week TS-RT there was a trend for improved OS (HR 0.93, P = .08). A TS-RT delayed >7 weeks is associated with worse overall survival. Treatment at academic centers may be associated with improved outcomes, and the benefit to care at specialized centers should continue to be explored. Treating teams should focus on shortening TS-RT, and unavoidable delays may warrant consideration of accelerated fractionation or other dose intensification strategies.