Risk factors and survival impact of severe radiation-related late toxicities in head and neck cancer-a cohort study.

Abstract

Radiation late toxicities (RLTs) are complications of curative-intent radiotherapy (RT) for head and neck cancer (HNC) and are increasingly relevant due to younger age at diagnosis and improved survival outcomes. We conducted a cohort study of HNC patients who received ≥50 Gy as part of curative treatment between January 2003 and December 2020 at a Canadian quaternary cancer center. Risk factors for severe RLTs (≥RTOG Grade 3) were evaluated using time-to-event analyses. Actuarial rates of RLT and overall survival (OS) were estimated using competing risk and Kaplan-Meier methods, respectively. Cox proportional hazard models identified factors associated with RLT and OS. Among 7622 patients, 12.6% (n = 958) developed RLTs without disease progression, with a 5-year actuarial incidence of 16% (95% CI: 15-16). A <i>survivors</i> subgroup (n = 4650) with ≥2 years of follow-up and no recurrence was also identified. Modifiable risk factors for RLTs included RT technique, dose, neck irradiation, neck dissection, smoking status, and chemotherapy (p ≤ 0.012). Non-modifiable factors included younger age, female sex, and oral cavity primaries (p ≤ 0.012). In multivariable analysis, RLTs were associated with increased mortality (HR = 2.1, 95% CI: 1.8-2.5, p < 0.001), but RLT's impact on OS was lessened among patients referred to the Adult Radiation Late Effects Clinic (ARLEC) (HR = 1.7, 95% CI: 1.3-2.4). RLTs are common and associated with worse survival among HNC survivors. Identification of modifiable risk factors provides opportunities for prevention. Multidisciplinary management of RLTs in specialized clinics may help improve the outcomes in this growing survivorship population. No external funding was utilized for this study.