Impact of tobacco smoking on radiotherapy outcomes in 1875 HPV-positive oropharynx cancer patients.

Abstract

6047 Background: This study investigates the impact of smoking on radiotherapy (RT) outcome and survival in a population based cohort of HPV+ oropharynx cancer (OPC). Methods: We identified all OPC with positive p16 staining from 2007 –2015 who received curative IMRT according to approved guidelines in two oncology groups. Associations between smoking and locoregional control (LRC) and distant control (DC) were estimated by competing risk regression. Disease free survival (DFS) and overall survival (OS) were estimated by proportional-hazards regression model. Multivariable analyses (MVA) adjusted for age, gender, performance status (PS), T- and N-category, and treatment regimen. Results: A total of 1875 patients were included. Median age was 59.2 [31.3-86.8]; 79% (1481) were males; 96% (1651) had PS <2; 71% (1337) received concurrent chemo-radiotherapy (CRT) +/- hypoxic modification (Nimorazole); and 538 (29%) received RT alone +/- Nimorazole. 23% (425) were current smokers (at time of diagnosis) and 46% (853) were ex-smokers. Median smoking pack-years (PY) was 20.1 in the total cohort, and higher in current smokers vs ex-smokers (38 vs 20 PY, p<0.001). 63% of current smokers had >30 PYs. Median follow-up was 4.8 years. Actuarial 5-year univariate analysis showed that current smokers had a reduced probability of LRC (85% vs 92%, p=0.002), DC (88% vs 92%, p=0.046), DFS (69% vs 84%, p<0.001), and OS (73% vs 88%, p=<0.001) compared to never-smokers (n=567). Outcomes for ex-smokers and never-smokers were similar. In MVA current smoking retained strong independent significance for LRC (HR 1.73 [1.18-2.53]), DFS (1.79 [1.35-2.36]) and OS (2.06 [1.49-2.84]). However, DC was not significantly influenced by current smoking status (1.27 [0.83-1.95]). Similar observations were found for >30PY. Conclusions: Heavy lifetime and current smoking negatively impacts LRC and survival in HPV+ OPC. While smoking mediated hypoxia could interfere with RT efficacy, a putative impact on tumor biology remains uncertain in the absence of a detriment to distant metastasis risk. The findings support encouraging smoking cessation to improve therapeutic efficacy of RT and to avoid excess smoking related mortality.