Active Tobacco Smoking and Distant Metastasis in Patients With Oropharyngeal Cancer

Abstract

Distant metastasis is the site of first relapse in approximately one-third of patients with locally advanced oropharyngeal carcinoma, irrespective of human papillomavirus status. Yet the risk factors associated with distant metastasis are not well characterized. We sought to characterize the relationship between smoking status and distant metastasis. We evaluated the association between tobacco smoking status and distant metastasis in a retrospective cohort study of 132 patients who underwent definitive radiation therapy and chemotherapy for Stage III-IVA/B oropharyngeal cancer. Information on tobacco smoking was prospectively collected by patient questionnaires and physician notes at the time of diagnosis. Thirty-three percent of the patients were nonsmokers, 51% were former smokers, 16% were active smokers. The cumulative lifetime tobacco smoking in pack-years was 20 (range, 0-150). With a median follow-up time of 52 months, the overall rate of distant metastasis at 4years was 8%. Distant metastasis was the most common first site of relapse, occurring in 56% of the patients with recurrences. Active smokers had higher rates of distant metastasis than non-active smokers (including never- and former smokers; 31% vs. 4%, p < 0.001) and former smokers (31% vs. 3%, p < 0.001). There was no statistically significant difference in the risk of distant metastasis for patients with lifetime cumulative pack-years >20 and ≤20 (10% vs. 4%, p= 0.19). In univariate analysis, active smoking (p = 0.0004) and N category (p=0.009) were predictive of increased risk of distant metastasis. In multivariate analysis, active smoking was the most significant predictive factor for increased risk of distant metastasis (hazard ratio, 12.7, p < 0.0001). This study identified a strong association between active smoking and distant metastasis in patients with oropharyngeal cancer.