Anxiety symptoms predict head and neck cancer survival: Exploring mediation by systemic inflammation and tumor response to treatment.

Abstract

Head and neck cancers (HNC) are associated with high rates of anxiety. Anxiety has been linked to biological pathways implicated in cancer progression, though little is known about its effects on overall survival. We hypothesized that higher pretreatment anxiety levels in patients with HNC would predict poorer 2-year overall survival and expected this relationship to be mediated by both systemic inflammation and tumor response to treatment. Patients (N=394) reported anxiety symptomatology via the GAD-7 at treatment planning. Pre-treatment hematology workup provided an index of systemic inflammation (SII; N=292). Clinical data review yielded tumor response and overall survival. Logistic and multiple regressions and Cox proportional hazard models tested hypothesized relationships. Higher pretreatment anxiety levels were significantly associated with poorer 2-year survival (hazard ratio [HR], 1.039; 95% confidence interval [CI], 1.014-1.066, p=0.002). The association between anxiety and SII was not significant, though anxiety was associated with poorer tumor response (odds ratio [OR], 1.033; 95% CI, 1.001-1.066, p=0.043). Tumor response fully mediated the relationship between anxiety symptoms and 2-year survival (HR, 9.290, 95% CI, 6.152-14.031, p<0.001). Anxiety was associated with overall survival. Tumor response, but not systemic inflammation, emerged as a potential biological pathway mediating this effect. Screening for anxiety may be beneficial to help prospectively address these concerns and ameliorate potentially detrimental impact on clinically meaningful cancer outcomes.