Systemic Inflammation Mediates the Prognostic Effect of Depressive Symptoms on Head and Neck Cancer Survival

BACKGROUND: Head and neck cancer patients suffer high rates of depression. Depression and systemic inflammation have been linked in numerous cancer types, often independently from disease status. Depression-related inflammation could elevate risks for poor treatment response and early mortality and comprise a mechanism by which depression predicts cancer survival. We tested mediation pathways incorporating pre-treatment depressive symptoms, pre-treatment inflammation, tumor response post-treatment, and survival.<br><br>METHODS: Patients (N=401) reported depressive symptoms at treatment planning (PHQ9). Pre-treatment hematology workup provided an index of systemic inflammation (SII; N=295). Clinical data review yielded treatment response and overall survival. Logistic and multiple regressions and Cox proportional hazard models tested hypothesized relationships. RESULTS: Depressive symptoms were significantly associated with inflammation (p=.005) and both depression and inflammation predicted early mortality (PHQ9: p=.002; SII: p=.008). The depression‐survival relationship was fully mediated by inflammation (p=.035). Depressive symptoms also predicted poor treatment response (p=.108), and the depression-survival relationship was partially mediated by treatment response (p&lt;.001). While systemic inflammation did predict significantly poorer treatment response (p=.049), survival was not mediated through this pathway.<br><br>CONCLUSIONS: Depression, inflammation and treatment response were all associated with survival. While systemic inflammation was revealed to be a strong candidate mechanism of the effects of depression on mortality, pharmacologic treatment inflammation may promote the tumor. Efforts to refine and improve curative head and neck cancer treatments are already underway. As such, only depression stands out as a highly feasible target for renewed clinical attention. Even mild symptoms of depression during the treatment planning phase may contribute to poor outcomes and should be clinically addressed.<br>