Depressive Symptoms, Systemic Inflammation, and Survival Among Patients With Head and Neck Cancer

Abstract

ImportancePatients with head and neck cancer experience high rates of depression. Depression and systemic inflammation have been found to be associated in numerous cancer types, often independently from disease status. Depression-related inflammation may elevate the risks for poor tumor response to treatment and early mortality, and comprises a mechanism by which depression is associated with survival in head and neck cancer.ObjectiveTo assess mediation pathways incorporating pretreatment depressive symptoms, pretreatment inflammation, and tumor response posttreatment on overall survival among patients with head and neck cancer.Design, Setting, and ParticipantsThis was a prospective observational cohort study of patients with head and neck cancer treated in a single multidisciplinary head and neck cancer clinic from May 10, 2013, to December 30, 2019, and followed up for 2 years. Data analysis was performed from June 29, 2022, to June 23, 2023.ExposuresPatient-reported depressive symptoms using the Patient Health Questionnaire−9 item (PHQ−9) at treatment planning; pretreatment hematology workup for systemic inflammation index (SII) score; and clinical data review for tumor response (complete vs incomplete) and overall survival.Main OutcomesTwo-year overall survival.ResultsThe total study cohort included 394 patients (mean [SD] age, 62.5 [11.5] years; 277 [70.3%] males) with head and neck cancer. Among 285 patients (72.3%) who scored below the clinical cutoff for depression on the PHQ−9, depressive symptoms were significantly associated with inflammation (partial r, 0.168; 95% CI, 0.007-0.038). In addition, both depression and inflammation were associated with early mortality (PHQ−9: hazard ratio [HR], 1.04; 95% CI, 1.02-1.07; SII: HR, 1.36; 95% CI, 1.08-1.71). The depression-survival association was fully mediated by inflammation (HR, 1.28; 95% CI, 1.00-1.64). Depressive symptoms were also associated with poorer tumor response (odds ratio, 1.05; 95% CI, 1.01-1.08), and the depression-survival association was partially mediated by tumor response (HR, 9.44; 95% CI, 6.23-14.32). Systemic inflammation was not associated with tumor response.ConclusionsIn this cohort study, systemic inflammation emerged as a novel candidate mechanism of the association of depression with mortality. Tumor response partially mediated effects of depression on mortality, replicating prior work. Thus, depression stands out as a highly feasible target for renewed clinical attention. Even mild symptoms of depression during the treatment-planning phase may be associated with higher systemic inflammation in addition to poorer tumor response to treatment and survival outcomes; therefore, depression should be clinically addressed.

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

“…These novel data suggest that pretreatment anxiety may be related to biological processes that impact prognosis in patients with HNC. Together with our other recent studies linking psychological symptoms in the diagnostic and pretreatment phases of HNC, [13][14][15] these results underscore the importance of early screening and intervention for mental health symptoms to help improve clinically meaningful outcomes for HNC patients.…”

“…Pretreatment anxiety was not significantly associated with systemic inflammation (SII; partial r = 0.070, p = 0.238); therefore, a survival model entering anxiety, inflammation and their interaction was not conducted. We have previously reported the significant relationship between tumor response and subsequent 2-year overall survival in this same sample of patients, and showed that the prerequisites for tests of mediation are met 15 ; reported in Table 2. Upon running the test of mediation, we observed that the relationship between pretreatment anxiety and 2-year overall survival was significantly and fully mediated by tumor response (Table 2; Figure 2).…”

“…In previous work with this same sample of patients, we observed a relationship between depression and SII. 15 The findings of the current study may have differed because of distinct mechanisms underlying the biological effects of anxiety and depression. For example, depressive symptoms have been found to predict steeper cortisol response and recovery curves following exposure to the Trier Social Stress Test (TSST), while anxiety symptoms were more strongly associated with a blunted cortisol curve.…”

“…We previously showed that pre-treatment depression is significantly associated with tumor response and overall survival among HNC patients. [13][14][15] The present study aimed to assess pre-treatment anxiety and systemic inflammation, tumor response 6-month post treatment, and 2-year overall survival. We hypothesized that higher pretreatment anxiety levels would predict poorer overall 2-year survival.…”