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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

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

Importance: Patients 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. Objective: To 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 Participants: This 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. Exposures: Patient-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 Outcomes: Two-year overall survival. Results: The 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. Conclusions: In 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.

Evaluating the Feasibility of a Novel Firearm Injury Prevention Program for Pre-adolescent Children Through Health Care and Community-Based Partnerships: The Future Healers Program Pilot Study.

BACKGROUND: Firearm violence is an American public health crisis that negatively impacts children and disproportionately affects Black youth. Few firearm injury prevention programs have been described in pre-adolescent children. The Future Healers Program is a novel collaboration constructed via partnership between the medical school, trauma center, academic surgery department, and local non-profit community organization. Our study sought to evaluate if (1) partnering with community organizations facilitated recruitment of children with prior exposure to firearm violence and (2) the health care community was a potential trusted partner appropriate for program delivery. METHODS: Children aged 4-13 were recruited to join the program via news outlets and social media and in partnership with a local non-profit organization. Of the children and parents participating in the program, 48% (44/92) and 59% (38/64), respectively, completed an IRB-approved survey study. Pearson's chi-square, percentages, and 95% confidence intervals evaluated differences between children and caregivers on sociodemographic characteristics, firearm exposure (FE), firearm violence exposure (FVE), and perception of health care. Participant's residence was geocoded in relationship to incidents of firearm injury (2008-2021) in the same region. RESULTS: Caregivers (95%) and children (84%) reported substantial exposure to firearm violence and resided in areas with frequent firearm injury incidents. Notably, 82% of caregivers and 66% of children reported having a family member injured by gunfire. A high percentage of caregivers (79%) and children (91%) self-reported trust in the health care system. CONCLUSION: Partnerships between community organizations and health care systems can develop prevention programs that effectively recruit and engage pre-adolescent children impacted by firearm violence.