Associations of Biological Aging with Perceived Stress in Patients with Head and Neck Cancer Undergoing Intensity-Modulated Radiotherapy: A Longitudinal Study

Abstract

Purpose: Accelerated biological aging increases morbidity and mortality in patients with head and neck cancer (HNC) undergoing intensity modulated radiation therapy (IMRT). Stress from HNC and IMRT may exacerbate this process, yet the link between biological aging and perceived stress during treatment remains unclear. The purpose of this study was to examine associations between biological aging and perceived stress in HNC patients receiving IMRT across 4 time points: pre-IMRT, the end of IMRT, and 3 and 12 months post-IMRT. Methods and materials: This prospective longitudinal study assessed perceived stress using the Perceived Stress Scale and various biological aging markers, including epigenetic age acceleration, Pace of Aging Calculated from the Epigenome (DunedinPACE), Klemera-Doubal biological age, phenotypic age (PhenoAge), homeostatic dysregulation, and inflammatory markers (interleukin [IL]-6, IL-1β, IL-10, IL-1ra, C-reactive protein, soluble tumor necrosis factor receptor (TNF) 2, and TNF-α). Linear mixed-effects models examined associations between each biological aging marker and perceived stress over time. Results: Among 146 HNC patients (mean age ± SD, 59.12 ± 10.05 years; 73% male; 81% non-Hispanic White), perceived stress increased during treatment, declined significantly posttreatment, and remained lower than the baseline level. Higher perceived stress was significantly associated with increased DunedinPACE (estimate = 10.82; 95% CI, 4.49, 17.15; p = .001), Klemera-Doubal biological age (estimate = 0.03; 95% CI, 0.01, 0.05; p = .003), PhenoAge (estimate = 0.25; 95% CI, 0.06, 0.44; p = .011), C-reactive protein (estimate = 1.42; 95% CI, 0.35, 2.48; p = .009), TNF-α (estimate = -3.92; 95% CI, -7.53, -0.31; p = .033), and IL-1ra (estimate = 4.89, 95% CI, 2.24, 7.54; p < .001) over time, after adjusting for covariates (eg, age, sex, race, marital status, income, tumor human papillomavirus status, and treatment). Conclusions: The strong association between biological aging and perceived stress suggests a critical role for stress in accelerating aging among patients with HNC. Future research should aim to investigate stress-inflammation management to decelerate aging and improve survival in these vulnerable cancer populations.