Background: Current treatment guidelines for head and neck squamous cell carcinoma (HNSCC) recommend that patients initiate postoperative radiation therapy (PORT) within six weeks of surgery and complete radiation therapy (RT) within seven weeks of initiation. Treatment adherence, measured by time-to-PORT initiation and RT completion time, is associated with improved survival rates in patients with HNSCC. Although patients with HNSCC experience higher rates of depression compared to those with other cancers, the effects of depression and anxiety on RT adherence have not been investigated.
Objective: To evaluate the relationship between symptoms of depression and anxiety with radiation therapy adherence as measured by time-to-PORT initiation and RT completion time.
Methods: This retrospective cohort study consisted of 314 HNSCC patients who had pre-RT PHQ-8 (depression) and GAD-7 (anxiety) evaluations and were treated with definitive or adjuvant RT at UPMC between 2016 and 2023. Outcome variables were adherent time-to-PORT initiation and adherent radiation completion time. Chi-squared testing was used to examine differences in treatment adherence across exposure variables of interest, including PHQ-8 scores, GAD-7 scores, and census block group Area Deprivation Index (ADI). Additional covariates of interest include age, sex, and cancer site and stage. For PHQ-8 and GAD-7 total scores, both the established clinical cutoffs and a study-specific threshold >10 were used to define high depression and anxiety severity, respectively. The impacts of depression and anxiety on treatment adherence were analyzed using mutually adjusted logistic regression.
Results: Of all 314 patients who received RT, 136 (43.3%) were adherent to treatment. Of the 183 patients who underwent surgery and had PORT, 63 (34.4%) were adherent to treatment. GAD-7 scores were not associated with time-to-PORT initiation or RT completion time, although non-adherent patients exhibited higher rates of clinically moderate/severe anxiety (18.6% versus 11.8%). Patients with high pre-RT depression scores (PHQ-8 >10) were less likely to adhere to RT completion guidelines (p=0.014) and had lower odds of adherent RT completion compared to those with scores <10 (odds ratio [OR]: 2.6, 95% confidence interval (CI): 1.1-6.5). A similar association was seen in patients with clinically moderately severe/severe depression, who had lower odds of adherence compared to those with minimal depression (OR: 0.19, 95% CI:0.03-0.74). Patients living in more deprived neighborhoods also had lower odds of adhering to time-to-PORT initiation (OR for each increasing quartile of ADI: 0.74, 95% CI: 0.58-0.94) and RT completion guidelines (OR for each increasing quartile of ADI: 0.83, 95% CI: 0.67-1.03).
Conclusions: High levels of depression are significantly associated with longer and non-adherent RT completion times in patients with HNSCC. Patients struggling with depression may experience a range of symptoms—including fatigue, lack of motivation, and difficulty concentrating—that may impede their capacity to follow medical advice and maintain the rigorous schedules often required during radiation therapy. Addressing mental health throughout cancer treatment could enhance treatment adherence, potentially reducing RT completion times and improving clinical outcomes. Therefore, there is an urgent need for interdisciplinary approaches that involve oncologists, mental health professionals, and support services to ensure the holistic needs of patients are met.