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Objective/Hypothesis To estimate the prevalence of baseline clinically significant distress (distress score ≥ 4) in head and neck cancer patients planned and treated with radical intent radiotherapy using the National Comprehensive Cancer Network Distress Thermometer (DT) and assess factors predictive of distress. Study Design Cross‐sectional study. Methods This was a cross‐sectional study evaluating distress in 600 head and neck cancer patients undergoing radiation therapy. The DT was used to screen patients for distress at baseline before radiotherapy. Results The median distress score of the entire cohort was 4 interquartile range (IQR) (IQR: 3–5), and 340 patients (56.7%) had clinically significant distress. On univariate analysis, the causal factors predictive of distress were low socioeconomic status (P = .04), presence of proliferative growth at presentation (P = .008), site of the tumor (oral cavity, P = .02), comorbidity (P = .04), and presence of Ryle's tube or tracheostomy tube at baseline (P = .01). Low socioeconomic status was significant (P = .04) on multivariate analysis for high levels of distress. Conclusions Among head and neck cancer patients, 56% of patients had clinically significant baseline distress, and patients with low socioeconomic status had high distress. There is a need for interventions to mitigate distress. Level of Evidence 4 Laryngoscope, 131:2023–2029, 2021

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