Sleep-related symptoms are associated with survival in oropharyngeal cancer radiotherapy survivors: Temporal characterization of patient-reported outcomes in a large-scale prospective longitudinal cohort.

PurposeSleep-related symptom prevalence is not well-characterized and likely under-recognized in head and neck cancer. We investigated longitudinal symptom severity trajectory, prevalence of moderate/severe symptoms, and association between severe sleep-related patient-reported symptoms and oncologic endpoints in oropharyngeal cancer (OPC) patients receiving radiotherapy (RT). MethodsA longitudinal cohort of 372 patients with OPC treated with curative-intent RT with/without chemotherapy at a single-site tertiary center was queried at RT start, end of RT, and six months post-RT. All completed baseline MD Anderson Symptom Inventory-Head and Neck (MDASI-HN) at start of RT. Sleep-related symptom items included "fatigue", "disturbed sleep", and "drowsiness" (mild, moderate, severe). Clinical data were collected, and overall survival (OS) was evaluated using Kaplan-Meier/log-rank tests and multivariable Cox proportional hazards models with covariate adjustment. ResultsSevere fatigue, disturbed sleep, and drowsiness were infrequent at baseline and at RT start, but peaked at RT end (26%, 15% and 18%) and returned to near-baseline prevalence by six months after RT (6%, 4%, 2%). In Cox proportional hazard models, severe longitudinal fatigue (HR 5.05, 95% CI 1.25-17.07, p = 0.013), sleep (HR 3.86, 95% CI 1.23 to 10.16, p = 0.0104), and drowsiness burden (HR 8.24, 95% CI 1.22 to 32.62, p = 0.008) were all independently associated with worse OS. Additionally, severe fatigue (HR = 3.58, 95% CI: 1.09 to 10.11, p = 0.0375), sleep disturbance (HR 5.08, 95% CI 1.60-13.51, p = 0.0081), and drowsiness (HR=7.76, 95% CI 1.45-33.47, p=0.0193) reported at RT start were also independently associated with significantly worse OS. Aside from age, severe average daily symptom scores, and severe symptoms reported at RT start, were independently associated with worse OS. ConclusionSevere sleep related symptoms were uncommon at baseline or RT start, but a substantial proportion of OPC patients experienced clinically meaningful sleep disturbances by the end of RT. At an average follow up of 84 months, severe longitudinal fatigue, sleep, and drowsiness burden were all independently associated with worse OS in OPC. Severe fatigue, drowsiness and sleep disturbance reported at RT start were also independently associated with worse OS. Assessment of sleep disturbances along with potential physiologic correlates are an important part of comprehensive care.