Symptom and Quality-Of-Life Trajectories After High-Intensity Focused Ultrasound in Patients with Advanced Cancer: Exploratory Associations with Overall Survival in a Prospective Pilot Study

Background: Patients with advanced cancer frequently experience substantial symptom burden and impaired quality of life (QoL). This study aimed to characterize longitudinal trajectories of patient-reported symptoms and QoL after high-intensity focused ultrasound (HIFU) and to explore their associations with subsequent overall survival (OS). Methods: This exploratory prospective longitudinal pilot cohort study enrolled 54 patients with malignant solid tumors who underwent HIFU. Patient-reported symptoms and QoL were assessed using a study-specific 14-item symptom checklist and the EORTC QLQ-C30 at five post-HIFU time points: day 1 (D1), week 1, month 1 (M1), month 2, and month 3. Longitudinal outcomes were summarized descriptively. Exploratory associations with OS were examined using Kaplan-Meier analyses and univariable Cox proportional hazards models. Results: At D1, the most prevalent symptoms were sleep disturbance (55.56%), back pain (44.44%), dry mouth (35.19%), hiccup (29.63%), and dysphoria (25.93%). The mean severity scores of the five most severe symptoms at D1 reached their lowest observed values at M1, while QoL reached its highest observed mean score at M1 (77.41). Median OS was 298 days (95% CI, 209 days to not reached). In exploratory univariable Cox analyses, back pain at D1 (HR = 2.25, 95% CI 1.13– 4.47; p = 0.021) and hiccup at D1 (HR = 2.12, 95% CI 1.06– 4.24; p = 0.034) were associated with a higher hazard of death. Each 10-point increase in global health status/QoL at D1 was associated with a lower hazard of death (HR = 0.81, 95% CI 0.68– 0.98; p = 0.024). Conclusion: In this exploratory pilot cohort, several patient-reported symptoms and QoL measures showed their most favorable observed values at approximately one month after HIFU. Back pain, hiccup, and QoL showed exploratory associations with OS. These preliminary findings may inform post-HIFU symptom and QoL assessment and warrant validation in larger prospective studies. Keywords: high-intensity focused ultrasound, advanced cancer, overall survival, symptom burden, quality of life, pilot study