Predictors of Skeletal-Related Events and Quality-of-Life Dimensions Among Patients With High-Risk Asymptomatic Bone Metastases With or Without Early Radiation Therapy: Secondary Analysis of a Multicenter Randomized Phase II Clinical Trial.

BACKGROUND

Early radiation therapy (RT) reduces the rate of skeletal-related events (SRE), which can affect patients' functionality and quality of life (QoL). We aimed to determine predictors of SRE and the effect of early RT on individual QoL dimensions.

METHODS

We conducted a secondary analysis of a multicenter, randomized phase II trial (ClinicalTrials.gov identifier: NCT03523351) assessing early RT to asymptomatic, high-risk bone metastases. A competing risks analysis evaluated patient-level factors associated with SRE. Linear mixed models evaluated dimensions of the EuroQol 5-Dimension 5-Level (EQ-5D-5L) QoL assessment (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) over time by study arm.

RESULTS

Overall, 78 patients with 122 bone metastases were enrolled; 71 (91%) patients were evaluable for the primary endpoint of SRE (35 patients in the early RT arm vs 36 in the control arm). A total of 15 SREs occurred among 11 unique patients during the 1-year follow-up period. Receipt of early RT was statistically significantly correlated with a lower risk of SRE (hazard ratio, 0.09; 95% CI, 0.01-0.66; P=.018). In the linear mixed model predicting self-care, the interaction between time and study arm was statistically significant (P=.022). At 6 months, the control arm had a decline in self-care, whereas patients in the RT arm experienced an improvement. Anxiety/depression was worse at 3 months in the RT arm, but this was not statistically significant (P=.120).

CONCLUSIONS

Rates of SRE were high among patients with bone metastases, and these findings underscore the importance of early RT in their prevention. Patient-reported QoL suggests preservation of self-care with early RT, and that survival beyond 6 months may be needed to observe a benefit. Further research regarding patient selection and the impact of SRE on QoL and functionality are needed, and a phase III randomized trial (NRG CC014; NCT06745024) is in progress.

CLINICALTRIALS: gov identifier: NCT03523351.