Single-Fraction Stereotactic vs Conventional Multifraction Radiotherapy for Pain Relief in Patients With Predominantly Nonspine Bone Metastases: A Randomized Phase 2 Trial

Abstract

Importance: Consensus is lacking as to the optimal radiotherapy dose and fractionation schedule for treating bone metastases.

Objective: To assess the relative efficacy of high-dose, single-fraction stereotactic body radiotherapy (SBRT) vs standard multifraction radiotherapy (MFRT) for alleviation of pain in patients with mostly nonspine bone metastases.

Design, setting, and participants: This prospective, randomized, single-institution phase 2 noninferiority trial conducted at a tertiary cancer care center enrolled 160 patients with radiologically confirmed painful bone metastases from September 19, 2014, through June 19, 2018. Patients were randomly assigned in a 1:1 ratio to receive either single-fraction SBRT (12 Gy for ≥4-cm lesions or 16 Gy for <4-cm lesions) or MFRT to 30 Gy in 10 fractions.

Main outcomes and measures: The primary end point was pain response, defined by international consensus criteria as a combination of pain score and analgesic use (daily morphine-equivalent dose). Pain failure (ie, lack of response) was defined as worsening pain score (≥2 points on a 0-to-10 scale), an increase in morphine-equivalent opioid dose of 50% or more, reirradiation, or pathologic fracture. We hypothesized that SBRT was noninferior to MFRT.

Results: In this phase 2 noninferiority trial of 96 men and 64 women (mean [SD] age, 62.4 [10.4] years), 81 patients received SBRT and 79 received MFRT. Among evaluable patients who received treatment per protocol, the single-fraction group had more pain responders than the MFRT group (complete response + partial response) at 2 weeks (34 of 55 [62%] vs 19 of 52 [36%]) (P = .01), 3 months (31 of 43 [72%] vs 17 of 35 [49%]) (P = .03), and 9 months (17 of 22 [77%] vs 12 of 26 [46%]) (P = .03). No differences were found in treatment-related toxic effects or quality-of-life scores after SBRT vs MFRT; local control rates at 1 and 2 years were higher in patients receiving single-fraction SBRT.

Conclusions and relevance: Delivering high-dose, single-fraction SBRT seems to be an effective treatment option for patients with painful bone metastases. Among evaluable patients, SBRT had higher rates of pain response (complete response + partial response) than did MFRT and thus should be considered for patients expected to have relatively long survival.

Trial registration: ClinicalTrials.gov identifier: NCT02163226.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Welsh serves on the scientific advisory boards of RefleXion Medical, MolecularMatch, Mavupharma, OncoResponse, and Checkmate; is a founder of Healios Oncology, MolecularMatch, and OncoResponse; and has received research and clinical trial support from Bristol-Myers Squibb; and research support from Merck, Aileron, Nanobiotix, Mavupharma, and Checkmate. Dr Fuller reports grants and nonfinancial support from Elekta AB and grants from the National Institutes of Health during the conduct of the study.

Figures

Figure 1.. Flow Diagram of Patient Inclusions and Exclusions

Figure 2.. Local Progression-Free Survival According to Treatment

MFRT indicates standard-dose multifraction radiation therapy (10 fractions of 3 Gy each, for a total of 30 Gy); SBRT, high-dose, single-fraction stereotactic radiation therapy with a dose of 12 Gy or 16 Gy (solid line).

Figure 3.. Overall Quality-Adjusted Product-Limit Survival According to Treatment

The Q-TWiST method was used to analyze quality-adjusted overall survival time, that is, the proportion of patients alive without significant toxic effects (all MD Anderson Symptom Inventory [MDASI] scores