Study protocol: Feasibility and safety of conventional external-beam radiotherapy with an integrated stereotactic lite gross-tumour-volume boost for painful bone metastases: The HYBRID study.

Abstract

Background: Bone metastases cause significant pain and functional limitation. Conventional external beam radiotherapy (EBRT) provides effective symptom relief, but local progression remains frequent. Stereotactic body radiotherapy (SBRT) offers improved local control but is often resource-intensive and associated with higher vertebral compression fracture (VCF) rates. Integrating a simultaneous gross tumour volume (GTV) boost within a conventional EBRT regimen may provide a feasible and safe alternative. Methods: This is a prospective, multicentre, multinational, single-arm study enrolling 100 adults with painful bone metastases from solid tumours. Eligible patients receive 20 Gy in 5 fractions with a 5 Gy “stereotactic-lite” GTV boost (total 25 Gy) or 30 Gy in 10 fractions with a 6 Gy boost (total 36 Gy), delivered using intensity modulated radiotherapy or volumetric modulated arc therapy. The primary endpoints are feasibility (commencement of radiotherapy within 10 working days of computed tomography simulation in at least 80% of patients) and safety (incidence of Common Terminology Criteria for Adverse Events version 5.0 grade ≥ 2 acute toxicity within 3 months). Secondary endpoints include pain response, radiation site-specific progression-free survival, rates of VCF and long bone fracture, skeletal-related events, quality of life changes via EORTC QLQ-C30 and BM22, and overall survival. Discussion: This protocol evaluates a hybrid EBRT approach with a simultaneous integrated boost as a practical strategy to enhance local tumour control and symptom relief without delaying palliation. If feasible and safe, this approach may bridge the gap between conventional EBRT and SBRT. Trial registration: Australian and New Zealand Clinical Trial Registry (ACTRN12625000615482).