Heterogeneity of study endpoints in stereotactic body radiation therapy studies for bone metastases: A systematic review
Shing Fung Lee, Henry Cy Wong, Eva Oldenburger, Srinivas Raman, Gustavo N Marta, Adrian W Chan, Dirk Rades, Yvette M Van Der Linden, Joanne M Van Der Velden, Quynh-Nhu Nguyen, J Isabelle Choi, Caroline Hircock, Chiara Doccioli, Claudia Cosma, Saverio Caini, Agata Rembielak, Vassilios Vassiliou, Pierluigi Bonomo, Peter As Johnstone, Sara Alcorn, Candice Johnstone, Charles B Simone Ii, Peter J Hoskin, Edward Chow and Samuel Ryu
Purpose: This systematic review evaluated variability in study endpoints among stereotactic body radiation therapy (SBRT) studies for bone metastases. Heterogeneity in endpoint definitions and reporting may hinder cross-study comparability and the establishment of consistent treatment protocols.
Methods: A comprehensive search of Ovid MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials identified prospective studies, including cohort studies, phase I/II trials, and randomised controlled trials (RCTs), published between 2014-01-01 and 2024-11-12. Studies were eligible if they: (1) included adult patients with bone metastases treated with SBRT, (2) were prospective, and (3) reported pre-defined clinical endpoints.
Results: A total of 58 studies were included: eight cohort studies, 37 phase I/II trials, and 13 RCTs. Pain-related endpoints were the most frequently reported primary endpoints, with pain response reported in 28% (16 studies). Other primary endpoints included toxicities (22%, 13 studies), survival metrics (12%, seven studies), and local control (9%, five studies). Secondary endpoints varied, with survival-related endpoints reported in 60% (35 studies) and toxicity in 41% (24 studies). Endpoint selection differed by clinical scenario, reflecting distinct objectives such as symptom relief, local control, and progression-free survival. Variability in definitions for endpoints, particularly pain flare and vertebral compression fracture, along with inconsistent radiological response criteria, was noted.
Conclusion: Considerable heterogeneity in endpoint selection, definitions, and measurement tools across SBRT reflects diverse clinical objectives. Consensus-driven standardisation of endpoints, response criteria, and follow-up schedules is essential to enhance comparability, facilitate evidence synthesis, and support integration of SBRT research findings into clinical practice.
Keywords: stereotactic body radiation therapy, prospective trials, bone metastases, primary endpoints, oligometastatic disease
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