Single Fraction and Multifraction Arc-Based Radiotherapy for Painful Bone Metastases

Single‐fraction radiotherapy (SFRT) is an established standard treatment for palliationof painful bone metastases. However, multifraction radiotherapy (MFRT) continues to bewidely used in clinical practice because of concerns regarding durability of pain controland retreatment. With the increasing use of modern arc‐based radiotherapy techniques suchas volumetric modulated arc therapy (VMAT), there is a need to evaluate whethersingle‐fraction radiotherapy can provide effective pain palliation while reducingtreatment burden and improving resource utilisation.The SMART trial is a prospective, single‐centre, randomised, open‐label, parallel‐grouppilot feasibility study comparing VMAT‐based SFRT (8 Gy in 1 fraction) with VMAT‐basedMFRT (20 Gy in 5 fractions) in patients with painful bone metastases, including spinalmetastases.Approximately 70 participants will be randomised in a 1:1 ratio to receive either SFRT orMFRT. Both treatment schedules will be delivered using VMAT with daily image‐guidedradiotherapy using cone‐beam computed tomography (CBCT)‐based image guidance.Stratified block randomisation will be used according to the site of metastasis (spineversus non‐spine) to maintain balance between the two treatment groups. Within eachstratum, computer‐generated variable block randomisation using block sizes of 4 and 6will be used. Allocation will be concealed using sequentially numbered, opaque, sealedenvelopes.Pain will be assessed using the Numeric Rating Scale (NRS‐11) and Wong‐Baker FACES PainScale at baseline and during follow‐up. Participants will be assessed at 2 weeks, 4 weeksand 12 weeks after radiotherapy.The primary aim of this pilot study is to assess the feasibility of conducting arandomised controlled trial at the participating tertiary oncology centre. Feasibilitywill include recruitment, treatment completion, follow‐up completion and completeness ofstudy data.The primary efficacy outcome will be overall pain response at 4 weeks followingradiotherapy. Secondary outcomes will include pain response at other follow‐up timepoints, retreatment rates, pain flare, treatment‐related toxicity, patient convenienceand resource utilisation.The study is not powered to provide a definitive non‐inferiority conclusion. Anon‐inferiority margin of 15% has been prespecified to guide estimation of the treatmenteffect and inform the design and sample size of a future definitive randomised trial. Theprimary efficacy analysis will compare overall pain response between the two treatmentgroups using the intention‐to‐treat population.The study will generate preliminary feasibility and clinical outcome data to inform thedesign of a future definitive randomised controlled trial evaluating single‐fractionversus multifraction radiotherapy for painful bone metastases.