Pain response after stereotactic body radiation therapy versus conventional radiotherapy in patients with bone metastases – a phase II, randomized controlled trial within a prospective cohort

Abstract Background Pain response after conventional external beam radiotherapy (cRT) in patients with painful bone metastases is observed in 60–70% of patients. The aim of the XXXXX trial was to investigate whether stereotactic body radiotherapy (SBRT) improves pain response. Methods This single center, phase 2, randomized controlled trial was conducted within the XXXXX cohort, which consists of patients referred for radiotherapy of bone metastases to our tertiary center. Cohort participants with painful bone metastases who gave broad informed consent for randomization, were randomly assigned to cRT or SBRT. Only patients in the intervention arm received information about the trial, and were offered SBRT (1x18 Gy, 3x10 Gy or 5x7 Gy) which they could accept or refuse. Refusing patients underwent standard cRT (1x8 Gy, 5x4 Gy or 10x3 Gy). Patients in the control arm were not informed. Primary endpoint was pain response at 3 months after radiotherapy. Secondary outcomes were pain response at any point within 3 months, mean pain scores, and toxicity. Data was analyzed intention to treat (ITT) and per protocol (PP). This trial was registered with Clinicaltrials.gov , XXXX Findings Between Jan 29, 2015, and March 20, 2019, 110 patients were randomized. Intention to treat analysis included 44 patients in the cRT arm and 45 patients in the SBRT arm. In the intervention arm, 12 patients (27%) declined SBRT and 7 patients (16%) were unable to complete the SBRT treatment. In ITT, 14/44 patients (32%, 95% CI 18–45%) in the control arm, and 18/45 patients (40%, 95%CI 26–54%) in the SBRT arm reported a pain response at 3 months (p=0.42). In PP, these proportions were 14/44 (32%, 95%CI 18–45%) and 12/23 (46%, 95%CI 27–66%) respectively (p=0.55). In ITT, a pain response within 3 months was reported by 30/44 control patients (82%, 95% CI 68%-90%), and 38/45 patients (84%, 95% CI 71%-92%) in the SBRT arm. (p=0.12). In PP, these proportions were 36/44 (82%, 95% CI 68%-90%) and 26/27 (96%, 95% CI 81%-100%) respectively, p=0.12. No grade 3 or 4 toxicity was observed in either arm. Interpretation SBRT did not significantly improve pain response in patients with painful bone metastases. One in four patients preferred to undergo cRT over SBRT and one in five patients starting SBRT was unable to complete this treatment. Due to this selective drop-out, which can be attributed to the character of the intervention, the trial was underpowered to detect the prespecified difference in pain response