Bone is a common metastatic site of advanced cancer. Durable pain control is a major goal of palliative care and important for maintaining quality of life cancer patients. Radiotherapy is the primary method for palliation of painful bone metastases, but there is no consensus regarding optimal dose and fractionation. Although no differences in pain relief rates were found between single- and multiple-fraction radiation in two meta-analyses, physicians remain reluctant to use single-fraction therapy. To assess the efficacy of different radiation modalities in relieving pain associated with bone metastases, a prospective, randomized, phase II noninferiority study, compared single-fraction stereotactic body radiotherapy (SBRT) to standard multifraction radiotherapy (MFRT) in 160 patients with painful, mostly nonspine, bone metastases.
Patients received either single-fraction SBRT (12 Gray [Gy] for lesions >4 cm or 16 Gy for lesions ≤4 cm) or standard MFRT (30 Gy given in 10 3Gy fractions). Patients in the per-protocol population who received SBRT were more likely to experience a pain response than those who received MFRT. At 2 weeks, 62% of patients in the SBRT group experienced a pain response, compared to 36% in the MFRT group (P = .01). Similar results were seen at 3 months (72% vs 49%; P = .03) and 9 months (77% vs 46%; P = .03). Among patients receiving SBRT, pain responses at 3 months were higher for those receiving 16-Gy compared to 12 Gy (62% vs 30%). Responses were most durable for patients receiving 16 Gy SBRT. At 9 months, the pain response rates were 42.9% for patients receiving 16 Gy SBRT, compared to 13.3% and 15.2% for 12 Gy SBRT and MFRT, respectively.
Patients receiving SBRT had improvements in local progression-free survival (PFS) compared to those receiving MFRT. At 1 year, the rates of local PFS were 100% and 90.5% in the two groups. Similarly, 2-year rates of local PFS were 100% with SBRT and 75.6% with MFRT (P = .01). Patients in the SBRT group were less likely to require reirradiation at 1 year (0% vs 3.3%) and 2 years (0% vs 5.3%), though this was not statistically significant. There were no differences in overall survival (OS) between the two treatment groups. However, when survival analysis was performed using the Q-TWIST (Quality adjusted Time Without Symptoms and Toxicity) method, an improvement in Q-TWIST survival was observed for patients receiving SBRT compared to those receiving MFRT.
There were no major differences in treatment-related adverse events (AEs) between the two treatment groups. The most common treatment-related AEs were grade 2/3 nausea, vomiting, and fatigue. Both treatments resulted in similar improvements in quality-of-life symptom scores.
The investigators concluded that high-dose, single-fraction SBRT was noninferior to conventionally fractioned radiotherapy in terms of pain control and local disease control and should be considered as standard of care for patients with good performance status, longer life expectancy, and limited bone metastases. Furthermore, they recommended a larger phase III study to test higher single-fraction SBRT doses.