Palliation of metastatic bone pain: single fraction versus multifraction radiotherapy - a systematic review of the randomised trials.

BACKGROUND Recent randomised studies reported that single fraction radiotherapy was as effective as multifraction radiotherapy in relieving pain due to bone metastasis. However, there are concerns about the higher re-treatment rates and the efficacy of preventing future complications such as pathological fracture and spinal cord compression by single fraction radiotherapy. OBJECTIVES To undertake a systematic review and meta-analysis of single fraction radiotherapy versus multifraction radiotherapy for metastatic bone pain relief and prevention of bone complications. SEARCH STRATEGY Trials were identified through MEDLINE, EMBASE, Cancerlit, reference lists of relevant articles and conference proceedings. Relevant data was extracted. SELECTION CRITERIA Randomised studies comparing single fraction radiotherapy with multifraction radiotherapy on metastatic bone pain DATA COLLECTION AND ANALYSIS The analyses were performed using intention-to-treat principle. The results were pooled using meta-analysis to estimate the effect of treatment on pain response, re-treatment rate, pathological fracture rate and spinal cord compression rate. MAIN RESULTS Eleven trials that involved 3435 patients were identified. Of 3435 patients, 52 patients were randomised more than once for different painful bone metastasis sites. Altogether, 3487 painful sites were randomised. The trials included patients with painful bone metastases of any primary sites, but were mainly prostate, breast and lung. The overall pain response rates for single fraction radiotherapy and multifraction radiotherapy were 60% (1059/1779) and 59% (1038/1769) respectively, giving an odds ratio of 1.03 (95% confidence interval [CI], 0.89 - 1.19) indicating no difference between the two radiotherapy schedules. There was also no difference in complete pain response rates for single fraction radiotherapy (34% [497/1441]) and multifraction radiotherapy (32% [463/1435]) with an odds ratio of 1.11 (95%CI 0.94-1.30). Patients treated by single fraction radiotherapy had a higher re-treatment rate with 21.5% (267/1240) requiring re-treatment compared to 7.4% (91/1236) of patients in the multifraction radiotherapy arm (odds ratio 3.44 [95%CI 2.67-4.43]). The pathological fracture rate was also higher in single fraction radiotherapy arm patients. Three percent (37/1240) of patients treated by single fraction radiotherapy developed pathological fracture compared to 1.6% (20/1236) for those treated by multifraction radiotherapy (odds ratio 1.82 [95%CI 1.06-3.11]). The spinal cord compression rates were similar for both arms (odds ratio 1.41 [95%CI 0.72-2.75]). Repeated analyses excluding dropout patients gave similar results. REVIEWERS' CONCLUSIONS Single fraction radiotherapy was as effective as multifraction radiotherapy in relieving metastatic bone pain. However, the re-treatment rate and pathological fracture rates were higher after single fraction radiotherapy. Studies with quality of life and health economic end points are warranted to find out the optimal treatment option.