When should we define the response rates in the treatment of bone metastases by palliative radiotherapy?

Aims: It is well established that palliative radiotherapy provides effective pain relief for symptomatic bone metastases, but controversy remains regarding the optimal dose fractionation. Several meta-analyses and systematic reviews of trials comparing the efficacy of single vs multiple fractionated radiotherapy schedules noted that it is difficult to reach a consensus when inconsistent response end point definitions are used. The purpose of this study was to determine when the most appropriate time to evaluate a response is. Materials and methods: Patients with symptomatic bone metastases treated with palliative radiotherapy between May 2003 and June 2005 were enrolled in the study. They were assessed with the Brief Pain Inventory at baseline, 1, 2 and 3 months after radiotherapy. Analgesic consumption during the preceding 24 h was recorded and converted into an equivalent total daily dose of oral morphine. The response to radiotherapy was assessed using the International Bone Metastases Consensus end point definitions at 1, 2 and 3 months of follow-up. Results: One hundred and ninety-nine patients were treated with palliative radiotherapy. All pain scores and functional interference items improved after radiotherapy. The proportion of evaluable patients with a complete response or a partial response increased between 1 month (58%) and 3 months of follow-up (67%). However, when considering intention-to-treatpercentages, which take attrition into consideration, overall response rates dropped from 35% at 1 month, to 32% at 2 months, and finally 24% at 3 months. Conclusion: We conclude that 2 months after radiotherapy is the most appropriate time point to measure response rates for two reasons: (i) the maximum pain relief for some patients may take more than 4 weeks to achieve and (ii) attrition poses a major problem when response rates are measured at a later date. Future trials should use standardised criteria for end points to facilitate comparison and analysis across clinical trials. Given the limitations of this study, however, further investigations are needed to confirm the response time points for palliative cancer patients.