Objectives: To compare and contrast the definitions of primary treatment endpoints in randomized studies of dose-fractionation schedules for treating bone metastases and to identify basic characteristics of treatment endpoint that may require consensus among investigators.
Methods: Randomized controlled trials (RCTs) of various dose-fractionation schedules for painful bone metastases, published between 1980 and 1999, and on-going trials whose protocols were available, were systematically reviewed based on the following features of the primary treatment endpoint: (i) degree of pain relief; (ii) timing of the pain response assessment; (iii) effect of co-interventions on pain relief; (iv) the reduction of analgesic as a treatment response; and (v) quantification of response duration.
Results: Ten published RCTs (each sampled over 100 patients), plus two current trial protocols were reviewed. Five of the 12 studies defined any reduction in pain score as the primary endpoint. Three trials defined response at pre-determined time points, whereas eight studies attributed pain improvement at any time during follow-up to the effect of radiotherapy. No trial incorporated effect of systemic treatments on response. Only two trials incorporated analgesic scores into the primary endpoint criteria, although several trials reported results of combined pain and analgesic relief. Eight trials reported duration of response. Three provided some estimation of duration with respect to survival: two of them employing actuarial time to pain progression, and one calculated the ratio of pain response to median survival duration (percent net relief). Quality of life was measured in four of 12 studies, as secondary endpoint.
Conclusion: Although available data suggest similarity in pain relief among various dose-fractionation schedules, accurate and consistent description of the degree of benefit from radiotherapy is lacking. While pain relief is a consistent primary treatment goal among randomized trials, a consensus on several important features of treatment endpoint is needed in order to establish common grounds for future trials in palliative radiotherapy.