Bias due to statistical handling of death and reirradiation in the assessment of duration of response after palliative radiotherapy: a scoping review and analysis of clinical data.

OBJECTIVES: We investigated the influence of handling death and reirradiation on the estimation of duration of response (DOR). METHODS: First, we performed a scoping review on methods to assess DOR in palliative radiotherapy. Second, we performed three different analyses on a subgroup of patients from a previously published prospective study. The first analysis was a competing risks analysis considering relapse of pain as the event of interest and death and reirradiation as competing events (Analysis A). The second and third analyses were standard survival analyses where the event of interest was a composite outcome of relapse of pain, death, or reirradiation (Analysis B) and relapse of pain (Analysis C), respectively. RESULTS: Death was considered as an event of interest in less than half of the papers, while reirradiation was not considered in any of the studies. Competing risks analysis was not performed in any of the studies. In the analysis of clinical data, competing risks analysis showed that relapse of pain predominated as the cause of the end of response. Median DOR was correctly estimated to be 4.1 months in Analyses A and B, but was overestimated to be 8.1 months in Analysis C. CONCLUSIONS: Death and reirradiation should be treated as the events of interest that mark the end of response (as in Analyses A and B) to avoid overestimation of treatment efficacy and an invalid assumption of independent censoring. ADVANCES IN KNOWLEDGE: The definition of end of response remains inconclusive in the assessment of DOR. We recommend competing risks analysis (Analysis A), by which we can estimate cumulative incidence of each event type and evaluate the necessity of reirradiation.