Pain Response Rates after Conventional Radiation Therapy for Bone Metastases Assessed Using International Consensus Pain Response Endpoints: A Systematic Review and Meta-Analysis of Initial Radiation Therapy and Re-Irradiation

Abstract

<h3>Purpose/Objective(s)</h3> Previous systematic reviews of conventional radiation therapy (RT) for painful bone metastases showed response rates of 72%<b>–</b>75% for initial RT and 68% for re-irradiation. However, the definition of pain response differed among studies included in these reviews. The International Consensus Pain Response Endpoints (ICPRE) was published in 2002 and revised in 2012 to unify evaluation methods for pain response internationally and has been used in many studies. We conducted a systematic review and meta-analysis to determine the pain response rates assessed by ICPRE for both initial RT and re-irradiation. <h3>Materials/Methods</h3> A literature search was conducted in PubMed and Scopus for articles published between 2002 and 2021. The inclusion criteria were as follows: (i) the study designs of randomized controlled trials (RCTs), prospective studies, or studies based on prospectively collected data; and (ii) studies in which pain response was assessed using ICPRE. Our primary outcomes of interest were overall response (OR) rates (sum of complete response rate and partial response rate) for both initial RT and re-irradiation. The following subgroup analyses were performed for OR rates of initial RT: RCT vs. non-randomized studies, with vs. without exclusion criteria for complicated bone metastases, with vs. without eligibility criteria for no change in analgesic use at enrollment, and timing of response assessment (≤1 month vs. >1 month). Random effects logistic models were used to estimate pooled response rates. <h3>Results</h3> Of the 6470 articles identified in our database search, 32 and 3 met the inclusion criteria for analysis of initial RT and re-irradiation, respectively. The OR rates of initial RT in evaluable patients (n = 4775) and intent-to-treat patients (n = 6775) were 60.4% (95% confidence interval [CI], 55.2–65.4) and 45.4% (95% CI, 38.7–52.4), respectively. The OR rates of re-irradiation in evaluable patients (n = 733) and intent-to-treat patients (n = 1085) were 70.8% (95% CI, 15.7–96.9) and 62.2% (95% CI, 5.3–98.0), respectively. Subgroup analyses of initial RT showed no significant differences in any of the comparisons, indicating similar response rates across different study designs. <h3>Conclusion</h3> We determined the pain response rates of initial RT for painful bone metastases assessed by ICPRE. The OR rate assessed by ICPRE was lower than previously reported. The present review may provide benchmarks for future RCTs and non-randomized studies. Regarding the response rate for re-irradiation, the wide range of the 95% CI warrants that the OR rate based on ICPRE requires further investigation.