Radiotherapy for bone metastases of hepatocellular carcinoma: a hybrid systematic review with meta-analyses

Introduction: External beam radiation therapy (EBRT) is commonly used as a palliative treatment for bone metastases of hepatocellular carcinoma (HCC). We planned a hybrid systematic review that meta-analyzed the efficacy and feasibility of EBRT and reviewed the literature to answer specific clinical questions. Methods: The PubMed, Medline, Embase, and Cochrane Library databases were searched through 1 December 2021. Primary endpoints were overall survival (OS) and response rate (RR). Secondary endpoints were comparative data, including treatment response and survival related to dose escalation, number of metastases, and fractionation scheme. Formal pooled analyses were performed on the primary endpoints, and the secondary endpoints were systematically reviewed. Complications were also reviewed. Results: Nineteen studies involving 1613 patients with HCC and bone metastases were included. The median OS was 6 months (range: 3–13 months). The pooled one-year OS was 23.1% (95% confidence interval [CI]: 18.4–28.6); pooled pain RR was 81.5% (95% CI: 76.4–85.7) and of pain complete remission was 26.5% (95% CI: 21.7–32.0). Pain response might be related to dose escalation, considering the moderate consistency of results and plausibility, with a low-quality grade of evidence^†. Considering the indeterminate results, we cannot suggest that dose escalation is correlated with OS. The oligometastasis status might be related to better OS, considering the high consistency of results and plausibility with low to moderate quality of evidence. Hypofractionated EBRT might yield comparable efficacy to conventional EBRT, with a low-quality grade of evidence. There were few complications of grade ≥3, except for hematologic complications, which ranged from 11.5to 34%. Conclusion: EBRT is an efficient and feasible palliative option. Clinical consideration of hematologic complications is necessary. Future studies are needed to increase the quality of evidence for actual clinical questions. ^†Reference to a system of the American Society for Radiation Oncology primary liver cancer clinical guidelines.