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

Abstract

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.

Keywords:

• Hepatocellular carcinoma
• liver cancer
• bone metastasis
• metastasis
• external beam radiation therapy
• radiotherapy

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

All data generated or analyzed during this study are included in this published article (and its Supplementary information files).

Additional information

Funding

This study was supported by the National Research Fund of Korea [NRF-2021R1I1A2047475]. The funders had no role in the study design, data collection and analysis, decision to publish, or manuscript preparation.

Notes on contributors

Chai Hong Rim

Chai Hong Rim is a radiation oncologist and specialized researcher on the intractable clinical situation of cancer. He has published more than 50 peer-reviewed articles in the last four years as one of the lead authors.

Sunmin Park

Sunmin Park is a radiation oncology fellow who specializes in treating rectal cancer, gynecological cancer, and metastatic disease.

Won Sup Yoon

Won Sup Yoon is the director of the Department of Radiation Oncology at Korea University Ansan Hospital, who provided supervision and expertise to this manuscript.

In-Soo Shin

In-soo Shin is a statistician who specializes in meta-analysis and was awarded a Ph.D. degree from Florida State University.

Hee Chul Park

Hee Chul Park is the director of the Department of Radiation Oncology at the Seoul Samsung Hospital and provided supervision and expertise to this manuscript. He has published 150 peer-reviewed articles related to cancer radiotherapy.