Comparison of proton vs. photon radiotherapy for liver cancer: a meta-analysis.

OBJECTIVE

To systematically evaluate the efficacy and safety of proton beam radiotherapy (PBT) compared with photon radiotherapy in the treatment of hepatocellular carcinoma (HCC), thereby providing evidence-based guidance for clinical decision-making in radiotherapy modality selection.

METHODS

A systematic search of PubMed, Web of Science, Cochrane Library, and EMBASE databases was conducted to identify clinical studies comparing PBT with photon radiotherapy for HCC. Study quality was assessed using the Newcastle-Ottawa Scale (NOS), and the certainty of evidence was evaluated using the GRADE system. Meta-analysis was performed using Review Manager 5.4. The primary outcomes assessed were overall survival (OS), radiation-induced liver injury (RILD), and non-classical RILD.

RESULTS

Four retrospective cohort studies were included. Meta-analysis results indicated that the PBT group had a hazard ratio for OS of 0.45 (95% CI: 0.34-0.60, P < 0.00001). However, moderate heterogeneity was observed for this outcome (I² = 48%), accompanied by significant publication bias, resulting in a low certainty of evidence. Conversely, PBT significantly reduced the risk of RILD (OR = 0.26, 95% CI: 0.15-0.46, P < 0.00001) and non-classical RILD (OR = 0.27, 95% CI: 0.15-0.47, P < 0.00001). Both outcomes demonstrated no heterogeneity (I² = 0%) and no significant publication bias, yielding a moderate certainty of evidence. The number needed to treat to prevent one case of liver injury was approximately five.

CONCLUSION

Compared with photon radiotherapy, PBT offers a clear advantage in reducing the risk of RILD and non-classical RILD in patients with HCC. However, the potential benefit of PBT in improving OS remains inconclusive due to limitations related to study design and publication bias, resulting in a low level of evidence. Clinical selection of radiotherapy modalities should be individualized based on patients' liver function reserve, tumor characteristics, and medical conditions. Large-scale, multicenter prospective studies are warranted to further validate the long-term survival benefits of PBT.