Background/objectives: Radiotherapy (RT) is a standard component of treatment for high-risk pediatric neuroblastoma. Proton beam therapy (PBT) offers dosimetric advantages over photon radiotherapy (XRT), but comparative clinical data remain limited.
Methods: As part of the review project at our facility, we conducted a systematic review and meta-analysis comparing survival outcomes between PBT and XRT. PubMed was searched for studies published between 1990 and 2022. Eligible studies included those for pediatric patients with neuroblastoma receiving curative-intent RT and reporting overall survival (OS) or progression-free survival (PFS). A random-effects meta-analysis and meta-regression were performed.
Results: Eighteen studies (6 PBT, 12 XRT) were included. The 1- and 2-year OS rates were 97.2% and 92.0% for PBT, and 89.1% and 81.3% for XRT. Corresponding PFS rates were 96.1% and 86.1% for PBT, and 78.6% and 64.5% for XRT. Meta-regression identified treatment modality as a significant factor for 2-year OS and PFS. However, variability in patient background and treatment protocols may have influenced the results. Limited toxicity data suggested low rates of grade ≥ 3 acute adverse events in both groups.
Conclusions: PBT gave survival outcomes that were at least comparable to XRT in pediatric neuroblastoma. Given its potential to reduce long-term toxicity, PBT may be a reasonable alternative in selected cases. Further prospective studies are needed to validate these findings.
Keywords: meta‐analysis; outcomes; pediatric neuroblastoma; photon radiotherapy; proton beam therapy.
© 2026 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.