Risk-adapted radiotherapy in pediatric neuroblastoma: current evidence, controversies, and future directions-a narrative review.
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BACKGROUND AND OBJECTIVE: Radiotherapy is an established component of treatment for high-risk neuroblastoma, but questions remain about dose escalation, target definition, and the selection of metastatic sites for irradiation. This narrative review examines the evidence informing radiotherapy decisions in children with neuroblastoma, with particular attention to local control, normal-tissue exposure, and late toxicity. METHODS: A targeted PubMed search covered English-language publications from database inception. The initial search was conducted on 30 June 2026 and updated on 11 August 2026. Topic-specific free-text searches addressed radiotherapy, metastatic disease, treatment techniques, molecular imaging, artificial intelligence (AI), and toxicity. Reference lists, cooperative-group reports, and guidelines provided additional sources. Studies were selected for their relevance to radiotherapy decisions. KEY CONTENT AND FINDINGS: Evidence supports consolidative primary-site radiotherapy in high-risk neuroblastoma. The Children's Oncology Group ANBL0532 study prescribed 21.6 Gy to the post-induction/preoperative primary tumor volume; a boost to postoperative gross residual disease did not significantly improve local control relative to a historical comparator. Metastasis-directed radiotherapy may be appropriate for selected residual, symptomatic, or anatomically high-risk lesions, but routine treatment of every initially involved metastatic site is not supported. Elective nodal irradiation is also not routinely indicated. Proton therapy, intraoperative radiotherapy (IORT), and advanced imaging have potential roles in selected patients, although their evidence bases differ and comparative outcome data remain limited. CONCLUSIONS: Radiotherapy decisions should reflect the clinical setting, response to systemic treatment, residual disease, and expected toxicity. Better reporting of target volumes, dose-volume parameters, imaging response, and long-term outcomes is needed to define which patients benefit from treatment intensification or reduction.