The Evidence for External Beam Radiotherapy in High-Risk Neuroblastoma of Childhood: A Systematic Review.

Abstract Aims External beam radiotherapy is widely used in various ways in the management of neuroblastoma. Despite extensive clinical experience, the precise role of radiotherapy in neuroblastoma remains unclear. The purpose of this systematic review was to survey the published literature to identify, without bias, the evidence for the clinical effectiveness of external beam radiotherapy as part of the initial multimodality treatment of high-risk neuroblastoma. We considered four areas: treatment of the tumour bed and residual primary tumour, identification of any dose–response relationship, treatment of metastatic sites, identification of any technical advances that may be beneficial. We also aimed to define uncertainties, which may be clarified in future clinical trials. Materials and methods Bibliographic databases were searched for neuroblastoma and radiotherapy. Reviewers assessed 1283 papers for inclusion by title and abstract, with consensus achieved through discussion. Data extraction on 57 included papers was carried out by one reviewer and checked by another. Studies were assessed for their level of evidence and risk of bias, and a descriptive analysis of data was carried out. Results Fifteen papers provided some evidence that radiotherapy to the tumour bed and residual tumour may possibly be of value. However, there is a significant risk of bias and no evidence that all subgroups will benefit. There is some suggestion from six papers that dose may be important, but no hard evidence. It remains unclear whether irradiation of metastatic sites is helpful. Technical advances may be of value in radiotherapy of high-risk neuroblastoma. Conclusions There are data that show that radiotherapy is of some efficacy in the management of high-risk neuroblastoma, but there is no level one evidence that shows that it is being used in the best possible way. Prospective randomised trials are necessary to provide more evidence to guide development of optimal radiotherapy treatment schedules. Highlights • A systematic review of radiotherapy for high-risk neuroblastoma. • Explored the need for radiotherapy, the dose and metastatic site irradiation. • All evidence identified was low quality, with a significant risk of bias. • Radiotherapy may be of value, but the evidence is unclear and conflicting. • Prospective randomised trials are essential to strengthen the evidence base. [ABSTRACT FROM AUTHOR]