Radical skeletal metastatic site irradiation in high-risk neuroblastoma: systematic review and proposal for a randomised trial

Abstract

Aim: Neuroblastoma has a variable outcome depending on age, stage, and molecular pathology. Distant metastatic disease is the central feature of high-risk disease. Recommendations for irradiating persistent metastatic deposits with curative intent after systemic therapy vary. It is unclear to what extent this practice may improve local control or survival. This study systematically reviewed the evidence for skeletal metastatic site irradiation and made evidence-based recommendations for clinical practice. Methods:We systematically reviewed the literature on radical radiotherapy of persistent metastases after chemotherapy. The aim was to determine whether a position could be taken regarding metastatic site irradiation in combined modality treatment protocols aiming for a cure and whether recommendations could be formulated. Results:The initial search yielded 445 results. After the title and abstract review, 13 full papers were retrieved. Ten papers were found suitable for data extraction. One additional paper was identified. All 11 were graded as Centre for Evidence-Based Medicine Step 4 in quality; there was no high-level evidence. There are suggestions of benefit for skeletal site irradiation in high-risk neuroblastoma; however, there is no certainty, and it was not possible to recommend a particular treatment policy. Conclusion:We recommend that consideration is given to a randomised evaluation of the benefits of radiotherapy to a limited number of residual post-induction-chemotherapy metastatic sites in good responders. This practice could be incorporated as an amendment to existing trials.