Late toxicity after upper abdominal radiotherapy in pediatric Wilms tumor and neuroblastoma survivors. A systematic review on behalf of SIOPEN and SIOP-RTSG

Background: Radiotherapy plays a crucial role in the multimodal treatment of Wilms tumor and neuroblastoma subtypes with an increased risk of locoregional failure. Unfortunately, radiotherapy can be associated with late toxicities in survivors. This systematic review provides an overview of the quality of evidence related to late effects following upper abdominal radiotherapy in survivors of Wilms tumor and neuroblastoma. Method: A systematic search was conducted using the PubMed database to address clinical questions regarding late effects on the liver, pancreas, vessels, kidney(s), musculoskeletal structures, second malignancy induction, spleen, and intestines. The Quality In Prognosis Studies (QUIPS) tool was utilized to assess the risk of bias in individual studies. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool was applied to evaluate the overall quality of evidence concerning late toxicity risks after upper abdominal radiotherapy. Results: Out of 3080 records, 55 studies were included. We identified high levels of evidence for the prevalence of metabolic syndrome, diabetes, and functional asplenia as late toxicities following upper abdominal radiotherapy. A moderate level of evidence was found for an increased risk of secondary malignant neoplasms (renal cell carcinomas and colorectal carcinomas) and chronic kidney disease. Very low evidence for prevalence of scoliosis/spinal deformity and aortic growth abnormalities was observed. Conclusion: This systematic review highlights the different levels of evidence of a spectrum of late toxicities, associated with upper abdominal radiotherapy in survivors from a Wilms tumor and neuroblastoma. Within the multi-disciplinary approach, modern radiotherapy has the potential to limit these late effects.