Survival and Toxicity Outcomes with Radiotherapy Technique and Timing in the Management of Wilms Tumor: a Systematic Review to Inform a National Clinical Practice Guideline Development

Abstract

Purpose: Wilms tumor (WT) management has evolved into a multimodality paradigm that includes radiotherapy (RT), usually as an adjuvant or consolidative modality. Protocols are refined to maximize cure and compliance while minimizing acute toxicity and long-term effects. RT technique and timing are two factors that could improve these outcomes. We reviewed the evidence on survival and toxicity outcomes among WT patients with conventional versus advanced RT techniques and early versus delayed RT to inform a Department of Health (DOH) commissioned guideline. Materials and Methods: We systematically searched PubMed, EuropePMC, EBSCOHost, HERDIN, systematic review and clinical trial registries and official websites of scientific societies for relevant publications and grey literature. Eligibility screening, risk-of-bias assessment and data extraction were performed using a single-reviewer approach. Given the study and data heterogeneity, only a qualitative synthesis was performed. Certainty of evidence assessment was done using the GRADE approach. Results: We screened 314 studies and included seven in the review, including a phase 1/2 trial and six retrospective studies, all from first-world countries (US, France, Netherlands), except one from a newly industrialized country (Brazil). The certainty of evidence on the survival and toxicity outcomes with advanced RT techniques was very low. Moderate-certainty evidence supports that giving RT >14 days after surgery leads to increased mortality. Conclusion: Current evidence does not support the routine use of advanced RT techniques; proper contextualization is necessary. Tertiary centers managing WT should strive to administer RT within 14 days after surgery whenever possible. Keywords: Wilms tumor, nephroblastoma, radiotherapy, intensity-modulated radiotherapy, survival, toxicity