Title: Selection of the Most Appropriate Radiation Treatment Modality for Children’s Cancers: A Paediatric Radiation Oncology Society (PROS) Position Paper on the Ethical Utilization of Proton TherapyRunning Title: Ethical Utilization of Proton Therapy in Pediatric OncologyAuthors: Natia Esiashvili¹; Daniel J. Indelicato²; Anita Mahajan³; Jeannette Parkes⁴; Arnold C. Paulino⁵; Guillaume Beljoudi, ⁶; Ingrid Kristensen⁷; Anne Laprie⁸; Yasmin Lassen⁹; Pauline Njoki Njiraini¹⁰; Bilal Mazhar Qureshi¹¹; Beatriz Garcia Robles¹²; Klaus Seiersen¹³; Beate Timmermann¹⁴; Mark N. Gaze¹⁵Affiliations: ¹Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA, USA ²Department of Radiation Oncology, University of Florida, Jacksonville, FL, USA ³Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA ⁴Department of Radiation Oncology, University of Cape Town, Cape Town, South Africa ⁵Department of Radiation Oncology, MD Anderson Cancer Center, Houston, TX, USA ⁶ Department of Physics, Léon Bérard Cancer Center, Lyon, France. ⁷ Department of Hematology, Oncology and Radiation Physics, Skane University Hospital, Lund, Sweden; Department of Oncology, Clinical Sciences, Lund University, Lund, Sweden. ⁸ Department of Radiation Oncology, Insitut Universitaire du Cancer de Toulouse, Oncopole Claudius Regaud, Université de Toulouse, Toulouse, France. ⁹Department of Oncology, Rigshospitalet, Copenhagen, Denmark ¹⁰Department of Radiation Oncology, Nairobi, Kenya ¹¹Department of Radiation Oncology, Aga Khan University, Karachi, Pakistan ¹²Department of Radiation Oncology, National Institute of Pediatrics, Mexico City, Mexico ¹³ Danish Centre for Particle Therapy, Aarhus University Hospital, Aarhus, Denmark. ¹⁴West German Proton Therapy Centre, Essen, Germany ¹⁵ Department of Oncology, University College London Hospitals NHS Foundation Trust, London, UK.Corresponding Author: Natia Esiashvili, MD Professor of Radiation Oncology Emory University School of Medicine 1365 Clifton Road NE, Atlanta, GA 30322, USA Email: [insert] | Phone: [insert]Word Count: 3619Figures/Tables: 3/1 Keywords: Pediatric radiation oncology; proton therapy; radiotherapy ethics; access to care; financial toxicity; health equity

Survival of Wilms tumor (WT) is >90% in high-resource settings but <30% in low-resource settings. Adapting a standardized surgical approach to WT is challenging in low-resource settings, but a local control strategy is crucial to improving outcomes. Objective: Provide resource-sensitive recommendations for the surgical management of WT. Methods: We performed a systematic review of PubMed and EMBASE through July 7, 2020, and used the GRADE approach to assess evidence and recommendations. Recommendations: Initiation of treatment should be expedited, and surgery should be done in a high-volume setting. Cross-sectional imaging should be done to optimize preoperative planning. For patients with typical clinical features of WT, biopsy should not be done before chemotherapy, and neoadjuvant chemotherapy should precede surgical resection. Also, resection should include a large transperitoneal laparotomy, adequate lymph node sampling, and documentation of staging findings. For WT with tumor thrombus in the inferior vena cava, neoadjuvant chemotherapy should be given before en bloc resection of the tumor and thrombus and evaluation for viable tumor thrombus. For those with bilateral WT, neoadjuvant chemotherapy should be given for 6–12 weeks. Neither routine use of complex hilar control techniques during nephron-sparing surgery, nor nephron-sparing resection for unilateral WT with a normal contralateral kidney is recommended. When indicated, postoperative radiotherapy should be administered within 14 days of surgery. Post-chemotherapy pulmonary oligometastasis should be resected when feasible, if local protocols allow omission of whole-lung irradiation in patients with non-anaplastic histology stage IV WT with pulmonary metastasis without evidence of extrapulmonary metastasis. Conclusion: We provide evidence-based recommendations for the surgical management of WT, considering the benefits/risks associated with limited-resource settings.