Review ArticleLate Toxicity After 3-Dimensional External Beam Radiotherapy Among Children With Cancer: A Systematic ReviewBeijer, Josien G.M. MSc*; Teepen, Jop C. PhD*; Streefkerk, Nina MD*; Heijnen, Richard M. BSc*; Janssens, Geert O. MD, PhD*,†; Kremer, Leontien C.M. MD, PhD*,‡; van Dalen, Elvira C. MD, PhD*; Ronckers, Cécile M. PhD*,§ Author Information *Princess Máxima Center for Pediatric Oncology †Department of Radiation Oncology, University Medical Center Utrecht, Utrecht ‡Department of Pediatrics, Emma Children’s Hospital, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands §Brandenburg Medical School, Institute of Biostatistics and Registry Research, Neuruppin, Germany E.C.v.D. and C.M.R. shared last authorship. C.M.R. reported a personal grant from the Dutch Cancer Society (grant no: UVA2012-5517). J.G.M.B. reported a grant from the Dutch Cancer Society (grant no: UVA2015-7655). The authors declare no conflict of interest. Reprints: Josien G.M. Beijer, MSc, Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, Utrecht 3584 CS, The Netherlands (e-mail: [email protected]). Journal of Pediatric Hematology/Oncology: May 2022 - Volume 44 - Issue 4 - p 117-134 doi: 10.1097/MPH.0000000000002445 Buy SDC Metrics Abstract Radiotherapy has evolved from 2-dimensional conventional radiotherapy (2D-RT) to 3-dimensional planned radiotherapy (3D-RT). Because 3D-RT improves conformity, an altered late health outcomes risk profile is anticipated. Here, we systematically reviewed the current literature on late toxicity after 3D-RT in children treated for cancer. PubMed was searched for studies describing late toxicity after 3D-RT for childhood cancer (below 21 y). Late toxicity was defined as somatic health outcomes occurring ≥90 days after treatment. We identified 13 eligible studies, describing most frequently head/neck area tumors. Included studies reported on crude frequencies of late toxicities including subsequent tumors and conditions of organ systems. Three studies offered a global assessment of the full spectrum of late toxicity; one study compared toxicities after 2D-RT and 3D-RT. Incidence rates were typically not provided. Heterogeneity in study characteristics, small study sizes and short follow-up times precluded multivariable modeling and pooling of data. In conclusion, among the first pediatric cohorts treated with 3D-RT, a broad variety of late toxicity is reported; precise estimates of incidence, and contributions of risk factors are unclear. Continued systematic evaluation of well-defined health outcomes in survivors treated with 3D-RT, including proton therapy, is needed to optimize evidence-based care for children with cancer and survivors. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.