Out-of-Field Second Cancers in Pediatric Patients Unlikely with Passive Scatter Proton Therapy

Presenting author:
Daniel Indelicato, MD

By J. Ben Wilkinson, MD, Coastal Radiation Oncology

Many radiation oncologists would acknowledge that it is reasonable to treat pediatric cancers with proton beam therapy to reduce the risk of side effects, as well as decrease the risk of treatment-related malignancies. While the integral dose using protons is significantly less than IMRT or 3-D CRT, one of the potential concerns within the proton community is whether the established passive-scatter method of diverging the proton beam that has historically been used is associated with unwanted out-of-field secondary cancers. While the equipment can usually be upgraded, most proton beam facilities that were constructed six to eight years ago or more will have this beam delivery system within at least one or more of their treatment rooms.

The source of the additional out-of-field risk theoretically comes from neutrons that are produced each time the proton beam interacts with diverging or modulating elements in the beam path. The pediatric radiation oncology team at University of Florida led by Danny Indelicato researched this potential concern to determine whether their extensive experience with passive-scatter proton beam therapy reveals any insight on this topic. Dr. Indelicato shared that this “study is the first to provide a cumulative incidence of second tumors, both malignant and non-malignant, following proton therapy in children.”

To generate these data, the team at UF Health Proton Therapy Institute evaluated detailed treatment records of over 1,700 children treated consecutively at their facility between 2006 and 2019. The median age at the time of treatment in this study was just over nine years and average follow up was three and a half years with over 400 patients having at least five years of follow up.  After accounting for tumor predisposition syndromes such as neurofibromatosis, retinoblastoma and Li-Fraumeni, the overall rate of secondary tumor formation at five years was 0.2% and at 10 years was 1.1%. Interestingly, when excluding children with genetic tumor predisposition syndromes, secondary malignant tumors only developed in patients who received radiation at five years old or younger and there were no tumors detected in areas receiving less than 50 Gy proton dose. In describing their data compared to similar cohorts of children treated with IMRT, Dr. Indelicato identified that “patients treated with proton therapy demonstrated a lower standardized incidence ratio and absolute excess risk of second tumor formation.

Dr. Indelicato concluded that “it is unlikely that neutrons from double-scattered proton therapy in children results in the theoretical increased rate of “out-of-field” second tumors.” Long-term follow up will definitively be needed, especially as more pencil-beam scanning centers come online and we observe outcomes for young patients treated with both technologies. While it is unlikely that future proton centers will be built with passive scatter systems, these data may be helpful in guiding allocation of pencil beam scanning technology to younger patients at centers with both scatter and scanning delivery nozzles and also further justify making proton beam therapy accessible to all families impacted by pediatric cancer.


Second Tumors in Pediatric Patients Treated with Double-Scattered Proton Therapy was presented on Saturday, October 24 in the Science Center, during the Quick Pitch (QP) session 04 – Pediatrics 01 – Focus on Pediatric Long Term Outcomes and Toxicity.

Published on: October 26, 2020

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