Proton therapy (PT) does not increase the risk of secondary neoplasms, when compared with intensity-modulated radiotherapy (IMRT), in patients with central nervous system (CNS) tumors, a new study suggests.1

The study was presented at the 20th International Symposium on Pediatric Neuro-Oncology (ISPNO) by Daniel J. Indelicato, MD, of the University of Florida in Jacksonville.

“It’s widely accepted that proton therapy delivers less radiation to developing tissues along the beam path compared to IMRT,” Dr Indelicato said. 

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However, a paper published in 20062 suggested that PT produces neutrons that deliver a total body equivalent radiation dose larger than leakage radiation from conventional linear accelerators. If this is true, given that children are physically smaller, their entire body may be at risk for receiving scattered radiation doses with PT, Dr Indelicato said.

He and his colleagues set out to evaluate whether this exposure poses an additional risk of secondary neoplasms (malignant or benign) in patients with CNS tumors who are younger than 21 years of age at the time of treatment. 

The researchers analyzed data from patients who received PT at the University of Florida (n=945) and patients who received IMRT at Memorial Sloan Kettering Cancer Center (n=99) between 1999 and 2020. The median follow-up was 6.5 years.

The IMRT cohort was significantly older than the PT cohort (median age, 10.4 vs 8.4 years; P <.001). Patients in the IMRT cohort were also more likely to receive craniospinal irradiation (31.3% vs 14.2%; P <.001) or alkylating chemotherapy (50.5% vs 29.7%; P <.0001).


There were no significant differences between the PT and IMRT cohorts for 5-year local control (89.9% and 83.8%, respectively), progression-free survival (83.8% vs 79.8%), or overall survival (94% vs 86.8%). 

Likewise, there was no significant difference in rates of secondary neoplasms at 10 years between the PT and IMRT groups — 2.4% and 2.2%, respectively.

However, secondary neoplasms at 10 years were more common among patients with tumor predisposition syndromes (34.3% vs 1.5%; P <.05) and among patients who received treatment before age 5 (4.9% vs 0.7%; P <.05).

In the entire cohort, the rate of secondary neoplasms was 0.7% at 5 years and 2.3% at 10 years. The incidence of solid tumors was 0.5% and 2.1%, respectively. 

Secondary neoplasms occurred between 0.8 years and 19.1 years after treatment. The median time to solid tumor diagnosis was 7.5 years, and the median time to hematologic malignancy diagnosis was 0.8 years.

“Reassuringly, contrary to the concerns raised … in 2006, it is unlikely that neutrons from double scattered proton therapy for CNS tumors result in an increased rate of out-of-field second neoplasms,” Dr Indelicato concluded.


1. Indelicato D, Tringale K, Bradley J, et al. Secondary neoplasms in children with central nervous system (CNS) tumors following radiotherapy in the modern era. Presented at ISPNO 2022; June 12-15, 2022. Abstract RONC-03. 

2. Hall EJ. Intensity-modulated radiation therapy, protons, and the risk of second cancers. Int J Radiat Oncol Biol Phys. 2006;65(1):1-7. doi:10.1016/j.ijrobp.2006.01.027