Better Intellectual Outcomes After Proton Beam for Brain Cancer

Roxanne Nelson, RN, BSN

January 09, 2020

A new study shows that children with medulloblastoma who were treated with radiotherapy had better intellectual outcomes when the radiation was delivered as proton beam therapy compared to traditional photon radiotherapy.

Proton beam radiotherapy remains controversial, mainly because it is more expensive than traditional radiotherapy and there is little evidence to show that the extra cost is worth it.

The main advantage claimed for proton therapy is a reduction in adverse effects. This has been particularly emphasized for children with brain cancer.

"Our findings show a clear cognitive advantage with proton radiotherapy, even in the context of craniospinal irradiation," said study author Lisa S. Kahalley, PhD, associate professor and director of research, Baylor College of Medicine and Texas Childrens Hospital, Houston.

"In the absence of a randomized clinical trial, it would be difficult to discount our findings, given the methodological strengths of our study, when making treatment decisions for patients who could feasibly receive protons instead of photons," she said.

The results were published in the Journal of Clinical Oncology.

"This supports what has been suspected, specifically, that decreased integral dose to the brain in developing brains has measurable benefit," said Sameer R. Keole, MD, a radiation oncologist at the Mayo Clinic, Phoenix, Arizona, who was approached for comment.

These are some of the best data he has seen, and they validate the benefit of proton therapy in pediatric brain tumors, Keole told Medscape Medical News.

"This is the closest we are going to get to a randomized clinical trial," he said, adding that the "likelihood of having one in this cohort is zero, and I don't think it would be ethical."

If not for the controversy regarding cost, "we wouldn't be having this discussion. We would be making greater use of proton therapy," Keole commented.

"The initial investment is intimidating," he said, "but we sometimes forget that it can cost about $30–$40 million to set up any state-of-the-art radiation center."

Study Details

The biggest claim for proton beam therapy is that it limits adverse effects in comparison with traditional radiotherapy. This has particularly been emphasized as a big advantage when treating the developing brains of children with cranial tumors.

Proton beam therapy decreases the amount of radiation that reaches healthy brain tissue beyond the boost margins, the authors explain.

"With less irradiation of healthy cerebellar tissue, cognitive outcomes improve, likely due to reduced white matter damage allowing for preserved or more recoverable cerebrocerebellar connections," study author Don Mabbott, PhD, professor of psychology at the University of Toronto and a member of the Pediatric Brain Tumor Program at the Hospital for Sick Children, Toronto, Canada, told Medscape Medical News.

For their study, Mabbott and colleagues compared children with medulloblastoma who underwent either craniospinal proton radiotherapy (n = 37) or photon radiotherapy (n = 42) between 2007 and 2018. The same treatment protocols were followed for both groups of patients.

The two cohorts came from the Hospital for Sick Children, Toronto, Canada, and Texas Children's Hospital in Houston. Patients at the Hospital for Sick Children all received standard radiotherapy, because Canada did not have a proton center at the time of the study. Children treated at Texas Children's Hospital received proton therapy, which has been standard of care since 2007 at the the MD Anderson Proton Therapy Center.

Baseline clinical and demographic variables were similar in both groups, but boost dose (P < .001) and boost margin (P = .001) were significantly higher in the cohort that received photon radiotherapy.

The results show that children who were treated with proton radiotherapy had significantly better scores for global intelligence quotient (IQ), perceptual reasoning, and working memory (P < .05). Conversely, patients who received traditional photon therapy showed significant declines in global IQ, working memory, and processing speed (P < .05).

Overall, the proton therapy group demonstrated stable scores for all outcomes except processing speed, which declined significantly over time (P = .003).

Patients treated with proton therapy had stable global IQ and working memory (global IQ mean, 0.3 [SE, 0.5]; P = .100; working memory mean, 0.1 [SE, 0.7]; P = .891). By contrast, the patients in the photon radiotherapy group experienced a decline of global IQ (mean, –0.9 [SE, 0.4]; P = .009) and working memory (mean, –2.2 [SE, 0.6]; P = .001).

A nonsignificant decline in verbal reasoning (–0.4; P = .141) and a significant decline in processing speed (–0.9; P = .003) were observed for both groups.

"This is the first longitudinal study that compared changes in intelligence indices over time between pediatric patients with medulloblastoma treated with proton beam therapy as compared to a matched cohort treated with standard radiotherapy," Kahalley told Medscape Medica News.

"This study is powerful because both MD Anderson and Toronto Sick Kids are considered centers of excellence for pediatric brain tumor care," commented Keole.

Although there were some differences between the cohorts, presumably due to practice differences, they were small, he noted. "Overall, these are remarkably well-balanced cohorts, and it is notable that the starting measure scores are equivalent between the two cohorts. This eliminated the argument of selection bias and is a distinguishing feature."

Keole also noted that the American Society of Radiation Oncology (ASTRO) has supported insurance coverage for proton beam therapy for pediatric patients since 2014, when the ASTRO model policy was first issued. "This model policy was updated in 2017 and represents ASTRO's current position with respect to insurance coverage for proton therapy," Keole said. "The 2017 model policy update continues to list pediatric tumors as a level I indication."

The study was supported by the National Institutes of Health and the Canadian Institute of Health Research. Mabbott, Kahalley, and Keole have disclosed no relevant financial relationships.

J Clin Oncol. Published online November 27, 2019. Abstract

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