February: Childhood

The Potential for Protons in Pediatrics

Dr. Madeleine Van de Kleut, PhD
Contact: mvandekl@uwo.ca
February 15, 2021

Radiation treatment to the brain, especially the developing brain of children, can lead to long-term impairment. Recent research provides evidence that proton radiation therapy as a treatment for brain cancer may protect a child’s intellect more than conventional x-ray radiation therapy. Each year in Canada, approximately 1000 children are diagnosed with cancer. While childhood cancer accounts for less than 1% of all new cancer diagnoses, it remains the most common disease-related cause of death in children. Of these cancers, brain and spinal cord cancers account for the majority of deaths. This article describes recent research – a first study of its kind – comparing different treatment methods for childhood brain cancer to evaluate their influence on intelligence test scores over time.

The brain and spinal cord comprise the central nervous system – the part of the body that regulates most bodily functions, including movement, sensation, thought, speech, and memory. Tumours located within the central nervous system are particularly difficult to treat because incidental damage to healthy tissues surrounding the tumour can lead to cognitive and motor impairment.

Radiation therapy, in addition to chemotherapy and surgery, is the current standard of care for treating brain and spinal cord tumours. The traditional approach of radiation therapy uses beams of high energy x-rays with the goal of targeting and destroying cancer cells, while limiting harm to surrounding healthy tissues. Techniques have been developed to shape the x-ray beam so it can be delivered to the patient while minimizing the amount of healthy tissue exposed to radiation, and therefore, minimizing side-effects.

Recently, scientists have been investigating the use of proton beam radiation therapy. Protons are charged subatomic particles that behave differently from x-rays in the body. A unique characteristic of protons is that once they enter the body, their final destination can be well-controlled. Because of their predictable behaviour, radiation oncologists and medical physicists are able to develop radiation treatment plans that very accurately deliver protons to a specific part of the body (i.e., the tumour). Compared to the use of high energy x-rays, high energy protons may be less damaging to healthy tissue surrounding the tumour.

Researchers at the Hospital for Sick Children, the Princess Margaret Cancer Center, and the University of Toronto in collaboration with the Baylor College of Medicine, Texas Children’s Hospital, the University of Texas MD Anderson Cancer Center, the Mayo Clinic, and St. Jude Children’s Research Hospital conducted the first longitudinal study comparing intellectual outcomes between children treated for brain cancer with conventional x-ray radiation therapy (XRT) and proton radiation therapy (PRT). Both groups of patients had the same brain tumour diagnosis, medulloblastoma, were the same age at the time of diagnosis (average age = 9 years), and had the same length of follow-up (average follow-up = 4 years). Before treatment and at each year after treatment, patients were assessed using age-appropriate tests evaluating standard intellectual scores: global IQ, verbal reasoning, perceptual reasoning, working memory, and processing speed (reflecting cognitive efficiency and fine motor functioning). The study found there were no differences in intellectual scores between patient groups prior to treatment.

Results from the tests demonstrated that PRT was associated with a retention of intellectual function not observed in the conventional XRT group. At the mean follow-up of four years, there were no declines in global IQ, verbal reasoning, perceptual reasoning, or working memory in the PRT group. In contrast, patients in the XRT groups demonstrated declines in global IQ, working memory, and processing speed. The authors of the paper suggest that there are indications that treatment with PRT does not affect a child’s intellect to the degree that XRT does.

So why not use proton radiation therapy all the time? First and foremost, it is expensive! A recent assessment by the province of Ontario has estimated that building and operating a proton facility [in Ontario] would cost approximately $125 million. Second, a proton facility takes up a lot of space – up to the length of a football field and three stories tall, in order to accelerate the protons and give them enough energy to kill the tumour. In most facilities, there just isn’t space. Third, the lack of randomized controlled trials (the highest standard for a comparative study) with long-term (greater than 10-year) follow-up comparing proton radiation therapy to x-ray radiation therapy makes it difficult to compare the two techniques without introducing sources of bias.

At this time, there are no proton facilities in Canada, and there are only 27 facilities in the United States (the patients treated with protons in this study were treated in the US). This introduces another area of debate for healthcare professionals – should Canadians have equitable access to proton therapy? In order to receive proton radiation therapy, which potentially offers a retention of intellectual outcomes to children diagnosed with medulloblastoma, patients and their parents/guardians must spend 6-8 weeks in the US, away from home. Those who can afford to do so are likely of a higher socioeconomic status. Presently, the province may choose to fund a patient’s proton therapy in the US if it is deemed the most appropriate treatment, though this approach is likely not sustainable long-term. Further research needs to ask the question: How much improvement in quality of life is needed to justify the implementation of new treatment techniques in Canada?

Overall, this research presents the first study comparing intellectual outcomes in children diagnosed with medulloblastoma treated with either x-ray radiation therapy or proton radiation therapy. The results highlight that patients treated with PRT showed a retention of intellectual outcomes, though due to the relatively short follow-up, secondary cancers and late effects were not assessed.

Original article: Kahalley, L. S., Peterson, R., Ris, M. D., Janzen, L., Okcu, M. F., Grosshans, D. R. et al. (2020). Superior intellectual outcomes after proton radiotherapy compared with photon radiotherapy for pediatric medulloblastoma. Journal of Clinical Oncology, 38(5), 454–461. https://doi.org/10.1200/JCO.19.01706