Effects of proton therapy on early cognitive outcomes

Key findings

• 60 patients (median age 12.3) who received proton radiation therapy as treatment were given cognitive assessments at the initiation of therapy and at one or more follow-up appointments, an average of 2.5 years later.
• No significant change was observed in mean full scale IQ, verbal comprehension, perceptual reasoning/organization, or working memory for these patients.
• However, processing speed scores declined significantly, with a much greater decline for subjects < 12 years at baseline and those with the highest baseline scores.
• Early cognitive outcomes following PRT for pediatric CNS tumors are encouraging compared to published outcomes from photon radiation therapy.

Proton radiation therapy makes treating tumors with minimal impact on surrounding healthy tissue possible. Although proton therapy is a precise option, it could still effect the cognitive function of patients treated with it, particularly younger patients whose brains are still developing.

Photon radiation therapy, often the alternative to proton therapy, is associated with a decline in overall IQ, including processing speed, and other cognitive functions. The severity of these impairments has been associated with the dose and extent of radiation, as well as age at treatment, with younger patients being most affected. Therefore, long-term effects of radiation therapy remain influential in treatment decisions.

The effects of proton therapy

Seeking to report on the longer-term cognitive outcomes of children treated with proton radiation therapy, researchers at Massachusetts General Hospital for Children and Massachusetts General Hospital focused a longitudinal study on patients who had been treated with proton therapy for brain and central nervous system (CNS) tumors. The study was published in International Journal of Radiation Oncology.

Torunn Yock, MD, director of the Department of Radiation Oncology at Massachusetts General Hospital for Children and her fellow researchers found that no significant change was observed in mean full scale IQ (FSIQ) and three of its components: verbal comprehension, perceptual reasoning/organization and working memory. However, processing speed scores (the fourth component of FSIQ) declined significantly, with a much greater decline for subjects less than 12 years old at baseline and those with the highest initial scores.

These scales were measured through cognitive assessments at the initiation of PRT and at one or more follow-up appointments, an average of 2.5 years later.

Measuring cognition

The study patients were individually treated with proton radiation, surgery and chemotherapy appropriate for their own diagnoses and the timely standard of care. Cognitive assessments were done using either the Wechsler Intelligence Scale for Children-4th Edition (ages 6–15 years) or the Wechsler Adult Intelligence Scale-3rd Edition (ages ≥ 16 years). Both scales yield index scores in the above-mentioned four cognitive categories. The four index scores combine to form the FSIQ, a measure of general cognitive functioning.

Of note, cognitive results differed by age group in certain areas, both at baseline and at follow-up. The younger patients scored much higher in FSIQ, perceptual reasoning and processing speed at baseline, and at follow-up, the younger group declined by 8.8 points in processing speed. By comparison, the older group improved by 4.5 points in processing speed at follow-up.

Cognitive outcome was not significantly related to gender, extent of radiation, radiation dose, tumor location, histology, socioeconomic status, chemotherapy or history of surgical resection.

The future of proton therapy

This report is the first detailed investigation of cognitive outcome in a large group of pediatric brain and CNS tumor patients treated with proton therapy. The exclusion of patients younger than six in this study for consistency in cognitive measurements indicates it probably is a better indication of overall cognitive outcome, since young age is widely associated with the largest cognitive effects of radiotherapy. The field would benefit from future reports presenting proton therapy outcomes for younger patients.

Funding: The project was supported by Award Number P01CA021239 from the National Cancer Institute.