Proton therapy improves neurocognitive outcomes of childhood craniopharyngioma

Craniopharyngioma is a rare brain tumor that forms in the central region of the brain, making it difficult to treat without exposing surrounding healthy brain tissue to radiation. Conventional radiation therapy, called photon therapy, increases the probability of five-year survival of pediatric patients with craniopharyngioma to 90%; however, patients may experience treatment-related neurocognitive late effects. 

In a recent phase 2 clinical trial for children with craniopharyngioma, researchers at St. Jude found that photon therapy and the more targeted proton therapy resulted in similar survival, but patients who received proton therapy had a better neurocognitive outcome than those who received photon therapy. This clinical trial may set the new “gold standard” for pediatric craniopharyngioma treatment. 

Photons pass through the tumor, whereas protons can be directed to stop within the tumor. Thus, proton therapy spares normal brain tissue and reduces collateral effects. This St. Jude trial highlights the therapeutic advantage of proton therapy for children and adolescents with craniopharyngioma for the first time.

“The trial is an unprecedented study comparing proton and photon therapy for craniopharyngioma,” said principal investigator Thomas Merchant, DO, PhD, Department of Radiation Oncology chair. “We found a benefit for cognitive outcomes in patients treated with proton therapy while maintaining a high survival rate.” 

The study, published in the Lancet Oncology, showed that overall survival, progression-free survival, and cognitive outcomes five years after treatment were improved with proton therapy when compared with other treatment approaches.

“We have long recognized a theoretical benefit of this approach but now have proof that proton therapy causes fewer cognitive side effects than photons,” said co-author Frederick Boop, MD, Department of Surgery. 

Although proton therapy was developed to decrease radiation exposure to the brain, no previous clinical trials for children with brain tumors had prospectively shown its functional benefit compared to photon therapy in a single tumor type. A unique feature of craniopharyngioma is that it is consistently located in the central part of the brain and intimately associated with the central blood supply, optic nerves and chiasm, hypothalamic-pituitary axis, and other critical areas associated with cognitive function.

The researchers compared proton therapy results over five years to a historical control group treated with photon therapy at St. Jude. Patients treated with photon therapy experienced an average loss of 1.09 more intelligence quotient points every year than those treated with proton therapy for the five years of the study. Similarly, patients exposed to photon therapy lost 1.48 more adaptive behavior points, a parental report of self-care skills, per year than those treated with proton therapy. The cognitive and adaptive behavior deficits of those treated with proton therapy were stable by the end of the study. 

“These results could be practice-changing if they convince caregivers to recommend proton beam therapy over radical surgery or referral of patients using proton beam therapy instead of radiotherapy using photons,” Merchant said. “The results of this trial are important for pediatric radiation oncology because they realize a goal to show the benefit of proton therapy over photon therapy. We’ve been waiting years for these results.”