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Updated: Oct 28, 2026
Proton Therapy Delivery and Its Clinical Application in Select Solid Tumor Malignancies
Published on: February 6, 2019
Model-Based Normal Tissue Complication Probability Comparison Between Proton and Photon Therapies for Brain Tumors
Hajime Higaki1, Kentaro Nishioka2, Kohei Yokokawa2
1Department of Radiation Oncology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo, Japan.
Purpose:
The benefit of proton beam therapy (PBT) for primary brain tumors compared with x-ray therapy has not been demonstrated by randomized controlled trials. We performed a model-based approach study to evaluate the potential benefit of PBT for brain tumors using the normal tissue complication probability (NTCP) models complying with the Radiotherapy Treatment plannINg study Guidelines (RATING).
Methods And Materials:
Sixty-six patients with primary brain tumors treated with PBT were registered. We used 11 NTCP models, calculated NTCP for each adverse event, and estimated the PBT and intensity modulated radiation therapy (IMRT) plans for the entire patient population and for groups classified by pathology. Wilcoxon signed-rank tests were performed for statistically significant differences between the 2 modalities, and a 2-tailed test was considered significant when <.05. A reduction was considered clinically meaningful when the difference in NTCP between the 2 modalities (ΔNTCP) exceeded the prespecified threshold.
Results:
Overall, PBT reduced NTCP from the cataracts, delayed recall, memory impairment, contralateral hearing impairment, and tinnitus. Patients with meningiomas and low-grade gliomas had similar tendencies. PBT was associated with a lower excess absolute risk of secondary cancer of the central nervous system in all patients. However, NTCPs for alopecia, blindness, and brain necrosis were higher in the PBT cohort, highlighting important clinical trade-offs. Thirty-one patients (47.0%) had at least 1 ΔNTCP above the specified threshold.
Conclusions:
In this model-based planning comparison, PBT was associated with lower estimated NTCPs for selected endpoints compared with virtual IMRT, whereas IMRT showed advantages for alopecia, blindness, and brain necrosis. PBT may offer meaningful clinical benefits, particularly in reducing the excess absolute risk of secondary cancer for patients with long-term survival. In addition, the comparison based on Radiotherapy Treatment plannINg study Guidelines made the study more objective than similar previous studies.
