Model-Based Normal Tissue Complication Probability Comparison Between Proton and Photon Therapies for Brain Tumors Complying With Planning Study Guidelines
In brief
Proton plans showed meaningful modeled benefit for 47% of brain tumor patients
In planning comparisons for 66 patients, proton therapy had lower estimated risks of cataracts, memory problems, hearing impairment, tinnitus, and secondary brain cancer than intensity-modulated radiation therapy; 31 patients had at least one difference exceeding the study's threshold for clinical importance. Proton plans also showed higher estimated risks of hair loss, blindness, and brain necrosis, and whether these modeled differences translate into patient outcomes remains unknown.
- Journal
- Advances in radiation oncology (Q1)
- Published
- 19 October 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Hajime Higaki, Kentaro Nishioka, Kohei Yokokawa, Keiji Nakazato, Izuru Otake, Keiji Kobashi, et al.
- PMID
- 42936426
- DOI
- 10.1016/j.adro.2026.102216
Why clinicians should know about it
- Picked for Medical Physics (top studies of the week, 1 November 2026): Model-based NTCP comparison, proton vs IMRT planning
- Picked for Radiation Oncology (top studies of the week, 1 November 2026): Proton versus IMRT toxicity trade-offs for brain tumors
- Picked for Radiology, Radiation Oncology, Nuclear Medicine, Medical Physics and Imaging (top studies of the week, 1 November 2026): Patient-specific proton-versus-IMRT plans compare modeled toxicity
Abstract
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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.