Model-Based Normal Tissue Complication Probability Comparison Between Proton and Photon Therapies for Brain Tumors Complying With Planning Study Guidelines

@article{higaki2026modelbased,
  title = {{Model-Based Normal Tissue Complication Probability Comparison Between Proton and Photon Therapies for Brain Tumors Complying With Planning Study Guidelines}},
  author = {Hajime Higaki and Kentaro Nishioka and Kohei Yokokawa and Keiji Nakazato and Izuru Otake and Keiji Kobashi and Atsushi Motegi and Hideyuki Sakurai and Masao Murakami and Hiroyasu Tamamura and Takahiro Waki and Takashi Ogino and Hiromitsu Iwata and Masaru Takagi and Tomoaki Okimoto and Sadamoto Zenda and Masayuki Araya and Shigeyuki Murayama and Hideya Yamazaki and Hidefumi Aoyama},
  journal = {Advances in Radiation Oncology},
  year = {2026},
  month = oct,
  doi = {10.1016/j.adro.2026.102216},
  url = {https://doi.org/10.1016/j.adro.2026.102216},
  note = {CC BY-NC 4.0},
}

TY  - JOUR
TI  - Model-Based Normal Tissue Complication Probability Comparison Between Proton and Photon Therapies for Brain Tumors Complying With Planning Study Guidelines
AU  - Hajime Higaki
AU  - Kentaro Nishioka
AU  - Kohei Yokokawa
AU  - Keiji Nakazato
AU  - Izuru Otake
AU  - Keiji Kobashi
AU  - Atsushi Motegi
AU  - Hideyuki Sakurai
AU  - Masao Murakami
AU  - Hiroyasu Tamamura
AU  - Takahiro Waki
AU  - Takashi Ogino
AU  - Hiromitsu Iwata
AU  - Masaru Takagi
AU  - Tomoaki Okimoto
AU  - Sadamoto Zenda
AU  - Masayuki Araya
AU  - Shigeyuki Murayama
AU  - Hideya Yamazaki
AU  - Hidefumi Aoyama
PY  - 2026
DA  - 2026/10/19
JO  - Advances in Radiation Oncology
DO  - 10.1016/j.adro.2026.102216
UR  - https://doi.org/10.1016/j.adro.2026.102216
AB  - 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.
SN  - 2452-1094
ER  -