A model-based risk-minimizing proton treatment planning concept for brain injury prevention in low-grade glioma patients

PURPOSE: Late-occurring contrast-enhancing brain lesions (CEBLs) have been observed on MRI follow-up in low-grade glioma (LGG) patients post-proton therapy. Predictive risk-models for this endpoint identified a dose-averaged linear energy transfer (LETd)-dependent proton relative biological effectiv...

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Main Authors: Sallem, Habiba (Author) , Harrabi, Semi B. (Author) , Traneus, Erik (Author) , Herfarth, Klaus (Author) , Debus, Jürgen (Author) , Bauer, Julia (Author)
Format: Article (Journal)
Language:English
Published: 10 October 2024
In: Radiotherapy and oncology
Year: 2024, Volume: 201, Pages: 1-7
ISSN:1879-0887
DOI:10.1016/j.radonc.2024.110579
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.radonc.2024.110579
Resolving-System, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S0167814024035576?via%3Dihub
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Author Notes:H. Sallem, S. Harrabi, E. Traneus, K. Herfarth, J. Debus, J. Bauer

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520 |a PURPOSE: Late-occurring contrast-enhancing brain lesions (CEBLs) have been observed on MRI follow-up in low-grade glioma (LGG) patients post-proton therapy. Predictive risk-models for this endpoint identified a dose-averaged linear energy transfer (LETd)-dependent proton relative biological effectiveness (RBE) effect on CEBL occurrence and increased radiosensitivity of the cerebral periventricular region (VP4mm). This work aimed to design a stable risk-minimizing treatment planning (TP) concept addressing these intertwined risk factors through a classically formulated optimization problem. - MATERIAL AND METHODS: The concept was developed in RayStation-research 11B IonPG featuring a variable-RBE-based optimizer involving 20 LGG patients with varying target volume localizations and risk-factor contributions. Classical cost functions penalizing dose, dose-volume-histogram points, and equivalent uniform dose were used to formulate the optimization problem, and a new set of structures was introduced to actively spare the VP4mm, control high LETd regions, and de-escalate the dose outside the gross tumor volume. Target volume coverage and organ-at-risk sparing were robustly evaluated, and Normal Tissue Complication Probabilities (NTCP) for CEBL occurrence were quantified. - RESULTS: The concept yielded stable optimization outcomes for all considered subjects. Risk hot spots were successfully mitigated, and an NTCP reduction of up to 79 % was observed compared to conventional TP while maintaining target coverage, demonstrating the feasibility of the chosen model-based approach. - CONCLUSION: With the proposed TP protocol, we close the gap between predictive risk-modeling and practical risk-mitigation in the clinic and provide a concept for CEBL avoidance with the potential to advance treatment precision for LGG patients. 
650 4 |a Brain Injuries 
650 4 |a Brain Neoplasms 
650 4 |a Cerebral ventricles 
650 4 |a Glioma 
650 4 |a Humans 
650 4 |a LET 
650 4 |a Magnetic Resonance Imaging 
650 4 |a Organs at Risk 
650 4 |a Proton therapy 
650 4 |a Proton Therapy 
650 4 |a Radiation Injuries 
650 4 |a Radiation injury 
650 4 |a Radiotherapy Dosage 
650 4 |a Radiotherapy Planning, Computer-Assisted 
650 4 |a Relative biological effectiveness 
650 4 |a Relative Biological Effectiveness 
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