ESTRO 2025 - Abstract Book

S3508

Physics - Optimisation, algorithms and applications for ion beam treatment planning

ESTRO 2025

2693

Proffered Paper Investigation of the combined effect of dose and linear energy transfer on brain necrosis after proton therapy Alessia Bazani 1 , Matteo Bagnalasta 1 , Giulia Fontana 1 , Sara Lillo 1 , Vittoria Pavanello 2 , Luca Trombetta 1 , Eleonora Rossi 1 , Silvia Molinelli 1 , Alberto Iannalfi 1 , Ester Orlandi 3,1 , Mario Ciocca 1 1 Clinical Department, CNAO National Center for Oncological Hadrontherapy, Pavia, Italy. 2 Physics, University School for Advanced Studies (IUSS), Pavia, Italy. 3 Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy Purpose/Objective: To evaluate the combined effect of relative biological effectiveness (RBE)-weighted dose (D RBE ) and dose-averaged linear energy transfer (LET d ) on the development of brain radionecrosis in patients with intracranial meningioma and solitary fibrous tumours treated with intensity modulated proton therapy (IMPT), using the dose LET d -volume histogram (DLVH) approach[1]. Material/Methods: A total of 124 patients treated with IMPT from 2014 to 2023 were included[2]. Dose prescriptions ranged between 54 and 66 Gy (RBE=1.1) administered in 28 to 33 fractions. Patients were classified in the adverse event (AE) group if a brain necrosis of grade ≥ 1, according to the CTCAE v5.0 scale, was reported at follow-up. The remaining constituted the control group. The healthy brain tissue was defined as the brain parenchyma minus GTV; the AE volume was contoured on the follow-up MRI images that first revealed the presence of necrosis, rigidly registered to the planning CT scan. All the plans were recalculated using our current clinical TPS. We extracted both D RBE and LET d distributions to build the DLVH cumulative histogram of the healthy brain (Figure 1).

Comparisons between the median cumulative DLVH of patients with and without AE were done using the Mann Whitney U test. The DLVH index was selected based on the variable AUROC (>0.7). Univariable and multivariable logistic regressions were fitted to explore the potential AE predictors (age, gender, WHO grade, number of surgeries (0, 1, >1), GTV volume, cumulative DLVH variable). All the tests were performed with a significance level of p<0.01. Results: With a median follow-up time of 47.4 months (range 5.8÷109.6), twenty-six patients reported AE of grade ≥ 1. WHO grade and cumulative DLVH reported a statistically significant association with AE in the univariable analysis, while only the cumulative DLVH (D RBE >42.9 GyE and LET d >4.6 keV/µm) was still significant when adjusted for the other clinical variable (OR: 1.18 [1.08; 1.31], p<0.001) and selected as the best performing predictor. The corresponding partial brain volume was 8.2cc for the AE group and 1.1cc for the control group (Figure 2).