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. 2025 Aug;52(8):e18045.
doi: 10.1002/mp.18045.

Predicting sacral insufficiency fractures in carbon ion therapy for sacral chordoma: The role of RBE-weighted dose, dose-averaged LET, and volume

Silvia Molinelli  1 , Matteo Bagnalasta  1 , Giuseppe Magro  1 , Marco Rotondi  1 , Stefania Russo  1 , Agnieszka Chalaszczyk  1 , Elettra Ferrari  1 , Sara Imparato  1 , Mario Ciocca  1 , Ester Orlandi  1   2 , Maria Rosaria Fiore  1
Affiliations

Predicting sacral insufficiency fractures in carbon ion therapy for sacral chordoma: The role of RBE-weighted dose, dose-averaged LET, and volume

Silvia Molinelli et al. Med Phys. 2025 Aug.

Abstract

Background: A previous retrospective analysis on clinical outcomes of carbon-ion radiation therapy (CIRT) for large sacral chordoma patients highlighted the potential correlation between tumor relapse and suboptimal dose-averaged LET (LETd) distribution, triggering the need for implementation of LETd-based objectives in clinical practice.

Purpose: To investigate the synergetic role played by RBE-weighted dose (DRBE) and LETd in the occurrence of sacral insufficiency fractures (SIF) after CIRT for sacral chordoma patients, in view of the clinical application of LETd-based plan optimization.

Methods: We retrospectively analyzed 73 patients, consecutively treated between 2013 and 2021, with radical CIRT and classified the occurrence of SIF during follow-up. The prescribed dose ranged from 70.4 to 76.8 Gy (RBE), in 16 fractions, according to the local-effect-model I (LEM). The median follow-up was 36 months (range 2-115). For all patients, sacral bone was contoured to calculate the corresponding DRBE- LETd- volume histogram (DLVH) with two RBE models. Logistic regression was used to investigate the relationship between median DLVH points of sacral bone and the likelihood of developing SIF. For patients reporting SIF at follow-up, the fracture was contoured on the corresponding MRI sequence for a loco-regional analysis.

Results: SIF was diagnosed in 50% of the patients, occurring after a median follow-up of 23 months (range 2-115). The volume of sacral bone receiving a DLEM higher than 69.8 Gy(RBE) and an LETd higher than 39.7 keV/µm was significantly higher in the fractured cohort (19.5 vs. 3.6 cc) and influenced the probability of toxicity over time (AUC 0.76). The majority of the fractures (63%) were located in the high-risk target volume.

Conclusion: Exposure of sacral bone to high-dose radiation with LETd values of the order of 40 keV/µm emerged as a significant predictor of SIF development. Further validation on larger patient cohorts is warranted to refine individual risk stratification and to inform safer LETd-based treatment planning.

Keywords: LETd optimization; carbon ion therapy; sacral chordoma.

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