Multi-model RBE and dose-averaged LET optimized carbon ion radiotherapy for sacral chordoma: results of the first year of clinical application.
prospective_cohort · Level II
Where this comes from
- Record sourced from PubMed, PMID 42595265.
- Also identified by DOI 10.1016/j.ijrobp.2026.07.062.
- No licence information is recorded for this record.
- Because redistribution is not established, this page shows the abstract only. Follow the links below for the full text.
Abstract
Carbon ion therapy (CIRT) optimization, driven by purely dosimetric and single-relative biological effectiveness (RBE) model may result in suboptimal solutions, particularly when considering dose-averaged LET (LET<sub>d</sub>) within the tumour. This study reports on the early outcomes of a clinical optimization strategy combining compliance with multi-RBE and explicit LET<sub>d</sub> escalation in a cohort of 10 sacral chordoma patients treated with CIRT. Treatment plans, optimized with dosimetric objectives to a prescribed RBE-weighted dose (D<sub>RBE</sub>) of 73.6 Gy(RBE), using the local effect model (LEM) (Plan-D), served as benchmark. The proposed strategy consisted of three steps: 1) plan optimization using the microdosimetric kinetic model (MKM) to 67.2 Gy(RBE); 2) iterative LEM-based recalculation to obtain plans compliant with RBE models; 3) inclusion of a cost-function term on the minimum LET<sub>d</sub> (LET<sub>d-min</sub>) to the GTV (plan-L). The selected LET<sub>d-min</sub> ensured compliance with clinical goals under both nominal and robust scenarios. Plan-D and Plan-L were compared using variations in D<sub>RBE</sub>, LEM and MKM, and LET<sub>d</sub> to target volume percentages. Re-evaluation CTs assessed inter-fraction robustness. Paired comparisons used the Wilcoxon signed-rank test. Acute toxicity was evaluated during treatment and at early follow-up. The median GTV volume was 171.1 cc [90.6-636.7]. The median LET<sub>d-min</sub> constraint applied was 44 keV/μm (range: 40-48). The median GTV LET<sub>d-98%</sub> increase was 29.2%, from 32.9 keV/μm (Plan-D) to 42.5 keV/μm (Plan-L). LEM-based dose deviations were not clinically relevant, while Plan-L showed significantly improved MKM dose homogeneity, compared with Plan-D. Inter-fraction robustness of target coverage was comparable for both dose and LET<sub>d</sub> metrics, with deviations below 2% relative to the nominal plan. The early toxicity profile was clinically acceptable. This study supports the feasibility of a novel optimization strategy for CIRT in large sacral chordomas, based on the synergistic maximization of dose, RBE, and LET<sub>d</sub> within the target, with acceptable robustness and well-tolerated acute toxicity in this initial patient series.