Multi-model RBE and dose-averaged LET optimized carbon ion radiotherapy for sacral chordoma: results of the first year of clinical application.

PURPOSE/OBJECTIVE: 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 (LETd) within the tumour. This study reports on the early outcomes of a clinical optimization strategy combining compliance with multi-RBE and explicit LETd escalation in a cohort of 10 sacral chordoma patients treated with CIRT. MATERIAL/METHODS: Treatment plans, optimized with dosimetric objectives to a prescribed RBE-weighted dose (DRBE) 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 LETd (LETd-min) to the GTV (plan-L). The selected LETd-min ensured compliance with clinical goals under both nominal and robust scenarios. Plan-D and Plan-L were compared using variations in DRBE, LEM and MKM, and LETd 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. RESULTS: The median GTV volume was 171.1 cc [90.6-636.7]. The median LETd-min constraint applied was 44 keV/μm (range: 40-48). The median GTV LETd-98% 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 LETd metrics, with deviations below 2% relative to the nominal plan. The early toxicity profile was clinically acceptable. CONCLUSION: 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 LETd within the target, with acceptable robustness and well-tolerated acute toxicity in this initial patient series.