Robust Optimization and Experimental Validation of LETd‑Escalated Carbon‑Ion Arc Therapy for Head and Neck Cancer
Abstract
Purpose
LETd escalation within the tumor shows promise in enhancing biological effectiveness in carbon-ion radiotherapy to combat radio-resistant factors such as tumor hypoxia. In this work, in silico investigations and experimental validations were performed to assess the optimization limitations, robustness and delivery feasibility of LETd‑escalated carbon‑ion intensity‑modulated particle therapy (IMPT) and arc therapy (ARC) for head and neck (H&N) cancer.
Methods
A patient cohort (N=5) was selected and robust CTV‑based plans were generated using (i) IMPT, and (ii) ARC, applying ±2.5% range and ±1 mm setup uncertainties. LETd escalation was increased incrementally in the GTV to determine the maximum prescribable LETd (Lmax) that preserved worst‑case CTV coverage (D95≥95%) and dose homogeneity (D2≤1.10×Dp). Dosimetric validations were performed using an anthropomorphic H&N phantom for IMPT and step‑and‑shoot ARC using a heavy ion gantry. Plans were delivered in three repeated setups, and doses were measured using PinPoint ion chambers to validate robustness of LETd-escalated plans.
Results
Across the patient cohort, ARC achieved higher Lmax within the GTV and superior LETd shaping compared to IMPT. Across patients, moderate LETd escalation (LETd,GTV,98 ≈ 55–70 keV/µm) remained robust, whereas strong escalation (LETd,GTV,98 ≈ 90–100 keV/µm) degraded dose homogeneity and violated robustness criteria. Phantom measurements confirmed these findings, with Lmax values reaching ~65 keV/µm for IMPT and ~90 keV/µm for ARC. IMPT and ARC with moderate LETd escalation maintained minimal delivery error (5%).
Conclusion
Robust optimization is essential for clinically viable LETd escalation in carbon‑ion therapy. ARC provides greater LETd‑escalation potential and robustness than IMPT. Moderate LETd escalation can be safely and robustly delivered. Strong LETd escalation compromises plan stability and should be avoided. This work marks the first delivery of ion ARC using a superconducting heavy-ion gantry system.