LETd Escalation Using Scanned Neon (20Ne) Ion Therapy for Radioresistant Tumors
Abstract
Purpose
Neon ions (²⁰Ne) offer substantially higher clinically achievable dose-averaged linear energy transfer (LETd) escalation in the target compared to protons or carbon ions. LETd escalation has the potential to enhance biological effectiveness against radio-resistant diseases such as hypoxic or large-volume tumors. The world’s first scanned 20Ne radiotherapy program has been commissioned, enabling rapid high-precision IMPT delivery and LET-guided treatment optimization not previously available. This work presents the physics, beam commissioning, and evaluation of treatment planning strategies for safe and effective LETd escalation using 20Ne.
Methods
Accelerator and beam delivery system settings were established to produce 50–430 MeV/u 20Ne beams. Physical and radiobiological interactions were simulated and experimentally measured. A scanned‑beam model was developed and implemented in the clinical treatment‑planning system (TPS) and validated for dose, LETd and relative biological effectiveness (RBE). Treatment planning studies (N=16) applying LETd optimization were conducted to determine and compare maximum achievable LETd escalation in the tumor with 20Ne relative to lighter ions (e.g., ¹²C, ¹⁶O) using IMPT and ion arc therapy (ARC).
Results
Commissioning measurements demonstrated accurate dose delivery for SOBPs in water, with measured and planned doses agreeing within <1–2%. Across various treatment sites, results indicate that 20Ne provides the highest achievable minimum target LETd (LETd,min) among all clinical ions evaluated. For a H&N patient cohort, LETd-optimized IMPT-20Ne achieved LETd,min of 131.3(±13.4)keV/µm, compared to 58.8(±4.6)keV/µm and 73.8(±4.9)keV/µm for LETd-optimized IMPT-12C and ARC-12C, respectively, exhibiting ~126% and ~78% increase. Consequently, IMPT 20Ne increases LETd in adjacent normal tissues.
Conclusion
The first clinical platform for scanned 20Ne radiotherapy was established. Studies demonstrate that 20Ne affords LETd escalation beyond levels achievable with lighter ions. Pre‑clinical 20Ne studies are ongoing within a multi‑ion program. Additional approaches (e.g., 20Ne mini‑beams, ARC‑20Ne, 20Ne‑FLASH) may further expand the therapeutic window while mitigating normal‑tissue effects historically associated with high‑LET neon radiation.