First Dosimetric and Biological Verification for Spot-Scanning Hadron Arc Radiation Therapy With Carbon Ions

Abstract

Purpose: Spot-scanning hadron arc radiation therapy (SHArc) is a novel delivery technique for ion beams with potentially improved dose conformity and dose-averaged linear energy transfer (LETd) redistribution. The first dosimetric validation and in vitro verification of carbon ion arc delivery is presented. Methods and Materials: Intensity-modulated particle therapy (IMPT) and SHArc plans were designed to deliver homogeneous physical dose or biological dose in a cylindrical polymethyl methacrylate (PMMA) phantom. Additional IMPT carbon plans were optimized for testing different LETd-boosting strategies. Verifications of planned doses were performed with an ionization chamber, and a clonogenic survival assay was conducted using A549 cancer lung cell line. Radiation-induced nuclear 53BP1 foci were assessed to evaluate the cellular response in both normoxic and hypoxic conditions. Results: Dosimetric measurements and clonogenic assay results showed a good agreement with planned dose and survival distributions. Measured survival fractions and foci confirmed carbon ions SHArc as a potential modality to overcome hypoxia-induced radioresistance. LETd-boosted IMPT plans reached similar LETd in the target as in SHArc plans, promising similar features against hypoxia but at the cost of an increased entrance dose. SHArc resulted, however, in a lower dose bath but in a larger volume around the target. Conclusions: The first proof-of-principle of carbon ions SHArc delivery was performed, and experimental evidence suggests this novel modality as an attractive approach for treating hypoxic tumors.