First-in-man validation of CT-based stopping-power prediction using prompt-gamma-based range verification

Introduction
Currently, the uncertainty in CT-based range prediction is substantially impairing the accuracy of particle therapy. Improvements like a determination of stopping-power ratio (SPR) from dual-energy CT (DECT) have been proposed. However, a validation of range prediction in patients has not been achieved by any means. Here, we present the first verification of proton range prediction in patients, using Prompt-Gamma-Imaging (PGI).

Materials & Methods
A PGI-slit-camera system was modified to enhance its positioning accuracy using a floor-based docking station. Its accuracy and positioning reproducibility were determined with x-ray and PGI measurements. The PGI system was clinically applied to monitor absolute proton ranges for a 1.5Gy field during eight fractions of hypo-fractionated treatment of two prostate-cancer patients using pencil beam scanning (Fig.1). For all monitored fractions, in-room control-CT scans were acquired in treatment position enabling PGI-based spot-by-spot range analysis for the actual patient anatomy. The PG measurements were compared to simulations of the expected PGI signal using either a standard CT-number-to-SPR conversion (HLUT) or a HLUT optimized with patient-specific DECT-derived SPR information (DECT-HLUT), respectively.

Results
The accuracy and precision for global range verification (averaging over multiple spots) was determined to be 0.6mm and 1.3mm (both 2σ-level), respectively. The precision is limited by remaining uncertainties in image registration and positioning reproducibility (1mm,2σ). To verify range prediction in patients, the histogram of range shifts was analyzed concerning its Gaussian mean (Fig. 2) as surrogate for the accuracy of the respective range prediction method, independent from random uncertainty contributions (e.g. positioning, statistical uncertainty in shift determination). The mean deviation for the DECT-HLUT and standard HLUT were -0.6mm and 1.3mm, respectively.

Conclusion
The accuracy of PGI-based range verification was improved to enable the verification of CT-based stopping-power prediction in patients for the first time. First data evaluation suggests a slight superiority of DECT-based range prediction.