First-in-human validation of CT-based proton range prediction using prompt gamma imaging in prostate-cancer treatments.

Abstract

PURPOSE\nUncertainty of CT-based range prediction is substantially impairing the accuracy of proton therapy. Direct determination of stopping-power ratio (SPR) from dual-energy CT (DECT) has been proposed (DirectSPR) and initial validation studies in phantoms and biological tissues have proven a high accuracy. However, a thorough validation of range prediction in patients has not yet been achieved by any means. Here, we present the first systematic validation of CT-based proton range prediction in patients using prompt gamma imaging (PGI).\n\n\nMATERIALS & METHODS\nA PGI slit camera system of improved positioning accuracy, using a floor-based docking station, was utilized. Its overall uncertainty for range prediction validation was determined experimentally with both X-ray and beam measurements. The accuracy of range prediction in patients was determined from clinical PGI measurements during hypo-fractionated treatment of five prostate-cancer patients; in total 30 fractions with in-room control-CTs. For each pencil-beam-scanning spot, the range shift was obtained by comparing the PGI measurement to a control-CT-based PGI simulation. Three different SPR prediction approaches were applied in simulations: a standard CT-number-to-SPR conversion (HLUT), an adapted HLUT (DECT-optimized), and\xa0DirectSPR. The spot-wise weighted mean range shift from all spots served as measure for the accuracy of the respective range prediction approach.\n\n\nRESULTS\nA mean range prediction accuracy of (0.0±0.5)%, (0.3±0.4)%, and (1.8±0.4)% were obtained for DirectSPR, adapted HLUT and standard HLUT, respectively. The overall validation uncertainty of the second-generation PGI slit camera is about 1\xa0mm (2σ) for all approaches, which is smaller than the range prediction uncertainty for deep-seated tumors.\n\n\nCONCLUSION\nFor the first time, range prediction accuracy was assessed in clinical routine using PGI range verification in prostate-cancer treatments. Both DECT-derived range prediction approaches agree well with the measured proton range from PGI verification, while the standard HLUT approach differs relevantly. These results endorse the recent reduction of clinical safety margins in DirectSPR-based treatment planning in our institution.