Reduction of clinical safety margins in proton therapy enabled by the clinical implementation of dual-energy CT for direct stopping-power prediction

Purpose: Quantification of range uncertainty in proton treatment planning using dual-energy computed tomography (DECT) for direct stopping-power prediction (DirectSPR) and its clinical implementation.
Methods and materials: To assess the overall uncertainty in stopping-power ratio (SPR) prediction of a DirectSPR implementation calibrated for different patient geometries, the influencing factors were categorized in imaging, modelling as well as others. The respective SPR uncertainty was quantified for lung, soft tissue and bone and translated into range uncertainty for several tumor entities. The uncertainty assessment was experimentally validated in various phantom geometries and compared to the standard look-up-table (HLUT) approach. Finally, the dosimetric effect of the assessed margins was quantified for a representative brain tumor patient.
Results: For bone, soft tissue and lung, an SPR uncertainty (1𝜎) of 1.6%, 1.3% and 1.3% was determined for DirectSPR, respectively. This allowed for a reduction of the clinically applied range uncertainty from currently (3.5%+2mm) to (1.7%+2mm) for brain tumor patients and (2.0%+2mm) for
prostate-cancer patients. In all phantom validation setups, DirectSPR outperformed the HLUT approach, with an accuracy in SPR prediction as high as 0.3% in an anthropomorphic head phantom (0.7% using HLUT). In the representative patient case, a dose reduction in organs at risk close-by to the target volume was achieved, with a mean dose reduction of up to 16% in the brainstem. Patient-specific DECT-based treatment planning with reduced safety margins was successfully introduced into clinical routine at our institute in April 2019. Within the first year, 90 brain-tumor and 60 prostate-cancer patients were treated using DirectSPR.
Conclusions: A substantial reduction of range uncertainty in clinical proton treatment planning was achieved by patient-specific DECT-based SPR prediction. Thereby, for the first time since the initial introduction of range margins in proton therapy in the 1980s, a relevant reduction of range uncertainty on a 2% level was achieved.