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

PURPOSE: To quantifiy the range uncertainty in proton treatment planning using dual-energy computed tomography (DECT) for a direct stopping-power prediction (DirectSPR) algorithm 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, modeling as well as others. The respective SPR uncertainty was quantified for lung, soft tissue and bone and translated into range uncertainty for several tumor types. The amount of healthy tissue spared was quantified for 250 patients treated with DirectSPR and the dosimetric impact was evaluated exemplarily 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% + 2 mm) to (1.7% + 2 mm) for brain-tumor and (2.0% + 2 mm) for prostate-cancer patients. The 150 brain-tumor and 100 prostate-cancer patients treated using DirectSPR benefitted from sparing on average 2.6 mm and 4.4 mm of healthy tissue in beam direction, respectively. In the representative patient case, dose reduction in organs at risk close 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. CONCLUSIONS: A substantial increase in range prediction accuracy in clinical proton treatment planning was achieved by patient-specific DECT-based SPR prediction. For the first time, a relevant imaging-based reduction of range prediction uncertainty on a 2% level has been achieved.

Refinement of the Hounsfield look-up table by retrospective application of patient-specific direct proton stopping-power prediction from dual-energy CT.

BACKGROUND AND PURPOSE: Proton treatment planning relies on an accurate determination of stopping-power ratio (SPR) from x-ray computed tomography (CT). A refinement of the heuristic CT-based SPR prediction using a state-of-the-art Hounsfield look-up table (HLUT) is proposed, which incorporates patient SPR information obtained from dual-energy CT (DECT) in a retrospective patient-cohort analysis. MATERIAL AND METHODS: SPR datasets of 25 brain-tumor patients, 25 prostate-cancer patients, and three nonsmall cell lung-cancer (NSCLC) patients were calculated from clinical DECT scans with the comprehensively validated DirectSPR approach. Based on the median frequency distribution of voxelwise correlations between CT number and SPR within the irradiated volume, a piecewise linear function was specified (DirectSPR-based adapted HLUT). Differences in dose distribution and proton range were assessed for the nonadapted and adapted HLUT in comparison to the DirectSPR method, which has been shown to be an accurate and reliable SPR estimation method. RESULTS: The application of the DirectSPR-based adapted HLUT instead of the nonadapted HLUT reduced the systematic proton range differences from 1.2% (1.1 mm) to -0.1% (0.0 mm) for brain-tumor patients, 1.7% (4.1 mm) to 0.2% (0.5 mm) for prostate-cancer patients, and 2.0% (2.9 mm) to -0.1% (0.0 mm) for NSCLC patients. Due to the large intra- and inter-patient tissue variability, range differences to DirectSPR larger than 1% remained for the adapted HLUT. CONCLUSIONS: The incorporation of patient-specific correlations between CT number and SPR, derived from a retrospective application of DirectSPR to a broad patient cohort, improves the SPR accuracy of the current state-of-the-art HLUT approach. The DirectSPR-based adapted HLUT has been clinically implemented at the University Proton Therapy Dresden (Dresden, Germany) in 2017. This already facilitates the benefits of an improved DECT-based tissue differentiation within clinical routine without changing the general approach for range prediction (HLUT), and represents a further step toward full integration of the DECT-based DirectSPR method for treatment planning in proton therapy.

Clinical Implementation of Dual-energy CT for Proton Treatment Planning on Pseudo-monoenergetic CT scans.

PURPOSE: To determine whether a standardized clinical application of dual-energy computed tomography (DECT) for proton treatment planning based on pseudomonoenergetic CT scans (MonoCTs) is feasible and increases the precision of proton therapy in comparison with single-energy CT (SECT). METHODS AND MATERIALS: To define an optimized DECT protocol, CT scan settings were analyzed experimentally concerning beam hardening, image quality, and influence on the heuristic conversion of CT numbers into stopping-power ratios (SPRs) and were compared with SECT scans with identical CT dose. Differences in range prediction and dose distribution between SECT and MonoCT were quantified for phantoms and a patient. RESULTS: Dose distributions planned on SECT and MonoCT datasets revealed mean range deviations of 0.3 mm, γ passing rates (1%, 1 mm) greater than 99.9%, and no clinically relevant changes in dose-volume histograms. However, image noise and CT-related uncertainties could be reduced by MonoCT compared with SECT, which resulted in a slightly decreased dependence of SPR prediction on beam hardening. Consequently, DECT was clinically implemented at the University Proton Therapy Dresden in 2015. Until October 2016, 150 patients were treated based on MonoCTs, and more than 950 DECT scans of 351 patients were acquired during radiation therapy. CONCLUSIONS: A standardized clinical use of MonoCT for treatment planning is feasible, leads to improved image quality and SPR prediction, extends diagnostic variety, and enables a stepwise clinical implementation of DECT toward a physics-based, patient-specific, nonheuristic SPR determination. Further reductions of CT-related uncertainties, as expected from such SPR approaches, can be evaluated on the resulting DECT patient database.

Dosimetry intercomparison of four proton therapy institutions in Germany employing spot scanning.

AIM: To verify the consistency of dose and range measurement in an interinstitution comparison among proton therapy institutions in Germany which use the pencil-beam scanning technique. METHODS: Following a peer-to-peer approach absorbed dose and range have been intercompared in several missions at two hosting centers with two or three visiting physics teams of participating institutions using their own dosimetry equipment. A meta-analysis has been performed integrating the results of the individual missions. Dose has been determined with ionization chambers according to the dosimetry protocol IAEA TRS-398. For determination of the depth of the distal 80% dose the teams used either a scanning water phantom, a variable water column or a multi-layer ionization chamber. RESULTS: The systematic deviation between measured doses of the participating institutions is less than 1%. Ranges differ systematically less than 0.4mm. CONCLUSIONS: The match of measured dose and range is better than expected from the respective uncertainties. As all physics teams agree on the assessment of absorbed dose and range, an important prerequisite for a start of joint clinical studies is fulfilled.