Citations

Background/Objectives: Adjuvant radiation for gynecologic malignancies often exposes organs at risk (OARs), such as the bone marrow, bowel, rectum, and bladder, to radiation, leading to toxicities that impact treatment tolerance and patient quality of life. Scanning proton beam therapy, particularly with Individual Field Simultaneous Optimization (IFSO), may offer dosimetric and biological advantages over volumetric modulated arc therapy (VMAT). This study evaluates the clinical impact of IFSO-based proton planning in post-operative gynecologic cancer patients. Materials and Methods: Fourteen patients receiving adjuvant proton therapy to 45 Gy in 25 fractions were retrospectively analyzed. Comparison VMAT plans were generated on the same datasets. Dose–volume metrics for key OARs and normal tissue complication probabilities (NTCPs) were compared using paired statistical tests. Robustness evaluations accounted for setup and range uncertainties. Results: Proton plans significantly reduced dose to bone marrow (V10Gy: 58% vs. 86%, p < 0.00001; V20Gy: 47% vs. 58%, p < 0.00001), small bowel (V20Gy: 21% vs. 56%, p < 0.00001), and femoral heads (left femoral head mean: 11Gy vs. 13Gy, p = 0.032; right femoral head mean: 11Gy vs. 13Gy, p = 0.022). NTCP modeling predicted significantly lower rates of bowel urgency (9.4% vs. 3.3%, p < 0.001) and hematologic toxicity (10.2% vs. 4.9%, p < 0.001) with proton therapy. Plans remained robust across uncertainty scenarios. Conclusions: IFSO-based scanning proton therapy provides clinically meaningful sparing of bone marrow and bowel, with the potential to reduce hematologic and gastrointestinal toxicities. These findings support its use in patients receiving adjuvant pelvic radiotherapy, particularly those undergoing extended field treatment or chemotherapy.

AbstractPurposeThe time structures of proton spot delivery in proton pencil beam scanning (PBS) radiation therapy are essential in many clinical applications. This study aims to characterize the time structures of proton PBS delivered by both synchrotron and synchrocyclotron accelerators using a non‐invasive technique based on scattered particle tracking.MethodsA pixelated semiconductor detector, AdvaPIX‐Timepix3, with a temporal resolution of 1.56 ns, was employed to measure time of arrival of secondary particles generated by a proton beam. The detector was placed laterally to the high‐flux area of the beam in order to allow for single particle detection and not interfere with the treatment. The detector recorded counts of radiation events, their deposited energy and the timestamp associated with the single events. Individual recorded events and their temporal characteristics were used to analyze beam time structures, including energy layer switch time, magnet switch time, spot switch time, and the scanning speeds in the x and y directions. All the measurements were repeated 30 times on three dates, reducing statistical uncertainty.ResultsThe uncertainty of the measured energy layer switch times, magnet switch time, and the spot switch time were all within 1% of average values. The scanning speeds uncertainties were within 1.5% and are more precise than previously reported results. The measurements also revealed continuous sub‐milliseconds proton spills at a low dose rate for the synchrotron accelerator and radiofrequency pulses at 7 µs and 1 ms repetition time for the synchrocyclotron accelerator.ConclusionThe AdvaPIX‐Timepix3 detector can be used to directly measure and monitor time structures on microseconds scale of the PBS proton beam delivery. This method yielded results with high precision and is completely independent of the machine log files.

Abstract Purpose . To enhance an in-house graphic-processing-unit accelerated virtual particle (VP)-based Monte Carlo (MC) proton dose engine (VPMC) to model aperture blocks in both dose calculation and optimization for pencil beam scanning proton therapy (PBSPT)-based stereotactic radiosurgery (SRS). Methods and materials . A module to simulate VPs passing through patient-specific aperture blocks was developed and integrated in VPMC based on simulation results of realistic particles (primary protons and their secondaries). To validate the aperture block module, VPMC was first validated by an opensource MC code, MCsquare, in eight water phantom simulations with 3 cm thick brass apertures: four were with aperture openings of 1, 2, 3, and 4 cm without a range shifter, while the other four were with same aperture opening configurations with a range shifter of 45 mm water equivalent thickness. Then, VPMC was benchmarked with MCsquare and RayStation MC for 10 patients with small targets (average volume 8.4 c.c. with range of 0.4–43.3 c.c.). Finally, 3 typical patients were selected for robust optimization with aperture blocks using VPMC. Results . In the water phantoms, 3D gamma passing rate (2%/2 mm/10%) between VPMC and MCsquare was 99.71 ± 0.23%. In the patient geometries, 3D gamma passing rates (3%/2 mm/10%) between VPMC/MCsquare and RayStation MC were 97.79 ± 2.21%/97.78 ± 1.97%, respectively. Meanwhile, the calculation time was drastically decreased from 112.45 ± 114.08 s (MCsquare) to 8.20 ± 6.42 s (VPMC) with the same statistical uncertainties of ~0.5%. The robustly optimized plans met all the dose–volume-constraints (DVCs) for the targets and OARs per our institutional protocols. The mean calculation time for 13 influence matrices in robust optimization by VPMC was 41.6 s and the subsequent on-the-fly ‘trial-and-error’ optimization procedure took only 71.4 s on average for the selected three patients. Conclusion . VPMC has been successfully enhanced to model aperture blocks in dose calculation and optimization for the PBSPT-based SRS.

AbstractBackgroundAccurate and efficient dose calculation is essential for on‐line adaptive planning in proton therapy. Deep learning (DL) has shown promising dose prediction results in photon therapy. However, there is a scarcity of DL‐based dose prediction methods specifically designed for proton therapy. Successful dose prediction method for proton therapy should account for more challenging dose prediction problems in pencil beam scanning proton therapy (PBSPT) due to its sensitivity to heterogeneities.PurposeTo develop a DL‐based PBSPT dose prediction workflow with high accuracy and balanced complexity to support on‐line adaptive proton therapy clinical decision and subsequent replanning.MethodsPBSPT plans of 103 prostate cancer patients (93 for training and the other 10 for independent testing) and 83 lung cancer patients (73 for training and the other 10 for independent testing) previously treated at our institution were included in the study, each with computed tomography scans (CTs), structure sets, and plan doses calculated by the in‐house developed Monte‐Carlo dose engine (considered as the ground truth in the model training and testing). For the ablation study, we designed three experiments corresponding to the following three methods: (1) Experiment 1, the conventional region of interest (ROI) (composed of targets and organs‐at‐risk [OARs]) method. (2) Experiment 2, the beam mask (generated by raytracing of proton beams) method to improve proton dose prediction. (3) Experiment 3, the sliding window method for the model to focus on local details to further improve proton dose prediction. A fully connected 3D‐Unet was adopted as the backbone. Dose volume histogram (DVH) indices, 3D Gamma passing rates with a criterion of 3%/3 mm/10%, and dice coefficients for the structures enclosed by the iso‐dose lines between the predicted and the ground truth doses were used as the evaluation metrics. The calculation time for each proton dose prediction was recorded to evaluate the method's efficiency.ResultsCompared to the conventional ROI method, the beam mask method improved the agreement of DVH indices for both targets and OARs and the sliding window method further improved the agreement of the DVH indices (for lung cancer, CTV D98 absolute deviation: 0.74 ± 0.18 vs. 0.57 ± 0.21 vs. 0.54 ± 0.15 Gy[RBE], ROI vs. beam mask vs. sliding window methods, respectively). For the 3D Gamma passing rates in the target, OARs, and BODY (outside target and OARs), the beam mask method improved the passing rates in these regions and the sliding window method further improved them (for prostate cancer, targets: 96.93% ± 0.53% vs. 98.88% ± 0.49% vs. 99.97% ± 0.07%, BODY: 86.88% ± 0.74% vs. 93.21% ± 0.56% vs. 95.17% ± 0.59%). A similar trend was also observed for the dice coefficients. This trend was especially remarkable for relatively low prescription isodose lines (for lung cancer, 10% isodose line dice: 0.871 ± 0.027 vs. 0.911 ± 0.023 vs. 0.927 ± 0.017). The dose predictions for all the testing cases were completed within 0.25 s.ConclusionsAn accurate and efficient deep learning‐augmented proton dose prediction framework has been developed for PBSPT, which can predict accurate dose distributions not only inside but also outside ROI efficiently. The framework can potentially further reduce the initial planning and adaptive replanning workload in PBSPT.

AbstractBackgroundMechanical accuracy should be verified before implementing a proton stereotactic radiosurgery (SRS) program. Linear accelerator (Linac)‐based SRS systems often use electronic portal imaging devices (EPIDs) to verify beam isocentricity. Because proton therapy systems do not have EPID, beam isocentricity tests of proton SRS may still rely on films, which are not efficient.PurposeTo validate that our proton SRS system meets mechanical precision requirements and to present an efficient method to evaluate the couch and gantry's rotational isocentricity for our proton SRS system.MethodsA dedicated applicator to hold brass aperture for proton SRS system was designed. The mechanical precision of the system was tested using a metal ball and film for 11 combinations of gantry and couch angles. A more efficient quality assurance (QA) procedure was developed, which used a scintillator device to replace the film. The couch rotational isocentricity tests were performed using orthogonal kV x‐rays with the couch rotated isocentrically to five positions (0°, 315°, 270°, 225°, and 180°). At each couch position, the distance between the metal ball in kV images and the imaging isocenter was measured. The gantry isocentricity tests were performed using a cone‐shaped scintillator and proton beams at five gantry angles (0°, 45°, 90°, 135°, and 180°), and the isocenter position and the distance of each beam path to the isocenter were obtained. Daily QA procedure was performed for 1 month to test the robustness and reproducibility of the procedure.ResultsThe gantry and couch rotational isocentricity exhibited sub‐mm precision, with most measurements within ±0.5 mm. The 1‐month QA results showed that the procedure was robust and highly reproducible to within ±0.2 mm. The gantry isocentricity test using the cone‐shaped scintillator was accurate and sensitive to variations of ±0.2 mm. The QA procedure was efficient enough to be completed within 30 min. The 1‐month isocentricity position variations were within 0.5 mm, which demonstrating that the overall proton SRS system was stable and precise.ConclusionThe proton SRS Winston–Lutz QA procedure using a cone‐shaped scintillator was efficient and robust. We were able to verify radiation delivery could be performed with sub‐mm mechanical precision.

AbstractBackgroundParallel‐opposed lateral beams are the conventional beam arrangements in proton therapy for prostate cancer. However, when considering linear energy transfer (LET) and RBE effects, alternative beam arrangements should be investigated.PurposeTo investigate the dose and dose averaged LET (LETd) impact of using new beam arrangements rotating beams 5°–15° posteriorly to the laterals in prostate cancer treated with pencil‐beam‐scanning (PBS) proton therapy.MethodsTwenty patients with localized prostate cancer were included in this study. Four proton treatment plans for each patient were generated utilizing 0°, 5°, 10°, and 15° posterior oblique beam pairs relative to parallel‐opposed lateral beams. Dose‐volume histograms (DVHs) from posterior oblique beams were analyzed. Dose‐LETd‐volume histogram (DLVH) was employed to study the difference in dose and LETd with each beam arrangement. DLVH indices, , defined as the cumulative absolute volume that has a dose of at least d (Gy[RBE]) and a LETd of at least l (keV/µm), were calculated for both the rectum and bladder to the whole group of patients and two‐sub groups with and without hydrogel spacer. These metrics were tested using Wilcoxon signed‐rank test.ResultsRotating beam angles from laterals to slightly posterior by 5°–15° reduced high LETd volumes while it increased the dose volume in the rectum and increased LETd in bladders. Beam angles rotated five degrees posteriorly from laterals (i.e., gantry in 95° and 265°) are proposed since they achieved the optimal balance of better LETd sparing and minimal dose increase in the rectum. A reduction of V(50 Gy[RBE], 2.6 keV/µm) from 7.41 to 3.96 cc (p < 0.01), and a slight increase of V(50 Gy[RBE], 0 keV/µm) from 20.1 to 21.6 cc (p < 0.01) were observed for the group without hydrogel spacer. The LETd sparing was less effective for the group with hydrogel spacer, which achieved the reduction of V(50 Gy[RBE], 2.6 keV/µm) from 4.28 to 2.10 cc (p < 0.01).ConclusionsPosterior oblique angle plans improved LETd sparing of the rectum while sacrificing LETd sparing in the bladder in the treatment of prostate cancer with PBS. Beam angle modification from laterals to slightly posterior may be a strategy to redistribute LETd and perhaps reduce rectal toxicity risks in prostate cancer patients treated with PBS. However, the effect is reduced for patients with hydrogel spacer.

AbstractBackgroundIn proton therapy dose calculation, Monte Carlo (MC) simulations are superior in accuracy but more time consuming, compared to analytical calculations. Graphic processing units (GPUs) are effective in accelerating MC simulations but may suffer thread divergence and racing condition in GPU threads that degrades the computing performance due to the generation of secondary particles during nuclear reactions.PurposeA novel concept of virtual particle (VP) MC (VPMC) is proposed to avoid simulating secondary particles in GPU‐accelerated proton MC dose calculation and take full advantage of the computing power of GPU.MethodsNeutrons and gamma rays were ignored as escaping from the human body; doses of electrons, heavy ions, and nuclear fragments were locally deposited; the tracks of deuterons were converted into tracks of protons. These particles, together with primary and secondary protons, are considered to be the realistic particles. Histories of primary and secondary protons were replaced by histories of multiple VPs. Each VP corresponded to one proton (either primary or secondary). A continuous‐slowing‐down‐approximation model, an ionization model, and a large angle scattering event model corresponding to nuclear interactions were developed for VPs by generating probability distribution functions (PDFs) based on simulation results of realistic particles using MCsquare. For efficient calculations, these PDFs were stored in the Compute Unified Device Architecture textures. VPMC was benchmarked with TOPAS and MCsquare in phantoms and with MCsquare in 13 representative patient geometries. Comparisons between the VPMC calculated dose and dose measured in water during patient‐specific quality assurance (PSQA) of the selected 13 patients were also carried out. Gamma analysis was used to compare the doses derived from different methods and calculation efficiencies were also compared.ResultsIntegrated depth dose and lateral dose profiles in both homogeneous and inhomogeneous phantoms all matched well among VPMC, TOPAS, and MCsquare calculations. The 3D–3D gamma passing rates with a criterion of 2%/2 mm and a threshold of 10% was 98.49% between MCsquare and TOPAS and 98.31% between VPMC and TOPAS in homogeneous phantoms, and 99.18% between MCsquare and TOPAS and 98.49% between VPMC and TOPAS in inhomogeneous phantoms, respectively. In patient geometries, the 3D–3D gamma passing rates with 2%/2 mm/10% between dose distributions from VPMC and MCsquare were 98.56 ± 1.09% in patient geometries. The 2D–3D gamma analysis with 3%/2 mm/10% between the VPMC calculated dose distributions and the 2D measured planar dose distributions during PSQA was 98.91 ± 0.88%. VPMC calculation was highly efficient and took 2.84 ± 2.44 s to finish for the selected 13 patients running on four NVIDIA Ampere GPUs in patient geometries.ConclusionVPMC was found to achieve high accuracy and efficiency in proton therapy dose calculation.

Abstract Objective. To investigate synchrotron-based proton pencil beam scanning (PBS) beam delivery time (BDT) using novel continuous scanning mode. Approach. A BDT calculation model was developed for the Hitachi particle therapy system. The model was validated against the measured BDT of 36 representative clinical proton PBS plans with discrete spot scanning (DSS) in the current Hitachi proton therapy system. BDTs were calculated with the next generation using Mayo Clinic Florida system operating parameters for conventional DSS, and novel dose driven continuous scanning (DDCS). BDTs of DDCS with and without Break Spots were investigated. Main results. For DDCS without Break Spots, the use of Stop Ratio to control the transit dose largely reduced the beam intensity and consequently, severely prolonged the BDT. DDCS with Break Spots was able to maintain a sufficiently high beam intensity while controlling transit dose. In DDCS with Break Spots, tradeoffs were made between beam intensity and number of Break Spots. Therefore, BDT decreased with increased beam intensity but reached a plateau for beam intensity larger than 10 MU s −1 . Averaging over all clinical plans, BDT was reduced by 10% for DDCS with Break Spots compared to DSS. Significance. DDCS with Break Spots reduced BDT. DDCS has the potential to further reduce BDT under the ideal scenario which requests both stable beam intensity extraction and accurately modelling the transit dose. Further investigation is warranted.

AbstractBackgroundBoth dose and linear energy transfer (LET) could play a substantial role in adverse event (AE) initialization of cancer patients treated with pencil‐beam‐scanning (PBS) proton therapy. However, not all the voxels within the AE regions are directly induced from the dose and LET effect. It is important to study the synergistic effect of dose and LET in AE initialization by only including a subset of voxels that are dosimetrically important.PurposeTo perform exploratory investigation of the dose and LET effects upon AE initialization in PBS using seed spots analysis.MethodsA total of 113 head‐and‐neck (H&N) cancer patients receiving curative PBS were included. Among them, 20 patients experienced unanticipated CTCAEv4.0 grade ≥3 AEs (AE group) and 93 patients did not (control group). Within the AE group, 13 AE patients were included in the seed spot analysis to derive the descriptive features of AE initialization and the remaining 7 mandible osteoradionecrosis patients and 93 control patients were used to derive the feature‐based volume constraint of mandible osteoradionecrosis. The AE regions were contoured and the corresponding dose–LET volume histograms of AE regions were generated for all patients in the AE group. We selected high LET voxels (the highest 5% of each dose bin) with a range of moderate‐to‐high dose (≥∼40‐Gy relative biological effectiveness) as critical voxels. Critical voxels that were contiguous with each other were grouped into clusters. Each cluster was considered a potential independent seed spot for AE initialization. Seed spots were displayed in a 2D dose–LET plane based on their mean dose and LET to derive the descriptive features of AE initialization. A volume constraint of mandible osteoradionecrosis was then established based on the extracted features using a receiver operating characteristic curve.ResultsThe product of dose and LET (xBD) was found to be a descriptive feature of seed spots leading to AE initialization in this preliminary study. The derived xBD volume constraint for mandible osteoradionecrosis showed good performance with an area under curve of 0.87 (sensitivity of 0.714 and specificity of 0.807 in the leave‐one‐out cross‐validation) for the very limited patient data included in this study.ConclusionOur exploratory study showed that both dose and LET were observed to be important in AE initializations. The derived xBD volume constraint could predict mandible osteoradionecrosis reasonably well in the very limited H&N cancer patient data treated with PBS included in this study.

AbstractPurposeTo develop an online graphic processing unit (GPU)‐accelerated Monte Carlo‐based adaptive radiation therapy (ART) workflow for pencil beam scanning (PBS) proton therapy to address interfraction anatomical changes in patients treated with PBS.Methods and MaterialsA four‐step workflow was developed using our in‐house developed GPU‐accelerated Monte Carlo‐based treatment planning system to implement online Monte Carlo‐based ART for PBS. The first step conducts diffeomorphic demon‐based deformable image registration (DIR) to propagate contours on the initial planning CT (pCT) to the verification CT (vCT) to form a new structure set. The second step performs forward dose calculation of the initial plan on the vCT with the propagated contours after manual approval (possible modifications involved). The third step triggers a reoptimization of the plan depending on whether the verification dose meets the clinical requirements or not. A robust evaluation will be done for both the verification plan in the second step and the reopotimized plan in the third step. The fourth step involves a two‐stage (before and after delivery) patient‐specific quality assurance (PSQA) of the reoptimized plan. The before‐delivery PSQA is to compare the plan dose to the dose calculated using an independent fast open‐source Monte Carlo code, MCsquare. The after‐delivery PSQA is to compare the plan dose to the dose recalculated using the log file (spot MU, spot position, and spot energy) collected during the delivery. Jaccard index (JI), dice similarity coefficients (DSCs), and Hausdorff distance (HD) were used to assess the quality of the propagated contours in the first step. A commercial plan evaluation software, ClearCheck™, was integrated into the workflow to carry out efficient plan evaluation. 3D Gamma analysis was used during the fourth step to ensure the accuracy of the plan dose from reoptimization. Three patients with three different disease sites were chosen to evaluate the feasibility of the online ART workflow for PBS.ResultsFor all three patients, the propagated contours were found to have good volume conformance [JI (lowest‐highest: 0.833–0.983) and DSC (0.909–0.992)] but suboptimal boundary coincidence [HD (2.37–20.76 mm)] for organs‐at‐risk. The verification dose evaluated by ClearCheck™ showed significant degradation of the target coverage due to the interfractional anatomical changes. Reoptimization on the vCT resulted in great improvement of the plan quality to a clinically acceptable level. 3D Gamma analyses of PSQA confirmed the accuracy of the plan dose before delivery (mean Gamma index = 98.74% with a threshold of 2%/2 mm/10%), and after delivery based on the log files (mean Gamma index = 99.05% with a threshold of 2%/2 mm/10%). The average time cost for the complete execution of the workflow was around 858 s, excluding the time for manual intervention.ConclusionThe proposed online ART workflow for PBS was demonstrated to be efficient and effective by generating a reoptimized plan that significantly improved the plan quality.