Shen, Jiajian

Background/Objectives: Proton therapy delivers highly conformal doses to the target area without producing an exit dose, minimizing cumulative doses to healthy liver tissue. This study aims to evaluate current practices, challenges, and variations in the implementation of proton stereotactic body radiation therapy (SBRT) and hypofractionated therapy for liver malignancies, with the goal of providing a technical assessment to promote broader adoption and support future clinical trials. Methods and Materials: An extensive survey was conducted by NRG Oncology across North American proton treatment centers to assess the current practices of proton liver SBRT and hypofractionated therapy. The survey focused on key aspects, including patient selection, prescription and normal tissue constraints, simulation and motion management, treatment planning, quality assurance (QA), treatment delivery, and the use of image-guided radiation therapy (IGRT). Results: This survey captures the current practice patterns and status of proton SBRT and hypofractionated therapy in liver cancer treatment. Proton therapy is increasingly preferred for treating inoperable liver malignancies due to its ability to minimize healthy tissue exposure. However, the precision required for proton therapy presents challenges, particularly in managing uncertainties and target motion during high-dose fractions and short treatment courses. Survey findings revealed significant variability in clinical practices across centers, highlighting differences in motion management, dose fractionation schedules, and QA protocols. Conclusion: Proton SBRT and hypofractionated therapy offer significant potential for treating liver malignancies. A comprehensive approach involving precise patient selection, treatment planning, and QA is essential for ensuring safety and effectiveness. This survey provides valuable insights into current practices and challenges, offering a foundation for technical recommendations to optimize the use of proton therapy and guide future clinical trials.

AbstractObjectiveThe aim of this study was to evaluate the feasibility and plan quality of spot‐scanning proton arc therapy (SPArc) using a synchrotron‐accelerator‐based proton therapy system compared to intensity‐modulated proton therapy (IMPT).ApproachFive representative disease sites, including head and neck, lung, liver, brain chordoma, and prostate cancers, were retrospectively selected. Both IMPT and SPArc plans are generated with the HITACHI ProBEAT PBS system's minimum MU constraints and physics beam model. The SPArc plans are generated with 2.5° sampling frequency. The static delivery time was simulated based on the previously published synchrotron delivery sequence model, and the dynamic delivery time was simulated using a proton arc gantry mechanical model integrated with the synchrotron delivery sequence. Both dosimetric plan quality and delivery efficiency are evaluated.Main resultsA superior plan quality is reached compared with the IMPT plans generated for the same disease site. However, a relatively prolonged static and dynamic delivery time post new challenge, as static time increased by 49.22% and dynamic time 59.10% on average.SignificanceThis study presents the first simulation results of delivering the SPArc plans using a synchrotron‐accelerated proton therapy system. The result shows its feasibility and limitations, which could guide future development.

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 Background Rescanning is a common technique used in proton pencil beam scanning to mitigate the interplay effect. Advances in machine operating parameters across different generations of particle therapy systems have led to improvements in beam delivery time (BDT). However, the potential impact of these improvements on the effectiveness of rescanning remains an underexplored area in the existing research. Methods We systematically investigated the impact of proton machine operating parameters on the effectiveness of layer rescanning in mitigating interplay effect during lung SBRT treatment, using the CIRS phantom. Focused on the Hitachi synchrotron particle therapy system, we explored machine operating parameters from our institution's current (2015) and upcoming systems (2025A and 2025B). Accumulated dynamic 4D dose were reconstructed to assess the interplay effect and layer rescanning effectiveness. Results Achieving target coverage and dose homogeneity within 2% deviation required 6, 6, and 20 times layer rescanning for the 2015, 2025A, and 2025B machine parameters, respectively. Beyond this point, further increasing the number of layer rescanning did not further improve the dose distribution. BDTs without rescanning were 50.4, 24.4, and 11.4 s for 2015, 2025A, and 2025B, respectively. However, after incorporating proper number of layer rescanning (six for 2015 and 2025A, 20 for 2025B), BDTs increased to 67.0, 39.6, and 42.3 s for 2015, 2025A, and 2025B machine parameters. Our data also demonstrated the potential problem of false negative and false positive if the randomness of the respiratory phase at which the beam is initiated is not considered in the evaluation of interplay effect. Conclusion The effectiveness of layer rescanning for mitigating interplay effect is affected by machine operating parameters. Therefore, past clinical experiences may not be applicable to modern machines.

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.

Abstract Objective . To investigate the impact of scan path optimization on the dose accuracy and beam delivery time (BDT) of proton pencil beam scanning in the dose-driven continuous scanning (DDCS). Approach . A diverse set of six clinical plans, representing various spot patterns and treatment sites, was used to evaluate the effectiveness of scan time optimization and scan length optimization. The DDCS dose discrepancy and BDT with optimized scan paths was compared to the default serpentine scan path. Main results . Both scan time optimization and scan path optimization were able to reduce the DDCS dose discrepancy compared to the default serpentine scan path. All plans, except for the layer repainting lung plan, achieved a 2%/2 mm gamma pass rate of over 99% and less than 1% PTV DVH root mean square error (RMSE) through scan path optimization. In the case of the layer repainting lung plan, when compared to the default serpentine scan path, the 2%/2 mm gamma pass rate showed improvements from 91.3% to 93.1% and 95.8%, while the PTV DVH RMSE decreased from 2.1% to 1.7% and 1.1% for scan time optimization and scan length optimization, respectively. Although scan time optimization resulted in shorter total scan times for all plans compared to the default scan path and scan length optimization tended to have longer total scan times. However, due to the short total scan times and their minimal contribution to the total BDT, the impact of scan path optimization on the total BDT was practically negligible. Significance . Both scan time optimization and scan length optimization proved to be effective in minimizing DDCS dose discrepancy. No definitive winner can be determined between these two optimization approaches. Both scan time and scan length optimization had minimal effect on the total BDT.

AbstractBackgroundDiscrete spot scanning (DSS) is the commonly used method for proton pencil beam scanning (PBS). There is lack of data on the dose‐driven continuous scanning (DDCS).PurposeTo investigate delivery benefits and dosimetric implications of DDCS versus DSS for PBS systems.MethodsThe irradiation duty factor, beam delivery time (BDT), and dose deviation were simulated for eight treatment plans in prostate, head and neck, liver, and lung, with both conventional fractionation and hypofractionation schemes. DDCS results were compared with those of DSS.ResultsThe DDCS irradiation duty factor (range, 11%–41%) was appreciably improved compared to DSS delivery (range, 4%–14%), within which, hypofractionation schemes had greater improvement than conventional fractionation. With decreasing stop ratio constraints, the DDCS BDT reduction was greater, but dose deviation also increased. With stop ratio constraints of 2, 1, 0.5, and 0, DDCS BDT reduction reached to 6%, 10%, 12%, and 15%, respectively, and dose deviation reached to 0.6%, 1.7%, 3.0%, and 5.2% root mean square error in PTV DVH, respectively. The 3%/2‐mm gamma passing rate was greater than 99% with stop ratio constraints of 2 and 1, and greater than 95% with a stop ratio of 0.5. When the stop ratio constraint was removed, five of the eight treatment plans had a 3%/2‐mm gamma passing rate greater than 95%, and the other three plans had a 3%/2‐mm gamma passing rate between 90% and 95%.ConclusionsThe irradiation duty factor was considerably improved with DDCS. Smaller stop ratio constraints led to shorter BDTs, but with the cost of larger dose deviations. Our finding suggested that a stop ratio of 1 constraint seems to yield acceptable DDCS dose deviation.

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.