Effect of the initial energy layer and spot placement parameters on IMPT delivery efficiency and plan quality.

PURPOSE: Improving efficiency of intensity modulated proton therapy (IMPT) treatment can be achieved by shortening the beam delivery time. The purpose of this study is to reduce the delivery time of IMPT, while maintaining the plan quality, by finding the optimal initial proton spot placement parameters. METHODS: Seven patients previously treated in the thorax and abdomen with gated IMPT and voluntary breath-hold were included. In the clinical plans, the energy layer spacing (ELS) and spot spacing (SS) were set to 0.6-0.8 (as a scale factor of the default values). For each clinical plan, we created four plans with ELS increased to 1.0, 1.2, 1.4, and SS to 1.0 while keeping all other parameters unchanged. All 35 plans (130 fields) were delivered on a clinical proton machine and the beam delivery time was recorded for each field. RESULTS: Increasing ELS and SS did not cause target coverage reduction. Increasing ELS had no effect on critical organ-at-risk (OAR) doses or the integral dose, while increasing SS resulted in slightly higher integral and selected OAR doses. Beam-on times were 48.4 ± 9.2 (range: 34.1-66.7) seconds for the clinical plans. Time reductions were 9.2 ± 3.3 s (18.7 ± 5.8%), 11.6 ± 3.5 s (23.1 ± 5.9%), and 14.7 ± 3.9 s (28.9 ± 6.1%) when ELS was changed to 1.0, 1.2, and 1.4, respectively, corresponding to 0.76-0.80 s/layer. SS change had a minimal effect (1.1 ± 1.6 s, or 1.9 ± 2.9%) on the beam-on time. CONCLUSION: Increasing the energy layers spacing can reduce the beam delivery time effectively without compromising IMPT plan quality; increasing the SS had no meaningful impact on beam delivery time and resulted in plan-quality degradation in some cases.

Variability in commercially available deformable image registration: A multi-institution analysis using virtual head and neck phantoms.

PURPOSE: The purpose of this study was to evaluate the performance of three common deformable image registration (DIR) packages across algorithms and institutions. METHODS AND MATERIALS: The Deformable Image Registration Evaluation Project (DIREP) provides ten virtual phantoms derived from computed tomography (CT) datasets of head-and-neck cancer patients over a single treatment course. Using the DIREP phantoms, DIR results from 35 institutions were submitted using either Velocity, MIM, or Eclipse. Submitted deformation vector fields (DVFs) were compared to ground-truth DVFs to calculate target registration error (TRE) for six regions of interest (ROIs). Statistical analysis was performed to determine the variability between each DIR software package and the variability of users within each algorithm. RESULTS: Overall mean TRE was 2.04 ± 0.35 mm for Velocity, 1.10 ± 0.29 mm for MIM, and 2.35 ± 0.15 mm for Eclipse. The MIM mean TRE was significantly different than both Velocity and Eclipse for all ROIs. Velocity and Eclipse mean TREs were not significantly different except for when evaluating the registration of the cord or mandible. Significant differences between institutions were found for the MIM and Velocity platforms. However, these differences could be explained by variations in Velocity DIR parameters and MIM software versions. CONCLUSIONS: Average TRE was shown to be <3 mm for all three software platforms. However, maximum errors could be larger than 2 cm indicating that care should be exercised when using DIR. While MIM performed statistically better than the other packages, all evaluated algorithms had an average TRE better than the largest voxel dimension. For the phantoms studied here, significant differences between algorithm users were minimal suggesting that the algorithm used may have more impact on DIR accuracy than the particular registration technique employed. A significant difference in TRE was discovered between MIM versions showing that DIR QA should be performed after software upgrades as recommended by TG-132.

Comparison of multi-institutional Varian ProBeam pencil beam scanning proton beam commissioning data.

PURPOSE: Commissioning beam data for proton spot scanning beams are compared for the first two Varian ProBeam sites in the United States, at the Maryland Proton Treatment Center (MPTC) and Scripps Proton Therapy Center (SPTC). In addition, the extent to which beams can be matched between gantry rooms at MPTC is investigated. METHOD: Beam data for the two sites were acquired with independent dosimetry systems and compared. Integrated depth dose curves (IDDs) were acquired with Bragg peak ion chambers in a 3D water tank for pencil beams at both sites. Spot profiles were acquired at different distances from the isocenter at a gantry angle of 0° as well as a function of gantry angles. Absolute dose calibration was compared between SPTC and the gantries at MPTC. Dosimetric verification of test plans, output as a function of gantry angle, monitor unit (MU) linearity, end effects, dose rate dependence, and plan reproducibility were compared for different gantries at MPTC. RESULTS: The IDDs for the two sites were similar, except in the plateau region, where the SPTC data were on average 4.5% higher for lower energies. This increase in the plateau region decreased as energy increased, with no marked difference for energies higher than 180 MeV. Range in water coincided for all energies within 0.5 mm. The sigmas of the spot profiles in air were within 10% agreement at isocenter. This difference increased as detector distance from the isocenter increased. Absolute doses for the gantries measured at both sites were within 1% agreement. Test plans, output as function of gantry angle, MU linearity, end effects, dose rate dependence, and plan reproducibility were all within tolerances given by TG142. CONCLUSION: Beam data for the two sites and between different gantry rooms were well matched.

Benchmarking of five commercial deformable image registration algorithms for head and neck patients.

Benchmarking is a process in which standardized tests are used to assess system performance. The data produced in the process are important for comparative purposes, particularly when considering the implementation and quality assurance of DIR algorithms. In this work, five commercial DIR algorithms (MIM, Velocity, RayStation, Pinnacle, and Eclipse) were benchmarked using a set of 10 virtual phantoms. The phantoms were previously developed based on CT data collected from real head and neck patients. Each phantom includes a start of treatment CT dataset, an end of treatment CT dataset, and the ground-truth deformation vector field (DVF) which links them together. These virtual phantoms were imported into the commercial systems and registered through a deformable process. The resulting DVFs were compared to the ground-truth DVF to determine the target registration error (TRE) at every voxel within the image set. Real treatment plans were also recalculated on each end of treatment CT dataset and the dose transferred according to both the ground-truth and test DVFs. Dosimetric changes were assessed, and TRE was correlated with changes in the DVH of individual structures. In the first part of the study, results show mean TRE on the order of 0.5 mm to 3 mm for all phan-toms and ROIs. In certain instances, however, misregistrations were encountered which produced mean and max errors up to 6.8 mm and 22 mm, respectively. In the second part of the study, dosimetric error was found to be strongly correlated with TRE in the brainstem, but weakly correlated with TRE in the spinal cord. Several interesting cases were assessed which highlight the interplay between the direction and magnitude of TRE and the dose distribution, including the slope of dosimetric gradients and the distance to critical structures. This information can be used to help clinicians better implement and test their algorithms, and also understand the strengths and weaknesses of a dose adaptive approach.

Dosimetric Evaluation and Reproducibility of Breath-hold Plans in Intensity Modulated Proton Therapy: An Initial Clinical Experience.

Purpose: Breath-hold (BH) technique can mitigate target motion, minimize target margins, reduce normal tissue doses, and lower the effect of interplay effects with intensity-modulated proton therapy (IMPT). This study presents dosimetric comparisons between BH and nonbreath-hold (non-BH) IMPT plans and investigates the reproducibility of BH plans using frequent quality assurance (QA) computed tomography scans (CT). Methods and Materials: Data from 77 consecutive patients with liver (n = 32), mediastinal/lung (n = 21), nonliver upper abdomen (n = 20), and malignancies in the gastroesophageal junction (n = 4), that were treated with a BH spirometry system (SDX) were evaluated. All patients underwent both BH CT and 4-dimensional CT simulations. Clinically acceptable BH and non-BH plans were generated on each scan, and dose-volume histograms of the 2 plans were compared. Reproducibility of the BH plans for 30 consecutive patients was assessed using 1 to 3 QA CTs per patient and variations in dose-volume histograms for deformed target and organs at risk (OARs) volumes were compared with the initial CT plan. Results: Use of BH scans reduced initial and boost target volumes to 72% ± 20% and 70% ± 17% of non-BH volumes, respectively. Additionally, mean dose to liver, stomach, kidney, esophagus, heart, and lung V20 were each reduced to 71% to 79% with the BH technique. Similarly, small and large bowels, heart, and spinal cord maximum doses were each lowered to 68% to 84%. Analysis of 62 QA CT scans demonstrated that mean target and OAR doses using BH scans were reproducible to within 5% of their nominal plan values. Conclusions: The BH technique reduces the irradiated volume, leading to clinically significant reductions in OAR doses. By mitigating tumor motion, the BH technique leads to reproducible target coverage and OAR doses. Its use can reduce motion-related uncertainties that are normally associated with the treatment of thoracic and abdominal tumors and, therefore, optimize IMPT delivery.

A comparison of the dosimetric effects of intrafraction motion on step-and-shoot, compensator, and helical tomotherapy-based IMRT.

Intrafraction motion during intensity-modulated radiation therapy can cause differences between the planned and delivered patient dose. The magnitude of these differences is dependent on a number of variables, including the treatment modality. This study was designed to compare the relative susceptibility of plans generated with three different treatment modalities to intrafraction motion. The dosimetric effects of motion were calculated using computational algorithms for seven lung tumor patients. Three delivery techniques - MLC-based step-and-shoot (SNS), beam attenuating compensators, and helical tomotherapy (HT) - were investigated. In total 840 motion-encoded dose-volume histograms (DVHs) were calculated for various combinations of CTV margins and sinusoidal CTV motion including CTV offsets. DVH-based metrics (e.g., D95% and D05%) were used to score plan degradations. For all three modalities, dosimetric degradations were typically smaller than 3% if the CTV displacement was smaller than the CTV margin. For larger displacements, technique and direction-specific sensitivities existed. While the HT plans show similar D95% degradations for motion in the SI and AP directions, SNS and compensator plans showed larger D95% degradations for motion in the SI direction than for motion in the AP direction. When averaged over all motion/margin combinations, compensator plans resulted in 0.9% and 0.6% smaller D95% reductions compared to SNS and HT plans, respectively. These differences were statistically significant. No statistically significant differences in D95% degradations were found between SNS and HT for data averaged over all margin and motion track combinations. For CTV motion that is larger than the CTV margin, the dosimetric impact on the CTV varies with treatment technique and the motion direction. For the cases presented here, the effect of motion on CTV dosimetry was statistically smaller for compensator deliveries than SNS and HT, likely due to the absence of the interplay effect which is present for the more dynamic treatment deliveries. The differences between modalities were, however, small and might not be clinically significant. As expected, margins that envelop the CTV motion provide dosimetric protection against motion for all three modalities.

Characterization of 250 MeV Protons from the Varian ProBeam PBS System for FLASH Radiation Therapy.

Shoot-through proton FLASH radiation therapy has been proposed where the highest energy is extracted from a cyclotron to maximize the dose rate (DR). Although our proton pencil beam scanning system can deliver 250 MeV (the highest energy), this energy is not used clinically, and as such, 250 MeV has yet to be characterized during clinical commissioning. We aim to characterize the 250-MeV proton beam from the Varian ProBeam system for FLASH and assess the usability of the clinical monitoring ionization chamber (MIC) for FLASH use. We measured the following data for beam commissioning: integral depth dose curve, spot sigma, and absolute dose. To evaluate the MIC, we measured output as a function of beam current. To characterize a 250 MeV FLASH beam, we measured (1) the central axis DR as a function of current and spot spacing and arrangement, (2) for a fixed spot spacing, the maximum field size that achieves FLASH DR (ie, > 40 Gy/s), and (3) DR reproducibility. All FLASH DR measurements were performed using an ion chamber for the absolute dose, and irradiation times were obtained from log files. We verified dose measurements using EBT-XD films and irradiation times using a fast, pixelated spectral detector. R90 and R80 from integral depth dose were 37.58 and 37.69 cm, and spot sigma at the isocenter were σx = 3.336 and σy = 3.332 mm, respectively. The absolute dose output was measured as 0.343 Gy*mm2/MU for the commissioning conditions. Output was stable for beam currents up to 15 nA and gradually increased to 12-fold for 115 nA. Dose and DR depended on beam current, spot spacing, and arrangement and could be reproduced with 6.4% and 4.2% variations, respectively. Although FLASH was achieved and the largest field size that delivers FLASH DR was determined as 35 × 35 mm2, the current MIC has DR dependence, and users should measure dose and DR independently each time for their FLASH applications.

Quality assurance for image-guided radiation therapy utilizing CT-based technologies: a report of the AAPM TG-179.

PURPOSE: Commercial CT-based image-guided radiotherapy (IGRT) systems allow widespread management of geometric variations in patient setup and internal organ motion. This document provides consensus recommendations for quality assurance protocols that ensure patient safety and patient treatment fidelity for such systems. METHODS: The AAPM TG-179 reviews clinical implementation and quality assurance aspects for commercially available CT-based IGRT, each with their unique capabilities and underlying physics. The systems described are kilovolt and megavolt cone-beam CT, fan-beam MVCT, and CT-on-rails. A summary of the literature describing current clinical usage is also provided. RESULTS: This report proposes a generic quality assurance program for CT-based IGRT systems in an effort to provide a vendor-independent program for clinical users. Published data from long-term, repeated quality control tests form the basis of the proposed test frequencies and tolerances. CONCLUSION: A program for quality control of CT-based image-guidance systems has been produced, with focus on geometry, image quality, image dose, system operation, and safety. Agreement and clarification with respect to reports from the AAPM TG-101, TG-104, TG-142, and TG-148 has been addressed.

Intensity Modulated Proton Therapy Treatment Planning for Postmastectomy Patients with Metallic Port Tissue Expanders.

PURPOSE: Proton beam therapy can significantly reduce cardiopulmonary radiation exposure compared with photon-based techniques in the postmastectomy setting for locally advanced breast cancer. For patients with metallic port tissue expanders, which are commonly placed in patients undergoing a staged breast reconstruction, dose uncertainties introduced by the high-density material pose challenges for proton therapy. In this report, we describe an intensity modulated proton therapy planning technique for port avoidance through a hybrid single-field optimization/multifield optimization approach. METHODS AND MATERIALS: In this planning technique, 3 beams are utilized. For each beam, no proton spot is placed within or distal to the metal port plus a 5 mm margin. Therefore, precise modeling of the metal port is not required, and various tissue expander manufacturers/models are eligible. The blocked area of 1 beam is dosimetrically covered by 1 or 2 of the remaining beams. Multifield optimization is used in the chest wall target region with blockage of any beam, while single-field optimization is used for remainder of chest wall superior/inferior to the port. RESULTS: Using this technique, clinical plans were created for 6 patients. Satisfactory plans were achieved in the 5 patients with port-to-posterior chest wall separations of 1.5 cm or greater, but not in the sixth patient with a 0.7 cm separation. CONCLUSIONS: We described a planning technique and the results suggest that the metallic port-to-chest wall distance may be a key parameter for optimal plan design.

Simultaneous dose and dose rate optimization (SDDRO) of the FLASH effect for pencil-beam-scanning proton therapy.

PURPOSE: Compared to CONV-RT (with conventional dose rate), FLASH-RT (with ultra-high dose rate) can provide biological dose sparing for organs-at-risk (OARs) via the so-called FLASH effect, in addition to physical dose sparing. However, the FLASH effect only occurs, when both dose and dose rate meet certain minimum thresholds. This work will develop a simultaneous dose and dose rate optimization (SDDRO) method accounting for both FLASH dose and dose rate constraints during treatment planning for pencil-beam-scanning proton therapy. METHODS: SDDRO optimizes the FLASH effect (specific to FLASH-RT) as well as the dose distribution (similar to CONV-RT). The nonlinear dose rate constraint is linearized, and the reformulated optimization problem is efficiently solved via iterative convex relaxation powered by alternating direction method of multipliers. To resolve and quantify the generic tradeoff of FLASH-RT between FLASH and dose optimization, we propose the use of FLASH effective dose based on dose modifying factor (DMF) owing to the FLASH effect. RESULTS: FLASH-RT via transmission beams (TB) (IMPT-TB or SDDRO) and CONV-RT via Bragg peaks (BP) (IMPT-BP) were evaluated for clinical prostate, lung, head-and-neck (HN), and brain cases. Despite the use of TB, which is generally suboptimal to BP for normal tissue sparing, FLASH-RT via SDDRO considerably reduced FLASH effective dose for high-dose OAR adjacent to the target. For example, in the lung SBRT case, the max esophageal dose constraint 27 Gy was only met by SDDRO (24.8 Gy), compared to IMPT-BP (35.3 Gy) or IMPT-TB (36.6 Gy); in the brain SRS case, the brain constraint V12Gy≤15cc was also only met by SDDRO (13.7cc), compared to IMPT-BP (43.9cc) or IMPT-TB (18.4cc). In addition, SDDRO substantially improved the FLASH coverage from IMPT-TB, e.g., an increase from 37.2% to 67.1% for lung, from 39.1% to 58.3% for prostate, from 65.4% to 82.1% for HN, from 50.8% to 73.3% for the brain. CONCLUSIONS: Both FLASH dose and dose rate constraints are incorporated into SDDRO for FLASH-RT that jointly optimizes the FLASH effect and physical dose distribution. FLASH effective dose via FLASH DMF is introduced to reconcile the tradeoff between physical dose sparing and FLASH sparing, and quantify the net effective gain from CONV-RT to FLASH-RT.

Analyzing the impact of intrafraction motion: correlation of different dose metrics with changes in target D95%.

PURPOSE: A number of techniques are available to determine the dosimetric impact of intrafraction motion during intensity modulated radiation therapy (IMRT). Motion-induced dose perturbations can be determined both computationally and experimentally using a number of different dosimetric metrics. However, these measures may lead to different conclusions regarding the clinical impact of motion. This study compares the analysis of identical dose perturbations using different dosimetric metrics. Calculated changes in target D95% are used as a reference. METHODS: A total of 3768 motion-encoded dose distributions were calculated for nine lung tumor patients. The motion-encoded dose distributions were compared to static dose distributions using three dosimetric metrics: 2D gamma, 3D gamma, and histogram analysis. Each of these metrics was used to analyze dose perturbations both globally and within the target structure. Furthermore, the failing voxels were analyzed separately according to failure mode, i.e., under vs. over-dosed voxels. Metrics were evaluated based on their agreement with changes in target D95%. Evaluations included the metrics' maximum average sensitivity and specificity (MASS) in detecting unacceptable deliveries, a coefficient correlated to ranking (tau), and the linear correlation coefficient, r. RESULTS: Of the evaluated metrics, the histogram metric restricted to the under-dosed voxels within the target agreed best with changes in target D95%. This metric achieved a MASS of 0.93, a tau of 0.69, and an r-value of 0.85. In comparison, the unrestricted 2D gamma metric achieved MASS = 0.77, tau = 0.40, and r = 0.67. Restricting the 2D gamma test both geographically and in failure mode increased the MASS to 0.85, tau to 0.70, and the r-value to 0.80. CONCLUSIONS: This study suggests that any clinical decisions based solely on an unrestricted 2D gamma metric are suboptimal. A geographic and failure mode restriction can improve results. The remaining uncertainties with non-DVH (dose volume histogram) based metrics should be kept in mind when they are used to evaluate the dosimetric impact of target motion.

Clinical practice vs. state-of-the-art research and future visions: Report on the 4D treatment planning workshop for particle therapy - Edition 2018 and 2019.

The 4D Treatment Planning Workshop for Particle Therapy, a workshop dedicated to the treatment of moving targets with scanned particle beams, started in 2009 and since then has been organized annually. The mission of the workshop is to create an informal ground for clinical medical physicists, medical physics researchers and medical doctors interested in the development of the 4D technology, protocols and their translation into clinical practice. The 10th and 11th editions of the workshop took place in Sapporo, Japan in 2018 and Krakow, Poland in 2019, respectively. This review report from the Sapporo and Krakow workshops is structured in two parts, according to the workshop programs. The first part comprises clinicians and physicists review of the status of 4D clinical implementations. Corresponding talks were given by speakers from five centers around the world: Maastro Clinic (The Netherlands), University Medical Center Groningen (The Netherlands), MD Anderson Cancer Center (United States), University of Pennsylvania (United States) and The Proton Beam Therapy Center of Hokkaido University Hospital (Japan). The second part is dedicated to novelties in 4D research, i.e. motion modelling, artificial intelligence and new technologies which are currently being investigated in the radiotherapy field.

QA for helical tomotherapy: report of the AAPM Task Group 148.

Helical tomotherapy is a relatively new modality with integrated treatment planning and delivery hardware for radiation therapy treatments. In view of the uniqueness of the hardware design of the helical tomotherapy unit and its implications in routine quality assurance, the Therapy Physics Committee of the American Association of Physicists in Medicine commissioned Task Group 148 to review this modality and make recommendations for quality assurance related methodologies. The specific objectives of this Task Group are: (a) To discuss quality assurance techniques, frequencies, and tolerances and (b) discuss dosimetric verification techniques applicable to this unit. This report summarizes the findings of the Task Group and aims to provide the practicing clinical medical physicist with the insight into the technology that is necessary to establish an independent and comprehensive quality assurance program for a helical tomotherapy unit. The emphasis of the report is to describe the rationale for the proposed QA program and to provide example tests that can be performed, drawing from the collective experience of the task group members and the published literature. It is expected that as technology continues to evolve, so will the test procedures that may be used in the future to perform comprehensive quality assurance for helical tomotherapy units.

Simultaneous dose and dose rate optimization (SDDRO) for FLASH proton therapy.

PURPOSE: FLASH radiotherapy (RT) can potentially reduce normal tissue toxicity while preserving tumoricidal effectiveness to improve the therapeutic ratio. The key of FLASH for sparing normal tissues is to irradiate tissues with an ultra-high dose rate (i.e., ≥40 Gy/s), for which proton RT can be used. However, currently available treatment plan optimization method only optimizes the dose distribution and does not directly optimize the dose rate. The contribution of this work to FLASH proton RT is the development of a novel treatment optimization method, that is, simultaneous dose and dose rate optimization (SDDRO), to optimize tissue-receiving dose rate distribution as well as dose distribution. METHODS: Distinguished from existing methods, SDDRO accounts for dose rate constraint and optimizes dose rate distribution. In terms of mathematical formulation, SDDRO is a constrained optimization problem with dose-volume constraint on dose distribution, minimum dose rate constraint on dose-averaged tissue-receiving dose rates, minimum monitor unit constraint on spot weight, and maximum intensity constraint on beam intensity. In terms of optimization algorithm, SDDRO is solved by iterative convex relaxation and alternating direction method of multipliers. SDDRO algorithms are presented for both scenarios with either constant or variable beam intensity. RESULTS: SDDRO was compared with intensity modulated proton therapy (IMPT) (dose optimization alone, and no dose rate optimization) using three lung cases. SDDRO substantially improved the dose rate distribution compared to IMPT, for example, increasing of the region-of-interest (ROI) volume (ROI = CTV_10mm: the ring sandwiched by 10 mm outer and inner expansion of CTV boundary) receiving at least 40 Gy/s from ~30-50% to at least 98%, and the lung volume receiving at least 40 Gy/s from ~30-40% to ~70-90%. Moreover, both dose and dose rate distributions from SDDRO were further considerably improved via the combined use of hypofractionation and multiple beams. CONCLUSIONS: We have developed a joint dose and dose rate optimization method for FLASH proton RT, namely SDDRO, which is first-of-its-kind to the best of our knowledge. The results suggest that (a) SDDRO can substantially improve the FLASH-dose rate coverage (e.g., in terms of dose rate volume histogram) compared to IMPT for the purpose of normal tissue sparing while preserving the dose distribution and (b) the combination of hypofractionation and multiple beams can further considerably improve the SDDRO plan quality in terms of both dose and dose rate distribution.

Technical Note: Plan-delivery-time constrained inverse optimization method with minimum-MU-per-energy-layer (MMPEL) for efficient pencil beam scanning proton therapy.

PURPOSE: This work aims to reduce dose delivery time of pencil beam scanning (PBS) proton plans, which is the dominant factor of total plan delivery time. A proton PBS system, such as Varian ProBeam proton therapy system, can be equipped with the proton dose rate that is linearly proportional to the minimum monitor unit (MU) (i.e., number of protons) of PBS spots before saturation. Thus dose delivery time can be potentially reduced by increasing the MU threshold. However, commercially available treatment planning systems and current methods only allow for a single MU threshold globally for all PBS spots (i.e., all energy layers), and consequently the room to increase this minimum-MU for reducing dose delivery time is very limited since higher minimum-MU can greatly degrade treatment plan quality. METHODS: Two major innovations of this work are the proposal of using variable MU thresholds locally adaptive to each energy layer, that is, minimum-MU-per-energy-layer (MMPEL), for reducing dose delivery time, and the joint optimization of plan delivery time and plan quality. Minimum-MU-per-energy-layer is formulated as a constrained optimization problem with objectives of dose-volume-histogram based planning constraints and plan delivery time, and minimum-MU constraints per energy layer for deliverable PBS spots. Minimum-MU-per-energy-layer is solved by iterative convex relaxations via alternating direction method of multipliers. RESULTS: Representative prostate, lung, brain, head-and-neck, breast, liver and pancreas cases were used to validate MMPEL. Minimum-MU-per-energy-layer reduced dose delivery time to 53%, 67%, 67%, 53%, 54%, 32%, and 14% respectively while maintaining a similar plan quality. Accepting a slightly degraded plan quality that still met all physician planning constraints, the treatment time could be further reduced to 26%, 35%, 41%, 34%, 32%, 16%, and 11% respectively, or in another word MMPEL accelerated the PBS plan delivery by 2-10 fold. CONCLUSIONS: A new proton PBS treatment planning method MMPEL with variable energy-adaptive MU thresholds is developed to optimize dose delivery time jointly with plan quality. The preliminary results suggest that MMPEL could substantially reduce dose delivery time.

Multiple Computed Tomography Robust Optimization to Account for Random Anatomic Density Variations During Intensity Modulated Proton Therapy.

PURPOSE: To propose a method of optimizing intensity modulated proton therapy (IMPT) plans robust against dosimetric degradation caused by random anatomic variations during treatment. METHODS AND MATERIALS: Fifteen patients with prostate cancer treated with IMPT to the pelvic targets were nonrandomly selected. On the repeated quality assurance computed tomography (QACTs) for some patients, bowel density changes were observed and caused dose degradation because the treated plans were not robustly optimized (non-RO). To mitigate this effect, we developed a robust planning method based on 3 CT images, including the native planning CT and its 2 copies, with the bowel structures being assigned to air and tissue, respectively. The RO settings included 5 mm setup uncertainty and 3.5% range uncertainty on 3 CTs. This method is called pseudomultiple-CT RO (pMCT-RO). Plans were also generated using RO on the native CT only, with the same setup and range uncertainties. This method is referred to as single-CT RO (SCT-RO). Doses on the QACTs and the nominal planning CT were compared for the 3 planning methods. RESULTS: All 3 plan methods provided sufficient clinical target volumes D95% and V95% on the QACTs. For pMCT-RO plans, the normal tissue Dmax on QACTs of all patients was at maximum 109.1%, compared with 144.4% and 116.9% for non-RO and SCT-RO plans, respectively. On the nominal plans, the rectum and bladder doses were similar among all 3 plans; however, the volume of normal tissue (excluding the rectum and bladder) receiving the prescription dose or higher is substantially reduced in either pMCT-RO plans or SCT-RO plans, compared with the non-RO plans. CONCLUSIONS: We developed a robust optimization method to further mitigate undesired dose heterogeneity caused by random anatomic changes in pelvic IMPT treatment. This method does not require additional patient CT scans. The pMCT-RO planning method has been implemented clinically since 2017 in our center.

Characterization of a new scintillation imaging system for proton pencil beam dose rate measurements.

The goal of this work was to create a technique that could measure all possible spatial and temporal delivery rates used in pencil-beam scanning (PBS) proton therapy. The proposed system used a fast scintillation screen for full-field imaging to resolve temporal and spatial patterns as it was delivered. A fast intensified CMOS camera used continuous mode with 10 ms temporal frame rate and 1 × 1 mm2 spatial resolution, imaging a scintillation screen during clinical proton PBS delivery. PBS plans with varying dose, dose rate, energy, field size, and spot-spacing were generated, delivered and imaged. The captured images were post processed to provide dose and dose rate values after background subtraction, perspective transformation, uniformity correction for the camera and the scintillation screen, and calibration into dose. The linearity in scintillation response with respect to varying dose rate, dose, and field size was within 2%. The quenching corrected response with varying energy was also within 2%. Large spatio-temporal variations in dose rate were observed, even for plans delivered with similar dose distributions. Dose and dose rate histograms and maximum dose rate maps were generated for quantitative evaluations. With the fastest PBS delivery on a clinical system, dose rates up to 26.0 Gy s-1 were resolved. The scintillation imaging technique was able to quantify proton PBS dose rate profiles with spot weight as low as 2 MU, with spot-spacing of 2.5 mm, having a 1 × 1 mm2 spatial resolution. These dose rate temporal profiles, spatial maps, and cumulative dose rate histograms provide useful metrics for the potential evaluation and optimization of dose rate in treatment plans.

Proton pencil beam scanning treatment with feedback based voluntary moderate breath hold.

Introduction The aim of this article is to introduce a novel protocol for proton pencil beam scanning treatment with moderate deep inspiration breath hold (mDIBH) and report on our clinical implementation results. Methods Three computed tomography (CT) scannings to build the patient's anatomy model were performed during the patient's voluntary mDIBH. All 3 CT scans were used in the optimization during the treatment planning process. Both orthogonal kV imaging and cone-beam computed tomography (CBCT) were implemented for patient alignment with BH prior to the treatment. The BH CBCT images were analyzed for BH reproducibility and the virtual total dose (VTD) retrospectively. To find the VTD, a series of deformable image registrations (DIR) were performed between CBCT and pCT. The effect of the variation of lung density on the dose distribution was also analyzed in the study. Results The values of the mean, standard deviation, maximum, and minimum of the tumor location difference between the CBCT and pCT were 1.9, 1.6, 4.7, and 0.0 mm, respectively. The percentage difference in D99% of CTVs between VTD and the nominal plan was within 1.5%. Conclusions The feedback-based voluntary moderate BH proton PBS treatment was successfully performed in our clinic. This study shows that there is a potential to implement the BH treatment widely in proton centers.

A planning study of focal dose escalations to multiparametric MRI-defined dominant intraprostatic lesions in prostate proton radiation therapy.

OBJECTIVES: The purpose of this study is to investigate the dosimetric effect and clinical impact of delivering a focal radiotherapy boost dose to multiparametric MRI (mp-MRI)-defined dominant intraprostatic lesions (DILs) in prostate cancer using proton therapy. METHODS: We retrospectively investigated 36 patients with pre-treatment mp-MRI and CT images who were treated using pencil beam scanning (PBS) proton radiation therapy to the whole prostate. DILs were contoured on co-registered mp-MRIs. Simultaneous integrated boost (SIB) plans using intensity-modulated proton therapy (IMPT) were created based on conventional whole-prostate-irradiation for each patient and optimized with additional DIL coverage goals and urethral constraints. DIL dose coverage and organ-at-risk (OAR) sparing were compared between conventional and SIB plans. Tumor control probability (TCP) and normal tissue complication probability (NTCP) were estimated to evaluate the clinical impact of the SIB plans. RESULTS: Optimized SIB plans significantly escalated the dose to DILs while meeting OAR constraints. SIB plans were able to achieve 125, 150 and 175% of prescription dose coverage in 74, 54 and 17% of 36 patients, respectively. This was modeled to result in an increase in DIL TCP by 7.3-13.3% depending on α/ß and DIL risk level. CONCLUSION: The proposed mp-MRI-guided DIL boost using proton radiation therapy is feasible without violating OAR constraints and demonstrates a potential clinical benefit by improving DIL TCP. This retrospective study suggested the use of IMPT-based DIL SIB may represent a strategy to improve tumor control. ADVANCES IN KNOWLEDGE: This study investigated the planning of mp-MRI-guided DIL boost in prostate proton radiation therapy and estimated its clinical impact with respect to TCP and NTCP.

A standardized commissioning framework of Monte Carlo dose calculation algorithms for proton pencil beam scanning treatment planning systems.

PURPOSE: Treatment planning systems (TPSs) from different vendors can involve different implementations of Monte Carlo dose calculation (MCDC) algorithms for pencil beam scanning (PBS) proton therapy. There are currently no guidelines for validating non-water materials in TPSs. Furthermore, PBS-specific parameters can vary by 1-2 orders of magnitude among different treatment delivery systems (TDSs). This paper proposes a standardized framework on the use of commissioning data and steps to validate TDS-specific parameters and TPS-specific heterogeneity modeling to potentially reduce these uncertainties. METHODS: A standardized commissioning framework was developed to commission the MCDC algorithms of RayStation 8A and Eclipse AcurosPT v13.7.20 using water and non-water materials. Measurements included Bragg peak depth-dose and lateral spot profiles and scanning field outputs for Varian ProBeam. The phase-space parameters were obtained from in-air measurements and the number of protons per MU from output measurements of 10 × 10 cm2 square fields at a 2 cm depth. Spot profiles and various PBS field measurements at additional depths were used to validate TPS. Human tissues in TPS, Gammex phantom materials, and artificial materials were used for the TPS benchmark and validation. RESULTS: The maximum differences of phase parameters, spot sigma, and divergence between MCDC algorithms are below 4.5 µm and 0.26 mrad in air, respectively. Comparing TPS to measurements at depths, both MC algorithms predict the spot sigma within 0.5 mm uncertainty intervals, the resolution of the measurement device. Beam Configuration in AcurosPT is found to underestimate number of protons per MU by ~2.5% and requires user adjustment to match measured data, while RayStation is within 1% of measurements using Auto model. A solid water phantom was used to validate the range accuracy of non-water materials within 1% in AcurosPT. CONCLUSIONS: The proposed standardized commissioning framework can detect potential issues during PBS TPS MCDC commissioning processes, and potentially can shorten commissioning time and improve dosimetric accuracies. Secondary MCDC can be used to identify the root sources of disagreement between primary MCDC and measurement.