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Background: Ultra high dose rate (UHDR) radiotherapy using ridge filter is a new treatment modality known as conformal FLASH that, when optimized for dose, dose rate (DR), and linear energy transfer (LET), has the potential to reduce damage to healthy tissue without sacrificing tumor killing efficacy via the FLASH effect., Purpose: Clinical implementation of conformal FLASH proton therapy has been limited by quality assurance (QA) challenges, which include direct measurement of UHDR and LET. Voxel DR distributions and LET spectra at planning target margins are paramount to the DR/LET-related sparing of organs at risk. We hereby present a methodology to achieve experimental validation of these parameters., Methods: Dose, DR, and LET were measured for a conformal FLASH treatment plan involving a 250-MeV proton beam and a 3D-printed ridge filter designed to uniformly irradiate a spherical target. We measured dose and DR simultaneously using a 4D multi-layer strip ionization chamber (MLSIC) under UHDR conditions. Additionally, we developed an "under-sample and recover (USRe)" technique for a high-resolution pixelated semiconductor detector, Timepix3, to avoid event pile-up and to correct measured LET at high-proton-flux locations without undesirable beam modifications. Confirmation of these measurements was done using a MatriXX PT detector and by Monte Carlo (MC) simulations., Results: MC conformal FLASH computed doses had gamma passing rates of >95% (3 mm/3% criteria) when compared to MatriXX PT and MLSIC data. At the lateral margin, DR showed average agreement values within 0.3% of simulation at 100 Gy/s and fluctuations ∼10% at 15 Gy/s. LET spectra in the proximal, lateral, and distal margins had Bhattacharyya distances of <1.3%., Conclusion: Our measurements with the MLSIC and Timepix3 detectors shown that the DR distributions for UHDR scenarios and LET spectra using USRe are in agreement with simulations. These results demonstrate that the methodology presented here can be used effectively for the experimental validation and QA of FLASH treatment plans., (© 2024 American Association of Physicists in Medicine.)

Purpose: The 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., Methods: A 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., Results: The 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., Conclusion: The 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., (© 2024 The Author(s). Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Stereotactic body radiation therapy (SBRT) and hypofractionation using pencil-beam scanning (PBS) proton therapy (PBSPT) is an attractive option for thoracic malignancies. Combining the advantages of target coverage conformity and critical organ sparing from both PBSPT and SBRT, this new delivery technique has great potential to improve the therapeutic ratio, particularly for tumors near critical organs. Safe and effective implementation of PBSPT SBRT/hypofractionation to treat thoracic malignancies is more challenging than the conventionally fractionated PBSPT because of concerns of amplified uncertainties at the larger dose per fraction. The NRG Oncology and Particle Therapy Cooperative Group Thoracic Subcommittee surveyed proton centers in the United States to identify practice patterns of thoracic PBSPT SBRT/hypofractionation. From these patterns, we present recommendations for future technical development of proton SBRT/hypofractionation for thoracic treatment. Among other points, the recommendations highlight the need for volumetric image guidance and multiple computed tomography-based robust optimization and robustness tools to minimize further the effect of uncertainties associated with respiratory motion. Advances in direct motion analysis techniques are urgently needed to supplement current motion management techniques., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: The recently proposed Integrated Physical Optimization Intensity Modulated Proton Therapy (IPO-IMPT) framework allows simultaneous optimization of dose, dose rate, and linear energy transfer (LET) for ultra-high dose rate (FLASH) treatment planning. Finding solutions to IPO-IMPT is difficult because of computational intensiveness. Nevertheless, an inverse solution that simultaneously specifies the geometry of a sparse filter and weights of a proton intensity map is desirable for both clinical and preclinical applications. Such solutions can reduce effective biologic dose to organs at risk in patients with cancer as well as reduce the number of animal irradiations needed to derive extra biologic dose models in preclinical studies., Methods and Materials: Unlike the initial forward heuristic, this inverse IPO-IMPT solution includes simultaneous optimization of sparse range compensation, sparse range modulation, and spot intensity. The daunting computational tasks vital to this endeavor were resolved iteratively with a distributed computing framework to enable Simultaneous Intensity and Energy Modulation and Compensation (SIEMAC). SIEMAC was demonstrated on a human patient with central lung cancer and a minipig., Results: SIEMAC simultaneously improves maps of spot intensities and patient-field-specific sparse range compensators and range modulators. For the patient with lung cancer, at our maximum nozzle current of 300 nA, dose rate coverage above 100 Gy/s increased from 57% to 96% in the lung and from 93% to 100% in the heart, and LET coverage above 4 keV/µm dropped from 68% to 9% in the lung and from 26% to <1% in the heart. For a simple minipig plan, the full-width half-maximum of the dose, dose rate, and LET distributions decreased by 30%, 1.6%, and 57%, respectively, again with similar target dose coverage, thus reducing uncertainty in these quantities for preclinical studies., Conclusions: The inverse solution to IPO-IMPT demonstrated the capability to simultaneously modulate subspot proton energy and intensity distributions for clinical and preclinical studies., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective . In current clinical practice for quality assurance (QA), intensity modulated proton therapy (IMPT) fields are verified by measuring planar dose distributions at one or a few selected depths in a phantom. A QA device that measures full 3D dose distributions at high spatiotemporal resolution would be highly beneficial for existing as well as emerging proton therapy techniques such as FLASH radiotherapy. Our objective is to demonstrate feasibility of 3D dose measurement for IMPT fields using a dedicated multi-layer strip ionization chamber (MLSIC) device. Approach. Our developed MLSIC comprises a total of 66 layers of strip ion chamber (IC) plates arranged, alternatively, in the x and y direction. The first two layers each has 128 channels in 2 mm spacing, and the following 64 layers each has 32/33 IC strips in 8 mm spacing which are interconnected every eight channels. A total of 768-channel IC signals are integrated and sampled at a speed of 6 kfps. The MLSIC has a total of 19.2 cm water equivalent thickness and is capable of measurement over a 25 × 25 cm 2 field size. A reconstruction algorithm is developed to reconstruct 3D dose distribution for each spot at all depths by considering a double-Gaussian-Cauchy-Lorentz model. The 3D dose distribution of each beam is obtained by summing all spots. The performance of our MLSIC is evaluated for a clinical pencil beam scanning (PBS) plan. Main results. The dose distributions for each proton spot can be successfully reconstructed from the ionization current measurement of the strip ICs at different depths, which can be further summed up to a 3D dose distribution for the beam. 3D Gamma Index analysis indicates acceptable agreement between the measured and expected dose distributions from simulation, Zebra and MatriXX. Significance. The dedicated MLSIC is the first pseudo-3D QA device that can measure 3D dose distribution in PBS proton fields spot-by-spot., (Creative Commons Attribution license.)

Purpose: An accurate estimation of range uncertainties is essential to exploit the potential of proton therapy. According to Paganetti's study, a value of 2.4% (1.5 standard deviation) is currently recommended for planning robust treatments with Monte Carlo dose engines. This number is based on a dominant contribution from the mean excitation energy of tissues. However, it was recently shown that expressing tissues as a mixture of water and "dry" material in the CT calibration process allowed for a significant reduction of this uncertainty. We thus propose an adapted framework for pencil beam scanning robust optimization. First, we move towards a spot-specific range uncertainty (SSRU) determination. Second, we use the water-based formalism to reduce range uncertainties and, potentially, to spare better the organs at risk., Methods: The stoichiometric calibration was adapted to provide a molecular decomposition (including water) of each voxel of the CT. The SSRU calculation was implemented in MCsquare, a fast Monte Carlo dose engine dedicated to proton therapy. For each spot, a ray-tracing method was used to propagate molecular I-values uncertainties and obtain the corresponding effective range uncertainty. These were then combined with other sources of range uncertainties, according to Paganetti's study of 2012. The method was then assessed on three head-and-neck patients. Two plans were optimized for each patient: the first one with the classical 2.4% flat range uncertainty (FRU), the second one with the variable range uncertainty. Both plans were then compared in terms of target coverage and OAR mean dose reduction. Robustness evaluations were also performed, using the SSRU for both plans in order to simulate errors as realistically as possible., Results: For patient 1, it was found that the median SSRU was 1.04% (1.5 standard deviation), yielding, therefore, a very large reduction from the 2.4% FRU. All three SSRU plans were found to have a very good robustness level at a 90% confidence interval while sparing OAR better than the classical plan. For instance, in nominal cases, average reductions in the mean dose of 15.7, 8.4, and 13.2% were observed in the left parotid, right parotid, and pharyngeal constrictor muscle, respectively. As expected, the classical plans showed a higher but unnecessary level of robustness., Conclusions: Promising results of the SSRU framework were observed on three head-and-neck cases, and more patients should now be considered. The method could also benefit to other tumor sites and, in the long run, the variable part of the range uncertainty could be generalized to other sources of uncertainty in order to move towards more and more patient-specific treatments., (© 2023 American Association of Physicists in Medicine.)

Purpose: Patient-specific ridge filters provide a passive means to modulate proton energy to obtain a conformal dose. Here we describe a new framework for optimization of filter design and spot maps to meet the unique demands of ultrahigh-dose-rate (FLASH) radiation therapy. We demonstrate an integrated physical optimization Intensity-modulated proton therapy (IMPT) (IPO-IMPT) approach for optimization of dose, dose-averaged dose rate (DADR), and dose-averaged linear energy transfer (LET d )., Methods and Materials: We developed an inverse planning software to design patient-specific ridge filters that spread the Bragg peak from a fixed-energy, 250-MeV beam to a proximal beam-specific planning target volume. The software defines patient-specific ridge filter pin shapes and uses a Monte Carlo calculation engine, based on Geant4, to provide dose and LET influence matrices. Plan optimization, using matRAD, accommodates the IPO-IMPT objective function considering dose, dose rate, and LET simultaneously with minimum monitor unit constraints. The framework enables design of both regularly spaced and sparse-optimized ridge filters, from which some pins are omitted to allow faster delivery and selective LET optimization. To demonstrate the framework, we designed ridge filters for 3 example patients with lung cancer and optimized the plans using IPO-IMPT., Results: The IPO-IMPT framework selectively spared the organs at risk by reducing LET and increasing dose rate, relative to IMPT planning. Sparse-optimized ridge filters were superior to regularly spaced ridge filters in dose rate. Depending on which parameter is prioritized, volume distributions and histograms for dose, DADR, and LET d , using evaluation structures specific to heart, lung, and esophagus, show high levels of FLASH dose-rate coverage and/or reduced LET d , while maintaining dose coverage within the beam specific planning target volume., Conclusions: This proof-of-concept study demonstrates the feasibility of using an IPO-IMPT framework to accomplish proton FLASH stereotactic body proton therapy, accounting for dose, DADR, and LET d simultaneously., (Copyright © 2023. Published by Elsevier Inc.)

Objective . The aim of this study was to investigate the feasibility of online monitoring of irradiation time (IRT) and scan time for FLASH proton radiotherapy using a pixelated semiconductor detector. Approach . Measurements of the time structure of FLASH irradiations were performed using fast, pixelated spectral detectors based on the Timepix3 (TPX3) chips with two architectures: AdvaPIX-TPX3 and Minipix-TPX3. The latter has a fraction of its sensor coated with a material to increase sensitivity to neutrons. With little or no dead time and an ability to resolve events that are closely spaced in time (tens of nanoseconds), both detectors can accurately determine IRTs as long as pulse pile-up is avoided. To avoid pulse pile-up, the detectors were placed well beyond the Bragg peak or at a large scattering angle. Prompt gamma rays and secondary neutrons were registered in the detectors' sensors and IRTs were calculated based on timestamps of the first charge carriers (beam-on) and the last charge carriers (beam-off). In addition, scan times in x , y , and diagonal directions were measured. The experiment was carried out for various setups: (i) a single spot, (ii) a small animal field, (iii) a patient field, and (iv) an experiment using an anthropomorphic phantom to demonstrate in vivo online monitoring of IRT. All measurements were compared to vendor log files. Main results . Differences between measurements and log files for a single spot, a small animal field, and a patient field were within 1%, 0.3% and 1%, respectively. In vivo monitoring of IRTs (95-270 ms) was accurate within 0.1% for AdvaPIX-TPX3 and within 6.1% for Minipix-TPX3. The scan times in x , y , and diagonal directions were 4.0, 3.4, and 4.0 ms, respectively. Significance . Overall, the AdvaPIX-TPX3 can measure FLASH IRTs within 1% accuracy, indicating that prompt gamma rays are a good surrogate for primary protons. The Minipix-TPX3 showed a somewhat higher discrepancy, likely due to the late arrival of thermal neutrons to the detector sensor and lower readout speed. The scan times (3.4 ± 0.05 ms) in the 60 mm distance of y -direction were slightly less than (4.0 ± 0.06 ms) in the 24 mm distance of x -direction, confirming the much faster scanning speed of the Y magnets than that of X. Diagonal scan speed was limited by the slower X magnets., (© 2023 Institute of Physics and Engineering in Medicine.)

Background: Ultra-high dose rate (FLASH) proton planning with only transmission beams (TBs) has limitations in normal tissue sparing. The single-energy spread-out Bragg peaks (SESOBPs) of the FLASH dose rate have been demonstrated feasible for proton FLASH planning., Purpose: To investigate the feasibility of combining TBs and SESOBPs for proton FLASH treatment., Methods: A hybrid inverse optimization method was developed to combine the TBs and SESOBPs (TB-SESOBP) for FLASH planning. The SESOBPs were generated field-by-field from spreading out the BPs by pre-designed general bar ridge filters (RFs) and placed at the central target by range shifters (RSs) to obtain a uniform dose within the target. The SESOBPs and TBs were fully placed field-by-field allowing automatic spot selection and weighting in the optimization process. A spot reduction strategy was conducted in the optimization process to push up the minimum MU/spot assuring the plan deliverability at beam current of 165 nA. The TB-SESOBP plans were validated in comparison with the TB only (TB-only) plans and the plans with the combination of TBs and BPs (TB-BP plans) regarding 3D dose and dose rate (dose-averaged dose rate) distributions for five lung cases. The FLASH dose rate coverage (V 40Gy/s ) was evaluated in the structure volume receiving > 10% of the prescription dose., Results: Compared to the TB-only plans, the mean spinal cord D 1.2cc drastically reduced by 41% (P < 0.05), the mean lung V 7Gy and V 7.4 Gy moderately reduced by up to 17% (P < 0.05), and the target dose homogeneity slightly increased in the TB-SESOBP plans. Comparable dose homogeneity was achieved in both TB-SESOBP and TB-BP plans. Besides, prominent improvements were achieved in lung sparing for the cases of relatively large targets by the TB-SESOBP plans compared to the TB-BP plans. The targets and the skin were fully covered with the FLASH dose rate in all three plans. For the OARs, V 40Gy/s  = 100% was achieved by the TB-only plans while V 40Gy/s  > 85% was obtained by the other two plans., Conclusion: We have demonstrated that the hybrid TB-SESOBP planning was feasible to achieve FLASH dose rate for proton therapy. With pre-designed general bar RFs, the hybrid TB-SESOBP planning could be implemented for proton adaptive FLASH radiotherapy. As an alternative FLASH planning approach to TB-only planning, the hybrid TB-SESOBP planning has great potential in dosimetrically improving OAR sparing while maintaining high target dose homogeneity., (© 2023 American Association of Physicists in Medicine.)

Purpose: Metallic implants have been correlated to local control failure for spinal sarcoma and chordoma patients due to the uncertainty of implant delineation from computed tomography (CT). Such uncertainty can compromise the proton Monte Carlo dose calculation (MCDC) accuracy. A component method is proposed to determine the dimension and volume of the implants from CT images., Methods: The proposed component method leverages the knowledge of surgical implants from medical supply vendors to predefine accurate contours for each implant component, including tulips, screw bodies, lockers, and rods. A retrospective patient study was conducted to demonstrate the feasibility of the method. The reference implant materials and samples were collected from patient medical records and vendors, Medtronic and NuVasive. Additional CT images with extensive features, such as extended Hounsfield units and various reconstruction diameters, were used to quantify the uncertainty of implant contours., Results: For in vivo patient implant estimation, the reference and the component method differences were 0.35, 0.17, and 0.04 cm 3 for tulips, screw bodies, and rods, respectively. The discrepancies by a conventional threshold method were 5.46, 0.76, and 0.05 cm 3 , respectively. The mischaracterization of implant materials and dimensions can underdose the clinical target volume coverage by 20 cm 3 for a patient with eight lumbar implants. The tulip dominates the dosimetry uncertainty as it can be made from titanium or cobalt-chromium alloys by different vendors., Conclusions: A component method was developed and demonstrated using phantom and patient studies with implants. The proposed method provides more accurate implant characterization for proton MCDC and can potentially enhance the treatment quality for proton therapy. The current proof-of-concept study is limited to the implant characterization for lumbar spine. Future investigations could be extended to cervical spine and dental implants for head-and-neck patients where tight margins are required to spare organs at risk., (© 2022 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Objective . Computed tomography (CT) to material property conversion dominates proton range uncertainty, impacting the quality of proton treatment planning. Physics-based and machine learning-based methods have been investigated to leverage dual-energy CT (DECT) to predict proton ranges. Recent development includes physics-informed deep learning (DL) for material property inference. This paper aims to develop a framework to validate Monte Carlo dose calculation (MCDC) using CT-based material characterization models. Approach. The proposed framework includes two experiments to validate in vivo dose and water equivalent thickness (WET) distributions using anthropomorphic and porcine phantoms. Phantoms were irradiated using anteroposterior proton beams, and the exit doses and residual ranges were measured by MatriXX PT and a multi-layer strip ionization chamber. Two pre-trained conventional and physics-informed residual networks (RN/PRN) were used for mass density inference from DECT. Additional two heuristic material conversion models using single-energy CT (SECT) and DECT were implemented for comparisons. The gamma index was used for dose comparisons with criteria of 3%/3 mm (10% dose threshold). Main results . The phantom study showed that MCDC with PRN achieved mean gamma passing rates of 95.9% and 97.8% for the anthropomorphic and porcine phantoms. The rates were 86.0% and 79.7% for MCDC with the empirical DECT model. WET analyses indicated that the mean WET variations between measurement and simulation were -1.66 mm, -2.48 mm, and -0.06 mm for MCDC using a Hounsfield look-up table with SECT and empirical and PRN models with DECT. Validation experiments indicated that MCDC with PRN achieved consistent dose and WET distributions with measurement. Significance . The proposed framework can be used to identify the optimal CT-based material characterization model for MCDC to improve proton range uncertainty. The framework can systematically verify the accuracy of proton treatment planning, and it can potentially be implemented in the treatment room to be instrumental in online adaptive treatment planning., (© 2022 Institute of Physics and Engineering in Medicine.)

Objective . Proton pencil beam scanning (PBS) treatment fields needs to be verified before treatment deliveries to ensure patient safety. In current practice, treatment beam quality assurance (QA) is measured at a few selected depths using film or a 2D detector array, which is insensitive and time-consuming. A QA device that can measure all key dosimetric characteristics of treatment beams spot-by-spot within a single beam delivery is highly desired. Approach . We developed a multi-layer strip ionization chamber (MLSIC) prototype device that comprises of two layers of strip ionization chambers (IC) plates for spot position measurement and 64 layers of plate IC for beam energy measurement. The 768-channel strip ion chamber signals are integrated and sampled at a speed of 3.125 kHz. It has a 25.6 cm × 25.6 cm maximum measurement field size and 2 mm spatial resolution for spot position measurement. The depth resolution and maximum depth were 2.91 mm and 18.6 cm for 1.6 mm thick IC plate, respectively. The relative weight of each spot was determined from total charge by all IC detector channels. Main results . The MLSIC is able to measure ionization currents spot-by-spot. The depth dose measurement has a good agreement with the ground truth measured using a water tank and commercial one-dimensional (1D) multi-layer plate chamber. It can verify the spot position, energy, and relative weight of clinical PBS beams and compared with the treatment plans. Significance . The MLSIC is a highly efficient QA device that can measure the key dosimetric characteristics of proton treatment beams spot-by-spot with a single beam delivery. It may improve the quality and efficiency of clinical proton treatments., (© 2022 Institute of Physics and Engineering in Medicine.)

Proton therapy requires accurate dose calculation for treatment planning to ensure the conformal doses are precisely delivered to the targets. The conversion of CT numbers to material properties is a significant source of uncertainty for dose calculation. The aim of this study is to develop a physics-informed deep learning (PIDL) framework to derive accurate mass density and relative stopping power maps from dual-energy computed tomography (DECT) images. The PIDL framework allows deep learning (DL) models to be trained with a physics loss function, which includes a physics model to constrain DL models. Five DL models were implemented including a fully connected neural network (FCNN), dual-FCNN (DFCNN), and three variants of residual networks (ResNet): ResNet-v1 (RN-v1), ResNet-v2 (RN-v2), and dual-ResNet-v2 (DRN-v2). An artificial neural network (ANN) and the five DL models trained with and without physics loss were explored to evaluate the PIDL framework. Two empirical DECT models were implemented to compare with the PIDL method. DL training data were from CIRS electron density phantom 062M (Computerized Imaging Reference Systems, Inc., Norfolk, VA). The performance of DL models was tested by CIRS adult male, adult female, and 5-year-old child anthropomorphic phantoms. For density map inference, the physics-informed RN-v2 was 3.3%, 2.9% and 1.9% more accurate than ANN for the adult male, adult female, and child phantoms. The physics-informed DRN-v2 was 0.7%, 0.6%, and 0.8% more accurate than DRN-v2 without physics training for the three phantoms, respectfully. The results indicated that physics-informed training could reduce uncertainty when ANN/DL models without physics training were insufficient to capture data structures or derived significant errors. DL models could also achieve better image noise control compared to the empirical DECT parametric mapping methods. The proposed PIDL framework can potentially improve proton range uncertainty by offering accurate material properties conversion from DECT., (© 2022 Institute of Physics and Engineering in Medicine.)

Purpose: Quality assurance computed tomography (QACT) is the current clinical practice in proton therapy to evaluate the needs for replan. QACT could falsely indicate replan because of setup issues that would be solved on the treatment machine. Deforming the treatment planning CT (TPCT) to the pretreatment CBCT may eliminate this issue. We investigated the performance of replan evaluation based on deformed TPCT (TPCTdir) for proton head and neck (H&N) therapy., Methods and Materials: Twenty-eight H&N datasets along with pretreatment CBCT and QACT were used to validate the method. The changes in body volume were analyzed between the no-replan and replan groups. The dose on the TPCTdir, the deformed QACT (QACTdir), and the QACT were calculated by applying the clinical plans to these image sets. Dosimetric parameters' changes, including ΔD95, ΔDmean, and ΔD1 for the clinical target volumes (CTVs) were calculated. Receiver operating characteristic curves for replan evaluation based on ΔD95 on QACT and TPCTdir were calculated, using ΔD95 on QACTdir as the reference. A threshold for replan based on ΔD95 on TPCTdir is proposed. The specificities for the proposed method were calculated., Results: The changes in the body contour were 95.8 ± 83.8 cc versus 305.0 ± 235.0 cc (p < 0.01) for the no-replan and replan groups, respectively. The ΔD95, ΔDmean, and ΔD1 are all comparable for all the evaluations. The differences between TPCTdir and QACTdir evaluations were 0.30% ± 0.86%, 0.00 ± 0.22 Gy, and -0.17 ± 0.61 Gy for CTV ΔD95, ΔDmean, and ΔD1, respectively. The corresponding differences between the QACT and QACTdir were 0.12% ± 1.1%, 0.02 ± 0.32 Gy, and -0.01 ± 0.71 Gy. CTV ΔD95 > 2.6% in TPCTdir was chosen as the threshold to trigger QACT/replan. The corresponding specificity was 94% and 98% for the clinical practice and the proposed method, respectively., Conclusions: The replan evaluation based on TPCTdir provides better specificity than that based on the QACT., (© 2022 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Dose uncertainty induced by respiratory motion remains a major concern for treating thoracic and abdominal lesions using particle beams. This Task Group report reviews the impact of tumor motion and dosimetric considerations in particle radiotherapy, current motion-management techniques, and limitations for different particle-beam delivery modes (i.e., passive scattering, uniform scanning, and pencil-beam scanning). Furthermore, the report provides guidance and risk analysis for quality assurance of the motion-management procedures to ensure consistency and accuracy, and discusses future development and emerging motion-management strategies. This report supplements previously published AAPM report TG76, and considers aspects of motion management that are crucial to the accurate and safe delivery of particle-beam therapy. To that end, this report produces general recommendations for commissioning and facility-specific dosimetric characterization, motion assessment, treatment planning, active and passive motion-management techniques, image guidance and related decision-making, monitoring throughout therapy, and recommendations for vendors. Key among these recommendations are that: (1) facilities should perform thorough planning studies (using retrospective data) and develop standard operating procedures that address all aspects of therapy for any treatment site involving respiratory motion; (2) a risk-based methodology should be adopted for quality management and ongoing process improvement., (© 2022 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

MRI-only treatment planning is highly desirable in the current proton radiation therapy workflow due to its appealing advantages such as bypassing MR-CT co-registration, avoiding x-ray CT exposure dose and reduced medical cost. However, MRI alone cannot provide stopping power ratio (SPR) information for dose calculations. Given that dual energy CT (DECT) can estimate SPR with higher accuracy than conventional single energy CT, we propose a deep learning-based method in this study to generate synthetic DECT (sDECT) from MRI to calculate SPR. Since the contrast difference between high-energy and low-energy CT (LECT) is important, and in order to accurately model this difference, we propose a novel label generative adversarial network-based model which can not only discriminate the realism of sDECT but also differentiate high-energy CT (HECT) and LECT from DECT. A cohort of 57 head-and-neck cancer patients with DECT and MRI pairs were used to validate the performance of the proposed framework. The results of sDECT and its derived SPR maps were compared with clinical DECT and the corresponding SPR, respectively. The mean absolute error for synthetic LECT and HECT were 79.98 ± 18.11 HU and 80.15 ± 16.27 HU, respectively. The corresponding SPR maps generated from sDECT showed a normalized mean absolute error as 5.22% ± 1.23%. By comparing with the traditional Cycle GANs, our proposed method significantly improves the accuracy of sDECT. The results indicate that on our dataset, the sDECT image form MRI is close to planning DECT, and thus shows promising potential for generating SPR maps for proton therapy.

The presence of artificial implants complicates the delivery of proton therapy due to inaccurate characterization of both the implant and the surrounding tissues. In this work, we describe a method to characterize implant and human tissue mimicking materials in terms of relative stopping power (RSP) using a novel proton counting detector. Each proton is tracked by directly measuring the deposited energy along the proton track using a fast, pixelated spectral detector AdvaPIX-TPX3 (TPX3). We considered three scenarios to characterize the RSPs. First, in-air measurements were made in the presence of metal rods (Al, Ti and CoCr) and bone. Then, measurements of energy perturbations in the presence of metal implants and bone in an anthropomorphic phantom were performed. Finally, sampling of cumulative stopping power (CSP) of the phantom were made at different locations of the anthropomorphic phantom. CSP and RSP information were extracted from energy spectra at each beam path. To quantify the RSP of metal rods we used the shift in the most probable energy (MPE) of CSP from the reference CSP without a rod. Overall, the RSPs were determined as 1.48, 2.06, 3.08, and 5.53 from in-air measurements; 1.44, 1.97, 2.98, and 5.44 from in-phantom measurements, for bone, Al, Ti and CoCr, respectively. Additionally, we sampled CSP for multiple paths of the anthropomorphic phantom ranging from 18.63 to 25.23 cm deriving RSP of soft tissues and bones in agreement within 1.6% of TOPAS simulations. Using minimum error of these multiple CSP, optimal mass densities were derived for soft tissue and bone and they are within 1% of vendor-provided nominal densities. The preliminary data obtained indicates the proposed novel method can be used for the validation of material and density maps, required by proton Monte Carlo Dose calculation, provided by competing multi-energy computed tomography and metal artifact reduction techniques.

Purpose: The purpose of this study was to present the proton beam characteristics of the first clinical single-room ProBeam Compact™ proton therapy system (SRPT) and comparison against multi-room ProBeam™ system (MRPT)., Materials and Methods: A newly designed SRPT with proton beam energies ranging from 70 to 220 MeV was commissioned in late 2019. Integrated depth doses (IDDs) were scanned using 81.6 mm diameter Bragg peak chambers and normalized by outputs at 15 mm WET and 1.1 RBE offset, following the methodology of TRS 398. The in-air beam spot profiles were acquired by a planar scintillation device, respectively, at ISO, upper and down streams, fitted with single Gaussian distribution for beam modeling in Eclipse v15.6. The field size effect was adjusted for the best overall accuracy of clinically relevant field QAs. The halo effects at near surface were quantified by a pinpoint ionization chamber. Its major dosimetric characteristics were compared against MRPT comparable beam dataset., Results: Contrast to MRPT, an increased proton straggling in the Bragg peak region was found with widened beam distal falloffs and elevated proximal transmission dose values. Integrated depth doses showed 0.105-0.221 MeV (energy sigma) or 0.30-0.94 mm broader Bragg peak widths (R b80 -R a80 ) for 130 MeV or higher energy beams and up to 0.48-0.79 mm extended distal falloffs (R b20 -R b80 ). Minor differences were identified in beam spot sizes, spot divergences, proton particles/MU, and field size output effects. High passing scores are reported for independent end-to-end dosimetry checks by IROC and for initial 108 field-specific QAs at 3%/3 mm Gamma index with fields regardless with or without range shifters., Conclusions: The author highlighted the dosimetry differences in IDDs mainly caused by the shortened beam transport system of SRPT, for which new acceptance criteria were adapted. This report offers a unique reference for future commissioning, beam modeling, planning, and analysis of QA and clinical studies., (© 2020 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Purpose: In this study, we investigated computationally and experimentally a hexagonal-pattern array of spatially fractionated proton minibeams produced by proton pencil beam scanning (PBS) technique. Spatial fractionation of dose delivery with millimeter or submillimeter beam size has proven to be a promising approach to significantly increase the normal tissue tolerance. Our goals are to obtain an optimized minibeam design and to show that it is feasible to implement the optimized minibeams at the existing proton clinics., Methods: An optimized minibeam arrangement is one that would produce high peak-to-valley dose ratios (PVDRs) in normal tissues and a PVDR approaching unity at the Bragg peak. Using Monte Carlo (MC) code TOPAS we simulated proton pencil beams that mimic those available at the existing proton therapy facilities and obtained a hexagonal-pattern array of minibeams by collimating the proton pencil beams through the 1-3 mm diameter pinholes of a collimator. We optimized the minibeam design by considering different combinations of parameters including collimator material and thickness (t), center-to-center (c-t-c) distance, and beam size. The optimized minibeam design was then evaluated for normal tissue sparing against the uniform pencil beam scanning (PBS) by calculating the therapeutic advantage (TA) in terms of cell survival fraction. Verification measurements using radiochromic films were performed at the Emory proton therapy center (EPTC)., Results: Optimized hexagonal-pattern minibeams having PVDRs of >10 at phantom surface and of >3 at depths up to 6 cm were achieved with 2 mm diameter modulated proton minibeams (with proton energies between 120 and 140 MeV) corresponding to a spread-out-Bragg-peak (SOBP) over the depth of 10-14 cm. The results of the film measurements agree with the MC results within 10%. The TA of the 2 mm minibeams against the uniform PBS is >3 from phantom surface to the depth of 5 cm and then smoothly drops to ~1.5 as it approaches the proximal edge of the SOBP. For 2 mm minibeams and 6 mm c-t-c distance, we delivered 1.72 Gy at SOBP for 7.2 × 7.2 × 4 cm 3 volume in 48 s., Conclusions: We conclude that it is feasible to implement the optimized hexagonal-pattern 2 mm proton minibeam radiotherapy at the existing proton clinics, because desirable PVDRs and TAs are achievable and the treatment time is reasonable., (© 2020 American Association of Physicists in Medicine.)

Purpose: To commission an open source Monte Carlo (MC) dose engine, "MCsquare" for a synchrotron-based proton machine, integrate it into our in-house C++-based I/O user interface and our web-based software platform, expand its functionalities, and improve calculation efficiency for intensity-modulated proton therapy (IMPT)., Methods: We commissioned MCsquare using a double Gaussian beam model based on in-air lateral profiles, integrated depth dose of 97 beam energies, and measurements of various spread-out Bragg peaks (SOBPs). Then we integrated MCsquare into our C++-based dose calculation code and web-based second check platform "DOSeCHECK." We validated the commissioned MCsquare based on 12 different patient geometries and compared the dose calculation with a well-benchmarked GPU-accelerated MC (gMC) dose engine. We further improved the MCsquare efficiency by employing the computed tomography (CT) resampling approach. We also expanded its functionality by adding a linear energy transfer (LET)-related model-dependent biological dose calculation., Results: Differences between MCsquare calculations and SOBP measurements were <2.5% (<1.5% for ~85% of measurements) in water. The dose distributions calculated using MCsquare agreed well with the results calculated using gMC in patient geometries. The average 3D gamma analysis (2%/2 mm) passing rates comparing MCsquare and gMC calculations in the 12 patient geometries were 98.0 ± 1.0%. The computation time to calculate one IMPT plan in patients' geometries using an inexpensive CPU workstation (Intel Xeon E5-2680 2.50 GHz) was 2.3 ± 1.8 min after the variable resolution technique was adopted. All calculations except for one craniospinal patient were finished within 3.5 min., Conclusions: MCsquare was successfully commissioned for a synchrotron-based proton beam therapy delivery system and integrated into our web-based second check platform. After adopting CT resampling and implementing LET model-dependent biological dose calculation capabilities, MCsquare will be sufficiently efficient and powerful to achieve Monte Carlo-based and LET-guided robust optimization in IMPT, which will be done in the future studies., (© 2020 American Association of Physicists in Medicine.)

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 cm 2 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., (© 2020 American Association of Physicists in Medicine.)

Purpose: For pencil-beam scanning proton therapy systems, in-air non-Gaussian halo can significantly impact output at small field sizes and low energies. Since the low-intensity tail of spot profile (halo) is not necessarily modeled in treatment planning systems (TPSs), this can potentially lead to significant differences in patient dose distribution. In this work, we report such impact for a Varian ProBeam system., Methods: We use a pair magnification technique to measure two-dimensional (2D) spot profiles of protons from 70 to 242 MeV at the treatment isocenter and 30 cm upstream of the isocenter. Measurements are made with both Gafchromic film and a scintillator detector coupled to a CCD camera (IBA Lynx). Spot profiles are measured down to 0.01% of their maximum intensity. Field size factors (FSFs) are compared among calculation using measured 2D profiles, calculation using a clinical treatment planning algorithm (Raystation 8A clinical Monte Carlo), and a CC04 small-volume ion chamber. FSFs were measured for square fields of proton energies ranging from 70 to 242 MeV., Results: All film and Lynx measurements agree within 1 mm for full width at half maximum beam intensity. The measured radial spot profiles disagree with simple Gaussian approximations, which are used for modeling in the TPS. FSF measurements show the magnitude of disagreements between beam output in reality and in the TPS without modeling halo. We found that the clinical TPS overestimated output by as much as 6% for small field sizes of 2 cm at the lowest energy of 70 MeV while the film and Lynx measurements agreed within 4% and 1%, respectively, for this FSF., Conclusions: If the in-air halo for low-energy proton beams is not fully modeled by the TPS, this could potentially lead to under-dosing small, shallow treatment volumes in PBS treatment plans., (© 2019 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Purpose: Monte Carlo (MC) dose calculation is generally superior to analytical dose calculation (ADC) used in commercial TPS to model the dose distribution especially for heterogeneous sites, such as lung and head/neck patients. The purpose of this study was to provide a validated, fast, and open-source MC code, MCsquare, to assess the impact of approximations in ADC on clinical pencil beam scanning (PBS) plans covering various sites., Methods: First, MCsquare was validated using tissue-mimicking IROC lung phantom measurements as well as benchmarked with the general purpose Monte Carlo TOPAS for patient dose calculation. Then a comparative analysis between MCsquare and ADC was performed for a total of 50 patients with 10 patients per site (including liver, pelvis, brain, head-and-neck, and lung). Differences among TOPAS, MCsquare, and ADC were evaluated using four dosimetric indices based on the dose-volume histogram (target Dmean, D95, homogeneity index, V95), a 3D gamma index analysis (using 3%/3 mm criteria), and estimations of tumor control probability (TCP)., Results: Comparison between MCsquare and TOPAS showed less than 1.8% difference for all of the dosimetric indices/TCP values and resulted in a 3D gamma index passing rate for voxels within the target in excess of 99%. When comparing ADC and MCsquare, the variances of all the indices were found to increase as the degree of tissue heterogeneity increased. In the case of lung, the D95s for ADC were found to differ by as much as 6.5% from the corresponding MCsquare statistic. The median gamma index passing rate for voxels within the target volume decreased from 99.3% for liver to 75.8% for lung. Resulting TCP differences can be large for lung (≤10.5%) and head-and-neck (≤6.2%), while smaller for brain, pelvis and liver (≤1.5%)., Conclusions: Given the differences found in the analysis, accurate dose calculation algorithms such as Monte Carlo simulations are needed for proton therapy, especially for disease sites with high heterogeneity, such as head-and-neck and lung. The establishment of MCsquare can facilitate patient plan reviews at any institution and can potentially provide unbiased comparison in clinical trials given its accuracy, speed and open-source availability., (© 2018 American Association of Physicists in Medicine.)

Monte Carlo (MC)-based dose calculations are generally superior to analytical dose calculations (ADC) in modeling the dose distribution for proton pencil beam scanning (PBS) treatments. The purpose of this paper is to present a methodology for commissioning and validating an accurate MC code for PBS utilizing a parameterized source model, including an implementation of a range shifter, that can independently check the ADC in commercial treatment planning system (TPS) and fast Monte Carlo dose calculation in opensource platform (MCsquare). The source model parameters (including beam size, angular divergence and energy spread) and protons per MU were extracted and tuned at the nozzle exit by comparing Tool for Particle Simulation (TOPAS) simulations with a series of commissioning measurements using scintillation screen/CCD camera detector and ionization chambers. The range shifter was simulated as an independent object with geometric and material information. The MC calculation platform was validated through comprehensive measurements of single spots, field size factors (FSF) and three-dimensional dose distributions of spread-out Bragg peaks (SOBPs), both without and with the range shifter. Differences in field size factors and absolute output at various depths of SOBPs between measurement and simulation were within 2.2%, with and without a range shifter, indicating an accurate source model. TOPAS was also validated against anthropomorphic lung phantom measurements. Comparison of dose distributions and DVHs for representative liver and lung cases between independent MC and analytical dose calculations from a commercial TPS further highlights the limitations of the ADC in situations of highly heterogeneous geometries. The fast MC platform has been implemented within our clinical practice to provide additional independent dose validation/QA of the commercial ADC for patient plans. Using the independent MC, we can more efficiently commission ADC by reducing the amount of measured data required for low dose "halo" modeling, especially when a range shifter is employed., (© 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Background: Existing data supporting the use of proton-beam therapy (PBT) for limited-stage small cell lung cancer (LS-SCLC) are limited to a single 6-patient case series. This is the first prospective study to evaluate clinical outcomes and toxicities of PBT for LS-SCLC., Methods: This study prospectively analyzed patients with primary, nonrecurrent LS-SCLC definitively treated with PBT and concurrent chemotherapy from 2011 to 2016. Clinical backup intensity-modulated radiotherapy (IMRT) plans were generated for each patient and were compared with PBT plans. Outcome measures included local control (LC), recurrence-free survival (RFS), and overall survival (OS) rates and toxicities., Results: Thirty consecutive patients were enrolled and evaluated. The median dose was 63.9 cobalt gray equivalents (range, 45-66.6 cobalt gray equivalents) in 33 to 37 fractions delivered daily (n = 18 [60.0%]) or twice daily (n = 12 [40.0%]). The concurrent chemotherapy was cisplatin/etoposide (n = 21 [70.0%]) or carboplatin/etoposide (n = 9 [30.0%]). In comparison with the backup IMRT plans, PBT allowed statistically significant reductions in the cord, heart, and lung mean doses and the volume receiving at least 5 Gy but not in the esophagus mean dose or the lung volume receiving at least 20 Gy. At a median follow-up of 14 months, the 1-/2-year LC and RFS rates were 85%/69% and 63%/42%, respectively. The median OS was 28.2 months, and the 1-/2-year OS rates were 72%/58%. There was 1 case each (3.3%) of grade 3 or higher esophagitis, pneumonitis, anorexia, and pericardial effusion. Grade 2 pneumonitis and esophagitis were seen in 10.0% and 43.3% of patients, respectively., Conclusions: In the first prospective registry study and largest analysis to date of PBT for LS-SCLC, PBT was found to be safe with a limited incidence of high-grade toxicities. Cancer 2017;123:4244-4251. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Purpose: To compare the difference in robustness of single-field optimized (SFO) and robust multifield optimized (rMFO) proton plans for oropharynx carcinoma patients by an improved robustness analysis., Methods and Materials: We generated rMFO proton plans for 11 patients with oropharynx carcinoma treated with SFO intensity modulated proton therapy with simultaneous integrated boost prescription. Doses from both planning approaches were compared for the initial plans and the worst cases from 20 optimization scenarios of setup errors and range uncertainties. Expected average dose distributions per range uncertainty were obtained by weighting the contributions from the respective scenarios with their expected setup error probability, and the spread of dose parameters for different range uncertainties were quantified. Using boundary dose distributions created from 56 combined setup error and range uncertainty scenarios and considering the vanishing influence of setup errors after 30 fractions, we approximated realistic worst-case values for the total treatment course. Error bar metrics derived from these boundary doses are reported for the clinical target volumes (CTVs) and organs at risk (OARs)., Results: The rMFO plans showed improved CTV coverage and homogeneity while simultaneously reducing the average mean dose to the constrictor muscles, larynx, and ipsilateral middle ear by 5.6 Gy, 2.0 Gy, and 3.9 Gy, respectively. We observed slightly larger differences during robustness evaluation, as well as a significantly higher average brainstem maximum and ipsilateral parotid mean dose for SFO plans. For rMFO plans, the range uncertainty-related spread in OAR dose parameters and many error bar metrics were found to be superior. The SFO plans showed a lower global maximum dose for single-scenario worst cases and a slightly lower mean oral cavity dose throughout., Conclusions: An enhanced robustness analysis has been proposed and implemented into clinical systems. The benefit of better CTV coverage and OAR dose sparing in oropharynx carcinoma patients by rMFO compared with SFO proton plans is preserved in a robustness analysis with consideration of setup error and range uncertainty., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Pencil-beam scanning (PBS) proton therapy (PT), particularly intensity modulated PT, represents the latest advanced PT technology for treating cancers, including thoracic malignancies. On the basis of virtual clinical studies, PBS-PT appears to have great potential in its ability to tightly tailor the dose to the target while sparing critical structures, thereby reducing treatment-related toxicities, particularly for tumors in areas with complicated anatomy. However, implementing PBS-PT for moving targets has several additional technical challenges compared with intensity modulated photon radiation therapy or passive scattering PT. Four-dimensional computed tomography-based motion management and robust optimization and evaluation are crucial for minimizing uncertainties associated with beam range and organ motion. Rigorous quality assurance is required to validate dose delivery both before and during the course of treatment. Active motion management (eg, breath hold), beam gating, rescanning, tracking, or adaptive planning may be needed for cases involving significant motion or changes in motion or anatomy over the course of treatment., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: While often managed with surgery alone, patients with thymic malignancies with high-risk features may benefit from adjuvant radiation therapy but are at risk for late toxicities. Previously, the risk of major cardiac events (MCEs) was reported to increase by 7% per one Gray (Gy) to the heart. In this study, we compare dose to organs at risk (OARs) with intensity-modulated (IMRT) versus proton beam therapy (PBT). We hypothesize a decrease risk of predicted MCEs with PBT., Material and Methods: Patients requiring adjuvant therapy for thymic malignancies were treated with double scattered proton beam therapy (DS-PBT). Clinical backup IMRT plans were generated. Predicted MCEs were calculated based on median dose to the heart. A Wilcoxon rank sum test was used for statistical comparisons., Results: Twenty-two consecutive patients were evaluated. DS-PBT resulted in statistically significant decreases in dose to the heart, lungs, left ventricle, esophagus, and spinal cord (all p ≤ .01). The increase in risk of MCEs from 0 to ≥20 years was lower with PBT (74% versus 135%, p = .04)., Discussion: DS-PBT results in decreased dose to OARs and may reduce the risk of MCEs compared with IMRT. Long-term follow-up is required to assess for clinical benefit from DS-PBT.

Background: For lung tumors with large motion amplitudes, the use of proton pencil beam scanning (PBS) can produce large dose errors. In this study, we assess under what circumstances PBS can be used to treat lung cancer patients who exhibit large tumor motion, based on the quantification of tumor motion and the dose interplay., Material and Methods: PBS plans were optimized on average 4DCT datasets using a beam-specific PTV method for 10 consecutive patients with locally advanced non-small-cell-lung-cancer (NSCLC) treated with proton therapy to 6660/180 cGy. End inhalation (CT0) and end exhalation (CT50) were selected as the two extreme scenarios to acquire the relative stopping power ratio difference (Δrsp) for a respiration cycle. The water equivalent difference (ΔWET) per radiological path was calculated from the surface of patient to the iCTV by integrating the Δrsp of each voxel. The magnitude of motion of voxels within the target follows a quasi-Gaussian distribution. A motion index (MI (>5mm WET)), defined as the percentage of target voxels with an absolute integral ΔWET larger than 5 mm, was adopted as a metric to characterize interplay. To simulate the treatment process, 4D dose was calculated by accumulating the spot dose on the corresponding respiration phase to the reference phase CT50 by deformable image registration based on spot timing and patient breathing phase., Results: The study indicated that the magnitude of target underdose in a single fraction plan is proportional to the MI (p < .001), with larger motion equating to greater dose degradation and standard deviations. The target homogeneity, minimum, maximum and mean dose in the 4D dose accumulations of 37 fractions varied as a function of MI., Conclusions: This study demonstrated that MI can predict the level of dose degradation, which potentially serves as a clinical decision tool to assess whether lung cancer patients are potentially suitable to receive PBS treatment.

AcurosPT is a Monte Carlo algorithm in the Eclipse 13.7 treatment planning system, which is designed to provide rapid and accurate dose calculations for proton therapy. Computational run-time in minimized by simplifying or eliminating less significant physics processes. In this article, the accuracy of AcurosPT was benchmarked against both measurement and an independent MC calculation, TOPAS. Such a method can be applied to any new MC calculation for the detection of potential inaccuracies. To validate multiple Coulomb scattering (MCS) which affects primary beam broadening, single spot profiles in a Solidwater ® phantom were compared for beams of five selected proton energies between AcurosPT, measurement and TOPAS. The spot Gaussian sigma in AcurosPT was found to increase faster with depth than both measurement and TOPAS, suggesting that the MCS algorithm in AcurosPT overestimates the scattering effect. To validate AcurosPT modeling of the halo component beyond primary beam broadening, field size factors (FSF) were compared for multi-spot profiles measured in a water phantom. The FSF for small field sizes were found to disagree with measurement, with the disagreement increasing with depth. Conversely, TOPAS simulations of the same FSF consistently agreed with measurement to within 1.5%. The disagreement in absolute dose between AcurosPT and measurement was smaller than 2% at the mid-range depth of multi-energy beams. While AcurosPT calculates acceptable dose distributions for typical clinical beams, users are cautioned of potentially larger errors at distal depths due to overestimated MCS and halo implementation., (© 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Purpose: To determine whether individual liver tumor patients can be safely treated with pencil beam scanning proton therapy. This study reports a planning preparation workflow that can be used for beam angle selection and the evaluation of the efficacy of abdominal compression (AC) to mitigate motion., Methods: Four-dimensional computed tomography scans (4DCT) with and without AC were available from 10 liver tumor patients with fluoroscopy-proven motion reduction by AC, previously treated using photons. For each scan, the motion amplitudes and the motion-induced variation of water-equivalent thickness (ΔWET) in each voxel of the target volume were evaluated during treatment plan preparation. Optimal proton beam angles were selected after volume analysis of the respective beam-specific planning target volume (BSPTV). M ⊥80 and ΔWET 80 derived from the 80th percentiles of perpendicular motion amplitude (M ⊥ ) and ΔWET were compared with and without AC. Proton plans were created on the average CT to achieve target coverage similar to that of the conventional photon treatments. 4D dynamic dose calculation was performed postplan by synchronizing proton beam delivery timing patterns to the 4DCT phases to assess interplay and fractionation effects, and to determine motion criteria for subsequent patient treatment., Results: Selected coplanar beam angles ranged between 180° and 39°, primarily from right lateral (oblique) and posterior (oblique) directions. While AC produced a significant reduction in mean Liver-GTV dose, any reduction in mean heart dose was patient dependent and not significant. Similarly, AC resulted in reductions in M ⊥ , ΔWET, and BSPTV volumes and improved dose degradation (ΔD 95 and ΔD 1 ) within the CTV. For small motion (M ⊥80 < 7 mm and ΔWET 80 < 5 mm), motion mitigation was not needed. For moderate motion (M ⊥80 7-10 mm or ΔWET 80 5-7 mm), AC produced a modest improvement. For large motion (M ⊥80 > 10 mm or ΔWET 80 > 7 mm), AC and/or some other form of mitigation strategies were required., Conclusion: A workflow for screening patients' motion characteristics and optimizing beam angle selection was established for the pencil beam scanning proton therapy treatment of liver tumors. Abdominal compression was found to be useful at mitigation of moderate and large motion., (© 2016 American Association of Physicists in Medicine.)

Purpose: To quantitatively assess the advantages of energy-layer specific dynamic collimation system (DCS) versus a per-field fixed aperture for spot scanning proton therapy (SSPT)., Methods: Five brain cancer patients previously planned and treated with SSPT were replanned using an in-house treatment planning system capable of modeling collimated and uncollimated proton beamlets. The uncollimated plans, which served as a baseline for comparison, reproduced the target coverage and organ-at-risk sparing of the clinically delivered plans. The collimator opening for the fixed aperture-based plans was determined from the combined cross sections of the target in the beam's eye view over all energy layers which included an additional margin equivalent to the maximum beamlet displacement for the respective energy of that energy layer. The DCS-based plans were created by selecting appropriate collimator positions for each row of beam spots during a Raster-style scanning pattern which were optimized to maximize the dose contributions to the target and limited the dose delivered to adjacent normal tissue., Results: The reduction of mean dose to normal tissue adjacent to the target, as defined by a 10 mm ring surrounding the target, averaged 13.65% (range: 11.8%-16.9%) and 5.18% (2.9%-7.1%) for the DCS and fixed aperture plans, respectively. The conformity index, as defined by the ratio of the volume of the 50% isodose line to the target volume, yielded an average improvement of 21.35% (19.4%-22.6%) and 8.38% (4.7%-12.0%) for the DCS and fixed aperture plans, respectively., Conclusions: The ability of the DCS to provide collimation to each energy layer yielded better conformity in comparison to fixed aperture plans.

Purpose: An adaptive proton therapy workflow using cone beam computed tomography (CBCT) is proposed. It consists of an online evaluation of a fast range-corrected dose distribution based on a virtual CT (vCT) scan. This can be followed by more accurate offline dose recalculation on the vCT scan, which can trigger a rescan CT (rCT) for replanning., Methods and Materials: The workflow was tested retrospectively for 20 consecutive lung cancer patients. A diffeomorphic Morphon algorithm was used to generate the lung vCT by deforming the average planning CT onto the CBCT scan. An additional correction step was applied to account for anatomic modifications that cannot be modeled by deformation alone. A set of clinical indicators for replanning were generated according to the water equivalent thickness (WET) and dose statistics and compared with those obtained on the rCT scan. The fast dose approximation consisted of warping the initial planned dose onto the vCT scan according to the changes in WET. The potential under- and over-ranges were assessed as a variation in WET at the target's distal surface., Results: The range-corrected dose from the vCT scan reproduced clinical indicators similar to those of the rCT scan. The workflow performed well under different clinical scenarios, including atelectasis, lung reinflation, and different types of tumor response. Between the vCT and rCT scans, we found a difference in the measured 95% percentile of the over-range distribution of 3.4 ± 2.7 mm. The limitations of the technique consisted of inherent uncertainties in deformable registration and the drawbacks of CBCT imaging. The correction step was adequate when gross errors occurred but could not recover subtle anatomic or density changes in tumors with complex topology., Conclusions: A proton therapy workflow based on CBCT provided clinical indicators similar to those using rCT for patients with lung cancer with considerable anatomic changes., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To quantify the dosimetric benefit of using a dynamic collimation system (DCS) for penumbra reduction during the treatment of brain tumors by pencil beam scanning proton therapy (PBS PT)., Methods and Materials: Collimated and uncollimated brain treatment plans were created for 5 patients previously treated with PBS PT and retrospectively enrolled in an institutional review board-approved study. The in-house treatment planning system, RDX, was used to generate the plans because it is capable of modeling both collimated and uncollimated beamlets. The clinically delivered plans were reproduced with uncollimated plans in terms of target coverage and organ at risk (OAR) sparing to ensure a clinically relevant starting point, and collimated plans were generated to improve the OAR sparing while maintaining target coverage. Physical and biological comparison metrics, such as dose distribution conformity, mean and maximum doses, normal tissue complication probability, and risk of secondary brain cancer, were used to evaluate the plans., Results: The DCS systematically improved the dose distribution conformity while preserving the target coverage. The average reduction of the mean dose to the 10-mm ring surrounding the target and the healthy brain were 13.7% (95% confidence interval [CI] 11.6%-15.7%; P<.0001) and 25.1% (95% CI 16.8%-33.4%; P<.001), respectively. This yielded an average reduction of 24.8% (95% CI 0.8%-48.8%; P<.05) for the brain necrosis normal tissue complication probability using the Flickinger model, and 25.1% (95% CI 16.8%-33.4%; P<.001) for the risk of secondary brain cancer. A general improvement of the OAR sparing was also observed., Conclusion: The lateral penumbra reduction afforded by the DCS increases the normal tissue sparing capabilities of PBS PT for brain cancer treatment while preserving target coverage., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To quantify improvement in target conformity in brain and head and neck tumor treatments resulting from the use of a dynamic collimation system (DCS) with two spot scanning proton therapy delivery systems (universal nozzle, UN, and dedicated nozzle, DN) with median spot sizes of 5.2 and 3.2 mm over a range of energies from 100 to 230 MeV., Methods: Uncollimated and collimated plans were calculated with both UN and DN beam models implemented within our in-house treatment planning system for five brain and ten head and neck datasets in patients previously treated with spot scanning proton therapy. The prescription dose and beam angles from the clinical plans were used for both the UN and DN plans. The average reduction of the mean dose to the 10-mm ring surrounding the target between the uncollimated and collimated plans was calculated for the UN and the DN. Target conformity was analyzed using the mean dose to 1-mm thickness rings surrounding the target at increasing distances ranging from 1 to 10 mm., Results: The average reductions of the 10-mm ring mean dose for the UN and DN plans were 13.7% (95% CI: 11.6%-15.7%; p < 0.0001) and 11.5% (95% CI: 9.5%-13.5%; p < 0.0001) across all brain cases and 7.1% (95% CI: 4.4%-9.8%; p < 0.001) and 6.3% (95% CI: 3.7%-9.0%; p < 0.001), respectively, across all head and neck cases. The collimated UN plans were either more conformal (all brain cases and 60% of the head and neck cases) than or equivalent (40% of the head and neck cases) to the uncollimated DN plans. The collimated DN plans offered the highest conformity., Conclusions: The DCS added either to the UN or DN improved the target conformity. The DCS may be of particular interest for sites with UN systems looking for a more economical solution than upgrading the nozzle to improve the target conformity of their spot scanning proton therapy system.

Background and Purpose: Radiation is an important modality in treatment of thymic tumors. However, toxicity may reduce its overall benefit. We hypothesized that double-scattering proton beam therapy (DS-PT) can achieve excellent local control with limited toxicity in patients with thymic malignancies., Methods and Materials: Patients with thymoma or thymic carcinoma treated with DS-PT between 2011 and 2015 were prospectively analyzed for toxicity and patterns of failure on an IRB-approved study., Results: Twenty-seven consecutive patients were evaluated. Patients were a median of 56 years and had thymoma (85%). They were treated with definitive (22%), salvage (15%) or adjuvant (63%) DS-PT to a median of 61.2/1.8 Gy [CGE]. No patient experienced grade ⩾3 toxicity. Acute grade 2 toxicities included dermatitis (37%), fatigue (11%), esophagitis (7%), and pneumonitis (4%). Late grade 2 toxicity was limited to a single patient with chronic dyspnea. At a median follow-up of 2 years, 100% local control was achieved. Three-year regional control, distant control, and overall survival rates were 96% (95% CI 76-99%), 74% (95% CI 41-90%), and 94% (95% CI 63-99%), respectively., Conclusions: This is the first cohort and prospective series of proton therapy to treat thymic tumors, demonstrating low rates of early toxicity and excellent initial outcomes., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Target coverage and organ-at-risk sparing were compared for 22 pediatric patients with primary brain tumors treated using two distinct nozzles in pencil beam scanning (PBS) proton therapy. Consecutive patients treated at our institution using a PBS-dedicated nozzle (DN) were replanned using a universal nozzle (UN) beam model and the original DN plan objectives. Various cranial sites were treated among the patients to prescription doses ranging from 45 to 54 Gy. Organs at risk (OARs) evaluated were patient-dependent; 15 unique OARs were analyzed, all of which were assessed in at least 10 patients. Clinical target volume (CTV) coverage and organ sparing were compared for the two nozzles using dose-volume histogram data. Statistical analysis using a confidence-interval approach demonstrates that CTV coverage is equivalent for UN and DN plans within ± 5% equivalence bounds. In contrast, average mean and maximum doses are significantly higher for nearly all 15 OARs in the UN plans. The average median increase over all OARs and patients is approximately 1.7 Gy, with an increase in the 25%-75% of 1.0-2.3 Gy; the median increase to the pituitary gland, temporal lobes, eyes and cochleas are 1.8, 1.7, 0.7, and 2.7 Gy, respectively. The CTV dose distributions fall off slower for UN than for the DN plans; hence, normal tissue structures in close proximity to CTVs receive higher doses in UN plans than in DN plans. The higher OAR doses in the UN plans are likely due to the larger spot profile in plans created with UN beams. In light of the high rates of toxicities in pediatric patients receiving cranial irradiation and in light of selected brain tumor types having high cure rates, this study suggests the smaller DN beam profile is preferable for the advantage of reducing dose to OARs.

The purpose of this study is to determine whether organ sparing and target coverage can be simultaneously maintained for pencil beam scanning (PBS) proton therapy treatment of thoracic tumors in the presence of motion, stopping power uncertainties, and patient setup variations. Ten consecutive patients that were previously treated with proton therapy to 66.6/1.8 Gy (RBE) using double scattering (DS) were replanned with PBS. Minimum and maximum intensity images from 4D CT were used to introduce flexible smearing in the determination of the beam specific PTV (BSPTV). Datasets from eight 4D CT phases, using ± 3% uncertainty in stopping power and ± 3 mm uncertainty in patient setup in each direction, were used to create 8 × 12 × 10 = 960 PBS plans for the evaluation of 10 patients. Plans were normalized to provide identical coverage between DS and PBS. The average lung V20, V5, and mean doses were reduced from 29.0%, 35.0%, and 16.4 Gy with DS to 24.6%, 30.6%, and 14.1 Gy with PBS, respectively. The average heart V30 and V45 were reduced from 10.4% and 7.5% in DS to 8.1% and 5.4% for PBS, respectively. Furthermore, the maximum spinal cord, esophagus, and heart doses were decreased from 37.1 Gy, 71.7 Gy, and 69.2 Gy with DS to 31.3 Gy, 67.9 Gy, and 64.6 Gy with PBS. The conformity index (CI), homogeneity index (HI), and global maximal dose were improved from 3.2, 0.08, 77.4 Gy with DS to 2.8, 0.04, and 72.1 Gy with PBS. All differences are statistically significant, with p-values <0.05, with the exception of the heart V45 (p = 0.146). PBS with BSPTV achieves better organ sparing and improves target coverage using a repainting method for the treatment of thoracic tumors. Incorporating motion-related uncertainties is essential.

Purpose: The purpose of this paper is to demonstrate the utility of a comprehensive test pattern in validating calculation models that include the halo component (low-dose tails) of proton pencil beam scanning (PBS) spots. Such a pattern has been used previously for quality assurance purposes to assess spot shape, position, and dose., Methods: In this study, a scintillation detector was used to measure the test pattern in air at isocenter for two proton beam energies (115 and 225 MeV) of two IBA universal nozzles (UN #1 and UN #2). Planar measurements were compared with calculated dose distributions based on the weighted superposition of location-independent (UN #1) or location-dependent (UN #2) spot profiles, previously measured using a pair-magnification method and between two nozzles., Results: Including the halo component below 1% of the central dose is shown to improve the gamma-map comparison between calculation and measurement from 94.9% to 98.4% using 2 mm/2% criteria for the 115 MeV proton beam of UN #1. In contrast, including the halo component below 1% of the central dose does not improve the gamma agreement for the 115 MeV proton beam of UN #2, due to the cutoff of the halo component at off-axis locations. When location-dependent spot profiles are used for calculation instead of spot profiles at central axis, the gamma agreement is improved from 98.0% to 99.5% using 2 mm/2% criteria. The two nozzles clearly have different characteristics, as a direct comparison of measured data shows a passing rate of 89.7% for the 115 MeV proton beam. At 225 MeV, the corresponding gamma comparisons agree better between measurement and calculation, and between measurements in the two nozzles., Conclusions: In addition to confirming the primary component of individual PBS spot profiles, a comprehensive test pattern is useful for the validation of the halo component at off-axis locations, especially for low energy protons.

The need to accurately and efficiently verify both output and dose profiles creates significant challenges in quality assurance of pencil beam scanning (PBS) proton delivery. A system for PBS QA has been developed that combines a new two-dimensional ionization chamber array in a waterproof housing that is scanned in a water phantom. The MatriXX PT has the same detector array arrangement as the standard MatriXX(Evolution) but utilizes a smaller 2 mm plate spacing instead of 5mm. Because the bias voltage of the MatriXX PT and Evolution cannot be changed, PPC40 and FC65-G ionization chambers were used to assess recombination effects. The PPC40 is a parallel plate chamber with an electrode spacing of 2mm, while the FC65-G is a Farmer chamber FC65-G with an electrode spacing of 2.8 mm. Three bias voltages (500, 200, and 100 V) were used for both detectors to determine which radiation type (continuous, pulse or pulse-scanned beam) could closely estimate Pion from the ratios of charges collected. In comparison with the MatriXX(Evolution), a significant improvement in measurement of absolute dose with the MatriXX PT was observed. While dose uncertainty of the MatriXX(Evolution) can be up to 4%, it is < 1% for the MatriXX PT. Therefore the MatriXX(Evolution) should not be used for QA of PBS for conditions in which ion recombination is not negligible. Farmer chambers should be used with caution for measuring the absolute dose of PBS beams, as the uncertainty of Pion can be > 1%; chambers with an electrode spacing of 2 mm or smaller are recommended.

Radiation therapy depends on predictably and reliably delivering dose to tumors and sparing normal tissues. Protons with kinetic energy of a few hundred MeV can selectively deposit dose to deep seated tumors without an exit dose, unlike x-rays. The better dose distribution is attributed to a phenomenon known as the Bragg peak. The Bragg peak is due to relatively high energy deposition within a given distance or high Linear Energy Transfer (LET). In addition, biological response to radiation depends on the dose, dose rate, and localized energy deposition patterns or LET. At present, the LET can only be measured at a given fixed point and the LET spatial distribution can only be inferred from calculations. The goal of this study is to develop and test a method to measure LET over extended areas. Traditionally, radiochromic films are used to measure dose distribution but not for LET distribution. We report the first use of these films for measuring the spatial distribution of the LET deposited by protons. The radiochromic film sensitivity diminishes for large LET. A mathematical model correlating the film sensitivity and LET is presented to justify relating LET and radiochromic film relative sensitivity. Protons were directed parallel to radiochromic film sandwiched between solid water slabs. This study proposes the scaled-normalized difference (SND) between the Treatment Planning system (TPS) and measured dose as the metric describing the LET. The SND is correlated with a Monte Carlo (MC) calculation of the LET spatial distribution for a large range of SNDs. A polynomial fit between the SND and MC LET is generated for protons having a single range of 20 cm with narrow Bragg peak. Coefficients from these fitted polynomial fits were applied to measured proton dose distributions with a variety of ranges. An identical procedure was applied to the protons deposited from Spread Out Bragg Peak and modulated by 5 cm. Gamma analysis is a method for comparing the calculated LET with the LET measured using radiochromic film at the pixel level over extended areas. Failure rates using gamma analysis are calculated for areas in the dose distribution using parameters of 25% of MC LET and 3 mm. The processed dose distributions find 5%-10% failure rates for the narrow 12.5 and 15 cm proton ranges and 10%-15% for proton ranges of 15, 17.5, and 20 cm and modulated by 5 cm. It is found through gamma analysis that the measured proton energy deposition in radiochromic film and TPS can be used to determine LET. This modified film dosimetry provides an experimental areal LET measurement that can verify MC calculations, support LET point measurements, possibly enhance biologically based proton treatment planning, and determine the polymerization process within the radiochromic film.

The presence of a low-dose envelope, or 'halo', in the fluence profile of a proton spot can increase the output of a pencil beam scanning field by over 10%. This study evaluated whether the Monte Carlo simulation code, TOPAS 1.0-beta 8, based on Geant4.9.6 with its default physics list, can predict the spot halo at depth in phantom by incorporating a halo model within the proton source distribution. Proton sources were modelled using three 2D Gaussian functions, and optimized until simulated spot profiles matched measurements at the phantom surface out to a radius of 100 mm. Simulations were subsequently compared with profiles measured using EBT3 film in Solidwater® phantoms at various depths for 100, 115, 150, 180, 210 and 225 MeV proton beams. Simulations predict measured profiles within a 1 mm distance to agreement for 2D profiles extending to the 0.1% isodose, and within 1 mm/1% Gamma criteria over the integrated curve of spot profile as a function of radius. For isodose lines beyond 0.1% of the central spot dose, the simulated primary spot sigma is smaller than the measurement by up to 15%, and can differ by over 1 mm. The choice of particle interaction algorithm and phantom material were found to cause ~1 mm range uncertainty, a maximal 5% (0.3 mm) difference in spot sigma, and maximal 1 mm and ~2 mm distance to agreement in isodoses above and below the 0.1% level, respectively. Based on these observations, therefore, the selection of physics model and the application of Solidwater® as water replacement material in simulation and measurement should be used with caution.

Purpose: To report on a universal bolus (UB) designed to replace the range shifter (RS); the UB allows the treatment of shallow tumors while keeping the pencil beam scanning (PBS) spot size small., Methods and Materials: Ten patients with brain cancers treated from 2010 to 2011 were planned using the PBS technique with bolus and the RS. In-air spot sizes of the pencil beam were measured and compared for 4 conditions (open field, with RS, and with UB at 2- and 8-cm air gap) in isocentric geometry. The UB was applied in our clinic to treat brain tumors, and the plans with UB were compared with the plans with RS., Results: A UB of 5.5 cm water equivalent thickness was found to meet the needs of the majority of patients. By using the UB, the PBS spot sizes are similar with the open beam (P>.1). The heterogeneity index was found to be approximately 10% lower for the UB plans than for the RS plans. The coverage for plans with UB is more conformal than for plans with RS; the largest increase in sparing is usually for peripheral organs at risk., Conclusions: The integrity of the physical properties of the PBS beam can be maintained using a UB that allows for highly conformal PBS treatment design, even in a simple geometry of the fixed beam line when noncoplanar beams are used., (Copyright © 2014. Published by Elsevier Inc.)

Because treatment planning systems (TPSs) generally do not provide monitor units (MUs) for double-scattered proton plans, models to predict MUs as a function of the range and the nominal modulation width requested of the beam delivery system, such as the one developed by the MGH group, have been proposed. For a given nominal modulation width, however, the measured modulation width depends on the accuracy of the vendor's calibration process and may differ from this nominal value, and also from one beamline to the next. Although such a difference can be replicated in our TPS, the output dependence on range and modulation width for each beam option or suboption has to be modeled separately for each beamline in order to achieve maximal 3% inaccuracy. As a consequence, the MGH output model may not be directly transferable. This work, therefore, serves to extend the model to more general clinic situations. In this paper, a parameterized linear-quadratic transformation is introduced to convert the nominal modulation width to the measured modulation width for each beam option or suboption on a per-beamline basis. Fit parameters are derived for each beamline from measurements of 60 reference beams spanning the minimum and maximum ranges, and modulation widths from 2 cm to full range per option or suboption. Using the modeled modulation width, we extract the MGH parameters for the output dependence on range and modulation width. Our method has been tested with 1784 patient-specific fields delivered across three different beamlines at our facility. For these fields, all measured outputs fall within 3%, and 64.4% fall within 1%, of our model. Using a parameterized linear-quadratic modulation width, MU calculation models can be established on a per-beamline basis for each double scattering beam option or suboption.

Dose calculation for pencil beam scanning proton therapy requires accurate measurement of the broad tails of the proton spot profiles for every nozzle in clinical use. By applying a pair/magnification method and merging film data, 200 mm × 240 mm dose kernels extending to 10(-4) of the central spot dose are generated for six selected energies of the IBA dedicated and universal nozzles (DN and UN). One-dimensional, circular profiles up to 100 mm in radius are generated from the asymmetric profiles to facilitate spot profile comparison. For the highest energy, 225 MeV, the output of both the DN and the UN for field sizes from 40 to 200 mm increases in parallel, slowest at the surface (∼1%) and fastest at a depth of 150 mm (∼9%). In contrast, at the lowest energy, 100 MeV, the output of the DN across the same range of field sizes increases 3-4% versus 6-7% for the UN throughout all the depths. The charge deficits in the measured depth-dose of Bragg peaks are similar between the UN and the DN. At 100 MeV, the field size factor difference at the surface between two orientations of a rectangular 40 mm × 200 mm field is 1.4% at isocentre for the DN versus 2% for the UN. Though the one-dimensional distributions are similar for the primary and tail components at different positions, the primary components of the DN spots are more elliptical 270 mm upstream than at isocentre.

Dose calculations of pencil beam scanning treatment plans rely on the accuracy of proton spot profiles; not only the primary component but also the broad tail components. Four films are placed at several locations in air and multiple depths in Solidwater® for six selected energies. The films used for the primary components are exposed to 50-200 MU to avoid saturation; the films used for the tail components are exposed to 800, 8000 and 80,000 MU. By applying a pair/magnification method and merging these data, dose kernels down to 10(-4) of the central spot dose can be generated. From these kernels one can calculate the dose-per-MU for different field sizes and shapes. Measurements agree within 1% of dose-kernel-based calculations for output versus field size comparisons. Asymmetric, comet-shaped profile tails have a bigger impact at superficial depths and low energies: the output difference between two orientations at the surface of a rectangular field of 40 mm×200 mm is about 2% at the isocentre at 100 MeV. Integration of these dose kernels from 0 to 40 mm radius shows that the charge deficit in the Bragg peak chamber varies <2% from entrance to the end of range for energies <180 MeV, but exceeds 5% at 225 MeV.

The configuration of a treatment planning system (TPS) for double-scattering-based proton therapy requires many user inputs. Most of these are either gathered during the routine collection of commissioning data, or can be supplied by the equipment vendor; however, this is not true of all. In this study we developed a technique both to (a) expedite the extraction of those undetermined TPS parameters related to the range modulator wheels that can only otherwise be obtained by the time-consuming process of trial-and-error, and (b) demonstrate how, for a commonly-employed, commercially-available TPS, the judicious determination of such parameters can be used to optimize the resultant modelling of longitudinal dose distributions delivered by a double scattering proton therapy system. Our technique is simple to implement, robust in nature and also provides insight allowing parameters that must be contrived in that model to be related directly to physical aspects of the beam delivery system.

Purpose: The authors we evaluate the uncertainty in proton therapy dose distribution for prostate cancer due to organ displacement, varying penumbra width of proton beams, and the amount of rectal gas inside the rectum., Methods and Materials: Proton beam treatment plans were generated for ten prostate patients with a minimum dose of 74.1 cobalt gray equivalent (CGE) to the planning target volume (PTV) while 95% of the PTV received 78 CGE. Two lateral or lateral oblique proton beams were used for each plan. The authors we investigated the uncertainty in dose to the rectal wall (RW) and the bladder wall (BW) due to organ displacement by comparing the dose-volume histograms (DVH) calculated with the original or shifted contours. The variation between DVHs was also evaluated for patients with and without rectal gas in the rectum for five patients who had 16 to 47 cc of visible rectal gas in their planning computed tomography (CT) imaging set. The uncertainty due to the varying penumbra width of the delivered protons for different beam setting options on the proton delivery system was also evaluated., Results: For a 5 mm anterior shift, the relative change in the RW volume receiving 70 CGE dose (V70) was 37.9% (5.0% absolute change in 13.2% of a mean V70). The relative change in the BW volume receiving 70 CGE dose (V70) was 20.9% (4.3% absolute change in 20.6% of a mean V70) with a 5 mm inferior shift. A 2 mm penumbra difference in beam setting options on the proton delivery system resulted in the relative variations of 6.1% (0.8% absolute change) and 4.4% (0.9% absolute change) in V70 of RW and BW, respectively. The data show that the organ displacements produce absolute DVH changes that generally shift the entire isodose line while maintaining the same shape. The overall shape of the DVH curve for each organ is determined by the penumbra and the distance of the target in beam's eye view (BEV) from the block edge. The beam setting option producing a 2 mm sharper penumbra at the isocenter can reduce the magnitude of maximal doses to the RW by 2% compared to the alternate option utilizing the same block margin of 7 mm. The dose to 0.1 cc of the femoral head on the distal side of the lateral-posterior oblique beam is increased by 25 CGE for a patient with 25 cc of rectal gas., Conclusion: Variation in the rectal and bladder wall DVHs due to uncertainty in the position of the organs relative to the location of sharp dose falloff gradients should be accounted for when evaluating treatment plans. The proton beam delivery option producing a sharper penumbra reduces maximal doses to the rectal wall. Lateral-posterior oblique beams should be avoided in patients prone to develop a large amount of rectal gas.

Purpose: To determine the target coverage for proton therapy with and without image guidance and daily prebeam reorientation., Methods and Materials: A total of 207 prostate positions were analyzed for 9 prostate cancer patients treated using our low-risk prostate proton therapy protocol (University of Florida Proton Therapy Institute 001). The planning target volume was defined as the prostate plus a 5-mm axial and 8-mm superoinferior extension. The prostate was repositioned using 5- and 10-mm shifts (anteriorly, inferiorly, posteriorly, and superiorly) and for Points A-D using a combination of 10-mm multidimensional movements (anteriorly or inferiorly; posteriorly or superiorly; and left or right). The beams were then realigned using the new prostate position. The prescription dose was 78 Gray equivalent (GE) to 95% of the planning target volume., Results: For small movements in the anterior, inferior, and posterior directions within the planning target volume (< or =5 mm), treatment realignment demonstrated small, but significant, improvements in the clinical target volume (CTV) coverage to the prescribed dose (78 GE). The anterior and posterior shifts also significantly increased the minimal CTV dose (Delta +1.59 GE). For prostate 10-mm movements in the inferior, posterior, and superior directions, the beam realignment produced larger and significant improvements for both the CTV V(78) (Delta +6.4%) and the CTV minimal dose (Delta +8.22 GE). For the compounded 10-mm multidimensional shifts, realignment significantly improved the CTV V(78) (Delta +11.8%) and CTV minimal dose (Delta +23.6 GE). After realignment, the CTV minimal dose was >76.6 GE (>98%) for all points (A-D)., Conclusion: Proton beam realignment after target shift will enhance CTV coverage for different prostate positions.

Purpose: To determine the impact of prostate motion on dose coverage in proton therapy., Methods and Materials: A total of 120 prostate positions were analyzed on 10 treatment plans for 10 prostate patients treated using our low-risk proton therapy prostate protocol (University of Florida Proton Therapy Institute 001). Computed tomography and magnetic resonance imaging T(2)-weighted turbo spin-echo scans were registered for all cases. The planning target volume included the prostate with a 5-mm axial and 8-mm superoinferior expansion. The prostate was repositioned using 5- and 10-mm one-dimensional vectors and 10-mm multidimensional vectors (Points A-D). The beam was realigned for the 5- and 10-mm displacements. The prescription dose was 78 Gy equivalent (GE)., Results: The mean percentage of rectum receiving 70 Gy (V(70)) was 7.9%, the bladder V(70) was 14.0%, and the femoral head/neck V(50) was 0.1%, and the mean pelvic dose was 4.6 GE. The percentage of prostate receiving 78 Gy (V(78)) with the 5-mm movements changed by -0.2% (range, 0.006-0.5%, p > 0.7). However, the prostate V(78) after a 10-mm displacement changed significantly (p < 0.003) with different movements: 3.4% (superior), -5.6% (inferior), and -10.2% (posterior). The corresponding minimal doses were also reduced: 4.5 GE, -4.7 GE, and -11.7 GE (p < or = 0.003). For displacement points A-D, the clinical target volume V(78) coverage had a large and significant reduction of 17.4% (range, 13.5-17.4%, p < 0.001) in V(78) coverage of the clinical target volume. The minimal prostate dose was reduced 33% (25.8 GE), on average, for Points A-D. The prostate minimal dose improved from 69.3 GE to 78.2 GE (p < 0.001) with realignment for 10-mm movements., Conclusion: The good dose coverage and low normal doses achieved for the initial plan was maintained with movements of < or = 5 mm. Beam realignment improved coverage for 10-mm displacements.