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A common limitation in clinical as well as investigational lung radiotherapy (RT) is that radiation-induced lung injury (RILI) is modeled primarily based on local-regional parenchymal damage. The predictive performance of these models is relatively poor. Mounting evidence from our studies and others suggests that damage to airways and pulmonary vasculature significantly impacts post- RT lung function. We hypothesize that including radiation-induced damage to airways in current (parenchyma-based) predictive dose-response models will improve the estimation of post-RT ventilation loss. Specifically, we develop and validate a model, [P+A] to estimate post-RT ventilation based on radiation damage to lung parenchyma [P] and radiation-induced partial and complete obstruction of airways [A]. Following informed consent, pre-RT breath-hold CTs (BHCTs) and pre- and post-RT 4DCTs were prospectively acquired from locally-advanced lung cancer patients receiving definitive treatment. For each patient, 9-12 generations of airways were segmented on the BHCT using a virtual bronchoscopy software. For each terminal airway, we defined a sub-lobar volume (SLV), comprising the nearest voxels within the containing lobe. 4DCT-based ventilation maps were calculated and used to estimate pre- and post-RT ventilation, serving as the model input and reference standard for model validation, respectively. For predictive modeling, ventilation loss due to parenchymal damage was estimated using a previous NTCP model. Ventilation loss due to partial or complete airway obstruction was estimated using our previous airway radiosensitivity model and fluid dynamics principles. We divided the data into training and test sets (Ntr and Nts in Table) and conducted a k-fold cross-validation by comparing predicted and actual post-RT ventilation in the SLVs in the test dataset and calculating receiver operating characteristic (ROC) metrics. Within a dataset of 560 SLVs from four evaluable patients, the P+A model outperformed the P model, with lower average RMSEs: 13 ± 3 percentile [P+A model] vs 24 ± 3 percentile [P model]. The P+A model aligned closely with the actual lobar post-RT ventilation maps derived from post-RT 4DCTs, particularly in high-dose regions. ROC analysis showed that the P+A model outperformed the P model by demonstrating higher sensitivity (0.98 vs. 0.07) and higher accuracy (0.87 vs. 0.25). These results address an important gap in our understanding of the role of radiation-induced airway damage and its role in accurately modeling RILI. [ABSTRACT FROM AUTHOR]

Purpose: Pencil-beam scanning proton therapy has been considered a potential modality for the 3D form of spatially fractionated radiation therapy called lattice therapy. However, few practical solutions have been introduced in the clinic. Existing limitations include degradation in plan quality and robustness when using single-field versus multifield lattice plans, respectively. We propose a practical and robust proton lattice (RPL) planning method using multifield and evaluate its dosimetric characteristics compared to clinically acceptable photon lattice plans., Methods and Materials: Seven cases previously treated with photon lattice therapy were used to evaluate a novel RPL planning technique using 2-orthogonal beams: a primary beam (PB) and a robust complementary beam (RCB) that deliver 67% and 33%, respectively, of the prescribed dose to vertices inside the gross target volume (GTV). Only RCB is robustly optimized for setup and range uncertainties. The number and volume of vertices, peak-to-valley dose ratios (PVDRs), and volume of low dose to GTV of proton and photon plans were compared. The RPL technique was then used in the treatment of 2 patients and their dosimetric parameters were reported., Results: The RPL strategy was able to achieve the clinical planning goals. Compared to previously treated photon plans, the average number of vertices increased by 30%, the average vertex volume by 49% (18.2 ± 25.9 cc vs 12.2 ± 14.5 cc, P = .21), and higher PVDR (10.5 ± 4.8 vs 2.5 ± 0.9, P < .005) was achieved. In addition, RPL plans show more conformal dose with less low dose to GTV (V30%, 60.9% ± 7.2% vs 81.6% ± 13.9% and V10%, 88.3% ± 4.5% vs 98.6% ± 3.6% [P < .01]). The RPL plan for 2 treated patients showed PVDRs of 4.61 and 14.85 with vertices-to-GTV ratios of 1.52% and 1.30%, respectively., Conclusions: A novel RPL planning strategy using a pair of orthogonal beams was developed and successfully translated to the clinic. The proposed method can generate better quality plans, a higher number of vertices, and higher PVDRs than currently used photon lattice plans., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Proton beam therapy (PBT) plays an important role in the management of primary spine tumors. The purpose of this consensus statement was to summarize safe and optimal delivery of PBT for spinal tumors., Methods and Materials: The Particle Therapy Cooperative Group Skull Base/Central nervous system/Sarcoma Subcommittee consisting of radiation oncologists and medical physicists with specific expertise in spinal irradiation developed expert recommendations discussing treatment planning considerations and current approaches in the treatment of primary spinal tumors., Results: Computed tomography simulation: factors that require significant consideration include (1) patient comfort, (2) setup reproducibility and stability, and (3) accessibility of appropriate beam angles., Spine Stabilization Hardware: If present, hardware should be placed with cross-links well above/below the level of the primary tumor to reduce the metal burden at the level of the tumor bed. New materials that can reduce uncertainties include polyether-ether-ketone and composite polyether-ether-ketone-carbon fiber implants., Field Arrangement: Appropriate beam selection is required to ensure robust target coverage and organ at risk sparing. Commonly, 2 to 4 treatment fields, typically from posterior and/or posterior-oblique directions, are used., Treatment Planning Methodology: Robust optimization is recommended for all pencil beam scanning plans (the preferred treatment modality) and should consider setup uncertainty (between 3 and 7 mm) and range uncertainty (3%-3.5%). In the presence of metal hardware, use of an increased range uncertainty up to 5% is recommended., Conclusions: The Particle Therapy Cooperative Group Skull Base/Central nervous system/Sarcoma Subcommittee has developed recommendations to enable centers to deliver PBT safely and effectively for the management of primary spinal tumors., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To explore the feasibility of a novel intensity-modulated proton arc technique that uses a single-energy beam from the cyclotron. The beam energy is externally modulated at each gantry angle by a tertiary energy modulator (EM). We hypothesize that irradiating in an arc without requiring an energy change from the cyclotron will achieve a faster delivery (main advantage of our technique) while keeping clinically desirable dosimetric results., Methods: In a retrospective cohort of four patients with female pelvis, prostate, lung, and brain cancers, we investigated our volumetric-modulated proton arc therapy (VPAT) technique. Arcs were simulated by sectors of 1°-spaced static beams. Keeping the energy requested from the cyclotron the same for each entire arc was supported by a predesigned EM placed in front of the nozzle. As a feasibility measure, EM thicknesses were calculated. Delivery times and doses to targets and organs at risk (OARs) were compared to those of the clinical plans., Results: VPAT plans were comparable to their clinical counterparts in achieving target dose conformity, being robust to uncertainties, and meeting clinical dose-volume constraints. Cyclotron energies for the four cases were within 159-220 MeV, and energy modulation range was 69-100 MeV, equivalent to 13-19 cm of water-equivalent thickness (WET). Plan delivery times were reduced from > 5 min in our clinical practice to < 3.5 min in VPAT., Conclusion: For the evaluated plans, the novel VPAT approach achieved shorter delivery times without sacrificing robustness, OAR sparing or target coverage. VPAT's EMs had WETs implementable in a clinical setup., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Purpose: Since the inaugural workshop "Understanding High-Dose, Ultra-High Dose Rate and Spatially Fractionated Radiotherapy." hosted by the NCI and sponsored by the Radiosurgery Society (RSS), growing collaborations and investigations have ensued among experts, practitioners, and researchers. The RSS GRID, Lattice, Microbeam & FLASH (GLMF) Working Groups were formed as a framework for these efforts and have focused on advancing the understanding of the biology, technical/physical parameters, trial design, and clinical practice of these new radiation therapy modalities., Methods and Materials: In view of the steadily increasing clinical interest in SFRT and FLASH, a full-day symposium entitled "Advancements in GRID, LATTICE, and FLASH Radiotherapy Symposium" was established in 2022 that immediately preceded the RSS scientific meeting. This well-attended symposium focused on clinical, technical, and physics approaches for SFRT, while closely examining relevant radiobiological underpinnings. Practical clinical trial development was a highlighted discussion. An additional section reviewed proton therapy and other particle-based techniques for the delivery of GRID and Lattice therapy. A treatment planning and delivery tutorial for GRID, Lattice, and proton GRID/Lattice was directed towards the real-world considerations for the development of new clinical GRID or LATTICE programs. An overall similar approach was applied to the discussion of FLASH. This report summarizes the content of the first GLMF Symposium and related work of the RSS GLMF Working Groups in the field of heterogeneous and ultra-high dose rate irradiation, over approximately 2 years., Results: The GLMF Working Groups have continued to expand in membership and attendance, and several resultant trial concepts, research efforts, academic discussions, and peer-reviewed publications have followed as the number of institutions and practitioners utilizing SFRT and FLASH continues to grow., Conclusions: The GLFM Working Groups and the RSS continue to demonstrate excellent progress in proliferating use of and improving understanding of SFRT and ultra-high dose rate radiotherapy techniques., Competing Interests: Declaration of competing interest The Radiosurgery Society and Varian Medical Systems logistically and financially supported the 2022 Symposium discussed in this effort. Dr. James W Snider declares consulting fees and honoraria from Siemens Healthineers, Varian Medical Systems, and Proton International LLC. Dr. Snider further declares honoraria from Florida Atlantic University. Dr. Snider declares meeting support from Varian Medical Systems and Proton International LLC. Dr. Snider holds a patent for spatially fractionated radiotherapy techniques. Dr. Snider maintains leadership roles with Proton International LLC, Chondrosarcoma Foundation, and the GLFM Working Group. Dr. Nina Mayr declares compensation for expert medical testimony and a leadership Co-Chair position with the GLFM Working Group. Dr. Arpit Chhabra declares consulting fees from Icotec Medical. Dr. Robert Griffin declares grant funding from the NIH, NCI, and Wintrop P Rockefeller Cancer Institute. Dr. Griffin also declares meeting registration support from the RSS and a leadership Co-Chair position with the GLFM Working Group. Dr. Beatriz Amendola declares a speaker's bureau position with Varian Medical Systems. Dr. Minglei Kang declares grant funding from Varian Medical Systems. Dr. Charles Limoli declares grant funding related to FLASH radiotherapy, consultant fees and honoraria from IBA Naipy Perez, MS declares a speaker's bureau position with Varian Medical Systems. Dr. Charles B Simone declares honoraria from Varian Medical Systems, a leadership Co-Chair position with the GLFM Working Group, and a Chair leadership position with the Varian FlashForward Consortium Clinical Committee., (Copyright © 2024. Published by Elsevier Inc.)

Background: Protoacoustic (PA) imaging has the potential to provide real-time 3D dose verification of proton therapy. However, PA images are susceptible to severe distortion due to limited angle acquisition. Our previous studies showed the potential of using deep learning to enhance PA images. As the model was trained using a limited number of patients' data, its efficacy was limited when applied to individual patients., Purpose: In this study, we developed a patient-specific deep learning method for protoacoustic imaging to improve the reconstruction quality of protoacoustic imaging and the accuracy of dose verification for individual patients., Methods: Our method consists of two stages: in the first stage, a group model is trained from a diverse training set containing all patients, where a novel deep learning network is employed to directly reconstruct the initial pressure maps from the radiofrequency (RF) signals; in the second stage, we apply transfer learning on the pre-trained group model using patient-specific dataset derived from a novel data augmentation method to tune it into a patient-specific model. Raw PA signals were simulated based on computed tomography (CT) images and the pressure map derived from the planned dose. The reconstructed PA images were evaluated against the ground truth by using the root mean squared errors (RMSE), structural similarity index measure (SSIM) and gamma index on 10 specific prostate cancer patients. The significance level was evaluated by t-test with the p-value threshold of 0.05 compared with the results from the group model., Results: The patient-specific model achieved an average RMSE of 0.014 ( p < 0.05 ${{{p}}}&lt;{0.05}$ ), and an average SSIM of 0.981 ( p < 0.05 ${{{p}}}&lt;{0.05}$ ), out-performing the group model. Qualitative results also demonstrated that our patient-specific approach acquired better imaging quality with more details reconstructed when comparing with the group model. Dose verification achieved an average RMSE of 0.011 ( p < 0.05 ${{{p}}}&lt;{0.05}$ ), and an average SSIM of 0.995 ( p < 0.05 ${{{p}}}&lt;{0.05}$ ). Gamma index evaluation demonstrated a high agreement (97.4% [ p < 0.05 ${{{p}}}&lt;{0.05}$ ] and 97.9% [ p < 0.05 ${{{p}}}&lt;{0.05}$ ] for 1%/3  and 1%/5 mm) between the predicted and the ground truth dose maps. Our approach approximately took 6 s to reconstruct PA images for each patient, demonstrating its feasibility for online 3D dose verification for prostate proton therapy., Conclusions: Our method demonstrated the feasibility of achieving 3D high-precision PA-based dose verification using patient-specific deep-learning approaches, which can potentially be used to guide the treatment to mitigate the impact of range uncertainty and improve the precision. Further studies are needed to validate the clinical impact of the technique., (© 2024 American Association of Physicists in Medicine.)

Purpose: A higher minimum monitor unit (minMU) for pencil-beam scanning proton beams in intensity-modulated proton therapy is preferred for more efficient delivery. However, plan quality may be compromised when the minMU is too large. This study aimed to identify the optimal minMU (OminMU) to improve plan delivery efficiency while maintaining high plan quality., Methods: We utilized clinical plans including six anatomic sites (brain, head and neck, breast, lung, abdomen, and prostate) from 23 patients previously treated with the Varian ProBeam system. The minMU of each plan was increased from the current clinical minMU of 1.1 to 3-24 MU depending on the daily prescribed dose (DPD). The dosimetric parameters of the plans were evaluated for consistency against a 1.1-minMU plan for target coverage as well as organs-at-risk dose sparing. DPD/minMU was defined as the ratio of DPD to minMU (cGy/MU) to find the OminMU by ensuring that dosimetric parameters did not differ by >1% compared to those of the 1.1-minMU plan., Results: All plans up to 5 minMU showed no significant dose differences compared to the 1.1-minMU plan. Plan qualities remained acceptable when DPD/minMU ≥35 cGy/MU. This suggests that the 35 cGy/MU criterion can be used as the OminMU, which implies that 5 MU is the OminMU for a conventional fraction dose of 180 cGy. Treatment times were decreased by an average of 32% (max 56%, min 7%) and by an average of 1.6 min when the minMU was increased from 1.1 to OminMU., Conclusion: A clinical guideline for OminMU has been established. The minMU can be increased by 1 MU for every 35 cGy of DPD without compromising plan quality for most cases analyzed in this study. Significant treatment time reduction of up to 56% was observed when the suggested OminMU is used., (© 2024 The Author(s). Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Background: Investigations on radiation-induced lung injury (RILI) have predominantly focused on local effects, primarily those associated with radiation damage to lung parenchyma. However, recent studies from our group and others have revealed that radiation-induced damage to branching serial structures such as airways and vessels may also have a substantial impact on post-radiotherapy (RT) lung function. Furthermore, recent results from multiple functional lung avoidance RT trials, although promising, have demonstrated only modest toxicity reduction, likely because they were primarily focused on dose avoidance to lung parenchyma. These observations emphasize the critical need for predictive dose-response models that effectively incorporate both local and distant RILI effects., Purpose: We develop and validate a predictive model for ventilation loss after lung RT. This model, referred to as P+A, integrates local (parenchyma [P]) and distant (central and peripheral airways [A]) radiation-induced damage, modeling partial (narrowing) and complete (collapse) obstruction of airways., Methods: In an IRB-approved prospective study, pre-RT breath-hold CTs (BHCTs) and pre- and one-year post-RT 4DCTs were acquired from lung cancer patients treated with definitive RT. Up to 13 generations of airways were automatically segmented on the BHCTs using a research virtual bronchoscopy software. Ventilation maps derived from the 4DCT scans were utilized to quantify pre- and post-RT ventilation, serving, respectively, as input data and reference standard (RS) in model validation. To predict ventilation loss solely due to parenchymal damage (referred to as P model), we used a normal tissue complication probability (NTCP) model. Our model used this NTCP-based estimate and predicted additional loss due radiation-induced partial or complete occlusion of individual airways, applying fluid dynamics principles and a refined version of our previously developed airway radiosensitivity model. Predictions of post-RT ventilation were estimated in the sublobar volumes (SLVs) connected to the terminal airways. To validate the model, we conducted a k-fold cross-validation. Model parameters were optimized as the values that provided the lowest root mean square error (RMSE) between predicted post-RT ventilation and the RS for all SLVs in the training data. The performance of the P+A and the P models was evaluated by comparing their respective post-RT ventilation values with the RS predictions. Additional evaluation using various receiver operating characteristic (ROC) metrics was also performed., Results: We extracted a dataset of 560 SLVs from four enrolled patients. Our results demonstrated that the P+A model consistently outperformed the P model, exhibiting RMSEs that were nearly half as low across all patients (13 ± 3 percentile for the P+A model vs. 24 ± 3 percentile for the P model on average). Notably, the P+A model aligned closely with the RS in ventilation loss distributions per lobe, particularly in regions exposed to doses ≥13.5 Gy. The ROC analysis further supported the superior performance of the P+A model compared to the P model in sensitivity (0.98 vs. 0.07), accuracy (0.87 vs. 0.25), and balanced predictions., Conclusions: These early findings indicate that airway damage is a crucial factor in RILI that should be included in dose-response modeling to enhance predictions of post-RT lung function., (© 2024 American Association of Physicists in Medicine.)

Objective . To fabricate and validate a novel focused collimator designed to spare normal tissue in a murine hemithoracic irradiation model using 250 MeV protons delivered at ultra-high dose rates (UHDRs) for preclinical FLASH radiation therapy (FLASH-RT) studies. Approach . A brass collimator was developed to shape 250 MeV UHDR protons from our Varian ProBeam. Six 13 mm apertures, of equivalent size to kV x-ray fields historically used to perform hemithorax irradiations, were precisely machined to match beam divergence, allowing concurrent hemithoracic irradiation of six mice while sparing the contralateral lung and abdominal organs. The collimated field profiles were characterized by film dosimetry, and a radiation survey of neutron activation was performed to ensure the safety of staff positioning animals. Main results . The brass collimator produced 1.2 mm penumbrae radiation fields comparable to kV x-rays used in preclinical studies. The penumbrae in the six apertures are similar, with full-width half-maxima of 13.3 mm and 13.5 mm for the central and peripheral apertures, respectively. The collimator delivered a similar dose at an average rate of 52 Gy s -1 for all apertures. While neutron activation produces a high (0.2 mSv h -1 ) initial ambient equivalent dose rate, a parallel work-flow in which imaging and setup are performed without the collimator ensures safety to staff. Significance . Scanned protons have the greatest potential for future translation of FLASH-RT in clinical treatments due to their ability to treat deep-seated tumors with high conformality. However, the Gaussian distribution of dose in proton spots produces wider lateral penumbrae compared to other modalities. This presents a challenge in small animal pre-clinical studies, where millimeter-scale penumbrae are required to precisely target the intended volume. Offering high-throughput irradiation of mice with sharp penumbrae, our novel collimator-based platform serves as an important benchmark for enabling large-scale, cost-effective radiobiological studies of the FLASH effect in murine models., (© 2024 Institute of Physics and Engineering in Medicine.)

Background: Proton linear energy transfer (LET) is associated with the relative biological effectiveness of radiation on tissues. Monte Carlo (MC) simulations have been known to be the preferred method to calculate LET. Detectors have also been built to measure LET, but they need to be calibrated with MC simulations., Purpose: To propose and test a MC-free method for determining LET from the measured integral depth dose (LFI) of the protons of interest., Method and Materials: LFI consists of three steps: (1) IDD measurements, (2) extraction of energy spectrum (ES) from the IDD, and (3) LET determination from the extracted ES and the stopping power of each energy. To validate the accuracy of the extraction of ES, we use Gaussian ES to synthesize IDD, extract ES from the synthesized IDD, and then compare the original (ground truth) and extracted ES. LETs calculated from the original and extracted ES are also compared. To obtain the LET of protons of interest, we measure IDDs by a large-area plane-parallel ionization chamber in water. Finally, TOPAS MC is employed to simulate IDDs, ES, and LETs. From the simulated IDD, the extracted ES and LET are compared with the simulations from TOPAS MC., Results: From the synthesized IDDs, the LETs agreed excellently when the peak energies ≥10 and 1.25 MeV with depth resolutions 0.1 and 0.01 mm, respectively. For energy <1.25 MeV, even higher depth resolution than 0.01 mm is required. From the MC simulated IDDs, our track-averaged LET excellently agreed with MC simulation, but not the LET d . Our LET d was smaller than MC simulated LET d in the shallow region but larger in the distal Bragg peak region., Conclusion: LET can be accurately determined from the IDD. This method can be used in the clinic to commission or validate LETs from other measurement methods or a treatment planning system., (© 2023 American Association of Physicists in Medicine.)

Purpose: The highly heterogeneous dose delivery of spatially fractionated radiation therapy (SFRT) is a profound departure from standard radiation planning and reporting approaches. Early SFRT studies have shown excellent clinical outcomes. However, prospective multi-institutional clinical trials of SFRT are still lacking. This NRG Oncology/American Association of Physicists in Medicine working group consensus aimed to develop recommendations on dosimetric planning, delivery, and SFRT dose reporting to address this current obstacle toward the design of SFRT clinical trials., Methods and Materials: Working groups consisting of radiation oncologists, radiobiologists, and medical physicists with expertise in SFRT were formed in NRG Oncology and the American Association of Physicists in Medicine to investigate the needs and barriers in SFRT clinical trials., Results: Upon reviewing the SFRT technologies and methods, this group identified challenges in several areas, including the availability of SFRT, the lack of treatment planning system support for SFRT, the lack of guidance in the physics and dosimetry of SFRT, the approximated radiobiological modeling of SFRT, and the prescription and combination of SFRT with conventional radiation therapy., Conclusions: Recognizing these challenges, the group further recommended several areas of improvement for the application of SFRT in cancer treatment, including the creation of clinical practice guidance documents, the improvement of treatment planning system support, the generation of treatment planning and dosimetric index reporting templates, and the development of better radiobiological models through preclinical studies and through conducting multi-institution clinical trials., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The first clinical trials to assess the feasibility of FLASH radiotherapy in humans have started (FAST-01, FAST-02) and more trials are foreseen. To increase comparability between trials it is important to assure treatment quality and therefore establish a standard for machine quality assurance (QA). Currently, the AAPM TG-224 report is considered as the standard on machine QA for proton therapy, however, it was not intended to be used for ultra-high dose rate (UHDR) proton beams, which have gained interest due to the observation of the FLASH effect., Purpose: The aim of this study is to find consensus on practical guidelines on machine QA for UHDR proton beams in transmission mode in terms of which QA is required, how they should be done, which detectors are suitable for UHDR machine QA, and what tolerance limits should be applied., Methods: A risk assessment to determine the gaps in the current standard for machine QA was performed by an international group of medical physicists. Based on that, practical guidelines on how to perform machine QA for UHDR proton beams were proposed., Results: The risk assessment clearly identified the need for additional guidance on temporal dosimetry, addressing dose rate (constancy), dose spillage, and scanning speed. In addition, several minor changes from AAPM TG-224 were identified; define required dose rate levels, the use of clinically relevant dose levels, and the use of adapted beam settings to minimize activation of detector and phantom materials or to avoid saturation effects of specific detectors. The final report was created based on discussions and consensus., Conclusions: Consensus was reached on what QA is required for UHDR scanning proton beams in transmission mode for isochronous cyclotron-based systems and how they should be performed. However, the group discussions also showed that there is a lack of high temporal resolution detectors and sufficient QA data to set appropriate limits for some of the proposed QA procedures., (© 2023 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Purpose: Noncoplanar plans (NCPs) are commonly used for proton treatment of bilateral head and neck (HN) malignancies. NCP requires additional verification setup imaging between beams to correct residual errors of robotic couch motion, which increases imaging dose and total treatment time. This study compared the quality and robustness of NCPs with those of coplanar plans (CPs)., Methods and Materials: Under an IRB-approved study, CPs were created retrospectively for 10 bilateral HN patients previously treated with NCPs maintaining identical beam geometry of the original plan but excluding couch rotations. Plan robustness to the inter-fractional variation (IV) of both plans was evaluated through the Dose Volume Histograms (DVH) of weekly quality assurance CT (QACT) sets (39 total). In addition, delivery efficiency for both plans was compared using total treatment time (TTT) and beam-on time (BOT)., Results: No significant differences in plan quality were observed in terms of clinical target volume (CTV) coverage (D95) or organ-at-risk (OAR) doses (p > 0.4 for all CTVs and OARs). No significant advantage of NCPs in the robustness to IV was found over CP, either. Changes in D95 of QA plans showed a linear correlation (slope = 1.006, R 2  > 0.99) between NCP and CP for three CTV data points (CTV1, CTV2, and CTV3) in each QA plan (117 data points for 39 QA plans). NCPs showed significantly higher beam delivery time than CPs for TTT (539 ± 50 vs. 897 ± 142 s; p < 0.001); however, no significant differences were observed for BOT., Conclusion: NCPs are not more robust to IV than CPs when treating bilateral HN tumors with pencil-beam scanning proton beams. CPs showed plan quality and robustness similar to NCPs while reduced treatment time (∼6 min). This suggests that CPs may be a more efficient planning technique for bilateral HN cancer proton therapy., (© 2023 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

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

Purpose: To assess treatment planning system (TPS) accuracy in estimating the stopping-power ratio (SPR) of immobilization devices commonly used in proton therapy and to evaluate the dosimetric effect of SPR estimation error for a set of clinical treatment plans., Methods: Computed tomography scans of selected clinical immobilization devices were acquired. Then, the water-equivalent thickness (WET) and SPR values of these devices based on the scans were estimated in a commercial TPS. The reference SPR of each device was measured using a multilayer ion chamber (MLIC), and the differences between measured and TPS-estimated SPRs were calculated. These findings were utilized to calculate corrected dose distributions of 15 clinical proton plans for three treatment sites: extremity, abdomen, and head-and-neck. The original and corrected dose distributions were compared using a set of target and organs-at-risk (OARs) dose-volume histogram (DVH) parameters., Results: On average, the TPS-estimated SPR was 19.5% lower (range, -35.1% to 0.2%) than the MLIC-measured SPR. Due to the relatively low density of most immobilization devices used, the WET error was typically <1 mm, but up to 2.2 mm in certain devices. Overriding the SPR of the immobilization devices to the measured values did not result in significant changes in the DVH metrics of targets and most OARs. However, some critical OARs showed noticeable changes of up to 6.7% in maximum dose., Conclusions: The TPS tends to underestimate the SPR of selected proton immobilization devices by an average of about 20%, but this does not induce major WET errors because of the low density of the devices. The dosimetric effect of this SPR error was negligible for most treatment sites, although the maximum dose of a few OARs exhibited noticeable variations., (© 2022 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Background: Proton beam therapy (PBT) is a non-surgical treatment that spares adjacent tissues compared to photon radiation and useful for Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). We present a single center experience in HCC and iCCA treated with Pencil Beam Scanning (PBS) PBT., Methods: Forty-four consecutive patients (22 patients in each group) receiving PBT were included and reviewed. PBT was delivered with hypofractionated or stereotactic body radiation therapy (SBRT) using PBS. Tumor size was approximated by clinical target volume (CTV). Outcomes were evaluated with Kaplan-Meier and liver toxicity was determined by MELD-Na and albumin-bilirubin (ALBI) grade., Results: Median follow up was 38.7 months, fourteen (35%) had multifocal disease and median CTV was 232.5cc. Four (9%) and 40 (91%) patients received SBRT and hypofractionated radiation, respectively. Two year overall survival was statistically higher for HCC (entire group: 68.9% months [95% CI: 61.3 - 76.3%]; iCCA: 49.8% [95% CI: 38.5% - 61.1%]; HCC: 89.4% [95% CI: 82.3 - 96.5%]; P <0.005). There was no statistical difference in progression-free survival or freedom from local failure. Biologically Equivalent Dose (BED) was greater than or equal to 80.5Gy in 37 (84%) patients. All iCCA patients had stable or improved ALBI grade following treatment. ALBI grade was stable in 83% of HCC patients and average MELD-Na score remained stable. Tumor size, pretreatment liver function, and total radiation dose were not associated with liver toxicity., Conclusions: PBT for unresectable HCC and iCCA is safe and effective, even for large and multifocal tumors. Liver function was preserved even in those with baseline cirrhosis in this advanced population with large tumors., Competing Interests: We thank the patients for trusting us with their care. Authors’ disclosure of potential conflicts of interest The authors have nothing to disclose., (© 2023 Old City Publishing, Inc.)