Purpose To report long-term outcomes for patients treated with salvage proton therapy (PT) following primary cryosurgery (CS) or high-intensity focused ultrasound (HIFU) for recurrent localized prostate cancer. Materials and Methods We assessed 31 patients who underwent salvage PT at our institution between 2007-2017 for biopsy-confirmed, localized prostate cancer recurrence after CS (n=21) or HIFU (n=10). Patients had no evidence of nodal or distant metastases. Median PT dose was 74 CGE (range, 70.2–82) delivered at 1.8–2 CGE/fraction. Androgen deprivation therapy was administered to 12 patients for a median of seven months (range, 6–24). Freedom from biochemical failure (FFBF) was defined per the Phoenix criteria. Freedom from regional failure (FFRF) and distant failure (FFDF) defined as the absence of radiologic or clinical evidence of metastatic disease in pelvic lymph nodes and distant to pelvic lymph nodes, respectively. Toxicities were graded using CTCAEV5. Patient-reported outcomes were assessed using the International Prostate Symptom Score (IPSS) and Expanded Prostate Index Composite (EPIC). Kaplan-Meier estimates were used to calculate survival and oncologic outcomes. Results Median follow-up was 8.0 years (range, 1.9–13.5). The 5- and 10-year FFBF rates were 72.4% and 64.7%, respectively. Overall survival at 5- and 10-years was 86.0% and 71.1%, respectively. At 10-years, FFRF was 73.7% and FFDF was 96.8%. One late grade 3 hematuria occurred (3.2%), and two transient late grade 2 rectal hemorrhages occurred (6.4%). Median EPIC and IPSS scores remained stable from pre-PT through 5-years after treatment. Conclusion Our results demonstrate salvage PT as a safe and effective option following CS or HIFU with low toxicity and minimal impact on reported quality of life. PT outcomes are comparable with recent prostate cancer ablation salvage reports. Future studies should include multi-center collaborations to investigate elective pelvic nodal radiation to optimize treatment strategies for recurrent prostate cancer.
Purpose Recent developments have further demonstrated the feasibility of CSI delivery using simplified beam arrangements, such as a single posterior brain beam. Extending these advances, CSI delivered in the lateral decubitus position within a fixed-beam proton room offers an opportunity to improve room utilization and treatment access, but introduces unique challenges in patient setup and image guidance. Methods This study compares two image-guided setup workflows for decubitus CSI to evaluate whether meaningful differences exist. We retrospectively analyzed 10 CSI patients treated in the decubitus position between 2024 and 2025 using the fixed-beam ProBeam system with three-iso technique. Two setup workflows were evaluated: (1) Continuous Full-Field Image Guidance (CFF-IG), in which all isocenters were aligned prior to treatment delivery, and (2) Selective Field-Based Image Guidance (SF-IG), in which full-field imaging was applied only at the initial fraction, followed by field-specific verification thereafter. Setup accuracy was quantified using translational and rotational deviations derived from oblique kV imaging, and dosimetric robustness was assessed through target coverage and junction dose gradient analysis. Setup efficiency was evaluated using treatment room time stamps. Results Across all three isocenters, mean translational deviations were below 4 mm and mean angular deviations were below 1.5°. Differences in target coverage (ΔD95) and junction dose gradients were small between the two workflows. No statistically significant differences in setup accuracy or dosimetric quality were observed. SF-IG was associated with shorter average setup time, with the majority of treatment sessions completed within 30 minutes. Conclusions Both CFF-IG and SF-IG achieved setup accuracy within institutional action levels and maintained dosimetric robustness for CSI delivered in the decubitus position using PBS. The absence of significant differences suggests that either approach may be clinically feasible for decubitus CSI delivery. SF-IG offers a more time-efficient workflow without compromising treatment quality, supporting its use as the preferred default strategy, while CFF-IG may be reserved for select cases requiring enhanced global realignment. These findings support decubitus CSI as a practical extension of modern single-beam and simplified PBS CSI techniques.
Background/Objectives Stereotactic radiosurgery and photon therapy for the locoregional management of head and neck paragangliomas (HNPGLs) has been shown to provide long-term tumor control and symptomatic relief. We report proton therapy outcomes for HNPGLs at a single institution and describe SRS and IMRT outcomes as institutional context for modality selection. The primary goal is to report outcomes including tumor control, toxicity, and overall recovery, while evaluating differences across radiation modalities. Materials/Methods This is a retrospective review of 52 adult patients with 54 non-metastatic HNPGLs receiving radiation therapy in a single institution. There were nine tumors treated with intensity-modulated radiation therapy (IMRT), 23 with stereotactic radiosurgery (SRS), and 22 with proton therapy. Median dose was 45 Gy (cobalt Gray equivalent [CGE]). Results Out of 52 patients (14 male, 38 female) with a current median age of 65 (range 27-93), there were 30 jugular paragangliomas (PGLs), 1 tympanic PGL, 8 jugulotympanic PGLs, 3 vagal PGLs, 11 carotid body tumors, and 1 spinal PGL. The median age at the start of treatment was 59.5 years (range 18-85). Median follow-up was 50.3 months (range 3.6-147.2 months) with 52 (100%) patients alive at last follow-up. Local control, distant control, and overall survival were 98%, 100%, and 100%, respectively. No grade 3-5 toxicities were reported. At the end of follow-up, 53 (98%) tumors had a partial treatment response or were stable and 20 (37%) experienced a decrease in volume. Of the 20 tumors that had a decrease in volume, 8 were treated with proton therapy, 8 with SRS, and 4 with IMRT. Proton therapy was used more frequently for larger or anatomically complex tumors; SRS was preferred for small, well-circumscribed lesions; and IMRT was selected for moderate-sized or irregularly shaped tumors near critical structures before proton therapy was available. Conclusion Proton therapy was particularly useful in treating large or anatomically-complex tumors, while SRS and IMRT offered strong outcomes for smaller or anatomically suitable lesions. We report favorable feasibility, local tumor control, survival, and toxicity of proton therapy for HNPGLs.
Purpose This review examines the role of artificial intelligence (AI) in particle therapy treatment planning, highlighting recent advancements, clinical potential, and existing challenges. Methods and Materials A review was conducted on AI applications in proton and heavy ion therapy, focusing on automated plan generation, dose prediction, treatment adaptation, and quality assurance. Results AI-driven methods have shown promise in optimizing treatment planning, enhancing dose prediction, and improving plan adaptation. However, challenges such as data limitations, model interpretability, and regulatory barriers hinder clinical implementation. Conclusion While AI offers significant potential to improve particle therapy treatment planning, further research is needed to enhance model robustness, clinical validation, and integration into existing workflows.
Purpose:Proton therapy (Pr) can spare normal tissue and reduce toxicity; however, it remains a limited resource. The aim of this study was to evaluate demographic and clinical differences in the use of Pr amongst adult cancer patients at a single institution, with particular attention to the impact of insurance coverage. Materials/Methods:Adult patients who underwent radiation between 2015 and 2021 were retrospectively reviewed. Multivariable (MVA) logistic regression analyses were used to assess associations between Pr use and variables including sex, sexual orientation, age, race, ethnicity, marital status, preferred language, smoking status, year of treatment, treatment intent, diagnosis, and distance to facility. Propensity score matching was then used to further validate associations between race and travel distance. Separately, Medicare-insured patients were considered an individual cohort and analyzed utilizing the same demographic variables noted. Results:Of 12,320 patients identified, 2342 and 9978 received Pr and Photon therapy (Ph), respectively. On MVA, Black and Asian race, current smoker, and shorter straight-line distance to the facility remained associated with lower likelihood of treatment with Pr. On propensity-matched scoring, Black patients and patients living within 250 mi of the center remained significantly less likely to receive Pr. Of 4258 Medicare-only patients, 1261 and 2997 received Pr and Ph therapy, respectively. On MVA analysis, female sex, Black race, and decreasing distance to the facility were associated with lower likelihood of receiving Pr therapy. On propensity-matched scoring, Black patients and patients living within 250 mi of the center remained significantly less likely to receive Pr. Conclusions:We identified significant differences in the use of Pr as a function of distance to site and race in both a heterogeneous adult patient cohort and a Medicare cohort. As health systems expand Pr therapy capacity, understanding how clinico-demographic factors shape access, even under conditions of broad insurance coverage, may inform future infrastructure planning.
Purpose Increasing interest in proton FLASH radiotherapy has led to a focus on target-specific (TS) devices and passive scattering (PS) techniques. However, these techniques often require expensive, time-consuming custom devices like single-use collimators and compensators. Our study aims to improve this by creating a flexible TS-PS setup adaptable to various needs, specifically for small target structures. Methods The collimating and compensating elements are made from 3D-printed polylactide containers filled with reusable copper or polypropylene spheres. We designed these TSPS elements using the modified Python package Porespy and conducted simulations in Tool for Particle Simulation Monte Carlo. We evaluated the collimator’s performance by comparing a solid collimator with our proposed approach. As a feasibility study, we developed 2 ”eco-friendly” PS setups for irradiating a simple spherical target and a complex small structure, a murine brain tumor. Results We validated the computational model and MC simulations through depth dose curve and beam size measurements, demonstrating an agreement within a few percent. The “eco-friendly” collimators effectively collimated the beam, but we observed a dose halo at high energies due to protons not being stopped by the plastic bore; using higher-density materials can address this issue. We designed and validated the 2 “eco-friendly” setups via dose measurements and demonstrated that we could effectively compensate and collimate the beam to conform the dose to the target shape. The total time required to print the setup was under 45 minutes, and the filament cost was under $1. Conclusions This innovative, “eco-friendly” approach using 3D printing allows for quick production of TS shapes, reducing waste and costs while enhancing conformity and improving the efficiency of PS treatments.
Purpose:The current study aimed to quantify potential dosimetric advantages of a novel, brass aperture-enhanced, proton-based stereotactic radiosurgery (SRS) technique compared to conventional photon linac-based SRS in patients with cerebral arteriovenous malformations (AVMs). Materials and Methods:A retrospective review was performed of patients treated with proton SRS for cerebral AVMs at our institution between 2023 and 2025. Volumetric modulated arc therapy linac-based SRS plans were generated for dosimetric comparison and normalized to match the clinical target volume (CTV) prescription coverage of the delivered proton plan. SRS plan quality was evaluated by Radiation Therapy Oncology Group conformity and homogeneity indices (CI, HI). The V12 Gy representing the normal brain volume receiving ≥ 12 Gy including the CTV (total brain) was measured. Results:Fourteen patients were included, and most had no prior hemorrhage (64%), embolization (79%), or AVM-directed radiotherapy (86%). Three patients received staged radiation, totaling 17 treatment plans for review. Mean AVM size was 8.8 cc (0.4-30.6). SRS dose ranged from 17 to 20 Gy with 3 larger AVMs treated using volumetric staging. For the 4 AVMs ≤2.0 cc in size, the average CI was 1.89 and 1.81 for photons and protons, respectively. The average CI for AVMs >2 cc was 1.15 and 1.17 for photons and protons, respectively. A statistically significant difference was observed with HI (P = .0034) and V12 Gy (P = .0017). Fourteen of 17 (82.4%) HI were lower with protons. There was on average a 5.86 cc improvement in V12 Gy with protons. Conclusion:Brass aperture-enhanced proton PBS SRS improved V12 Gy in 15 of 17 plans (88.2%), including small volume AVMs and AVMs close to the brainstem. These findings are hypothesis-generating and must be interpreted cautiously. Maturation of our clinical outcome data (AVM obliteration and symptomatic radionecrosis rates) will yield further insights.
Purpose:Proton therapy offers excellent distal tissue sparing; however, precise control of the lateral penumbra is critical for protecting adjacent healthy tissues. This study systematically evaluated improvements in lateral penumbra in proton pencil beam scanning (PBS) using a surface-contacted 3-dimensional printed bolus (3DBS), compared with conventional plans employing a nozzle-mounted range shifter (RS), for beams with and without a multi-leaf collimator (MLC). Methods:A total of 460 uniform-dose PBS plans were generated for a cubic target (60 × 60 × 54 mm³) positioned at 9 different depths ranging from 0 to 280 mm in water. Plan configurations included plans with 3 different materials for 3DBSs (silicone, resin, and thermoplastic polyurethane) and were compared with plans with a polyethylene RS. Each configuration was further subdivided into plans with and without MLC. Air gaps ranging from 50 to 300 mm were evaluated. Lateral penumbra widths and mean doses to surrounding organs at risk (OARs) within a 30-mm margin were evaluated. Two-dimensional dose distributions for selected beams were experimentally verified using a 2D ionization chamber array and radiochromic films. Results:All plans with 3DBSs improved lateral penumbra and reduced mean OAR doses compared with plans with RS, under equivalent MLC conditions, except for a limited subset of plans at depths greater than 200 mm with minimal air gaps. Measured dose distributions demonstrated acceptable agreement with calculated plans. Comparisons among the 3 3DBS materials indicated feasibility in material selection based on required bolus geometry and clinical implementation considerations. Conclusions:The combined use of MLC and 3DBS provides a systematic and effective strategy for lateral penumbra control in proton PBS. This approach enables improved dosimetric precision in clinically sensitive scenarios where even small reductions in dose to surrounding tissues are critical.
Purpose:FLASH radiotherapy delivers ultra-high dose rate radiation (>40 Gy/s) has shown promise in reducing normal tissue toxicity while maintaining tumor control. IBA's single-room proton system, equipped with S2C2 superconducting synchrocyclotron accelerator, has recently demonstrated to achieve UHDR delivery. Integrating the UHDR beam line in the treatment planning system (TPS) is crucial for accurate dose calculation in preclinical study, optimization of the 2D dose profile as well as paving the way for further accessory development for spread-out Bragg peak FLASH. This study aims to commission and validate a synchrocyclotron-based pencil beam scanning UHDR proton beamline on the IBA ProteusONE system in RayStation TPS. The goal is to establish a framework for TPS modeling and validation, facilitating preclinical FLASH radiotherapy studies. Methods:The transmission UHDR beamline using scanning proton beam energy of 228 MeV was characterized at gantry 0° using comprehensive point dose and 2D lateral profiles measurements. The beam model was developed in RayStation, incorporating key parameters such as virtual source position, spot size, integrated depth dose (IDD), and absolute dose calibration. Extensive validations were conducted using ionization chambers, film dosimetry, and 2D scintillation detectors, with gamma analysis performed to assess the accuracy of the TPS model with open field and field in the presence of brass apertures. Results:The UHDR beamline achieved ultra-high dose rates exceeding 40 Gy/s (average dose rate for a 2.5 x 2.5 cm field) with consistent dose output validated across multiple detectors. The nozzle current was measured to be linear with respect to the requested MU in the range of 45 to 126 nA. The RayStation beam model demonstrated excellent agreement with experimental measurements, achieving less than 2.5% deviation for all point dose measurements. For 2D profile measurements, gamma passing rates >95% under 2%/2 mm criteria for all fields. The TPS allowed optimization of the spot pattern for UHDR FLASH beams aligned closely with clinical beam profiles, enabling accurate preclinical study comparisons. Conclusions:A synchrocyclotron-based UHDR beamline was successfully commissioned and validated through a reliable TPS model for transmission FLASH application. The results provide a foundation for preclinical FLASH-RT research and future clinical applications, demonstrating the feasibility of integrating FLASH-RT into existing proton therapy platforms. Future work will extend the commissioning to all gantry angles and explore spread-out Bragg peak FLASH delivery for improved dose conformality.
Purpose:This study aimed to compare the robustness of beam-specific planning target volume (bs-PTV)-based single-field uniform dose (SFUD) and robustly optimized intensity-modulated proton therapy (IMPT) plans against setup, range, and anatomical uncertainties in ultra-hypofractionated (UHF) proton therapy for localized prostate cancer. Methods:SFUD and IMPT plans were generated and compared using imaging datasets from ten consecutive patients who underwent proton therapy for prostate cancer at our institution. SFUD plans using a bs-PTV and IMPT plans using robust optimization were generated with 36.25 Gy equivalent (GyE) to the clinical target volume (CTV) in 5 fractions. To evaluate robustness against setup and range uncertainties, 20 error scenarios were applied, including combined ±3 mm isocenter shifts and ±3.5% Hounsfield Unit (HU) variations. Additionally, the SFUD and IMPT plans were recalculated using virtual CT (vCT) derived from weekly cone-beam CT (wCBCT) to estimate accumulated doses under anatomical changes. The worst-case and accumulated doses to the CTV, rectum, and bladder were compared. Results:Both SFUD and IMPT plans demonstrated stable target coverage under setup, range, and anatomical uncertainties. Variations in CTV D99 remained within commonly accepted robustness criteria for all patients. Although a statistically significant difference in worst-case CTV D99 was observed between SFUD and IMPT plans, the magnitude of this difference was small. Dose variations under uncertainties were smaller for selected organs at risk (OAR) dose metrics in IMPT. Across the nominal, worst-case, and accumulated dose evaluations, IMPT plans achieved lower low- and intermediate-dose metrics for the rectum and bladder. Conclusion:Both bs-PTV-based SFUD and robustly optimized IMPT plans maintained adequate target coverage under uncertainties in UHF proton therapy for prostate cancer. The lower OAR doses and slightly improved OAR robustness observed with IMPT likely reflect the combined effects of differences in planning techniques and uncertainty management strategies, suggesting a modest dosimetric benefit.
Purpose:We present long-term outcomes of men young aged 50 years or younger treated for localized prostatic adenocarcinoma with image-guided proton therapy (PT). Patient and Methods:We identified 85 patients with localized prostate cancer treated with PT between 2006 and 2017 at our institution. Patients were treated with double scattered PT to a median dose of 78 GyRBE (range, 78-82) delivered at 2 GyRBE/fraction. Nine (11%) received androgen deprivation therapy for a median of 6 months (range, 6-7). Biochemical control was defined by the Phoenix Definition. Physician-reported toxicity assessed according to CTCAE v5.0. Patient reported outcomes were assessed with the International Prostate Symptom Score and Expanded Prostate Index Composite (EPIC). Freedom from Biochemical Failure (FFBF) was tabulated with Kaplan-Meier method. Results:Median follow-up was 12.3 years (range, 1.58-17.4). FFBF rates by risk category at 10 years were very low 100%, low 100%, favorable intermediate 92%, unfavorable intermediate 93%, and high 100%. Three developed disease progression at 10 years. All had biochemical progression, and one recurred with regional nodal metastases. Grade 2+ gastrointestinal toxicity occurred in 2 (2.4%), and grade 3+ urologic toxicity occurred in 2 (2.4%). Median EPIC summary scores for urinary and bowel outcomes were 97.1 and 98.1 at baseline and 95.8 and 96.4 at 10 years respectively. Median EPIC sexual summary score was 82.7 at baseline and 69.2 at 10 years respectively. Two patients developed a second cancer, and both were out-of-field. One occurred in the submandibular gland 7 years after treatment, and the other in the pancreas 10 years after treatment. Conclusion:PT provides excellent tumor control for patients 50 years or younger with localized prostate cancer and has a low risk for high-grade toxicities. No in-field secondary cancers were observed. Findings from this relatively small population should be confirmed in a larger study population.
Purpose:Proton therapy is challenged by tumor motion, particularly for lung tumors affected by respiratory-induced motion. Conventional planning strategies compensate for this motion by introducing safety margins or by using robust optimization, increasing irradiation of surrounding healthy tissues. Real-time plan adaptation during delivery represents a promising alternative to mitigate intrafractional motion effects. Materials and Methods:We propose a patient-specific deep Reinforcement Learning (RL)-based control framework for proton pencil beam scanning, formulated as a first step toward a real-time plan adaptation problem under respiratory motion. RL agents are trained independently on 3 patients on their mid-position planning CT to sequentially control beam position and spot delivery. At inference, the learned policy is executed on the respiratory phases of each patient's 4DCT without any online re-training or model parameters adaptation. The agent is provided with 2D observations encoding target geometry, beam position, and prior spot delivery. The approach is evaluated against conventional static gross tumor volume-based (GTV-based) and internal target volume-based (ITV-based) planning strategies. Results:The agents improve target coverage under respiratory motion by exploiting new information in the observations during delivery compared with static gross tumor volume-based plans, with an average gain of 4.54 Gy in D 95 GTV over the whole treatment for Patient 1. Compared with ITV-based plans, the RL-based approach generally reduces dose exposure to organ-at-risk, with an average reduction of 0.42, 4.12, and 3.14 Gy in D mean Lung-GTV for the 3 patients, respectively, and a decrease of 1.41 Gy in D mean Heart for Patient 3, who has the largest motion amplitude. Conclusion:This study should be interpreted as a proof-of-concept and highlights the potential of RL-based control strategies for proton therapy delivery under intrafractional motion. While the current framework relies on static training, it establishes a foundation for future extensions toward fully dynamic and adaptive treatments.
Purpose:Monte Carlo (MC) simulations provide gold standard dose calculations in radiation therapy but generate large phase space (PHSP) files that limit clinical implementation. We developed NeRP-MC, the first neural representation learning approach for PHSP data modeling, and evaluated its ability to model particle distributions from minimal training data. Materials and Methods:We investigated proton PHSP modeling at 242 and 140 MeV. For both energies, a reference proton pencil beam PHSP containing 25 million particles was generated using TOPAS. A multi-layer perceptron with Fourier feature encoding was trained to predict particle energies from spatial and momentum inputs. We evaluated NeRP-MC in 3 scenarios: 1) compact energy modeling given full spatial and momentum information, 2) energy modeling from sparse PHSP data (1.25 million particles, 20-fold reduction), and 3) replacing the PHSP with parametric Gaussian spatial/momentum distributions and network-predicted energies conditioned on the Gaussian-sampled inputs. Validation used in-water dose distributions compared via gamma index analysis. Results:The trained network requires only 600 KB for storage versus 3 GB for the original PHSP and predicts 25 million particle energies in under 0.5 seconds on an NVIDIA A100 GPU. NeRP-MC generated energies showed close agreement with reference data across all 3 scenarios. Depth-dose profiles, lateral profiles, and penumbra regions were accurately reproduced. Gamma pass rates exceeded 99% at 3%/2 mm and 90% at the strictest 1%/1 mm criterion. Conclusion:NeRP-MC offers compact modeling and fast prediction of particle energies from particle spatial and momentum information and promises to replace the large-scale PHSP with a parametric Gaussian model of spatial and angular variables and the NeRP model of particle energy variables. NeRP-MC has the potential to advance MC simulation efficiency for radiation therapy through a substantial reduction in computational and storage requirements while maintaining dosimetric accuracy.
Purpose: Proton spot-scanning arc therapy (ARC) is an emerging technique that can enhance high-dose conformity to targets compared with standard intensity-modulated proton therapy (IMPT). Although proton ARC is highly desirable, it is not yet clinically available. Multiple IMPT plans delivered over different fractions and optimized simultaneously provide a practical means to approximate ARC-plan quality. However, existing multiple IMPT approaches are not optimized to be biologically comparable to proton ARC because they neglect the fractionation effect during treatment planning. This work proposes a biologically optimized multiple IMPT (multi-IMPT) framework that achieves comparable performance to proton ARC in terms of the biologically effective dose (BED). This is achieved through direct optimization of BED by explicitly incorporating the fractionation effect during planning, thereby ensuring biological comparability between multi-IMPT and proton ARC treatments. Materials and Methods: The proposed multi-IMPT method utilizes a different subset of limited number of beam angles in each fraction for dose delivery. Due to the different dose delivered to organs at risk (OAR) in each fraction, the BED delivered to OAR and the physical dose delivered to target is optimized in each fraction. The BED-based multi-IMPT inverse optimization problem is solved via the iterative convex relaxation method and the alternating direction method of multipliers. The effectiveness of the proposed multi-IMPT method is evaluated in terms of BED objectives in comparison with ARC and IMPT. Results: Multi-IMPT provided similar plan quality with ARC. For example, multi-IMPT provided better OAR sparing and slightly better target dose coverage for the prostate case; similar dose distribution for the lung case; slightly worse dose coverage for the brain case; better dose coverage but slightly higher BED in OAR for the head-and-neck case. Conclusion: A multi-IMPT approach is proposed that delivers ARC-comparable plan quality under the evaluated conditions in terms of BED.
Background:This study aimed to evaluate the efficacy of respiratory-gated irradiation using visual feedback (VF) in carbon-ion radiotherapy (CIRT). Furthermore, in patients with liver cancer undergoing CIRT, the treatment times of treatments with and without VF (non-VF) were compared. Material and methods:Thirty-three patients with liver cancer were analyzed. VF system was applied in 10 patients with liver tumors. To evaluate the efficacy of VF, patients treated non-VF were selected as a control group. All treatments were performed under free-breathing conditions in both the VF and non-VF groups. For each VF patient, 1-3 candidate non-VF patients were identified by matching the CTV size and irradiation gate width (amplitude). From these candidates, 1 non-VF patient was selected as a matched control for each VF patient. The average treatment time for each VF patient was compared with that of the corresponding non-VF patient. The effect of the reduced treatment time for VF was calculated by comparing each VF patient with the corresponding non-VF patient. To quantify respiratory variability, the root mean square error and standard deviation were calculated. Results:The treatment time was reduced in 8 of 10 pairs. Further, in 6 of 8 pairs, the treatment time was reduced by more than 5 minutes when using VF compared with non-VF. The RMSE value was significantly reduced at 50% and 100% (P < .05). The RMSE value decreased by 28.2% in the VF compared with non-VF. VF was effective in improving respiratory waveform reproducibility in most pairs. Conclusion:The results suggest that VF contributes to a reduction in treatment time, indicating improved time efficiency during irradiation sessions. In addition, VF improves respiratory waveform reproducibility, which may contribute to enhanced treatment accuracy. Furthermore, shortening the treatment time may reduce the treatment burden on patients and improve overall treatment workflow.
Purpose:Proton therapy is considered an attractive alternative to conventional radiotherapy in oncology, as its dose-depth curve favors tumor control while minimizing the risk of radiation-induced side effects in healthy tissue. Preclinical investigation into proton Relative Biological Effectiveness (RBE) is imperative to improve the current clinical RBE standard and subsequently optimize therapeutic efficacy. Materials and Methods:A low-energy cyclotron-based proton irradiation set-up for in vitro research was optimized at ICNAS-University of Coimbra. The system dosimetry was assessed using a calibration curve from a standard radiotherapy linear accelerator applied to proton-irradiated Gafchromic EBT4 films while recording integrated beam charge in real time. Pulsed dose rate measurements were performed by determination of target exposure time. As proof of concept, glioblastoma cell lines (U373 and U87) were subjected to proton irradiation for quantification of cell survival and DNA damage. Results:Homogeneous dose profiles were achieved on a 21 mm-diameter circular area at the target region for an incident proton energy of 14 MeV. A linear relation was found between proton dose at the target and integrated beam charge for pulsed dose rates from 10.8 to 16.2 Gy/s and a proton flux of ∼ 107 protons/(s ∙ cm2). Proton irradiation of U373 cells yielded effects on cell survival comparable to kilovoltage X-ray exposure. U87 cells exhibited unrepaired DNA damage following proton exposure. Conclusion:A cyclotron-based pulsed proton beam was successfully optimized for in vitro radiobiological research, as evidenced by the first irradiation studies for evaluation of cell survival and DNA damage in glioblastoma cellular models.
Purpose:This systematic review aims to provide a summary of outcomes of pediatric brain tumor patients treated with proton therapy (PT). Outcomes focused on include long-term efficacy and late toxicities. This study provides an analysis of survival, disease control, and safety outcomes across major pediatric brain tumor histologies to support contemporary clinical decision-making. Methods:A literature search was conducted across PubMed, Scopus, and Web of Science to identify studies reporting overall survival (OS), progression-free survival (PFS), local control (LC), or late toxicity in patients under 21 years with brain tumors treated with PT. Weighted linear regression was performed on survival outcomes modeling trends over post-treatment follow-up. Safety outcomes were qualitatively assessed based on histology and pooled where possible to facilitate cross-study comparison. Results:Seventy-seven studies were included, with 40 reporting on OS following PT in a total of 3798 patients. Statistically significant time-dependent models were obtained for medulloblastoma (PFS: P = .0018), ependymoma (OS: P = .0002, PFS: P = .0006, LC: P = .001), base of skull (BOS) chordoma (OS: P = .0498), and the mixed histology group (OS: P = .028), with trends observed in other histologies. LGG and craniopharyngioma demonstrated high survival, showing over 95% OS up to 10 years after treatment. Toxicity outcomes revealed common late toxicities, including endocrinopathies (ranging from 11.7% in ependymoma to 94% in craniopharyngioma), vasculopathy (1%: LGG - 36%: craniopharyngioma), hearing loss (4%: ependymoma - 26.3%: medulloblastoma), and neurocognitive decline (no significant decline: LGG - 1.5 points annual decline: medulloblastoma), with wide variations in incidence across histology reflecting differences in tumor location and treatment burden. Conclusion:Statistically significant trends in medulloblastoma, ependymoma, and BOS chordoma were identified, along with consistent outcomes in LGG and craniopharyngioma outcomes. Together, these findings provide clinicians with clearer expectations of prognosis following PT and establish reference benchmarks that can inform treatment planning, counsel families, and serve as a comparative foundation for future clinical research.
Purpose:To create LET-optimized pencil beam scanning proton prostate cancer treatment plans with clinically acceptable range robustness and urethral sparing. Methods:Two-beam, four-beam, and arc LET-optimized treatment plans were created for a prostate cancer patient with varying levels of robustness to evaluate LETd and several performance metrics. Urethral sparing was incorporated by de-escalating the physical dose to the urethra while maintaining high LETd to prevent underdosing the periurethral prostate by merit of its lower α / β . Four-beam and arc plans were created with a targeted robustness level for 12 patients along with reference SFO plans, and statistical comparisons were performed on clinical target volume prostate and seminal vesicles minus urethra (CTV PSV-U) mean LETd, target volume and organs at risk (OAR) relative biological effectiveness (RBE)-doses, minimum average RBE-doses, target-to-OAR dose ratios (TODRs), and OAR volumes receiving at least 80% of the CTV PSV D95 dose (V80%). Results:A tradeoff between robustness and high LETd was demonstrated. Statistically significant differences in LETd were found, with 2.5 keV/µm in SFO plans, 3.3 keV/µm in arc plans, and 3.5 keV/µm in four-beam plans. Statistically significant increases in CTV PSV-U D95 RBE-dose resulted in 6.3%-8.1% increases in four-beam plans over SFO. High LETd in the periurethral prostate prevented underdosage with urethral sparing. V80%s were statistically decreased in four-beam and most arc comparisons relative to SFO. While increased TODRs were demonstrated in a test patient, lack of statistical significance (or superiority in SFO over arc in the case of the rectum) in the 12 patient cohort occurred due to some patients already having low OAR RBE-doses in SFO plans, which could be addressed with additional optimization objectives at lower doses. Conclusion:LET-optimized treatment plans were created with high LETd and clinically acceptable robustness with the potential to increase the therapeutic ratio and implemented urethral sparing without underdosing the periurethral prostate.
Up to half of prostate cancer recurrences following definitive external beam radiotherapy (EBRT) occur exclusively within the prostate and are thus potentially amenable to curative salvage treatment. A meta-analysis of six randomized prostate cancer radiotherapy trials suggested that untreated local recurrences may lead to quicker distant metastases and, therefore, worse survival. Despite these prognostic implications, palliative measures such as androgen deprivation therapy (ADT) are most commonly employed to treat locally recurrent disease, whereas local salvage therapies are utilized in just 2% of cases. Surgical procedures such as salvage prostatectomy, cryotherapy, and high intensity focused ultrasound (HiFU) carry a substantial complication risk after radiation. Likewise, re-treatment with conventionally fractionated photon EBRT is limited by high cumulative doses to surrounding organs at risk (OARs) and can result in more than 20% genitourinary (GU) and 40% gastrointestinal (GI) grade 3+ toxicity, respectively.There is little published on the use of salvage proton beam therapy (PBT) for local or regional radio-recurrent prostate cancer. PBT allows for precise dose deposition within the target volume with the advantage of lower integral dose to surrounding normal tissues compared to photon radiation. In the reirradiation setting, PBT has been shown to provide improved efficacy and reduced toxicity compared to photons for recurrent thoracic and head and neck (H&N) tumors. Such dosimetric advantages may also be valuable in the re-treatment of prostate cancer, which is routinely treated to doses approaching or surpassing 80 Gy. Furthermore, some studies suggest that proton therapy is associated with greater radiobiologic damage to malignant cells, which may be important in disease that has already proven to be resistant to treatment with photons.Herein, members of the Particle Therapy Co-Operative Group (PTCOG) genitourinary subcommittee critically evaluate the potential advantages and challenges of proton therapy for radio-recurrent prostate cancer and propose appropriate candidates for proton reirradiation.
