Scanning Proton Therapy Research Articles

Evaluation of monte carlo to support commissioning of the treatment planning system of new pencil beam scanning proton therapy facilities

ABSTRACT Objective. To demonstrate the potential of Monte Carlo (MC) to support the resource-intensive measurements that comprise the commissioning of the treatment planning system (TPS) of new proton therapy facilities. Approach. Beam models of a pencil beam scanning system (Varian ProBeam) were developed in GATE (v8.2), Eclipse proton convolution superposition algorithm (v16.1, Varian Medical Systems) and RayStation MC (v12.0.100.0, RaySearch Laboratories), using the beam commissioning data. All models were first benchmarked against the same commissioning data and validated on seven spread-out Bragg peak (SOBP) plans. Then, we explored the use of MC to optimise dose calculation parameters, fully understand the performance and limitations of TPS in homogeneous fields and support the development of patient-specific quality assurance (PSQA) processes. We compared the dose calculations of the TPSs against measurements (DDTPSvs.Meas.) or GATE (DDTPSvs.GATE) for an extensive set of plans of varying complexity. This included homogeneous plans with varying field-size, range, width, and range-shifters (RSs) (n = 46) and PSQA plans for different anatomical sites (n = 11). Main results. The three beam models showed good agreement against the commissioning data, and dose differences of 3.5% and 5% were found for SOBP plans without and with RSs, respectively. DDTPSvs.Meas. and DDTPSvs.GATE were correlated in most scenarios. In homogeneous fields the Pearson’s correlation coefficient was 0.92 and 0.68 for Eclipse and RayStation, respectively. The standard deviation of the differences between GATE and measurements (±0.5% for homogeneous and ±0.8% for PSQA plans) was applied as tolerance when comparing TPSs with GATE. 72% and 60% of the plans were within the GATE predicted dose difference for both TPSs, for homogeneous and PSQA cases, respectively. Significance. Developing and validating a MC beam model early on into the commissioning of new proton therapy facilities can support the validation of the TPS and facilitate comprehensive investigation of its capabilities and limitations.

Disease and toxicity outcomes for a modern cohort of patients with squamous cell carcinoma of cutaneous origin involving the parotid gland: Comparison of volumetric modulated arc therapy and pencil beam scanning proton therapy

ObjectivesWe sought to describe outcomes for locally advanced cutaneous squamous cell carcinoma (SCC) involving the parotid treated with volumetric modulated arc therapy (VMAT) versus pencil beam scanning proton beam therapy (PBT). Materials and MethodsPatients were gathered from 2016 to 2022 from 5 sites of a large academic RT department; included patients were treated with RT and had parotid involvement by: direct extension of a cutaneous primary, parotid regional spread from a previously or contemporaneously resected but geographically separate cutaneous primary, or else primary parotid SCC (with a cutaneous primary ostensibly occult). Acute toxicities were provider-reported (CTCAE v5.0) and graded at each on treatment visit. Statistical analyses were conducted. ResultsMedian follow-up was 12.9 months (1.3 – 72.8); 67 patients were included. Positive margins/extranodal extension were present in 34 cases; gross disease in 17. RT types: 39 (58.2 %) VMAT and 28 (41.8 %) PBT. Concurrent systemic therapy was delivered in 10 (14.9 %) patients. There were 17 treatment failures (25.4 %), median time of 168 days. Pathologically positive neck nodes were associated with locoregional recurrence (p = 0.015). Oral cavity, pharyngeal constrictor, and contralateral parotid doses were all significantly lower for PBT. Median weight change was −3.8 kg (-14.1 – 5.1) for VMAT and −3 kg (-16.8 – 3) for PBT (p = 0.013). Lower rates of ≥ grade 1 xerostomia (p = 0.002) and ≥ grade 1 dysguesia (p < 0.001) were demonstrated with PBT. ConclusionsCutaneous SCC involving the parotid can be an aggressive clinical entity despite modern multimodal therapy. PBT offers significantly lower dose to organs at risk compared to VMAT, which seemingly yields diminished acute toxicities.

Modelling small block aperture in an in-house developed GPU-accelerated Monte Carlo-based dose engine for pencil beam scanning proton therapy

Purpose. To enhance an in-house graphic-processing-unit accelerated virtual particle (VP)-based Monte Carlo (MC) proton dose engine (VPMC) to model aperture blocks in both dose calculation and optimization for pencil beam scanning proton therapy (PBSPT)-based stereotactic radiosurgery (SRS). Methods and materials. A module to simulate VPs passing through patient-specific aperture blocks was developed and integrated in VPMC based on simulation results of realistic particles (primary protons and their secondaries). To validate the aperture block module, VPMC was first validated by an opensource MC code, MCsquare, in eight water phantom simulations with 3 cm thick brass apertures: four were with aperture openings of 1, 2, 3, and 4 cm without a range shifter, while the other four were with same aperture opening configurations with a range shifter of 45 mm water equivalent thickness. Then, VPMC was benchmarked with MCsquare and RayStation MC for 10 patients with small targets (average volume 8.4 c.c. with range of 0.4–43.3 c.c.). Finally, 3 typical patients were selected for robust optimization with aperture blocks using VPMC. Results. In the water phantoms, 3D gamma passing rate (2%/2 mm/10%) between VPMC and MCsquare was 99.71 ± 0.23%. In the patient geometries, 3D gamma passing rates (3%/2 mm/10%) between VPMC/MCsquare and RayStation MC were 97.79 ± 2.21%/97.78 ± 1.97%, respectively. Meanwhile, the calculation time was drastically decreased from 112.45 ± 114.08 s (MCsquare) to 8.20 ± 6.42 s (VPMC) with the same statistical uncertainties of ~0.5%. The robustly optimized plans met all the dose–volume-constraints (DVCs) for the targets and OARs per our institutional protocols. The mean calculation time for 13 influence matrices in robust optimization by VPMC was 41.6 s and the subsequent on-the-fly ‘trial-and-error’ optimization procedure took only 71.4 s on average for the selected three patients. Conclusion. VPMC has been successfully enhanced to model aperture blocks in dose calculation and optimization for the PBSPT-based SRS.

FLASH radiotherapy sparing effect on the circulating lymphocytes in pencil beam scanning proton therapy: impact of hypofractionation and dose rate

Purpose. The sparing effect of ultra-high dose rate (FLASH) radiotherapy has been reported, but its potential to mitigate depletion of circulating blood and lymphocytes (CL) has not been investigated in pencil-beam scanning-based (PBS) proton therapy, which could potentially reduce the risk of radiation-induced lymphopenia. Material and methods. A time-dependent framework was used to score the dose to the CL during the course of radiotherapy. For brain patients, cerebral vasculatures were semi-automatic segmented from 3T MR-angiography data. A dynamic beam delivery system was developed capable of simulating spatially varying instantaneous dose rates of PBS treatment plans, and which is based on realistic beam delivery parameters that are available clinically. We simulated single and different hypofractionated PBS intensity modulated proton therapy (IMPT) FLASH schemes using 600 nA beam current along with conventionally fractionated IMPT treatment plan at 2 nA beam current. The dosimetric impact of treatment schemes on CL was quantified, and we also evaluated the depletion in subsets of CL based on their radiosensitivity. Results. The proton FLASH sparing effect on CL was observed. In single-fraction PBS FLASH, just 1.5% of peripheral blood was irradiated, whereas hypofractionated FLASH irradiated 7.3% of peripheral blood. In contrast, conventional fractionated IMPT exposed 42.4% of peripheral blood to radiation. PBS FLASH reduced the depletion rate of CL by 69.2% when compared to conventional fractionated IMPT. Conclusion. Our dosimetric blood flow model provides quantitative measures of the PBS FLASH sparing effect on the CL in radiotherapy for brain cancer. FLASH Single treatment fraction offers superior CL sparing when compared to hypofractionated FLASH and conventional IMPT, supporting assumptions about reducing risks of lymphopenia compared to proton therapy at conventional dose rates. The results also indicate that faster conformal FLASH delivery, such as passive patient-specific energy modulation, may further enhance the sparing of the immune system.

Calibration assessment of the PSI proton therapy Gantry 2 scanning system after 10 years of operation

Sub-millimetre precision is a crucial criterion for beam delivery in Pencil Beam Scanning (PBS) proton therapy. Nowadays, most of the therapy systems use PBS technique where single beams with a regulated number of protons are delivered sequentially to different locations within the target. Beam energy defines the depth of the beam in the target and scanner magnets deflect the beam to the desired lateral position.The PSI Gantry 2 was among the first gantries to use the PBS technique. Available clinical proton beam energies ranging from 70 MeV to 230 MeV are achieved by de-grading a 250 MeV beam, initially provided by a super-conducting cyclotron. Beam scanning is performed just before the last bending magnet producing a nearly parallel beam at iso-centre with a well-focused beam over the full scan area of 20×12 cm2. We developed a calibration algorithm for the scanner magnets in order to achieve the desirable precision of the beam in the target. Measuring the beam position with a strip ion chamber in the gantry nozzle, we parametrized the propagation of the beam to the target calculating the beam angle at different scan positions as well as all gantry angles. During 10 years of operation we performed regular Quality Assurance (QA) tests to validate parameters obtained during the system commissioning. The QA data proved a stable system operation and no parametrization update was required so far. In this contribution, we describe the calibration pro-cess of scanning magnets with respect to beam position at the isocentre and show the stability of this implementation over the time.

Multi-institutional consensus on machine QA for isochronous cyclotron-based systems delivering ultra-high dose rate (FLASH) pencil beam scanning proton therapy in transmission mode.

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. 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. 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. 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. 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.

Anatomical changes in resection cavity during brain radiotherapy.

Brain tumors are in general treated with a maximal safe resection followed by radiotherapy of remaining tumor including the resection cavity (RC) and chemotherapy. Anatomical changes of the RC during radiotherapy can have impact on the coverage of the target volume. The aim of the current study was to quantify the potential changes of the RC and to identify risk factors for RC changes. Sixteen patients treated with pencil beam scanning proton therapy between October 2019 and April 2020 were retrospectively analyzed. The RC was delineated on pre-treatment computed tomography (CT) and magnetic resonance imaging, and weekly CT-scans during treatment. Isotropic expansions were applied to the pre-treatment RC (1-5mm). The percentage of volume of the RC during treatment within the expanded pre-treatment volumes was quantified. Potential risk factors (volume of RC, time interval surgery-radiotherapy and relationship of RC to the ventricles) were evaluated using Spearman's rank correlation coefficient. The average variation in relative RC volume during treatment was 26.1% (SD 34.6%). An expansion of 4mm was required to cover > 95% of the RC volume in > 90% of patients. There was a significant relationship between the absolute volume of the pre-treatment RC and the volume changes during treatment (Spearman's ρ = -0.644; p = 0.007). RCs are dynamic after surgery. Potentially, an additional margin in brain cancer patients with an RC should be considered, to avoid insufficient target coverage. Future research on local recurrence patterns is recommended.

Optimization of a YAP(Ce) prompt X-ray camera for imaging with spot scanning proton beams at clinical dose levels

Prompt secondary electron bremsstrahlung X-ray (prompt X-ray) imaging using a low-energy X-ray camera is a promising method for observing the beam shape from outside a subject. However, it has sometimes been necessary to conduct such imaging at a higher dose than the clinical level to acquire images with acceptable quality. To solve this problem, we optimized a prompt X-ray imaging system to use for spot scanning proton therapy system. The new camera had more than one order higher sensitivity to image several types of beams, including those at the clinical dose level. The optimized prompt X-ray imaging system uses a 4 mm diameter pinhole collimator to increase sensitivity, and it is combined with a larger YAP(Ce) scintillator to increase the magnification ratio and thus improve spatial resolution. We used a list-mode data-acquisition system with high count rate capability. Prompt X-ray images were acquired by irradiating a water phantom with proton beams from the spot scanning proton therapy system. Measurements were taken for pencil beams, spread-out Bragg peak (SOBP) beams, and a beam utilized in actual clinical therapy. For all of the beams, we could measure scanning spot images within a spill and evaluate the ranges for the accumulated images at the clinical dose level. From the list-mode data, we measured the temporarily altered positions of the scanning beams as well as the accumulations of the prompt X-ray images. The optimized prompt X-ray imaging system could improve sensitivity while maintaining better spatial resolution. The new system realized prompt X-ray imaging at the clinical dose level and holds promise for future clinical imaging of prompt X-rays.

Total scalp irradiation using pencil beam scanning proton therapy for dermatofibrosarcoma protuberans: case study and photon dosimetric comparison—a case report

Total scalp irradiation using pencil beam scanning proton therapy for dermatofibrosarcoma protuberans: case study and photon dosimetric comparison—a case report

Treating recurrent metastatic breast cancer to the skin with proton therapy

Proton therapy offers unique physical properties that make it an excellent choice for treating metastatic breast cancer, particularly when recurrent disease occurs near previously irradiated tissues. This case study demonstrates the dosimetric benefits of proton therapy in patients with metastatic breast cancer to the skin. The case consists of one patient with 5 separate areas treated with Pencil Beam Scanning (PBS) proton therapy over a period of 2 years using Monte Carlo calculation and robust optimization. The results demonstrate that proton therapy effectively spared healthy tissues while delivering the prescribed dose to the tumor. This case demonstrates the feasibility of developing effective radiation plans for skin metastases using proton therapy, highlighting its dosimetric advantages and minimal impact on nearby organs.

Pencil Beam Scanning Proton Therapy for Pregnant Patients With Brain and Head and Neck Cancers

When radiation therapy is medically necessary for pregnant patients, photon-based treatments (XRT) have traditionally been used, whereas proton radiation therapy (PRT) is avoided due to concerns about neutron dose. This retrospective study analyzes pregnant patients treated with XRT and models the equivalent dose that would have been delivered to the fetus with proton radiation compared with XRT. The purpose of this work is to provide a comprehensive analysis of pencil beam scanning proton therapy (PBS-PRT) for pregnant patients and to evaluate whether PBS-PRT should be the new standard of practice for treating pregnant patients with brain and head and neck cancers. PBS-PRT plans were made for seven pregnant patients who received XRT: four treated for brain tumors and three for head and neck tumors. Measurements were performed with the patient plans using an anthropomorphic phantom and Wendi-2 meter placed at the phantom's abdomen. Patient-specific measurements were used to determine the total fetal equivalent dose from PBS-PRT compared with XRT. Imaging dose was also evaluated with a Fluke 451 dose meter. The average measured fetal equivalent dose, accounting for photons and neutrons, for the brain plans was 0.4 mSv for PBS-PRT and 7 mSv for XRT. For the head and neck plans, it was 6 mSv and 90 mSv for PBS-PRT and XRT, respectively. The PBS-PRT plans were preferred by the physicians for both tumor coverage and normal-tissue sparing. Daily imaging added between 0.05 and 1.5 mSv to the total dose. This retrospective study showed that when treating brain or head and neck cancers in pregnant patients, fetal equivalent dose is reduced by approximately a factor of 10 with PBS-PRT compared with XRT without making any compromises in treatment planning objectives. These results support a change of practice to using PBS-PRT as the new standard for treating pregnant patients with brain or head and neck tumors compared with XRT.

Implementing dispersion measurement as part of scanning proton therapy commissioning and quality assurance

Introduction. Dispersion in an accelerator quantifies the deviation of the proton trajectory when there is a momentum deviation. We present for the first time a safe method of measuring dispersion in the clinic, using a scintillator detector and the momentum deviations within a spill. This is an important accelerator quantity as we found that this is the reason behind the large dose fluctuation in our absolute dosimetry measurement. Methods. Dispersions are measured for nine energies in a Hitachi ProBeat system at three locations (isocenter and at two profile monitors) and at two gantry angles (0 and 90 degrees) by first measuring the spot position and momentum drift within a spill. The spot position drift is measured by the XRV-4000 at the isocenter, and by the two profile monitors located at 0.57 and 2.27 m from the isocenter. The momentum drift is calculated from the intra-spill range drift which is measured using the Ranger accessory. The dispersion at isocenter and its gradient are calculated using the weighted least square regression on the measured dispersions at the three locations. A constraint is formulated on the dispersion and its gradient to ensure minimal intra-spill spot position deviation around the isocenter. Results. The measured intra-spill range and spot positional drift at isocenter are less than and respectively. The momentum spread calculated from the range drift are less than 0.08%. The dispersion at the isocenter ranged from to and the zero-crossing happens upstream of isocenter for all energies. 2 of the 9 energies (168.0 and 187.5 MeV) violated the constraint and has an intra-spill spot positional deviation greater than within from the isocenter. Conclusion. This measurement is recommended as part of commissioning and annual quality assurance for accelerator monitoring and to ensure intra-spill spot deviations remain low.

Oncological Outcomes, Long-Term Toxicities, Quality of Life and Sexual Health after Pencil-Beam Scanning Proton Therapy in Patients with Low-Grade Glioma.

To assess oncological outcomes, toxicities, quality of life (QoL) and sexual health (SH) of low-grade glioma (LGG) patients treated with pencil-beam scanning proton therapy (PBS-PT). We retrospectively analyzed 89 patients with LGG (Neurofibromatosis type 1; n = 4 (4.5%) patients) treated with PBS-PT (median dose 54 Gy (RBE)) from 1999 to 2022 at our institution. QoL was prospectively assessed during PBS-PT and yearly during follow-up from 2015 to 2023, while a cross-sectional exploration of SH was conducted in 2023. Most LGGs (n = 58; 65.2%) were CNS WHO grade 2 and approximately half (n = 43; 48.3%) were located in the vicinity of the visual apparatus/thalamus. After a median follow-up of 50.2 months, 24 (27%) patients presented with treatment failures and most of these (n = 17/24; 70.8%) were salvaged. The 4-year overall survival was 89.1%. Only 2 (2.2%) and 1 (1.1%) patients presented with CTCAE grade 4 and 3 late radiation-induced toxicity, respectively. No grade 5 late adverse event was observed. The global health as a domain of QoL remained stable and comparable to the reference values during PBS-PT and for six years thereafter. Sexual satisfaction was comparable to the normative population. LGG patients treated with PBS-PT achieved excellent long-term survival and tumor control, with exceptionally low rates of high-grade late toxicity, and favorable QoL and SH.

Patient-Specific Quality Assurance in Pencil Beam Scanning by 2-Dimensional Array

PurposeThis study aimed to determine the characteristics of 2D ionization chamber array and the confidence limits of the gamma passing rate in pencil beam scanning proton therapy. Materials and Methods:The Varian ProBeam Compact spot-scanning system and the PTW OCTAVIUS 1500XDR array were used as a proton therapy system and detector, respectively. Our methods consisted of 2 parts: (1) the characteristics of the detector were tested and (2) patient-specific quality assurance was performed and evaluated by gamma analysis using dose-difference and distance-to-agreement criteria of 3% and 2 mm, respectively, with 123 treatment plans in head and neck, breast, chest, abdomen, and pelvic regions. Results:The PTW OCTAVIUS 1500XDR array had good reproducibility, uniformity, linearity, repetition rate, and monitor unit per spot within 0.1%, with accuracy, energy dependence, and measurement depth within 0.5%. The overall uncertainty of the PTW OCTAVIUS 1500XDR array was 2.49%. For field size and range shifter, using gamma analysis, the passing rate was 100%. The overall results of patient-specific quality assurance with the gamma evaluation were 98.9% ± 1.6% in 123 plans and confidence limit was 95.7%. Conclusion:The PTW OTAVIUS 1500XDR offered effective performance in pencil beam scanning proton therapy.

Pencil Beam Scanning Proton Therapy for Adolescents and Young Adults with Head and Neck Sarcomas

PurposeTo assess clinical outcomes of adolescents and young adults (AYAs) with head and neck sarcomas (HNSs) treated with pencil beam scanning proton therapy (PBSPT) and to report quality of life (QoL). Materials and MethodsTwenty-eight AYAs (aged 15 to 39 years) with HNS treated between January 2001 and July 2022 at our institution were included. The median age was 21.6 years. Rhabdomyosarcoma (39.3%), Ewing sarcoma (17.9%), chondrosarcoma (14.3%), and osteosarcoma (14.3%) were the most frequent diagnoses. Three (10.7%) patients were metastatic before PBSPT and 13 (46.4%) patients had a tumor with intracranial extension. The median total radiation dose was 63 GyRBE (range, 45 to 74 GyRBE). Thirteen (46.4%) patients received concomitant chemotherapy. Toxicity was reported according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US National Institutes of Health, Bethesda, Maryland). Survival was estimated using the Kaplan-Meier method. QoL was assessed using a PEDQOL (Pediatric Quality of Life Questionnaire) questionnaire. Self-reported outcomes were assessed using institutional questionnaires. ResultsWith a median follow-up of 57 months (range, 3.7 to 243 months), 5 patients (17.8%) had local failure (LF) only, 2 (7.1%) experienced distant failure (DF) only, and 2 (7.1%) had LF and DF. The estimated 5-year local control (LC) and distant control (DC) rates were 71.8% and 80.5%, respectively. The median times to LF and DF were 13.4 and 22.2 months, respectively. Four (14.3%) patients died, all but one from their HNS. Estimated 5-year overall survival was 90.7%. Six (21.4%) patients developed nonocular grade ≥3 toxicity, which consisted of otitis media (n = 2), hearing impairment (n = 2), osteoradionecrosis (n = 1), and sinusitis (n = 1). Four (14.3%) patients developed cataracts that required surgery. The 5-year freedom from nonocular grade 3 toxicity was 91.1%. No grade 4 or higher toxicity was observed. Adolescents rated their quality of life before treatment worse than their parents did. ConclusionExcellent outcomes with acceptable late-toxicity rates were observed for AYAs with HNS after PBSPT.

Integration and dosimetric validation of a dynamic collimation system for pencil beam scanning proton therapy

Objective. To integrate a Dynamic Collimation System (DCS) into a pencil beam scanning (PBS) proton therapy system and validate its dosimetric impact. Approach. Uncollimated and collimated treatment fields were developed for clinically relevant targets using an in-house treatment plan optimizer and an experimentally validated Monte Carlo model of the DCS and IBA dedicated nozzle (DN) system. The dose reduction induced by the DCS was quantified by calculating the mean dose in 10- and 30-mm two-dimensional rinds surrounding the target. A select number of plans were then used to experimentally validate the mechanical integration of the DCS and beam scanning controller system through measurements with the MatriXX-PT ionization chamber array and EBT3 film. Absolute doses were verified at the central axis at various depths using the IBA MatriXX-PT and PPC05 ionization chamber. Main results. Simulations demonstrated a maximum mean dose reduction of 12% for the 10 mm rind region and 45% for the 30 mm rind region when utilizing the DCS. Excellent agreement was observed between Monte Carlo simulations, EBT3 film, and MatriXX-PT measurements, with gamma pass rates exceeding 94.9% for all tested plans at the 3%/2 mm criterion. Absolute central axis doses showed an average verification difference of 1.4% between Monte Carlo and MatriXX-PT/PPC05 measurements. Significance. We have successfully dosimetrically validated the delivery of dynamically collimated proton therapy for clinically relevant delivery patterns and dose distributions with the DCS. Monte Carlo simulations were employed to assess dose reductions and treatment planning considerations associated with the DCS.

The Applications and Pitfalls of Cone-Beam Computed Tomography-Based Synthetic Computed Tomography for Adaptive Evaluation in Pencil-Beam Scanning Proton Therapy.

The study evaluates the efficacy of cone-beam computed tomography (CBCT)-based synthetic CTs (sCT) as a potential alternative to verification CT (vCT) for enhanced treatment monitoring and early adaptation in proton therapy. Seven common treatment sites were studied. Two sets of sCT per case were generated: direct-deformed (DD) sCT and image-correction (IC) sCT. The image qualities and dosimetric impact of the sCT were compared to the same-day vCT. The sCT agreed with vCT in regions of homogeneous tissues such as the brain and breast; however, notable discrepancies were observed in the thorax and abdomen. The sCT outliers existed for DD sCT when there was an anatomy change and for IC sCT in low-density regions. The target coverage exhibited less than a 5% variance in most DD and IC sCT cases when compared to vCT. The Dmax of serial organ-at-risk (OAR) in sCT plans shows greater deviation from vCT than small-volume dose metrics (D0.1cc). The parallel OAR volumetric and mean doses remained consistent, with average deviations below 1.5%. The use of sCT enables precise treatment and prompt early adaptation for proton therapy. The quality assurance of sCT is mandatory in the early stage of clinical implementation.

The implementation of an image-guided system at a proton therapy center facility.

Pencil Beam Scanning (PBS) proton therapy has similar requirements on patient alignment to within 1mm and 1-degree accuracy as photon radiosurgery. This study describes general workflow, acceptance, and commissioning test procedures and their respective results for an independent robotic arm used for Image Guided Radiotherapy (IGRT) for a Proton Therapy System. The system is equipped with kV-imaging techniques capable of orthogonal and Cone-Beam Computed Tomography (CBCT) imaging modalities mounted on an independent robotic arm gantry attached to the ceiling. The imaging system is capable of 360-degree rotation around patients to produce CBCT and kilovoltage orthogonal images. The imaging hardware is controlled by Ehmet Health XIS software, and MIM Software handles the image fusion and registration to an acceptable accuracy of ≤1-mm shifts for patients' alignment. The system was tested according to the requirements outlined in the American Association of Physicists in Medicine (AAPM) Task Group (TG) 142 and TG 179. The system tests included (1) safety, functionality, and connectivity, (2) mechanical testing, (3) image quality, (4) image registration, and (5) imaging dose. Additional tests included imaging gantry isocentricity with a laser tracker and collision-avoiding system checks. The orthogonal and volumetric imaging are comparable in quality to other commercially available On-Board Imagers (OBI) systems. The resulting spatial resolution values were 1.8-, 0.8-, and 0.5-Line Pairs per Millimeter (lp/mm) for orthogonal, full-fan CBCT, and half-fan CBCT, respectively. The image registration is accurate to within 1mm and 1 degree. The data shows consistent imaging-guided system performance with standard deviations in x, y, and z of 0.7, 0.8, and 0.7mm, respectively. The system provides excellent image quality and performance, which can be used for IGRT. The proven accuracy of the x-ray imaging and positioning system at McLaren Proton Therapy Center (MPTC) is 1mm, making it suitable for proton therapy.

Oncologic Outcomes of Conventionally Fractionated, Hypofractionated, and Stereotactic Body Spot-Scanned Proton Radiation Therapy for Prostate Cancer: The Mayo Clinic Experience.

Spot/pencil beam scanned proton therapy is a relatively new technology with fundamental differences from double scattered or IMRT. We aimed to report the long-term oncologic outcomes of a contemporary prospective series of patients treated with spot-scanned proton therapy (SSPT). An IRB-approved prospective registry identified patients with prostate cancer treated with proton therapy between January 2016 and December 2018. Descriptive statistics were calculated for all patients. Clinical, demographic, and treatment characteristics were gathered and analyzed. Kaplan-Meier curves were generated to estimate survival and recurrence rates. Outcomes assessed included 5-year overall survival (OS), 5-year local control (LC), biochemical failure (BF), regional and distant failures, and physician-reported adverse events (AEs). Biochemical failure was defined as rise in PSA ≥ 2.0 ng/mL above nadir PSA. Acute and chronic gastrointestinal (GI) and genitourinary (GU) grade 2+ and grade 3+ baseline-adjusted AEs were assigned using CTCAE v5.0. All failures were re-staged with PET C-11 or PSMA. With a median follow up of 4.4 years (IQR 3.7 - 5), two hundred and eighty-six prostate cancer patients with a median age of 72 (IQR 67.5 - 77) were treated with spot-scanned proton radiation. The median Gleason grade group was 3 (IQR 2 - 4). The median pre-RT PSA was 6.9 ng/mL (IQR 4.3 - 10.5). Median T-stage was T1c. Nearly 64% of all patients were on androgen deprivation therapy at the time of initiating radiation treatment. The median total radiation dose was 79.2 Gy delivered over 44 fractions, 70 Gy over 28 fractions, and 38 Gy over 5 fractions for CF, HF, and SBRT regimens, respectively. The BF rate for all patients was 8.4%. The 5-year LC rates for CF, HF, and SBRT were 100% (95% CI: 100 - 100), 100% (95% CI: 100 - 100), and 97.3% (95% CI: 92.2 - 100), respectively (p = 0.07). Regional recurrences occurred in 12 (4.2%) patients: 8 (5.6%) treated with CF, 2 (2.1%) with HF, and 2 (4.3%) with SBRT (p = 0.62). Distant metastatic failures occurred in 12 patients (4.2%): 5 (3.5%) treated with CF, 7 (7.4%) with HF, and none with SBRT (0%) (p = 0.052). The 5-year OS for patients treated with CF, HF, and SBRT SSPT were 88.2% (95% CI: 81.8 - 95), 86.2% (95% CI: 77.6 - 95.6), and 97.2% (95% CI: 92 - 100), respectively (p = 0.1). Acute and chronic grade 2+ GI baseline-adjusted AEs occurred in 8 (2.8%) and 51 (17.8%) patients, respectively. Acute and chronic grade 3+ GI baseline-adjusted AEs occurred in 3 (1%) and 4 (1.4%) patients, respectively. Acute and chronic grade 2+ GU-related AEs were observed in 72 (25.2%) and 63 (22%) patients, respectively. Acute and chronic grade 3+ GU toxicity was observed in 3 (1%) and 6 (2.1%) patients, respectively. Spot-scanned proton radiation therapy provides high local control rates and excellent oncologic outcomes across different fractionation schedules with low long-term AE rates.

Selection of breathing phase number in 4D scanned proton treatment planning optimization for lung tumors

The standard four-dimensional (4D) treatment planning includes all breathing states in the optimization process, which is time-consuming. This work was aimed to optimize the number of intermediate phases needed for 4D proton treatment planning optimization to reduce the computational cost. Five 4D optimization strategies adopting different numbers of intermediate states and one three-dimensional (3D) optimization plan were studied for fifteen lung cancer patients treated with scanned protons, optimizing on all ten phases (4D_10), two extreme phases (4D_2), six phases during the exhalation stage (4D_6EX), six phases during the inhalation stage (4D_6IN), two extreme phases plus an intermediate state (4D_3) and average computed tomography image (3D), respectively. The 4D dose evaluation was conducted on all the ten phases, considering the interplay effect. The resulting doses accumulated on the reference phase were computed and compared. Compared to the 4D optimization plans, the 3D optimization plan performed inferiorly in target coverage, but superiorly in organ at risks (OARs) sparing. For the 4D optimization, all the five 4D plans showed similar performance in OARs protection. However, the 4D_6EX and 4D_6IN strategies out-performed the 4D_2 and 4D_3 plans in dose homogeneity. The computing times of the 4D_2, 4D_3, 4D_6EX and 4D_6IN approaches decreased to 32%, 41%, 66% and 67% of the 4D_10 method, respectively. Thus, our study suggested that the use of all phases during inhalation or exhalation stage might be a feasible approach substituting for the full phase strategy to reduce the calculation load while guaranteeing the plan quality for scanned proton therapy.