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Purpose: Targeted radiopharmaceutical therapy (RPT) in combination with external beam radiation therapy (EBRT) shows promise as a method to increase tumor control and mitigate potential high-grade toxicities associated with re-treatment for patients with recurrent head and neck cancer. This work establishes a patient-specific dosimetry framework that combines Monte Carlo-based dosimetry from the 2 radiation modalities at the voxel level using deformable image registration (DIR) and radiobiological constructs for patients enrolled in a phase 1 clinical trial combining EBRT and RPT., Methods and Materials: Serial single-photon emission computed tomography (SPECT)/computed tomography (CT) patient scans were performed at approximately 24, 48, 72, and 168 hours postinjection of 577.2 MBq/m 2 (15.6 mCi/m 2 ) CLR 131, an iodine 131-containing RPT agent. Using RayStation, clinical EBRT treatment plans were created with a treatment planning CT (TPCT). SPECT/CT images were deformably registered to the TPCT using the Elastix DIR module in 3D Slicer software and assessed by measuring mean activity concentrations and absorbed doses. Monte Carlo EBRT dosimetry was computed using EGSnrc. RPT dosimetry was conducted using RAPID, a GEANT4-based RPT dosimetry platform. Radiobiological metrics (biologically effective dose and equivalent dose in 2-Gy fractions) were used to combine the 2 radiation modalities., Results: The DIR method provided good agreement for the activity concentrations and calculated absorbed dose in the tumor volumes for the SPECT/CT and TPCT images, with a maximum mean absorbed dose difference of -11.2%. Based on the RPT absorbed dose calculations, 2 to 4 EBRT fractions were removed from patient EBRT treatments. For the combined treatment, the absorbed dose to target volumes ranged from 57.14 to 75.02 Gy. When partial volume corrections were included, the mean equivalent dose in 2-Gy fractions to the planning target volume from EBRT + RPT differed -3.11% to 1.40% compared with EBRT alone., Conclusions: This work demonstrates the clinical feasibility of performing combined EBRT + RPT dosimetry on TPCT scans. Dosimetry guides treatment decisions for EBRT, and this work provides a bridge for the same paradigm to be implemented within the rapidly emerging clinical RPT space., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Patients receiving pencil beam scanning (PBS) proton therapy with the addition of a dynamic collimation system (DCS) are potentially subject to an additional neutron dose from interactions between the incident proton beam and the trimmer blades. This study investigates the secondary neutron dose rates for both single-field uniform dose (SFUD) and intensity modulated proton therapy treatments., Methods and Materials: Secondary neutron dose distributions were calculated for both a dynamically collimated and an uncollimated, dual-field chordoma treatment plan and compared with previously published neutron dose rates from other contemporary scanning treatment modalities. Monte Carlo N-Particle transport code was used to track all primary and secondary particles generated from nuclear reactions within the DCS during treatment through a model of the patient geometry acquired from the computed tomography planning data set. Secondary neutron ambient dose equivalent distributions were calculated throughout the patient using a meshgrid with a tally resolution equivalent to that of the treatment planning computed tomography., Results: The median healthy-brain neutron ambient dose equivalent for a dynamically collimated intracranial chordoma treatment plan using a DCS was found to be 0.97 mSv/Gy for the right lateral SFUD field, 1.37 mSv/Gy for the apex SFUD field, and 1.24 mSv/Gy for the composite intensity modulated proton therapy distribution from 2 fields., Conclusions: These results were at least 55% lower than what has been reported for uniform scanning modalities with brass apertures. However, they still reflect an increase in the excess relative risk of secondary cancer incidence compared with an uncollimated PBS treatment using only a graphite range shifter. Regardless, the secondary neutron dose expected from the DCS for these PBS proton therapy treatments appears to be on the order of, or below, what is expected for alternative collimated proton therapy techniques., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To introduce a method to model the 3D dose distribution of laterally asymmetric proton beamlets resulting from collimation. The model enables rapid beamlet calculation for spot scanning (SS) delivery using a novel penumbra-reducing dynamic collimation system (DCS) with two pairs of trimmers oriented perpendicular to each other., Methods: Trimmed beamlet dose distributions in water were simulated with MCNPX and the collimating effects noted in the simulations were validated by experimental measurement. The simulated beamlets were modeled analytically using integral depth dose curves along with an asymmetric Gaussian function to represent fluence in the beam's eye view (BEV). The BEV parameters consisted of Gaussian standard deviations (sigmas) along each primary axis (σ(x1),σ(x2),σ(y1),σ(y2)) together with the spatial location of the maximum dose (μ(x),μ(y)). Percent depth dose variation with trimmer position was accounted for with a depth-dependent correction function. Beamlet growth with depth was accounted for by combining the in-air divergence with Hong's fit of the Highland approximation along each axis in the BEV., Results: The beamlet model showed excellent agreement with the Monte Carlo simulation data used as a benchmark. The overall passing rate for a 3D gamma test with 3%/3 mm passing criteria was 96.1% between the analytical model and Monte Carlo data in an example treatment plan., Conclusions: The analytical model is capable of accurately representing individual asymmetric beamlets resulting from use of the DCS. This method enables integration of the DCS into a treatment planning system to perform dose computation in patient datasets. The method could be generalized for use with any SS collimation system in which blades, leaves, or trimmers are used to laterally sharpen beamlets.

Neutron production is of concern for proton therapy, especially for passive scattering proton beam delivery methods. The levels of neutron dose equivalent vary significantly with system design and treatment parameters. The purpose of this study was to examine neutron dose equivalent per therapeutic dose (H/D) around the Mevion S250 proton therapy system, a novel design of proton therapy systems. The benchmark comparisons between measurement and simulation were found to be within a factor of 2 for most cases. The H/D values were evaluated as a function of various parameters. The results showed that, at a standard reference condition (10 × 10 cm(2) field size, distance 1 m detector-to-isocenter lateral to the primary proton beam direction), the H/D values range from 0.72 to 3.37 mSv Gy(-1) for all configurations studied. The H/D values generally (1) decreased as the neutron detectors moved away from the isocenter, (2) decreased with increasing aperture field sizes, (3) increased with increasing angle from the initial beam axis and (4) were independent of treatment nozzle position. The H/D trends were consistent with other existing passive scattering proton accelerators reported in the literature.

Purpose: The radiobiological benefits afforded by spatially fractionated (GRID) radiation therapy pairs well with the dosimetric advantages of proton therapy. Inspired by the emergence of energy‐layer specific collimators in pencil beam scanning (PBS), this work investigates how the spot spacing and collimation can be optimized to maximize the therapeutic gains of a GRID treatment while demonstrating the integration of a dynamic collimation system (DCS) within a commercial beamline to deliver GRID treatments and experimentally benchmark Monte Carlo calculation methods. Methods: GRID profiles were experimentally benchmarked using a clinical DCS prototype that was mounted to the nozzle of the IBA‐dedicated nozzle system. Integral depth dose (IDD) curves and lateral profiles were measured for uncollimated and GRID‐collimated beamlets. A library of collimated GRID dose distributions were simulated by placing beamlets within a specified uniform grid and weighting the beamlets to achieve a volume‐averaged tumor cell survival equivalent to an open field delivery. The healthy tissue sparing afforded by the GRID distribution was then estimated across a range of spot spacings and collimation widths, which were later optimized based on the radiosensitivity of the tumor cell line and the nominal spot size of the PBS system. This was accomplished by using validated models of the IBA universal and dedicated nozzles. Results: Excellent agreement was observed between the measured and simulated profiles. The IDDs matched above 98.7% when analyzed using a 1%/1‐mm gamma criterion with some minor deviation observed near the Bragg peak for higher beamlet energies. Lateral profile distributions predicted using Monte Carlo methods agreed well with the measured profiles; a gamma passing rate of 95% or higher was observed for all in‐depth profiles examined using a 3%/2‐mm criteria. Additional collimation was shown to improve PBS GRID treatments by sharpening the lateral penumbra of the beamlets but creates a trade‐off between enhancing the valley‐to‐peak ratio of the GRID delivery and the dose‐volume effect. The optimal collimation width and spot spacing changed as a function of the tumor cell radiosensitivity, dose, and spot size. In general, a spot spacing below 2.0 cm with a collimation less than 1.0 cm provided a superior dose distribution among the specific cases studied. Conclusions: The ability to customize a GRID dose distribution using different collimation sizes and spot spacings is a useful advantage, especially to maximize the overall therapeutic benefit. In this regard, the capabilities of the DCS, and perhaps alternative dynamic collimators, can be used to enhance GRID treatments. Physical dose models calculated using Monte Carlo methods were experimentally benchmarked in water and were found to accurately predict the respective dose distributions of uncollimated and DCS‐collimated GRID profiles. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this work was to develop and experimentally validate a Dynamic Collimation Monte Carlo (DCMC) simulation package specifically designed for the simulation of collimators in pencil beam scanning proton therapy (PBS‐PT). The DCMC package was developed using the TOPAS Monte Carlo platform and consists of a generalized PBS source model and collimator component extensions. Methods: A divergent point‐source model of the IBA dedicated nozzle (DN) at the Miami Cancer Institute (MCI) was created and validated against on‐axis commissioning measurements taken at MCI. The beamline optics were mathematically incorporated into the source to model beamlet deflections in the X and Y directions at the respective magnet planes. Off‐axis measurements taken at multiple planes in air were used to validate both the off‐axis spot size and divergence of the source model. The DCS trimmers were modeled and incorporated as TOPAS geometry extensions that linearly translate and rotate about the bending magnets. To validate the collimator model, a series of integral depth dose (IDD) and lateral profile measurements were acquired at MCI and used to benchmark the DCMC performance for modeling both pristine and range shifted beamlets. The water equivalent thickness (WET) of the range shifter was determined by quantifying the shift in the depth of the 80% dose point distal to the Bragg peak between the range shifted and pristine uncollimated beams. Results: A source model of the IBA DN system was successfully commissioned against on‐ and off‐axis IDD and lateral profile measurements performed at MCI. The divergence of the source model was matched through an optimization of the source‐to‐axis distance and comparison against in‐air spot profiles. The DCS model was then benchmarked against collimated IDD and in‐air and in‐phantom lateral profile measurements. Gamma analysis was used to evaluate the agreement between measured and simulated lateral profiles and IDDs with 1%/1 mm criteria and a 1% dose threshold. For the pristine collimated beams, the average 1%/1 mm gamma pass rates across all collimator configurations investigated were 99.8% for IDDs and 97.6% and 95.2% for in‐air and in‐phantom lateral profiles. All range shifted collimated IDDs passed at 100% while in‐air and in‐phantom lateral profiles had average pass rates of 99.1% and 99.8%, respectively. The measured and simulated WET of the polyethylene range shifter was determined to be 40.9 and 41.0 mm, respectively. Conclusions: We have developed a TOPAS‐based Monte Carlo package for modeling collimators in PBS‐PT. This package was then commissioned to model the IBA DN system and DCS located at MCI using both uncollimated and collimated measurements. Validation results demonstrate that the DCMC package can be used to accurately model other aspects of a DCS implementation via simulation. [ABSTRACT FROM AUTHOR]

Purpose: When designing a collimation system for pencil beam spot scanning proton therapy, a decision must be made whether or not to rotate, or focus, the collimator to match beamlet deflection as a function of off‐axis distance. If the collimator is not focused, the beamlet shape and fluence will vary as a function of off‐axis distance due to partial transmission through the collimator. In this work, we quantify the magnitude of these effects and propose a focused dynamic collimation system (DCS) for use in proton therapy spot scanning. Methods: This study was done in silico using a model of the Miami Cancer Institute's (MCI) IBA Proteus Plus system created in Geant4‐based TOPAS. The DCS utilizes rectangular nickel trimmers mounted on rotating sliders that move in synchrony with the pencil beam to provide focused collimation at the edge of the target. Using a simplified setup of the DCS, simulations were performed at various off‐axis locations corresponding to beam deflection angles ranging from 0° to 2.5°. At each off‐axis location, focused (trimmer rotated) and unfocused (trimmer not rotated) simulations were performed. In all simulations, a 4 cm water equivalent thickness range shifter was placed upstream of the collimator, and a voxelized water phantom that scored dose was placed downstream, each with 4 cm airgaps. Results: Increasing the beam deflection angle for an unfocused trimmer caused the collimated edge of the beamlet profile to shift 0.08–0.61 mm from the baseline 0° simulation. There was also an increase in low‐dose regions on the collimated edge ranging from 14.6% to 192.4%. Lastly, the maximum dose, Dmax, was 0–5% higher for the unfocused simulations. With a focused trimmer design, the profile shift and dose increases were all eliminated. Conclusions: We have shown that focusing a collimator in spot scanning proton therapy reduces dose at the collimated edge compared to conventional, unfocused collimation devices and presented a simple, mechanical design for achieving focusing for a range of source‐to‐collimator distances. [ABSTRACT FROM AUTHOR]