Commercial Treatment Planning System Research Articles

Dose averaged linear energy transfer optimization for large sacral chordomas in carbon ion therapy.

Carbon ion beams are well accepted as densely ionizing radiation with a high linear energy transfer (LET). However, the current clinical practice does not fully exploit the highest possible dose-averaged LET (LETd) and, consequently, the biological potential in the target. This aspect becomes worse in larger tumors for which inferior clinical outcomes and corresponding lower LETd wasreported. The vicinity to critical organs in general and the inferior overall survival reported for larger sacral chordomas treated with carbon ion radiotherapy (CIRT), makes the treatment of such tumors challenging. In this work it was aimed to increase the LETd in large volume tumors while maintaining the relative biological effectiveness (RBE)-weighted dose, utilizing the LETd optimization functions of a commercial treatment planning system (TPS). Ten reference sequential boost carbon ion treatment plans, designed to mimic clinical plans for large sacral chordoma tumors, were generated. High dose clinical target volumes (CTV-HD) larger than were considered as large targets. The total RBE-weighted median dose prescription with the local effect model (LEM) was in 16 fractions (nine to low dose and seven to high dose planning target volume). No LETd optimization was performed in the reference plans, while LETd optimized plans used the minimum LETd (Lmin) optimization function in RayStation2023B. Three different Lmin values were investigated and specified for the seven boost fractions: , and . To compare the LETd optimized against reference plans, LETd and RBE-weighted dose based goals similar to and less strict than clinical ones were specified for the target. The goals for the organs at risk (OAR) remained unchanged. Robustness evaluation was studied for eight scenarios ( range uncertainty and setup uncertainty along the main three axes). The optimization method with resulted in an optimal LETd distribution with an average increase of (and ) in the CTV-HD by ( ) (and ( )), without significant difference in the RBE-weighted dose. By allowing over- and under-dosage in the target, the (and ) can be increased by ( ) (and ( )), using the optimization parameters . The pass rate for the OAR goals in the LETd optimized plans was in the same level as the reference plans. LETd optimization lead to less robust plans compared to referenceplans. Compared to conventionally optimized treatment plans, the LETd in the target was increased while maintaining the RBE-weighted dose using TPS LETd optimization functionalities. Regularly assessing RBE-weighted dose robustness and acquiring more in-room images remain crucial and inevitable aspects duringtreatment.

The use of carbon fiber/polyetheretherketone (CF/PEEK) in pedicle screw fixation for spinal neoplasms-potential advantages in postoperative imaging and radiotherapy planning.

Titanium pedicle screw fixation complicates postoperative care in patients with spinal neoplasms due to postoperative imaging artefacts and dose perturbation. This study aims to measure the benefits of using carbon fiber/polyetheretherketone (CF/PEEK) pedicle fixation compared to titanium in postoperative imaging, radiotherapy planning and delivery for spinal neoplasms treated with conventional external beam radiotherapy with a commercial treatment planning system. The properties of CF/PEEK pedicle fixation systems were compared to titanium in radiotherapy dose planning accuracy and postoperative computed tomography (CT) image quality. Dose profiles through the screw, tulip and longitudinal axis of the screw were acquired with radiochromic films and compared to a collapsed cone algorithm simulation, to measure dose agreement. The image quality of postoperative CTs were compared by defining four regions of interest around the vertebrae and screws in water phantom models and previous planning CTs, and comparing calculated artefact indexes (AIs). CF/PEEK screws have non-inferior dosimetric prediction accuracy up to 50 mm beneath the screw for collapsed-cone algorithm planning systems. There is a statistically significant reduction in the absolute difference between calculated and measured dose at a depth of 2 mm beneath the screw. There is minimal attenuation with CF/PEEK relative to the surrounding dose, extending to 50 mm beneath the screw. There is a statistically significant improvement in CT imaging quality with reduced AIs in CF/PEEK fixation compared to titanium in both model and patient CT plans. CF/PEEK pedicle fixation can provide benefits in postoperative imaging and photon radiotherapy planning and delivery to patients with spinal neoplasms.

A generalized model for monitor units determination in ocular proton therapy using machine learning: A proof-of-concept study

Objective. Determining and verifying the number of monitor units is crucial to achieving the desired dose distribution in radiotherapy and maintaining treatment efficacy. However, current commercial treatment planning system(s) dedicated to ocular passive eyelines in proton therapy do not provide the number of monitor units for patient-specific plan delivery. Performing specific pre-treatment field measurements, which is time and resource consuming, is usually gold-standard practice. This proof-of-concept study reports on the development of a multi-institutional-based generalized model for monitor units determination in proton therapy for eye melanoma treatments. Approach. To cope with the small number of patients being treated in proton centers, three European institutes participated in this study. Measurements data were collected to address output factor differences across the institutes, especially as function of field size, spread-out Bragg peak modulation width, residual range, and air gap. A generic model for monitor units prediction using a large number of 3748 patients and broad diversity in tumor patterns, was evaluated using six popular machine learning algorithms: (i) decision tree; (ii) random forest, (iii) extra trees, (iv) K-nearest neighbors, (v) gradient boosting, and (vi) the support vector regression. Features used as inputs into each machine learning pipeline were: Spread-out Bragg peak width, range, air gap, fraction and calibration doses. Performance measure was scored using the mean absolute error, which was the difference between predicted and real monitor units, as collected from institutional gold-standard methods. Main results. Predictions across algorithms were accurate within 3% uncertainty for up to 85.2% of the plans and within 10% uncertainty for up to 98.6% of the plans with the extra trees algorithm. Significance. A proof-of-concept of using machine learning-based generic monitor units determination in ocular proton therapy has been demonstrated. This could trigger the development of an independent monitor units calculation tool for clinical use.

Commissioning and initial validation of Eclipse eMC algorithm for the electron FLASH research extension (FLEX) system for pre-clinical studies.

To investigate the feasibility of commissioning the 16 MeV electron FLASH Extension (FLEX) in the commercial treatment planning system (TPS) for biomedical research with cell and mouse models, and in silico treatment planning studies. To commission the FLEX system with the electron Monte Carlo (eMC) algorithm in the commercial TPS, radiochromic film was used to measure the vendor-recommended beam data. Once the beam model was generated for the eMC algorithm, supplemental measurements were collected for validation purposes and compared against the TPS-calculated results. Additionally, the newly commissioned 16 MeV FLASH beam was compared to the corresponding 16 MeV conventional electron beam. The eMC algorithm effectively modeled the FLEX system. The eMC-calculated PDDs and profiles for the 16 MeV electron FLASH beam agreed with measured values within 1%, on average, for 6×6 cm2 and 10×10cm2 applicators. Flatness and symmetry deviated by less than 1%, while FWHM and penumbra agreed within 1mm for both eMC-calculated and measured profiles. Additionally, the small field (i.e., 2-cm diameter cutout) that was measured for validation purposes agreed with TPS-calculated results within 1%, on average, for both the PDD and profiles. The FLASH and conventional dose rate 16 MeV electron beam were in agreement in regard to energy, but the profiles for larger field sizes began to deviate(>10×10cm2) due to the forward-peaked nature of the FLASH beam. For cell irradiation experiments, the measured and eMC-calculated in-plane and cross-plane absolute dose profiles agreed within 1%, on average. The FLEX system was successfully commissioned in the commercial TPS using the eMC algorithm, which accurately modeled the forward-peaked nature of the FLASH beam. A commissioned TPS for FLASH will be useful for pre-clinical cell and animal studies, as well as in silico FLASH treatment planning studies for future clinical implementation.

Intraoperative radiation therapy with 50kV x-rays: A multi-institutional review.

This report covers clinical implementation of a low kV intraoperative radiation therapy (IORT) program with the INTRABEAM® System (Carl Zeiss Meditec AG, Jena, Germany). Based on collective user experience from eight institutions, we discuss best methods of INTRABEAM quality assurance (QA) tests, commissioning measurements, clinical workflow, treatment planning, and potential avenues for research. The guide provides pertinent background information and clinical justification for IORT. It describes the INTRABEAM system and commissioning measurements along with a TG100 risk management analysis to ensure safety and accuracy of the IORT program. Following safety checks, dosimetry measurements are performed for verification of field flatness and symmetry, x-ray output, and depth dose. Also discussed are dose linearity checks, beam isotropy, ion chamber measurements, calibration protocols, and in-vivo dosimetry with optically stimulated luminescence dosimeters OSLDs, and radiochromic film. Emphasis is placed on the importance of routine QA procedures (daily, monthly, and annual) performed at regular intervals for a successful IORT program. For safe and accurate dose delivery, tests of important components of IORT clinical workflow are emphasized, such as, dose prescription, pre-treatment QA, treatment setup, safety checks, radiation surveys, and independent checks of delivered dose. Challenges associated with in-vivo dose measurements are discussed, along with special treatment procedures and shielding requirements. The importance of treatment planning in IORT is reviewed with reference to a Monte Carlo-based commercial treatment planning system highlighting its main features and limitations. The report concludes with suggested topics for research including CT-based image-guided treatment planning and improved prescription dose accuracy. We hope that this multi-institutional report will serve as a guidance document on the clinical implementation and use of INTRABEAM IORT.

Deep learning MRI-only synthetic-CT generation for pelvis, brain and head and neck cancers

Background and purposeMRI-only planning relies on dosimetrically accurate synthetic-CT (sCT) generation to allow dose calculation. Here we validated the dosimetric accuracy of sCTs generated using a deep learning algorithm for pelvic, brain and head and neck (H&N) cancer sites using variable MRI data from multiple scanners. MethodssCT generation models were trained using a cycle-GAN algorithm, using paired MRI-CT patient data. Input MRI sequences were: T2 for pelvis, T1 with gadolinium (T1Gd) and T2 FLAIR for brain and T1 for H&N. Patient validation sCTs were generated for each site (49 - pelvis, 25 - brain and 30 - H&N). VMAT plans, following local clinical protocols, were calculated on planning CTs and recalculated on sCTs. HU and dosimetric differences were assessed, including DVH differences and gamma index (2 %/2mm). ResultsMean absolute error (MAE) HU differences were; 48.8 HU (pelvis), 118 HU (T2 FLAIR brain), 126 HU (T1Gd brain) and 124 HU (H&N). Mean primary PTV D95% dose differences for all sites were < 0.2 % (range: −0.9 to 1.0 %). Mean 2 %/2mm and 1 %/1mm gamma pass rates for all sites were > 99.6 % (min: 95.3 %) and > 97.3 % (min: 80.1 %) respectively. For all OARs for all sites, mean dose differences were < 0.4 %. ConclusionGenerated sCTs had excellent dosimetric accuracy for all sites and sequences. The cycle-GAN model, available on the research version of a commercial treatment planning system, is a feasible method for sCT generation with high clinical utility due to its ability to use variable input data from multiple scanners and sequences.

Comparison of volumetric modulated arc therapy and helical tomotherapy for prostate cancer using Pareto fronts.

Studies comparing different radiotherapy treatment techniques-such as volumetric modulated arc therapy (VMAT) and helical tomotherapy (HT)-typically compare one treatment plan per technique. Often, some dose metrics favor one plan and others favor the other, so the final plan decision involves subjective preferences. Pareto front comparisons provide a more objective framework for comparing different treatment techniques. A Pareto front is the set of all treatment plans where improvement in one criterion is possible only by worsening another criterion. However, different Pareto fronts can be obtained depending on the chosen machine settings. To compare VMAT and HT using Pareto fronts and blind expert evaluation, to explain the observed differences, and to illustrate limitations of using Pareto fronts. We generated Pareto fronts for twenty-four prostate cancer patients treated at our clinic for VMAT and HT techniques using an in-house script that controlled a commercial treatment planning system. We varied the PTV under-coverage (100%-V95%) and the rectum mean dose, and fixed the mean doses to the bladder and femoral heads. In order to ensure a fair comparison, those fixed mean doses were the same for the two treatment techniques and the sets of objective functions were chosen so that the conformity indexes of the two treatment techniques were also the same. We used the same machine settings as are used in our clinic. Then, we compared the VMAT and HT Pareto fronts using a specific metric (clinical distance measure) and validated the comparison using a blinded expert evaluation of treatment plans on these fronts for all patients in the cohort. Furthermore, we investigated the observed differences between VMAT and HT and pointed out limitations of using Pareto fronts. Both clinical distance and blind treatment plan comparison showed that VMAT Pareto fronts were better than HT fronts. VMAT fronts for 10 and 6MV beam energy were almost identical. HT fronts improved with different machine settings, but were still inferior to VMAT fronts. That VMAT Pareto fronts are better than HT fronts may be explained by the fact that the linear accelerator can rapidly vary the dose rate. This is an advantage in simple geometries that might vanish in more complex geometries. Furthermore, one should be cautious when speaking about Pareto optimal plans as the best possible plans, as their calculation depends on many parameters.

The effect of vaginal cylinder inhomogeneity on the HDR brachytherapy dose calculations using Monte Carlo simulations.

To analytically assess the heterogeneity effect of vaginal cylinders (VC) made of high-density plastics on dose calculations, considering the prescription point (surface or 5mm beyond the surface), and benchmark the accuracy of a commercial model-based dose calculation (MBDC) algorithm using Monte Carlo (MC) simulations. The GEANT4 MC code was used to simulate a commercial 192 Ir HDR source and VC, with diameters ranging from 20 to 35mm, inside a virtual water phantom. Standard plans were generated from a commercial treatment planning system [TPS-BrachyVision ACUROS (BV)] optimized for a treatment length of 5cm through two dose calculation approaches: (1) assuming all the environment as water (i.e., Dw,w-MC & Dw,w-TG43 ) and (2) accounting for the heterogeneity of VC applicators (i.e., Dw,w-App-MC & Dw,w-App-MBDC ). The compared isodose lines, and dose & energy difference maps were extracted for analysis. In addition, the dose difference on the peripheral surface, along the applicator and at middle of treatment length, as well as apical tip was evaluated. The Dw,w-App-MC results indicated that the VC heterogeneity can cause a dose reduction of (up to) % 6.8 on average (for all sizes) on the peripheral surface, translating to 1mm shrinkage of the isodose lines compared to Dw,w-MC . In addition, the results denoted that BV overestimates the dose on the peripheral surface and apical tip of about 3.7% and 17.9%, respectively, (i.e., Dw,w-App-MBDC vs Dw,w-App-MC ) when prescribing to the surface. However, the difference between the two were negligible at the prescription point when prescribing to 5mm beyond the surface. The VCs' heterogeneity could cause dose reduction when prescribing dose to the surface of the applicator, and hence increases the level of uncertainty. Thus, reviewing the TG43 results, in addition to ACUROS, becomes prudent, when evaluating the surface coverage at the apex.

A single centre intercomparison between commercial treatment planning systems for 90Y radioembolization using virtual and experimental phantoms

IntroductionDedicated Treatment Planning Systems (TPSs) were developed to personalize 90Y-transarterial radioembolization. This study evaluated the agreement among four commercial TPSs assessing volumes of interest (VOIs) volumes and dose metrics. MethodsA homogeneous (EH) and an anthropomorphic phantom with hot and cold inserts (EA) filled with 99mTc-pertechnetate were acquired with a SPECT/CT scanner. Their virtual versions (VH and VA, respectively) and a phantom with activity inside a single voxel (VK) were generated by an in-house MATLAB script. Images and delineated VOIs were imported into the TPSs to compute voxel-based absorbed dose distributions with various dose deposition approaches: local deposition method (LDM) and dose kernel convolution (DKC) with/without local density correction (LDC). VOI volumes and mean absorbed doses were assessed against their median value across TPSs. Dose-volume histograms (DVHs) and VK-derived dose profiles were evaluated. ResultsSmall (<2.1 %) and large (up to 42.4 %) relative volume differences were observed on large (>500 ml) and small VOIs, respectively. Mean absorbed doses relative differences were < 3 % except for small VOIs with steep dose gradients (up to 89.1 % in the VA Cold Sphere VOI). Within the same TPS, LDC negligibly affected the mean absorbed dose, while DKC and LDM showed differences up to 63 %. DHVs were mostly overlapped in experimental phantoms, with some differences in the virtual versions. Dose profiles agreed within 1 %. ConclusionTPSs showed an overall good agreement except for small VOI volumes and mean absorbed doses of VOIs with steep dose gradients. These discrepancies should be considered in the dosimetry uncertainty assessment, thus requiring an appropriate harmonization.

Enhancing Precision in L-band Electron Paramagnetic Resonance Tooth Dosimetry: Incorporating Digital Image Processing and Radiation Therapy Plans for Geometric Correction.

Following unforeseen exposure to radiation, quick dose determination is essential to prioritize potential patients that require immediate medical care. L-band electron paramagnetic resonance tooth dosimetry can be efficiently used for rapid triage as this poses no harm to the human incisor, although geometric variations among human teeth may hinder accurate dose estimation. Consequently, we propose a practical geometric correction method using a mobile phone camera. Donated human incisors were irradiated with calibrated 6-MV photon beam irradiation, and dose-response curves were developed by irradiation with a predetermined dose using custom-made poly(methyl methacrylate) slab phantoms. Three radiation treatment plans for incisors were selected and altered to suit the head phantom. The mean doses on tooth structures were calculated using a commercial treatment planning system, and the electron paramagnetic resonance signals of the incisors were measured. The enamel area was computed from camera-acquired tooth images. The relative standard uncertainty was rigorously estimated both with and without geometric correction. The effects on the electron paramagnetic resonance signal caused by axial and rotational movements of tooth samples were evaluated through finite element analysis. The mean absolute deviations of mean doses both with and without geometric correction showed marginal improvement. The average relative differences without and with geometric correction significantly decreased from 21.0% to 16.8% (p = 0.01). The geometric correction method shows potential in improving dose precision measurement with minimal delay. Furthermore, our findings demonstrated the viability of using treatment planning system doses in dose estimation for L-band electron paramagnetic resonance tooth dosimetry.

Application of the Integrated Deep Reinforcement Learning Solution in Automatic IMRT Planning for Gastric Cancer

The intensity-modulated radiation therapy (IMRT) treatment planning optimization process is usually a manual, tedious and time-consuming task. An unsupervised integrated automatic IMRT planning solution was discussed and implemented to simulate the manual operation during the whole planning process. Based on knowledge-based planning (KBP) and deep reinforcement learning (DRL) schemes, a novel integrated solution combining the multi-objectives optimization policy network (MOPN) and three-dimensional dose prediction module (3D-DPM) was proposed. The MOPN was trained to learn how to adjust multiple optimization objectives in commercial Eclipse treatment planning system (TPS). The 3D-DPM was developed to generate the patient-specific initial optimization objectives to reduce the overall exploration space during MOPN training. The Eclipse 15.6 TPS Scripting Application Programming Interface (ESAPI) was used to realize the automatic interaction between models and TPS. In this study, 100 previously treated gastric cancer cases were selected from the clinical database, 70 cases were used for the training of dose prediction model and MOPN, the remaining 30 cases for evaluating the feasibility and effectiveness of automatic treatment planning solution. For all tested cases, the complete automatic treatment plan for a new case was generated based on the integrated solution, with about 6 min. Compared with the MOPN initial plans, the actual dose of spinal cord, liver, kidney-left, kidney-right, and intestine in the MOPN final plans reduced 42.4%, 25.2%, 52.4%, 37.8%, 11.8% respectively. The dose result of OARs in the MOPN final plans was similar to those in the clinical plans. In addition, a new case was able to complete optimization with about 15 adjustment steps by the trained MOPN. We successfully developed an integrated solution for automatic treatment planning. It first includes the dose prediction module for obtaining patient-specific initial optimization objectives. We demonstrated that the trained MOPN can mimic the operations of the physicians to adjust multiple objectives and obtain a high-quality plan in a shorter time. This integrated solution contributes to improving the efficiency of the overall planning workflow and reducing the variation of plan quality in clinical practice. Although improvement is warranted, the proposed integrated solution is a promising practical and effective approach for automatic planning in commercial TPS.

Commissioning and Initial Validation of Commercial Treatment Planning System for the Electron FLASH Research Extension

The aim of this study was to investigate the feasibility of commissioning the 16 MeV electron FLASH beam in a commercial treatment planning system (TPS) for pre-clinical research purposes. The delivery system consisted of a new commercial solution for which a linear accelerator was modified into a FLASH Research Extension platform. Additionally, preliminary radiation biology results were highlighted to showcase the future use of this system. To commission a commercial electron Monte Carlo (MC) for dose calculation of a 16 MeV FLASH beam in the TPS, radiochromic film was used to measure the vendor-required beam data, e.g., profiles and percent depth dose (PDD) curves for cone sizes of 6 × 6 cm2, 10 × 10 cm2, and 15 × 15 cm2 as well as an in-air profile for a 40 × 40 cm2 open field (no cone). Once the electron MC beam model was generated, additional measurements were collected for validation and compared against the calculated dose from the TPS. A treatment planning comparison between the newly commissioned FLASH beam and the conventional electron beam was conducted. Specifically, the dose-volume histograms (DVHs) for target volumes and organs at risk were investigated for skin cancer cases previously treated with conventional electron beams. Lastly, the FLASH dose distribution predicted by the electron MC for an in vitro cell study setup was validated with radiochromic film measurements, and initial radiobiology tests were conducted using FLASH and conventional dose-rate electron beams. The electron MC calculated dose for the 16 MeV electron FLASH beam agreed with measured PDDs within 1% for all field sizes. The beam profile characteristics, such as penumbra, shape, and full width at half maximum, demonstrated good agreement with less than 0.5 mm difference between the TPS and measurements. There were noticeable differences in the profiles of large fields between the FLASH and conventional dose-rate beam models due to the more forward-peaked FLASH beam. For treatment planning, Regarding DVH, the FLASH dose-rate plan provided comparable plan quality to the conventional dose-rate plan, achieving adequate coverage for the target volumes and sparing the healthy organs and tissues. The electron MC dose prediction for the FLASH beam was also found to be in good agreement with the film measurements of the in vitro cell study setup. Furthermore, the FLASH beam was observed to be more effective with a 20 % increase in killing pancreatic cancer cells compared to the conventional dose rate. The study successfully incorporated the 16 MeV electron FLASH Research Extension into the commercial TPS using electron Monte Carlo for dose calculation. This will be valuable for pre-clinical cell and animal studies. This research also enables FLASH treatment planning studies, a key component for the future implementation of FLASH into clinical care. Further research is necessary to incorporate the radiation biology effect of FLASH into the treatment planning system.

Cobalt Compensator-Based IMRT for Gynecologic Cancer Treatment in Low- and Middle-Income Countries: Equivalence to LINAC-Based IMRT

Cobalt intensity modulated radiation therapy (IMRT) has the potential to impact global oncology by improving access to precision radiation therapy, particularly in low- and middle-income countries, and a novel compensator-based machine has been developed. Previously, cobalt compensator-based IMRT and LINAC-based IMRT were shown to achieve similar target goals and dose constraints for head and neck clinical cases. Additionally, the fidelity of those calculations was supported by Monte Carlo simulations and gamma analysis. The current study investigates the use of cobalt compensator IMRT for another application - gynecologic cancer patients. A commercial treatment planning system was previously commissioned for the cobalt compensator-based device using Monte Carlo simulations from a simulation toolkit. Patient-specific compensators were modeled. Clinical gynecologic cancer cases were planned and compared to clinical plans with a 6MV LINAC using IMRT. The prescribed dose was 45 Gy in 25 fractions. Dosimetric plan quality endpoints for the planning target volume (PTV) and organs-at-risk (OARs) were compared. Parametric t-testing was used for statistical analysis, and criteria for significance was p<0.05. Dose statistics of 10 cases showed similar target coverage and normal tissue sparing between IMRT plans using a 6 MV LINAC and using a cobalt compensator-based device. Greater than 95% of the dose to greater than 95% of the PTV was achieved for all 10 cases using both the LINAC-based and cobalt compensator-based plans. There was no significant difference in the mean percentage of the PTV receiving 95% of the dose between LINAC-based and cobalt compensator-based plans (98.0 ± 1.88% vs 97.1 ± 1.90%, respectively, p = 0.313). Additionally, both the LINAC-based and cobalt compensator-based plans, for all 10 cases, met dose constraints for the OARs, including Spinal Cord Dmax < 4500 cGy, Kidney Dmean < 1800 cGy, Bladder Dmax < 5750 cGy, Rectum Dmax < 5500 cGy, Small Bowel Dmax < 5400 cGy, Bone Marrow V4000 < 37%, and Femoral Heads Dmax < 5000 cGy. Cobalt compensator-based IMRT may provide comparable quality treatment plans to LINAC-based IMRT for gynecologic cancer patients. Physical development of the cobalt compensator device has been completed and will be commissioned for further research to assess clinical outcomes.

Superiority of BNCT Treatment Planning Metrics Achieved Using Novel vs. Reference (BPA-F) Pharmaceuticals in Head and Neck Locations

Several novel boron delivery compounds currently under investigation by our group have demonstrated formulation, biodistribution, and dose response benefits in small animal models [1]. In this study we analyze the potential clinical impact of these compounds for boron neutron capture therapy (BNCT) in human patients. Pharmacokinetic models were used to estimate the tumor and normal tissue boron concentrations after continuous infusion of the novel compounds and BPA-F. Patient model segmentation, material assignment, and alignment of one or more treatment beams were exported from a commercial treatment planning system (TPS) to a novel dose calculation tool. This information was used to generate a voxelized model that incorporated the source, beam shaping assembly, collimator, and patient materials so that the full albedo effect was included in each dose calculation. Physical dose from 10B(n,α), 14N(n,p), 1H(n,n') interactions plus gamma rays from 1H(n,γ) and other reactions within the patient and treatment equipment were calculated by Monte Carlo transport of particles originating in a pre-generated phase space at the cover surface. RBE and CBE weighting factors are applied to combine these four physical dose volumes into an equivalent dose volume, and these five dose volumes were passed back to the TPS for evaluation. Tumor dose was increased by up to 2.6x for the novel compounds while normal tissue doses were constant or slightly reduced in comparison to BPA-F plans. Alternatively, for identical tumor dose the normal tissue doses and treatment time were reduced by up to 2.6x. In addition, in some cases it was possible to generate a single beam treatment plan using the new compounds that delivered higher tumor dose and lower normal tissues doses than a multiple beam plan using BPA-F. This study demonstrates both dosimetric and practical benefits of the new compounds in comparison to BPA-F, including the potential to deliver treatment using fewer beam directions and correspondingly easier treatment setups and higher patient throughput. The potential of these compounds to extend the range of clinical indications for BNCT is also discussed. These results motivate upcoming experimental testing of the key assumptions involved in their calculation.

Clinical Experience with Commissioning a GRID Collimator for Spatially Fractionated Radiation Therapy

In this study, we report our physics commissioning experience for clinically implementing a GRID collimator based Spatially Fractionated Radiation Therapy (SFRT). For SFRT commissioning, we utilized a commercially available brass GRID collimator (DotDecimal, Sanford, FL) that is mounted on a blocking tray for positioning into the accessory mount of the Linac. The brass GRID is 7.62 cm thick and weighs 15.8 kg. The GRID has a total of 149 divergent holes arranged in a hexagonal pattern (1.43 cm in diameter and hole-centers spaced at 2.11 cm when projected at the isocenter distance). The GRID encompasses a maximum field size of 25 × 25 cm at the isocenter. A commercial 48 × 48 × 48 cm water phantom scanning system was used to collect GRID output factors (GRID field to open field ratio), depth dose and beam profile data. Output measurements were performed using a 0.13 cm3 active volume ion-chamber and beam scans were obtained with a diode detector. Data was collected for both flattening and flattening-free beams of nominal energies 6 MV and 10 MV photons. The measurement depths were at dmax (1.5 cm for 6 MV and 2.5 cm for 10 MV), 5-cm and 10-cm respectively. For each energy and depth of measurement, collimator settings were varied from 5 × 5 cm to 28 × 28 cm. From scan profiles at different depths, the valley (lowest) to peak (highest) dose ratios (VPDR) were calculated. A commercial treatment planning system (TPS) was used to test the accuracy of dose calculations with GRID. This was accomplished by importing vendor generated DICOM RT file into the TPS. A block transmission factor of 7% for 6 MV and 10.2% for 10 MV energy beams were applied. All measured data were compared with corresponding TPS calculated data. Test patient treatment plans with GRID were created in TPS and planned distributions were verified using a commercial detector array with 2.5 mm detector spacing. The VPDR, expressed as %, are presented in Table 1. Measured and TPS calculated output factors agreed within 2% for 6 MV and within 3% for 10 MV photon beams. Percent depth doses were lower in magnitude for GRID field compared to open field for all energies studied (for e.g., 6 MV depth dose at 10 cm depth for 10 cm x10cm field 62% for GRID field vs. 66% for open field). Measured and calculated GRID beam profiles agreed within 5% dose difference and 1 mm distance-to agreement. For all test cases, the planned vs. measured dose distributions passed at an average gamma passing rate of 96.5% using a 3% dose difference/ 3 mm distance to agreement and 10% threshold criteria. The Dot Decimal GRID collimator provides a simple way of achieving SFRT in the clinic, albeit heavy to use and has an irradiation field size limitation of 25 cm × 25 cm.

Clinical Implementation of an Automated IMRT/VMAT Treatment Planning Tool

To create an in-house automated treatment planning tool for IMRT/VMAT treatments and evaluate the dosimetric plan quality against manually generated plans. A scripting application programming interface is employed to interact with a commercial treatment planning system (TPS) to implement automatic plan evaluation and update optimization parameters by mimicking the human planning process. The automated planning performs in an iterative fashion until reaching an acceptable tradeoff among target coverage/dose homogeneity and sparing of critical organs at risk. In each iteration, the dose constraints, priorities, and optimization structures for are automatically updated based on the results of the current iteration. Twenty previously treated plans (10 prostate and 10 head and neck), were preliminarily used to evaluate the performance of the automated planning tool. The differences in target and organ-at-risk metrics from the manually generated clinical plans were analyzed using paired t-test to evaluate clinical acceptability of tour automated planning tool. The current in-house-developed automated planning solution is able to create plans for different disease sites, including head & neck, prostate, pelvis, and lung. So far, the VMAT plans for more than 150 different cases have been generated with the tool. The results for these were also evaluated. Compared to the manually generated clinical head and neck plans, all auto plans achieved PTV D95% coverage and critical organs at risk sparing without statistically significant change in average global Dmax (107.4% for manual vs 107.3% for automated plans). The auto-planning solution provided reduced maximum doses to brainstem and spinal cord (average reductions with standard deviations of 5.1 ± 2.6 Gy and 2.9 ± 1.4 Gy, respectively, all p <0.03), reduced average mean doses to contralateral parotid, ipsilateral parotid, contralateral submandibular gland, pharynx, esophagus, cochleae (reductions of 2.2 ± 2.9 Gy, 4.8 ± 4.7 Gy, 3.6 ± 5.2 Gy, 2.0 ± 7.1 Gy, 3.9 ± 2.6 Gy, 3.8 ± 5.0 Gy, respectively, all p < 0.045). Similar results were observed for the prostate plans. With the same PTV coverage and without statistically significant change in average global Dmax (106.5% for manual vs 106.8% for automated plans), the automated solution provided superior sparing for both bladder and rectum. Bladder V75, V70, V65 were reduced by 0.6% ± 2.1%, 0.8% ± 2.5%, and 0.9% ± 2.9% (all p <0.04), respectively. Rectum V75, V70, V65, V60 were reduced by 1.0% ± 2.3%, 1.2% ± 2.8%, 1.3% ± 3.2%, 1.6% ± 3.6% (all p < 0.01), respectively. Our automated treatment planning solution is capable of efficiently generating VMAT plans for different disease sites with superior dosimetric indices compared to manually generated plans. Our tool is integrated within a commercial TPS platform, so it has the advantage of seamless adoption into the standard workflow to improve plan quality and treatment planning efficiency in our clinic.

Intensity-Modulated Neutron Therapy (IMNT) for Head and Neck Cancer: Early Toxicity Outcomes

Locally advanced head & neck cancers (HNC) are challenging to treat due to abutment of critical, dose-limiting structures. Fast neutron radiotherapy (NT) is a high linear energy transfer (LET) modality that provides better local control than photons for radioresistant cancers such as salivary gland tumors, but there have been concerns of toxicity with 3D conformal neutron therapy in the past. Recent technological advances have enabled the planning and delivery of IMNT, which improves target conformality and may reduce toxicity compared to 3D conformal NT. We report the first clinical evaluation of early toxicity outcomes of IMNT for HNC. Study is a single-institution retrospective review of all HNC patients treated with curative-intent IMNT from 10/2022 to 2/2023, using a hospital-based cyclotron (50.5 MeV 1H+ beam incident on a Be target) equipped with an isocentric gantry and multileaf collimator (MLC). A commercial treatment planning system with custom neutron-specific scattering kernels was used for IMNT planning using 4-6 fields. Patient-specific quality assurance included ionization chamber measurements and a novel 12C(n,2n)11C positron emission portal imaging system. kV portal imaging was used to confirm patient setup prior to each treatment session. All patients were prescribed 18.4 Gy at 1.15 Gy/fraction, delivered 4 days/week, which is equivalent to an x-ray EQD2 of approximately 70 Gy (RBE ∼ 3.8). Clinical observations suggest the RBE for radioresistant HNC may be as large as 8. Patients underwent weekly toxicity assessment, and acute toxicities were graded (G) by CTCAE v5.0. Ten patients received IMNT, median age 61 (range 34-78). Primary tumor sites were base of tongue (n = 3), sinonasal (n = 3), parotid (n = 2), submandibular (n = 1), larynx (n = 1). Tumor histologies included adenoid cystic carcinoma (n = 7), other salivary gland carcinomas (n = 2) and mucosal melanoma (n = 1). Most had T4 disease (n = 8) and one had N3b disease. Six had surgical resection with high-risk features, and 6 had gross measurable disease prior to IMNT. None had concurrent systemic therapy. Uninvolved salivary glands were spared in most patients. All patients completed treatment. Median follow up was 22 days (0-48). Acute toxicities (n, G 1, 2, 3) included skin (8, 3, 0), dysgeusia (1, 6, 0), xerostomia (3, 5, 0), mucositis (2, 0, 5), nausea (3, 0, 1). One patient had >10% weight loss and brief admission for supportive care and PEG placement; one patient had prophylactic PEG; both regained oral independence during follow-up. There was no Grade 4+ toxicity. IMNT improves the therapeutic ratio compared to 3D conformal NT and expands indications for NT in patients with radiorefractory tumors. Acute toxicity compares favorably with photons. Longer clinical and toxicity follow-up is anticipated. A prospective trial is planned to evaluate quality of life measures.

Decay Series Dose Delivery Validation of a Biology-Guided Radiotherapy (BgRT) Methodology

In this work, we compared the accuracy between the planned dose estimated by a commercial BgRT treatment planning system to the measured delivered dose by the BgRT treatment delivery device. The dose delivered was measured with the Sun Nuclear ArcCHECK device containing a customized phantom filled with fluorodeoxyglucose F18 (FDG) with a fixed target to background activity concentration ratio. The BgRT approach was evaluated for its capacity to accurately deliver a planned dose to a phantom target of an increasingly limited PET signal due to radioactive decay. The Sun Nuclear ArcCHECK is a helical detector assembly of 1,386 diodes around a 15 cm diameter cavity designed for quality assurance of linear accelerator (LINAC) driven therapies. In this work, the ArcCHECK was loaded with a cylindrical phantom containing a 22 mm diameter homogenous ball and a C-shape insert. The ball target was designated as an organ at risk (OAR) with appropriate dose constraints applied, and the C-shaped insert was designated as the target. The C-shaped target was used to simulate a tumor with a necrotic core. A cylindrical planning/gross tumor volume was placed around the C-shape, providing a test case of delivery to a partially PET-avid target. The target and OAR were filled with 58.46 kBq/mL of FDG and the background with 7.30 kBq/mL, giving an approximate target to background ratio of 8:1. A kVCT localization scan, a short PET pre-treatment scan, and a LINAC treatment sequence (1000 cGy per fraction) were performed each run with four runs performed over a duration of ∼3.5 hours (1.9 half-lives). The ArcCHECK measured the delivered dose during each LINAC treatment sequence and compared it to the plan predicted dose. The relative dose (RD) and absolute dose (AD) gamma values were then calculated for each run using Sun Nuclear's proprietary software with a gamma pass rate criterion of 3mm/3%. The PET scans for runs 1-4 were completed with background activity concentrations of 5.49 kBq/ml, 3.95 kBq/ml, 2.79 kBq/ml, and 2.02 kBq/ml, respectively. The scans further reported 17.48 kBq/ml, 12.26 kBq/ml, 7.93 kBq/ml, and 6.95 kBq/ml as the mean activity concentrations for the cylindrical gross tumor volume of the planned treatment. After treatment delivery, the resulting RD gamma values were 98%, 94%, 93%, and 95% and AD gamma values were 98%, 93%, 92%, and 94% for runs 1-4. Results from this study demonstrated treatment delivery stability with consistent repeatability in the 8:1 target to background contrast condition even with diminishing PET signal from the phantom target as the activity decayed. This work shows that BgRT is capable of delivering to a cylindrical target volume that is very different from the PET avid C-shaped that was used for the plan and delivery.

Estimating Potential Benefits of Online Adaptive Proton Therapy for Head-and-Neck Cancer: A Retrospective Study

Proton therapy is highly sensitive to anatomical changes and setup variations in head-and-neck (HN) treatments. To address this issue, proton centers often acquire patient CT images weekly to monitor patient anatomical changes during the treatment course and perform offline plan adaptation when needed. However, offline adaptation cannot fully account for daily setup variations or the anatomical changes occurring with high frequency. There are a few groups endeavoring to develop advanced technologies to enable online adaptive proton therapy (APT). However, the necessity of online APT remains controversial, as it is unknown that whether online APT will significantly improve treatment quality and outcomes compared to offline APT. The purpose of this study is to estimate the clinical potential of online APT in the management of HN cancers in relation to the current offline APT. Our retrospective study was conducted with four HN patients (35 fractions per patient), who had been treated with intensity modulated proton therapy and had offline adaptation once or twice during their treatment courses. Synthetic CT (sCT) images were generated from 140 daily CBCT images for us to recalculate the dose of the treatment plan in patient's actual treatment anatomy for each treatment fraction and adapt the plan when warranted. These adaptations were assumed to be performed online before treatment delivery to mimic an online APT course. Accumulative doses were calculated for both courses using the CBCT-based sCT images of every fraction for us to compare the target coverage, organ at risk (OAR) sparing, tumor control probability (TCP) and normal tissue complication probability (NTCP). An in-house script was developed to semi-automate this process in a commercial treatment planning system to facilitate our study. All patients would benefit from online APT to different extents. For the first patient, with OAR doses comparable to the actual offline course, the retrospective online APT course improved dose coverages of the three CTVs from 95.2%, 98.64% and 89.53% to 98.88%, 99.81%, 98.97%, which would lead to a 4.52% improvement in TCP. Similarly, online APT would yield a 2.66% improvement in TCP for the second patient. For the third patient, with comparable CTV dose coverages, the mean doses of right parotid and oral cavity were decreased from 29.52 Gy relative biological effectiveness (RBE) and 41.89 Gy RBE to 22.16 Gy RBE and 34.61 Gy RBE, leading to a reduce of 1.67% and 3.40% in NTCP. The mean dose of right parotid was decreased from 21.71 Gy RBE to 19.37 Gy RBE for the last patient, leading to a reduce of 0.73% in NTCP. Our results showed that online APT could better maintain the treatment plan quality than offline APT for all the four patients, despite their significant anatomical changes. Future investigation will focus on collecting more patient data to obtain statistically significant results and help identify the patients to whom the online APT will be of most benefit.

Comparison of Dynamic Trajectory Radiotherapy and Volumetric Modulated Arc Therapy for Loco-Regionally Advanced Oropharyngeal Cancer

Dynamic trajectory radiotherapy (DTRT) extends volumetric modulated arc therapy (VMAT) with dynamic table and collimator rotation. We investigate the potential benefit of DTRT over VMAT with respect to organ-at-risk (OAR) sparing for patients with loco-regionally advanced oropharyngeal cancer (OPC). We created DTRT and VMAT plans for 46 cases with prescribed doses of 50-70 Gy (2 Gy fractions, sequential boost) using 6 MV flattened beam on c-arm Linacs. For DTRT: case-specific collision avoidance maps were created and gantry-table paths were determined based on contoured structures to minimize fractional target/OAR overlap in beam's eye view. Gantry-collimator paths minimized field width in the leaf-travel direction. DTRT paths were imported in a research version of a commercial treatment planning system for intensity modulation optimization using the same optimizer and dose calculation algorithms as for VMAT. Plans at each dose level were normalized with 100% of the prescribed dose to 95% of the planning target volume (PTV). PTV coverage and OAR sparing for DTRT and VMAT were compared using Wilcoxon matched-pair signed rank test (5% significance level). The correlation between the fractional OAR/PTV50Gy volume overlap and difference in OAR Dmean between the two techniques was evaluated using Spearman's correlation coefficient. Plans at each dose level were all acceptable and had D0.03cc<110% prescription dose (difference between DTRT and VMAT were not statistically significant). In the combined plans, PTV50Gy D95% and D98% and PTV70Gy D95% were significantly higher with DTRT compared to VMAT. Differences in PTV66Gy coverage and PTV70Gy D5% were not statistically significant. Mean Dmean to the contralateral (CL) parotid gland was 13.99 / 15.28 Gy for DTRT / VMAT respectively, it was 25.75 / 28.05 Gy for the CL submandibular gland, 44.88 / 45.82 Gy for the pharynx and 30.90 / 33.93 Gy for the oral cavity (all with p<.001). Mean Dmean to the ipsilateral (IL) parotid gland was 29.00 / 29.28 Gy for DTRT / VMAT respectively (p = .77) and 57.71 / 57.91 Gy for the IL submandibular gland (p = .99). Significantly higher doses were observed with DTRT than with VMAT for the optical and auditory OARs and for the brain, but well below the clinical goals. The difference in Dmean (VMAT-DTRT) was negatively correlated to the fractional OAR/PTV50Gy overlap for the CL parotid and submandibular gland and the IL submandibular gland (r = -0.55 to -0.51, p<.001) but not for IL parotid gland (r = -0.17, p = .26), oral cavity (r = -0.13, p = .41) or pharynx (r = -011, p = .47). For at least the same target coverage, DTRT statistically significantly improves sparing for OARs related to salivary and swallowing functions compared to state-of-the-art VMAT. The advantage of DTRT decreases with increasing fractional OAR/PTV50Gy volume overlap for some salivary glands but not for pharynx or oral cavity. DTRT is promising to reduce treatment-related toxicity for patients with OPC.