Radiochromic Film Research Articles

Dose mapping of hard X-ray radiation due to runaway electrons in Alvand tokamak using combination of high-dose and low-dose level dosimeters

Tokamaks are one of the strongest types of hard x-ray (HXR) sources that always generate energetic hard x-rays because of the bremsstrahlung radiation, when energetic runaway electrons are accelerated in the presence of the toroidal electric field. In addition, the characteristics of small-sized tokamaks make them capable of having a considerable population of runaway electrons during discharge time. In this research, the hard x-ray dose distribution of Alvand tokamak is measured and calculated using EBT3 radiochromic film and GR-200 TLD as a high-dose and low-dose dosimeters, respectively. The purpose of this measurement is to obtain a dose distribution map in the Alvand tokamak laboratory (35 m × 13 m) and its environment. It has been determined that the maximum absorbed dose on the equatorial plane of the vacuum chamber is approximately 73 mSv/shot for a 3 ms discharge. According to the observations, the occurrence of Z instability in the vertical position of the plasma leads to the concentration of a substantial amount of radiation in an upward conical shell, which reaches up to 250 mSv/shot at a 60-degree angle above the horizontal line. Calculating the amount of radiation attenuation of the concrete shield installed in the vicinity of Alvand tokamak Laboratory, which is about 99.3 % ± 0.35, is an important result from the radiation protection point of view. This result indicates that the dose limit in public area is about background level and this area is effectively protected from the intense radiation of Alvand tokamak by the concrete shield.

RADT-04. DOSE PAINTING WITH THE GAMMA KNIFE LIGHTNING OPTIMIZER TO ESCALATE RADIATION DOSE TO RESIDUAL TUMOR WITHIN BRAIN METASTASIS RESECTION CAVITIES

Abstract BACKGROUND The novel Gamma Knife (GK) Lightning optimizer allows simultaneous automated optimization of multiple intracranial radiotherapy targets. We used this optimizer to create a dose-painting treatment plan where an escalated dose was prescribed to residual disease within a brain metastasis resection cavity. We validated this method by measuring dose-delivery accuracy using radiochromic film in an anthropomorphic phantom. METHODS A 15.7cc irregular contour was drawn to represent a brain metastasis resection cavity, a 2mm expansion contour created, and a 1.6cc contour drawn representing a nodule of residual disease. In GammaPlan v11.3.1, three targets were created with overlapping dose matrices. Targets were prescribed 3Gy (2mm expansion), 4Gy (resection cavity), and 5Gy (residual disease) in one fraction. On the GK Icon system, an occipital mold was made, an unexposed film placed in the phantom’s cranium, cone-beam coregistration conducted, and treatment delivered. The film was scanned and calibrated for absolute dosimetry. To evaluate dose-painting accuracy, global gamma index (GI) analyses were performed at various dose and distance tolerances, excluding points below 30% of the maximum dose. RESULTS An 18-minute treatment plan with 40 shots was created and delivered. Prescription isodose lines were 3Gy at 55% (2mm expansion, mean 4.8Gy), 4Gy at 69% (resection cavity, mean 5.2Gy), and 5Gy at 75% (residual disease, mean 6.1Gy). All target volumes had ≥ 99% prescription dose coverage and the maximum dose was 6.9Gy. Paddick conformality indices were 0.79 (2mm expansion), 0.74 (resection cavity), and 0.15 (residual disease). Gamma index pass rate/mean GI/median GI were 73%/0.68/0.55 at 1%/1mm tolerance, 85%/0.58/0.48 at 2%/1mm tolerance, and 97%/0.34/0.28 at 2%/2mm tolerance. An average of 17,883 points were evaluated per analysis. CONCLUSIONS We successfully performed GK dose painting with the Lightning optimizer, verifying dose delivery within clinically acceptable tolerances. Future work is needed to determine optimal dose levels for use in clinical practice.

A comparison of three-film analysis software for stereotactic radiotherapy patient-specific quality assurance.

The aim of this study was to investigate the suitability of three radiochromic film analysis software for stereotactic radiotherapy patient-specific quality assurance (PSQA): FilmQA Pro v5.0, SNC Patient v6.2, and eFilmQA v5.0. Film calibration was conducted for each software followed by three sets of measurements. The first set assessed calibration accuracy by comparing measured and delivered doses at increments different from those used for calibration. The second set used each software to conduct PSQA through gamma analysis on 10 stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT) patients. The third set utilized SNC Patient and eFilmQA to carry out gamma analysis on a collection of four digital test images, eliminating delivery and scanning uncertainties from impacting the analysis. Key supporting features within each software for conducting gamma analysis were identified. Overall, FilmQA Pro and eFilmQA were deemed comparable and favoured over SNC Patient due to the presence of key features such as triple-channel dosimetry, auto-optimization, and dose scaling. FilmQA Pro has a substantial user base and established reputation. eFilmQA, having been introduced more recently, serves as a viable alternative to FilmQA Pro, having been further refined for stereotactic radiotherapy PSQA. This study investigated the suitability of three film analysis software (FilmQA Pro, eFilmQA, and SNC Patient) for stereotactic radiotherapy PSQA. Results from the investigation indicated that both FilmQA Pro and eFilmQA are comparably suitable and are preferred over SNC Patient. Both FilmQA Pro and eFilmQA are recommended for radiotherapy clinics.

FLASH radiotherapy and the associated dosimetric challenges

At Lund University and Skåne University Hospital in Lund, Sweden, we have, as the first clinic, modified a clinical Elekta Precise linear accelerator for convertible delivery of ultra-high dose rate (FLASH) irradiation. Whereas recently published reviews highlighted the need for standardised protocols for ultra-high dose rate beam dosimetry to be able to determine the true potential of FLASH irradiation, several dosimetry studies as well as in-vitro and in-vivo experiments have been carried out at our unit. Dosimetric procedures for verification of accurate dose delivery of FLASH irradiation to cell cultures, zebrafish embryos and small animals have been established using radiochromic films and thermo-luminescent dosimeters. Also, recently the first experience of electron FLASH radiotherapy (FLASH-RT) in canine patients in our clinical setting was published. Our research facilities also include a laboratory for 3D polymer gel manufacturing. Recently, we started investigating the feasibility of a NIPAM polymer gel dosimeter for ultra-high dose rate dosimetry. Furthermore, in the bunker of the modified Elekta linear accelerator, a Surface Guided Radiotherapy (SGRT) system is accessible. The Catalyst™ system (C-Rad Positioning, Uppsala, Sweden) provides optical surface imaging for patient setup, real-time motion monitoring and breathing adapted treatment. Aiming at treating patients using ultra-high dose rates, a real-time validation of the alignment between the beam and the target is crucial as the dose is delivered in a fraction of a second. Our research group has during the last decade investigated and developed SGRT workflows which improved patient setup and breathing adapted treatment for several cancer patient groups. Recently, we also started investigating the feasibility of a real-time motion monitoring system for surface guided FLASH-RT. Both FLASH related studies; 3D polymer gel dosimetry and surface guided FLASH-RT are to our knowledge the first of their kind. Following an introduction to the field of FLASH and the associated dosimetric challenges, we here aim to present the two ongoing studies including some preliminary results.

Novel Monthly Quality Assurance Regimen and 5-Year Analysis Using a Proton Metrology System

PurposeTo develop a novel, monthly quality assurance (QA) regimen for a proton therapy system that uses 2 custom phantoms, each housing a commercial scintillator detector and a charge-coupled device camera. The novel metrology system assessed QA trends at a pediatric proton therapy center from 2018 to 2022. Materials and MethodsThe measurement system was designed to accommodate horizontal and vertical positioning of the commercial device and to enable gantry and couch isocentricity measurements (using a star shot procedure), proton spot profile verification, and imaging and radiation congruence tests to be performed simultaneously in the dual-phantom setup. Gantry angles and proton beam energies were varied and alternated each month, using gantry angles of 0°, 30°, 60°, 90°, 120°, 150°, and 180° and discrete beam energies of 69.4, 84.5, 100, 139.1, 180.4, 200.4, and 221.3 MeV after radiographic verification. A total of 1176 individual monthly QA measurements of gantry and couch isocentricity, spot size, and congruence were analyzed. ResultsGantry and couch star shot measurements showed beam isocentricities of 0.3 ± 0.2 mm and 0.2 ± 0.2 mm, respectively, which were within the threshold of 1.0 mm. Spot sizes for each discrete energy were within the threshold of ± 10% of the baseline values for all 3 proton rooms. The imaging and radiation coincidence test results for the 1176 individual monthly QA measurements were 0.5 mm for the 50th percentile and 1.2 mm (the clinical threshold) for the 97.6th percentile. ConclusionsIntegrating a commercial device with custom phantoms improved the quality of proton system checks compared with previous methods using radiochromic films, loose ball bearings, and foam. The scheme of alternating beam angles with discrete energies in the monthly QA-enabled, clinically meaningful verification of beam energy and gantry angle combinations while the machine performance and accuracy were being checked.

Dose profile evaluation for small fields of a LINAC 6 MV beam using a solid water phantom

Radiotherapy is basically used in oncology and consists of the use of ionizing radiation to stop neoplastic cells from reproducing or to kill cells. Radiotherapy is one of the three main modalities of treatment for malignant diseases such as cancer, the other two are chemotherapy and radiosurgery. Unlike other medical specialties that rely primarily on the clinical knowledge and experience of specialist physicians, radiotherapy relies heavily on modern technology and the collaborative effort of several professionals whose coordinated team approach greatly influences the outcome of treatment. Linear accelerators with jaw or multileaf (MLC) field colimators are used to irradiate patients undergoing therapy and use fields with dimensions ranging from 4×4 to 40×40 cm². However, looking for the delivery of prescribed doses increasingly conforming to the target volume, small field beam openings are being used in advanced photon beam radiotherapy. In this work, the absorbed dose distribution of an X-ray beam was recorded using a solid water phantom. This phantom was irradiated using small fields with 1×1, 2×2, 3×3 and 5×5 cm². The 6 MV X-ray beam was generated on a Synergy Platform model linear accelerator from the manufacturer Elekta, and sheets of radiochromic film were used to record the dose profiles within the phantom. The solid water phantom loaded with radiochromic film was positioned 1.0 m away from the focus of the X-ray beam. The longitudinal profile of absorbed dose obtained showed the maximum dose value at 1.26 cm (peak) depth inside the phantom. The smaller field size (1×1) generated a smaller maximum absorbed dose (peak). Axial dose profiles were recorded at 1 cm depth and showed a plateau in the central region of the field. The mean absorbed dose at the plateau measured at 1 cm depth ranged from 98% to 90% of the maximum dose for the 5x5 and 1x1 cm² fields, respectively. The experiments performed showed a variations in the absorbed dose values due to the size of the fields. These variations occurred as in the amplitude of peak value in the depth profile as in the axial plane of distribution.

Proof-of-Principle of Absolute Dosimetry Using an Absorbed Dose Portable Calorimeter with Laser-Driven Proton Beams

Charged particle beams driven to ultra-high dose rates (UHDRs) have been shown to offer potential benefits for future clinical applications, particularly in the reduction of normal-tissue toxicity. Studies of the so-called FLASH effect have shown promise, generating huge interest in high dose rate radiation studies. With laser-driven proton beams, where the duration of the proton burst delivered to a sample can be as short as hundreds of picoseconds, the instantaneous dose rates are several orders of magnitude higher than those used for conventional radiotherapy. The dosimetry of these beam modalities is not trivial, with conventional active detectors, such as ionisation chambers, experiencing saturation effects making them unusable at the extremely high dose rates. Calorimeters, measuring the radiation-induced temperature rise in an absorber, offer an ideal candidate for the dosimetry of UHDR beams. However, their application in the measurement of laser-driven UHDR beams has so far not been trialled, and their effective suitability to work with the quasi-instantaneous and inhomogeneous dose deposition patterns and the harsh environment of a laser-plasma experiment has not been tested. The measurement of the absorbed dose of laser-driven proton beams was conducted in a first-of-its-kind investigation, employing the VULCAN-PW laser system of the Central Laser Facility (CLF) at the Rutherford Appleton Laboratory (RAL), using a small-body portable graphite calorimeter (SPGC) developed at the National Physical Laboratory (NPL) and radiochromic films. A small number of shots were recorded, with the corresponding absorbed dose measurements resulting from the induced temperature rise. The effect of the electromagnetic pulse (EMP) generated during laser–target interaction was assessed on the system, showing no significant effects on the derived signal-to-noise ratio. These proof-of-principle tests highlight the ability of calorimetry techniques to measure the absorbed dose for laser-driven proton beams.

Particular issues to be considered in small field dosimetry for TrueBeam STx commissioning

This study aims to report the relevant issues concerning small fields in the commissioning of a TrueBeam STx for photon energies of 6MV, 10MV, 6FFF, and 10FFF. Percent depth doses, profiles, and field output factors were measured according to the beam model configuration of the treatment planning system. Multiple detectors were used based on the IAEA TRS-483 protocol as well as EBT3 radiochromic film. Analytical Anisotropic and Acuros XB algorithms, were configured and validated through basic dosimetry comparisons and end-to-end clinical tests.

A study on quality control check of dose distribution in blood bags irradiated by 137Cs source blood irradiator by using EBT3 radiochromic film dosimetry

In this study, the dose homogeneity in the blood bags delivered by a137Cs blood irradiator is investigated by using EBT3 radiochromic film dosimetry. The dose delivered to blood bags is an important factor for protection to TA-GVHD patients during transfusion in medicine. To do this, the dose results experimentally determined by EBT3 films were then compared with those of a MCNPX simulation in which the irradiation canister containing the blood bags was irradiated with a MSD Gammacell 3000 Elan. In the simulation, two different irradiation situations were modeled; one is the canister full with blood bags and the other is half-full of blood bags. The simulation dose results showed that when the canister was filled fully with blood bags, a dose of 24.4 ± 0.1 Gy was estimated in the canister center line. When the canister was half-full with the bags, a 28.8 ± 0.1 Gy dose was estimated in the canister center line. Whereas the dose of 31.3 ± 0.6 Gy dose was experimentally determined in the canister center line when the canister was filled (3 blood bags) half full. As a result, the dose homogeneity in the irradiated blood bags can easily checked by means of a two-dimensional EBT3 film dosimetry technique. Hence, this study showed that EBT3 film dosimetry is still powerful method for quality control check of dose homogeneity of any blood bags before it was used in patient.

New opto-electro-mechanical sensor for two-dimensions dosimetry based on radiochromic films

This work presents the validation of a new Opto‒Electro-Mechanical (MOEM) system consisting of a matrix of photodetectors for two-dimensional dosimetry evaluation with radiochromic films. The proposed system is based on a 5 × 10 matrix of photodetectors controlled by both in-house electronic circuit and graphical user interface, which enables optical measurements directly. We present the first tests performed in an X-ray machine and 137Cs source with that array by using Gafchromic EBT3 films. We obtained similar results than with a standard method (e.g. flat-bed scanner). Results were compared with Monte Carlo simulations and very good agreement was found. Results show the feasibility of using this system for dose evaluations. To the best of our knowledge, this is the first MOEM sensor for radiotherapy. Further developments are ongoing to create an advanced 16 × 16 LDRs system covering 1.6 cm × 1.6 cm with a 1 mm of spatial resolution. We point to develop a portable dosimetry tool delivering dose maps in real time to improve the clinical application of radiochromic films.

Extracting the gradient component of the gamma index using the Lie derivative method

Objective. The gamma index (γ) has been extensively investigated in the medical physics and applied in clinical practice. However, γ has a significant limitation when used to evaluate the dose-gradient region, leading to inconveniences, particularly in stereotactic radiotherapy (SRT). This study proposes a novel evaluation method combined with γ to extract clinically problematic dose-gradient regions caused by irradiation including certain errors. Approach. A flow-vector field in the dose distribution is obtained when the dose is considered a scalar potential. Using the Lie derivative from differential geometry, we defined L, S, and U to evaluate the intensity, vorticity, and flow amount of deviation between two dose distributions, respectively. These metrics multiplied by γ (γL, γS, γU), along with the threshold value σ, were verified in the ideal SRT case and in a clinical case of irradiation near the brainstem region using radiochromic films. Moreover, Moran’s gradient index (MGI), Bakai’s χ factor, and the structural similarity index (SSIM) were investigated for comparisons. Main results. A high L-metric value mainly extracted high-dose-gradient induced deviations, which was supported by high S and U metrics observed as a robust deviation and an influence of the dose-gradient, respectively. The S-metric also denotes the measured similarity between the compared dose distributions. In the γ distribution, γL sensitively detected the dose-gradient region in the film measurement, despite the presence of noise. The threshold σ successfully extracted the gradient-error region where γ > 1 analysis underestimated, and σ = 0.1 (plan) and σ = 0.001 (film measurement) were obtained according to the compared resolutions. However, the MGI, χ, and SSIM failed to detect the clinically interested region. Significance. Although further studies are required to clarify the error details, this study demonstrated that the Lie derivative method provided a novel perspective for the identifying gradient-induced error regions and enabled enhanced and clinically significant evaluations of γ.

Optically stimulated luminescence system as an alternative for radiochromic film for 2D reference dosimetry in UHDR electron beams

Radiotherapy is part of the treatment of over 50% of cancer patients. Its efficacy is limited by the radiotoxicity to the healthy tissue. FLASH-RT is based on the biological effect that ultra-high dose rates (UHDR) and very short treatment times strongly reduce normal tissue toxicity, while preserving the anti-tumoral effect. Despite many positive preclinical results, the translation of FLASH-RT to the clinic is hampered by the lack of accurate dosimetry for UHDR beams. To date radiochromic film is commonly used for dose assessment but has the drawback of lengthy and cumbersome read out procedures. In this work, we investigate the equivalence of a 2D OSL system to radiochromic film dosimetry in terms of dose rate independency. The comparison of both systems was done using the ElectronFlash linac. We investigated the dose rate dependence by variation of the (1) modality, (2) pulse repetition frequency, (3) pulse length and (4) source to surface distance. Additionally, we compared the 2D characteristics by field size measurements. The OSL calibration showed transferable between conventional and UHDR modality. Both systems are equally independent of average dose rate, pulse length and instantaneous dose rate. The OSL system showed equivalent in field size determination within 3 sigma. We show the promising nature of the 2D OSL system to serve as alternative for radiochromic film in UHDR electron beams. However, more in depth characterization is needed to assess its full potential.

Investigation of boosted proton energies through proton radiography of target normal sheath acceleration fields in the multi-ps regime

Multi-kilojoule, multi-picosecond short-pulse lasers, such as the National Ignition Facility-Advanced Radiographic Capability laser and the OMEGA-Extended Performance laser, which have been constructed over the last two decades, enable exciting opportunities to produce high-brightness, high-energy laser-driven proton sources for applications in high-energy-density science like proton fast ignition for inertial fusion energy, particle radiography, and materials science studies. Results on these platforms have demonstrated enhanced accelerated proton energies and electron temperatures when compared to established scaling laws. Recent work has developed a new scaling for proton TNSA in the multi-ps regime. However, this new physics in the multi-ps regime motivates the need to understand the origin of the enhancement in proton energies. Toward this goal, this work presents the first measurements of the TNSA accelerating sheath field in the multi-ps regime for pulse durations of 0.6, 5, and 10 ps. This measurement was achieved by using a separate TNSA proton source to radiograph the spatiotemporal profile of the accelerating sheath that is responsible for proton acceleration. The use of stacked radiochromic film detectors allows for a discrete time profile of the radiographs, thus enabling the measurement of the temporal and spatial evolution of the accelerating field. In performing this measurement, we extract quantities such as the sheath strength as a function of time and pulse duration, which shows that longer pulse durations sustain a stronger electric field for a longer duration when compared to sub-ps laser pulses, which may enable the observed boosted proton energies and proton conversion efficiencies.

Initial Experience with the Commercial Electron FLASH Research Extension

The purpose of this study was to introduce a new commercial electron FLASH system that has the potential to become widely available for FLASH researchers globally. In this study, we first present the initial acceptance and commissioning tests for the FLASH system, and second, we highlight preliminary FLASH effect results from our cell studies. A linear accelerator was converted into a commercial research platform with the FLASH Research Extension, enabling the generation of a powerful 16 MeV electron FLASH beam. The dosimetric and stability tests were conducted using various dosimeters (i.e., radiochromic film, optically stimulated luminescent dosimeters (OSLDs), and a plane-parallel ionization chamber). To evaluate the FLASH effect, normal and cancer cell lines were FLASH irradiated using different pulse repetition frequencies (PRF) of 18 pulses/s and 180 pulses/s. The electron FLASH mode was able to generate over 1 Gy per pulse at the isocenter and a dose rate of up to 690 Gy/s near the accessory mount of the Linac gantry head. The charge collected by the plane-parallel ionization chamber at the highest PRF (i.e., 180 pulses/s) showed a linear relationship with the delivered number of pulses (i.e., 1 to 99 pulses) with a coefficient of determination (R2) of 0.9996. The absorbed dose measured using radiochromic film and OSLDs agreed within 3%, on average, and followed an inverse square law as the source-to-axis distance (SAD) varied for which the R2 values were 0.9972 and 0.9955 for radiochromic film and OSLDs, respectively. The profile of the FLASH beam was symmetrical but was not as flat as the conventional 16 MeV electron beam due to the use of a thinner custom scattering foil to reduce the degradation of the ultra-high dose rate. The depth-dose curve beyond the build-up region for the FLASH beam was similar to the conventional 16 MeV electron beam for which the range at 50% the maximum dose (R50) agreed within 0.5 mm. The FLASH beam output remained consistent over a 4-month period with a variation of 2.5%, on average. The FLASH sparing effect was observed in vitro for healthy human pancreatic cells. Furthermore, we observed that the highest PRF beam (180 pulses/s) was more effective at destroying pancreatic cancerous cells while minimizing damage to healthy cells compared to the lowest PRF beam (18 pulses/s). The novel commercial FLASH Research Extension system was dosimetrically characterized for pre-clinical FLASH research, and preliminary in vitro results demonstrated the FLASH effect. Given the prevalence of linear accelerators, this new commercial system has the potential to greatly increase the access to FLASH research.

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.

Evaluation of Treatment Interruptions and Recovery during Biology-Guided Radiotherapy Delivery

A Biology-guided Radiotherapy (BgRT) based device is designed to use Positron Emission Tomography (PET) signals to achieve tracked dose delivery. The goal of this study is to investigate the dose delivery accuracy in case of interruption during BgRT treatment, and resumption in a separate treatment session for a multi-target delivery, as the PET activity continues to decay. A custom-built large anthropomorphic phantom (LAP) including a 26 mm spherical target with 3D independent motion and two 22 mm spherical targets with 1D sinusoidal motion embedded in water was used. All three targets were filled with FGD in an 8:1 target to background uptake ratio (41.52 kBq/ml in target and 5.19 kBq/ml in background). During BgRT delivery, the treatment was intentionally paused during delivery to the second target and the current treatment session was ended to generate a partial fraction. Then the partial fraction was continued in a new session, where the CT scan localization and PET pre-scan were repeated using the existing PET activity present in the phantom. The newly acquired PET pre-scan, was then used to determine if sufficient PET counts were present to resume treatment delivery. The interruption and recovery algorithm is designed to calculate the fluence that needs to be delivered to the remaining targets as well as the residual fluence to be given to the targets that have already received partial dose prior to the interruption. Once the new fluence is recomputed, the treatment is resumed. The delivered doses were captured using radiochromic film (EBT-XD) inserted in the target as well as post-treatment dose calculations based on the delivered beamlet sequence to evaluate the results in terms of dosimetric coverage and margin loss. The margin loss is calculated as the maximum difference between the distance from the Clinical Target Volume (CTV) contour to the 97% isodose contour in the treatment plan and the on the film. The dosimetric coverage is defined as the percentage of voxels within the CTV that lies within 97% and 130% of the prescribed dose. As shown in the table below, a margin loss of less than 3 mm for all targets and 100% CTV coverage was achieved. After treatment interruptions, the PET safety evaluation based on the PET pre-scan helped to determine whether the treatment could be continued on the same day using the same injected PET activity (an NTS value ≧ 2 and AC value ≧ 5 kBq/ml). This study demonstrated that the BgRT system is able to deliver the prescribed dose to all targets with independent motion, even when an interruption and resumption occurs during treatment. In case such an interruption if the remaining PET activity satisfies the BgRT safety evaluation, the treatment can continue to deliver the remainder of the BgRT doses.

Combination Immunotherapy with Partial Versus Whole Tumor Radiotherapy in a Preclinical Melanoma Tumor Model

Partial tumor radiotherapy (PTRT) with immune checkpoint inhibition (ICI) is currently the subject of clinical trials and may be used clinically for large volume tumors when the full gross tumor volume (GTV) cannot be safely treated with full dose. PTRT delivers RT to a portion of the GTV, underdosing or not treating the remainder of the GTV, hypothesizing that ICI-mediated tumor infiltrating lymphocyte (TIL) infiltration will produce adequate disease control in un- or under-irradiated GTV. Standard treatment is whole tumor radiotherapy (WTRT), and potential differences in disease control between PTRT and WTRT with ICI have not been robustly assessed. We hypothesized that PTRT with ICI and WTRT with ICI will demonstrate similar tumor regression, and both RT regimens will demonstrate superior tumor regression as compared to ICI alone. B78 melanoma flank tumors were generated in C57B/L6 mice, with randomization at tumor size of 1 cm to experimental cohorts of PTRT + ICI and WTRT + ICI and control groups of no RT ± ICI. Custom lead shields were fabricated to deliver 16 Gy single fraction PTRT (50% tumor treatment) and WTRT, with dosimetry confirmation via radiochromic film. ICI was delivered through I.P. injection of murine anti-CTLA4 and anti-PD-L1 at days 0, 3, and 6 post-RT. Tumor regression was assessed via differences in tumor volume at ten days post completion of ICI, and mean cohort tumor volumes were compared with ANOVA (α <0.05). Variances between individual cohorts were assessed via t-test (α <0.05). Treatment cohorts demonstrated significant variance in tumor volume at ten days following treatment completion (p = 0.007, Table 1). WTRT + ICI demonstrated superior tumor regression when compared to PTRT + ICI (p = 0.006), ICI alone (p = 0.002), and control cohorts (p = 0.013). There was no difference in tumor regression between PTRT + ICI and ICI alone (p = 0.709), and PTRT + ICI did not achieve significant regression when compared to control (p = 0.083). Tumor regression did not differ between cohorts receiving no RT ± ICI (p = 0.103). Our results in this ICI resistant melanoma model demonstrated superior tumor regression with WTRT + ICI as compared to PTRT + ICI and ICI alone, suggesting that even with concurrent ICI, PTRT may not be sufficient treatment for melanoma. PTRT + ICI tumor regression was similar to ICI alone, suggesting that PTRT may not overcome immune resistance in the unirradiated tumor volume. Further investigation of optimal RT regimens to potentiate ICI response is warranted and correlative studies examining spatial immunomodulation in unirradiated and irradiated portions of the same tumor are underway.

Treatment Plan Creation and Delivery with and without BgRT for Static and Motion Trajectories

In this work we try to validate the motion tracking capabilities of BgRT for periodic and step motion trajectories. SBRT plans that matches the corresponding BgRT plans are created and delivered to the same phantom with and without motion and results are evaluated. Using BgRT based SBRT plans eliminates any user bias and creates SBRT plans that would represent treatment delivery scenarios that could have happened if the PET guided BgRT was not present for that treatment. To validate SBRT plans that matches the BgRT plans, we used three different types of motion patterns (1) static, (2) lung tumor motion and (3) one-centimeter step-shift. The lung tumor motion (∼25 mm in IEC-Y, ∼7 mm in IEC-X and ∼ 10 mm in IEC-Z) was used as it represents a continuous motion of the target for the entire length of the study while the step-shift case corresponds to the patient or tumor shifting between the localization CT and the start of treatment. First, a 10 Gy per fraction BgRT plan was created for each of the three experiments based on the corresponding PET image. Then, the BgRT plans were delivered to the corresponding targets with and without motion and results are evaluated. To perform a comparative study that assess the performance of BgRT and traditional SBRT (planning and delivery methods), the exact same plan fluence of BgRT plan for each experiment was used to create the corresponding SBRT plans. The newly created SBRT plans were delivered to the corresponding phantom experiments and were compared against BgRT delivery in terms of dose coverage and target margin loss using radiochromic film that moves with the target. The margin loss was calculated as the difference between the distance from the CTV contour to the 97% isodose contour in the treatment plan and the CTV contour to the 97% isodose contour on the film. Dosimetric coverage was on the other hand calculated as the percentage of the voxels within the CTV that lies within 97% and 130% of the prescribed dose. The results showed that the margin loss for BgRT is less than 3 mm, while for the SBRT plans were more than 3 mm when target motion is present. The dosimetric coverage for BgRT was 100% for all three cases, however less than 100% for the SBRT cases with motion. Table showing margin loss for the various experiments for a prescription dose of 10 Gy. The results shows that BgRT is capable of tracking the tumor motion and delivering the prescribed dose to the moving target.

Characterization of Biology-Guided Radiotherapy Accuracy as a Function of PET Tracer Uptake

To characterize the tracking capability and dosimetric accuracy of biology-guided radiotherapy (BgRT) under clinically relevant PET tracer uptake scenarios relative to the background. A custom-made anthropomorphic phantom filled with a liquid 18F-FDG solution including two embedded fillable 22 mm diameter spherical structures mimicking GTV (= CTV) and OAR was coupled to motion stages to create an independent 3D respiratory motion with 22 mm maximum range for target and a 5 mm 1D sinusoidal motion in the OAR. The biology-tracking zone (BTZ) was generated by adding 5 mm margin to the motion extent. The three BgRT scenarios studied were representative of tumors with good (8:1), borderline (4:1) and undesired (2:1) PET biodistributions compared to background. The clinical safety limit of BgRT uses Activity Concentration within the BTZ (AC ≥ 5 kBq/ml) and Normalized Target Signal as a contrast metric (NTS ≧ 2.7 for planning and ≧ 2 for delivery). The BgRT deliveries were repeated 3 times with radiochromic film and integrated ion chamber capturing the target and OAR doses. Tracked dosimetry was assessed using a margin-loss calculation defined as the maximum linear difference in distance between the planned and delivered 97% prescription iso-dose lines. The imaging-only PET images used to create BgRT plans had an AC of 7.0, 5.3, and 1.6 kBq/ml with an NTS of 6.8, 5.3, and 1.8 for 8:1, 4:1, and 2:1 concentrations, respectively. Qualitatively, the target was not visible on the planning PET images 2:1 loading scenario. At delivery, the mean pre-scan activity concentrations were 6.8, 4.7, and 3.7 kBq/ml with corresponding mean NTS of 3.7, 2.6, 1.5 for 8:1, 4:1 and 2:1 deliveries. The pre-scan values of AC or NTS did not satisfy the clinical system safety limits for 4:1 and 2:1 ratio experiments, but the engineering software allowed for the delivery to capture the resulting doses. The deliveries showed a prescription dose coverage to the CTV of 100% for the 8:1 and 4:1 cases, but 88% for the 2:1 case. When compared to the planned dose values, the delivered minimum doses were -7.6%, -8.6% and -10.9%, whereas the maximum dose differences in CTV were 1.2%, 0% and -4.8% of the planned dose distributions of the 8:1, 4:1 and 2:1 cases, respectively. Calculated margin losses were -2.3, -3.8, and -5.5 mm, for the 8:1, 4:1, and 2:1 cases, respectively. The maximum OAR doses were less than the maximum doses predicted on the bounded DVH curves for all scenarios. With sufficient tracer uptake in the target, BgRT can deliver tracked dosimetry for targets with a large respiratory motion profile. Both the good BgRT candidate and borderline cases produced clinically acceptable delivered doses, even though the borderline case was flagged by the clinical system safety checks. As expected, the delivered BgRT dose distributions were suboptimal with reduced tumor over background PET contrast.

Reference Materials of Absorbed Dose: Expanding Dynamic Range and Improving Measurement Accuracy

Establishment and control of metrological characteristics of measurements of absorbed ionizing radiation doses in the range of 0.01 and 200 kGy by reference materials is an urgent task due to their wide application in various industries. The most convenient means of metrological support for transferring a unit of absorbed dose rate of intense photon, electron, and beta radiation to measuring instruments in radiation technologies are reference materials with established metrological traceability to the International System of Units (SI). In the present study, a method for expanding the dynamic range of measuring the absorbed dose of high-intensity ionizing radiation by radiochromic film dosimetry systems was considered and tested. The accuracy (uncertainty) of dose measurements was estimated depending on the initial optical density of the radiation-sensitive layer of the radiochromic composition. The possibility of expanding the dose characteristics and improving the metrological characteristics of the existing reference materials of absorbed dose (in water) for use as secondary standards (Measures) of the absorbed dose of ionizing radiation reproducing and (or) storing one or more points of the selected measurement scale of the absorbed dose with increased accuracy (uncertainty) of the measured values of the absorbed dose (in water) in an extended dynamic range was shown.