Preclinical Models of Anal Cancer Combined-Modality Therapy.

INTRODUCTION: There have been no significant changes in anal cancer treatment options in 4 decades. In this study, we highlight two preclinical models designed to assess anal cancer treatments. MATERIALS AND METHODS: Transgenic K14E6/E7 mice were treated with 7, 12-dimethylbenz(a)anthracene until anal tumors developed. Mice were treated with localized radiation in addition to chemotherapy (combined-modality therapy [CMT]) and compared to no treatment control (NTC). K14E6/E7 mouse anal spheroids with and without Pik3ca mutations were isolated and treated with vehicle, LY3023414 (LY3) (a drug previously shown to be effective in cancer prevention), CMT, or CMT + LY3. RESULTS: In the in vivo model, there was a significant increase in survival in the CMT group compared to the NTC group (P = 0.0392). In the ex vivo model, there was a significant decrease in the mean diameter of CMT and CMT + LY3-treated spheroids compared to vehicle (P ≤ 0.0001). For LY3 alone compared to vehicle, there was a statistically significant decrease in spheroid size in the K14E6/E7 group without mutation (P = 0.0004). CONCLUSIONS: We have provided proof of concept for two preclinical anal cancer treatment models that allow for the future testing of novel therapies for anal cancer.

IMRT QA result prediction via MLC transmission decomposition.

BACKGROUND: Quality assurance measurement of IMRT/VMAT treatment plans is resource intensive, and other more efficient methods to achieve the same confidence are desirable. PURPOSE: We aimed to analyze treatment plans in the context of the treatment planning systems that created them, in order to predict which ones will fail a standard quality assurance measurement. To do so, we sought to create a tool external to the treatment planning system that could analyze a set of MLC positions and provide information that could be used to calculate various evaluation metrics. METHODS: The tool was created in Python to read in DICOM plan files and determine the beam fluence fraction incident on each of seven different zones, each classified based on the RayStation MLC model. The fractions, termed grid point fractions, were validated by analyzing simple test plans. The average grid point fractions, over all control points for 46 plans were then computed. These values were then compared with gamma analysis pass percentages and median dose differences to determine if any significant correlations existed. RESULTS: Significant correlation was found between the grid point fraction metrics and median dose differences, but not with gamma analysis pass percentages. Correlations were positive or negative, suggesting differing model parameter value sensitivities, as well as potential insight into the treatment planning system dose model. CONCLUSIONS: By decomposing MLC control points into different transmission zones, it is possible to create a metric that predicts whether the analyzed plan will pass a quality assurance measurement from a dose calculation accuracy standpoint. The tool and metrics developed in this work have potential applications in comparing clinical beam models or identifying their weak points. Implementing the tool within a treatment planning system would also provide more potential plan optimization parameters.

AAPM medical physics practice guideline 13.a: HDR brachytherapy, part A.

The American Association of Physicists in Medicine (AAPM) is a nonprofit professional society whose primary purposes are to advance the science, education, and professional practice of medical physics. The AAPM has more than 8000 members and is the principal organization of medical physicists in the United States. The AAPM will periodically define new practice guidelines for medical physics practice to help advance the science of medical physics and to improve the quality of service to patients throughout the United States. Existing medical physics practice guidelines (MPPGs) will be reviewed for the purpose of revision or renewal, as appropriate, on their fifth anniversary or sooner. Each medical physics practice guideline represents a policy statement by the AAPM, has undergone a thorough consensus process in which it has been subjected to extensive review, and requires the approval of the Professional Council. The medical physics practice guidelines recognize that the safe and effective use of diagnostic and therapeutic radiology requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guidelines and technical standards by those entities not providing these services is not authorized. The following terms are used in the AAPM practice guidelines: (1) Must and must not: Used to indicate that adherence to the recommendation is considered necessary to conform to this practice guideline. (2) Should and should not: Used to indicate a prudent practice to which exceptions may occasionally be made in appropriate circumstances. Approved by AAPM's Executive Committee April 28, 2022.

Characterization of imaging performance of a novel helical kVCT for use in image-guided and adaptive radiotherapy.

ClearRT helical kVCT imaging for the Radixact helical tomotherapy system recently received FDA approval and is available for clinical use. The system is intended to enhance image fidelity in radiation therapy treatment planning and delivery compared to the prior MV-based onboard imaging approach. The purpose of this work was to characterize the imaging performance of this system and compare this performance with that of clinical systems used in image-guided and/or adaptive radiotherapy (ART) or computed tomography (CT) simulation, including Radixact MVCT, TomoTherapy MVCT, Varian TrueBeam kV OBI CBCT, and the Siemens SOMATOM Definition Edge kVCT. A CT image quality phantom was scanned across clinically relevant acquisition modes for each system to evaluate image quality metrics, including noise, uniformity, contrast, spatial resolution, and CT number linearity. Similar noise levels were observed for ClearRT and Siemens Edge, whereas noise for the other systems was ∼1.5-5 times higher. Uniformity was best for Siemens Edge, whereas most scans for ClearRT exhibited a slight "cupping" or "capping" artifact. The ClearRT and Siemens Edge performed best for contrast metrics, which included low-contrast visibility and contrast-to-noise ratio evaluations. Spatial resolution was best for TrueBeam and Siemens Edge, whereas the three kVCT systems exhibited similar CT number linearity. Overall, these results provide an initial indication that ClearRT image quality is adequate for image guidance in radiotherapy and sufficient for delineating anatomic structures, thus enabling its use for ART. ClearRT also showed significant improvement over MVCT, which was previously the only onboard imaging modality available on Radixact. Although the acquisition of these scans does come at the cost of additional patient dose, reported CTDI values indicate a similar or generally reduced machine output for ClearRT compared to the other systems while maintaining comparable or improved image quality overall.

Using 4D dose accumulation to calculate organ-at-risk dose deviations from motion-synchronized liver and lung tomotherapy treatments.

Tracking systems such as Radixact Synchrony change the planned delivery of radiation during treatment to follow the target. This is typically achieved without considering the location changes of organs at risk (OARs). The goal of this work was to develop a novel 4D dose accumulation framework to quantify OAR dose deviations due to the motion and tracked treatment. The framework obtains deformation information and the target motion pattern from a four-dimensional computed tomography dataset. The helical tomotherapy treatment plan is split into 10 plans and motion correction is applied separately to the jaw pattern and multi-leaf collimator (MLC) sinogram for each phase based on the location of the target in each phase. Deformable image registration (DIR) is calculated from each phase to the references phase using a commercial algorithm, and doses are accumulated according to the DIR. The effect of motion synchronization on OAR dose was analyzed for five lung and five liver subjects by comparing planned versus synchrony-accumulated dose. The motion was compensated by an average of 1.6 cm of jaw sway and by an average of 5.7% of leaf openings modified, indicating that most of the motion compensation was from jaw sway and not MLC changes. OAR dose deviations as large as 19 Gy were observed, and for all 10 cases, dose deviations greater than 7 Gy were observed. Target dose remained relatively constant (D95% within 3 Gy), confirming that motion-synchronization achieved the goal of maintaining target dose. Dose deviations provided by the framework can be leveraged during the treatment planning process by identifying cases where OAR doses may change significantly from their planned values with respect to the critical constraints. The framework is specific to synchronized helical tomotherapy treatments, but the OAR dose deviations apply to any real-time tracking technique that does not consider location changes of OARs.

Effects of variable-width jaw motion on beam characteristics for Radixact Synchrony®.

PURPOSE: Radixact Synchrony corrects for target motion during treatment by adjusting the jaw and MLC positions in real time. As the jaws move off axis, Synchrony attempts to adjust for a loss in output due to the un-flattened 6 MV beam by increasing the jaw aperture width. The purpose of this work was to assess the impact of the variable-width aperture on delivered dose using measurements and simulations. METHODS: Longitudinal beam profile measurements were acquired using an Edge diode with static gantry. Jaw-offset peak, width, and integral factors were calculated for profiles with the jaws in the extreme positions using both variable-width (Synchrony) and fixed-width apertures. Treatment plans with target motion and compensation were compared to planned doses to study the impact of the variable aperture on volumetric dose. RESULTS: The jaw offset peak factor (JOPF) for the Synchrony jaw settings were 0.964 and 0.983 for the 1.0- and 2.5-cm jaw settings, respectively. These values decreased to 0.925 and 0.982 for the fixed-width settings, indicating that the peak value of the profile would decrease by 7.5% compared to centered if the aperture width was held constant. The IMRT dose distributions reveal similar results, where gamma pass rates are above tolerance for the Synchrony jaw settings but fall significantly for the fixed-width 1-cm jaws. CONCLUSIONS: The variable-width behavior of Synchrony jaws provides a larger output correction for the 1-cm jaw setting. Without the variable-aperture correction, plans with the 1-cm jaw setting would underdose the target if the jaws spend a significant amount of time in the extreme positions. This work investigated the change in delivered dose with jaws in the extreme positions, therefore overall changes in dose due to offset jaws are expected to be less for composite treatment deliveries.

Technical note: On the impact of the kV imaging configuration on doses from planar images during motion-synchronized treatments on Radixact®.

Kilovoltage radiographs are acquired during motion-synchronized treatments on Radixact to localize the tumor during the treatment. Several previous publications have provided estimates of patient dose from these planar radiographs. However, a recent hardware update changed several aspects of the kV imaging system, including a new X-ray tube, an extended source-to-axis distance (SAD), and a larger field size. This is denoted the extended configuration. The purpose of this work was to assess the impact of the configuration change on patient dose from these procedures. Point doses in water were measured using the TG-61 protocol for tube potentials between 100 and 140 kVp for both the standard and extended configurations under the same water tank setup. Comparisons were made for equal mAs since the same protocols (kVp, mAs) will be used for both configurations. In comparison to the standard configuration, doses per mAs from the extended configuration were found to be ~66% less and falloff less steep due to the increased SAD. However, a larger volume of tissue is irradiated due to the larger field size. Beam quality for a given tube potential was the same as determined by half-value layer measurements. Both kV configurations are available from the vendor, therefore, the values in this work can be used to compare values previously published in the literature for the standard configuration or to intercompare doses from these two system configurations.

Evaluation of radixact motion synchrony for 3D respiratory motion: Modeling accuracy and dosimetric fidelity.

The Radixact® linear accelerator contains the motion Synchrony system, which tracks and compensates for intrafraction patient motion. For respiratory motion, the system models the motion of the target and synchronizes the delivery of radiation with this motion using the jaws and multi-leaf collimators (MLCs). It was the purpose of this work to determine the ability of the Synchrony system to track and compensate for different phantom motions using a delivery quality assurance (DQA) workflow. Thirteen helical plans were created on static datasets from liver, lung, and pancreas subjects. Dose distributions were measured using a Delta4® Phantom+ mounted on a Hexamotion® stage for the following three case scenarios for each plan: (a) no phantom motion and no Synchrony (M0S0), (b) phantom motion and no Synchrony (M1S0), and (c) phantom motion with Synchrony (M1S1). The LEDs were placed on the Phantom+ for the 13 patient cases and were placed on a separate one-dimensional surrogate stage for additional studies to investigate the effect of separate target and surrogate motion. The root-mean-square (RMS) error between the Synchrony-modeled positions and the programmed phantom positions was <1.5 mm for all Synchrony deliveries with the LEDs on the Phantom+. The tracking errors increased slightly when the LEDs were placed on the surrogate stage but were similar to tracking errors observed for other motion tracking systems such as CyberKnife Synchrony. One-dimensional profiles indicate the effects of motion interplay and dose blurring present in several of the M1S0 plans that are not present in the M1S1 plans. All 13 of the M1S1 measured doses had gamma pass rates (3%/2 mm/10%T) compared to the planned dose > 90%. Only two of the M1S0 measured doses had gamma pass rates > 90%. Motion Synchrony offers a potential alternative to the current, ITV-based motion management strategy for helical tomotherapy deliveries.

Experimental Evolution of Extreme Resistance to Ionizing Radiation in Escherichia coli after 50 Cycles of Selection.

In previous work (D. R. Harris et al., J Bacteriol 191:5240-5252, 2009, https://doi.org/10.1128/JB.00502-09; B. T. Byrne et al., Elife 3:e01322, 2014, https://doi.org/10.7554/eLife.01322), we demonstrated that Escherichia coli could acquire substantial levels of resistance to ionizing radiation (IR) via directed evolution. Major phenotypic contributions involved adaptation of organic systems for DNA repair. We have now undertaken an extended effort to generate E. coli populations that are as resistant to IR as Deinococcus radiodurans After an initial 50 cycles of selection using high-energy electron beam IR, four replicate populations exhibit major increases in IR resistance but have not yet reached IR resistance equivalent to D. radiodurans Regular deep sequencing reveals complex evolutionary patterns with abundant clonal interference. Prominent IR resistance mechanisms involve novel adaptations to DNA repair systems and alterations in RNA polymerase. Adaptation is highly specialized to resist IR exposure, since isolates from the evolved populations exhibit highly variable patterns of resistance to other forms of DNA damage. Sequenced isolates from the populations possess between 184 and 280 mutations. IR resistance in one isolate, IR9-50-1, is derived largely from four novel mutations affecting DNA and RNA metabolism: RecD A90E, RecN K429Q, and RpoB S72N/RpoC K1172I. Additional mechanisms of IR resistance are evident.IMPORTANCE Some bacterial species exhibit astonishing resistance to ionizing radiation, with Deinococcus radiodurans being the archetype. As natural IR sources rarely exceed mGy levels, the capacity of Deinococcus to survive 5,000 Gy has been attributed to desiccation resistance. To understand the molecular basis of true extreme IR resistance, we are using experimental evolution to generate strains of Escherichia coli with IR resistance levels comparable to Deinococcus Experimental evolution has previously generated moderate radioresistance for multiple bacterial species. However, these efforts could not take advantage of modern genomic sequencing technologies. In this report, we examine four replicate bacterial populations after 50 selection cycles. Genomic sequencing allows us to follow the genesis of mutations in populations throughout selection. Novel mutations affecting genes encoding DNA repair proteins and RNA polymerase enhance radioresistance. However, more contributors are apparent.

Calculating dose from a 2.5 MV imaging beam using a commercial treatment planning system.

Patient dose from 2.5 MV images on the TrueBeam linear accelerator is not easily quantified, primarily because this beam energy is not normally modeled by commercial treatment planning systems. In this work we present the feasibility of using the Eclipse® treatment planning system to model this beam. The Acuros XB and the AAA dose calculation algorithms were tested. Profiles, PDDs, and output factors were measured for the 2.5 MV unflattened imaging beam and used for beam modeling. The algorithms were subsequently verified using MPPG 5.a guidelines. Calculated doses with both algorithms agreed with the measurement data to within the following criteria recommended for conventional therapeutic MV beams: 2% local dose-difference in the high-dose region, 3% global difference in the low-dose region, 3 mm distance to agreement in the penumbra, and a gamma pass rate of >95% for 3%/3 mm criteria. Acuros was able to accurately calculate dose through cork and bone-equivalent heterogeneities. AAA was able to accurately calculate dose through the bone-equivalent heterogeneity but did not pass within the recommended criteria for the cork heterogeneity. For the 2.5 MV imaging beam, both the AAA and Acuros algorithms provide calculated doses that agree with measured results well within the 20% criteria for imaging beams recommended by AAPM TG-180.

An analysis of the ArcCHECK-MR diode array's performance for ViewRay quality assurance.

The ArcCHECK-MR diode array utilizes a correction system with a virtual inclinometer to correct the angular response dependencies of the diodes. However, this correction system cannot be applied to measurements on the ViewRay MR-IGRT system due to the virtual inclinometer's incompatibility with the ViewRay's multiple simultaneous beams. Additionally, the ArcCHECK's current correction factors were determined without magnetic field effects taken into account. In the course of performing ViewRay IMRT quality assurance with the ArcCHECK, measurements were observed to be consistently higher than the ViewRay TPS predictions. The goals of this study were to quantify the observed discrepancies and test whether applying the current factors improves the ArcCHECK's accuracy for measurements on the ViewRay. Gamma and frequency analysis were performed on 19 ViewRay patient plans. Ion chamber measurements were performed at a subset of diode locations using a PMMA phantom with the same dimensions as the ArcCHECK. A new method for applying directionally dependent factors utilizing beam information from the ViewRay TPS was developed in order to analyze the current ArcCHECK correction factors. To test the current factors, nine ViewRay plans were altered to be delivered with only a single simultaneous beam and were measured with the ArcCHECK. The current correction factors were applied using both the new and current methods. The new method was also used to apply corrections to the original 19 ViewRay plans. It was found the ArcCHECK systematically reports doses higher than those actually delivered by the ViewRay. Application of the current correction factors by either method did not consistently improve measurement accuracy. As dose deposition and diode response have both been shown to change under the influence of a magnetic field, it can be concluded the current ArcCHECK correction factors are invalid and/or inadequate to correct measurements on the ViewRay system.

Non-contact scintillator imaging dosimetry for total body irradiation in radiotherapy.

Objective.The goal of this work was to assess the potential use of non-contact scintillator imaging dosimetry for tracking delivery in total body irradiation (TBI).Approach. Studies were conducted to measure the time-gated light signals caused by radiation exposure to scintillators that were placed on tissue. The purpose was to assess efficacy in conditions common for TBI, such as the large source to surface distance (SSD) commonly used, the reduced dose rate, the inclusion of a plexiglass spoiler, angle of incidence and effects of peripheral patient support structures. Dose validation work was performed on phantoms that mimicked human tissue optical properties and body geometry. For this work, 1.5 cm diameter scintillating disks were developed and affixed to phantoms under various conditions. A time-gated camera synchronized to the linac pulses was used for imaging. Scintillation intensity was quantified in post processing and the values verified with simultaneous thermolumiescent dosimeter (TLD) measurements. Mean scintillation values in each region were compared to TLD measurements to produce dose response curves, and scatter effects from the spoiler and patient bed were quantified.Main results.The dose determined by scintillators placed in TBI conditions agreed with TLD dose determinations to within 2.7%, and did so repeatedly within 1.0% standard deviation variance. A linear fit between scintillator signal and TLD dose was achieved with anR2= 0.996 across several body sites. Scatter from the patient bed resulted in a maximum increase of 19% in dose.Significance.This work suggests that non-contact scintillator imaging dosimetry could be used to verify dose in real time to patients undergoing TBI at the prescribed long SSD and low dose rate. It also has shown that patient transport stretchers can significantly influence surface dose by increasing scatter.

Thermoluminescent dosimeters (TLD-100) for absorbed dose measurements in alpha-emitting radionuclides.

Early works that used thermoluminescent dosimeters (TLDs) to measure absorbed dose from alpha particles reported relatively high variation (10%) between TLDs, which is undesirable for modern dosimetry applications. This work outlines a method to increase precision for absorbed dose measured using TLDs with alpha-emitting radionuclides by applying an alpha-specific chip factor (CF) that individually characterizes the TLD sensitivity to alpha particles. Variation between TLDs was reduced from 21.8% to 6.7% for the standard TLD chips and 7.9% to 3.3% for the thin TLD chips. It has been demonstrated by this work that TLD-100 can be calibrated to precisely measure the absorbed dose to water from alpha-emitting radionuclides.

Patient-specific quality assurance of dynamically-collimated proton therapy treatment plans.

BACKGROUND: The dynamic collimation system (DCS) provides energy layer-specific collimation for pencil beam scanning (PBS) proton therapy using two pairs of orthogonal nickel trimmer blades. While excellent measurement-to-calculation agreement has been demonstrated for simple cube-shaped DCS-trimmed dose distributions, no comparison of measurement and dose calculation has been made for patient-specific treatment plans. PURPOSE: To validate a patient-specific quality assurance (PSQA) process for DCS-trimmed PBS treatment plans and evaluate the agreement between measured and calculated dose distributions. METHODS: Three intracranial patient cases were considered. Standard uncollimated PBS and DCS-collimated treatment plans were generated for each patient using the Astroid treatment planning system (TPS). Plans were recalculated in a water phantom and delivered at the Miami Cancer Institute (MCI) using an Ion Beam Applications (IBA) dedicated nozzle system and prototype DCS. Planar dose measurements were acquired at two depths within low-gradient regions of the target volume using an IBA MatriXX ion chamber array. RESULTS: Measured and calculated dose distributions were compared using 2D gamma analysis with 3%/3 mm criteria and low dose threshold of 10% of the maximum dose. Median gamma pass rates across all plans and measurement depths were 99.0% (PBS) and 98.3% (DCS), with a minimum gamma pass rate of 88.5% (PBS) and 91.2% (DCS). CONCLUSIONS: The PSQA process has been validated and experimentally verified for DCS-collimated PBS. Dosimetric agreement between the measured and calculated doses was demonstrated to be similar for DCS-collimated PBS to that achievable with noncollimated PBS.

Simultaneous photon counting and charge integrating for pulse pile-up correction in paralyzable photon counting detectors.

Objective.In photon counting detectors (PCDs), electric pulses induced by two or more x-ray photons can pile up and result in count losses when their temporal separation is less than the detector dead time. The correction of pulse pile-up-induced count loss is particularly difficult for paralyzable PCDs since a given value of recorded counts can correspond to two different values of true photon interactions. In contrast, charge (energy) integrating detectors work by integrating collected electric charge induced by x-rays over time and do not suffer from pile-up losses. This work introduces an inexpensive readout circuit element to the circuits of PCDs to simultaneously collect time-integrated charge to correct pile-up-induced count losses.Approach.Prototype electronics were constructed to collect time-integrated charges simultaneously with photon counts. A splitter was used to feed the electric signal in parallel to both a digital counter and a charge integrator. After recording PCD counts and integrating collected charge, a lookup table can be generated to map raw counts in the total- and high-energy bins and total charge to estimate pile-up-free true counts. Proof-of-concept imaging experiments were performed with a CdTe-based PCD array to test this method.Main results.The proposed electronics successfully recorded photon counts and time-integrated charge simultaneously, and whereas photon counts exhibited paralyzable pulse pile-up, time-integrated charge using the same electric signal as the counts measurement was linear with x-ray flux. With the proposed correction, paralyzable PCD counts became linear with input flux for both total- and high-energy bins. At high flux levels, uncorrected post-log measurements of PMMA objects severely overestimated radiological path lengths for both energy bins. After the proposed correction, the non-monotonic measurements again became linear with flux and accurately represented the true radiological path lengths. No impact on the spatial resolution was observed after the proposed correction in images of a line-pair test pattern.Significance.Time-integrated charge can be used to correct for pulse pile-up in paralyzable PCDs where analytical solutions may be difficult to use, and integrated charge can be collected simultaneously with counts using inexpensive electronics.

On the perturbation effect and LET dependence of beam quality correction factors in carbon ion beams.

BACKGROUND: In a recent study, we reported beam quality correction factors, fQ , in carbon ion beams using Monte Carlo (MC) methods for a cylindrical and a parallel-plate ionization chamber (IC). A non-negligible perturbation effect was observed; however, the magnitude of the perturbation correction due to the specific IC subcomponents was not included. Furthermore, the stopping power data presented in the International Commission on Radiation Units and Measurements (ICRU) report 73 were used, whereas the latest stopping power data have been reported in the ICRU report 90. PURPOSE: The aim of this study was to extend our previous work by computing fQ correction factors using the ICRU 90 stopping power data and by reporting IC-specific perturbation correction factors. Possible energy or linear energy transfer (LET) dependence of the fQ correction factor was investigated by simulating both pristine beams and spread-out Bragg peaks (SOBPs). METHODS: The TOol for PArticle Simulation (TOPAS)/GEANT4 MC code was used in this study. A 30 × 30 × 50 cm3 water phantom was simulated with a uniform 10 × 10 cm2 parallel beam incident on the surface. A Farmer-type cylindrical IC (Exradin A12) and two parallel-plate ICs (Exradin P11 and A11) were simulated in TOPAS using the manufacturer-provided geometrical drawings. The fQ correction factor was calculated in pristine carbon ion beams in the 150-450 MeV/u energy range at 2 cm depth and in the middle of the flat region of four SOBPs. The kQ correction factor was calculated by simulating the fQo correction factor in a 60 Co beam at 5 cm depth. The perturbation correction factors due to the presence of the individual IC subcomponents, such as the displacement effect in the air cavity, collecting electrode, chamber wall, and chamber stem, were calculated at 2 cm depth for monoenergetic beams only. Additionally, the mean dose-averaged and track-averaged LET was calculated at the depths at which the fQ was calculated. RESULTS: The ICRU 90 fQ correction factors were reported. The pdis correction factor was found to be significant for the cylindrical IC with magnitudes up to 1.70%. The individual perturbation corrections for the parallel-plate ICs were <1.0% except for the A11 pcel correction at the lowest energy. The fQ correction for the P11 IC exhibited an energy dependence of >1.00% and displayed differences up to 0.87% between pristine beams and SOBPs. Conversely, the fQ for A11 and A12 displayed a minimal energy dependence of <0.50%. The energy dependence was found to manifest in the LET dependence for the P11 IC. A statistically significant LET dependence was found only for the P11 IC in pristine beams only with a magnitude of <1.10%. CONCLUSIONS: The perturbation and kQ correction factor should be calculated for the specific IC to be used in carbon ion beam reference dosimetry as a function of beam quality.

Evaluating on-board kVCT- and MVCT-based dose calculation accuracy using a thorax phantom for helical tomotherapy treatments.

Purpose.To evaluate the impact of CT number calibration and imaging parameter selection on dose calculation accuracy relative to the CT planning process in thoracic treatments for on-board helical CT imaging systems used in helical tomotherapy.Methods and Materials.Direct CT number calibrations were performed with appropriate protocols for each imaging system using an electron density phantom. Large volume and SBRT treatment plans were simulated and optimized for planning CT scans of an anthropomorphic thorax phantom and transferred to registered kVCT and MVCT scans of the phantom as appropriate. Relevant DVH metrics and dose-difference maps were used to evaluate and compare dose calculation accuracy relative to the planning CT based on a variation in imaging parameters applied for the on-board systems.Results.For helical kVCT scans of the thorax phantom, median differences in DVH parameters for the large volume treatment plan were less than ±1% with dose to the target volume either over- or underestimated depending on the imaging parameters utilized for CT number calibration and thorax phantom acquisition. For the lung SBRT plan calculated on helical kVCT scans, median dose differences were up to -2.7% with a more noticeable dependence on parameter selection. For MVCT scans, median dose differences for the large volume plan were within +2% with dose to the target overestimated regardless of the imaging protocol.Conclusion.Accurate dose calculations (median errors of <±1%) using a thorax phantom simulating realistic patient geometry and scatter conditions can be achieved with images acquired with a helical kVCT system on a helical tomotherapy unit. This accuracy is considerably improved relative to that achieved with the MV-based approach. In a clinical setting, careful consideration should be made when selecting appropriate kVCT imaging parameters for this process as dose calculation accuracy was observed to vary with both parameter selection and treatment type.

PETRA: A pencil beam trimming algorithm for analytical proton therapy dose calculations with the dynamic collimation system.

BACKGROUND: The Dynamic Collimation System (DCS) has been shown to produce superior treatment plans to uncollimated pencil beam scanning (PBS) proton therapy using an in-house treatment planning system (TPS) designed for research. Clinical implementation of the DCS requires the development and benchmarking of a rigorous dose calculation algorithm that accounts for pencil beam trimming, performs monitor unit calculations to produce deliverable plans at all beam energies, and is ideally implemented with a commercially available TPS. PURPOSE: To present an analytical Pencil bEam TRimming Algorithm (PETRA) for the DCS, with and without its range shifter, implemented in the Astroid TPS (.decimal, Sanford, Florida, USA). MATERIALS: PETRA was derived by generalizing an existing pencil beam dose calculation model to account for the DCS-specific effects of lateral penumbra blurring due to the nickel trimmers in two different planes, integral depth dose variation due to the trimming process, and the presence and absence of the range shifter. Tuning parameters were introduced to enable agreement between PETRA and a measurement-validated Dynamic Collimation Monte Carlo (DCMC) model of the Miami Cancer Institute's IBA Proteus Plus system equipped with the DCS. Trimmer position, spot position, beam energy, and the presence or absence of a range shifter were all used as variables for the characterization of the model. The model was calibrated for pencil beam monitor unit calculations using procedures specified by International Atomic Energy Agency Technical Report Series 398 (IAEA TRS-398). RESULTS: The integral depth dose curves (IDDs) for energies between 70 MeV and 160 MeV among all simulated trimmer combinations, with and without the ranger shifter, agreed between PETRA and DCMC at the 1%/1 mm 1-D gamma criteria for 99.99% of points. For lateral dose profiles, the median 2-D gamma pass rate for all profiles at 1.5%/1.5 mm was 99.99% at the water phantom surface, plateau, and Bragg peak depths without the range shifter and at the surface and Bragg peak depths with the range shifter. The minimum 1.5%/1.5 mm gamma pass rates for the 2-D profiles at the water phantom surface without and with the range shifter were 98.02% and 97.91%, respectively, and, at the Bragg peak, the minimum pass rates were 97.80% and 97.5%, respectively. CONCLUSION: The PETRA model for DCS dose calculations was successfully defined and benchmarked for use in a commercially available TPS.

Creation of waterproof, TLD probes for dose measurements to validate image-based radiopharmaceutical therapy dosimetry workflow.

Voxel-level dosimetry based on nuclear medicine images offers patient-specific personalization of radiopharmaceutical therapy (RPT) treatments. Clinical evidence is emerging demonstrating improvements in treatment precision in patients when voxel-level dosimetry is used compared to MIRD. Voxel-level dosimetry requires absolute quantification of activity concentrations in the patient, but images from SPECT/CT scanners are not quantitative and require calibration using nuclear medicine phantoms. While phantom studies can validate a scanner's ability to recover activity concentrations, these studies provide only a surrogate for the true metric of interest: absorbed doses. Measurements using thermoluminescent dosimeters (TLDs) are a versatile and accurate method of measuring absorbed dose. In this work, a TLD probe was manufactured that can fit into currently available nuclear medicine phantoms for the measurement of absorbed dose of RPT agents. Next, 748 MBq of I-131 was administered to a 16 ml hollow source sphere placed in a 6.4 L Jaszczak phantom in addition to six TLD probes, each holding 4 TLD-100 1 × 1 × 1 mm TLD-100 (LiF:Mg,Ti) microcubes. The phantom then underwent a SPECT/CT scan in accordance with a standard SPECT/CT imaging protocol for I-131. The SPECT/CT images were then input into a Monte Carlo based RPT dosimetry platform named RAPID and a three dimensional dose distribution in the phantom was estimated. Additionally, a GEANT4 benchmarking scenario (denoted 'idealized') was created using a stylized representation of the phantom. There was good agreement for all six probes, the differences between measurement and RAPID ranged between -5.5% and 0.9%. The difference between the measured and the idealized GEANT4 scenario was calculated and ranged from -4.3% and -20.5%. This work demonstrates good agreement between TLD measurements and RAPID. In addition, it introduces a novel TLD probe that can be easily introduced into clinical nuclear medicine workflows to provide QA of image-based dosimetry for RPT treatments.

Dosimetric delivery validation of dynamically collimated pencil beam scanning proton therapy.

Objective. Pencil beam scanning (PBS) proton therapy target dose conformity can be improved with energy layer-specific collimation. One such collimator is the dynamic collimation system (DCS), which consists of four nickel trimmer blades that intercept the scanning beam as it approaches the lateral extent of the target. While the dosimetric benefits of the DCS have been demonstrated through computational treatment planning studies, there has yet to be experimental verification of these benefits for composite multi-energy layer fields. The objective of this work is to dosimetrically characterize and experimentally validate the delivery of dynamically collimated proton therapy with the DCS equipped to a clinical PBS system.Approach. Optimized single field, uniform dose treatment plans for 3 × 3 × 3 cm3target volumes were generated using Monte Carlo dose calculations with depths ranging from 5 to 15 cm, trimmer-to-surface distances ranging from 5 to 18.15 cm, with and without a 4 cm thick polyethylene range shifter. Treatment plans were then delivered to a water phantom using a prototype DCS and an IBA dedicated nozzle system and measured with a Zebra multilayer ionization chamber, a MatriXX PT ionization chamber array, and Gafchromic™ EBT3 film.Main results. For measurements made within the SOBPs, average 2D gamma pass rates exceeded 98.5% for the MatriXX PT and 96.5% for film at the 2%/2 mm criterion across all measured uncollimated and collimated plans, respectively. For verification of the penumbra width reduction with collimation, film agreed with Monte Carlo with differences within 0.3 mm on average compared to 0.9 mm for the MatriXX PT.Significance. We have experimentally verified the delivery of DCS-collimated fields using a clinical PBS system and commonly available dosimeters and have also identified potential weaknesses for dosimeters subject to steep dose gradients.