Stereotactic body radiation therapy (SBRT) following Yttrium-90 (90Y) selective internal radiation therapy (SIRT): a feasibility planning study using90Y delivered dose.

Objective.90Y selective internal radiation therapy (SIRT) treatment of hepatocellular carcinoma (HCC) can potentially underdose lesions, as identified on post-therapy PET/CT imaging. This study introduces a methodology and explores the feasibility for selectively treating SIRT-underdosed HCC lesions, or lesion subvolumes, with stereotactic body radiation therapy (SBRT) following post-SIRT dosimetry.Approach. We retrospectively analyzed post-treatment PET/CT images of 20 HCC patients after90Y SIRT. Predicted tumor response from SIRT was quantified based on personalized post-therapy dosimetry and corresponding response models. Predicted non-responding tumor regions were then targeted with a hypothetical SBRT boost plan using a framework for selecting eligible tumors and tumor subregions. SBRT boost plans were compared to SBRT plans targeting all tumors irrespective of SIRT dose with the same prescription and organ-at-risk (OAR) objectives. The potential benefit of SIRT followed by a SBRT was evaluated based on OAR dose and predicted toxicity compared to the independent SBRT treatment.Main results. Following SIRT, 14/20 patients had at least one predicted non-responding tumor considered eligible for a SBRT boost. When comparing SBRT plans, 10/14 (71%) SBRTboostand 12/20 (60%) SBRTaloneplans were within OAR dose constraints. For three patients, SBRTboostplans were within OAR constraints while SBRTaloneplans were not. Across the 14 eligible patients, SBRTboostplans had significantly less dose to the healthy liver (decrease in mean dose was on average ± standard deviation, 2.09 Gy ± 1.99 Gy, ) and reduced the overall targeted PTV volume (39% ± 21%) compared with SBRTalone.Significance. A clinical methodology for treating HCC using a synergized SIRT and SBRT approach is presented, demonstrating that it could reduce normal tissue toxicity risk in a majority of our retrospectively evaluated cases. Selectively targeting SIRT underdosed HCC lesions, or lesion subvolumes, with SBRT could improve tumor control and patient outcomes post-SIRT and allow SIRT to function as a target debulking tool for cases when SBRT is not independently feasible.

A Multicenter Study on Observed Discrepancies Between Vendor-Stated and PET-Measured 90Y Activities for Both Glass and Resin Microsphere Devices.

Dosimetry-guided treatment planning in selective internal radiation therapy relies on accurate and reproducible measurement of administered activity. This 4-center, 5-PET-device study compared the manufacturer-declared 90Y activity in vials with quantitative 90Y PET/CT assessment of the same vials. We compared 90Y PET-measured activity (APET) for 56 90Y-labeled glass and 18 90Y-labeled resin microsphere vials with the calibrated activity specified by the manufacturer (AM). Additionally, the same analysis was performed for 4 90Y-chloride vials. The mean APET/AM ratio was 0.79 ± 0.04 (range, 0.71-0.89) for glass microspheres and 1.15 ± 0.06 (range, 1.05-1.25) for resin microspheres. The mean APET/AM ratio for 90Y-chloride vials was 1.00 ± 0.04 (range, 0.96-1.06). Thus, we found an average difference of 46% between glass and resin microsphere activity calibrations, whereas close agreement was found for chloride solutions. We expect that the reported discrepancies will promote further investigations to establish reliable and accurate patient dosimetry and dose-effect assessments.

Experimental validation of Monte Carlo dosimetry for therapeutic beta emitters with radiochromic film in a 3D-printed phantom.

PURPOSE: Validation of dosimetry software, such as Monte Carlo (MC) radiation transport codes used for patient-specific absorbed dose estimation, is critical prior to their use in clinical decision making. However, direct experimental validation in the clinic is generally not performed for low/medium-energy beta emitters used in radiopharmaceutical therapy (RPT) due to the challenges of measuring energy deposited by short-range particles. Our objective was to design a practical phantom geometry for radiochromic film (RF)-based absorbed dose measurements of beta-emitting radionuclides and perform experiments to directly validate our in-house developed Dose Planning Method (DPM) MC code dedicated to internal dosimetry. METHODS: The experimental setup was designed for measuring absorbed dose from beta emitters that have a range sufficiently penetrating to ∼200 µm in water as well as to capture any photon contributions to absorbed dose. Assayed 177 Lu and 90 Y liquid sources, 13-450 MBq estimated to deliver 0.5-10 Gy to the sensitive layer of the RF, were injected into the cavity of two 3D-printed half-cylinders that had been sealed with 12.7 µm or 25.4 µm thick Kapton Tape. A 3.8 × 6 cm strip of GafChromic EBT3 RF was sandwiched between the two taped half-cylinders. After 2-48 h exposures, films were retrieved and wipe tested for contamination. Absorbed dose to the RF was measured using a commercial triple-channel dosimetry optimization method and a calibration generated via 6 MV photon beam. Profiles were analyzed across the central 1 cm2 area of the RF for validation. Eleven experiments were completed with 177 Lu and nine with 90 Y both in saline and a bone equivalent solution. Depth dose curves were generated for 177 Lu and 90 Y stacking multiple RF strips between a single filled half-cylinder and an acrylic backing. All experiments were modeled in DPM to generate voxelized MC absorbed dose estimates. We extended our study to benchmark general purpose MC codes MCNP6 and EGSnrc against the experimental results as well. RESULTS: A total of 20 experiments showed that both the 3D-printed phantoms and the final absorbed dose values were reproducible. The agreement between the absorbed dose estimates from the RF measurements and DPM was on average -4.0% (range -10.9% to 3.2%) for all single film 177 Lu experiments and was on average -1.0% (range -2.7% to 0.7%) for all single film 90 Y experiments. Absorbed depth dose estimates by DPM agreed with RF on average 1.2% (range -8.0% to 15.2%) across all depths for 177 Lu and on average 4.0% (range -5.0% to 9.3%) across all depths for 90 Y. DPM absorbed dose estimates agreed with estimates from EGSnrc and MCNP across the board, within 4.7% and within 3.4% for 177 Lu and 90 Y respectively, for all geometries and across all depths. MC showed that absorbed dose to RF from betas was greater than 92% of the total (betas + other radiations) for 177 Lu, indicating measurement of dominant beta contribution with our design. CONCLUSIONS: The reproducible results with a RF insert in a simple phantom designed for liquid sources demonstrate that this is a reliable setup for experimentally validating dosimetry algorithms used in therapies with beta-emitting unsealed sources. Absorbed doses estimated with the DPM MC code showed close agreement with RF measurement and with results from two general purpose MC codes, thereby validating the use of this algorithms for clinical RPT dosimetry.

A Pipeline for Automated Voxel Dosimetry: Application in Patients with Multi-SPECT/CT Imaging After 177Lu-Peptide Receptor Radionuclide Therapy.

Patient-specific dosimetry in radiopharmaceutical therapy (RPT) is impeded by the lack of tools that are accurate and practical for the clinic. Our aims were to construct and test an integrated voxel-level pipeline that automates key components (organ segmentation, registration, dose-rate estimation, and curve fitting) of the RPT dosimetry process and then to use it to report patient-specific dosimetry in 177Lu-DOTATATE therapy. Methods: An integrated workflow that automates the entire dosimetry process, except tumor segmentation, was constructed. First, convolutional neural networks (CNNs) are used to automatically segment organs on the CT portion of one post-therapy SPECT/CT scan. Second, local contour intensity-based SPECT--SPECT alignment results in volume-of-interest propagation to other time points. Third, dose rate is estimated by explicit Monte Carlo (MC) radiation transport using the fast, Dose Planning Method code. Fourth, the optimal function for dose-rate fitting is automatically selected for each voxel. When reporting mean dose, we apply partial-volume correction, and uncertainty is estimated by an empiric approach of perturbing segmentations. Results: The workflow was used with 4-time-point 177Lu SPECT/CT imaging data from 20 patients with 77 neuroendocrine tumors, segmented by a radiologist. CNN-defined kidneys resulted in high Dice values (0.91-0.94) and only small differences (2%-5%) in mean dose when compared with manual segmentation. Contour intensity-based registration led to visually enhanced alignment, and the voxel-level fitting had high R 2 values. Across patients, dosimetry results were highly variable; for example, the average of the mean absorbed dose (Gy/GBq) was 3.2 (range, 0.2-10.4) for lesions, 0.49 (range, 0.24-1.02) for left kidney, 0.54 (range, 0.31-1.07) for right kidney, and 0.51 (range, 0.27-1.04) for healthy liver. Patient results further demonstrated the high variability in the number of cycles needed to deliver hypothetical threshold absorbed doses of 23 Gy to kidney and 100 Gy to tumor. The uncertainty in mean dose, attributable to variability in segmentation, averaged 6% (range, 3%-17%) for organs and 10% (range, 3%-37%) for lesions. For a typical patient, the time for the entire process was about 25 min (∼2 min manual time) on a desktop computer, including time for CNN organ segmentation, coregistration, MC dosimetry, and voxel curve fitting. Conclusion: A pipeline integrating novel tools that are fast and automated provides the capacity for clinical translation of dosimetry-guided RPT.

DblurDoseNet: A deep residual learning network for voxel radionuclide dosimetry compensating for single-photon emission computerized tomography imaging resolution.

PURPOSE: Current methods for patient-specific voxel-level dosimetry in radionuclide therapy suffer from a trade-off between accuracy and computational efficiency. Monte Carlo (MC) radiation transport algorithms are considered the gold standard for voxel-level dosimetry but can be computationally expensive, whereas faster dose voxel kernel (DVK) convolution can be suboptimal in the presence of tissue heterogeneities. Furthermore, the accuracies of both these methods are limited by the spatial resolution of the reconstructed emission image. To overcome these limitations, this paper considers a single deep convolutional neural network (CNN) with residual learning (named DblurDoseNet) that learns to produce dose-rate maps while compensating for the limited resolution of SPECT images. METHODS: We trained our CNN using MC-generated dose-rate maps that directly corresponded to the true activity maps in virtual patient phantoms. Residual learning was applied such that our CNN learned only the difference between the true dose-rate map and DVK dose-rate map with density scaling. Our CNN consists of a 3D depth feature extractor followed by a 2D U-Net, where the input was 11 slices (3.3 cm) of a given Lu-177 SPECT/CT image and density map, and the output was the dose-rate map corresponding to the center slice. The CNN was trained with nine virtual patient phantoms and tested on five different phantoms plus 42 SPECT/CT scans of patients who underwent Lu-177 DOTATATE therapy. RESULTS: When testing on virtual patient phantoms, the lesion/organ mean dose-rate error and the normalized root mean square error (NRMSE) relative to the ground truth of the CNN method was consistently lower than DVK and MC, when applied to SPECT images. Compared to DVK/MC, the average improvement for the CNN in mean dose-rate error was 55%/53% and 66%/56%; and in NRMSE was 18%/17% and 10%/11% for lesion and kidney regions, respectively. Line profiles and dose-volume histograms demonstrated compensation for SPECT resolution effects in the CNN-generated dose-rate maps. The ensemble noise standard deviation, determined from multiple Poisson realizations, was improved by 21%/27% compared to DVK/MC. In patients, potential improvements from CNN dose-rate maps compared to DVK/MC were illustrated qualitatively, due to the absence of ground truth. The trained residual CNN took about 30 s on a single GPU (Tesla V100) to generate a 512 × $\; \times \;$ 512 × $\; \times \;$ 130 dose-rate map for a patient. CONCLUSION: The proposed residual CNN, trained using phantoms generated from patient images, has potential for real-time patient-specific dosimetry in clinical treatment planning due to its demonstrated improvement in accuracy, resolution, noise, and speed over the DVK/MC approaches.

Y-90 SIRT: evaluation of TCP variation across dosimetric models.

INTRODUCTION: Much progress has been made in implementing selective internal radiation therapy (SIRT) as a viable treatment option for hepatic malignancies. However, there is still much need for improved options for calculating the amount of activity to be administered. To make advances towards this goal, this study examines the relationship between predicted biological outcomes of liver tumors via tumor control probabilities (TCP) and parenchyma via normal tissue complication probabilities (NTCP) given variations in absorbed dose prescription methodologies. METHODS: Thirty-nine glass microsphere treatments in 35 patients with hepatocellular carcinoma or metastatic liver disease were analyzed using 99mTc-MAA SPECT/CT and 90Y PET/CT scans. Predicted biological outcomes corresponding to the single compartment (standard) model and multi-compartment (partition) dosimetry model were compared using our previously derived TCP dose-response curves over a range of 80-150 Gy prescribed absorbed dose to the perfused volume, recommended in the package insert for glass microspheres. Retrospective planning dosimetry was performed on the MAA SPECT/CT; changes from the planned infused activity due to selection of absorbed dose level and dosimetry model (standard or partition) were used to scale absorbed doses reported from 90Y PET/CT including liver parenchyma and lesions (N = 120) > 2 ml. A parameterized charting system was developed across all potential prescription options to enable a clear relationship between standard prescription vs. the partition model-based prescription. Using a previously proposed NTCP model, the change in prescribed dose from a standard model prescription of 120 Gy to the perfused volume to a 15% NTCP prescription to the normal liver was explored. RESULTS: Average TCP predictions for the partition model compared with the standard model varied from a 13% decrease to a 32% increase when the prescribed dose was varied across the range of 80-150 Gy. In the parametrized chart comparing absorbed dose prescription ranges across the standard model and partition models, a line of equivalent absorbed dose to a tumor was identified. TCP predictions on a per lesion basis varied between a 26% decrease and a 81% increase for the most commonly chosen prescription options when comparing the partition model with the standard model. NTCP model was only applicable to a subset of patients because of the small volume fraction of the liver that was targeted in most cases. CONCLUSION: Our retrospective analysis of patient imaging data shows that the choice of prescribed dose and which model to prescribe potentially contribute to a wide variation in average tumor efficacy. Biological response data should be included as one factor when looking to improve patient care in the clinic. The use of parameterized charting, such as presented here, will help direct physicians when transitioning to newer prescription methods.

Development and comprehensive commissioning of an automated brachytherapy plan checker.

PURPOSE: To present on the commissioning of an automated brachytherapy plan checker (BPC) for the evaluation of high-dose-rate brachytherapy treatment plans in support of standardized workflows and patient safety. METHODS AND MATERIALS: A BPC was developed using an applications programming interface in a commercial treatment planning system based on different inputs (e.g., regulations, professional society recommendations, and user feedback) and leveraged our experience with an in-house developed external beam plan checker. The BPC was commissioned using a comprehensive suite of test plans with known errors and anonymized clinical plans. RESULTS: During commissioning, the BPC was successfully executed on a total of 87 test plans. Commissioning tests spanned a range of treatment sites and evaluated that pass and fail states were correct. Administration settings were changed in a nonclinical database to evaluate tests involving the source and afterloader. Clinical testing of the BPC was then performed in parallel with a manual review process before clinical implementation. CONCLUSIONS: To commission the BPC for clinical use, a comprehensive suite of test plans was developed and used to ensure the BPC correctly detected and reported errors. A summary of the test plans is presented to help guide users developing similar automated tools. The BPC represents a process-improvement initiative designed to reduce errors and improve safety for brachytherapy patients. By using a comprehensive test suite for commissioning, tests are available for periodic quality assurance and after software upgrades.

Prediction of Tumor Control in 90Y Radioembolization by Logit Models with PET/CT-Based Dose Metrics.

The aim of this work was to develop models for tumor control probability (TCP) in radioembolization with 90Y PET/CT-derived radiobiologic dose metrics. Methods: Patients with primary liver cancer or liver metastases who underwent radioembolization with glass microspheres were imaged with 90Y PET/CT for voxel-level dosimetry to determine lesion absorbed dose (AD) metrics, biological effective dose (BED) metrics, equivalent uniform dose, and equivalent uniform BED for 28 treatments (89 lesions). The lesion dose-shrinkage correlation was assessed on the basis of RECIST and, when available, modified RECIST (mRECIST) at first follow-up. For a subset with mRECIST, logit regression TCP models were fit via maximum likelihood to relate lesion-level binary response to the dose metrics. As an exploratory analysis, the nontumoral liver dose-toxicity relationship was also evaluated. Results: Lesion dose-shrinkage analysis showed that there were no significant differences between model parameters for primary and metastatic subgroups and that correlation coefficients were superior with mRECIST. Therefore, subsequent TCP analysis was performed for the combined group using mRECIST only. The overall lesion-level mRECIST response rate was 57%. The AD and BED metrics yielding 50% TCP were 292 and 441 Gy, respectively. All dose metrics considered for TCP modeling, including mean AD, were significantly associated with the probability of response, with high areas under the curve (0.87-0.90, P < 0.0001) and high sensitivity (>0.75) and specificity (>0.83) calculated using a threshold corresponding to 50% TCP. Because nonuniform AD deposition by microspheres cannot be determined by PET at a microscopic scale, radiosensitivity values extracted here by fitting models to clinical response data were substantially lower than reported for in vitro cell cultures or for external-beam radiotherapy clinical studies. There was no correlation between nontumoral liver AD and toxicity measures. Conclusion: Despite the heterogeneous patient cohort, logistic regression TCP models showed a strong association between various dose metrics and the probability of response. The performance of mean AD was comparable to that of radiobiologic dose metrics that involve more complex calculations. These results demonstrate the importance of considering TCP in treatment planning for radioembolization.

Transarterial Radioembolization for Hepatocellular Carcinoma and Hepatic Metastases: Clinical Aspects and Dosimetry Models.

Transarterial radioembolization (TARE) with Yttrium-90 (90Y) microspheres is a liver-directed therapy for primary and metastatic disease. This manuscript provides a review of the clinical literature on TARE indications and efficacy with overviews of patient-selection and toxicity. Current dosimetry models used in practice are safe, relatively simple, and easy for clinicians to use. Planning currently relies on the imperfect surrogate, 99mTc macroaggregated albumin. Post-therapy quantitative imaging (90Y SPECT/CT or 90Y PET/CT) of microspheres can be used to calculate the macroscopic in vivo absorbed dose distribution. Similar to the evolution of other brachytherapy dose calculations, TARE is moving toward more patient-specific dosimetry that includes calculating and reporting nonuniform dose distributions throughout tumors and normal uninvolved liver.

Assessing Spatial Concordance Between Theranostic Pairs Using Phantom and Patient-Specific Acceptance Criteria: Application to 99mTc-MAA SPECT/90Y-Microsphere PET.

PURPOSE: Predictive 3-dimensional dosimetry requires spatial concordance between diagnostic and therapeutic activity distributions. We assess similarity between theranostic pairs (99mTc-macroaggregated albumin [MAA] single photon emission computed tomography [SPECT] and 90Y microsphere positron emission tomography [PET]) in patients using criteria that account for spatial resolution differences and misregistration. METHODS AND MATERIALS: Phantom-based acceptance criteria were determined using a liver phantom filled with 99mTc and 90YCl3 and scanned with SPECT/computed tomography [CT] and PET/CT, respectively. Gaussian blurring was applied to PET to match 99mTc phantom scan image quality. After rigid registration between SPECT/CT and PET/CT, perturbations up to ±3 voxels were applied to determine the similarity metric (SM) sensitivity. 99mTc-MAA SPECT/CT and 90Y microsphere PET/CT image pairs/patients (n = 23) were processed analogously. SMs calculated included the Pearson correlation coefficient (ρr), Lin's concordance correlation coefficient (ρc), Spearman's rank correlation coefficient (ρs), the mean squared difference, and the Dice similarity coefficient (DSC). Patient-specific acceptance criteria were determined by evaluating the SMs of the blurred PET compared with itself misregistered. RESULTS: After transforming PET to SPECT resolution, high similarity was found in phantom, with ρc, ρr, ρs > 0.98 ± 0.01, a mean squared difference of (4.1 ± 0.3) × 10-4 and DSC > 0.85 ± 0.01 for investigated thresholds (5%, 30%, and 50%). SMs for patients varied from poor to good. A small percentage (13%-30%) of patient scans were acceptable using phantom-based acceptance criteria. The percentage increased slightly (17%-35%) using patient-specific acceptance criteria. DSC for most patients were substantially lower (average 0.95 vs 0.61 for 5% threshold) than phantom values. CONCLUSIONS: At best, 35% of patients had an SM within the acceptance criteria established to account for imaging-related effects impacting spatial concordance between 99mTc-MAA SPECT and 90Y PET. Additional clinical factors should be evaluated in the future. The procedure of accounting for image-related effects when assessing spatial concordance can be applied to other theranostic pairs.

Dose volume histogram-based optimization of image reconstruction parameters for quantitative 90 Y-PET imaging.

PURPOSE: 90 Y-microsphere radioembolization or selective internal radiation therapy is increasingly being used as a treatment option for tumors that are not candidates for surgery and external beam radiation therapy. Recently, volumetric 90 Y-dosimetry techniques have been implemented to explore tumor dose-response on the basis of 3D 90 Y-activity distribution from PET imaging. Despite being a theranostic study, the optimization of quantitative 90 Y-PET image reconstruction still uses the mean activity concentration recovery coefficient (RC) as the objective function, which is more relevant to diagnostic and detection tasks than is to dosimetry. The aim of this study was to optimize 90 Y-PET image reconstruction by minimizing errors in volumetric dosimetry via the dose volume histogram (DVH). We propose a joint optimization of the number of equivalent iterations (the product of the iterations and subsets) and the postreconstruction filtration (FWHM) to improve the accuracy of voxel-level 90 Y dosimetry. METHODS: A modified NEMA IEC phantom was used to emulate clinically relevant 90 Y-PET imaging conditions through various combinations of acquisition durations, activity concentrations, sphere-to-background ratios, and sphere diameters. PET data were acquired in list mode for 300 min in a single-bed position; we then rebinned the list mode PET data to 60, 45, 30, 15, and 5 min per bed, with 10 different realizations. Errors in the DVH were calculated as root mean square errors (RMSE) of the differences in the image-based DVH and the expected DVH. The new optimization approach was tested in a phantom study, and the results were compared with the more commonly used objective function of the mean activity concentration RC. RESULTS: In a wide range of clinically relevant imaging conditions, using 36 equivalent iterations with a 5.2-mm filtration resulted in decreased systematic errors in volumetric 90 Y dosimetry, quantified as image-based DVH, in 90 Y-PET images reconstructed using the ordered subset expectation maximization (OSEM) iterative reconstruction algorithm with time of flight (TOF) and point spread function (PSF) modeling. Our proposed objective function of minimizing errors in DVH, which allows for joint optimization of 90 Y-PET iterations and filtration for volumetric quantification of the 90 Y dose, was shown to be superior to conventional RC-based optimization approaches for image-based absorbed dose quantification. CONCLUSION: Our proposed objective function of minimizing errors in DVH, which allows for joint optimization of iterations and filtration to reduce errors in the PET-based volumetric quantification 90 Y dose, is relevant to dosimetry in therapy procedures. The proposed optimization method using DVH as the objective function could be applied to any imaging modality used to assess voxel-level quantitative information.

Impact of 90Y PET gradient-based tumor segmentation on voxel-level dosimetry in liver radioembolization.

BACKGROUND: The purpose was to validate 90Y PET gradient-based tumor segmentation in phantoms and to evaluate the impact of the segmentation method on reported tumor absorbed dose (AD) and biological effective dose (BED) in 90Y microsphere radioembolization (RE) patients. A semi-automated gradient-based method was applied to phantoms and patient tumors on the 90Y PET with the initial bounding volume for gradient detection determined from a registered diagnostic CT or MR; this PET-based segmentation (PS) was compared with radiologist-defined morphologic segmentation (MS) on CT or MRI. AD and BED volume histogram metrics (D90, D70, mean) were calculated using both segmentations and concordance/correlations were investigated. Spatial concordance was assessed using Dice similarity coefficient (DSC) and mean distance to agreement (MDA). PS was repeated to assess intra-observer variability. RESULTS: In phantoms, PS demonstrated high accuracy in lesion volumes (within 15%), AD metrics (within 11%), high spatial concordance relative to morphologic segmentation (DSC > 0.86 and MDA < 1.5 mm), and low intra-observer variability (DSC > 0.99, MDA < 0.2 mm, AD/BED metrics within 2%). For patients (58 lesions), spatial concordance between PS and MS was degraded compared to in-phantom (average DSC = 0.54, average MDA = 4.8 mm); the average mean tumor AD was 226 ± 153 and 197 ± 138 Gy, respectively for PS and MS. For patient AD metrics, the best Pearson correlation (r) and concordance correlation coefficient (ccc) between segmentation methods was found for mean AD (r = 0.94, ccc = 0.92), but worsened as the metric approached the minimum dose (for D90, r = 0.77, ccc = 0.69); BED metrics exhibited a similar trend. Patient PS showed low intra-observer variability (average DSC = 0.81, average MDA = 2.2 mm, average AD/BED metrics within 3.0%). CONCLUSIONS: 90Y PET gradient-based segmentation led to accurate/robust results in phantoms, and showed high concordance with MS for reporting mean tumor AD/BED in patients. However, tumor coverage metrics such as D90 exhibited worse concordance between segmentation methods, highlighting the need to standardize segmentation methods when reporting AD/BED metrics from post-therapy 90Y PET. Estimated differences in reported AD/BED metrics due to segmentation method will be useful for interpreting RE dosimetry results in the literature including tumor response data.

The value of 99mTc-MAA SPECT/CT for lung shunt estimation in 90Y radioembolization: a phantom and patient study.

BACKGROUND: A major toxicity concern in radioembolization therapy of hepatic malignancies is radiation-induced pneumonitis and sclerosis due to hepatopulmonary shunting of 90Y microspheres. Currently, 99mTc macroaggregated albumin (99mTc-MAA) imaging is used to estimate the lung shunt fraction (LSF) prior to treatment. The aim of this study was to evaluate the accuracy/precision of LSF estimated from 99mTc planar and SPECT/CT phantom imaging, and within this context, to compare the corresponding LSF and lung-absorbed dose values from 99mTc-MAA patient studies. Additionally, LSFs from pre- and post-therapy imaging were compared. RESULTS: A liver/lung torso phantom filled with 99mTc to achieve three lung shunt values was scanned by planar and SPECT/CT imaging with repeat acquisitions to assess accuracy and precision. To facilitate processing of patient data, a workflow that relies on SPECT and CT-based auto-contouring to define liver and lung volumes for the LSF calculation was implemented. Planar imaging-based LSF estimates for 40 patients, obtained from their medical records, were retrospectively compared with SPECT/CT imaging-based calculations with attenuation and scatter correction. Additionally, in a subset of 20 patients, the pre-therapy estimates were compared with 90Y PET/CT-based measurements. In the phantom study, improved accuracy in LSF estimation was achieved using SPECT/CT with attenuation and scatter correction (within 13% of the true value) compared with planar imaging (up to 44% overestimation). The results in patients showed a similar trend with planar imaging significantly overestimating LSF compared to SPECT/CT. There was no correlation between lung shunt estimates and the delay between 99mTc-MAA administration and scanning, but off-target extra hepatic uptake tended to be more likely in patients with a longer delay. The mean lung absorbed dose predictions for the 28 patients who underwent therapy was 9.3 Gy (range 1.3-29.4) for planar imaging and 3.2 Gy (range 0.4-13.4) for SPECT/CT. For the patients with post-therapy imaging, the mean LSF from 90Y PET/CT was 1.0%, (range 0.3-2.8). This value was not significantly different from the mean LSF estimate from 99mTc-MAA SPECT/CT (mean 1.0%, range 0.4-1.6; p = 0.968), but was significantly lower than the mean LSF estimate based on planar imaging (mean 4.1%, range 1.2-15.0; p = 0.0002). CONCLUSIONS: The improved accuracy demonstrated by the phantom study, agreement with 90Y PET/CT in patient studies, and the practicality of using auto-contouring for liver/lung definition suggests that 99mTc-MAA SPECT/CT with scatter and attenuation corrections should be used for lung shunt estimation prior to radioembolization.

The impact of a high-definition multileaf collimator for spine SBRT.

PURPOSE: Advanced radiotherapy delivery systems designed for high-dose, high-precision treatments often come equipped with high-definition multi-leaf collimators (HD-MLC) aimed at more finely shaping radiation dose to the target. In this work, we study the effect of a high definition MLC on spine stereotactic body radiation therapy (SBRT) treatment plan quality and plan deliverability. METHODS AND MATERIALS: Seventeen spine SBRT cases were planned with VMAT using a standard definition MLC (M120), HD-MLC, and HD-MLC with an added objective to reduce monitor units (MU). M120 plans were converted into plans deliverable on an HD-MLC using in-house software. Plan quality and plan deliverability as measured by portal dosimetry were compared among the three types of plans. RESULTS: Only minor differences were noted in plan quality between the M120 and HD-MLC plans. Plans generated with the HD-MLC tended to have better spinal cord sparing (3% reduction in maximum cord dose). HD-MLC plans on average had 12% more MU and 55% greater modulation complexity as defined by an in-house metric. HD-MLC plans also had significantly degraded deliverability. Of the VMAT arcs measured, 94% had lower gamma passing metrics when using the HD-MLC. CONCLUSION: Modest improvements in plan quality were noted when switching from M120 to HD-MLC at the expense of significantly less accurate deliverability in some cases.

Selective Internal Radiation Therapy With Yttrium-90 Glass Microspheres: Biases and Uncertainties in Absorbed Dose Calculations Between Clinical Dosimetry Models.

PURPOSE: To quantify differences that exist between dosimetry models used for 90Y selective internal radiation therapy (SIRT). METHODS AND MATERIALS: Retrospectively, 37 tumors were delineated on 19 post-therapy quantitative 90Y single photon emission computed tomography/computed tomography scans. Using matched volumes of interest (VOIs), absorbed doses were reported using 3 dosimetry models: glass microsphere package insert standard model (SM), partition model (PM), and Monte Carlo (MC). Univariate linear regressions were performed to predict mean MC from SM and PM. Analysis was performed for 2 subsets: cases with a single tumor delineated (best case for PM), and cases with multiple tumors delineated (typical clinical scenario). Variability in PM from the ad hoc placement of a single spherical VOI to estimate the entire normal liver activity concentration for tumor (T) to nontumoral liver (NL) ratios (TNR) was investigated. We interpreted the slope of the resulting regression as bias and the 95% prediction interval (95%PI) as uncertainty. MCNLsingle represents MC absorbed doses to the NL for the single tumor patient subset; other combinations of calculations follow a similar naming convention. RESULTS: SM was unable to predict MCTsingle or MCTmultiple (p>.12, 95%PI >±177 Gy). However, SMsingle was able to predict (p<.012) MCNLsingle, albeit with large uncertainties; SMsingle and SMmultiple yielded biases of 0.62 and 0.71, and 95%PI of ±40 and ± 32 Gy, respectively. PMTsingle and PMTmultiple predicted (p<2E-6) MCTsingle and MCTmultiple with biases of 0.52 and 0.54, and 95%PI of ±38 and ± 111 Gy, respectively. The TNR variability in PMTsingle increased the 95%PI for predicting MCTsingle (bias = 0.46 and 95%PI = ±103 Gy). The TNR variability in PMTmultiple modified the bias when predicting MCTmultiple (bias = 0.32 and 95%PI = ±110 Gy). CONCLUSIONS: The SM is unable to predict mean MC tumor absorbed dose. The PM is statistically correlated with mean MC, but the resulting uncertainties in predicted MC are large. Large differences observed between dosimetry models for 90Y SIRT warrant caution when interpreting published SIRT absorbed doses. To reduce uncertainty, we suggest the entire NL VOI be used for TNR estimates when using PM.

Comparing voxel-based absorbed dosimetry methods in tumors, liver, lung, and at the liver-lung interface for (90)Y microsphere selective internal radiation therapy.

BACKGROUND: To assess differences between four different voxel-based dosimetry methods (VBDM) for tumor, liver, and lung absorbed doses following (90)Y microsphere selective internal radiation therapy (SIRT) based on (90)Y bremsstrahlung SPECT/CT, a secondary objective was to estimate the sensitivity of liver and lung absorbed doses due to differences in organ segmentation near the liver-lung interface. METHODS: Investigated VBDM were Monte Carlo (MC), soft-tissue kernel with density correction (SKD), soft-tissue kernel (SK), and local deposition (LD). Seventeen SIRT cases were analyzed. Mean absorbed doses ([Formula: see text]) were calculated for tumor, non-tumoral liver (NL), and right lung (RL). Simulations with various SPECT spatial resolutions (FHWMs) and multiple lung shunt fractions (LSs) estimated the accuracy of VBDM at the liver-lung interface. Sensitivity of patient RL and NL [Formula: see text] on segmentation near the interface was assessed by excluding portions near the interface. RESULTS: SKD, SK, and LD were within 5 % of MC for tumor and NL [Formula: see text]. LD and SKD overestimated RL [Formula: see text] compared to MC on average by 17 and 20 %, respectively; SK underestimated RL [Formula: see text] on average by -60 %. Simulations (20 mm FWHM, 20 % LS) showed that SKD, LD, and MC were within 10 % of the truth deep (>39 mm) in the lung; SK significantly underestimated the absorbed dose deep in the lung by approximately -70 %. All VBDM were within 10 % of truth deep (>12 mm) in the liver. Excluding 1, 2, and 3 cm of RL near the interface changed the resulting RL [Formula: see text] by -22, -38, and -48 %, respectively, for all VBDM. An average change of -7 % in the NL [Formula: see text] was realized when excluding 3 cm of NL from the interface. [Formula: see text] was realized when excluding 3 cm of NL from the interface. CONCLUSIONS: SKD, SK, and LD are equivalent to MC for tumor and NL [Formula: see text]. SK underestimates RL [Formula: see text] relative to MC whereas LD and SKD overestimate. RL [Formula: see text] is strongly influenced by the liver-lung interface.

Dosimetric influence of seed spacers and end-weld thickness for permanent prostate brachytherapy.

PURPOSE: The aim of this study was to analyze the dosimetric influence of conventional spacers and a cobalt chloride complex contrast (C4) agent, a novel marker for MRI that can also serve as a seed spacer, adjacent to (103)Pd, (125)I, and (131)Cs sources for permanent prostate brachytherapy. METHODS AND MATERIALS: Monte Carlo methods for radiation transport were used to estimate the dosimetric influence of brachytherapy end-weld thicknesses and spacers near the three sources. Single-source assessments and volumetric conditions simulating prior patient treatments were computed. Volume-dose distributions were imported to a treatment planning system for dose-volume histogram analyses. RESULTS: Single-source assessment revealed that brachytherapy spacers primarily attenuated the dose distribution along the source long axis. The magnitude of the attenuation at 1 cm on the long axis ranged from -10% to -5% for conventional spacers and approximately -2% for C4 spacers, with the largest attenuation for (103)Pd. Spacer perturbation of dose distributions was less than manufacturing tolerances for brachytherapy sources as gleaned by an analysis of end-weld thicknesses. Volumetric Monte Carlo assessment demonstrated that TG-43 techniques overestimated calculated doses by approximately 2%. Specific dose-volume histogram metrics for prostate implants were not perturbed by inclusion of conventional or C4 spacers in clinical models. CONCLUSIONS: Dosimetric perturbations of single-seed dose distributions by brachytherapy spacers exceeded 10% along the source long axes adjacent to the spacers. However, no dosimetric impact on volumetric parameters was noted for brachytherapy spacers adjacent to (103)Pd, (125)I, or (131)Cs sources in the context of permanent prostate brachytherapy implants.

Commissioning of a grid-based Boltzmann solver for cervical cancer brachytherapy treatment planning with shielded colpostats.

PURPOSE: We sought to commission a gynecologic shielded colpostat analytic model provided from a treatment planning system (TPS) library. We have reported retrospectively the dosimetric impact of this applicator model in a cohort of patients. METHODS AND MATERIALS: A commercial TPS with a grid-based Boltzmann solver (GBBS) was commissioned for (192)Ir high-dose-rate (HDR) brachytherapy for cervical cancer with stainless steel-shielded colpostats. Verification of the colpostat analytic model was verified using a radiograph and vendor schematics. MCNPX v2.6 Monte Carlo simulations were performed to compare dose distributions around the applicator in water with the TPS GBBS dose predictions. Retrospectively, the dosimetric impact was assessed over 24 cervical cancer patients' HDR plans. RESULTS: Applicator (TPS ID #AL13122005) shield dimensions were within 0.4 mm of the independent shield dimensions verification. GBBS profiles in planes bisecting the cap around the applicator agreed with Monte Carlo simulations within 2% at most locations; differing screw representations resulted in differences of up to 9%. For the retrospective study, the GBBS doses differed from TG-43 as follows (mean value ± standard deviation [min, max]): International Commission on Radiation units [ICRU]rectum (-8.4 ± 2.5% [-14.1, -4.1%]), ICRUbladder (-7.2 ± 3.6% [-15.7, -2.1%]), D2cc-rectum (-6.2 ± 2.6% [-11.9, -0.8%]), D2cc-sigmoid (-5.6 ± 2.6% [-9.3, -2.0%]), and D2cc-bladder (-3.4 ± 1.9% [-7.2, -1.1%]). CONCLUSIONS: As brachytherapy TPSs implement advanced model-based dose calculations, the analytic applicator models stored in TPSs should be independently validated before clinical use. For this cohort, clinically meaningful differences (>5%) from TG-43 were observed. Accurate dosimetric modeling of shielded applicators may help to refine organ toxicity studies.

Impact of heterogeneity-based dose calculation using a deterministic grid-based Boltzmann equation solver for intracavitary brachytherapy.

PURPOSE: To investigate the dosimetric impact of the heterogeneity dose calculation Acuros (Transpire Inc., Gig Harbor, WA), a grid-based Boltzmann equation solver (GBBS), for brachytherapy in a cohort of cervical cancer patients. METHODS AND MATERIALS: The impact of heterogeneities was retrospectively assessed in treatment plans for 26 patients who had previously received (192)Ir intracavitary brachytherapy for cervical cancer with computed tomography (CT)/magnetic resonance-compatible tandems and unshielded colpostats. The GBBS models sources, patient boundaries, applicators, and tissue heterogeneities. Multiple GBBS calculations were performed with and without solid model applicator, with and without overriding the patient contour to 1 g/cm(3) muscle, and with and without overriding contrast materials to muscle or 2.25 g/cm(3) bone. Impact of source and boundary modeling, applicator, tissue heterogeneities, and sensitivity of CT-to-material mapping of contrast were derived from the multiple calculations. American Association of Physicists in Medicine Task Group 43 (TG-43) guidelines and the GBBS were compared for the following clinical dosimetric parameters: Manchester points A and B, International Commission on Radiation Units and Measurements (ICRU) report 38 rectal and bladder points, three and nine o'clock, and (D2cm3) to the bladder, rectum, and sigmoid. RESULTS: Points A and B, D(2) cm(3) bladder, ICRU bladder, and three and nine o'clock were within 5% of TG-43 for all GBBS calculations. The source and boundary and applicator account for most of the differences between the GBBS and TG-43 guidelines. The D(2cm3) rectum (n = 3), D(2cm3) sigmoid (n = 1), and ICRU rectum (n = 6) had differences of >5% from TG-43 for the worst case incorrect mapping of contrast to bone. Clinical dosimetric parameters were within 5% of TG-43 when rectal and balloon contrast were mapped to bone and radiopaque packing was not overridden. CONCLUSIONS: The GBBS has minimal impact on clinical parameters for this cohort of patients with unshielded applicators. The incorrect mapping of rectal and balloon contrast does not have a significant impact on clinical parameters. Rectal parameters may be sensitive to the mapping of radiopaque packing.

Dosimetric comparison of Acuros XB deterministic radiation transport method with Monte Carlo and model-based convolution methods in heterogeneous media.

PURPOSE: The deterministic Acuros XB (AXB) algorithm was recently implemented in the Eclipse treatment planning system. The goal of this study was to compare AXB performance to Monte Carlo (MC) and two standard clinical convolution methods: the anisotropic analytical algorithm (AAA) and the collapsed-cone convolution (CCC) method. METHODS: Homogeneous water and multilayer slab virtual phantoms were used for this study. The multilayer slab phantom had three different materials, representing soft tissue, bone, and lung. Depth dose and lateral dose profiles from AXB v10 in Eclipse were compared to AAA v10 in Eclipse, CCC in Pinnacle3, and EGSnrc MC simulations for 6 and 18 MV photon beams with open fields for both phantoms. In order to further reveal the dosimetric differences between AXB and AAA or CCC, three-dimensional (3D) gamma index analyses were conducted in slab regions and subregions defined by AAPM Task Group 53. RESULTS: The AXB calculations were found to be closer to MC than both AAA and CCC for all the investigated plans, especially in bone and lung regions. The average differences of depth dose profiles between MC and AXB, AAA, or CCC was within 1.1, 4.4, and 2.2%, respectively, for all fields and energies. More specifically, those differences in bone region were up to 1.1, 6.4, and 1.6%; in lung region were up to 0.9, 11.6, and 4.5% for AXB, AAA, and CCC, respectively. AXB was also found to have better dose predictions than AAA and CCC at the tissue interfaces where backscatter occurs. 3D gamma index analyses (percent of dose voxels passing a 2%/2 mm criterion) showed that the dose differences between AAA and AXB are significant (under 60% passed) in the bone region for all field sizes of 6 MV and in the lung region for most of field sizes of both energies. The difference between AXB and CCC was generally small (over 90% passed) except in the lung region for 18 MV 10 x 10 cm2 fields (over 26% passed) and in the bone region for 5 x 5 and 10 x 10 cm2 fields (over 64% passed). With the criterion relaxed to 5%/2 mm, the pass rates were over 90% for both AAA and CCC relative to AXB for all energies and fields, with the exception of AAA 18 MV 2.5 x 2.5 cm2 field, which still did not pass. CONCLUSIONS: In heterogeneous media, AXB dose prediction ability appears to be comparable to MC and superior to current clinical convolution methods. The dose differences between AXB and AAA or CCC are mainly in the bone, lung, and interface regions. The spatial distributions of these differences depend on the field sizes and energies.