FLASH Radiotherapy Using Single-Energy Proton PBS Transmission Beams for Hypofractionation Liver Cancer: Dose and Dose Rate Quantification

PurposeThis work aims to study the dose and ultra-high-dose rate characteristics of transmission proton pencil beam scanning (PBS) FLASH radiotherapy (RT) for hypofractionation liver cancer based on the parameters of a commercially available proton system operating under FLASH mode.Methods and MaterialsAn in-house treatment planning software (TPS) was developed to perform intensity-modulated proton therapy (IMPT) FLASH-RT planning. Single-energy transmission proton PBS plans of 4.5 Gy × 15 fractions were optimized for seven consecutive hepatocellular carcinoma patients, using 2 and 5 fields combined with 1) the minimum MU/spot chosen between 100 and 400, and minimum spot time (MST) of 2 ms, and 2) the minimum MU/spot of 100, and MST of 0.5 ms, based upon considerations in target uniformities, OAR dose constraints, and OAR FLASH dose rate coverage. Then, the 3D average dose rate distribution was calculated. The dose metrics for the mean dose of Liver-GTV and other major OARs were characterized to evaluate the dose quality for the different combinations of field numbers and minimum spot times compared to that of conventional IMPT plans. Dose rate quality was evaluated using 40 Gy/s volume coverage (V40Gy/s).ResultsAll plans achieved favorable and comparable target uniformities, and target uniformity improved as the number of fields increased. For OARs, no significant dose differences were observed between plans of different field numbers and the same MST. For plans using shorter MST and the same field numbers, better sparing was generally observed in most OARs and was statistically significant for the chest wall. However, the FLASH dose rate coverage V40Gy/s was increased by 20% for 2-field plans compared to 5-field plans in most OARs with 2-ms MST, which was less evident in the 0.5-ms cases. For 2-field plans, dose metrics and V40Gy/s of select OARs have large variations due to the beam angle selection and variable distances to the targets. The transmission plans generally yielded inferior dosimetric quality to the conventional IMPT plans.ConclusionThis is the first attempt to assess liver FLASH treatment planning and demonstrates that it is challenging for hypofractionation with smaller fractional doses (4.5 Gy/fraction). Using fewer fields can allow higher minimum MU/spot, resulting in higher OAR FLASH dose rate coverages while achieving similar plan quality compared to plans with more fields. Shorter MST can result in better plan quality and comparable or even better FLASH dose rate coverage.

Reference phantom selection in pediatric computed tomography using data from a large, multicenter registry

Background Radiation dose metrics vary by the calibration reference phantom used to report doses. By convention, 16-cm diameter cylindrical polymethyl-methacyrlate phantoms are used for head imaging and 32-cm diameter phantoms are used for body imaging in adults. Actual usage patterns in children remain under-documented. Objective This study uses the University of California San Francisco International CT Dose Registry to describe phantom selection in children by patient age, body region and scanner manufacturer, and the consequent impact on radiation doses. Materials and methods For 106,837 pediatric computed tomography (CT) exams collected between Jan. 1, 2015, and Nov. 2, 2020, in children up to 17 years of age from 118 hospitals and imaging facilities, we describe reference phantom use patterns by body region, age and manufacturer, and median and 75th-percentile dose–length product (DLP) and volume CT dose index (CTDIvol) doses when using 16-cm vs. 32-cm phantoms. Results There was relatively consistent phantom selection by body region. Overall, 98.0% of brain and skull examinations referenced 16-cm phantoms, and 95.7% of chest, 94.4% of abdomen and 100% of cervical-spine examinations referenced 32-cm phantoms. Only GE deviated from this practice, reporting chest and abdomen scans using 16-cm phantoms with some frequency in children up to 10 years of age. DLP and CTDIvol values from 16-cm phantom-referenced scans were 2–3 times higher than 32-cm phantom-referenced scans. Conclusion Reference phantom selection is highly consistent, with a small but significant number of abdomen and chest scans (~5%) using 16-cm phantoms in younger children, which produces DLP values approximately twice as high as exams referenced to 32-cm phantoms

A Dosimetric Comparison of CT- and Photogrammetry- Generated 3D Printed HDR Brachytherapy Surface Applicators

In this study, we investigate whether an acceptable dosimetric plan can be obtained for a surface applicator designed using photogrammetry and compare the plan quality to a CT-derived applicator. The nose region of a RANDO anthropomorphic phantom was selected as the treatment site due to its high curvature. Photographs were captured using a Nikon D5600 DSLR camera and reconstructed using Agisoft Metashape while CT data was obtained using a Canon Aquillion scanner. Virtual surface applicators were designed in Blender and printed with ABS plastic. Treatment plans with a prescription dose of 3.85 Gy x 10 fractions with 100 % dose to PTV on the bridge of the nose at 2 mm depth were generated separately using AcurosBV in the Varian BrachyVision TPS. PTV D98%, D90% and V100%, and OAR D0.1cc, D2cc and V50% dose metrics and dwell times were evaluated, with the applicator fit assessed by air-gap volume measurements. Both types of surface applicators were printed with minimal defects and visually fitted well to the target area. The measured air-gap volume between the photogrammetry applicator and phantom surface was 44 % larger than the CT-designed applicator, with a mean air gap thickness of 3.24 and 2.88 mm, respectively. The largest difference in the dose metric observed for the PTV and OAR was the PTV V100% of -1.27 % and skin D0.1cc of -0.28 %. PTV D98% and D90% and OAR D2cc and V50% for the photogrammetry based plan were all within 0.5 % of the CT based plan. Total dwell times were also within 5 %. A 3D printed surface applicator for the nose was successfully constructed using photogrammetry techniques. Although it produced a larger air gap between the surface applicator and phantom surface, a clinically acceptable dose plan was created with similar PTV and OAR dose metrics to the CT-designed applicator. Additional future work is required to comprehensively evaluate its suitability in a clinically environment.

Evaluating predictive factors for toxicities experienced by head & neck cancer patients undergoing radiotherapy

Purpose The purpose of this study was to evaluate if HPV status serves as an independent predictor of early and late dysphagia outcomes when considered alongside standard patient characteristics and dose metrics for head and neck cancer patients treated with radiotherapy. Methods and materials The age, sex, smoking history, cancer type (oropharyngeal vs non-oropharyngeal), HPV status, and early and late dysphagia outcomes were obtained for 99 retrospective head and neck cancer patients treated at our clinic with radiotherapy. Additionally for each patient, the mean radiation dose to the pharynx, superior/middle/inferior pharyngeal constrictor muscles, and cricopharyngeus was calculated. The predictive power of these clinical characteristics and radiation metrics was evaluated using chi-square tests for categorical variables and t-tests for continuous variables. Then multi-variate logistic models were built for each outcome using a single dose metric at a time, and either HPV status, cancer type, or both. Multi-variate models were built using both top-down and bottom-up technique to establish the most predictive independent covariates. Results In the univariate analysis for early dysphagia, cancer type (p = 0.04) and four dose metrics (p ≤ 0.02) were significantly associated with outcome, while for late dysphagia, only cancer type (p = 0.04) was associated with outcome. In the multivariate analysis for early dysphagia, cancer type, smoking history, and mean dose to the five structures were consistently selected as covariates. For late dysphagia, either HPV status or cancer type was selected in each model and the mean dose to the cricopharyngeus was selected in one model. Conclusion While HPV is a known contributing factor for tumor prognosis in oropharyngeal cancers, its role in normal tissue toxicities for head and neck cancers has not previously been evaluated. Our results indicate having an oropharyngeal cancer may increase a patient’s risk of high-grade early and late dysphagia while HPV status was seldom selected.

Precision Dosimetry in Yttrium-90 Radioembolization through CT Imaging of Radiopaque Microspheres in a Rabbit Liver Model

Purpose To perform precision dosimetry in yttrium-90 radioembolization through CT imaging of radiopaque microspheres in a rabbit liver model, and to compare extracted dose metrics to those produced from conventional PET-based dosimetry. Materials and Methods A CT calibration phantom was designed to contain posts having nominal microsphere concentrations of 0.5 mg/mL, 5.0 mg/mL, and 25.0 mg/mL. The mean Hounsfield unit was extracted from the post volumes to generate a calibration curve to relate Hounsfield units to microsphere concentration. A nominal bolus of 40 mg of microspheres was administered to the livers of 8 rabbits followed by PET/CT imaging. A CT-based activity distribution was calculated through the application of the calibration curve to the CT liver volume. Post-treatment dosimetry was performed through the convolution of yttrium-90 dose-voxel kernels and the PET- and CT-based cumulated activity distributions. The mean dose to the liver in PET- and CT-based dose distributions was compared through linear regression, ANOVA, and Bland-Altman analysis. Results A linear least-squares fit to the average Hounsfield unit and microsphere concentration data in the calibration phantom confirmed a strong correlation (r2 > 0.999) with a slope of 14.13 HU/mg/mL. A poor correlation was found between the mean dose derived from CT and PET (r2 = 0.374) while the ANOVA analysis revealed statistically significant differences (p < 10–12) between the MIRD-derived mean dose and the PET- and CT-derived mean dose. Bland-Altman analysis predicted an offset of 15.0 Gy between the mean dose in CT and PET. The dose within the liver was shown to be more heterogeneous in CT than in PET with an average coefficient of variation equal to 1.99 and 1.02, respectively. Conclusion The benefits of a CT-based approach to post-treatment dosimetry in yttrium-90 radioembolization include improved visualization of the dose distribution, reduced partial volume effects, a better representation of dose heterogeneity, and the mitigation of respiratory motion effects. Post-treatment CT imaging of radiopaque microspheres in yttrium-90 radioembolization provides the means to perform precision dosimetry and extract accurate dose metrics used to refine the understanding of the dose-response relationship, which can permit an individualized approach to treatment planning that translates into improved patient outcomes.

Effect of Contrast Agent Administration on Size-Specific Dose Estimates (SSDE) Calculations based on Water Equivalent Diameter in CT Head Examinations

Size-specific dose estimate (SSDE) is dose metrics of computed tomography, to calculate SSDE we first calculate the patient's body size. In CT head examination, the head size is better to use water-equivalent diameter (Dw), because Dw considers tissue attenuation. CT Head examination with contrast agent increased patient attenuation and increased Dw. In this study, we observed the effect of contrast agent on the Dw value on the axial image of patients with CT head examination. A total of 96 patients underwent a CT Head examination with a contrast agent in the two CT scan modalities. 46 patients underwent CT Head examination with contrast agent using CT Scanner Toshiba Alexion 16 and 50 patients underwent CT Head examination with contrast agent using CT Scanner GE Medical System Optima CT660. Dw value is calculated automatically using IndoseCT version 20b. We compared the Dw pre-contrast and Dw post-contrast values with the two independent sample t-test statistical analysis. To consider the effect of changing Dw values on SSDE we normalized dose coefficient (NDC). We did not find a significant difference between Dw pre-contrast and Dw post-contrast. The P-value statistical analysis results for the CT Scanner Toshiba Alexion 16 and the CT Scanner GE Medical System Optima CT660 were 0.65 and 0.45. The NDC change in this study was below 20%. On CT Head examination, the Dw and SSDE pre-contrast values can be used to estimate the Dw and SSDE post-contrast values.