Targeting the GTV in medically inoperable endometrial cancer using brachytherapy.

PURPOSE: We aimed to determine the relationship between gross tumor volume (GTV) dose and tumor control in women with medically inoperable endometrial cancer, and to demonstrate the feasibility of targeting a GTV-focused volume using imaged-guided brachytherapy. METHODS AND MATERIALS: An endometrial cancer database was used to identify patients. Treatment plans were reviewed to determine doses to GTV, clinical target volume (CTV), and OARs. Uterine recurrence-free survival was evaluated as a function of CTV and GTV doses. Brachytherapy was replanned with a goal of GTV D98 EQD2 ≥ 80 Gy, without regard for coverage of the uninvolved uterus and while respecting OAR dose constraints. RESULTS: Fifty-four patients were identified. In the delivered plans, GTV D90 EQD2 ≥ 80 Gy was achieved in 36 (81.8%) patients. Uterine recurrence-free survival was 100% in patients with GTV D90 EQD2 ≥ 80 Gy and 66.7% in patients with EQD2 < 80 Gy (p = 0.001). On GTV-only replans, GTV D98 EQD2 ≥ 80 Gy was achieved in 39 (88.6%) patients. Mean D2cc was lower for bladder (47.1 Gy vs. 73.0 Gy, p < 0.001), and sigmoid (47.0 Gy vs. 58.0 Gy, p = 0.007) on GTV-only replans compared to delivered plans. Bladder D2cc was ≥ 80 Gy in 11 (25.0%) delivered plans and four (9.1%) GTV-only replans (p = 0.043). Sigmoid D2cc was ≥ 65 Gy in 20 (45.4%) delivered plans and 10 (22.7%) GTV-only replans (p = 0.021). CONCLUSIONS: OAR dose constraints should be prioritized over CTV coverage if GTV coverage is sufficient. Prospective evaluation of image-guided brachytherapy to a reduced, GTV-focused volume is warranted.

Radiation-induced Hounsfield unit change correlates with dynamic CT perfusion better than 4DCT-based ventilation measures in a novel-swine model.

To analyze radiation induced changes in Hounsfield units and determine their correlation with changes in perfusion and ventilation. Additionally, to compare the post-RT changes in human subjects to those measured in a swine model used to quantify perfusion changes and validate their use as a preclinical model. A cohort of 5 Wisconsin Miniature Swine (WMS) were studied. Additionally, 19 human subjects were recruited as part of an IRB approved clinical trial studying functional avoidance radiation therapy for lung cancer and were treated with SBRT. Imaging (a contrast enhanced dynamic perfusion CT in the swine and 4DCT in the humans) was performed prior to and post-RT. Jacobian elasticity maps were calculated on all 4DCT images. Contours were created from the isodose lines to discretize analysis into 10 Gy dose bins. B-spline deformable image registration allowed for voxel-by-voxel comparative analysis in these contours between timepoints. The WMS underwent a research course of 60 Gy in 5 fractions delivered locally to a target in the lung using an MRI-LINAC system. In the WMS subjects, the dose-bin contours were copied onto the contralateral lung, which received < 5 Gy for comparison. Changes in HU and changes in Jacobian were analyzed in these contours. Statistically significant (p < 0.05) changes in the mean HU value post-RT compared to pre-RT were observed in both the human and WMS groups at all timepoints analyzed. The HU increased linearly with dose for both groups. Strong linear correlation was observed between the changes seen in the swine and humans (Pearson coefficient > 0.97, p < 0.05) at all timepoints. Changes seen in the swine closely modeled the changes seen in the humans at 12 months post RT (slope = 0.95). Jacobian analysis showed between 30 and 60% of voxels were damaged post-RT. Perfusion analysis in the swine showed a statistically significant (p < 0.05) reduction in contrast inside the vasculature 3 months post-RT compared to pre-RT. The increases in contrast outside the vasculature was strongly correlated (Pearson Correlation 0.88) with the reduction in HU inside the vasculature but were not correlated with the changes in Jacobians. Radiation induces changes in pulmonary anatomy at 3 months post-RT, with a strong linear correlation with dose. The change in HU seen in the non-vessel lung parenchyma suggests this metric is a potential biomarker for change in perfusion. Finally, this work suggests that the WMS swine model is a promising pre-clinical model for analyzing radiation-induced changes in humans and poses several benefits over conventional swine models.

Evaluation of a commercial deformable image registration algorithm for dual-energy CT processing.

PURPOSE: Several dual-energy computed tomography (DECT) techniques require a deformable image registration to correct for motion between the acquisition of low and high energy data. However, current DECT software does not provide tools to assess registration accuracy or allow the user to export deformed images, presenting a unique challenge for image registration quality assurance (QA). This work presents a methodology to evaluate the accuracy of DECT deformable registration and to quantify the impact of registration errors on end-product images. METHODS: The deformable algorithm implemented in Siemen Healthineers's Syngo was evaluated using a deformable abdomen phantom and a rigid phantom to mimic sliding motion in the thorax. Both phantoms were imaged using sequential 80 and 140 kVp scans with motion applied between the two scans. Since Syngo does not allow the export of the deformed images, this study focused on quantifying the accuracy of various end-product, dual-energy images resulting from processing of deformed images. RESULTS: The Syngo algorithm performed well for the abdomen phantom with a mean registration error of 0.4 mm for landmark analysis, Dice similarity coefficients (DSCs) > 0.90 for five organs contoured, and mean iodine concentrations within 0.2 mg/mL of values measured on static images. For rigid sliding motion, the algorithm performed poorer and resulted in noticeable registration errors toward the superior and inferior scan extents and DSCs as low as 0.41 for iodine rods imaged in the phantom. Additionally, local iodine concentration errors in areas of misregistration exceeded 3 mg/mL. CONCLUSIONS: This work represents the first methodology for DECT image registration QA using commercial software. Our data support the clinical use of the Syngo algorithm for abdominal sites with limited motion (i.e., pancreas and liver). However, dual-energy images generated with this algorithm should be used with caution for quantitative measurements in areas with sliding motion.

Investigating split-filter dual-energy CT for improving liver tumor visibility for radiation therapy.

PURPOSE: Accurate liver tumor delineation is crucial for radiation therapy, but liver tumor volumes are difficult to visualize with conventional single-energy CT. This work investigates the use of split-filter dual-energy CT (DECT) for liver tumor visibility by quantifying contrast and contrast-to-noise ratio (CNR). METHODS: Split-filter DECT contrast-enhanced scans of 20 liver tumors including cholangiocarcinomas, hepatocellular carcinomas, and liver metastases were acquired. Analysis was performed on the arterial and venous phases of mixed 120 kVp-equivalent images and VMIs at 57 keV and 40 keV gross target volume (GTV) contrast and CNR were calculated. RESULTS: For the arterial phase, liver GTV contrast was 12.1 ± 10.0 HU and 43.1 ± 32.3 HU (P < 0.001) for the mixed images and 40 keV VMIs. Image noise increased on average by 116% for the 40 keV VMIs compared to the mixed images. The average CNR did not change significantly (1.6 ± 1.5, 1.7 ± 1.4, 2.4 ± 1.7 for the mixed, 57 keV and 40 keV VMIs (P > 0.141)). For individual cases, however, CNR increases of up to 607% were measured for the 40 keV VMIs compared to the mixed image. Venous phase 40 keV VMIs demonstrated an average increase of 35.4 HU in GTV contrast and 121% increase in image noise. Average CNR values were also not statistically different, but for individual cases CNR increases of up to 554% were measured for the 40 keV VMIs compared to the mixed image. CONCLUSIONS: Liver tumor contrast was significantly improved using split-filter DECT 40 keV VMIs compared to mixed images. On average, there was no statistical difference in CNR between the mixed images and VMIs, but for individual cases, CNR was greatly increased for the 57 keV and 40 keV VMIs. Therefore, although not universally successful for our patient cohort, split-filter DECT VMIs may provide substantial gains in tumor visibility of certain liver cases for radiation therapy treatment planning.

Monte Carlo and 60 Co-based kilovoltage x-ray dosimetry methods.

PURPOSE: This work seeks to investigate new methods to determine the absorbed dose to water from kilovoltage x rays. Current methods are based on measurements in air and rely on correction factors in order to account for differences between the photon spectrum in air and at depth in phantom, between the photon spectra of the calibration beam and the beam of interest, or in the radiation absorption properties of air and water. This work aims to determine the absorbed dose to water in the NIST-matched x-ray beams at the University of Wisconsin Accredited Dosimetry Calibration Laboratory (UWADCL). This will facilitate the use of detectors in terms of dose to water, which will allow for a simpler determination of dose to water in clinical kilovoltage x-ray beams. MATERIALS AND METHODS: A model of the moderately filtered x-ray beams at the UWADCL was created using the BEAMnrc user code of the EGSnrc Monte Carlo code system. This model was validated against measurements and the dose to water per unit air kerma was calculated in a custom built water tank. Using this value and the highly precise measurement of the air kerma made by the UWADCL, the dose to water was determined in the water tank for the x-ray beams of interest. The dose to water was also determined using the formalism defined in the report of AAPM Task Group 61 and using a method that makes use of a 60 Co absorbed dose-to-water calibration coefficient and a beam quality correction factor to account for differences in beam quality between the 60 Co calibration and kilovoltage x-ray beam of interest. The dose to water values as determined by these different methods was then compared. RESULTS: The BEAMnrc models used in this work produced simulations of transverse and depth dose profiles that agreed with measurements with a 2%/2 mm criteria gamma test. The dose to water as determined from the different methods used here agreed within 3.5% at the surface of the water tank and agreed within 1.8% at a depth of 2 cm in phantom. The dose-to-water values all agreed within the associated uncertainties of the methods used in this work. Both the Monte Carlo-based method and the 60 Co-based method had a lower uncertainty than the TG-61 methodology for all of the x-ray beams used in this work. CONCLUSION: Two new dose determination methods were used to determine the dose to water in the NIST-matched x-ray beams at the UWADCL and they showed good agreement with previously established techniques. Due to the improved Monte Carlo calculation techniques used in this work, both of the methods have lower uncertainties compared to TG-61. The methods presented in this work compare favorably with calorimetry-based standards established at other institutions.

Design of a modulated orthovoltage stereotactic radiosurgery system.

PURPOSE: To achieve stereotactic radiosurgery (SRS) dose distributions with sharp gradients using orthovoltage energy fluence modulation with inverse planning optimization techniques. METHODS: A pencil beam model was used to calculate dose distributions from an orthovoltage unit at 250 kVp. Kernels for the model were derived using Monte Carlo methods. A Genetic Algorithm search heuristic was used to optimize the spatial distribution of added tungsten filtration to achieve dose distributions with sharp dose gradients. Optimizations were performed for depths of 2.5, 5.0, and 7.5 cm, with cone sizes of 5, 6, 8, and 10 mm. In addition to the beam profiles, 4π isocentric irradiation geometries were modeled to examine dose at 0.07 mm depth, a representative skin depth, for the low energy beams. Profiles from 4π irradiations of a constant target volume, assuming maximally conformal coverage, were compared. Finally, dose deposition in bone compared to tissue in this energy range was examined. RESULTS: Based on the results of the optimization, circularly symmetric tungsten filters were designed to modulate the orthovoltage beam across the apertures of SRS cone collimators. For each depth and cone size combination examined, the beam flatness and 80-20% and 90-10% penumbrae were calculated for both standard, open cone-collimated beams as well as for optimized, filtered beams. For all configurations tested, the modulated beam profiles had decreased penumbra widths and flatness statistics at depth. Profiles for the optimized, filtered orthovoltage beams also offered decreases in these metrics compared to measured linear accelerator cone-based SRS profiles. The dose at 0.07 mm depth in the 4π isocentric irradiation geometries was higher for the modulated beams compared to unmodulated beams; however, the modulated dose at 0.07 mm depth remained <0.025% of the central, maximum dose. The 4π profiles irradiating a constant target volume showed improved statistics for the modulated, filtered distribution compared to the standard, open cone-collimated distribution. Simulations of tissue and bone confirmed previously published results that a higher energy beam (≥ 200 keV) would be preferable, but the 250 kVp beam was chosen for this work because it is available for future measurements. CONCLUSIONS: A methodology has been described that may be used to optimize the spatial distribution of added filtration material in an orthovoltage SRS beam to result in dose distributions with decreased flatness and penumbra statistics compared to standard open cones. This work provides the mathematical foundation for a novel, orthovoltage energy fluence-modulated SRS system.

Response of TLD-100 in mixed fields of photons and electrons.

PURPOSE: Thermoluminescent dosimeters (TLDs) are routinely used for dosimetric measurements of high energy photon and electron fields. However, TLD response in combined fields of photon and electron beam qualities has not been characterized. This work investigates the response of TLD-100 (LiF:Mg,Ti) to sequential irradiation by high-energy photon and electron beam qualities. METHODS: TLDs were irradiated to a known dose by a linear accelerator with a 6 MV photon beam, a 6 MeV electron beam, and a NIST-traceable (60)Co beam. TLDs were also irradiated in a mixed field of the 6 MeV electron beam and the 6 MV photon beam. The average TLD response per unit dose of the TLDs for each linac beam quality was normalized to the average response per unit dose of the TLDs irradiated by the (60)Co beam. Irradiations were performed in water and in a Virtual Water™ phantom. The 6 MV photon beam and 6 MeV electron beam were used to create dose calibration curves relating TLD response to absorbed dose to water, which were applied to the TLDs irradiated in the mixed field. RESULTS: TLD relative response per unit dose in the mixed field was less sensitive than the relative response in the photon field and more sensitive than the relative response in the electron field. Application of the photon dose calibration curve to the TLDs irradiated in a mixed field resulted in an underestimation of the delivered dose, while application of the electron dose calibration curve resulted in an overestimation of the dose. CONCLUSIONS: The relative response of TLD-100 in mixed fields fell between the relative response in the photon-only and electron-only fields. TLD-100 dosimetry of mixed fields must account for this intermediate response to minimize the estimation errors associated with calibration factors obtained from a single beam quality.