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A stochastic model of cell survival for high‐Z nanoparticle radiotherapy

PURPOSE The authors present a stochastic framework for the assessment of cell survival in gold nanoparticle radiotherapy. METHODS The authors derive the equations for the effective macroscopic dose enhancement for a population of cells with nonideal distribution of gold nanoparticles (GNP), allowing different number of GNP per cell and different distances with respect to the cellular target. They use the mixed Poisson distribution formalism to model the impact of the aforementioned physical factors on the effective dose enhancement. RESULTS The authors show relatively large differences in the estimation of cell survival arising from using approximated formulae. They predict degeneration of the cell killing capacity due to different number of GNP per cell and different distances with respect to the cellular target. CONCLUSIONS The presented stochastic framework can be used in interpretation of experimental cell survival or tumor control probability studies.

Targeted radiotherapy enhancement during electronic brachytherapy of accelerated partial breast irradiation (APBI) using controlled release of gold nanoparticles

Several studies have demonstrated low rates of local recurrence with brachytherapy-based accelerated partial breast irradiation (APBI). However, long-term outcomes on toxicity (e.g. telangiectasia) and cosmesis remain a major concern. The purpose of this study is to investigate the dosimetric feasibility of using targeted non-toxic radiosensitizing gold nanoparticles (GNPs) for localized dose enhancement to the planning target volume (PTV) during electronic brachytherapy APBI while reducing normal tissue toxicity. We propose to incorporate GNPs into a micrometer-thick polymer film on the surface of routinely used lumpectomy balloon applicators and provide subsequent treatment using a 50 kVp Xoft device. An experimentally determined diffusion coefficient was used to determine space-time customizable distribution of GNPs for feasible in-vivo concentrations of 7 mg/g and 43 mg/g. An analytical approach from previously published work was employed to estimate the dose enhancement due to GNPs as a function of distance up to 1 cm from the lumpectomy cavity surface. Clinically significant dose enhancement values of at least 1.2, due to 2 nm GNPs, were found at 1 cm away from the lumpectomy cavity wall when using electronic brachytherapy APBI. Higher customizable dose enhancement was also achieved at other distances as a function of nanoparticle size. Our preliminary results suggest that significant dose enhancement can be achieved to residual tumor cells targeted with GNPs during APBI with electronic brachytherapy.

Low-Z linac targets for low-MV gold nanoparticle radiation therapy

PURPOSE To investigate the potential of low-Z/low-MV (low-Z) linac targets for gold nanoparticle radiotherapy (GNPT) and to determine the microscopic dose enhancement ratio (DER) due to GNP for the alternative beamlines. In addition, to evaluate the degradation of dose enhancement arising from the increased attenuation of x rays and larger skin dose in water for the low-MV beams compared to the standard linac. METHODS Monte Carlo simulations were used to compute dose and DER for various flattening-filter-free beams (2.5, 4, 6.5 MV). Target materials were beryllium, diamond, and tungsten-copper high-Z target. Target thicknesses were selected based on 20%, 60%, 70%, and 80% of the continuous slowing down approximation electron ranges for a given target material and energy. Evaluation of the microscopic DER was carried out for 100 nm GNP including the degradation factors due to beam attenuation. RESULTS The greatest increase in DER compared to the standard 6.5 MV linac was for a 2.5 MV Be-target (factor of ∼ 2). Skin dose ranged from ∼ 10% (Be, 6.5 MV-80%) to ∼ 85% (Be, 2.5 MV-20%) depending on the target case. Attenuation of 2.5 MV beams at 22 cm was higher by ∼ 75% compared with the standard beam. Taking into account the attenuation at 22 cm depth, the effective dose enhancement was up to ∼ 60% above the DER of the high-Z target. For these cases the effective DER ranged between ∼ 1.6 and 6 compared with the standard linac. CONCLUSIONS Low-Z (2.5 MV) GNPT is possible even after accounting for greater beam attenuation for deep-seated tumors (22 cm) and the increased skin dose. Further, it can lead to significant sparing of normal tissue while simultaneously escalating the dose in the tumor cells.

SU‐E‐T‐35: Optimal Clinical Megavoltage X‐Ray Beam Quality for Contrast Enhanced RT (CERT)

Purpose: To determine the optimal beam quality of MV‐x‐rays for Contrast Enhanced RT (CERT) based on analysis of a broad database of clinical beams. Methods: EGSnrc was used to calculate spectra and doses for various irradiation conditions (6MV EX linac): flattened (STD) vs unflattened (FFF) beams, open/IMRT fields, in‐/out‐off‐field areas as a function of depth in water and field size. Spectral differences were quantified and related to dose enhancement (DE) effects by introducing two metrics: an energy‐dependent dose enhancement ratio DER(E) and an effective DER for the entire spectrum. Using these two metrics the dosimetric impact of spectral changes were studied for different materials (gadolinium‐oxysulfide (Gd2O2S) and gold).Results: DER proved to be a good predictor for high‐DE effects for the whole spectrum of each beam. However, the DER(E) metric revealed energy‐specific effects hidden in the overall analysis. Spectral analysis with DER(E) showed that all DE effects are directly related to the spectral region <∼200KeV. The highest DE effects appear for FFF spectra and out‐of‐field cases. Differences in DER values can reach over one order of magnitude, depending on the case and the heterogeneity of the medium. For shallower depths behavior of FFF/STD beams is practically the same but as depth increases DE effects of FFF beams undergo more changes than STD beams. Conclusions: DER increases with depth, field size, distance from the CAX and OB vs IMRT due to the increased scatter and concomitant softening of the beam. Differences in DER can be more than one order of magnitude, depending on the case and the medium. The greatest dose enhancement is achieved with FFF (lower effective energy) and with other beams of large scatter content. Complex IMRT is better for CERT compared to conformal plans because of much greater photon scatter from various sources increasing the fluence below 200KeV.

WE-D-303-03: 3D Delivered Dose Assessment Using a 4DCT-Based Motion Model

Purpose: To develop a clinically feasible method of calculating actual delivered dose for patients with significant respiratory motion during the course of SBRT. Methods: This approach can be specified in three steps. (1) At planning stage, a patient-specific motion model is created from planning 4DCT using a principal components analysis (PCA) algorithm. (2) During treatment, 2D time-varying projection images (either kV or MV projections) are acquired, from which time-varying ‘fluoroscopic’ 3D images of the patient are reconstructed using the motion model. (3) A 3D dose distribution is computed for each timepoint in the set of 3D fluoroscopic images, from which the total effective 3D delivered dose is calculated by accumulating dose distributions onto a reference image. This approach was validated using two modified XCAT phantoms with lung tumors and different respiratory motions. The estimated doses were compared to the dose that would be calculated for 4DCT-based planning and to the actual delivered dose that was calculated using “ground truth” XCAT phantoms. The approach was also tested using one set of patient data. Results: For the XCAT phantom with a regular breathing pattern, the errors in D95 are 0.11% and 0.83% respectively for kV and MV reconstructions compared to the ground truth, which is comparable to 4DCT (0.093%). For the XCAT phantom with an irregular breathing pattern, the errors are 0.81% and 1.75% for kV and MV reconstructions, both better than that of 4DCT (4.01%). For real patient, the dose estimation is clinically reasonable and demonstrates differences between 4DCT and MV reconstruction-based estimation. Conclusions: Using kV or MV projections, the proposed approach is able to assess delivered doses for all respiratory phases during treatment. Compared to the 4DCT dose, the dose estimation using reconstructed 3D fluoroscopic images is as good for regular respiratory pattern and better for irregular respiratory pattern.

SU‐E‐T‐352: Effects of Skull Attenuation and Missing Backscatter On Brain Dose in HDR Treatment of the Head with Surface Applicators

Purpose: To calculate the effect of lack of backscatter from air and attenuation of bone on dose distributions in brachytherapy surface treatment of head. Existing treatment planning systems based on TG43 do not account for heterogeneities, and thus may overestimate the dose to the brain. While brachytherapy generally has rapid dose falloff, the dose to the deeper tissues (in this case, the brain) can become significant when treating large curved surfaces. Methods: Applicator geometries representing a range of clinical cases were simulated in MCNP5. An Ir-192 source was modeled using the energy spectrum presented by TG-43. The head phantom was modeled as a 7.5-cm radius water sphere, with a 7 -mm thick skull embedded 5-mm beneath the surface. Dose values were calculated at 20 points inside the head, in which 10 of them were on the central axis and the other 10 on the axis connecting the central of the phantom with the second to last source from the applicator edge. Results: Central and peripheral dose distributions for a range of applicator and head sizes are presented. The distance along the central axis at which the dose falls to 80% of the prescribed dose (D80) was 7 mm for a representative small applicator and 9 mm for a large applicator. Corresponding D50 and D30 for the same small applicator were 17 mm and 32 mm respectively. D50 and D30 for the larger applicator were 32 mm and 60 mm respectively. These results reflect the slower falloff expected for larger applicators on a curved surface. Conclusion: Our results can provide guidance for clinicians to calculate the dose reduction effect due to bone attenuation and the lack of backscatter from air to estimate the brain dose for the HDR treatments of surface lesions.

SU-E-I-03: Lateral Truncation Artifact Correction for 4DCBCT-Based Motion Modeling and Dose Assessment

Purpose: To allow accurate motion modeling and dose assessment based on 4DCBCT by addressing the limited field of view (FOV) and lateral truncation artifacts in current clinical CBCT systems. Due to the size and geometry of onboard flat panel detects, CBCT often cannot cover the entire thorax of adult patients. We implement method to extend the images generated from 4DCBCT-based motion models and correct lateral truncation artifacts. Methods: The method is based on deforming a reference 4DCT image containing the entire patient anatomy to the (smaller) CBCT image within the higher quality CBCT FOV. Next, the displacement vector field (DVF) derived inside the CBCT FOV is smoothly extrapolated out to the edges of the body. These extrapolated displacement vectors are used to generate a new body contour and HU values outside of the CBCT FOV. This method is applied to time-varying volumetric images (3D fluoroscopic images) generated from a 4DCBCT-based motion model at 2 Hz. Six XCAT phantoms are used to test this approach and reconstruction accuracy is investigated. Results: The normalized root mean square error between the corrected images generated from the 4DCBCT-based motion model and the ground truth XCAT phantom at each time point is generally less than 20%. These results are comparable to results from 4DCT-based motion models. The anatomical structures outside the CBCT FOV can be reconstructed with an error comparable to that inside the FOV. The resulting noise is comparable to that of 4DCT. Conclusions: The proposed approach can effectively correct the artifact due to lateral truncation in 4DCBCT-based motion models. The quality of the resulting images is comparable to images generated from 4DCT-based motion models. Capturing the body contour and anatomy outside the CBCT FOV makes more reasonable dose calculations possible.

WE-G-207-06: 3D Fluoroscopic Image Generation From Patient-Specific 4DCBCT-Based Motion Models Derived From Physical Phantom and Clinical Patient Images

Purpose: Respiratory-correlated cone-beam CT (4DCBCT) images acquired immediately prior to treatment have the potential to represent patient motion patterns and anatomy during treatment, including both intra- and inter-fractional changes. We develop a method to generate patient-specific motion models based on 4DCBCT images acquired with existing clinical equipment and used to generate time varying volumetric images (3D fluoroscopic images) representing motion during treatment delivery. Methods: Motion models are derived by deformably registering each 4DCBCT phase to a reference phase, and performing principal component analysis (PCA) on the resulting displacement vector fields. 3D fluoroscopic images are estimated by optimizing the resulting PCA coefficients iteratively through comparison of the cone-beam projections simulating kV treatment imaging and digitally reconstructed radiographs generated from the motion model. Patient and physical phantom datasets are used to evaluate the method in terms of tumor localization error compared to manually defined ground truth positions. Results: 4DCBCT-based motion models were derived and used to generate 3D fluoroscopic images at treatment time. For the patient datasets, the average tumor localization error and the 95th percentile were 1.57 and 3.13 respectively in subsets of four patient datasets. For the physical phantom datasets, the average tumor localization error and the 95th percentile were 1.14 and 2.78 respectively in two datasets. 4DCBCT motion models are shown to perform well in the context of generating 3D fluoroscopic images due to their ability to reproduce anatomical changes at treatment time. Conclusion: This study showed the feasibility of deriving 4DCBCT-based motion models and using them to generate 3D fluoroscopic images at treatment time in real clinical settings. 4DCBCT-based motion models were found to account for the 3D non-rigid motion of the patient anatomy during treatment and have the potential to localize tumor and other patient anatomical structures at treatment time even when inter-fractional changes occur. This project was supported, in part, through a Master Research Agreement with Varian Medical Systems, Inc., Palo Alto, CA. The project was also supported, in part, by Award Number R21CA156068 from the National Cancer Institute.