S Benedict

Tumor cell survival dependence on helical tomotherapy, continuous arc and segmented dose delivery

The temporal pattern of radiation delivery has been shown to influence the tumor cell survival fractions for the same radiation dose. To study the effect more specifically for state of the art rotational radiation delivery modalities, 2 Gy of radiation dose was delivered to H460 lung carcinoma, PC3 prostate cancer cells and MCF-7 breast tumor cells by helical tomotherapy (HT), seven-field LINAC (7F), and continuous dose delivery (CDD) over 2 min that simulates volumetric rotational arc therapy. Cell survival was measured by the clonogenic assay. The number of viable H460 cell colonies was 23.2 +/- 14.4% and 27.7 +/- 15.6% lower when irradiated by CDD compared with HT and 7F, respectively, and the corresponding values were 36.8 +/- 18.9% and 35.3 +/- 18.9% lower for MCF7 cells (p < 0.01). The survival of PC3 was also lower when irradiated by CDD than by HT or 7F but the difference was not as significant (p = 0.06 and 0.04, respectively). The higher survival fraction from HT delivery was unexpected because 90% of the 2 Gy was delivered in less than 1 min at a significantly higher dose rate than the other two delivery techniques. The results suggest that continuous dose delivery at a constant dose rate results in superior in vitro tumor cell killing compared with prolonged, segmented or variable dose rate delivery.

The implication of non-cyclic intrafractional longitudinal motion in SBRT by TomoTherapy

To determine the dosimetric impact of non-cyclic longitudinal intrafractional motion, TomoTherapy plans with different field sizes were interrupted during a phantom delivery, and a displacement between -5 mm and 5 mm was induced prior to the delivery of the completion procedure. The planar dose was measured by film and a cylindrical phantom, and under-dosed or over-dosed volume was observed for either positive or negative displacement. For a 2.5 cm field, there was a 4% deviation for every mm of motion and for a 1 cm field, the deviation was 8% per mm. The dimension of the under/over-dosed area was independent of the motion but dependent on the field size. The results have significant implication in small-field high-dose treatments (i.e. stereotactic body radiation therapy (SBRT)) that deliver doses in only a few fractions. Our studies demonstrate that a small longitudinal motion may cause a dose error that is difficult to compensate; however, dividing a SBRT fraction into smaller passes is helpful to reduce such adverse effects.

Novel FRET-Based Radiosensitization Using Quantum Dot-Photosensitizer Conjugates

A novel radiosensitizer was synthesized by covalently conjugating quantum dots (QDs) to a photosensitizer. We hypothesized that QDs excited by 6-MV X-rays would serve as an energy donor to activate the photosensitizer. Photon emission from QDs was linearly proportional to radiation dose rate. Donor quenching in conjugates indicated that activation of photosensitizer occurred by Forster resonance energy transfer. Radiation treatment of lung carcinoma cells with conjugate increased cell killing by 34% compared to radiation alone. Cell toxicity in non-irradiated controls was negligible. Thus, this conjugate acts via a novel mechanism of radiosensitization that will improve treatment of deeply seated tumors.

Quantification of regional lung ventilation from tagged hyperpolarized helium-3 MRI

In this paper we propose a new scheme for measuring regional ventilation from tagged hyperpolarized helium-3 MR images. A new registration cost function that incorporates both the intensity information (SSD) and the shape feature (SSBMD) from the images is proposed for registering end inspiration to the end expiration image. The smoothness of the displacement field is maintained by incorporating the Laplacian regularization constraint (LAP) in the total cost function. The ventilation is quantified using the Jacobian determinant of the resulting displacement field from the proposed registration algorithm. Tags are automatically segmented from the images to evaluate the registration accuracy. The average tag positioning error is on the order of 2 mm after registration for all three subjects. These results may provide new method for assessing regional lung ventilation and may be used to track regional function changes of lung cancer patients following radiation therapy.

SRT and SBRT: Current practices for QA dosimetry and 3D

The major feature that separates stereotactic radiation therapy (cranial SRT) and stereotactic body radiation therapy (SBRT) from conventional radiation treatment is the delivery of large doses in a few fractions which results in a high biological effective dose (BED). In order to minimize the normal tissue toxicity, quality assurance of the conformation of high doses to the target and rapid fall off doses away from the target is critical. The practice of SRT and SBRT therefore requires a high-level of confidence in the accuracy of the entire treatment delivery process. In SRT and SBRT confidence in this accuracy is accomplished by the integration of modern imaging, simulation, treatment planning and delivery technologies into all phases of the treatment process; from treatment simulation and planning and continuing throughout beam delivery. In this report some of the findings of Task group 101 of the AAPM will be presented which outlines the best-practice guidelines for SBRT. The task group report includes a review of the literature to identify reported clinical findings and expected outcomes for this treatment modality. Information in this task group is provided for establishing an SBRT program, including protocols, equipment, resources, and QA procedures.

SU‐E‐T‐790: The Effect of Pulmonary Emphysema on Lung SBRT Dosimetry

Purpose: The purpose of this study is to systematically analyze the effect of pulmonary emphysema (PE) on the dosimetric results for intensity modulated arc therapy (IMAT). Methods: One patient diagnosed with non‐small cell lungcancer was chosen as the model patient. Hypothetic tumors with volumes of 2cc, 48cc and 169cc were contoured in the right middle lung. GPU based helical tomotherapy IMRT planning system is used in the study. 50 Gy in 5 fractions were prescribed to planning target volume (PTV). The planning parameters include a jaw size of 2.5 cm and 1cm, a pitch of 0.287 and 0.1, and dosimetric constrains according to RTOG 0813. To simulate emphysema lung density was overwritten from 0.05 to 0.4 g/cc. The dosimetric results such as tumor coverage, R50, and lung V20 were analyzed. Results: All plans satisfy 95% of PTV receiving 50Gy prescription. Lung density has a significant effect on the dosimetric results for all tumor sizes studied. For plans with jaw size of 2.5 cm and pitch of 0.287, R50 increases by as much as 92%, 55% and 35% for PTV of 2cc, 48cc and 169cc, when the lung density was reduced from 0.3 to 0.05 g/cc. Similarly, lung V20 increases by 32%, 20% and 18% for PTV of 2cc, 48cc and 169cc, respectively. Interestingly, for plans with jaw size of 1cm and pitch of 0.1, although the R50 for different tumor sizes follows similar trend as 2.5cm plans, the effect of lung density on V20 is non‐linear. For PTV of 2cc and 48cc, V20 plot shows a peak with varying lung densities. Conclusions: Systematic planning studies show that lower lung densities generally result in poorer dosimetry due to the greater difficulty to achieve electron equilibrium. Therefore, the lung density should be taken into consideration in the lungSBRT protocol.

SU‐E‐J‐158: A Phantom Study Based Simulation to Quantify the Motion and Tumor Volume Affected 18F‐FDG PET Uptake Distribution Within the Tumor

Purpose: Molecular imaging studies reveal tumor heterogeneity which may explain therapeutic resistance. Alternatively, variations observed in the SUV uptake may not be due to intrinsic heterogeneity of the tumor, but due to effects of position resolution (volume dependence) or tumor motion . The objective of this study is to evaluate motion artifacts on PET SUV uptake within tumors for different volumes. Methods: We conducted a phantom study: spheres of homogeneous18F‐FDG activity of motion amplitudes (0, 5, 10, 15, 20, 25, 30 mm) and volumes (internal diameter 10, 13, 17, 22, 28, 37 mm). Any variation observed in SUV uptake distribution with homogeneous activity spheres must be due to motion and volume effects. Therefore, we used this data to quantify uptake variations as a function of motion and volume. PET SUV uptake values for each tumor were fit with a Woods‐Saxon model with 2 parameters: radius and skin depth. When the ratio of radius to skin depth becomes small, this simplifies to a Gaussian. By using this parameterization for stationary phantoms, using the probability density function for motion, and using an image convolution technique we were able to simulate the SUV uptake distribution of moving tumor in the central 2D plane. Taking voxel by voxel SUV uptake distribution in 2D we quantified the accuracy of our simulation for motion affected, tumor volume affected SUV uptake heterogeneity within the phantom. Results: Phantom study for stationary spheres show motion has a high impact on SUV uptake distributions. Maximum percentage uptake variation across the phantoms was 22%. Convolution results confirm that motion is the largest contributor to the SUV heterogeneity of the tumors. Average difference between convolution and measurement is 6.7%. Conclusion: These results will impact the studies that utilize tumor heterogeneity such as tumor detection, planning with dose painting, and treatment response. UVA Radiation Oncology george Amarino Grant ‐ 2012

SU‐E‐T‐32: The Use of Monte Carlo Method as an Independent Dose Verification Calculation Tool for TomoTherapy

Purpose: It has been widely recognized, as stated in a ICRP 2009 report, that a secondary calculation, independent from treatment‐planning‐system (TPS), has proven to be an efficient tool for prevention of major errors in dose delivery. The purpose of this study is to develop such tool for TomoTherapy system. Methods: A Monte Carlo tool that has been validated previously, TomoPen, was modified to have better integration with the TomoTherapy software. Patient plan and CT information is DICOM exported. The Monte Carlo tool reads the plan and CT information from the dicom file and computes the dose. The Monte Carlo computed dose is compared with the TPS dose to make sure no major deviation is observed. Results: The tool has been tested on several clinical patient plans. By using a coarse dose grid, a decent dose distribution can be obtained in less than an hour on an Intel i7 CPU. The run time can be further reduced by using a computer cluster. The time takes for this secondary calculation is comparable with the standard DQA plan creation and measurement. However, the secondary calculation does not take the treatment machine time as well as physicists time. Conclusions: A Monte Carlo based secondary calculation tool is developed to prevent major errors in TomoTherapy delivery. It is shown that it can be fitted into the current clinical workflow.

SU‐D‐BRB‐05: Small Animal Lung Compliance Imaging: Assessment System for Tissue Sensitivity to Radiation Induced Lung Injury

PURPOSE Recent clinical trials and animal studies have indicated that the tissue sensitivity to radiation induced lung injury (RILI) may be region- specific. In this study, we propose a new 4D cone beam CT (CBCT) basedcompliance imaging method to measure regional pulmonary function change in precisely irradiated small animal under CBCT guidance on small animal radiation research platform (SARRP) to facilitate our understanding of region-specific tissue sensitivity to RILI. METHODS Four Sprague-Dawley rats underwent prospective pressure gated 4D CBCT on SARRP. Three animals were selected as control group which underwent a second 4D CBCT scan. The fourth animal was irradiated in the central lung (24 Gy) using 3 × 3 mm collimating cone 2 months prior to the scan. The specific compliance (Csp) was calculated via the real time pressure measurement from the ventilator and displacement field from 3D B-spline image registration between the end of inhale and end of exhale phases from the 4D CBCT scan. The 3D Csp maps from the control animal group were mapped to the irradiated animal as a Csp functional atlas for statistical analysis. We alsoevaluated the repeatability of the Csp measurement on a voxel-by-voxel basis. RESULTS No significant Csp difference is found after two month of radiation between the irradiated rat (0.22±0.05) and the functional atlas (0.21±0.07). The observation is consistent with previous publications. The averaged linear correlation coefficient between the voxel-by-voxel Csp measurements from initial and repeat scans in control group is 0.98. CONCLUSIONS We proposed a method that uses 4D CBCT based compliance imaging to measure region-specific tissue sensitivity of RILI. We compared the irradiated animal two months after radiation with the control group. Our study shows an excellent robustness of the proposed method for regional lung tissue specific compliance measurement. This work was supported in part by UVa George Amorino Pilot Grant.

SU‐E‐J‐192: Static Breath‐Hold MRI Based Measurement of Change in Pulmonary Function Following a Course of Radiation Therapy

PURPOSE Radiation Therapy (RT) induced pulmonary function change may depend on the location, underlying function of that lung prior to radiations, radiation dose/fractionation and other factors. We propose to evaluate the radiation induced pulmonary function change using static breath-hold MRI scans with vascular information and 3D deformable image registration which can provide pulmonary function relative to RT dose on a regional basis. METHODS A MRI scan pair near the end of inhale and near the end of exhale with breath hold were acquired for one lung cancer patient before RT and 6 months after RT. The patient was treated with SBRT with 55 Gy to PTVs in the right and the left lung respectively. B-spline based vesselness preserving image registration algorithm was applied to register the MRI pair for the calculation of local lung expansion as a measurement of regional pulmonary function (PF). The PF maps before RT and after RT were then mapped to the planning CT using the same algorithm tuned for MRI-CT registration. The pulmonary function change was calculated via the PF ratio between two MRI pairs. RESULTS Strong spatial correlation was found between the irradiated lung region and the region with greatly decreased PF. Based on dose and PFC distribution, no strong determinant factor was found for PF lost in the left lung while the right lung shows that all the lung tissue receiving dose larger than 28 Gy will have a decreased PF. CONCLUSIONS We demonstrated a method that uses static breath-hold MRI based lung imaging to evaluate radiation induced pulmonary function change which can be applied to study the dose and the pulmonary function change in a regional basis. This work is supported by NIH grant support 1R21CA144063.