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At least 613 records · Page 34

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DOE OSTI2015

Technical Note: Intrafractional changes in time lag relationship between anterior–posterior external and superior–inferior internal motion signals in abdominal tumor sites

Purpose: To investigate constancy, within a treatment session, of the time lag relationship between implanted markers in abdominal tumors and an external motion surrogate. Methods: Six gastroesophageal junction and three pancreatic cancer patients (IRB-approved protocol) received two cone-beam CTs (CBCT), one before and one after treatment. Time between scans was less than 30 min. Each patient had at least one implanted fiducial marker near the tumor. In all scans, abdominal displacement (Varian RPM) was recorded as the external motion signal. Purpose-built software tracked fiducials, representing internal signal, in CBCT projection images. Time lag between superior–inferior (SI) internal and anterior–posterior external signals was found by maximizing the correlation coefficient in each breathing cycle and averaging over all cycles. Time-lag-induced discrepancy between internal SI position and that predicted from the external signal (external prediction error) was also calculated. Results: Mean ± standard deviation time lag, over all scans and patients, was 0.10 ± 0.07 s (range 0.01–0.36 s). External signal lagged the internal in 17/18 scans. Change in time lag between pre- and post-treatment CBCT was 0.06 ± 0.07 s (range 0.01–0.22 s), corresponding to 3.1% ± 3.7% (range 0.6%–10.8%) of gate width (range 1.6–3.1 s). In only one patient, change in time lag exceeded 10% of the gate width. External prediction error over all scans of all patients varied from 0.1 ± 0.1 to 1.6 ± 0.4 mm. Conclusions: Time lag between internal motion along SI and external signals is small compared to the treatment gate width of abdominal patients examined in this study. Change in time lag within a treatment session, inferred from pre- to post-treatment measurements is also small, suggesting that a single measurement of time lag at the session start is adequate. These findings require confirmation in a larger number of patients.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

Gradient maintenance: A new algorithm for fast online replanning

Purpose: Clinical use of online adaptive replanning has been hampered by the unpractically long time required to delineate volumes based on the image of the day. The authors propose a new replanning algorithm, named gradient maintenance (GM), which does not require the delineation of organs at risk (OARs), and can enhance automation, drastically reducing planning time and improving consistency and throughput of online replanning. Methods: The proposed GM algorithm is based on the hypothesis that if the dose gradient toward each OAR in daily anatomy can be maintained the same as that in the original plan, the intended plan quality of the original plan would be preserved in the adaptive plan. The algorithm requires a series of partial concentric rings (PCRs) to be automatically generated around the target toward each OAR on the planning and the daily images. The PCRs are used in the daily optimization objective function. The PCR dose constraints are generated with dose–volume data extracted from the original plan. To demonstrate this idea, GM plans generated using daily images acquired using an in-room CT were compared to regular optimization and image guided radiation therapy repositioning plans for representative prostate and pancreatic cancer cases. Results: The adaptive replanning using the GM algorithm, requiring only the target contour from the CT of the day, can be completed within 5 min without using high-power hardware. The obtained adaptive plans were almost as good as the regular optimization plans and were better than the repositioning plans for the cases studied. Conclusions: The newly proposed GM replanning algorithm, requiring only target delineation, not full delineation of OARs, substantially increased planning speed for online adaptive replanning. The preliminary results indicate that the GM algorithm may be a solution to improve the ability for automation and may be especially suitable for sites with small-to-medium size targets surrounded by several critical structures.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

SU-C-210-04: Considerable Pancreatic Tumor Motion During Breath-Hold Measured Using Intratumoral Fiducials On Fluoroscopic Movies

Purpose: Using a breath hold (BH) technique during radiotherapy of pancreatic tumors is expected to reduce intra-fractional motion. The aim of this study was to evaluate the tumor motion during BH. Methods: In this pilot study, we included 8 consecutive pancreatic cancer patients. All had 2– 4 intratumoral gold fiducials. Patients were asked to perform 3 consecutive 30-second end-inhale BHs on day 5, 10 and 15 of their three-week treatment. During BH, airflow through a mouthpiece was measured using a spirometer. Any inadvertent flow of air during BH was monitored for all patients. We measured tumor motion on lateral fluoroscopic movies (57 in total) made during BH. In each movie the fiducials as a group were tracked over time in superior-inferior (SI) and anterior-posterior (AP) direction using 2-D image correlation between consecutive frames. We determined for each patient the range of intra-BH motion over all movies; we also determined the absolute means and standard deviations (SDs) for the entire patient group. Additionally, we investigated the relation between inadvertent airflow during BH and the intra-BH motion. Results: We found intra-BH tumor motion of up to 12.5 mm (range, 1.0–12.5 mm) in SI direction and up to 8.0 mm (range, 1.0–8.0 mm) in AP direction. The absolute mean motion over the patient population was 4.7 (SD: 3.0) mm and 2.8 (SD: 1.2) mm in the SI and AP direction, respectively. Patients were able to perform stable consecutive BHs; during only 20% of the movies we found very small airflows (≤ 65 ml). These were mostly stepwise in nature and could not explain the continuous tumor motions we observed. Conclusion: We found substantial (up to 12.5 mm) pancreatic tumor motion during BHs. We found minimal inadvertent airflow, seen only during a minority of BHs, and this did not explain the obtained results. This work was supported by the foundation Bergh in het Zadel through the Dutch Cancer Society (KWF Kankerbestrijding) project No. UVA 2011-5271.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

SU-C-210-05: Evaluation of Robustness: Dosimetric Effects of Anatomical Changes During Fractionated Radiation Treatment of Pancreatic Cancer Patients

Purpose: Pancreatic tumors show large interfractional position variations. In addition, changes in gastrointestinal air volume and body contour take place during treatment. We aim to investigate the robustness of the clinical treatment plans by quantifying the dosimetric effects of these anatomical changes. Methods: Calculations were performed for up to now 3 pancreatic cancer patients who had intratumoral fiducials for daily CBCT-based positioning during their 3-week treatment. For each patient, deformable image registration of the planning CT was used to assign Hounsfield Units to each of the 13—15 CBCTs; air volumes and body contour were copied from CBCT. The clinical treatment plan was used (CTV-PTV margin = 10 mm; 36Gy; 10MV; 1 arc VMAT). Fraction dose distributions were calculated and accumulated. The V95% of the clinical target volume (CTV) and planning target volume (PTV) were analyzed, as well as the dose to stomach, duodenum and liver. Dose accumulation was done for patient positioning based on the fiducials (as clinically used) as well as for positioning based on bony anatomy. Results: For all three patients, the V95% of the CTV remained 100%, for both fiducial- and bony anatomy-based positioning. For fiducial-based positioning, dose to duodenum en stomach showed no discernable differences with planned dose. For bony anatomy-based positioning, the PTV V95% of the patient with the largest systematic difference in tumor position (patient 1) decreased to 85%; the liver Dmax increased from 33.5Gy (planned) to 35.5Gy. Conclusion: When using intratumoral fiducials, CTV dose coverage was only mildly affected by the daily anatomical changes. When using bony anatomy for patient positioning, we found a decline in PTV dose coverage due to the interfractional tumor position variations. Photon irradiation treatment plans for pancreatic tumors are robust to variations in body contour and gastrointestinal gas, but the use of fiducial-based daily position verification is imperative. This work was supported by the foundation Bergh in het Zadel through the Dutch Cancer Society (KWF Kankerbestrijding) project No. UVA 2011-5271.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

SU-E-J-33: Comparison Between Soft Tissue Alignment and Bony Alignment for Pancreatic Cancer Radiotherapy

Purpose An IGRT modality for pancreatic cancer treatment with dose escalation at our institution is in-room daily CT imaging. The purpose of this study is to assess the difference between soft tissue alignment and bony alignment for pancreatic tumor localization. Methods Eighteen patients with pancreatic tumors who underwent IMRT treatment with an inspiration breath-hold technique between July 2012 and February 2015 are included in this study. Prior to each treatment, a CT scan was acquired. The CT image guidance started with auto-alignment to either the bony anatomy (vertebral bodies) or fiducials (for the six patients with the stent in/near the tumor) and then, when necessary, manual adjustments were made based on soft tissue alignment using clinical software (CT-Assisted Targeting system). The difference between soft tissue alignment and bony/fiducial alignment was evaluated. Results Of all 380 treatments, manual adjustment was made in 225 treatments, ranging from 11% (3 treatments out of 28) to 96% (27 treatments out of 28) per patient. The mean of the difference between soft tissue alignment and bony/fiducial alignment per patient ranged from −3.6 to 0.3 mm, −1.5 to 2.8 mm, and −3.3 to 3.4 mm in the AP, SI, and RL directions, respectively. The maximum difference over all treatments was −9.5, −14.6, and −14.6 mm in the AP, SI, and RL directions, respectively. Conclusion About 60% of the time, manual adjustment based on soft tissue alignment was required. The extent of manual adjustment was usually small but varied significantly from patient to patient. The ultimate goal of the IGRT modality using daily CT imaging is not to fully cover the target but to spare organs-at-risk as much as possible to avoid them moving into higher dose gradients than accepted in the treatment plan. To this end, manual adjustment based on soft tissue alignment is critically important.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

SU-E-J-45: The Correlation Between CBCT Flat Panel Misalignment and 3D Image Guidance Accuracy

Purpose To simulate the impact of CBCT flat panel misalignment on the image quality, the calculated correction vectors in 3D image guided proton therapy and to determine if these calibration errors can be caught in our QA process. Methods The X-ray source and detector geometrical calibration (flexmap) file of the CBCT system in the AdaPTinsight software (IBA proton therapy) was edited to induce known changes in the rotational and translational calibrations of the imaging panel. Translations of up to ±10 mm in the x, y and z directions (see supplemental) and rotational errors of up to ±3° were induced. The calibration files were then used to reconstruct the CBCT image of a pancreatic patient and CatPhan phantom. Correction vectors were calculated for the patient using the software’s auto match system and compared to baseline values. The CatPhan CBCT images were used for quantitative evaluation of image quality for each type of induced error. Results Translations of 1 to 3 mm in the x and y calibration resulted in corresponding correction vector errors of equal magnitude. Similar 10mm shifts were seen in the y-direction; however, in the x-direction, the image quality was too degraded for a match. These translational errors can be identified through differences in isocenter from orthogonal kV images taken during routine QA. Errors in the z-direction had no effect on the correction vector and image quality.Rotations of the imaging panel calibration resulted in corresponding correction vector rotations of the patient images. These rotations also resulted in degraded image quality which can be identified through quantitative image quality metrics. Conclusion Misalignment of CBCT geometry can lead to incorrect translational and rotational patient correction vectors. These errors can be identified through QA of the imaging isocenter as compared to orthogonal images combined with monitoring of CBCT image quality.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

SU-E-J-154: Image Quality Assessment of Contrast-Enhanced 4D-CT for Pancreatic Adenocarcinoma in Radiotherapy Simulation

Purpose: This study presents quantitative and qualitative assessment of the image qualities in contrast-enhanced (CE) 3D-CT, 4D-CT and CE 4D-CT to identify feasibility for replacing the clinical standard simulation with a single CE 4D-CT for pancreatic adenocarcinoma (PDA) in radiotherapy simulation. Methods: Ten PDA patients were enrolled and underwent three CT scans: a clinical standard pair of CE 3D-CT immediately followed by a 4D-CT, and a CE 4D-CT one week later. Physicians qualitatively evaluated the general image quality and regional vessel definitions and gave a score from 1 to 5. Next, physicians delineated the contours of the tumor (T) and the normal pancreatic parenchyma (P) on the three CTs (CE 3D-CT, 50% phase for 4D-CT and CE 4D-CT), then high density areas were automatically removed by thresholding at 500 HU and morphological operations. The pancreatic tumor contrast-to-noise ratio (CNR), signal-tonoise ratio (SNR) and conspicuity (C, absolute difference of mean enhancement levels in P and T) were computed to quantitatively assess image quality. The Wilcoxon rank sum test was used to compare these quantities. Results: In qualitative evaluations, CE 3D-CT and CE 4D-CT scored equivalently (4.4±0.4 and 4.3±0.4) and both were significantly better than 4D-CT (3.1±0.6). In quantitative evaluations, the C values were higher in CE 4D-CT (28±19 HU, p=0.19 and 0.17) than the clinical standard pair of CE 3D-CT and 4D-CT (17±12 and 16±17 HU, p=0.65). In CE 3D-CT and CE 4D-CT, mean CNR (1.8±1.4 and 1.8±1.7, p=0.94) and mean SNR (5.8±2.6 and 5.5±3.2, p=0.71) both were higher than 4D-CT (CNR: 1.1±1.3, p<0.3; SNR: 3.3±2.1, p<0.1). The absolute enhancement levels for T and P were higher in CE 4D-CT (87, 82 HU) than in CE 3D-CT (60, 56) and 4DCT (53, 70). Conclusions: The individually optimized CE 4D-CT is feasible and achieved comparable image qualities to the clinical standard simulation. This study was supported in part by Philips Healthcare.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

SU-E-J-272: Auto-Segmentation of Regions with Differentiating CT Numbers for Treatment Response Assessment

Purpose: It has been reported recently that the change of CT number (CTN) during and after radiation therapy (RT) may be used to assess RT response. The purpose of this work is to develop a tool to automatically segment the regions with differentiating CTN and/or with change of CTN in a series of CTs. Methods: A software tool was developed to identify regions with differentiating CTN using K-mean Cluster of CT numbers and to automatically delineate these regions using convex hull enclosing method. Pre- and Post-RT CT, PET, or MRI images acquired for sample lung and pancreatic cancer cases were used to test the software tool. K-mean cluster of CT numbers within the gross tumor volumes (GTVs) delineated based on PET SUV (standard uptake value of fludeoxyglucose) and/or MRI ADC (apparent diffusion coefficient) map was analyzed. The cluster centers with higher value were considered as active tumor volumes (ATV). The convex hull contours enclosing preset clusters were used to delineate these ATVs with color washed displays. The CTN defined ATVs were compared with the SUV- or ADC-defined ATVs. Results: CTN stability of the CT scanner used to acquire the CTs in this work is less than 1.5 Hounsfield Unit (HU) variation annually. K-mean cluster centers in the GTV have difference of ∼20 HU, much larger than variation due to CTN stability, for the lung cancer cases studied. The dice coefficient between the ATVs delineated based on convex hull enclosure of high CTN centers and the PET defined GTVs based on SUV cutoff value of 2.5 was 90(±5)%. Conclusion: A software tool was developed using K-mean cluster and convex hull contour to automatically segment high CTN regions which may not be identifiable using a simple threshold method. These CTN regions were reasonably overlapped with the PET or MRI defined GTVs.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

SU-E-T-131: Artificial Neural Networks Applied to Overall Survival Prediction for Patients with Periampullary Carcinoma

Purpose: Artificial neural networks (ANN) can be used to discover complex relations within datasets to help with medical decision making. This study aimed to develop an ANN method to predict two-year overall survival of patients with peri-ampullary cancer (PAC) following resection. Methods: Data were collected from 334 patients with PAC following resection treated in our institutional pancreatic tumor registry between 2006 and 2012. The dataset contains 14 variables including age, gender, T-stage, tumor differentiation, positive-lymph-node ratio, positive resection margins, chemotherapy, radiation therapy, and tumor histology.After censoring for two-year survival analysis, 309 patients were left, of which 44 patients (∼15%) were randomly selected to form testing set. The remaining 265 cases were randomly divided into training set (211 cases, ∼80% of 265) and validation set (54 cases, ∼20% of 265) for 20 times to build 20 ANN models. Each ANN has one hidden layer with 5 units. The 20 ANN models were ranked according to their concordance index (c-index) of prediction on validation sets. To further improve prediction, the top 10% of ANN models were selected, and their outputs averaged for prediction on testing set. Results: By random division, 44 cases in testing set and the remaining 265 cases have approximately equal two-year survival rates, 36.4% and 35.5% respectively. The 20 ANN models, which were trained and validated on the 265 cases, yielded mean c-indexes as 0.59 and 0.63 on validation sets and the testing set, respectively. C-index was 0.72 when the two best ANN models (top 10%) were used in prediction on testing set. The c-index of Cox regression analysis was 0.63. Conclusion: ANN improved survival prediction for patients with PAC. More patient data and further analysis of additional factors may be needed for a more robust model, which will help guide physicians in providing optimal post-operative care. This project was supported by PA CURE Grant.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

SU-E-T-346: Effect of Jaw Position On Dose to Critical Structures in 3-D Conformal Radiotherapy Treatment of Pancreatic Cancer

Purpose: Three-dimensional conformal therapy remains a valid and widely used modality for pancreatic radiotherapy treatment. It usually meets dose constraints on critical structures. However, careful positioning of collimation jaws can reduce dose to the critical structures. Here we investigate the dosimetric effect of jaw position in MLC-based 3-D conformal treatment planning on critical structures. Methods: We retrospectively selected seven pancreatic cancer patients treated with 3-D conformal radiotherapy. We started with treatment plans (Varian Truebeam LINAC, Eclipse TPS, AAA, 18MV) having both x and y jaws aligned with the farthest extent of the block outline (8mm around PTV). Then we subsequently moved either both x-jaws or all x and y jaws outwards upto 3 cm in 1 cm increments and investigated their effect on average and maximum dose to neighboring critical structures keeping the same coverage to treatment volume. Results: Lateral displacement of both x-jaws by 1cm each increased kidney and spleen mean dose by as much as 1.7% and 1.3% respectively and superior inferior displacement increased liver, right kidney, stomach and spleen dose by as much as 2.1%, 2%, 5.2% and 1.6% respectively. Displacement of all x and y-jaws away by 1cm increased the mean dose to liver, right kidney, left kidney, bowels, cord, stomach and spleen by as much as 4.9%, 5.9%, 2.1%, 2.8%, 7.4%, 10.4% and 4.2% respectively. Percentage increase in mean dose due to 2 and 3cm jaw displacement increased almost linearly with the displaced distance. Changes in maximum dose were much smaller (mostly negligible) than the changes in mean dose. Conclusion: Collimation jaw position affects dose mostly to critical structures adjacent to it. Though treatment plans with MLCs conforming the block margin usually meet dose constraints to critical structures, keeping jaws all the way in, to the edge of the block reduces dose to the critical structures during radiation treatment.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

SU-E-T-426: Feasibility of Stereotactic Body Radiation Therapy (SBRT) Treatment of Pancreatic Cancer Using Volumetric Modulated Arc Therapy (VMAT) with Active Breathing Control (ABC)

Purpose: SBRT shows excellent tumor control and toxicity rates for patients with locally advanced pancreatic cancer (PCA). Herein, we evaluate the feasibility of using VMAT with ABC for PCA SBRT. Methods: Nine PCA patients previously treated via SBRT utilizing 11-beam step-and-shoot IMRT technique in our center were retrospectively identified, among whom eight patients received 3300cGy in 5 fractions while one received 3000cGy in 5 fractions. A VMAT plan was generated on each patient’s planning CT in Pinnacle v9.8 on Elekta Synergy following the same PCA SBRT clinical protocol. Three partial arcs (182°–300°, 300°-60°, and 60°-180°) with 2°/4° control-point spacing were used. The dosimetric difference between the VMAT and the original IMRT plans was analyzed. IMRT QA was performed for the VMAT plans using MapCheck2 in MapPHAN and the total delivery time was recorded. To mimic the treatment situation with ABC, where patients hold their breath for 20–30 seconds, the delivery was intentionally interrupted every 20–30 seconds. For each plan, the QA was performed with and without beam interruption. Gamma analysis (2%/2mm) was used to compare the planned and measured doses. Results: All VMAT plans with 2mm dose grid passed the clinic protocol with similar PTV coverage and OARs sparing, where PTV V-RxDose was 92.7±2.1% (VMAT) vs. 92.1±2.6% (IMRT), and proximal stomach V15Gy was 3.60±2.69 cc (VMAT) vs. 4.80±3.13 cc (IMRT). The mean total MU and delivery time of the VMAT plans were 2453.8±531.1 MU and 282.1±56.0 seconds. The gamma passing rates of absolute dose were 94.9±3.4% and 94.5±4.0% for delivery without and with interruption respectively, suggesting the dosimetry of VMAT delivery with ABC for SBRT won’t be compromised. Conclusion: This study suggests that PCA SBRT using VMAT with ABC is a feasible technique without compromising plan dosimetry. The combination of VMAT with ABC will potentially reduce the SBRT treatment time.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

MO-DE-210-03: Ultrasound imaging is an attractive method for image guided radiation treatment (IGRT), by itself or to complement other imaging modalities

Ultrasound imaging is an attractive method for image guided radiation treatment (IGRT), by itself or to complement other imaging modalities. It is inexpensive, portable and provides good soft tissue contrast. For challenging soft tissue targets such as pancreatic cancer, ultrasound imaging can be used in combination with pre-treatment MRI and/or CT to transfer important anatomical features for target localization at time of treatment. The non-invasive and non-ionizing nature of ultrasound imaging is particularly powerful for intra-fraction localization and monitoring. Recognizing these advantages, efforts are being made to incorporate novel robotic approaches to position and manipulate the ultrasound probe during irradiation. These recent enabling developments hold potential to bring ultrasound imaging to a new level of IGRT applications. However, many challenges, not limited to image registration, robotic deployment, probe interference and image acquisition rate, need to be addressed to realize the full potential of IGRT with ultrasound imaging. Learning Objectives: Understand the benefits and limitations in using ultrasound to augment MRI and/or CT for motion monitoring during radiation therapy delivery. Understanding passive and active robotic approaches to implement ultrasound imaging for intra-fraction monitoring. Understand issues of probe interference with radiotherapy treatment. Understand the critical clinical workflow for effective and reproducible IGRT using ultrasound guidance. The work of X.L. is supported in part by Elekta; J.W. and K.D. is supported in part by a NIH grant R01 CA161613 and by Elekta; D.H. is support in part by a NIH grant R41 CA174089.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

MO-FG-BRA-07: Theranostic Gadolinium-Based AGuIX Nanoparticles for MRI-Guided Radiation Therapy

Purpose: AGuIX are gadolinium-based nanoparticles, initially developed for MRI, that have a potential role in radiation therapy as a radiosensitizer. Our goal is to demonstrate that these nanoparticles can both be used as an MRI contrast agent, as well as to obtain local dose enhancement in a pancreatic tumor when delivered in combination with an external beam irradiation. Methods: We performed in vitro cell uptake and radiosensitization studies of a pancreatic cancer cell line in a low energy (220kVp) beam, a standard clinical 6MV beam (STD) and a flattening filter free clinical 6MV beam (FFF). After injection of 40mM of nanoparticles, a biodistribution study was performed in vivo on mice with subcutaneous xenograft pancreatic tumors. In vivo radiation therapy studies were performed at the time point of maximum tumor uptake. Results: The concentration of AGuIX nanoparticles in Panc-1 pancreatic cancer cells, determined in vitro by MRI and ICPMS, peaks after 30 minutes with 0.3% of the initial concentration (5mg/g). Clonogenic assays show a significant effect (p<0.05) when the AGuIX are coupled with MV photon irradiation (DEF20%=1.31). Similar AGuIX tumor uptake is found in vivo by both MRI and ICPMS 30 minutes after intravenous injection. For long term survival studies, the choice of the radiation dose is determined with 5 control groups (3mice/group) irradiated with 0, 5, 10, 15, and 20Gy. Afterwards, 4 groups (8mice/group) are used to evaluate the effect of the nanoparticles. A Logrank test is performed as a statistical test to evaluate the effect of the nanoparticles. Conclusion: The combination of the MRI contrast and radiosensitization properties of gadolinium nanoparticles reveals a strong potential for usage with MRI-guided radiation therapy.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

TU-CD-BRB-08: Radiomic Analysis of FDG-PET Identifies Novel Prognostic Imaging Biomarkers in Locally Advanced Pancreatic Cancer Patients Treated with SBRT

Purpose: This study aims to identify novel prognostic imaging biomarkers in locally advanced pancreatic cancer (LAPC) using quantitative, high-throughput image analysis. Methods: 86 patients with LAPC receiving chemotherapy followed by SBRT were retrospectively studied. All patients had a baseline FDG-PET scan prior to SBRT. For each patient, we extracted 435 PET imaging features of five types: statistical, morphological, textural, histogram, and wavelet. These features went through redundancy checks, robustness analysis, as well as a prescreening process based on their concordance indices with respect to the relevant outcomes. We then performed principle component analysis on the remaining features (number ranged from 10 to 16), and fitted a Cox proportional hazard regression model using the first 3 principle components. Kaplan-Meier analysis was used to assess the ability to distinguish high versus low-risk patients separated by median predicted survival. To avoid overfitting, all evaluations were based on leave-one-out cross validation (LOOCV), in which each holdout patient was assigned to a risk group according to the model obtained from a separate training set. Results: For predicting overall survival (OS), the most dominant imaging features were wavelet coefficients. There was a statistically significant difference in OS between patients with predicted high and low-risk based on LOOCV (hazard ratio: 2.26, p<0.001). Similar imaging features were also strongly associated with local progression-free survival (LPFS) (hazard ratio: 1.53, p=0.026) on LOOCV. In comparison, neither SUVmax nor TLG was associated with LPFS (p=0.103, p=0.433) (Table 1). Results for progression-free survival and distant progression-free survival showed similar trends. Conclusion: Radiomic analysis identified novel imaging features that showed improved prognostic value over conventional methods. These features characterize the degree of intra-tumor heterogeneity reflected on FDG-PET images, and their biological underpinnings warrant further investigation. If validated in large, prospective cohorts, this method could be used to stratify patients based on individualized risk.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

WE-AB-204-07: Spatiotemporal Distribution of the FDG PET Tracer in Solid Tumors: Contributions of Diffusion and Convection Mechanisms

Purpose: In this study, a mathematical model is utilized to simulate FDG distribution in tumor tissue. In contrast to conventional compartmental modeling, tracer distributions across space and time are directly linked together (i.e. moving beyond ordinary differential equations (ODEs) to utilizing partial differential equations (PDEs) coupling space and time). The diffusion and convection transport mechanisms are both incorporated to model tracer distribution. We aimed to investigate the contributions of these two mechanisms on FDG distribution for various tumor geometries obtained from PET/CT images. Methods: FDG transport was simulated via a spatiotemporal distribution model (SDM). The model is based on a 5K compartmental model. We model the fact that tracer concentration in the second compartment (extracellular space) is modulated via convection and diffusion. Data from n=45 patients with pancreatic tumors as imaged using clinical FDG PET/CT imaging were analyzed, and geometrical information from the tumors including size, shape, and aspect ratios were classified. Tumors with varying shapes and sizes were assessed in order to investigate the effects of convection and diffusion mechanisms on FDG transport. Numerical methods simulating interstitial flow and solute transport in tissue were utilized. Results: We have shown the convection mechanism to depend on the shape and size of tumors whereas diffusion mechanism is seen to exhibit low dependency on shape and size. Results show that concentration distribution of FDG is relatively similar for the considered tumors; and that the diffusion mechanism of FDG transport significantly dominates the convection mechanism. The Peclet number which shows the ratio of convection to diffusion rates was shown to be of the order of 10−{sup 3} for all considered tumors. Conclusion: We have demonstrated that even though convection leads to varying tracer distribution profiles depending on tumor shape and size, the domination of the diffusion phenomenon prevents these factors from modulating FDG distribution.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

SU-C-BRA-01: Interactive Auto-Segmentation for Bowel in Online Adaptive MRI-Guided Radiation Therapy by Using a Multi-Region Labeling Algorithm

Purpose: In MRI-guided online adaptive radiation therapy, re-contouring of bowel is time-consuming and can impact the overall time of patients on table. The study aims to auto-segment bowel on volumetric MR images by using an interactive multi-region labeling algorithm. Methods: 5 Patients with locally advanced pancreatic cancer underwent fractionated radiotherapy (18–25 fractions each, total 118 fractions) on an MRI-guided radiation therapy system with a 0.35 Tesla magnet and three Co-60 sources. At each fraction, a volumetric MR image of the patient was acquired when the patient was in the treatment position. An interactive two-dimensional multi-region labeling technique based on graph cut solver was applied on several typical MRI images to segment the large bowel and small bowel, followed by a shape based contour interpolation for generating entire bowel contours along all image slices. The resulted contours were compared with the physician’s manual contouring by using metrics of Dice coefficient and Hausdorff distance. Results: Image data sets from the first 5 fractions of each patient were selected (total of 25 image data sets) for the segmentation test. The algorithm segmented the large and small bowel effectively and efficiently. All bowel segments were successfully identified, auto-contoured and matched with manual contours. The time cost by the algorithm for each image slice was within 30 seconds. For large bowel, the calculated Dice coefficients and Hausdorff distances (mean±std) were 0.77±0.07 and 13.13±5.01mm, respectively; for small bowel, the corresponding metrics were 0.73±0.08and 14.15±4.72mm, respectively. Conclusion: The preliminary results demonstrated the potential of the proposed algorithm in auto-segmenting large and small bowel on low field MRI images in MRI-guided adaptive radiation therapy. Further work will be focused on improving its segmentation accuracy and lessening human interaction.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

SU-D-BRA-06: Duodenal Interfraction Motion with Abdominal Compression

Purpose: To quantify the effect of abdominal compression on duodenal motion during pancreatic radiotherapy. Methods: Seven patients treated for pancreatic cancer were selected for analysis. Four patients were treated with abdominal compression and three without. The duodenum was contoured by the same physician on each CBCT (five CBCTs for patients with compression, four for non-compression patients). CBCTs were rigidly registered using a soft tissue match and contours were copied to the delivered plans which were all radical (BED > 50 Gy). The distance between the duodenum on the planning CT and each CBCT was quantified by calculating the root mean square (RMS) distance. The DVHs of each abdominal compression patient was converted to an EQD2 DVH (alpha/beta = 10) using an in-house tool and volumes receiving at least 25, 35, 45, and 50 Gy were recorded. Results: The maximum variation in duodenal volumes on the CBCTs for the four abdominal compression patients were 19.1 cm{sup 3} (32.8%), 19.1 cm{sup 3} (20.6%), 19.9 cm{sup 3} (14.3%), and 12.9 cm{sup 3} (27.3%) compared to 15.2 cm{sup 3} (17.6%), 34.7 cm{sup 3} (83.4%), and 56 cm{sup 3} (60.2%) for non-compression patients. The average RMS distance between the duodenum on the planning CT and each CBCT for all abdominal compression patients was 0.3 cm compared to 0.7 cm for non-compressed patients. The largest (and average) difference between the planning CT and CBCTs in volume of duodenum receiving more than 25, 35, 45 and 50 Gy for abdominal compression patients was 11% (5%), 9% (3%), 9% (2%), and 6% (1%). Conclusion: Abdominal compression reduces variation in volume and absolute position of the duodenum throughout treatment. This is seen as an improvement but does not eliminate the need to consider dosimetric effects of motion. Abdominal compression is particularly useful in SBRT when only a few fractions are delivered. Alon Witztum is supported by an MRC/Gray Institute DPhil Studentship. Daniel Holyoake is supported by a CRUK/Nuffield Clinical Research Fellowship. Sam Warren and Mike Partridge are supported by CRUK grant C5255/A15935. Maria Hawkins received an MRC Fellowship MC-PC-12001/2.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

SU-F-J-07: Evaluating the Adequacy of Biopsy Specimens for Genetic Signature Assessment by Measuring the Metabolic Activity in Specimens Obtained Under 18F-FDG PET/CT Guidance

Purpose: Genetic profiling of biopsied tissue is the basis for personalized cancer therapy. However biopsied materials may not contain sufficient amounts of DNA needed for analysis. We propose a method to determine the adequacy of specimens for performing genetic profiling by quantifying metabolic activity. Methods: We measured the response of two radiation detectors to the activity contained in the minimum amount of tumor cells needed for genetic profiling in biopsy specimens obtained under 2-deoxy-2-({sup 18}F)fluoro-D-glucose ({sup 18}F-FDG) PET/CT guidance. The expected tumor cell concentration in biopsy specimens was evaluated from the amount of DNA needed (∼100 µg) and the number of pathology sections typically used for the analysis. The average {sup 18}F-FDG uptake per cell was measured by incubating KPC-4662 pancreatic tumor cells and HT-29 colorectal adenocarcinoma tumor cells in {sup 18}F-FDG containing solution (activity concentrations between 0.0122 and 1.51 MBq/mL and glucose concentrations of 3.1 and 1 g/L) for 1 to 1.75 hours and then measuring the activity of a known number of cells. Measurements of surrogate specimens obtained using 18G needle biopsies of gels containing these cells in expected concentrations (∼10{sup 4} µL{sup −1}) were performed using an autoradiography CCD based device (up to 20 min exposure) and a scintillation well counter (∼1 min measurements) about 3 and 5 hours after the end of incubation respectively. Results: At start of autoradiography there were between 0.16 and 1.5 {sup 18}F-FDG molecules/cell and between 1.14 and 5.43×10{sup 7} {sup 18}F-FDG molecules/mL. For the scintillation well counter, sample to minimum-detectable-count rate ratios were greater than 7 and the counting error was less than 25% for ≤80 s measurement times. Images of the samples were identifiable on the autoradiograph for ∼10 min and longer exposure times. Conclusion: Scintillation well counter measurements and CCD based autoradiography have adequate sensitivity to detect the tumor burden needed for genetic profiling in 18G core needle biopsies. Supported in part through the NIH/NCI Cancer Center Support Grant P30 CA008748 and by a sponsored research agreement with Biospace Lab S.A.

60 APPLIED LIFE SCIENCES↗