I. Vergalasova

Potential underestimation of the internal target volume (ITV) from free-breathing CBCT.

PURPOSE Localization prior to delivery of SBRT to free-breathing patients is performed by aligning the planning internal target volume (ITV) from 4DCT with an on-board free-breathing cone-beam CT (FB-CBCT) image. The FB-CBCT image is assumed to also generate an ITV that captures the full range of motion, due to the acquisition spanning multiple respiratory cycles. However, the ITV could potentially be underestimated when the ratio of time spent in inspiration versus time spent in expiration (I/E ratio) deviates from unity. Therefore, the aim of this study was to investigate the effect of variable I/E ratios on the FB ITV generated from a FB-CBCT scan. METHODS This study employed both phantom and patient imaging data. For the phantom study, five periodic respiratory cycles were simulated with different I/E ratios. Six patient respiratory cycles with variable I/E ratios were also selected. All profiles were then programmed into a motion phantom for imaging and modified to exhibit three peak-to-peak motion amplitudes (0.5, 1.0, and 2.0 cm). Each profile was imaged using two spherical targets with 1.0 and 3.0 cm diameters. 2D projections were acquired with full gantry rotation of a kiloVoltage (kV) imager mounted onto the gantry of a modem linear accelerator. CBCT images were reconstructed from 2D projections using a standard filtered back-projection reconstruction algorithm. Quantitative analyses for the phantom study included computing the change in contrast along the direction of target motion as well as determining the area (which is proportional to the target volume) inside of the contour extracted using a Canny edge detector. For the patient study, projection data that were previously acquired under an investigational 4D CBCT slow-gantry imaging protocol were used to generate both FB-CBCT and 4D CBCT images. Volumes were then manually contoured from both datasets (using the same window and level) for quantitative comparison. RESULTS The phantom study indicated a reduction in contrast at the inferior edge of the ITV (corresponding to inspiration) as the ratio decreased, for both simulated and patient respiratory cycles. For the simulated phantom respiratory cycles, the contrast reduction of the smallest I/E ratio was 27.6% for the largest target with the smallest amplitude and 89.7% for the smallest target with the largest amplitude. For patient respiratory cycles, these numbers were 22.3% and 94.0%, respectively. The extracted area from inside of the target contours showed a decreasing trend as the I/E ratio decreased. In the patient study, the FB-CBCT ITVs of both lung tumors studied were underestimated when compared with their corresponding 4D CBCT ITV. The underestimations found were 40.1% for the smaller tumor and 24.2% for the larger tumor. CONCLUSIONS The ITV may be underestimated in a FB-CBCT image when a patients respiratory pattern is characterized by a disparate length of time spent in inspiration versus expiration. Missing the full target motion information during on-board verification imaging may result in localization errors.

A novel technique for markerless, self-sorted 4D-CBCT: Feasibility study

PURPOSE Four-dimensional CBCT (4D-CBCT) imaging in the treatment room can provide verification of moving targets, facilitating the potential for margin reduction and consequent dose escalation. Reconstruction of 4D-CBCT images requires correlation of respiratory phase with projection acquisition, which is often achieved with external surrogate measures of respiration. However, external measures may not be a direct representation of the motion of the internal anatomy and it is therefore the aim of this work to develop a novel technique for markerless, self-sorted 4D-CBCT reconstruction. METHODS A novel 4D-CBCT reconstruction technique based on the principles of Fourier transform (FT) theory was investigated for markerless extraction of respiratory phase directly from projection data. In this FT technique, both phase information (FT-phase) and magnitude information (FT-magnitude) were separately implemented in order to discern projections corresponding to peak inspiration, which then facilitated the proceeding sort and bin processes involved in retrospective 4D image reconstruction. In order to quantitatively evaluate the accuracy of the Fourier methods, peak-inspiration projections identified each by FT-phase and FT-magnitude were compared to those manually identified by visual tracking of structures. The average phase difference as assigned by each method vs the manual technique was calculated per projection dataset. The percentage of projections that were assigned within 10% phase of each other was also computed. Both Fourier methods were tested on two phantom datasets, programmed to exhibit sinusoidal respiratory cycles of 2.0 cm in amplitude with respiratory cycle lengths of 3 and 6 s, respectively. Additionally, three sets of patient projections were studied. All of the data were previously acquired at slow-gantry speeds ranging between 0.6°/s and 0.7°/s over a 200° rotation. Ten phase bins with 10% phase windows were selected for 4D-CBCT reconstruction of one phantom and one patient case for visual and quantitative comparison. Line profiles were plotted for the 0% and 50% phase images as reconstructed by the manual technique and each of the Fourier methods. RESULTS As compared with the manual technique, the FT-phase method resulted in average phase differences of 1.8% for the phantom with the 3 s respiratory cycle, 3.9% for the phantom with the 6 s respiratory cycle, 2.9% for patient 1, 5.0% for patient 2, and 3.8% for patient 3. For the FT-magnitude method, these numbers were 2.1%, 4.0%, 2.9%, 5.3%, and 3.5%, respectively. The percentage of projections that were assigned within 10% phase by the FT-phase method as compared to the manual technique for the five datasets were 100.0%, 100.0%, 97.6%, 93.4%, and 94.1%, respectively, whereas for the FT-magnitude method these percentages were 98.1%, 92.3%, 98.7%, 87.3%, and 95.7%. Reconstructed 4D phase images for both the phantom and patient case were visually and quantitatively equivalent between each of the Fourier methods vs the manual technique. CONCLUSIONS A novel technique employing the basics of Fourier transform theory was investigated and demonstrated to be feasible in achieving markerless, self-sorted 4D-CBCT reconstruction.

Strategies for automatic online treatment plan reoptimization using clinical treatment planning system: a planning parameters study.

PURPOSE Adaptive radiation therapy for prostate cancer using online reoptimization provides an improved control of interfractional anatomy variations. However, the clinical implementation of online reoptimization is currently limited by the low efficiency of current strategies and the difficulties associated with integration into the current treatment planning system. This study investigates the strategies for performing fast (~2 min) automatic online reoptimization with a clinical fluence-map-based treatment planning system; and explores the performance with different input parameters settings: dose-volume histogram (DVH) objective settings, starting stage, and iteration number (in the context of real time planning). METHODS Simulated treatments of 10 patients were reoptimized daily for the first week of treatment (5 fractions) using 12 different combinations of optimization strategies. Options for objective settings included guideline-based RTOG objectives, patient-specific objectives based on anatomy on the planning CT, and daily-CBCT anatomy-based objectives adapted from planning CT objectives. Options for starting stages involved starting reoptimization with and without the original plans fluence map. Options for iteration numbers were 50 and 100. The adapted plans were then analyzed by statistical modeling, and compared both in terms of dosimetry and delivery efficiency. RESULTS All online reoptimized plans were finished within ~2 min with excellent coverage and conformity to the daily target. The three input parameters, i.e., DVH objectives, starting stage, and iteration number, contributed to the outcome of optimization nearly independently. Patient-specific objectives generally provided better OAR sparing compared to guideline-based objectives. The benefit in high-dose sparing from incorporating daily anatomy into objective settings was positively correlated with the relative change in OAR volumes from planning CT to daily CBCT. The use of the original plan fluence map as the starting stage reduced OAR dose at the mid-dose region, but increased the monitor units by 17%. Differences of only 2cc or less in OAR V50%/V70Gy/V76Gy were observed between 100 and 50 iterations. CONCLUSIONS It is feasible to perform automatic online reoptimization in ~2 min using a clinical treatment planning system. Selecting optimal sets of input parameters is the key to achieving high quality reoptimized plans, and should be based on the individual patients daily anatomy, delivery efficiency, and time allowed for plan adaptation.

Evaluation of the effect of respiratory and anatomical variables on a Fourier technique for markerless, self-sorted 4D-CBCT

A novel technique based on Fourier transform theory has been developed that directly extracts respiratory information from projections without the use of external surrogates. While the feasibility has been demonstrated with three patients, a more extensive validation is necessary. Therefore, the purpose of this work is to investigate the effects of a variety of respiratory and anatomical scenarios on the performance of the technique with the 4D digital extended cardiac torso phantom. FT-phase and FT-magnitude methods were each applied to identify peak-inspiration projections and quantitatively compared to the gold standard of visual identification. Both methods proved to be robust across the studied scenarios with average differences in respiratory phase <10% and percentage of projections assigned within 10% of the gold standard >90%, when incorporating minor modifications to region-of-interest (ROI) selection and/or low-frequency location for select cases of DA and lung percentage in the field of view of the projection. Nevertheless, in the instance where one method initially faltered, the other method prevailed and successfully identified peak-inspiration projections. This is promising because it suggests that the two methods provide complementary information to each other. To ensure appropriate clinical adaptation of markerless, self-sorted four-dimensional cone-beam CT (4D-CBCT), perhaps an optimal integration of the two methods can be developed.

Clinical Study of Orthogonal-View Phase-Matched Digital Tomosynthesis for Lung Tumor Localization:

Background and Purpose: Compared to cone-beam computed tomography, digital tomosynthesis imaging has the benefits of shorter scanning time, less imaging dose, and better mechanical clearance for tumor localization in radiation therapy. However, for lung tumors, the localization accuracy of the conventional digital tomosynthesis technique is affected by the lack of depth information and the existence of lung tumor motion. This study investigates the clinical feasibility of using an orthogonal-view phase-matched digital tomosynthesis technique to improve the accuracy of lung tumor localization. Materials and Methods: The proposed orthogonal-view phase-matched digital tomosynthesis technique benefits from 2 major features: (1) it acquires orthogonal-view projections to improve the depth information in reconstructed digital tomosynthesis images and (2) it applies respiratory phase-matching to incorporate patient motion information into the synthesized reference digital tomosynthesis sets, which helps to improve the localization accuracy of moving lung tumors. A retrospective study enrolling 14 patients was performed to evaluate the accuracy of the orthogonal-view phase-matched digital tomosynthesis technique. Phantom studies were also performed using an anthropomorphic phantom to investigate the feasibility of using intratreatment aggregated kV and beams’ eye view cine MV projections for orthogonal-view phase-matched digital tomosynthesis imaging. The localization accuracy of the orthogonal-view phase-matched digital tomosynthesis technique was compared to that of the single-view digital tomosynthesis techniques and the digital tomosynthesis techniques without phase-matching. Results: The orthogonal-view phase-matched digital tomosynthesis technique outperforms the other digital tomosynthesis techniques in tumor localization accuracy for both the patient study and the phantom study. For the patient study, the orthogonal-view phase-matched digital tomosynthesis technique localizes the tumor to an average (± standard deviation) error of 1.8 (0.7) mm for a 30° total scan angle. For the phantom study using aggregated kV–MV projections, the orthogonal-view phase-matched digital tomosynthesis localizes the tumor to an average error within 1 mm for varying magnitudes of scan angles. Conclusion: The pilot clinical study shows that the orthogonal-view phase-matched digital tomosynthesis technique enables fast and accurate localization of moving lung tumors.

SU‐E‐T‐99: A Patient Specific QA Protocol for Verification of 4D Dosimetry

Purpose: Presently, there is no patient specific dosimetric QA for radiation treatment of moving targets. Here we present a patient specific QA protocol for verification of 4D dosimetry delivered to a moving target in SBRT of lung and livertumors. Methods and Materials: The protocol proceeds as follows. The patients breathing pattern is recorded during 4D simulation and imported to a dynamic phantom incorporating a target that moves within an artificial lung or liver respectively. The patients treatment plan (e.g. VMAT) is then recalculated on the free‐breathing CT of the dynamic phantom. The target is replaced with a 3D dosimeter (Presage), which is then irradiated while moving with the patients breathing pattern. The dose in Presage is determined by optical‐CT, and compared with the planned dose, to generate a 4D dose verification index. An end‐to‐end test of the protocol was performed on a target undergoing known motion (amplitude 1.5cm, frequency 5s). Under‐dose and interplay effects were studied in 3DCRT, IMRT, and VMAT treatment plans, where the static target volume was covered 100% with a prescribed dose of 10Gy. Results: The whole process from sample preparation to completion of analysis takes about 1.5 hours for a non‐interruptive operation in the chain. Measured 3D dose distributions were obtained for moving phantom targets, for all plans, with isotropic resolution of 1mm3. In the control study, where motion was absent, good agreement was observed between planned and measured dose distributions with a 90% 3D gamma pass rate. Clear evidence of interplay and target under‐dosing was observed in all motion deliveries under free‐breathing. The under‐dose at the edge of both ends of the dosimeter along the moving direction was in excess of 30%. Conclusion: Comprehensive patient specific QA of 4D dosimetry for SBRT of moving lung and liver targets is feasible with the Presage/Optical‐CT system.

SU‐DD‐A3‐03: How Accurately Can the Internal Target Volume (ITV) from a Free‐Breathing Cone Beam Computed Tomography (FB‐CBCT) Scan Be Used for Target Verification?

Purpose: An internal target volume (ITV) is often identified by acquiring a free‐breathing cone‐beam computed tomography scan (FB‐CBCT) to verify patient setup of tumors affected by respiratory motion. However, its accuracy is not well understood. The purpose of this study is to characterize the potential underestimation of the ITV when a FB‐CBCT is acquired with irregular respiratory cycles. Methods & Materials: Five patient respiratory profiles were programmed into a 4D Dynamic Thorax (CIRS Model 008) phantom containing a spherical target, 2cm in diameter. The superior‐inferior motion was 3cm with respiratory cycles approximately 5 seconds in length. Five 360° CBCT scans of each profile were acquired using a gantry mounted kV imaging system. A FB‐CBCT, as well as a 4DCBCT of 10 phase bins with 10% phase windows were reconstructed for each profile. Inspiration (0%) and expiration (50%) phase images were compared to FB‐CBCT images. The ITV of each FB‐CBCT displayed a sharp and a smeared region. The percent reduction in contrast‐to‐noise ratio (CNR) between these regions was calculated, as well as the ratio of the average time spent in inspiration versus expiration. The relationship between contrast reduction and the ratio of time spent per phase was investigated. Results: For the five profiles studied, the CNR reductions ranged from 37% to 70%, corresponding to ratios of average time spent in inspiration versus expiration that ranged from 0.42 to 0.12, respectively. As the difference between time spent in expiration versus inspiration increased, the reduction in contrast also generally increased (r2=0.873). Conclusions: The observed loss of contrast in the ITV for irregular respiratory cycles may lead to the potential underestimation of this volume obtained from a FB‐CBCT. Extra caution is required when using an ITV for on‐board target localization when respiratory cycles exhibit large time differences between inspiration and expiration periods.

Simultaneous integrated boost (SIB) for treatment of gynecologic carcinoma: Intensity-modulated radiation therapy (IMRT) vs volumetric-modulated arc therapy (VMAT) radiotherapy

The aim of this study was to quantitatively compare dosimetric criteria between intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) plans for patients undergoing radiation treatment of gynecologic carcinoma with a simultaneous integrated boost (SIB) technique. IMRT and VMAT plans were retrospectively analyzed for 20 patients. The elective volume was planned to receive 45 Gy in 25 fractions of 1.8 Gy, with the integrated boost volume (involved nodes) receiving 55 Gy simultaneously. The same dose constraints were employed during the optimization of both techniques. IMRT plans consisted of 9 to 11 fields at equally spaced gantry angles. VMAT plans consisted of 3 full arcs of 360°. A large variety of dose metrics across planning target volume (PTV)45, PTV55, bladder, rectum, sigmoid, bowel, kidneys, and femoral heads were extracted per patient, per plan. Conformity and homogeneity indices were also calculated and compared for each target volume. The total number of monitor units as well as the integral dose was also compared between IMRT and VMAT. The Wilcoxon signed rank test was performed to evaluate any significant differences between parameters, with an applied Bonferroni correction to account for multiple testing (significance level, p < 0.0006). The results demonstrate the equivalence of the 2 planning techniques across all studied parameters, with the exception of the expected decrease in monitor units that VMAT is capable of achieving. The findings of this study suggest that IMRT and VMAT are both acceptable options for applying simultaneous integrated boost techniques for the treatment of gynecologic cancers. The technique of choice will be dependent on departmental resources and should be considered on a case-by-case basis.

SU-E-J-124: FDG PET Metrics Analysis in the Context of An Adaptive PET Protocol for Node Positive Gynecologic Cancer Patients

PURPOSE To compare PET extracted metrics and investigate the role of a gradient-based PET segmentation tool, PET Edge (MIM Software Inc., Cleveland, OH), in the context of an adaptive PET protocol for node positive gynecologic cancer patients. METHODS An IRB approved protocol enrolled women with gynecological, PET visible malignancies. A PET-CT was obtained for treatment planning prescribed to 45-50.4Gy with a 55- 70Gy boost to the PET positive nodes. An intra-treatment PET-CT was obtained between 30-36Gy, and all volumes re-contoured. Standard uptake values (SUVmax, SUVmean, SUVmedian) and GTV volumes were extracted from the clinician contoured GTVs on the pre- and intra-treament PET-CT for primaries and nodes and compared with a two tailed Wilcoxon signed-rank test. The differences between primary and node GTV volumes contoured in the treatment planning system and those volumes generated using PET Edge were also investigated. Bland-Altman plots were used to describe significant differences between the two contouring methods. RESULTS Thirteen women were enrolled in this study. The median baseline/intra-treatment primary (SUVmax, mean, median) were (30.5, 9.09, 7.83)/(16.6, 4.35, 3.74), and nodes were (20.1, 4.64, 3.93)/(6.78, 3.13, 3.26). The p values were all < 0.001. The clinical contours were all larger than the PET Edge generated ones, with mean difference of +20.6 ml for primary, and +23.5 ml for nodes. The Bland-Altman revealed changes between clinician/PET Edge contours to be mostly within the margins of the coefficient of variability. However, there was a proportional trend, i.e. the larger the GTV, the larger the clinical contours as compared to PET Edge contours. CONCLUSION Primary and node SUV values taken from the intratreament PET-CT can be used to assess the disease response and to design an adaptive plan. The PET Edge tool can streamline the contouring process and lead to smaller, less user-dependent contours.

MO‐F‐WAB‐11: Investigation of CBCT‐Based Patient Positioning Accuracy in Lung SBRT: Correlation with Breathing Irregularity

PURPOSE To evaluate breathing irregularity induced error in CBCT-based patient positioning in lung SBRT and correlate the error with a measure of breathing variability. METHODS The 4D extended cardiac-torso (XCAT) digital phantom was used to generate 10-phase 4DCT and CBCT images using in-house developed simulation programs. Images were generated for various respiratory profiles (one regular sinusoidal and 10 irregular) and tumor sizes (1 cm, 2 cm, 3 cm). Maximum intensity projection (MIP) and average intensity projection (AIP) images were generated from 4DCT images. Image registrations between CBCT and AIP were performed for each respiratory profile and tumor size by four clinicians (two physicians and two physicists) based on target volume matching. Error of registration was determined as the difference between manual CBCT-to-AIP registration and known registration between the two. Breathing irregularities of the respiratory profiles were measured and correlated to errors of registration. RESULTS Inter-observer variation of registration was 0.15 mm, 0.34 mm, and 0.69 mm, in the medial-lateral (ML), anterior-posterior (AP), and superior-inferior (SI) direction, respectively. For the regular profile, negligible errors of registration were found in all directions (median<0.5 mm). For the irregular profiles and all tumor sizes, small errors (median=0.5 mm) were found in the ML and AP directions, while non-trivial errors were seen in the SI direction (median (+/- SD): 2.10 (+/- 2.27) mm). No significant difference in mean error of registration was found for different tumor sizes (p>0.6). Maximum error of registration in the ML, AP, and SI direction was 1.2 mm, 2.6 mm, and 8.4 mm, respectively. Mild correlations (R2 range: 0.37 to 0.47) were observed between error of registration error and breathing irregularity for all tumor sizes. CONCLUSION Irregular breathing can induce error in CBCT-based image registration in lung SBRT. This error increases as the breathing irregularity increases.