Nuzhat Jan

Evaluation of 4-dimensional Computed Tomography to 4-dimensional Cone-Beam Computed Tomography Deformable Image Registration for Lung Cancer Adaptive Radiation Therapy

PURPOSE To evaluate 2 deformable image registration (DIR) algorithms for the purpose of contour mapping to support image-guided adaptive radiation therapy with 4-dimensional cone-beam CT (4DCBCT). METHODS AND MATERIALS One planning 4D fan-beam CT (4DFBCT) and 7 weekly 4DCBCT scans were acquired for 10 locally advanced non-small cell lung cancer patients. The gross tumor volume was delineated by a physician in all 4D images. End-of-inspiration phase planning 4DFBCT was registered to the corresponding phase in weekly 4DCBCT images for day-to-day registrations. For phase-to-phase registration, the end-of-inspiration phase from each 4D image was registered to the end-of-expiration phase. Two DIR algorithms-small deformation inverse consistent linear elastic (SICLE) and Insight Toolkit diffeomorphic demons (DEMONS)-were evaluated. Physician-delineated contours were compared with the warped contours by using the Dice similarity coefficient (DSC), average symmetric distance, and false-positive and false-negative indices. The DIR results are compared with rigid registration of tumor. RESULTS For day-to-day registrations, the mean DSC was 0.75 ± 0.09 with SICLE, 0.70 ± 0.12 with DEMONS, 0.66 ± 0.12 with rigid-tumor registration, and 0.60 ± 0.14 with rigid-bone registration. Results were comparable to intraobserver variability calculated from phase-to-phase registrations as well as measured interobserver variation for 1 patient. SICLE and DEMONS, when compared with rigid-bone (4.1 mm) and rigid-tumor (3.6 mm) registration, respectively reduced the average symmetric distance to 2.6 and 3.3 mm. On average, SICLE and DEMONS increased the DSC to 0.80 and 0.79, respectively, compared with rigid-tumor (0.78) registrations for 4DCBCT phase-to-phase registrations. CONCLUSIONS Deformable image registration achieved comparable accuracy to reported interobserver delineation variability and higher accuracy than rigid-tumor registration. Deformable image registration performance varied with the algorithm and the patient.

Interfraction displacement of primary tumor and involved lymph nodes relative to anatomic landmarks in image guided radiation therapy of locally advanced lung cancer.

PURPOSE To analyze primary tumor (PT) and lymph node (LN) position changes relative to each other and relative to anatomic landmarks during conventionally fractionated radiation therapy for patients with locally advanced lung cancer. METHODS AND MATERIALS In 12 patients with locally advanced non-small cell lung cancer PT, LN, carina, and 1 thoracic vertebra were manually contoured on weekly 4-dimensional fan-beam CT scans. Systematic and random interfraction displacements of all contoured structures were identified in the 3 cardinal directions, and resulting setup margins were calculated. Time trends and the effect of volume changes on displacements were analyzed. RESULTS Three-dimensional displacement vectors and systematic/random interfraction displacements were smaller for carina than for vertebra both for PT and LN. For PT, mean (SD) 3-dimensional displacement vectors with carina-based alignment were 7 (4) mm versus 9 (5) mm with bony anatomy (P<.0001). For LN, smaller displacements were found with carina- (5 [3] mm, P<.0001) and vertebra-based (6 [3] mm, P=.002) alignment compared with using PT for setup (8 [5] mm). Primary tumor and LN displacements relative to bone and carina were independent (P>.05). Displacements between PT and bone (P=.04) and between PT and LN (P=.01) were significantly correlated with PT volume regression. Displacements between LN and carina were correlated with LN volume change (P=.03). CONCLUSIONS Carina-based setup results in a more reproducible PT and LN alignment than bony anatomy setup. Considering the independence of PT and LN displacement and the impact of volume regression on displacements over time, repeated CT imaging even with PT-based alignment is recommended in locally advanced disease.

Effect of atelectasis changes on tissue mass and dose during lung radiotherapy

Purpose: To characterize mass and density changes of lung parenchyma in non-small cell lung cancer (NSCLC) patients following midtreatment resolution of atelectasis and to quantify the impact this large geometric change has on normal tissue dose. Methods: Baseline and midtreatment CT images and contours were obtained for 18 NSCLC patients with atelectasis. Patients were classified based on atelectasis volume reduction between the two scans as having either full, partial, or no resolution. Relative mass and density changes from baseline to midtreatment were calculated based on voxel intensity and volume for each lung lobe. Patients also had clinical treatment plans available which were used to assess changes in normal tissue dose constraints from baseline to midtreatment. The midtreatment image was rigidly aligned with the baseline scan in two ways: (1) bony anatomy and (2) carina. Treatment parameters (beam apertures, weights, angles, monitor units, etc.) were transferred to each image. Then, dose was recalculated. Typical IMRT dose constraints were evaluated on all images, and the changes from baseline to each midtreatment image were investigated. Results: Atelectatic lobes experienced mean (stdev) mass changes of −2.8% (36.6%), −24.4% (33.0%), and −9.2% (17.5%) and density changes of −66.0% (6.4%), −25.6% (13.6%), and −17.0% (21.1%) for full, partial, and no resolution, respectively. Means (stdev) of dose changes to spinal cord Dmax, esophagus Dmean, and lungs Dmean were 0.67 (2.99), 0.99 (2.69), and 0.50 Gy (2.05 Gy), respectively, for bone alignment and 0.14 (1.80), 0.77 (2.95), and 0.06 Gy (1.71 Gy) for carina alignment. Dose increases with bone alignment up to 10.93, 7.92, and 5.69 Gy were found for maximum spinal cord, mean esophagus, and mean lung doses, respectively, with carina alignment yielding similar values. 44% and 22% of patients had at least one metric change by at least 5 Gy (dose metrics) or 5% (volume metrics) for bone and carina alignments, respectively. Investigation of GTV coverage showed mean (stdev) changes in VRx, Dmax, and Dmin of −5.5% (13.5%), 2.5% (4.2%), and 0.8% (8.9%), respectively, for bone alignment with similar results for carina alignment. Conclusions: Resolution of atelectasis caused mass and density decreases, on average, and introduced substantial changes in normal tissue dose metrics in a subset of the patient cohort.

SU-C-WAB-03: Assessing the Correlation Between Quantitative Measures of Contour Variability and Physician's Qualitative Measure for Clinical Usefulness of Auto-Segmentation in Prostate Cancer Radiotherapy

PURPOSE To assess the correlation between quantitative measures of contour variability and physicians qualitative measure for clinical usefulness of auto-segmentation in prostate cancer radiotherapy Methods: Our study was based on three serial CT images (one planning and two under-treatment image sets) for each of five prostate cancer patients. On each CT image, bladder, prostate and rectum were manually contoured by three experienced physicians. Deformable image registration (ITK Demons) was used to register each of the under-treatment CT images to the planning CT image. The resultant displacement vector fields were used to automatically segment planning CT organs by deformably mapping manual contours on the treatment CTs to the planning CT. For qualitative assessment of automatic and manual contours, trial was conducted with four radiation oncology residents. Each resident was shown sets of randomly chosen manual or automatic bladder, prostate and rectum contours overlaid on the planning CT image in Pinnacle (Philips TPS) using a total of hundred-thirty-five contours. Residents were asked to accept/reject contour based on its clinical usability. Quantitatively, surface distances and DICE coefficient were computed between inter-observer manual contours (manual/manual) and between each automatic and its corresponding manual contour (auto/manual). RESULTS No statistically significant differences were found in mean surface distances between manual/manual and auto/manual contours for bladder and rectum while manual/manual contour distances were significantly smaller for prostate. The distribution of DICE values between manual/manual and auto/manual contours were also similar. Qualitatively, acceptance rates for manual contours were significantly higher than that for automatic contours. CONCLUSION No correspondence was found between qualitative and quantitative measure for manual and automatic contours for rectum and bladder while the two measures appear to be related for prostate. This study suggests that using quantitative measures for evaluating auto-segmentation without a qualitative calibration might not always be predictive of its clinical usefulness.(Supported by NIH P01CA166602) This work was supported by NIH Grant P01 CA 166602 E. Weiss and J. Williamson have grants from Varian medical systems and Philips Radiation Oncology Systems.

Effect of variations in atelectasis on tumor displacement during radiation therapy for locally advanced lung cancer

Purpose Atelectasis (AT), or collapsed lung, is frequently associated with central lung tumors. We investigated the variation of atelectasis volumes during radiation therapy and analyzed the effect of AT volume changes on the reproducibility of the primary tumor (PT) position. Methods and materials Twelve patients with lung cancer who had AT and 10 patients without AT underwent repeated 4-dimensional fan beam computed tomography (CT) scans during radiation therapy per protocols that were approved by the institutional review board. Interfraction volume changes of AT and PT were correlated with PT displacements relative to bony anatomy using both a bounding box (BB) method and change in center of mass (COM). Linear regression modeling was used to determine whether PT and AT volume changes were independently associated with PT displacement. PT displacement was compared between patients with and without AT. Results The mean initial AT volume on the planning CT was 189 cm3 (37-513 cm3), and the mean PT volume was 93 cm3 (12-176 cm3). During radiation therapy, AT and PT volumes decreased on average 136.7 cm3 (20-369 cm3) for AT and 40 cm3 (−7 to 131 cm3) for PT. Eighty-three percent of patients with AT had at least one unidirectional PT shift that was greater than 0.5 cm outside of the initial BB during treatment. In patients with AT, the maximum PT COM shift was ≥0.5 cm in all patients and >1 cm in 58% of patients (0.5-2.4 cm). Changes in PT and AT volumes were independently associated with PT displacement (P < .01), and the correlation was smaller with COM (R2 = 0.58) compared with the BB method (R2 = 0.80). The median root mean squared PT displacement with the BB method was significantly less for patients without AT (0.45 cm) compared with those with AT (0.8cm, P = .002). Conclusions Changes in AT and PT volumes during radiation treatment were significantly associated with PT displacements that often exceeded standard setup margins. Repeated 3-dimensional imaging is recommended in patients with AT to evaluate for PT displacements during treatment.

CALIPER: A deformable image registration algorithm for large geometric changes during radiotherapy for locally advanced non‐small cell lung cancer

PURPOSE Locally advanced non-small cell lung cancer (NSCLC) patients may experience dramatic changes in anatomy during radiotherapy and could benefit from adaptive radiotherapy (ART). Deformable image registration (DIR) is necessary to accurately accumulate dose during plan adaptation, but current algorithms perform poorly in the presence of large geometric changes, namely atelectasis resolution. The goal of this work was to develop a DIR framework, named Consistent Anatomy in Lung Parametric imagE Registration (CALIPER), to handle large geometric changes in the thorax. METHODS Registrations were performed on pairs of baseline and mid-treatment CT datasets of NSCLC patients presenting with atelectasis at the start of treatment. Pairs were classified based on atelectasis volume change as either full, partial, or no resolution. The evaluated registration algorithms consisted of several combinations of a hybrid intensity- and feature-based similarity cost function to investigate the ability to simultaneously match healthy lung parenchyma and adjacent atelectasis. These components of the cost function included a mass-preserving intensity cost in the lung parenchyma, use of filters to enhance vascular structures in the lung parenchyma, manually delineated lung lobes as labels, and several intensity cost functions to model atelectasis change. Registration error was quantified with landmark-based target registration error and post-registration alignment of atelectatic lobes. RESULTS The registrations using both lobe labels and vasculature enhancement in addition to intensity of the CT images were found to have the highest accuracy. Of these registrations, the mean (SD) of mean landmark error across patients was 2.50 (1.16) mm, 2.80 (0.70) mm, and 2.04 (0.13) mm for no change, partial resolution, and full atelectasis resolution, respectively. The mean (SD) atelectatic lobe Dice similarity coefficient was 0.91 (0.08), 0.90 (0.08), and 0.89 (0.04), respectively, for the same groups. Registration accuracy was comparable to healthy lung registrations of current state-of-the-art algorithms reported in literature. CONCLUSIONS The CALIPER algorithm developed in this work achieves accurate image registration for challenging cases involving large geometric and topological changes in NSCLC patients, a requirement for enabling ART in this patient group.

Evaluation of Image Registration Accuracy for Tumor and Organs at Risk in the Thorax for Compliance With TG 132 Recommendations

Purpose To evaluate accuracy for 2 deformable image registration methods (in-house B-spline and MIM freeform) using image pairs exhibiting changes in patient orientation and lung volume and to assess the appropriateness of registration accuracy tolerances proposed by the American Association of Physicists in Medicine Task Group 132 under such challenging conditions via assessment by expert observers. Methods and Materials Four-dimensional computed tomography scans for 12 patients with lung cancer were acquired with patients in prone and supine positions. Tumor and organs at risk were delineated by a physician on all data sets: supine inhale (SI), supine exhale, prone inhale, and prone exhale. The SI image was registered to the other images using both registration methods. All SI contours were propagated using the resulting transformations and compared with physician delineations using Dice similarity coefficient, mean distance to agreement, and Hausdorff distance. Additionally, propagated contours were anonymized along with ground-truth contours and rated for quality by physician-observers. Results Averaged across all patients, the accuracy metrics investigated remained within tolerances recommended by Task Group 132 (Dice similarity coefficient >0.8, mean distance to agreement <3 mm). MIM performed better with both complex (vertebrae) and low-contrast (esophagus) structures, whereas the in-house method performed better with lungs (whole and individual lobes). Accuracy metrics worsened but remained within tolerances when propagating from supine to prone; however, the Jacobian determinant contained regions with negative values, indicating localized nonphysiologic deformations. For MIM and in-house registrations, 50% and 43.8%, respectively, of propagated contours were rated acceptable as is and 8.2% and 11.0% as clinically unacceptable. Conclusions The deformable image registration methods performed reliably and met recommended tolerances despite anatomically challenging cases exceeding typical interfraction variability. However, additional quality assurance measures are necessary for complex applications (eg, dose propagation). Human review rather than unsupervised implementation should always be part of the clinical registration workflow.

SU-F-J-67: Dosimetric Changes During Radiotherapy in Lung Cancer Patients with Atelectasis

PURPOSE Large geometric changes which occur during thoracic radiotherapy alter normal anatomy and target position and may induce clinically important dose changes. This study investigates variation of organ-at-risk (OAR) dose caused by atelectasis resolution during radiotherapy. METHODS 3D IMRT treatment plans were obtained for 14 non-small-cell lung cancer patients. Dose of the clinical plan was recalculated on a baseline scan in which lung was collapsed and on a midtreatment scan in which lung re-aeration had occurred. The changes in OAR doses were compared between the two time points. RTOG-0617 and inhouse dose-volume constraints were chosen for investigation and included spinal cord, esophagus, heart, and healthy lung. RESULTS 17 dose metrics were evaluated. The mean (SD) of change in mean lung dose, from baseline to mid-treatment (average taken across all patients), was 0.2 Gy (2.2 Gy) and ranged from -3.2 Gy to 6.0 Gy. 50% of patients experienced relative changes in mean lung dose of greater than 5% of baseline value. The mean (SD) of changes in heart V40 , V45 , and V60 were 3.2% (3.4%), 3.0% (2.9%), and 1.4% (2.1%), respectively, and were significant for the study cohort (Wilcoxon signed-rank test, p=0.0107 for V40 , p=0.0052 for V45 , and p= 0.0353 for V60 . Ranges in changes of Heart V40 , V45 , and V60 were -1.9% to 8.6%, -1.7% to 7.5%, and -2.1% to 4.5%, respectively. The mean (SD) of changes in Esophagus PRV Dmean and V60 were 0.3 Gy (3.3 Gy) and 0.8% (7.7%), respectively, and ranged from -4.8 Gy to 6.8 Gy for Dmean and -15.2% to 14.6% for V60 . CONCLUSION Patients with atelectasis present at the start of radiotherapy experience significant increases in heart dose. Substantial increases in mean lung dose also occur in a subset of patients. This work supported by the National Cancer Institute of National Institutes of Health under Award Number R01CA166119. Disclosures: Phillips Medical systems (Hugo, Weiss), National Institutes of Health (Hugo, Weiss, Christensen), and Roger Koch (Christensen) support, UpToDate (Weiss) royalties, and Varian Medical Systems (Hugo, Weiss) license. No potential conflicts of interest.

TU-AB-303-04: Characterizing CT-Derived Mass Change of Non-Tumor Pathology During Lung Radiotherapy

Purpose: Atelectasis and other commonly-observed non-tumor lung pathologies (NTPs) can change during thoracic radiotherapy altering normal anatomy and inducing large changes in tumor position. However, the characteristics of these changes are not well understood. This study investigates longitudinal NTP tissue mass change during radiotherapy. Methods: Delineation of corresponding atelectatic regions before and after re-aeration is challenging since it is difficult to detect atelectatic-region boundaries after re-aeration. Therefore, individual lobes were delineated and analyzed instead. A radiation oncologist contoured the tumor and individual lobes in the planning and mid-treatment CTs for 7 patients. Each lobe was eroded by 2–4 voxels, which was found to reduce effects of inadvertent chest wall in the lobe delineation but still preserve the mean density of the lobe. The mass of each lobe was calculated after removing the tumor region. The uninvolved lobes were used as controls. Results: Mean mass change for contralateral, ipsilateral without NTP, and NTP lobes were +2.1 (18.0) %, −9.4 (18.2) %, and −13.4 (40.1) %, respectively. For NTP lobes, the degree and direction of change depended on atelectasis resolution type (full or partial), with mean mass change for full resolution of −43.1 (16.2) % and +4.5 (40.1) % for partial. The standard deviation for NTP lobes is likely higher due to actual changes in mass as well as increased delineation variability in the presence of tumor and lung consolidation. Median mean density change was −46.4% for NTP lobes, showing significant difference from contralateral (p=8.2×10−⁴) and NTP-free ipsilateral lobes (p=0.006). Conclusion: No noticeable mass change occurred for pathology-free lobes. As NTP fully resolved, mass of the lobe decreased. One possible explanation is that the release of retained fluid and infiltrate commonly associated with NTP accounts for the reduced mass. This work was supported by the National Cancer Institute of the National Institutes of Health under Award Number R01CA166119. The authors have no conflicts of interest.

SU-E-J-151: Dosimetric Evaluation of DIR Mapped Contours for Image Guided Adaptive Radiotherapy with 4D Cone-Beam CT

PURPOSE To estimate dosimetric errors resulting from using contours deformably mapped from planning CT to 4D cone beam CT (CBCT) images for image-guided adaptive radiotherapy of locally advanced non-small cell lung cancer (NSCLC). METHODS Ten locally advanced non-small cell lung cancer (NSCLC) patients underwent one planning 4D fan-beam CT (4DFBCT) and weekly 4DCBCT scans. Multiple physicians delineated the gross tumor volume (GTV) and normal structures in planning CT images and only GTV in CBCT images. Manual contours were mapped from planning CT to CBCTs using small deformation, inverse consistent linear elastic (SICLE) algorithm for two scans in each patient. Two physicians reviewed and rated the DIR-mapped (auto) and manual GTV contours as clinically acceptable (CA), clinically acceptable after minor modification (CAMM) and unacceptable (CU). Mapped normal structures were visually inspected and corrected if necessary, and used to override tissue density for dose calculation. CTV (6mm expansion of GTV) and PTV (5mm expansion of CTV) were created. VMAT plans were generated using the DIR-mapped contours to deliver 66 Gy in 33 fractions with 95% and 100% coverage (V66) to PTV and CTV, respectively. Plan evaluation for V66 was based on manual PTV and CTV contours. RESULTS Mean PTV V66 was 84% (range 75% - 95%) and mean CTV V66 was 97% (range 93% - 100%) for CAMM scored plans (12 plans); and was 90% (range 80% - 95%) and 99% (range 95% - 100%) for CA scored plans (7 plans). The difference in V66 between CAMM and CA was significant for PTV (p = 0.03) and approached significance for CTV (p = 0.07). CONCLUSION The quality of DIR-mapped contours directly impacted the plan quality for 4DCBCT-based adaptation. Larger safety margins may be needed when planning with auto contours for IGART with 4DCBCT images. Reseach was supported by NIH P01CA116602.