Christopher L. Guy

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.

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-120: Evaluation of the Combined Effect of Body Orientation and Breathing On Organ Movement in Thorax Using Multi-Step Deformable Image Registration

PURPOSE Use deformable registration to map more complex anatomies that include changes associated with both different body positions and breathing, and evaluate the resultant respiratory excursions for tumors and relevant organs at risk. METHODS Same-day exhale and inhale datasets from prone and supine 4D CT scans of lung cancer patients have been registered using the Elastix software package through a 3 step process: (1) rigid registration for bony alignment (2) deformable multiresolution B-Spline registration of entire anatomy (3) deformable multiresolution B-Spline registration of lung parenchyma (to improve lung vasculature alignment).Manual contours were propagated from the supine-inhale phase to supine-exhale, prone-exhale and prone-inhale, via the resulting registration transformations. Motion excursions between exhale and inhale for both body orientations were computed for tumors, heart, esophagus, vertebrae (T2, T5, T12). RESULTS The registration accuracy was evaluated by visual inspection of the deformed contours by physicians and minimal contour adjustments were made where deemed appropriate. The average supine [mm] / prone [mm] motion amplitudes for the initial 5-patient sample are as follows: Tumor - 5.8/6.5, T5 - 1.4/2.0, T2 - 0.5/1.6, T12 - 1.7/2.9, Heart- 4.9/9.0, Upper esophagus - 1.6/3.8, Middle esophagus - 3.8/5.0, Lower esophagus - 4.1/6.7. Differences between prone and supine excursions for heart, esophagus, T2 and T12 were significant at 95% level (one-sided Wilcoxon Mann-Whitney test).On average, the right and left lung volumes increased by 10% at inhale prone and by 5% at exhale prone from their respective values in supine position. CONCLUSION A multi-step deformable registration sequence was implemented and successfully used for supine-prone image registration of thorax. In prone position, lungs are larger, likely owing to increased pulmonary compliance and decreased compressive force of the heart on lungs when prone. Breathing motion excursion is enhanced in prone, possible consequence of rib cage stabilization and increased diaphragmatic motion. Elisabeth Weiss: Research support from Philips Healthcare and National Institutes of Health; Licensing agreement with Varian Medical Systems, UpToDate royalties.

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.

Clinically relevant investigation of flattening filter-free skin dose

As flattening filter-free (FFF) photon beams become readily available for treatment delivery in techniques such as SBRT, thorough investigation of skin dose from FFF photon beams is necessary under clinically relevant conditions. Using a parallel-plate PTW Markus chamber placed in a custom water-equivalent phantom, surface-dose measurements were taken at 2×2,3×3,4×4,6×6,8×8,10×10,20×20, and 30×30 cm2 field sizes, at 80, 90, and 100 cm source-to-surface distances (SSDs), and with fields defined by jaws and multileaf collimator (MLC) using multiple beam energies (6X, 6XFFF, 10X, and 10XFFF). The same set of measurements was repeated with the chamber at a reference depth of 10 cm. Each surface measurement was normalized by its corresponding reference depth measurement for analysis. The FFF surface doses at 100 cm SSD were higher than flattened surface doses by 45% at 2×2 cm2 to 13% at 20×20 cm2 for 6 MV energy. These surface dose differences varied to a greater degree as energy increased, ranging from +63% at 2×2 cm2 to -2% at 20×20 cm2 for 10 MV. At small field sizes, higher energy increased FFF surface dose relative to flattened surface dose; while at larger field sizes, relative FFF surface dose was higher for lower energies. At both energies investigated, decreasing SSD caused a decrease in the ratios of FFF-to-flattened surface dose. Variability with SSD of FFF-to-flattened surface dose differences increased with field size and ranged from 0% to 6%. The field size at which FFF and flattened beams gave the same skin dose increased with decreasing beam energy. Surface dose was higher with MLC fields compared to jaw fields under most conditions, with the difference reaching its maximum at a field size between 4×4 cm2 and 6×6 cm2 for a given energy and SSD. This study conveyed the magnitude of surface dose in a clinically meaningful manner by reporting results normalized to 10 cm depth dose instead of depth of dose maximum. PACS number(s): 87.53.Bn, 87.53.Ly, 87.55.-x, 87.55.N-, 87.56.N.As flattening filter‐free (FFF) photon beams become readily available for treatment delivery in techniques such as SBRT, thorough investigation of skin dose from FFF photon beams is necessary under clinically relevant conditions. Using a parallel‐plate PTW Markus chamber placed in a custom water‐equivalent phantom, surface‐dose measurements were taken at 2×2,3×3,4×4,6×6,8×8,10×10,20×20, and 30×30 cm2 field sizes, at 80, 90, and 100 cm source‐to‐surface distances (SSDs), and with fields defined by jaws and multileaf collimator (MLC) using multiple beam energies (6X, 6XFFF, 10X, and 10XFFF). The same set of measurements was repeated with the chamber at a reference depth of 10 cm. Each surface measurement was normalized by its corresponding reference depth measurement for analysis. The FFF surface doses at 100 cm SSD were higher than flattened surface doses by 45% at 2×2 cm2 to 13% at 20×20 cm2 for 6 MV energy. These surface dose differences varied to a greater degree as energy increased, ranging from +63% at 2×2 cm2 to −2% at 20×20 cm2 for 10 MV. At small field sizes, higher energy increased FFF surface dose relative to flattened surface dose; while at larger field sizes, relative FFF surface dose was higher for lower energies. At both energies investigated, decreasing SSD caused a decrease in the ratios of FFF‐to‐flattened surface dose. Variability with SSD of FFF‐to‐flattened surface dose differences increased with field size and ranged from 0% to 6%. The field size at which FFF and flattened beams gave the same skin dose increased with decreasing beam energy. Surface dose was higher with MLC fields compared to jaw fields under most conditions, with the difference reaching its maximum at a field size between 4×4 cm2 and 6×6 cm2 for a given energy and SSD. This study conveyed the magnitude of surface dose in a clinically meaningful manner by reporting results normalized to 10 cm depth dose instead of depth of dose maximum. PACS number(s): 87.53.Bn, 87.53.Ly, 87.55.‐x, 87.55.N‐, 87.56.N‐

SU-E-T-185: Clinically-Relevant Investigation of Flattening Filter Free Skin Dose

Purpose: Flattening-filter-free (FFF) beams are increasingly used for small-field treatments due to inherent advantages like higher MU efficiency and reduced treatment time and scatter dose. Removal of the flattening-filter increases the electron contamination and low-energy x-rays. As such, surface-dose characteristics are different from traditional flattened (FF) beams. The goal of this work is to investigate surface dose of 6/10 MV FFF and FF beams under conditions representative of emerging complex techniques like small-field stereotactic treatments which use small fields formed with multi-leaf-collimators (MLCs) at closer SSDs. Methods: A parallel-plate PTW Markus-chamber (N23343) placed in custom air- and water-equivalent phantoms was used to measure surface-dose at 2/3/4/6/8/10/20/30 cm2 field sizes, at 80/90/100 cm source-to-surface distances, and at fields defined by jaws and MLCs. The effect of dose rate (600 and 1400/2400 MU/min) was also investigated at 100 cm SSD. Measurements were performed on TrueBeam linac (Varian Medical Systems, Palo Alto, CA) for 6X/6XFFF/10X/10XFFF beam energies. Results: No dose-rate dependence was seen for FFF skin-dose. Air-phantom measurements were, on average, 5±3% larger than for water-phantom measurements. With SSD increase from 80 to 100 cm, skin-dose decreased by an average of 3.9±2.5%. FFF beams were found to be more sensitive to SSD changes in comparison to FF beams. The difference in skin dose between MLC- and jaw-fields was less variable with field size for FFF compared to FF beams. 10 MV beams showed greater difference in FFF-to-FF ratio, 50% (jaws) and 22% (MLC), between the largest and smallest field sizes compared to 6 MV beams, 30% (jaws) and 9% (MLC). Conclusion: Under clinically-relevant conditions, surface dose for FFF beams was higher at small field size (<10 cm), lower at largest field size (30 cm), more sensitive to SSD changes, and had less variation with field size compared to dose for FF beams.

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.