Clinically relevant investigation of flattening filter-free skin dose.

As flattening filter-free (FFF) photon beams become readily available for treat-ment 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 10cm. 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 6MV 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 meaning-ful manner by reporting results normalized to 10 cm depth dose instead of depth of dose maximum.

Fatal Radiation Pneumonitis: Literature Review and Case Series.

PURPOSE: Fatal radiation pneumonitis is a rare event. In recent years, higher incidences of grade 5 pneumonitis have been reported. Based on 3 cases in our clinic, a literature review was performed to assess specific clinical features and risk factors for fatal pneumonitis. METHODS AND MATERIALS: Three patients with nonsmall cell lung cancer were treated with conventionally fractionated radiation therapy, 2 with volumetric modulated arc therapy and one with intensity modulated radiation therapy. All 3 patients had high volumes of 5 Gy in the total lung and contralateral lungs. Patients died of pneumonitis between 2 and 5 months after the end of radiation therapy. A literature review focused on grade 5 pneumonitis was performed for conventionally fractioned and stereotactic radiation therapy for lung cancer. RESULTS: Patients with grade 5 pneumonitis develop symptoms sooner than lower grade pneumonitis. Symptoms often do not respond to steroid treatment or return after steroid taper. Imaging features extend beyond the high dose area and involve the contralateral lung. Dosimetric risk factors include both low dose and high dose lung volumes. For patients undergoing stereotactic radiation therapy interstitial lung disease has been described as a risk factor. CONCLUSIONS: Despite decades of investigating radiation pneumonitis, the question of the optimum dose distribution in the lung, a large dose to a small volume versus a small dose to a large volume, is still unresolved. When both low and high dose lung volume constraints are followed, the risk for grade 5 pneumonitis has been shown to be low even with intensity modulated radiation therapy and concurrent chemotherapy. In addition to dose factors, underlying clinical and radiographic parameters play an important role for the development of grade 5 pneumonitis.

Characterization of Respiration-Induced Motion in Prone Versus Supine Patient Positioning for Thoracic Radiation Therapy.

PURPOSE: Variations in the breathing characteristics, both on short term (intrafraction) and long term (interfraction) time scales, may adversely affect the radiation therapy process at all stages when treating lung tumors. Prone position has been shown to improve consistency (ie, reduced intrafraction variability) and reproducibility (ie, reduced interfraction variability) of the respiratory pattern with respect to breathing amplitude and period as a result of natural abdominal compression, with no active involvement required from the patient. The next natural step in investigating breathing-induced changes is to evaluate motion amplitude changes between prone and supine targets or organs at risk, which is the purpose of the present study. METHODS AND MATERIALS: Patients with lung cancer received repeat helical 4-dimensional computed tomography scans, one prone and one supine, during the same radiation therapy simulation session. In the maximum-inhale and maximum-exhale phases, all thoracic structures were delineated by an expert radiation oncologist. Geometric centroid trajectories of delineated structures were compared between patient orientations. Motion amplitude was measured as the magnitude of difference in structure centroid position between inhale and exhale. RESULTS: Amplitude of organ motion was larger when the patient was in the prone position compared with supine for all structures except the lower left lobe and left lung as a whole. Across all 12 patients, significant differences in mean motion amplitude between orientations were identified for the right lung (3.0 mm, P = .01), T2 (0.5 mm, P = .01) and T12 (2.1 mm, P < .001) vertebrae, the middle third of the esophagus (4.0 mm, P = .03), and the lung tumor (1.7 mm, P = .02). CONCLUSIONS: Respiration-induced thoracic organ motion was quantified in the prone position and compared with that of the supine position for 12 patients with thoracic lesions. The prone position induced larger organ motion compared with supine, particularly for the lung tumor, likely requiring increases in planning margins compared with supine.

A fast and scalable method for quality assurance of deformable image registration on lung CT scans using convolutional neural networks.

PURPOSE: To develop and evaluate a method to automatically identify and quantify deformable image registration (DIR) errors between lung computed tomography (CT) scans for quality assurance (QA) purposes. METHODS: We propose a deep learning method to flag registration errors. The method involves preparation of a dataset for machine learning model training and testing, design of a three-dimensional (3D) convolutional neural network architecture that classifies registrations into good or poor classes, and evaluation of a metric called registration error index (REI) which provides a quantitative measure of registration error. RESULTS: Our study shows that, despite having limited number of training images available (10 CT scan pairs for training and 17 CT scan pairs for testing), the method achieves 0.882 AUC-ROC on the test dataset. Furthermore, the combined standard uncertainty of the estimated REI by our model lies within ± 0.11 (± 11% of true REI value), with a confidence level of approximately 68%. CONCLUSIONS: We have developed and evaluated our method using original clinical registrations without generating any synthetic/simulated data. Moreover, test data were acquired from a different environment than that of training data, so that the method was validated robustly. The results of this study showed that our algorithm performs reasonably well in challenging scenarios.

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.

Technical Note: A method for quality assurance of landmark sets for use in evaluation of deformable image registration accuracy of lung parenchyma.

PURPOSE: To develop a quality control method to improve the accuracy of corresponding landmark sets used for deformable image registration (DIR) evaluation in the lung parenchyma. METHODS: An iterative workflow was developed as a method for quality assurance of landmark sets. Starting with the initial landmark set for a given image pair, a landmark-based deformation was applied to one of the images. A difference image and a color overlay were generated using the deformed image and the other image of the pair. Inspection of these generated images at locations of landmarks allowed for the identification of misplaced landmarks. The observer responsible for creating the initial landmark set was tasked with review and revision of points flagged by the quality assurance procedure. Using the updated landmark sets, the process was repeated until all points were acceptable to the reviewer. RESULTS: Eighteen landmark sets, containing a mean (SD) of 170 (31) landmarks, were created using CT images from non-small cell lung cancer patients exhibiting large geometric changes and atelectasis resolution, making landmark specification challenging. Following the quality assurance procedure, the final landmark sets contained a mean (SD) of 165 (25) landmarks, as points too difficult to match were removed and points were added to regions deficient in landmarks. For landmark sets in which changes were made, maximum and mean differences in landmark positions before and after quality assurance ranged between 8.7-81.5 mm and 0.3-9.6 mm, respectively. CONCLUSIONS: An effective method for improving the accuracy of landmark correspondence was presented. This quality assurance approach enables more accurate evaluation of DIR for lung parenchyma in clinical image pairs in the absence of a ground truth deformation and may be applicable to other feature-rich anatomical sites.

The vaginal cylinder: Misunderstood, misused, or trivial? An in-depth dosimetric and multiinstitutional outcome investigation.

PURPOSE: The purpose of the study was to investigate the impact on dose distribution and radiobiological metrics of common high-dose-rate vaginal brachytherapy treatment parameters and to analyze multiinstitutional data for clinically significant impact on outcomes in early-stage endometrial cancer. METHODS AND MATERIALS: Treatment plans were created for all combinations of prescription parameters and used to quantify the dosimetric impact of each parameter and to estimate the dose delivered using common voxel-integrated radiobiological metrics. A rating system, based on risk grouping from GOG and PORTEC trials, was used to consolidate staging information into a cancer "aggressiveness" measure. Correlations between the rating, toxicity, disease recurrence, and plan parameters were investigated. RESULTS: When prescribing to 5 mm depth, the variation caused by the diameter was very large across all dose metrics, ranging from 51% to 175% increase with the most divergence in BEDmax. For surface prescription, changing the cylinder diameter from 4 cm to 2 cm caused the dose metrics of BEDmin, Dmin, and gBEUD (a = -3) to increase by 117%, 67%, and 52%, respectively. Prescription to 5-mm depth caused changes across all dose metrics of 260% compared with surface prescription for a 2-cm cylinder. Deeper prescription point (p = 0.005) and longer treatment length (p = 0.01) were correlated with increased stenosis rates. No correlation between recurrence and any plan parameter was found. CONCLUSIONS: Dramatic differences in dose distributions arise by small variations of plan parameters, with large impact on rates of vaginal stenosis, but no clear relation with local recurrence. To help radiation oncologists interpret the magnitude of these effects for their patients, we created a tool that allows comparison between dose and fractionation parameters.

Dynamic Modulated Brachytherapy (DMBT) Balloon Applicator for Accelerated Partial Breast Irradiation.

PURPOSE: To propose a novel high-dose-rate brachytherapy applicator for balloon-based dynamic modulated brachytherapy (DMBT) for accelerated partial breast irradiation (APBI) and to demonstrate its dosimetric advantage compared to the widely used Contura applicator. METHODS AND MATERIALS: The DMBT balloon device consists of a fixed central channel enabling real-time, in vivo dosimetry and an outer motion-dynamic, adjustable-radius channel capable of moving to any angular position within the balloon. This design allows placement of dwell positions anywhere within the balloon volume, guaranteeing optimal placement and generation of the applicator and treatment plan, respectively. Thirteen clinical treatment plans for patients with early-stage breast cancer receiving APBI after lumpectomy using Contura were retrospectively obtained under institutional review board approval. New treatment plans were created by replacing the Contura with the DMBT device. DMBT plans were limited to 4 angular positions and an outer channel radius of 1.5 cm. The new plans were optimized to limit dose to ribs and skin while maintaining target coverage similar to that of the clinical plan. RESULTS: Similar target coverage was obtained for the DMBT plans compared with clinical Contura plans. Across all patients the mean (standard deviation) reductions in D0.1 cc to the ribs and skin were 6.70% (6.28%) and 5.13% (6.54%), respectively. A threshold separation distance between the balloon surface and the organ at risk (OAR), below which dosimetric changes of greater than 5% were obtained, was observed to be 12 mm for ribs and skin. When both OARs were far from the balloon, DMBT plans were of similar quality to Contura plans, as expected. CONCLUSIONS: This study demonstrates the superior ability of the APBI DMBT applicator to spare OARs while achieving target coverage comparable to current treatment plans, especially when in close proximity. The DMBT balloon may enable new modes of dynamic high-dose-rate treatment delivery and allow for ultrahypofractionated dose regimens to be safely used.

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.

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.