Murat Surucu

Markerless motion tracking of lung tumors using dual‐energy fluoroscopy

PURPOSE To evaluate the efficacy of dual-energy (DE) vs single-energy (SE) fluoroscopic imaging of lung tumors using a markerless template-based tracking algorithm. METHODS Ten representative patient breathing patterns were programmed into a Quasar™ motion phantom. The phantom was modified by affixing pork ribs to the surface, and a cedar insert with a small spherical volume was used to simulate lung and tumor, respectively. Sequential 60 kVp (6 mA) and 120 kVp (1.5 mA) fluoroscopic sequences were acquired. Frame-by-frame weighted logarithmic subtraction was performed resulting in a DE fluoroscopic sequence. A template-based algorithm was then used to track tumor motion throughout the DE and SE fluoroscopy sequences. Tracking coordinates were evaluated against ground-truth tumor locations. Fluoroscopic images were also acquired for two lung cancer patients, neither of which had implanted fiducials. RESULTS For phantom imaging, a total of 1925 frames were analyzed. The algorithm successfully tracked the target on 99.9% (1923/1925) of DE frames vs 90.7% (1745/1925) SE images (p < 0.01). The displacement between tracking coordinates and ground truth for the phantom was 1.4 mm ± 1.1 mm for DE vs 2.0 mm ± 1.3 mm for SE (p < 0.01). Images from two patients, one with a larger tumor and one with a smaller tumor, were also analyzed. For the patient with the larger tumor, the average displacement from physician defined ground truth was 1.2 mm ± 0.6 mm for DE vs 1.4 mm ± 0.7 mm for SE (p = 0.016). For the patient that presented with a smaller tumor, the average displacement from physician defined ground truth was 2.2 mm ± 1.0 mm for DE vs 3.2 mm ± 1.4 mm for SE (p < 0.01). Importantly, for this single patient with the smaller tumor, 15.6% of the SE frames had >5 mm displacements from the ground truth vs 0% for DE fluoroscopy. CONCLUSIONS This work indicates the potential for markerless tumor tracking utilizing DE fluoroscopy. With DE imaging, the algorithm showed improved detectability vs SE fluoroscopy and was able to accurately track the tumor in nearly all cases.

Decision Trees Predicting Tumor Shrinkage for Head and Neck Cancer Implications for Adaptive Radiotherapy

Objective: To develop decision trees predicting for tumor volume reduction in patients with head and neck (H&N) cancer using pretreatment clinical and pathological parameters. Methods: Forty-eight patients treated with definitive concurrent chemoradiotherapy for squamous cell carcinoma of the nasopharynx, oropharynx, oral cavity, or hypopharynx were retrospectively analyzed. These patients were rescanned at a median dose of 37.8 Gy and replanned to account for anatomical changes. The percentages of gross tumor volume (GTV) change from initial to rescan computed tomography (CT; %GTVΔ) were calculated. Two decision trees were generated to correlate %GTVΔ in primary and nodal volumes with 14 characteristics including age, gender, Karnofsky performance status (KPS), site, human papilloma virus (HPV) status, tumor grade, primary tumor growth pattern (endophytic/exophytic), tumor/nodal/group stages, chemotherapy regimen, and primary, nodal, and total GTV volumes in the initial CT scan. The C4.5 Decision Tree induction algorithm was implemented. Results: The median %GTVΔ for primary, nodal, and total GTVs was 26.8%, 43.0%, and 31.2%, respectively. Type of chemotherapy, age, primary tumor growth pattern, site, KPS, and HPV status were the most predictive parameters for primary %GTVΔ decision tree, whereas for nodal %GTVΔ, KPS, site, age, primary tumor growth pattern, initial primary GTV, and total GTV volumes were predictive. Both decision trees had an accuracy of 88%. Conclusions: There can be significant changes in primary and nodal tumor volumes during the course of H&N chemoradiotherapy. Considering the proposed decision trees, radiation oncologists can select patients predicted to have high %GTVΔ, who would theoretically gain the most benefit from adaptive radiotherapy, in order to better use limited clinical resources.

Adaptive Radiotherapy for Head and Neck Cancer: Implications for Clinical and Dosimetry Outcomes.

Objective: To investigate the effects of adaptive radiotherapy on dosimetric, clinical, and toxicity outcomes for patients with head and neck cancer undergoing chemoradiotherapy with intensity-modulated radiotherapy. Methods: Fifty-one patients with advanced head and neck cancer underwent definitive chemoradiotherapy with the original plan optimized to deliver 70.2 Gy. All patients were resimulated at a median dose of 37.8 Gy (range, 27.0-48.6 Gy) due to changes in tumor volume and/or patient weight loss (>15% from baseline). Thirty-four patients underwent adaptive replanning for their boost planning (21.6 Gy). The dosimetric effects of the adaptive plan were compared to the original plan and the original plan copied on rescan computed tomography. Acute and late toxicities and tumor local control were assessed. Gross tumor volume reduction rate was calculated. Results: With adaptive replanning, the maximum dose to the spinal cord, brain stem, mean ipsilateral, and contralateral parotid had a median reduction of −4.5%, −3.0%, −6.2%, and −2.5%, respectively (median of 34 patients). Median gross tumor volume and boost planning target volume coverage improved by 0.8% and 0.5%, respectively. With a median follow-up time of 17.6 months, median disease-free survival and overall survival was 14.8 and 21.1 months, respectively. Median tumor volume reduction rate was 35.2%. For patients with tumor volume reduction rate ≤35.2%, median disease-free survival was 8.7 months, whereas it was 16.9 months for tumor volume reduction rate >35.2%. Four patients had residual disease after chemoradiotherapy, whereas 64.7% (20 of 34) of patients achieved locoregional control. Conclusion: Implementation of adaptive radiotherapy in head and neck cancer offers benefits including improvement in tumor coverage and decrease in dose to organs at risk. The tumor volume reduction rate during treatment was significantly correlated with disease-free survival and overall survival.

How one institution overcame the challenges to start an MRI-based brachytherapy program for cervical cancer

Purpose Adaptive magnetic resonance imaging (MRI)-based brachytherapy results in improved local control and decreased high-grade toxicities compared to historical controls. Incorporating MRI into the workflow of a department can be a major challenge when initiating an MRI-based brachytherapy program. This project aims to describe the goals, challenges, and solutions when initiating an MRI-based cervical cancer brachytherapy program at our institution. Material and methods We describe the 6-month multi-disciplinary planning phase to initiate an MRI-based brachytherapy program. We describe the specific challenges that were encountered prior to treating our first patient. Results We describe the solutions that were realized and executed to solve the challenges that we faced to establish our MRI-based brachytherapy program. We emphasize detailed coordination of care, planning, and communication to make the workflow feasible. We detail the imaging and radiation physics solutions to safely deliver MRI-based brachytherapy. The focus of these efforts is always on the delivery of optimal, state of the art patient care and treatment delivery within the context of our available institutional resources. Conclusions Previous publications have supported a transition to MRI-based brachytherapy, and this can be safely and efficiently accomplished as described in this manuscript.

A multi‐institutional study to assess adherence to lung stereotactic body radiotherapy planning goals

PURPOSE A multi-institutional planning study was performed to evaluate the frequency that current guidelines established by Radiation Therapy Oncology Group (RTOG) protocols and other literature for lung stereotactic body radiotherapy (SBRT) treatments are followed. METHODS A total of 300 patients receiving lung SBRT treatments in four different institutions were retrospectively reviewed. The treatments were delivered using Linac based SBRT (160 patients) or image guided robotic radiosurgery (140). Most tumors were located peripherally (250/300). Median fractional doses and ranges were 18 Gy (8-20 Gy), 12 Gy (6-15 Gy), and 10 Gy (5-12 Gy) for three, four, and five fraction treatments, respectively. The following planning criteria derived from RTOG trials and the literature were used to evaluate the treatment plans: planning target volumes, PTVV 100 ≥ 95% and PTVV 95 ≥ 99%; conformality indices, CI100% < 1.2 and CI50% range of 2.9-5.9 dependent on PTV; total lung-ITV: V20Gy < 10%, V12.5Gy < 15%, and V5Gy < 37%; contralateral lung V5Gy < 26%; and maximum doses for spinal cord, esophagus, trachea/bronchus, and heart and great vessels. Populations were grouped by number of fractions, and dosimetric criteria satisfaction rates (CSRs) were reported. RESULTS Five fraction regimens were the most common lung SBRT fractionation (46%). The median PTV was 27.2 cm(3) (range: 3.8-419.5 cm(3)). For all plans: mean PTVV 100 was 94.5% (±5.6%, planning CSR: 69.8%), mean PTVV 95 was 98.1% (±4.1%, CSR: 69.5%), mean CI100% was 1.14 (±0.21, CSR: 79.1%, and 16.5% within minor deviation), and mean CI50% was 5.63 (±2.8, CSR: 33.0%, and 28.0% within minor deviation). When comparing plans based on location, peripherally located tumors displayed higher PTVV 100 and PTVV 95 CSR (71.5% and 71.9%, respectively) than centrally located tumors (61.2% and 57.1%, respectively). Overall, the planning criteria were met for all the critical structure such as lung, heart, spinal cord, esophagus, and trachea/bronchus for at least 85% of the patients. CONCLUSIONS Among the various parameters that were used to evaluate the SBRT plans, the CI100% and CI50% were the most challenging criteria to meet. Although the CSRs of organs at risk were higher among all cases, their proximity to the PTV was a significant factor.

Decreased Risk of Radiation Pneumonitis With Coincident Concurrent Use of Angiotensin-converting Enzyme Inhibitors in Patients Receiving Lung Stereotactic Body Radiation Therapy.

Objectives: Angiotensin-converting enzyme inhibitors (ACEi) have demonstrated decreased rates of radiation-induced lung injury in animal models and clinical reports have demonstrated decreased pneumonitis in the setting of conventionally fractionated radiation to the lung. We tested the role of ACEi in diminishing rates of symptomatic (grade ≥2) pneumonitis in the setting of lung stereotactic body radiation therapy (SBRT). Methods: We analyzed patients treated with thoracic SBRT to 48 to 60 Gy in 4 to 5 fractions from 2006 to 2014. We reviewed pretreatment and posttreatment medication profiles to document use of ACEi, angiotensin receptor blockers, bronchodilators, aspirin, PDE-5 inhibitors, nitrates, and endothelin receptor antagonists. Pneumonitis was graded posttreatment based on Common Terminology Criteria for Adverse Events Version 4.0. Univariate and multivariate analysis was performed and time to development of pneumonitis was evaluated by the Kaplan-Meier method. Results: A total of 189 patients were evaluated with a median follow-up of 24.8 months. The overall 1-year rate of symptomatic pneumonitis was 13.2%. The 1-year rate of symptomatic pneumonitis was 4.2% for ACEi users versus 16.3% in nonusers (P=0.03). On univariate analysis, the odds of developing grade 2 or greater pneumonitis were significantly lower for patients on ACEi (P=0.03). On multivariate analysis, after controlling for clinicopathologic characteristics and dosimetric endpoints, there was a significant association between ACEi use and decreased risk of clinical pneumonitis (P=0.04). Angiotensin receptor blockers or other bronchoactive medications did not show significant associations with development of pneumonitis. Conclusions: Incidental concurrent use of ACEi demonstrated efficacy in diminishing rates of symptomatic pneumonitis in the setting of lung SBRT.

Leukemia Cutis of the Face, Scalp, and Neck Treated with Non-coplanar Split Field Volumetric Modulated Arc Therapy: A Case Report

Malignancies with a superficial involvement of the scalp present a unique technical challenge for radiation treatment planning. As an example of this, leukemic infiltration of the superficial skin as the only presentation of the disease is a rare entity. For such cases, radiation oncologists have typically treated with 3D conformal radiotherapy with matched electron fields, a technique that can lead to significant dose inhomogeneity. In this report, we describe the case of a patient with leukemia cutis with a superficial involvement of the scalp, face, and shoulders that was treated with volumetric modulated arc radiotherapy, with an impressive clinical response.

Evaluation of Deformable Image Registration-Based Contour Propagation From Planning CT to Cone-Beam CT:

Purpose: We evaluated the performance of organ contour propagation from a planning computed tomography to cone-beam computed tomography with deformable image registration by comparing contours to manual contouring. Materials and Methods: Sixteen patients were retrospectively identified based on showing considerable physical change throughout the course of treatment. Multiple organs in the 3 regions (head and neck, prostate, and pancreas) were evaluated. A cone-beam computed tomography from the end of treatment was registered to the planning computed tomography using rigid registration, followed by deformable image registration. The contours were copied on cone-beam computed tomography image sets using rigid registration and modified by 2 radiation oncologists. Contours were compared using Dice similarity coefficient, mean surface distance, and Hausdorff distance. Results: The mean physician-to-physician Dice similarity coefficient for all organs was 0.90. When compared to each physician’s contours, the overall mean for rigid was 0.76 (P < .001), and it was improved to 0.79 (P < .001) for deformable image registration. Comparing deformable image registration to physicians resulted in a mean Dice similarity coefficient of 0.77, 0.74, and 0.84 for head and neck, prostate, and pancreas groups, respectively; whereas, the physician-to-physician mean agreement for these sites was 0.87, 0.90, and 0.93 (P < .001, for all sites). The mean surface distance for physician-to-physician contours was 1.01 mm, compared to 2.58 mm for rigid-to-physician contours and 2.24 mm for deformable image registration-to-physician contours. The mean physician-to-physician Hausdorff distance was 11.32 mm, and when compared to any physician’s contours, the mean for rigid and deformable image registration was 12.1 mm and 12.0 mm (P < .001), respectively. Conclusion: The physicians had a high level of agreement via the 3 metrics; however, deformable image registration fell short of this level of agreement. The automatic workflows using deformable image registration to deform contours to cone-beam computed tomography to evaluate the changes during treatment should be used with caution.

A novel surrogate to identify anatomical changes during radiotherapy of head and neck cancer patients.

Purpose: To develop a novel method to monitor external anatomical changes in head and neck cancer patients in order to triage possible adaptive radiotherapy needs. Methods: The presented approach aims to provide information on internal anatomical changes based on variations observed in external anatomy. Setup Cone Beam Computed Tomography (CBCT) images are processed to produce an accurate external contour of the patients skin. After registering the CBCTs to the reference planning CT, the external contours from each CBCT are transferred to the initial — first week — CBCT. Contour radii, defined as the distances between an external contour and the isocenter projection in each CBCT slice, are calculated for each scan over the full 360 degrees. The changes in external anatomy are then quantified by the difference in radial distance between the external contours of any secondary CBCT relative to the initial CBCT. Finally, the radial difference is displayed in cylindrical coordinates as a 2D intensity map to highlight regions of interests with significant changes. Weekly CBCT scans from 15 head and neck patients were retrospectively analyzed to demonstrate the utility of this approach as a proof of principle. External changes suggested by the 2D radial difference map of an example patient after 23 fractions were then correlated with the changes in the gross tumor volumes and organs at risks. The resulting dosimetric effects were evaluated. An interactive standalone software application has been developed to facilitate the generation and the interpretation of the 2D intensity map. Results: The 2D radial difference maps provided qualitative and quantitative information, such as the location and the magnitude of external contour changes and the rate at which these deviations occur. Out of the 15 patients, 10 presented clear evidence of general external volume shrinkage due to weight loss, and nine patients had at least one site of local shrinkage. Only two patients showed no signs of anatomical change during their entire treatment course. For the example patient, the mean (±σ) radial difference was 6.7 (±3.0) mm for the left parotid and 7.3 (±2.5) mm for the right parotid. The mean dose to the left and right parotids increased from 20.1 Gy to 30 Gy and from 16.3 Gy to 29.6 Gy, respectively. Conclusion: This novel method provides an efficient tool to visualize 3D external anatomical changes on a single 2D map. It quickly pinpoints the location of differences in anatomy during the course of radiotherapy, which can help physicians determine if a treatment plan needs to be adapted. The interactive graphic user interface developed in this study will be evaluated in an adaptive radiotherapy workflow for head and neck patients in a future prospective trial.

Metal Artifact Reduction in Cone-Beam Computed Tomography for Head and Neck Radiotherapy.

Purpose: To evaluate a method for reducing metal artifacts, arising from dental fillings, on cone-beam computed tomography images. Materials and Methods: A projection interpolation algorithm is applied to cone-beam computed tomography images containing metal artifacts from dental fillings. This technique involves identifying metal regions in individual cone-beam computed tomography projections and interpolating the surrounding values to remove the metal from the projection data. Axial cone-beam computed tomography images are then reconstructed, resulting in a reduction in the streak artifacts produced by the metal. Both phantom and patient imaging data are used to evaluate this technique. Results: The interpolation substitution technique successfully reduced metal artifacts in all cases. Corrected images had fewer or no streak artifacts compared to their noncorrected counterparts. Quantitatively, regions of interest containing the artifacts showed reduced variance in the corrected images versus the uncorrected images. Average pixel values in regions of interest around the metal object were also closer in value to nonmetal regions after artifact reduction. Artifact correction tended to perform better on patient images with less complex metal objects versus those with multiple large dental fillings. Conclusion: The interpolation substitution is potentially an efficient and effective technique for reducing metal artifacts caused by dental fillings on cone-beam computed tomography image. This technique may be effective in reducing such artifacts in patients with head and neck cancer receiving daily image-guided radiotherapy.