Joanne Moseley

Pelvic Radiotherapy for Cancer of the Cervix: Is What You Plan Actually What You Deliver?

PURPOSE Whole pelvic intensity-modulated radiotherapy (IMRT) is increasingly being used to treat cervix cancer and other gynecologic tumors. However, tumor and normal organ movement during treatment can substantially detract from the benefits of this approach. This study explored the effect of internal anatomic changes on the dose delivered to the tumor and organs at risk using a strategy integrating deformable soft-tissue modeling with simulated dose accumulation. METHODS AND MATERIALS Twenty patients with cervix cancer underwent baseline and weekly pelvic magnetic resonance imaging during treatment. Interfraction organ motion and delivered (accumulated) dose was modeled for three treatment scenarios: four-field box, large-margin whole pelvic IMRT (20-mm planning target volume, but 10 mm inferiorly) and small-margin IMRT (5-mm planning target volume). RESULTS Individually, the planned dose was not the same as the simulated delivered dose; however, when taken as a group, this was not statistically significant for the four-field box and large-margin IMRT plans. The small-margin IMRT plans yielded adequate target coverage in most patients; however, significant target underdosing occurred in 1 patient who displayed excessive, unpredictable internal target movement. The delivered doses to the organs at risk were significantly reduced with the small-margin plan, although substantial variability was present among the patients. CONCLUSION Simulated dose accumulation might provide a more accurate depiction of the target and organ at risk coverage during fractionated whole pelvic IMRT for cervical cancer. The adequacy of primary tumor coverage using 5-mm planning target volume margins is contingent on the use of daily image-guided setup.

Contact surface and material nonlinearity modeling of human lungs

A finite element model has been developed to investigate the effect of contact surfaces and hyperelastic material properties on the mechanical behavior of human lungs of one lung cancer patient. The three-dimensional model consists of four parts, namely the left lung, right lung, tumor in the left lung and chest wall. The interaction between the lungs and chest wall was modeled using frictionless surface-based contact. Hyperelastic material properties of the lungs are used in the model. The effect of the two parameters is investigated by tracking the tumor movement, and by comparing the analytical results to the patient bifurcation points: 45 points in each lung and 18 points around the tumor. The accuracy of the model is improved by including the contact surface and hyperelastic material properties. The average error and the standard deviation (SD) in modeling the displacement in the SI direction are reduced from 0.68 (SD = 0.34) cm in the elastic model to 0.09 (0.21) cm in the contact-hyperelastic model. Similarly, the average error (SD) of tumor location decreases from 0.71 (0.21) cm in the elastic material without contact to -0.03 (0.24) cm in the hyperelastic material with contact model.

Effect of breathing motion on radiotherapy dose accumulation in the abdomen using deformable registration.

PURPOSE To investigate the effect of breathing motion and dose accumulation on the planned radiotherapy dose to liver tumors and normal tissues using deformable image registration. METHODS AND MATERIALS Twenty-one free-breathing stereotactic liver cancer radiotherapy patients, planned on static exhale computed tomography (CT) for 27-60 Gy in six fractions, were included. A biomechanical model-based deformable image registration algorithm retrospectively deformed each exhale CT to inhale CT. This deformation map was combined with exhale and inhale dose grids from the treatment planning system to accumulate dose over the breathing cycle. Accumulation was also investigated using a simple rigid liver-to-liver registration. Changes to tumor and normal tissue dose were quantified. RESULTS Relative to static plans, mean dose change (range) after deformable dose accumulation (as % of prescription dose) was -1 (-14 to 8) to minimum tumor, -4 (-15 to 0) to maximum bowel, -4 (-25 to 1) to maximum duodenum, 2 (-1 to 9) to maximum esophagus, -2 (-13 to 4) to maximum stomach, 0 (-3 to 4) to mean liver, and -1 (-5 to 1) and -2 (-7 to 1) to mean left and right kidneys. Compared to deformable registration, rigid modeling had changes up to 8% to minimum tumor and 7% to maximum normal tissues. CONCLUSION Deformable registration and dose accumulation revealed potentially significant dose changes to either a tumor or normal tissue in the majority of cases as a result of breathing motion. These changes may not be accurately accounted for with rigid motion.

Interfraction Liver Shape Variability and Impact on GTV Position During Liver Stereotactic Radiotherapy Using Abdominal Compression

PURPOSE For patients receiving liver stereotactic body radiotherapy (SBRT), abdominal compression can reduce organ motion, and daily image guidance can reduce setup error. The reproducibility of liver shape under compression may impact treatment delivery accuracy. The purpose of this study was to measure the interfractional variability in liver shape under compression, after best-fit rigid liver-to-liver registration from kilovoltage (kV) cone beam computed tomography (CBCT) scans to planning computed tomography (CT) scans and its impact on gross tumor volume (GTV) position. METHODS AND MATERIALS Evaluable patients were treated in a Research Ethics Board-approved SBRT six-fraction study with abdominal compression. Kilovoltage CBCT scans were acquired before treatment and reconstructed as respiratory sorted CBCT scans offline. Manual rigid liver-to-liver registrations were performed from exhale-phase CBCT scans to exhale planning CT scans. Each CBCT liver was contoured, exported, and compared with the planning CT scan for spatial differences, by use of in house-developed finite-element model-based deformable registration (MORFEUS). RESULTS We evaluated 83 CBCT scans from 16 patients with 30 GTVs. The mean volume of liver that deformed by greater than 3 mm was 21.7%. Excluding 1 outlier, the maximum volume that deformed by greater than 3 mm was 36.3% in a single patient. Over all patients, the absolute maximum deformations in the left-right (LR), anterior-posterior (AP), and superior-inferior directions were 10.5 mm (SD, 2.2), 12.9 mm (SD, 3.6), and 5.6 mm (SD, 2.7), respectively. The absolute mean predicted impact of liver volume displacements on GTV by use of center of mass displacements was 0.09 mm (SD, 0.13), 0.13 mm (SD, 0.18), and 0.08 mm (SD, 0.07) in the left-right, anterior-posterior, and superior-inferior directions, respectively. CONCLUSIONS Interfraction liver deformations in patients undergoing SBRT under abdominal compression after rigid liver-to-liver registrations on respiratory sorted CBCT scans were small in most patients (<5 mm).

Automated Weekly Replanning for Intensity-Modulated Radiotherapy of Cervix Cancer

PURPOSE The adoption of intensity-modulated radiotherapy (IMRT) to treat cervical malignancies has been limited in part by complex organ and tumor motion during treatment. This study explores the limits of a highly adaptive, small-margin treatment scenario to accommodate this motion. In addition, the dosimetric consequences of organ and tumor motion are modeled using a combination of deformable registration and fractional dose accumulation techniques. METHODS AND MATERIALS Thirty-three cervix cancer patients had target volumes and organs-at-risk contoured on fused, pretreatment magnetic resonance-computed tomography images and weekly magnetic resonance scans taken during treatment. The dosimetric impact of interfraction organ and target motion was compared for two hypothetical treatment scenarios: a 3-mm margin plan with no replanning, and a 3-mm margin plan with an automated replan performed on the updated weekly patient geometry. RESULTS Of the 33 patients, 24 (73%) met clinically acceptable target coverage (98% of the clinical target volume receiving at least 95% of the prescription dose) using the 3-mm margin plan without replanning. The range in dose to 98% of the clinical target volume across all patients was 7.9% of the prescription dose if no replanning was performed. After weekly replanning, this range was tightened to 2.6% of the prescription dose and all patients met clinically acceptable target coverage while maintaining organ-at-risk dose sparing. CONCLUSIONS The dosimetric impact of anatomical motion underscores the challenges of applying IMRT to treat cervix cancer. An appropriate adaptive strategy can ensure target coverage for small-margin IMRT treatments and maintain favorable organ-at-risk dose sparing.

Sliding characteristic and material compressibility of human lung: Parametric study and verification

PURPOSE To find and verify the optimum sliding characteristics and material compressibility that provide the minimum error in deformable image registration of the lungs. METHODS A deformable image registration study has been conducted on a total of 16 lung cancer patients. Patient specific three dimensional finite element models have been developed to model left and right lungs, chest (body), and tumor based on 4D CT images. Contact surfaces have been applied to lung-chest cavity interfaces. Experimental test data are used to model nonlinear material properties of lungs. A parametric study is carried out on seven patients, 20 conditions for each, to investigate the sliding behavior and the tissue compressibility of lungs. Three values of coefficient of friction of 0, 0.1, and 0.2 are investigated to model lubrication and sliding restriction on the lung-chest cavity interface. The effect of material compressibility of lungs is studied using Poissons ratios of 0.35, 0.4, 0.45, and 0.499. The model accuracy is examined by calculating the difference between the image-based displacement of bronchial bifurcation points identified in the lung images and the calculated corresponding model-based displacement. Furthermore, additional bifurcation points around the tumor and its center of mass are used to examine the effect of the mentioned parameters on the tumor localization. RESULTS The frictionless contact model with 0.4 Poissons ratio provides the smallest residual errors of 1.1 +/- 0.9, 1.5 +/- 1.3, and 2.1 +/- 1.6 mm in the LR, AP, and SI directions, respectively. Similarly, this optimum model provides the most accurate location of the tumor with residual errors of 1.0 +/- 0.6, 0.9 +/- 0.7, and 1.4 +/- 1.0 mm in all three directions. The accuracy of this model is verified on an additional nine patients with average errors of 0.8 +/- 0.7, 1.3 +/- 1.1, and 1.7 +/- 1.6 mm in the LR, AP, and SI directions, respectively. CONCLUSIONS The optimum biomechanical model with the smallest registration error is when frictionless contact model and 0.4 Poissons ratio are applied. The overall accuracies of all bifurcation points in all 16 patients including tumor points are 1.0 +/- 0.7, 1.2 +/- 1.0, and 1.7 +/- 1.4 mm in the LR, AP, and SI directions, respectively.

Improving image-guided target localization through deformable registration

Purpose. To quantify the improvements in online target localization using kV cone beam CT (CBCT) with deformable registration. Methods and material. Twelve patients treated under a 6 fraction liver cancer radiation therapy protocol were imaged in breath hold using kV CBCT at each treatment fraction. The images were imported into the treatment planning software and rigidly registered by fitting the liver, identified on the daily kV CBCT image, into the liver contours, previously drawn on the planning CT. The liver was then manually contoured on each CBCT image. Deformable registration was automatically performed, aligning the CT liver to the liver on each CBCT image using MORFEUS, a biomechanical model based deformable registration algorithm. The tumor, defined on planning CT, was mapped onto the CBCT, through MORFEUS. The center of mass (COM) displacement of the tumor was computed. Results. The mean (SD) displacement magnitude (absolute value) of the COM following deformable registration was 0.08 (0.07), 0.10 (0.11), and 0.10 (0.17) cm in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions, respectively. The maximum displacement of the COM was 0.34, 0.65, and 0.97 cm in the LR, AP, and SI directions, respectively. Fifteen percent of the treatment fractions had a COM displacement of greater than 0.3 cm and 33% of patients had at least 1 fraction with a displacement of greater than 0.3 cm. The deformable registration, excluding the manual contouring of the liver, was performed in less than 1 minute, on average. Discussion. Rigid registration of the liver volume between planning CT and verification kV CBCT localizes the tumor to within 0.3 cm for the majority (66%) of patients; however, larger offsets in tumor position can be observed due to liver deformation.

Toward efficient biomechanical-based deformable image registration of lungs for image-guided radiotherapy

Both accuracy and efficiency are critical for the implementation of biomechanical model-based deformable registration in clinical practice. The focus of this investigation is to evaluate the potential of improving the efficiency of the deformable image registration of the human lungs without loss of accuracy. Three-dimensional finite element models have been developed using image data of 14 lung cancer patients. Each model consists of two lungs, tumor and external body. Sliding of the lungs inside the chest cavity is modeled using a frictionless surface-based contact model. The effect of the type of element, finite deformation and elasticity on the accuracy and computing time is investigated. Linear and quadrilateral tetrahedral elements are used with linear and nonlinear geometric analysis. Two types of material properties are applied namely: elastic and hyperelastic. The accuracy of each of the four models is examined using a number of anatomical landmarks representing the vessels bifurcation points distributed across the lungs. The registration error is not significantly affected by the element type or linearity of analysis, with an average vector error of around 2.8 mm. The displacement differences between linear and nonlinear analysis methods are calculated for all lungs nodes and a maximum value of 3.6 mm is found in one of the nodes near the entrance of the bronchial tree into the lungs. The 95 percentile of displacement difference ranges between 0.4 and 0.8 mm. However, the time required for the analysis is reduced from 95 min in the quadratic elements nonlinear geometry model to 3.4 min in the linear element linear geometry model. Therefore using linear tetrahedral elements with linear elastic materials and linear geometry is preferable for modeling the breathing motion of lungs for image-guided radiotherapy applications.

Accumulated Dose in Liver Stereotactic Body Radiotherapy: Positioning, Breathing, and Deformation Effects

PURPOSE To investigate the accumulated dose deviations to tumors and normal tissues in liver stereotactic body radiotherapy (SBRT) and investigate their geometric causes. METHODS AND MATERIALS Thirty previously treated liver cancer patients were retrospectively evaluated. Stereotactic body radiotherapy was planned on the static exhale CT for 27-60 Gy in 6 fractions, and patients were treated in free-breathing with daily cone-beam CT guidance. Biomechanical model-based deformable image registration accumulated dose over both the planning four-dimensional (4D) CT (predicted breathing dose) and also over each fractions respiratory-correlated cone-beam CT (accumulated treatment dose). The contribution of different geometric errors to changes between the accumulated and predicted breathing dose were quantified. RESULTS Twenty-one patients (70%) had accumulated dose deviations relative to the planned static prescription dose >5%, ranging from -15% to 5% in tumors and -42% to 8% in normal tissues. Sixteen patients (53%) still had deviations relative to the 4D CT-predicted dose, which were similar in magnitude. Thirty-two tissues in these 16 patients had deviations >5% relative to the 4D CT-predicted dose, and residual setup errors (n = 17) were most often the largest cause of the deviations, followed by deformations (n = 8) and breathing variations (n = 7). CONCLUSION The majority of patients had accumulated dose deviations >5% relative to the static plan. Significant deviations relative to the predicted breathing dose still occurred in more than half the patients, commonly owing to residual setup errors. Accumulated SBRT dose may be warranted to pursue further dose escalation, adaptive SBRT, and aid in correlation with clinical outcomes.

Subjectivity in interpretation of portal films

PURPOSE We have measured the variability in identifying geometric errors and the variability in clinical decision making when using portal films. METHODS AND MATERIALS Eight observers (four radiation oncologists and four radiation therapists) viewed 40 film pairs from 40 different patients. All films, which were acquired using conventional simulator and portal film cassettes, were selected retrospectively from a large clinical database. The observers compared the simulator and portal films under standard conditions, identified the field placement errors, and decided whether adjustments in treatment were required. In addition, all films were digitized and the field placement errors were measured objectively using image registration software. RESULTS There was much variability in identifying field placement errors and even more variability in the number of recommended adjustments. The field placement errors identified by the different observers differed by up to 50 mm for the same film pair. The number of adjustments of treatment or block position recommended by the observers also varied between 8 and 25 for the same set of films. The average field placement error, before correction, for AP lung, AP pelvis, and lateral pelvis films was 5.7 mm, 6.3 mm, and 8.9 mm, while the average error after correction (i.e., correcting all errors identified by the observers) was 5.5 mm, 4.9 mm, and 5.7 mm, respectively. Thus, for lateral pelvis films, where the initial errors were larger, the observers were able to make an improvement in patient setup. CONCLUSIONS The results suggest that human observers have difficulty identifying field placement errors accurately when the errors are around 5 mm or smaller. Although there is some evidence that experience influenced the performance of the observers, the effect of experience is not large. In routine clinical environments, the use of visual inspection will detect large field placement errors. However, tools other than visual inspection will be required if field placement errors 5 mm or smaller are to be identified accurately.