Hans C.J. de Boer

Inclusion of geometrical uncertainties in radiotherapy treatment planning by means of coverage probability

PURPOSE Following the ICRU-50 recommendations, geometrical uncertainties in tumor position during radiotherapy treatments are generally included in the treatment planning by adding a margin to the clinical target volume (CTV) to yield the planning target volume (PTV). We have developed a method for automatic calculation of this margin. METHODS AND MATERIALS Geometrical uncertainties of a specific patient group can normally be characterized by the standard deviation of the distribution of systematic deviations in the patient group (Sigma) and by the average standard deviation of the distribution of random deviations (sigma). The CTV of a patient to be planned can be represented in a 3D matrix in the treatment room coordinate system with voxel values one inside and zero outside the CTV. Convolution of this matrix with the appropriate probability distributions for translations and rotations yields a matrix with coverage probabilities (CPs) which is defined as the probability for each point to be covered by the CTV. The PTV can then be chosen as a volume corresponding to a certain iso-probability level. Separate calculations are performed for systematic and random deviations. Iso-probability volumes are selected in such a way that a high percentage of the CTV volume (on average > 99%) receives a high dose (> 95%). The consequences of systematic deviations on the dose distribution in the CTV can be estimated by calculation of dose histograms of the CP matrix for systematic deviations, resulting in a so-called dose probability histogram (DPH). A DPH represents the average dose volume histogram (DVH) for all systematic deviations in the patient group. The consequences of random deviations can be calculated by convolution of the dose distribution with the probability distributions for random deviations. Using the convolved dose matrix in the DPH calculation yields full information about the influence of geometrical uncertainties on the dose in the CTV. RESULTS The model is demonstrated to be fast and accurate for a prostate, cervix, and lung cancer case. A CTV-to-PTV margin size which ensures at least 95% dose to (on average) 99% of the CTV, appears to be equal to about 2Sigma + 0.7sigma for three all cases. Because rotational deviations are included, the resulting margins can be anisotropic, as shown for the prostate cancer case. CONCLUSION A method has been developed for calculation of CTV-to-PTV margins based on the assumption that the CTV should be adequately irradiated with a high probability.

Analysis and reduction of 3D systematic and random setup errors during the simulation and treatment of lung cancer patients with CT-based external beam radiotherapy dose planning

PURPOSE To determine the magnitude of the errors made in (a) the setup of patients with lung cancer on the simulator relative to their intended setup with respect to the planned treatment beams and (b) in the setup of these patients on the treatment unit. To investigate how the systematic component of the latter errors can be reduced with an off-line decision protocol for setup corrections. METHODS AND MATERIALS For 39 patients with CT planning, digitally-reconstructed radiographs (DRRs) were calculated for anterior-posterior and lateral beams. Retrospectively, the position of the visible anatomy relative to the planned isocenter was compared with the corresponding position on the digitized simulator radiographs using contour match software. The setup accuracy at the treatment unit relative to the simulator setup was measured for 40 patients for at least 5 fractions per patient in 2 orthogonal beams with the aid of an electronic portal imaging device (EPID). Setup corrections were applied, based on an off-line decision protocol, with parameters derived from knowledge of the random setup errors in the studied patient group. RESULTS The standard deviations (SD) of the simulator setup errors relative to the CT planning setup in the lateral, longitudinal, and anterior-posterior directions were 4.0, 2.8, and 2.5 mm, respectively. The SD of rotations around the anterior-posterior axis was 1.6 degrees and around the left-right axis 1.3 degrees. The setup error at the treatment unit had a small random component in all three directions (1 SD = 2 mm). The systematic components were larger, particularly in the longitudinal direction (1 SD = 3.6 mm), but were reduced with the decision protocol to 1 SD < 2 mm with, on average, 0.6 setup correction per patient. CONCLUSION Setup errors at the simulator, which become systematic errors if the simulation defines the reference setup, were comparable to the systematic setup errors at the treatment unit in case no off-line protocol would have been applied. Hence, the omission of a separate simulation step can reduce systematic errors as efficiently as the application of an off-line correction protocol during treatment. The random errors were sufficiently small to make an off-line protocol feasible.

Electronic portal image assisted reduction of systematic set-up errors in head and neck irradiation.

PURPOSE To quantify systematic and random patient set-up errors in head and neck irradiation and to investigate the impact of an off-line correction protocol on the systematic errors. MATERIAL AND METHODS Electronic portal images were obtained for 31 patients treated for primary supra-glottic larynx carcinoma who were immobilised using a polyvinyl chloride cast. The observed patient set-up errors were input to the shrinking action level (SAL) off-line decision protocol and appropriate set-up corrections were applied. To assess the impact of the protocol, the positioning accuracy without application of set-up corrections was reconstructed. RESULTS The set-up errors obtained without set-up corrections (1 standard deviation (SD)=1.5-2mm for random and systematic errors) were comparable to those reported in other studies on similar fixation devices. On an average, six fractions per patient were imaged and the set-up of half the patients was changed due to the decision protocol. Most changes were detected during weekly check measurements, not during the first days of treatment. The application of the SAL protocol reduced the width of the distribution of systematic errors to 1mm (1 SD), as expected from simulations. A retrospective analysis showed that this accuracy should be attainable with only two measurements per patient using a different off-line correction protocol, which does not apply action levels. CONCLUSIONS Off-line verification protocols can be particularly effective in head and neck patients due to the smallness of the random set-up errors. The excellent set-up reproducibility that can be achieved with such protocols enables accurate dose delivery in conformal treatments.

Reduction of Respiratory Liver Tumor Motion by Abdominal Compression in Stereotactic Body Frame, Analyzed by Tracking Fiducial Markers Implanted in Liver

PURPOSE To investigate in a three-dimensional framework the effectiveness and reproducibility of reducing the respiratory motion of liver tumors using abdominal compression in a stereotactic body frame. METHODS AND MATERIALS A total of 12 patients with liver tumors, who were treated with stereotactic body radiotherapy, were included in this study. These patients had three gold fiducial markers implanted in the healthy liver tissue surrounding the tumor. Fluoroscopic videos were acquired on the planning day and before each treatment fraction to visualize the motion of the fiducial markers during free breathing and varying levels of abdominal compression. Software was developed to track the fiducial markers and measure their excursions. RESULTS Abdominal compression reduced the patient group median excursion by 62% in the craniocaudal and 38% in the anteroposterior direction with respect to the median free-breathing excursions. In the left-right direction, the median excursion increased 15% (maximal increase 1.6 mm). The median residual excursion was 4.1 mm in the craniocaudal, 2.4 mm in the anteroposterior, and 1.8 mm in the left-right direction. The mean excursions were reduced by compression to <5 mm in all patients and all directions, with two exceptions (craniocaudal excursion reduction of 20.5 mm to 7.4 mm and of 21.1 mm to 5.9 mm). The residual excursions reproduced well during the treatment course, and the craniocaudal excursions measured on the treatment days were never significantly (alpha = 0.05) greater than on the planning days. Fine tuning the compression did not considerably change the excursion on the treatment days. CONCLUSIONS Abdominal compression effectively reduced liver tumor motion, yielding small and reproducible excursions in three dimensions. The compression level established at planning could have been safely used on the treatment days.

Deformation of prostate and seminal vesicles relative to intraprostatic fiducial markers.

PURPOSE To quantify the residual geometric uncertainties after on-line corrections with intraprostatic fiducial markers, this study analyzed the deformation of the prostate and, in particular, the seminal vesicles relative to such markers. PATIENTS AND METHODS A planning computed tomography (CT) scan and three repeat CT scans were obtained for 21 prostate cancer patients who had had three to four cylindrical gold markers placed. The prostate and whole seminal vesicles (clinical target volume [CTV]) were delineated on each scan at a slice thickness of 1.5 mm. Rigid body transformations (translation and rotation) mapping the markers onto the planning scan positions were obtained. The translation only (T(only)) or both translation and rotation were applied to the delineated CTVs. Next, the residue CTV surface displacements were determined using nonrigid registration of the delineated contours. For translation and rotation of the CTV, the residues represented deformation; for T(only), the residues stemmed from deformation and rotation. T(only) represented the residues for most currently applied on-line protocols. The patient and population statistics of the CTV surface displacements were calculated. The intraobserver delineation variation was similarly quantified using repeat delineations for all patients and corrected for. RESULTS The largest CTV deformations were observed at the anterior and posterior side of the seminal vesicles (population average standard deviation </=3 mm). Prostate deformation was small (standard deviation </=1 mm). The increase in these deviations when neglecting rotation (T(only)) was small. CONCLUSION Although prostate deformation with respect to implanted fiducial markers was small, the corresponding deformation of the seminal vesicles was considerable. Adding marker-based rotational corrections to on-line translation corrections provided a limited reduction in the estimated planning margins.

On-line set-up corrections during radiotherapy of patients with gynecologic tumors

PURPOSE Positioning of patients with gynecologic tumors for radiotherapy has proven to be relatively inaccurate. To improve the accuracy and reduce the margins from clinical target volume (CTV) to planning target volume (PTV), on-line set-up corrections were investigated. METHODS AND MATERIALS Anterior-posterior portal images of 14 patients were acquired using the first six monitor units (MU) of each irradiation fraction. The set-up deviation was established by matching three user-defined landmarks in portal and simulator image. If the two-dimensional deviation exceeded 4 mm, the table position was corrected. A second portal image was acquired using 30 MU of the remaining dose. This image was analyzed off-line using a semiautomatic contour match to obtain the final set-up accuracy. To verify the landmark match accuracy, the contour match was retrospectively performed on the six MU images as well. RESULTS The standard deviation (SD) of the distribution of systematic set-up deviations after correction was < 1 mm in left-right and cranio-caudal directions. The average random deviation was < 2 mm in these directions (1 SD). Before correction, all standard deviations were 2 to 3 mm. The landmark match procedure was sufficiently accurate and added on average 3 min to the treatment time. The application of on-line corrections justifies a CTV-to-PTV margin reduction to about 5 mm. CONCLUSIONS On-line set-up corrections significantly improve the positioning accuracy. The procedure increases treatment time but might be used effectively in combination with off-line corrections.

An analysis of anatomic landmark mobility and setup deviations in radiotherapy for lung cancer

PURPOSE To identify thoracic structures that exhibit little internal motion during irradiation and to determine setup variations in patients with lung cancer. METHODS AND MATERIALS Intrafractional images were generated with an electronic portal-imaging device from the AP fields of 10 patients, during several fractions. To determine the intrafractional mobility of thoracic structures, visible structures were contoured in every image and matched with a reference image by means of a cross-correlation algorithm. Setup variations were determined by comparing portal images with the digitized simulator films using the stable structures as landmarks. RESULTS Mobility was limited in the lateral direction for the trachea, thoracic wall, paraspinal line, and aortic notch, and in the craniocaudal direction for the clavicle, aortic notch, and thoracic.wall. Analysis of patient setup revealed random deviations of 2.0 mm (1 SD) in the lateral direction and 2.8 mm in the craniocaudal direction, while the systematic deviations were 2.5 and 2.0 mm (1 SD) respectively. CONCLUSIONS We have identified thoracic structures that exhibit little internal motion in the frontal plane, and recommend that these structures be used for verifying patient setup during radiotherapy. The daily variation in the setup of lung cancer patients at our center appears to be acceptable.

POTENTIALS AND LIMITATIONS OF GUIDING LIVER STEREOTACTIC BODY RADIATION THERAPY SET-UP ON LIVER-IMPLANTED FIDUCIAL MARKERS

PURPOSE We investigated the potentials and limitations of guiding liver stereotactic body radiation therapy (SBRT) set-up on liver-implanted fiducial markers. METHODS AND MATERIALS Twelve patients undergoing compression-supported SBRT in a stereotactic body frame received fluoroscopy at treatment preparation and before each treatment fraction. In fluoroscopic videos we localized the markers and diaphragm tip at expiration and the spine (measurements on free-breathing and abdominal compression). Day-to-day displacements, rotations (markers only), and deformations were determined. Marker guidance was compared to conventional set-up strategies in treatment set-up simulations. RESULTS For compression, day-to-day motion of markers with respect to their centers of mass (COM) was sigma = 0.9 mm (random error SD), Sigma = 0.4 mm (systematic error SD), and <2.1 mm (maximum). Consequently, assuming that markers were closely surrounding spherical tumors, marker COM-guided set-up would have required safety margins of approximately 2 mm. Using marker COM as the gold standard, other set-up methods (using no correction, spine registration, and diaphragm tip craniocaudal registration) resulted in set-up errors of 1.4 mm < sigma < 2.8 mm, 2.6 mm < Sigma < 5.1 mm, and 6.3 mm < max < 12.4 mm. Day-to-day intermarker motion of <16.7%, 2.2% median, and rotations between 3.5 degrees and 7.2 degrees were observed. For markers not surrounding the tumor, e.g., 5 cm between respective COMs, these changes could effect residual tumor set-up errors up to 8.4 mm, 1.1 mm median (deformations), and 3.1 mm to 6.3 mm (rotations). Compression did not systematically contribute to deformations and rotations, since similar results were observed for free-breathing. CONCLUSIONS If markers can be implanted near and around the tumor, residual set-up errors by marker guidance are small compared to those of conventional set-up methods, allowing high-precision tumor radiation set-up. However, substantial errors may result if markers are not implanted precisely, requiring further research to obtain adequate safety margins.

Reduction of irradiated small bowel volume and accurate patient positioning by use of a bellyboard device in pelvic radiotherapy of gynecological cancer patients

PURPOSE To reduce the volume of small bowel within pelvic treatment fields for gynecological cancer using a bellyboard device and to determine the accuracy of the prone treatment position. MATERIALS AND METHODS Fifteen consecutive patients with a gynecologic malignancy who were treated with postoperative pelvic radiotherapy were selected for this study. The volume of small bowel within the treatment fields was calculated for both the supine and prone treatment positions. The patients were treated in the prone position in a so-called bellyboard device. During treatment sessions electronic portal images were obtained. An off-line setup verification and correction protocol was used and the setup accuracy of the positioning in the bellyboard was determined. RESULTS The average volume of small bowel within the treatment fields was 229 cm(3) and 66 cm(3) in the supine and prone treatment, respectively, which means an average volume reduction in the prone position of 64% (95% CI 56-72%), as compared with the supine position. For the position of the patient in the field, the systematic error defined by the standard deviation (SD) of the mean difference per patient between simulation and treatment images was 1.7 mm in the lateral direction, 2.1 mm in the craniocaudal direction and 1.7 mm in the ventrodorsal direction. On average, only 0.4 setup correction per patient was required to achieve this accuracy. The random day-to-day variations were 1.9 (1SD), 2.6 and 2.3 mm, respectively. Standard deviations of the systematic differences between patient positioning relative to the bellyboard were 6.2 mm in lateral direction and 9.1 mm in craniocaudal direction. CONCLUSIONS Treatment of gynecological cancer patients in the prone position using a bellyboard reduces the volume of irradiated small bowel. An off-line verification and correction protocol ensures accurate patient positioning. Daily setup variations using the bellyboard were small (1 SD<3 mm). Therefore for pelvic radiotherapy in patients with a gynecological malignancy, the use of a bellyboard is recommended.

Margin evaluation in the presence of deformation, rotation, and translation in prostate and entire seminal vesicle irradiation with daily marker-based setup corrections.

PURPOSE To develop a method for margin evaluation accounting for all measured displacements during treatment of prostate cancer. METHODS AND MATERIALS For 21 patients treated with stereographic targeting marker-based online translation corrections, dose distributions with varying margins and gradients were created. Sets of possible cumulative delivered dose distributions were simulated by moving voxels and accumulating dose per voxel. Voxel motion was simulated consistent with measured distributions of systematic and random displacements due to stereographic targeting inaccuracies, deformation, rotation, and intrafraction motion. The method of simulation maintained measured correlation of voxel motions due to organ deformation. RESULTS For the clinical target volume including prostate and seminal vesicles (SV), the probability that some part receives <95% of the prescribed dose, the changes in minimum dose, and volume receiving 95% of prescription dose compared with planning were 80.5% ± 19.2%, 9.0 ± 6.8 Gy, and 3.0% ± 3.7%, respectively, for the smallest studied margins (3 mm prostate, 5 mm SV) and steepest dose gradients. Corresponding values for largest margins (5 mm prostate, 8 mm SV) with a clinical intensity-modulated radiotherapy dose distribution were 46.5% ± 34.7%, 6.7 ± 5.8 Gy, and 1.6% ± 2.3%. For prostate-only clinical target volume, the values were 51.8% ± 17.7%, 3.3 ± 1.6 Gy, and 0.6% ± 0.5% with the smallest margins and 5.2% ± 7.4%, 1.8 ± 0.9 Gy, and 0.1% ± 0.1% for the largest margins. Addition of three-dimensional rotation corrections only improved these values slightly. All rectal planning constraints were met in the actual reconstructed doses for all studied margins. CONCLUSION We developed a system for margin validation in the presence of deformations. In our population, a 5-mm margin provided sufficient dosimetric coverage for the prostate. In contrast, an 8-mm SV margin was still insufficient owing to deformations. Addition of three-dimensional rotation corrections was of minor influence.