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Short communication: CT-MRI image fusion for 3D conformal prostate radiotherapy: use in patients with altered pelvic anatomy.

We describe the application of CT-MRI fusion software for 3D conformal radiotherapy in two patients with localized prostate cancer who had significantly altered pelvic anatomy due to prior surgery. Patient A had a hemipelvectomy for fibrosarcoma and Patient B had an abdominoperineal resection (APR) for rectal carcinoma. Using the Picker AcQSIM 3D treatment planning software equipped with CT-MRI fusion capabilities, we were able to construct 3D conformal treatment plans for the two patients. The CT-MRI fusion was invaluable in the 3D conformal treatment planning of these cases with distorted pelvic anatomy. It allowed for accurate identification of the clinical target volume (CTV) and was also able to better visualize normal structures so that the radiation beams could be placed to minimize toxicity to the normal tissues.

Adenocarcinoma↗

Impact of neoadjuvant androgen ablation and other factors on late toxicity after external beam prostate radiotherapy.

PURPOSE: To evaluate the late toxicity profile of prostate cancer patients treated with external beam radiotherapy, to investigate the possible risk factors for late toxicity, and to determine whether neoadjuvant androgen ablation (NAA) is a factor. METHODS AND MATERIALS: The study population consisted of 1192 patients with > or =24 months' follow-up. Late GI and GU toxicities were scored with a modified Radiation Therapy Oncology Group/Subjective, Objective, Management, and Analytic scale. All patients were treated with external beam radiotherapy (52.5 Gy in 20 fractions to 72 Gy in 36 fractions), using either conventional or three-dimensional conformal techniques. Of the 1192 patients, 40% received NAA (median 5 months). Risk factors investigated on multivariate analysis were age, past medical history, use of pelvic fields, dose, fractionation, use and duration of neo- and adjuvant androgen ablation, and acute toxicity (Grade 2 or greater). RESULTS: The median follow-up for the group was 49 months (range 24-105). The incidence of late Grade 2-3 GI or GU toxicity was 30% at 5 years (GI 12% and GU 20%). The incidence of late Grade 3 GI or GU toxicity was 8% at 5 years (GI 2.7% and GU 5.5%). No Grade 4 toxicity occurred. The risk factors of significance in relation to the development of late Grade 3 GU toxicity were coexisting GU disease (p = 0.02), prior transurethral resection of the prostate or transurethral resection of bladder tumor (p <0.0001), and presence of acute GU toxicity (p = 0.012). For late Grade 3 GI toxicity, short-term (< or =2 months) NAA (p = 0.0002) and coexisting GI disease (p = 0.017) were risk factors. CONCLUSION: Short-term (< or =2 months) NAA, but not longer durations of NAA, increases the risk of developing Grade 3 GI late toxicity. The possible mechanism of this phenomenon is unclear.

Aged↗

Evaluation of a contour-alignment technique for CT-guided prostate radiotherapy: an intra- and interobserver study.

PURPOSE: The recent introduction of integrated CT/linear accelerator systems may mean that daily CT localization can become a reality in the clinic, possibly allowing further dose escalation to the prostate while limiting unwanted doses to the rectum and bladder. However, the implementation of CT localization is currently impeded by the lack of precise and robust techniques to align the treatment plan with the daily CT images. The purpose of this study was to evaluate a manual alignment technique, in which the gross target volume contours are overlaid on the daily CT images and then shifted to match the structures visible in the images. METHODS AND MATERIALS: A total of 28 CT image sets were taken before the standard delivery of intensity-modulated radiotherapy for prostate cancer for 2 patients. Seven observers (four radiation oncologists and three medical physicists) manually shifted the gross target volume contours from the treatment plan to best match the daily CT images. One observer repeated the process 1 week later to evaluate intraobserver variations. The experiment was then repeated, but the CT images from the original treatment plan were used as a reference to reduce interobserver uncertainty when aligning the contours. The shifts in prostate position found by different observers, both with and without reference data, were evaluated using a factorial analysis of variance to determine the standard errors of measurement for the intra- and interobserver uncertainty (SEM(intra) and SEM(inter), respectively). The differences in the SEM for the two groups of observers (radiation oncologists and medical physicists), the two alignment techniques (with and without reference information), and the two patients were evaluated using the t test at 90% confidence levels. RESULTS: With no reference information, the SEM(inter) using one patient data set (Patient 1) was 0.8 mm, 2.0 mm, and 2.2 mm in the right-left (RL), anterior-posterior (AP), and superior-inferior (SI) directions, respectively. The use of the treatment plan as a reference reduced the SEM(inter) to 0.7 mm, 1.0 mm, and 1.6 mm in the RL, AP, and SI directions, respectively. In Patient 2, localization of the prostate was more difficult; the best SEM(inter) achieved with this patient was 0.8 mm, 1.9 mm, and 2.0 mm in the RL, AP, and SI directions, respectively. The SEM(intra) values with Patient 1 were also slightly better than with Patient 2. When reference data were used, the SEM(intra) value was 0.5 mm, 0.7 mm, and 0.5 mm for Patient 1 and 0.6 mm, 1.0 mm, and 0.7 mm for Patient 2 in the RL, AP, and SI directions, respectively. Despite the larger than expected interobserver variation reported here, the SEM(inter) was smaller than the typical day-to-day variation in prostate position. The contour alignment technique may still be useful to aid daily prostate localization or in a correction scheme to minimize the effect of target positional error. CONCLUSION: The interobserver uncertainties associated with aligning the gross target volume contours with daily CT images were sufficiently small that this method may be used for daily CT localization of the prostate. The use of a reference image is important to improve the consistency among different users in this technique.

Analysis of Variance↗

A practical approach to inverse planning for high-precision dose escalated conformal prostate radiotherapy.

The problem of choosing the best gantry angles and beam weights for dose-escalated conformal prostate treatment planning is formulated using a mixed-integer linear programming approach, to account for tumour dose homogeneity and dose-volume constraints. The formulation allows the number of beams to be restricted and for some of the beams to be compulsory. The present planning algorithm interfaces with and utilizes the three-dimensional planning capabilities of a commercial treatment planning system. A case study is illustrated, which represents a particularly challenging planning problem due to a large planning target volume and an unusually small bladder. Treatment plans with different numbers of beams are generated to compare with each other and with the standard six-field plan. Significant improvement is shown in the reduction of hot regions within the femoral heads and rectal wall, while not unduly compromising homogeneity constraints for the tumour.

Humans↗

Improvements in prostate radiotherapy from the customization of beam directions.

A methodology for optimizing the beam directions in radiotherapy treatment planning has been developed and tested on a cohort of twelve prostate patients. An optimization algorithm employing a an objective cost function was used, based on beam's-eye-view volumetrics but also employing a simple dose model and biological considerations for organs-at-risk (OARs). The cost function embodies information about the volume of OARs in a single field and their position relative to the planning target volume (PTV). The proximity of the PTV to the surface of the patient is also included. Within the algorithm "importance factor" were used to model the clinical importance of different organs-at-risk so that all organs-at-risk were included in a single objective score. "Gantry-angle-windows" were introduced to restrict the available beam directions. The methodology was applied to twelve prostate patients to determine the optimum beam directions for three-field direction plans. Orientation-optimized and standard treatment plans were compared via measures of tumor control probability (TCP) and normal tissue complication probability (NTCP). Standard plans had fixed beam directions whereas orientation-optimized plans contained beam directions chosen by the algorithm. The beam-weights of both the orientation-optimized and standard plans were optimized using a dose-based simulated annealing algorithm to allow the improvements by optimizing the beam directions to be studied in isolation. The results of the comparison show that optimization of the beam directions yielded better plans, in terms of TCP and NTCP, than the standard plans. When the dose to the isocenter was scaled to produce a rectal NTCP of 1%, the average TCP of the orientation-optimized plans was (5.7 +/- 1.4)% greater than that for the standard plans. In conclusion, the customization of beam directions in the treatment planning of prostate patients using and objective cost function and allowed gantry-angle-windows produces superior three-field direction plans compared to standard treatment plans.

Algorithms↗

A prospective comparison of three systems of patient immobilization for prostate radiotherapy.

PURPOSE: The study compared the setup reliability of 3 patient immobilization systems, a rubber leg cushion, the alpha cradle, and the thermoplastic Hipfix device, in 77 patients with cT1-T3, N0, M0 prostate cancer receiving conformal radiotherapy. METHODS AND MATERIALS: Port films were analyzed and compared to simulation films to estimate the setup errors in the three coordinate axes (anterior-posterior, cranial-caudal, medial-lateral). A total vector error was calculated from these shifts. RESULTS: The Hipfix was found significantly superior to the other two devices in reducing mean setup errors in all axes (p < 0.005). The average field-positioning error with the Hipfix ranged from 1.9 mm to 2.6 mm for all axes, whereas the deviation for the other two systems ranged from 2.7 to 3. 4 mm. Errors greater than 10 mm were virtually eliminated with the Hipfix system. There was a reduction in the mean total vector error in the alpha cradle and Hipfix patient cohorts over time, reflecting improved efficacy as a result of experience. CONCLUSION: There was a significant difference in the performance of each immobilization device. The Hipfix was consistently more reliable in reducing setup errors than the other devices.

Analysis of Variance↗

Method comparison of ultrasound and kilovoltage x-ray fiducial marker imaging for prostate radiotherapy targeting.

Several measurement techniques have been developed to address the capability for target volume reduction via target localization in image-guided radiotherapy; among these have been ultrasound (US) and fiducial marker (FM) software-assisted localization. In order to assess interchangeability between methods, US and FM localization were compared using established techniques for determination of agreement between measurement methods when a 'gold-standard' comparator does not exist, after performing both techniques daily on a sequential series of patients. At least 3 days prior to CT simulation, four gold seeds were placed within the prostate. FM software-assisted localization utilized the ExacTrac X-Ray 6D (BrainLab AG, Germany) kVp x-ray image acquisition system to determine prostate position; US prostate targeting was performed on each patient using the SonArray (Varian, Palo Alto, CA). Patients were aligned daily using laser alignment of skin marks. Directional shifts were then calculated by each respective system in the X, Y and Z dimensions before each daily treatment fraction, previous to any treatment or couch adjustment, as well as a composite vector of displacement. Directional shift agreement in each axis was compared using Altman-Bland limits of agreement, Lin's concordance coefficient with Partik's grading schema, and Deming orthogonal bias-weighted correlation methodology. 1,019 software-assisted shifts were suggested by US and FM in 39 patients. The 95% limits of agreement in X, Y and Z axes were +/-9.4 mm, +/-11.3 mm and +/-13.4, respectively. Three-dimensionally, measurements agreed within 13.4 mm in 95% of all paired measures. In all axes, concordance was graded as 'poor' or 'unacceptable'. Deming regression detected proportional bias in both directional axes and three-dimensional vectors. Our data suggest substantial differences between US and FM image-guided measures and subsequent suggested directional shifts. Analysis reveals that the vast majority of all individual US and FM directional measures may be expected to agree with each other within a range of 1-1.5 cm. Since neither system represents a gold standard, clinical judgment must dictate whether such a difference is of import. As IMRT protocols seek dose escalation and PTV reduction predicated on US- and FM-guided imaging, future studies are needed to address these potential clinically relevant issues regarding the interchangeability and accuracy of novel positional verification techniques. Comparison series with multiple image-guidance systems are needed to refine comparisons between targeting methods. However, we do not advocate interchangeability of US and FM localization methods.

Calibration↗

Numerical analysis of a model of organ motion using serial imaging measurements from prostate radiotherapy.

We previously proposed a model for incorporating the effects of organ motion, including the changes in organ shape, into the calculation of dose in a statistical fashion based on serial imaging measurements of organ motion. In the present paper, numerical studies were used to investigate how the accuracy of the statistical calculation of dose depends on the number of organ motion measurements provided as input into the model. The dose calculated statistically with the model was consistently more accurate than the one obtained by directly resampling the serial measurements of organ motion. It was also more robust relative to the random variabilities present in the input organ motion measurements. The results confirm that the model can reproduce the statistical distribution of the organ motions measured in a serial imaging study, including the changes in organ shape, without making any assumptions about the functional form of this distribution. The model allows a more accurate calculation of dose to be performed from a given number of measurements of organ motion than would otherwise be obtained by directly resampling the measured data. It thus maximizes the information that is extracted from serial imaging measurements.

Algorithms↗

Feasibility of penumbra compensating filters for conformal prostate radiotherapy.

Radiation therapy beams demonstrate a gradual dose fall off at the field edges, due to factors affecting the physical penumbra and transport of radiation. Adequate target coverage requires an increase in field size larger than the target volume itself for a uniform dose to be delivered to that target volume. A method is presented for the design and fabrication of penumbra compensating filters (PCFs) which essentially sharpen the penumbra on a field-by-field basis and are used in conjunction with custom shielding blocks. We have explored the feasibility of using PCFs to reduce the field margins required for our four-field conformal prostate treatments. The penumbra compensation is designed based on a profile measured along the direction perpendicular to the blocked field edge that shows the greatest 50% to 95% isodose distance for a typical conformal prostate patient. Rigid foam material is milled and filled with a low melting point alloy material to create a filter which provides dose compensation in the field periphery of the custom shielding block. The accuracy of our methodology has been established using film dosimetry. By employing PCFs, the reduction in the rectal margin ranges from approximately 4 mm in the posterior region to 13 mm in the superior-posterior region, as compared with the shielding blocks alone. The reduction in bladder margin ranges from approximately 4 mm in the superior-anterior region to 10 mm in the superior region. Dose-volume histograms for an idealized cylindrical rectum indicate a substantial reduction in the volume treated to high doses. The calculated normal tissue complication probability values were 8.7% and 10.5% with and without PCFs included in the blocked fields respectively. The advantages of using PCFs, compared with multileaf collimator based techniques, are discussed.

Equipment Design↗

A gradient feature weighted Minimax algorithm for registration of multiple portal images to 3DCT volumes in prostate radiotherapy.

PURPOSE: To develop an accurate, fast, and robust algorithm for registering portal and computed tomographic (CT) images for radiotherapy using a combination of sparse and dense field data that complement each other. METHODS AND MATERIALS: Gradient Feature Weighted Minimax (GFW Minimax) method was developed to register multiple portal images to three-dimensional CT images. Its performance was compared with that of three others: Minimax, Mutual Information, and Gilhuijs' method. Phantom and prostate cancer patient images were used. Effects of registration errors on tumor control probability (TCP) and normal tissue complication probability (NTCP) were investigated as a relative measure. RESULTS: Registration of four portals to CTs resulted in 30% lower error when compared with registration with two portals. Computation time increased by nearly 50%. GFW Minimax performed the best, followed by Gilhuijs' method, the Minimax method, and Mutual Information. CONCLUSIONS: Using four portals instead of two lowered the registration error. Reduced fields of view images with full feature sets gave similar results in shorter times as full fields of view images. In clinical situations where soft tissue targets are of importance, GFW Minimax algorithm was significantly more accurate and robust. With registration errors lower than 1 mm, margins may be scaled down to 4 mm without adversely affecting TCP and NTCP.

Algorithms↗

Dosimetric implications of changes in patient repositioning and organ motion in conformal radiotherapy for prostate cancer.

PURPOSE: To assess the influence of patient repositioning and organ motion on dose distribution within the prostate and the seminal vesicles (clinical target volume, (CTV)). MATERIAL AND METHODS: Nine patients were simulated and treated in the supine position, with an empty bladder, and without immobilization devices. While on treatment, patients underwent weekly pelvic computed tomography (CT) scans under conditions identical to those at simulation. Patients were aligned using lasers on anterior and lateral skin tattoos, onto which lead markers were placed. After each CT scan (n=53) the CTV was redefined by contouring, and a new isocenter was obtained. A six-field technique was used. The field margins around the CTV were 20 mm in the cranio-caudal axis, and 13 mm in the other axes, except in the lateral fields where a 10 mm posterior margin was used. Dose-volume histograms (DVHs) for each organ were compared with those determined at simulation, using the notion of the proportional change in the area under the CTV-DVH curve resulting from a change in treatment plan (cDVH). RESULTS: The reproducibility of the dose distribution was good for the prostate (%cDVH, mean+/-SD: -0.97+/-2.11%) and less than optimal for the seminal vesicles (%cDVH, mean+/-SD: -4.66+/-10.45%). When correlating prostate %cDVH variations with displacements of the isocenter in the Y axis (antero-posterior) the %cDVH exceeded (-)5% in only two dosimetries, both with an isocenter shift of >10 mm. For the seminal vesicles, however, ten out of 53 dosimetries showed a %cDVH exceeding (-) 5%. In nine of these ten dose distribution studies the posterior shift of the isocenter exceeded 8 mm. CONCLUSIONS: Precise targeting of prostate radiotherapy is primarily dependent on careful daily set-up and on random changes in rectal geometry. Margins no less than 10 mm around the prostate and at least 15 mm around the seminal vesicles are probably necessary to insure adequate target coverage with a six-field technique.

Humans↗

On-line aSi portal imaging of implanted fiducial markers for the reduction of interfraction error during conformal radiotherapy of prostate carcinoma.

PURPOSE: An on-line system to ensure accuracy of daily setup and therapy of the prostate has been implemented with no equipment modification required. We report results and accuracy of patient setup using this system. METHODS AND MATERIALS: Radiopaque fiducial markers were implanted into the prostate before radiation therapy. Lateral digitally reconstructed radiographs (DRRs) were obtained from planning CT data. Before each treatment fraction, a lateral amorphous silicon (aSi) portal image was acquired and the position of the fiducial markers was compared to the DRRs using chamfer matching. Couch translation only was used to account for marker position displacements, followed by a second lateral portal image to verify isocenter position. Residual displacement data for the aSi and previous portal film systems were compared. RESULTS: This analysis includes a total of 239 portal images during treatment in 17 patients. Initial prostate center of mass (COM) displacements in the superior, inferior, anterior, and posterior directions were a maximum of 7 mm, 9 mm, 10 mm and 11 mm respectively. After identification and correction, prostate COM displacements were <3 mm in all directions. The therapists found it simple to match markers 88% of the time using this system. Treatment delivery times were in the order of 9 min for patients requiring isocenter adjustment and 6 min for those who did not. CONCLUSIONS: This system is technically possible to implement and use as part of an on-line correction protocol and does not require a longer than standard daily appointment time at our center with the current action limit of 3 mm. The system is commercially available and is more efficient and user-friendly than portal film analysis. It provides the opportunity to identify and accommodate interfraction organ motion and may also permit the use of smaller margins during conformal prostate radiotherapy. Further integration of the system such as remote table control would improve efficiency.

Humans↗