Accurate Targeting of Liver Tumors in Stereotactic Radiation Therapy

This doctoral thesis concerns the treatment of liver cancer patients using external beam radiotherapy. The quality of this treatment greatly depends on delivering a high radiation dose to the tumor while keeping the dose as low as possible to surrounding healthy tissues. One of the major challenges is locating the tumor at the moment of dose delivery. In this ork, the uncertainty of locating the tumor was investigated. For this purpose, gold markers were implanted in the liver tissue and visualized on X-ray images. The markers were used to measure day-to-day tumor mobility and motion due to respiration. Furthermore, it was found that major improvements in the targeting accuracy can be achieved by using the markers for guiding the treatment procedure

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 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. (C) 2010 Elsevier Inc

Foodborne Trematodiasis and Opisthorchis felineus Acquired in Italy

Medical Microbiolog

Automated non-coplanar beam direction optimization improves IMRT in SBRT of liver metastasis

Purpose: To investigate whether automatically optimized coplanar, or non-coplanar beam setups improve intensity modulated radiotherapy (IMRT) treatment plans for stereotactic body radiotherapy (SBRT) of liver tumors, compared to a reference equi-angular IMRT plan. Methods: For a group of 13 liver patients, an in-house developed beam selection algorithm (Cycle) was used for generation of 3D-CRT plans with either optimized coplanar-, or non-coplanar beam setups. These 10 field, coplanar and non-coplanar setups, and an 11 field, equi-angular coplanar reference setup were then used as input for generation of IMRT plans. For all plans, the PTV dose was maximized in an iterative procedure by increasing the prescribed PTV dose in small steps until further increase was prevented by constraint violation(s). Results: For optimized non-coplanar setups, D-PTV,D- (max) increased by on average 30% (range 8-64%) compared to the corresponding reference IMRT plan. Similar increases were observed for D-PTV, 99% and gEUD(a). For optimized coplanar setups, mean PTV dose increases were only similar to 4%. After re-scaling all plans to the clinically applied dose, optimized non-coplanar configurations resulted in the best sparing of organs at risk (healthy liver, spinal cord, bowel). Conclusion: Compared to an equi-angular beam setup, computer optimized non-coplanar setups do result in substantial improvements in IMIRT plans for SBRT of liver tumors. (C) 2008 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 88 (2008) 376-381

Treatment precision of image-guided liver SBRT using implanted fiducial markers depends on marker-tumour distance

The purpose of this study is to assess the accuracy of day-to-day predictions of liver tumour position using implanted gold markers as surrogates and to compare the method with alternative set-up strategies, i.e. no correction, vertebrae and 3D diaphragm-based set-up. Twenty patients undergoing stereotactic body radiation therapy (SBRT) with abdominal compression for primary or metastatic liver cancer were analysed. We determined the day-today correlation between gold marker and tumour positions in contrast-enhanced CT scans acquired at treatment preparation and before each treatment session. The influence of marker-tumour distance on the accuracy of prediction was estimated by introducing a method extension of the set-up error paradigm. The distance between gold markers and the centre of the tumour varied between 5 and 96 mm. Marker-guidance was superior to guiding treatment using other surrogates, although both the random and systematic components of the prediction error SD depended on the tumour-marker distance. For a marker-tumour distance of 4 cm, we observed sigma = 1.3 mm and Sigma = 1.6 mm. The 3D position of the diaphragm dome was the second best predictor. In conclusion, the tumour position can be predicted accurately using implanted markers, but marker-guided set-up accuracy decreases with increasing distance between implanted markers and the tumour

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. (C) 2008 Elsevier Inc

Stereotactic body radiation therapy for colorectal liver metastases

Background: Stereotactic body radiation therapy (SBRT) is a treatment option for colorectal liver metastases. Local control, patient survival and toxicity were assessed in an experience of SBRT for colorectal liver metastases. Methods: SBRT was delivered with curative intent to 20 consecutively treated patients with colorectal hepatic metastases who were candidates for neither resection nor radiofrequency ablation (RFA). The median number of metastases was I (range 1-3) and median size was 2.3 (range 0.7-6.2) cm. Toxicity was scored according to the Common Toxicity Criteria version 3.0. Local control rates were derived on tumour-based analysis. Results: Median follow-up was 26 (range 6-57) months. Local failure was observed in nine of 31 lesions after a median interval of 22 (range 12-52) months. Actuarial 2-year local control and survival rates were 74 and 83 per cent respectively. Hepatic toxicity grade 2 or less was reported in 18 patients. Two patients bad an episode of hepatic toxicity grade 3. Conclusion: SBRT is a treatment option for patients with colorectal liver metastases who are not candidates for resection or RFA