Wouter Wunderink

Stereotactic body radiation therapy for primary and metastatic liver tumors: A single institution phase i-ii study

The feasibility, toxicity and tumor response of stereotactic body radiation therapy (SBRT) for treatment of primary and metastastic liver tumors was investigated. From October 2002 until June 2006, 25 patients not suitable for other local treatments were entered in the study. In total 45 lesions were treated, 34 metastases and 11 hepatocellular carcinoma (HCC). Median follow-up was 12.9 months (range 0.5–31). Median lesion size was 3.2 cm (range 0.5–7.2) and median volume 22.2 cm3 (range 1.1–322). Patients with metastases, HCC without cirrhosis, and HCC < 4 cm with cirrhosis were mostly treated with 3×12.5 Gy. Patients with HCC ≥4cm and cirrhosis received 5×5 Gy or 3×10 Gy. The prescription isodose was 65%. Acute toxicity was scored following the Common Toxicity Criteria and late toxicity with the SOMA/LENT classification. Local failures were observed in two HCC and two metastases. Local control rates at 1 and 2 years for the whole group were 94% and 82%. Acute toxicity grade ≥3 was seen in four patients; one HCC patient with Child B developed a liver failure together with an infection and died (grade 5), two metastases patients presented elevation of gamma glutamyl transferase (grade 3) and another asthenia (grade 3). Late toxicity was observed in one metastases patient who developed a portal hypertension syndrome with melena (grade 3). SBRT was feasible, with acceptable toxicity and encouraging local control. Optimal dose-fractionation schemes for HCC with cirrhosis have to be found. Extreme caution should be used for patients with Child B because of a high toxicity risk.

Stereotactic body radiation therapy for colorectal liver metastases

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.

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.

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.

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-to-day 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 σ = 1.3 mm and Σ = 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.

STEREOTACTIC BODY RADIATION THERAPY FOR LIVER TUMORS: IMPACT OF DAILY SETUP CORRECTIONS AND DAY-TO-DAY ANATOMIC VARIATIONS ON DOSE IN TARGET AND ORGANS AT RISK

PURPOSE To assess day-to-day differences between planned and delivered target volume (TV) and organ-at-risk (OAR) dose distributions in liver stereotactic body radiation therapy (SBRT), and to investigate the dosimetric impact of setup corrections. METHODS AND MATERIALS For 14 patients previously treated with SBRT, the planning CT scan and three treatment scans (one for each fraction) were included in this study. For each treatment scan, two dose distributions were calculated: one using the planned setup for the body frame (no correction), and one using the clinically applied (corrected) setup derived from measured tumor displacements. Per scan, the two dose distributions were mutually compared, and the clinically delivered distribution was compared with planning. Doses were recalculated in equivalent 2-Gy fraction doses. Statistical analysis was performed with the linear mixed model. RESULTS With setup corrections, the mean loss in TV coverage relative to planning was 1.7%, compared with 6.8% without corrections. For calculated equivalent uniform doses, these figures were 2.3% and 15.5%, respectively. As for the TV, mean deviations of delivered OAR doses from planning were small (between -0.4 and +0.3 Gy), but the spread was much larger for the OARs. In contrast to the TV, the mean impact of setup corrections on realized OAR doses was close to zero, with large positive and negative exceptions. CONCLUSIONS Daily correction of the treatment setup is required to obtain adequate TV coverage. Because of day-to-day patient anatomy changes, large deviations in OAR doses from planning did occur. On average, setup corrections had no impact on these doses. Development of new procedures for image guidance and adaptive protocols is warranted.

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, 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 approximately 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 IMRT plans for SBRT of liver tumors.

Evaluation of the setup margins for cone beam computed tomography-guided cranial radiosurgery: A phantom study.

The aim of this study is to evaluate the setup margins from the clinical target volume (CTV) to planning target volume (PTV) for cranial stereotactic radiosurgery (SRS) treatments guided by cone beam computed tomography (CBCT). We designed an end-to-end (E2E) test using a skull phantom with an embedded 6mm tungsten ball (target). A noncoplanar plan was computed (E2E plan) to irradiate the target. The CBCT-guided positioning of the skull phantom on the linac was performed. Megavoltage portal images were acquired after 15 independent deliveries of the E2E plan. The displacement 2-dimensional (2D) vector between the centers of the square field and the ball target on each portal image was used to quantify the isocenter accuracy. Geometrical margins on each patient׳s direction (left-right or LR, anterior-posterior or AP, superior-inferior or SI) were calculated. Dosimetric validation of the margins was performed in 5 real SRS cases: 3-dimesional (3D) isocenter deviations were mimicked, and changes in CTV dose coverage and organs-at-risk (OARs) dosage were analyzed. The CTV-PTV margins of 1.1mm in LR direction, and 0.7mm in AP and SI directions were derived from the E2E tests. The dosimetric analysis revealed that a 1-mm uniform margin was sufficient to ensure the CTV dose coverage, without compromising the OAR dose tolerances. The effect of isocenter uncertainty has been estimated to be 1mm in our CBCT-guided SRS approach.

WE‐D‐351‐07: Daily CT Guidance in Liver Stereotactic Body Radiation Therapy; Impact of a Non‐Rigid Patient Anatomy On OAR Dose

Purpose: To investigate the influence of daily tumor‐based setup corrections, derived from pre‐treatment CT‐scans, on the organs‐at‐risk (OARs) dose distributions in stereotactic body radiation therapy(SBRT) of livertumors.Method and Materials: Fifteen patients diagnosed with liver metastases and treated with SBRT were included in this study. Patients were positioned in a stereotactic body frame and abdominal compression was applied to decrease the respiratory tumor displacement. A total dose of 37.5 Gy at the 65% isodose was delivered in three fractions. Sixty CT data sets, corresponding to the planning and consecutive treatment days, were reviewed. Relevant OARs were delineated on all CT sets. Daily 3D dose distributions were calculated using the daily CT sets, both without and with taking the clinically applied setup correction into account. Dose‐volume histograms and relevant dosimetric parameters for the PTV and all OARs were calculated. Results: Large shape and volume variations were seen for OARs (especially the oesophagus, duodenum and stomach), causing large variations in the dose to these organs. In 27% of the treatment fractions, it was seen that after setup correction the dose to an OAR exceeded the constraints, while the planning was within constraints; in one case, the constraint was exceeded by a factor of two. Setup correction yielded a significant increase in PTV coverage, but for the OARs no significant dosimetric effect was seen. Conclusion: Daily tumor‐based CT‐guidance is effective to increase PTV coverage, but does not significantly affect dose to the OARs. This is due to their non‐rigid motion and volume variations. Both may cause substantial OAR constraint violations, even after set‐up correction. However, for most fractions the dose to the OARs is within constraints. To obtain optimal sparing of OARs, adaptive treatment explicitly accounting for non‐rigid anatomy may be required, especially when the tumordose is escalated.