M. L. Bahner

Stereotactic Single-Dose Radiation Therapy of Liver Tumors: Results of a Phase I/II Trial

PURPOSE To investigate the feasibility and the clinical response of a stereotactic single-dose radiation treatment for liver tumors. PATIENTS AND METHODS Between April 1997 and September 1999, a stereotactic single-dose radiation treatment of 60 liver tumors (four primary tumors, 56 metastases) in 37 patients was performed. Patients were positioned in an individually shaped vacuum pillow. The applied dose was escalated from 14 to 26 Gy (reference point), with the 80% isodose surrounding the planning target volume. Median tumor size was 10 cm(3) (range, 1 to 132 cm(3)). The morbidity, clinical outcome, laboratory findings, and response as seen on computed tomography (CT) scan were evaluated. RESULTS Follow-up data could be obtained from 55 treated tumors (35 patients). The median follow-up period was 5.7 months (range, 1.0 to 26.1 months; mean, 9.5 months). The treatment was well tolerated by all patients. There were no major side effects. Fifty-four (98%) of 55 tumors were locally controlled after 6 weeks at the initial follow-up based on the CT findings (22 cases of stable disease, 28 partial responses, and four complete responses). After a dose-escalating and learning phase, the actuarial local tumor control rate was 81% at 18 months after therapy. A total of 12 local failures were observed during follow-up. So far, the longest local tumor control is 26.1 months. CONCLUSION Stereotactic single-dose radiation therapy is a feasible method for the treatment of singular inoperable liver metastases with the potential of a high local tumor control rate and low morbidity.

EXTRACRANIAL STEREOTACTIC RADIATION THERAPY: SET-UP ACCURACY OF PATIENTS TREATED FOR LIVER METASTASES

PURPOSE Patients with liver metastases might benefit from high-dose conformal radiation therapy. A high accuracy of repositioning and a reduction of target movement are necessary for such an approach. The set-up accuracy of patients with liver metastases treated with stereotactic single dose radiation was evaluated. METHODS AND MATERIALS Twenty-four patients with liver metastases were treated with single dose radiation therapy on 26 occasions using a self-developed stereotactic frame. Liver movement was reduced by abdominal pressure. The effectiveness was evaluated under fluoroscopy. CT scans were performed on the planning day and directly before treatment. Representative reference marks were chosen and the coordinates were calculated. In addition, the target displacement was quantitatively evaluated after treatment. RESULTS Diaphragmal movement was reduced to median 7 mm (range: 3-13 mm). The final set-up accuracy of the body was limited to all of median 1.8 mm in latero-lateral direction (range: 0.3-5.0 mm) and 2.0 mm in anterior-posterior direction (0.8-3.8 mm). Deviations of the body in cranio-caudal direction were always less than the thickness of one CT slice (<5 mm). However, a repositioning was necessary in 16 occasions. The final target shift was median 1.6 mm (0.2-7.0 mm) in latero-lateral and 2.3 mm in anterior-posterior direction (0.0-6.3 mm). The median shift in cranio-caudal direction was 4.4 mm (0.0-10.0 mm). CONCLUSIONS In patients with liver metastases, a high set-up accuracy of the body and the target can be achieved. This allows a high-dose focal radiotherapy of these lesions. However, a control CT scan should be performed directly before therapy to confirm set-up accuracy and possibly prompt necessary corrections.

NONINVASIVE PATIENT FIXATION FOR EXTRACRANIAL STEREOTACTIC RADIOTHERAPY

PURPOSE To evaluate the setup accuracy that can be achieved with a novel noninvasive patient fixation technique based on a body cast attached to a recently developed stereotactic body frame during fractionated extracranial stereotactic radiotherapy. METHODS AND MATERIALS Thirty-one CT studies (> or = 20 slices, thickness: 3 mm) from 5 patients who were immobilized in a body cast attached to a stereotactic body frame for treatment of paramedullary tumors in the thoracic or lumbar spine were evaluated with respect to setup accuracy. The immobilization device consisted of a custom-made wrap-around body cast that extended from the neck to the thighs and a separate head mask, both made from Scotchcast. Each CT study was performed immediately before or after every second or third actual treatment fraction without repositioning the patient between CT and treatment. The stereotactic localization system was mounted and the isocenter as initially located stereotactically was marked with fiducials for each CT study. Deviation of the treated isocenter as compared to the planned position was measured in all three dimensions. RESULTS The immobilization device can be easily handled, attached to and removed from the stereotactic frame and thus enables treatment of multiple patients with the same stereotactic frame each day. Mean patient movements of 1.6 mm+/-1.2 mm (laterolateral [LL]), 1.4 mm+/-1.0 mm (anterior-posterior [AP]), 2.3 mm+/-1.3 mm (transversal vectorial error [VE]) and < slice thickness = 3 mm (craniocaudal [CC]) were recorded for the targets in the thoracic spine and 1.4 mm+/-1.0 mm (LL), 1.2 mm+/-0.7 mm (AP), 1.8 mm+/-1.2 mm (VE), and < 3 mm (CC) for the lumbar spine. The worst case deviation was 3.9 mm for the first patient with the target in the thoracic spine (in the LL direction). Combining those numbers (mean transversal VE for both locations and maximum CC error of 3 mm), the mean three-dimensional vectorial patient movement and thus the mean overall accuracy can be safely estimated to be < or = 3.6 mm. CONCLUSION The presented combination of a body cast and head mask system in a rigid stereotactic body frame ensures reliable noninvasive patient fixation for fractionated extracranial stereotactic radiotherapy and may enable dose escalation for less radioresponsive tumors that are near the spinal cord or otherwise critically located while minimizing the risk of late sequelae.

ASSESSMENT OF FOCAL LIVER REACTION BY MULTIPHASIC CT AFTER STEREOTACTIC SINGLE-DOSE RADIOTHERAPY OF LIVER TUMORS

PURPOSE To characterize and quantitatively assess focal radiation reactions in the liver after stereotactic single-dose radiotherapy for liver malignancies. METHODS AND MATERIALS A total of 131 multiphasic CT scans were performed in 36 patients before and after stereotactic radiotherapy for liver tumors. The examination protocol included a nonenhanced scan and contrast-enhanced scans at different times after contrast injection. The volume of the reaction was determined in each scan and the threshold dose calculated using the dose-volume histogram of the treatment plan. RESULTS Every patient showed a focal radiation reaction on at least one follow-up examination. In 74% of the posttherapeutic scans, a sharply demarcated hypodense area surrounded the treated tumor in the nonenhanced scans. The reaction occurred at a median of 1.8 months (range 1.2-4.6) after radiotherapy. The median threshold dose was 13.7 Gy (range 8.9-19.2). The threshold dose strongly correlated with the time of detection after therapy (r = 0.7). Radiologically, three reaction types were found on the enhanced scans: type 1, portal-venous phase: hypodense and late phase: isodense; type 2, portal-venous phase: hypodense and late phase: hyperdense; and type 3, portal-venous phase: isodense/hyperdense and late phase: hyperdense. Type 1 or 2 reactions were observed significantly earlier than type 3 (p <0.05). The median threshold dose for type 1 or 2 reactions was significantly lower than for type 3 (p <0.05). The reaction volume decreased with longer follow-up (2-4 months: median 40% of initial volume). The reaction types shifted with follow-up: 58% were of type 1 at the initial manifestation and 58% were of type 3 at the next examination thereafter. CONCLUSION A focal radiation reaction occurs after stereotactic single-dose therapy in the liver. The volume of the reaction decreases and changes its radiologic appearance during follow-up. This reaction has to be differentiated from recurrent tumor.

Improved vascular opacification in cerebral computed tomography angiography with 80 kVp

Purpose:We sought to intraindividually compare computed tomography angiographies (CTAs) acquired at 80 kVp and 120 kVp with respect to vessel contrast, noise level, and radiation dose. Material and Methods:CTA was performed on a single-slice CT scanner using tube voltages of 80 kVp and 120 kVp in 29 patients with arteriovenous malformations. Mean Hounsfield Units (HU) were evaluated for different vessels and brain parenchyma. To determine contrast-to-noise ratios (CNRs), noise levels were estimated from phantom measurements. Results:The calculated effective dose to male/female patients was 0.4/0.5 mSv for 80 kVp and 0.7/0.8 mSv for 120 kVp. CT density in blood vessels was between 297 and 458 HU for 80 kVp and 152 and 229 HU for 120 kVp (P < 0.0001). Despite an increased noise level in the low-voltage images, the CNR was 26–59% higher at 80 kVp than at 120 kVp (P < 0.05). Conclusion:The use of a reduced tube potential leads to improved CNR in CTA of the cerebral vasculature and a markedly reduced radiation exposure to patients.

Virtual planning of liver resections: image processing, visualization and volumetric evaluation

Operability of a liver tumor depends on its three dimensional relation to the intrahepatic vascular trees as well as the volume ratio of healthy to tumorous tissue. Precise operation planning is complicated by anatomic variability and distortion of the vascular trees by the tumor or preceding liver resections. We have developed a computer based 3D virtual operation planning system which is ready to go in routine use. The main task of a system in this domain is a quantifiable patient selection by exact prediction of post-operative liver function. It provides the means to measure absolute and relative volumes of the organ structures and resected parenchyma. Another important step in the pre-operative phase is to visualize the relation between the tumor, the liver and the vessel trees for each patient. The new 3D operation planning system offers quantifiable liver resection proposals based on individualized liver anatomy. The results are presented as 3D movies or as interactive visualizations as well as in quantitative reports.

Usability of semiautomatic segmentation algorithms for tumor volume determination

RATIONALE AND OBJECTIVES Tumor volume is an important parameter for clinical decision making. At present, semiautomatic image segmentation is not a standard for tumor volumetry. The aim of this work was to investigate the usability of semiautomatic algorithms for tumor volume determination. METHODS Semiautomatic region- and volume-growing, isocontour, snakes, hierarchical, and histogram-based segmentation algorithms were tested for accuracy, contour variability, and time performance. The test were performed on a newly developed organic phantom for the simulation of a human liver and liver metastases. The real tumor volumes were measured by water displacement. These measured volumes were used as the gold standard for determining the accuracy of the algorithms. RESULTS Variability of the segmented volumes ranging from 3.9 +/- 3.2% (isocontour algorithm) to 11.5 +/- 13.9% (hierarchical segmentation) was observed. The segmentation time per slice varied between 32 (volume-growing) and 72 seconds (snakes) on an IBM/RS6000 workstation. CONCLUSIONS Only the region-growing and isocontour algorithms have the potential to be used for tumor volumetry. However, further improvements of these algorithms are necessary before they can be placed into clinical use.

Near-infrared imaging of the breast using omocianine as a fluorescent dye: results of a placebo-controlled, clinical, multicenter trial.

Objectives:To evaluate the efficacy of the near-infrared (NIR) dye Omocianine in a placebo-controlled, dose-escalating multicenter trial for the detection of malignant breast lesions by using a NIR imaging system. Materials and Methods:The study was approved by the ethical review board of Berlin and Münster,, and all participants provided written informed consent. Fifty-two consecutive patients were examined with NIR imaging before, during, and after intravenous injection of Omocianine. Three-dimensional absorption and fluorescence diffuse optical tomography scans were recorded simultaneously on a prototype NIR imaging unit (Computed Tomography Laser Mammography, Imaging Diagnostic Systems, Inc., Ft. Lauderdale, FL). Two readers assessed the images in consensus and assigned visibility scores to lesions seen on the absorption and absorption-corrected fluorescence diffuse optical tomography mammograms. Imaging results were compared with histopathologic findings. To analyze whether lesion detection rate for malignant lesions depended on the size of the lesion, lesions were dichotomized into those measuring less than 20 mm and those measuring 20 mm or more. Moreover, the shortest diameter between the center of the target lesions and the skin was measured on axial optical mammography data. Results:There were a total of 53 target lesions. Histopathologically, 22 target lesions were diagnosed as benign and 31 target lesions as malignant. In the absorption mode, a detection rate of 11.8% for benign and 44.4% for malignant lesions across all dose groups was found. In the fluorescence mode, a detection rate of 17.6% was revealed for benign and 55.6% for malignant lesions across all dose groups. For dose group 0.1 mg/kg, a detection rate of 100% was found for malignant lesions in the fluorescence mode and 71.4% in the absorption mode. Across all dose groups in the fluorescence mode, detection rate for malignant target lesions in breasts smaller than the median axial breast diameter of 12.8 cm was higher with 69.2% than in median diameters ≥12.8 cm with 46.2%. Omocianine-enhanced fluorescence optical mammography allowed a better detection of more superficially located lesions, with detection rates for a lesion-skin distance <20 mm of 63.6%, for <30 mm of 47.4% and for ≥30 mm of 25%. Malignant target lesions with a diameter ≥20 mm were slightly better detected with 61.5% in contrast to suspicious lesions <20 mm with 53.8%. Optimal imaging time points varied strongly among the different target lesions and Omocianine dose groups, with a mean optimal time point for malignant lesions at 188 ± 385 minutes. Conclusion:Preliminary data suggest that fluorescence imaging after Omocianine administration has the potential to detect malignant breast lesions. As our study showed considerable variations in the detection of breast cancer at different fluorophore concentrations ranging from 20% to 100%, future work needs to be done to assess the suitable dose for NIR imaging.

Spiral CT vs incremental CT: Is spiral CT superior in imaging of the brain?

Abstract. The aim of this study was to evaluate image quality of spiral CT of the brain as compared with incremental CT using identical scanning parameters. Incremental or spiral cranial CT was performed on 46 consecutive, randomized patients with non-traumatic disease of the brain on a Siemens (Erlangen, Germany) Somatom Plus 4. Evaluation was done in a randomized blinded way by two experienced radiologists. Different anatomical structures, image noise, and artifacts were scaled 1 (bad) to 4 (very good). Statistical analysis was done using the F-test of variance for partial sums of squares as well as Students t-test. Incremental CT was superior to spiral CT for evaluation of the internal capsule, supratentorial artifacts, gray/white matter differentiation, and image noise. No statistically significant differences were seen for evaluation of the pons, infratentorial artifacts, and eye muscles. With identical scanning parameters incremental CT is superior to spiral CT in the assessment of small, complex structures in a low-contrast setting. No differences are seen for larger structures or small structures in a medium-contrast range. Artifacts localized close to the skull in spiral CT can easily mimic hemorrhage in traumatized patients. Spiral CT should therefore only be used for CT angiography and if 3D reconstructions are needed.

Stereotaktische Bestrahlung von Lebermetastasen

ZusammenfassungFragestellung. Für die Behandlung inoperabler Lebermetastasen wurde eine Reihe mehr oder weniger minimal-invasiver Behandlungsmethoden entwickelt. Durch einen stereotaktischen Bestrahlungsansatz lässt sich auf nichtinvasivem Weg eine hohe Bestrahlungsdosis unter Schonung des umgebenden Gewebes auf den Tumorherd konzentrieren. Methodik. Im Rahmen einer Phase-2-Studie wurden 66 inoperable Lebermetastasen bei 43 Patienten mittels einer einmaligen stereotaktischen Bestrahlung behandelt. Ergebnisse. Die Therapie wurde von den Patienten sehr gut vertragen, es traten keine größeren Nebenwirkungen (>Grad 2) auf. Die aktuarische lokale Kontrollrate lag nach 18 Monaten bei 82%. Das aktuarische mediane Gesamtüberleben der Patienten betrug 24 Monate. Jedoch zeigte sich ein signifikant besseres Überleben bei Patienten, die keine weiteren extrahepatischen Metastasen aufwiesen gegenüber Patienten, die rein palliativ behandelt wurden (87% vs. 24% nach 18 Monaten, p=0,001(log-rank). Schlussfolgerung. Mit der stereotaktischen Einzeitbestrahlung steht eine nichtinvasive und sichere Behandlungsmethode inoperabler Lebermetastasen zur Verfügung. Diese weist eine hohe lokale Kontrollrate auf und wird in Phase-III-Studien weiter evaluiert.AbstractPurpose. A number of minimal-invasive methods have been developed for the treatment of non-resectable liver metastases. A focused high dose can be delivered to a liver tumor with sparing of surrounding normal liver tissue using non-invasive stereotactic techniques. Methods. Sixty-six metastases were treated stereotactically in 43 patients during a phase 2 trial. Results. There were no major side effects observed. The actuarial local control was 82% after 18 months. The median actuarial survival was 24 months. However, there was a significantly improved survival in patients without additional extrahepatic tumor manifestation at the time of treatment compared to those, who were treated in palliative intention (87% vs. 24% after 18 months, p=0.001 (log-rank). Conclusion. Stereotactic single dose irradiation is a non-invasive and safe treatment option for patients with inoperable liver metastases. Phase III studies will further evaluate this new approach.