N. Di muzio, F. Alongi, S. Schipani, M. Picchio, V. Bettinardi, F. Fazio; Milano/IT

Purpose
The advent of three-dimensional-conformal treatment planning with dose-volume histogram analysis has made the study of partial liver irradiation possible. Limited portions of the liver may withstand high doses of radiation with minimal risk of RIDL (Radiation Induced Liver Disease). Patients with solitary unresectable liver tumors may be treated with high dose radiotherapy with curative intent. Recently the feasibility of stereotactically guided treatment techniques with a single fraction or few treatment sessions has been explored in numerous institutions. Accurate target delineation and treatment reproducibility are the key to the success of this novel treatment approach, and specific treatment planning techniques and patient set up procedures must be developed to implement it. The aim of this study is to evaluated the feasibility and the results of irradiation with Tomotherapy, of limited number of liver metastasis by means of a complex 4D Pet/Tc study.

Material and methods
From May 2005 to April 2006, 4 patients with liver metastasis were treated with Tomotherapy. 2/4 had 2 focal lesions (diameter< 3cm.), 2/4 had a single lesion. The primary neoplasms were 2/4 colo-rectal cancer,1/4 sarcoma,1/4 prostate ( single lesion with 6 cm. of diameter). Helical Tomotherapy has been designed to use CT imaging technology to plan, deliver and verify that the delivery has been carried out as planned. Helical Tomotherapy represents the fusion of a linac with a helical CT scanner. With this system, a fan beam may be used to acquire and MVCT (Megavoltage CT) of the patients just before a treatment and potentially even during treatment. During treatment, a dedicated binary MLC ( Multi Leaf Collimator) is used to modulated the same fan beam to provide rotational IMRT. The beam rotation in synchronized with continuous longitudinal movement of the couch through the bore of the gantry, forming a helical beam pattern from the patient’s point of view. The set of binary collimator leaves rapidly transitions between open and closed states. There are a number of verification processes that are possible with a CT scanner on board. Immediately after the MGVCT scan, the scan can be fused with a planning CT scan to determine if the patient is set up correctly and the 3D shape and position of the target volume before radiotherapy. Operating the CT detectors during treatment can also be used to reconstruct the dose delivered to the patient. Before treatment each patient underwent a standard Whole body(WB) 18F-FDG-PET/CT scan for staging, followed by a single field of view (FOV) 4D-PET/CT study on the region of interesting (the abdomen). All patients were trained to regulary breath prior PET. 4D scans were performed during free breathing, monitored by the Real Time Position Management (RPM,Varian) system which allows the synchronizing of 4DPET and 4D CT scans to the respiratory cycle of the patient. 4D-PET and 4DCT studies allow a set of images (phases) to be generated, synchronized to the respiratory cycle and describing the tumor motion induced by patient respiration. The sets of 4DPET and 4DCT image phases were then collapsed to single “integral” PET and CT images representing the full tumor motion. In these images Gross Tumor Volume (GTV) and Biological Target Volume(BTV) were defined by contouring the “standard” CT image (GTV), the “integral” 4DCT image (4DGTV) and the “integral” 4DPET image(4DBTV). Finally the “integral” GVT was expanded to a CTV “integral (plus 5mm.) and a PTV “integral” (plus 3 mm.) that could explicitly represent patient-specific target respiratory motion in order to ensure its correct dose coverage when free breathing is present during beam delivery. The planned dose was 40Gy in 5/daily fractions.

Results
With a median F-UP of 7months (4-11) all patients were in Complete Response in morpho-functional imaging studies with 18F-FDG-PET/CT. Only one patients manifested G1 toxicity with upper gastrointestinal symptoms (nausea).

Conclusion
Our preliminary data suggest that Image Guided high dose helical Tomotherapy is technically feasible for the treatment of inoperable liver malignancies with the potential of high local control and low morbidity. As well 4D study PET/TC allow us to determine a personalized margin to decrease the irradiation of tissue surrounding the target in order to reduced acute and late side effects. Further patients will be studied to validate this method.