Feasibility study of hypofractionated gated irradiation using a real-time tumor-tracking radiation therapy system for malignant liver tumors

Purpose/Objective: Radiotherapy has seldom been considered as a curative treatment option for liver tumors because of their movement within body and the lower tolerance dose of the surrounding normal tissues. Fluoroscopic real-time tumor-tracking radiation therapy (RTRT) with insertion of a fiducial marker promises to deliver an accurate dose to the moving tumor while producing the smallest margin. The purpose of this study was to evaluate the feasibility of RTRT for patients with malignant liver tumors. Materials/Methods: A 2 mm-fiducial gold marker was implanted at the margin of the tumor through the use of image-guided procedures. The raw data of computed tomography (CT) for treatment planning was acquired by multidetector CT at the exhalation phase. Clinical target volume (CTV) was defined as the gross tumor volume (GTV) on CT with 1-5 mm margin. The planning goal was to provide adequate coverage of the planning target volume (PTV) using the 80% isodose, while sparing the gastrointestinal tract and extrahepatic biliary and vascular systems. The PTV was defined as the CTV plus a 5 mm margin in three-dimensions with optional reduction near the critical organ. The non-coplanar or coplanar conformal technique was used. The tumor was irradiated only when the marker was within the permitted dislocation (±1-3mm) from the planned position. The prescribed total dose and fractionation were determined based on the criteria regarding distance between the tumor and the organs at risk, the tumor location within the liver, and the size of the tumor. Local control rate was evaluated using the Kaplan-Meier method and log-rank test. Results: Between 1999 and 2001, 25 lesions in 22 patients with unresectable malignant liver tumors--hepatocellular carcinoma (HCC) in 14, cholangiocellular carcinoma (CCC) in 5, metastatic tumors (Mets) in 6--were the subject of this study. Mean tumor diameter was 5.0±2.2 cm (range: 1.5-10.2 cm). The number of patients for each bin was 20 Gy/single fraction (fr) in 4, 35 Gy/4 fr in 7, 40 Gy/4 fr in 4, 40 Gy/8 fr in 8, and 48 Gy/8 fr in 2. No major adverse effect was observed. Fever during the treatment period was observed in six patients (24%), and only two patients (8%) experienced an asymptomatic mild elevation of serum liver enzymes within a month after the treatment. With a median follow-up period of 12 months (range: 4-25 months), local control was obtained in 19 lesions (76%), of which 9 showed complete responses, 5 showed partial responses, and 5 showed stable diseases determined by the CT findings of 25 lesions. The 1-year actuarial local control rates of overall, HCC, CCC, and Mets were 75%, 86%, 50%, and 75%, respectively. The difference in the local control of HCC vs. CCC and Mets was statistically significant (p=0.04). Local failure at the margin of the CTV occurred in one case of HCC (7%), 2 Mets (33%), and 3 CCCs (60%). Conclusions: Hypofractionated gated irradiation using the RTRT system was demonstrated to be feasible and effective especially for HCC. The higher incidence of marginal relapse in CCC suggested the difficulties of determination of its CTV based on CT findings.