Overall response of both intrahepatic tumor and portal vein tumor thrombosis is a good prognostic factor for hepatocellular carcinoma patients receiving concurrent chemoradiotherapy

摘要

One hundred HCC patients with PVTT who received radiotherapy and iA concurrent chemotherapy at Severance Hospital at the Yonsei University between April 2002 and March 2011 were retrospectively analyzed. A diagnosis of HCC was made according to the Korean Liver Cancer Study group guidelines, either histologically or based on typical radiologic findings of HCC using two dynamic imaging studies (CT, magnetic resonance imaging, or hepatic angiography) or one positive image finding with an elevated serum alpha-fetoprotein (AFP) level of 200 ng/ml. Prior to CT simulation, all patients underwent respiration training to maintain regular breathing. Contrast-enhanced CT was performed using a slice thickness of approximately 3–5 mm. The gross tumor volume (GTV) was defined as the volume of the tumor visible on the planning CT or fused magnetic resonance imaging. Salvage or curative aim radiotherapy was given; the radiation target volume included all sites of residual disease and previously treated lesions. All of the viable tumors in the liver and PVTT were included in the GTV. The clinical target volume (CTV) was defined as the GTV plus a 0.5-cm margin. All cases of PVTT were continuous with the main tumor and there were no cases of thrombi without the tumor component. There were no cases of PVTT without continuum with the tumor in patients with multifocal PVTT. Diaphragm movement was checked using a fluoroscope and was incorporated when defining the internal target volume (ITV). Since 2010, we have used 4D CT to set the ITV according to respiration. The planning target volume (PTV) was defined by adding a 0.5-cm margin to the ITV, and a 0.7-cm block margin was added. Patients were treated with 3D conformal RT (72 patients) and helical tomotherapy (28 patients; Madison, WI, USA). Because a higher RT dose was recommended for a response [8], patients were selected with a cumulative dose ≥45 Gy in the present study. The median total dose was 45.0 Gy (range, 45.0–60.0 Gy), delivered in a fractional dose of 1.8–3.0 Gy. Most patients who were treated with 3D conformal RT received a total dose of 45 Gy in 25 fractions. For patients treated with helical tomotherapy, the simultaneous integrated boost technique was applied, and most patients received 50 Gy to the GTV and 45 Gy to the CTV delivered in 20 fractions. The median total biologic effective dose (BED) was 53.1 Gy₁₀ (range, 53.1–78.0 Gy₁₀). For radiation treatment planning, the entire liver, except for the CTV, was defined as the remaining liver, and we kept this volume greater than 800 ml. The mean dose to the remaining liver was kept under 26 Gy, and the volume of the remaining liver receiving over 30 Gy (V30) was less than 60% [10, 11]. For the dose constraint for normal organs such as the stomach and duodenum, we kept the volume to receive over 45 Gy to less than 2 ml. Additionally, for the heart, we set the mean dose to less than 26 Gy and 30% of the volume to receive less than 45 Gy. For the kidneys, we set the equivalent dose for at least one kidney to less than 20 Gy. The results of treatment were evaluated using CT or MRI one month after RT and at three to six months during follow up. The treatment response at six months after RT showed the maximum response and was used to define the treatment response. SPSS? version 18 was used for statistical analysis. The chi-square test and Fisher's exact test were used to identify the correlations between the tumor and PVTT responses and various factors. To identify the correlation between PVTT size (axial diameter) and treatment response, binary logistic regression was used. For analysis of survival rate, the Kaplan–Meier method was used for univariate analysis and the Cox proportional hazards model was used for multivariate analysis. The median follow-up period for all patients was 9.7 months. All patients were treated for both the tumor and the PVTT. Table 1 describes the clinical characteristics of the patients. The median age of the patients was 55 years, and 88.0% were males. Out of 100 patients, 84 (84.0%) had viral hepatitis B, 8 (8.0%) had viral hepatitis C, and 8 (8.0%) had non-B, non-C hepatitis. The main site (82.0%) of PVTT was the main trunk or the first branch. Four of the patients with PVTT in the main trunk had a tumor thrombus in the inferior vena cava (IVC). IVC thrombus was included in the target volume in all of the four patients (categorized to PVTT in the main trunk since all of them had main portal vein thrombus concurrently). The median PVTT size was 4.4 cm. Of the 100 patients, 70 (70.0%) had a single tumor, and 30 (30.0%) had multiple tumors (pre-treatment intrahepatic metastasis within the area of RT); 16 (16.0%) had a tumor size of 5 cm, 43 (43.0%) had a tumor size between 5 and 10 cm, and 41 (41.0%) had a tumor size 10 cm (median tumor size, 9 cm). There were 12 T2N0 patients enrolled who had inadequate liver function for TACE or vascular invas