Hepatic arterial infusion chemotherapy using 5-fluorouracil and systemic interferon-α for advanced hepatocellular carcinoma in combination with or without three-dimensional conformal radiotherapy to venous tumor thrombosis in hepatic vein or inferior vena
Departments of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science Radiation Oncology, Division of Genome Radiobiology and Medical Science Diagnostic Radiology, Division of Medical Intelligence and Informatics, Hiroshima University, Hiroshima, Japan.
Hepatology Research (Impact Factor: 2.74). 12/2011; 42(5):442-53. DOI: 10.1111/j.1872-034X.2011.00943.x
Aim: We investigated the efficacy of hepatic arterial infusion chemotherapy (HAIC) using 5-fluorouracil (5-FU) and systemic interferon (IFN)-α (HAIC-5-FU/IFN) for advanced hepatocellular carcinoma (HCC) with venous tumor thrombosis (VTT) in the hepatic vein trunk (Vv2) or inferior vena cava (Vv3).
Methods: Thirty-three patients with HCC/Vv2/3 underwent HAIC with 5-FU (500 mg/body weight/day, into hepatic artery on days 1–5 on the first and second weeks) and IFN-α (recombinant IFN-α-2b 3 000 000 U or natural IFN-α 5 000 000 U, intramuscularly on days 1, 3 and 5 of each week). Three-dimensional conformal radiotherapy (3D-CRT) was used in combination with HAIC-5-FU/IFN in 14 of 33 patients to reduce VTT.
Result: The median survival time (MST) was 7.9 months, and 1- and 2-year survival rates were 30% and 20%, respectively. Evaluation of intrahepatic response after two cycles of HAIC-5-FU/IFN showed complete response (CR) in three (9%) and partial response (PR) in seven (21%), with an objective response rate of 30%. Multivariate analysis identified reduction of VTT (P = 0.0006), size of largest tumor (P = 0.013) and intrahepatic response CR/PR (P = 0.030) as determinants of survival. CR/PR correlated significantly with tumor liver occupying rate (P = 0.016) and hepatitis C virus Ab (P = 0.010). Reduction of VTT correlated significantly with radiotherapy (P = 0.021) and platelet count (P = 0.015). Radiotherapy-related reduction in VTT significantly improved survival of 16 patients with Vv3 and non-CR/PR response of HAIC-5-FU/IFN (P = 0.028).
Conclusion: As for advanced HCC with VTT of Vv2/3, HAIC-5-FU/IFN responsive patients could obtain favorable survival. Despite ineffective HAIC-5-FU/IFN, the combination with effective radiotherapy to VTT might improve patients' prognosis.
"Radiotherapy (RT) can produce survival benefits in patients with advanced HCC and macroscopic hepatic vascular invasion [7,16-18]. We previously reported that the use of three-dimensional conformal RT (3D-CRT) resulted in a good disease control rate and prolonged survival in these patients. "
[Show abstract][Hide abstract] ABSTRACT: Background
This study investigated the survival benefits of sorafenib vs. radiotherapy (RT) in patients with unresectable hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT) in the main trunk or the first branch.
Ninety-seven patients were retrospectively reviewed. Forty patients were enrolled by the Kanagawa Liver Study Group and received sorafenib, and 57 consecutive patients received RT in our hospital. Overall survival was compared between the two groups with PVTT by propensity score (PS) analysis. Factors associated with survival were evaluated by multivariate analysis.
The median treatment period with sorafenib was 45 days, while the median total radiation dose was 50 Gy. The Child-Pugh class and the level of invasion into hepatic large vessels were significantly more advanced in the RT group than in the sorafenib group. Median survival did not differ significantly between the sorafenib group (4.3 months) and the RT group (5.9 months; P = 0.115). After PS matching (n = 28 per group), better survival was noted in the RT group than in the sorafenib group (median survival, 10.9 vs. 4.8 months; P = 0.025). A Cox model showed that des-γ-carboxy prothrombin <1000 mAU/mL at enrollment and RT were significant independent predictors of survival in the PS model (P = 0.024, HR, 0.508; 95% CI, 0.282 to 0.915; and P = 0.007, HR, 0.434; 95% CI, 0.235 to 0.779; respectively).
RT is a better first-line therapy than sorafenib in patients who have advanced unresectable HCC with PVTT.
[Show abstract][Hide abstract] ABSTRACT: We examined whether treatment sequence and secondary therapy affected prognosis in advanced hepatocellular carcinoma (HCC) of Child-Pugh A without metastasis. The study included 148 patients: 83 who primarily received Hepatic Arterial Infusion Chemotherapy (HAIC), 53 who received Sorafenib, and 12 with best supportive care (BSC). These treatment groups were stratified by presence (+)/absence (-) of secondary therapy. Although a significant difference in the response rate was found between the HAIC group and the Sorafenib group, there were no differences in disease control rate and survival. Additionally, both prolonged survival compared to the BSC group. Sorafenib (+) group showed the highest cumulative survival rate, which was an independent prognostic factor in multivariate analysis. Furthermore, the initial Sorafenib dose per body weight was a contributing factor for treatability with HAIC as secondary therapy subsequent to Sorafenib. The prognosis of advanced HCC might be improved by Sorafenib per body weight followed by HAIC.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to clarify the clinical features of patients with isolated HCC metastases to the heart. A 66-year-old female hospitalized with a hepatocellular carcinoma (HCC) ranging from the right to the left lobe and with a tumor thrombus in the main portal vein, was treated with intraarterial cisplatin, 5-fluouracil, adriamycin and mitomycin. Computed tomography (CT) one month later revealed that the HCC had progressed with multiple lung metastases and moderate ascites. The patient had no symptoms. Magnetic resonance imaging (MRI) and echocardiography revealed a round, movable tumor with a diameter of 2 cm in the right atrium (RA). The patient succumbed to HCC five months later. An autopsy revealed HCC with portal tumor thrombi and metastases to the lungs, inferior vena cava (IVC) and RA. The metastases in the RA and IVC were not continous with the intrahepatic tumor and were histologically attached to the endocardium and endothelium, respectively. An isolated metastasis of a HCC of the RA and IVC is extremely rare. In conclusion, although the majority of isolated metastases of HCC to the heart were diagnosed by echocardiography and were treated with mainly surgery, they had poor prognosis. The echocardiography should be performed for patients with advanced HCC. A novel treatment including molecular targeted drugs is required.
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