The role of transarterial chemoembolization (TACE) as the standard therapy for intermediate-stage hepatocellular carcinoma (HCC) is being challenged by increasing studies which showed that liver resection (LR) is a safe and feasible procedure with better survival outcomes than TACE does. In light of this, the investigators have constructed a Markov model to simulate comparing LR and TACE in the treatment of intermediate-stage HCC. The results suggested that LR may provide survival benefit over TACE for the treatment of intermediate-stage HCC in cirrhotic patients. However, validating the simulated result by a study with higher quality (e.g. prospective clinical trial) would be of great value in providing a more convincing finding. Therefore, based on the established Markov model, the investigators aimed to prospectively compare the treatment efficacy and safety of LR with TACE for consecutive patients with intermediate-stage HCC.
Hepatocellular carcinoma (HCC) is the 5th most common cancer worldwide and the third most frequent cause of death of cancer. However, the management strategies for intermediate-stage HCC remain controversial without global consensus. On one hand, Barcelona Clinic Liver Cancer (BCLC) staging system recommends liver resection (LR) for very early and early-stage HCC, and transarterial chemoembolization (TACE) for intermediate-stage HCC. On the other hand, observational studies in both Eastern and Western countries have emerged to suggest that LR was safe and achieved better survival than TACE for patients with intermediate-stage HCC, but only very few studies have been conducted to directly compare LR with TACE for these patients. In light of this, the investigators have conducted a multistate Markov model simulating a randomized clinical trial comparing LR with TACE over a follow-up period of 15 years. The results suggested that LR may provide survival benefit over TACE for the treatment of intermediate-stage HCC in cirrhotic patients. However, validating the simulated result by a study with higher quality (e.g. prospective clinical trial) would be of great value in providing a more convincing finding.Therefore, based on the established Markov model,the investigators aimed to prospectively compare the treatment efficacy and safety of LR with TACE for consecutive patients with intermediate-stage HCC.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
198
Intraoperative ultrasound was routinely used during surgery. Anatomic resection was carried out in the form of segmentectomy or/and subsegmentectomy.In segmentectomy, the hepatic parenchyma was transacted at the intersegmental plane as described by Couinaud. If the hepatic parenchymal transaction plane needed to go beyond the intersegmental plane to achieve the desired extent of resection margin, the small portal branches supplying the liver parenchyma up to the intended transaction plane were punctured under US guidance and injected with methylthioninium chloride, and then liver subsegmentectomy was performed either alone or in combination with segmentectomy along the plane of demarcation as delineated by the injected methylthioninium chloride. Nonanatomic resection with a negative resection margin was performed when anatomical resection may cause inadequate liver remnant. Pringle's maneuver was used if necessary with a clamp/unclamp time of 10 min/5 min.
A microcatheter was inserted into the feeding arteries as selectively as possible through the lobar, segmental, or subsegmental arteries, dependent on the tumor distribution and hepatic functional reserve. Hepatic artery infusion chemotherapy was performed using 300 mg carboplatin. Subsequently, chemolipiodolization was performed mixed with 5 ml of lipiodol. According to the number and size of the lesions, and liver and kidney function of the patient, the chemotherapeutic agents, including epirubicin (50-100 mg), pirarubicin (30-50 mg), hydroxycamptothecin (10-30 mg) and fluorouracil (500-1000 mg), were determined by the multidisciplinary team. If residual flow remained after infusion of these agents, additional lipiodol was injected. Embolization was performed with absorbable gelatin sponge particles 350-560 μm in diameter.
Hepatic artery infusion chemotherapy was performed using 300 mg carboplatin (Bristol-Myers Squibb, New York, NY).
Chemolipiodolization was performed mixed with 5 ml of lipiodol (Lipiodol Ultra-Fluide; André Guerbet Laboratories, Aulnay-sous-Bois, France).
The chemotherapeutic agents, including epirubicin (50-100 mg), pirarubicin (30-50 mg), hydroxycamptothecin (10-30 mg) and fluorouracil (500-1000 mg), were determined by the multidisciplinary team.
Embolization was performed with absorbable gelatin sponge particles (Gelfoam; Hangzhou Bi-Trumed Biotech Co., Ltd., Hangzhou, Zhejiang, China) 350-560 μm in diameter.
The First Affiliated Hospital of Sun Yat-sen University
Guangzhou, Guangdong, China
RECRUITINGOverall survival
1-year overall survival
Time frame: 1 year
Mortality
1-month mortality
Time frame: 1 month
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