Microwave Ablation Combined With TACE in the Treatment of Unresectable Huge Hepatocellular Carcinoma Huge

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Despite the widespread application of surveillance programs in high-risk populations, patients continue to present with huge (≥ 10 cm) HCCs.And it's still a challenge to treat huge HCC nowadays.Surgical resection is currently the only curative treatment for huge HCCs ; however, only a minority of patients are candidates for curative resection. Sorafenib is recommended for the treatment of advanced HCCs, including huge HCCs, but the usage is severely limited by high adverse event rates and low efficiency. Thus, transarterial chemoembolization (TACE) is considered the first choice for huge unresectable HCCs. Several studies have concluded that TACE effectively improves the overall survival of patients with huge HCCs. Meanwhile, microwave ablation (MWA) now has been shown to be safe and effective for local tumor control in HCC patients. However, neither MWA nor TACE alone can achieve complete control of large HCCs . Therefore, the combination of TACE and MWA (TACE+MWA) is an appealing approach to treat HCCs. TACE+MWA now has been shown to improve overall survival rates compared with TACE alone in patients with small to large HCCs. But little data is available on TACE+MWA in patients with huge unresectable HCCs. Thus, the study was designed.

• TACE (Procedure), also known as Transcatheter arterial chemoembolization procedure: TACE: With the patient under local anesthesia, a 5F French catheter was introduced into the abdominal aorta via the femoral artery using the Seldinger technique. Hepatic arterial angiography was performed using fluoroscopy to guide the catheter into the celiac and superior mesenteric arteries. Then, the feeding arteries, tumor, and vascular anatomy surrounding the tumor were identified. Subsequently, a microcatheter was super-selectively inserted into the feeding arteries. Then, a mixture solution containing chemotherapeutic agents and embolic agents were infused into the artery according to the size and blood supply of the tumors.
• MWA (Procedure), also known as Microwave ablation: MWA: All patients were instructed to fast from all foods for 12 hours preoperatively. During the procedure, a CT scan was used to locate the liver tumors, and to design the optimal puncture needle route. Routine disinfection and local anesthesia was applied around the puncture point, and a 16-gauge microwave antenna was gradually inserted into the tumor along the pre-determined angle. Settings of the MWA parameters depended on the manufacturer's recommendation and our experience.
• MWA system (Device), also known as Microwave ablation system: MWA system is a kind of medical treatment instrument to restrain and kill tumor based on microwave heating technique and biology heating effect theory.
• Chemoembolization (Drug), also known as Chemotherapeutic drugs and Embolic agent: Chemotherapeutic drugs: adriamycin，epirubicin and pirarubicin. Embolic agent: lipiodol and embolic microspherea The mixture solution containing chemotherapeutic drugs and embolic agent were infused into the artery according to by the number and size of the lesions, liver and kidney function of the patient, and blood supply of the tumors.

Primary outcomes

• Overall survival (OS) [up to 3 years]: Overall survival (OS) will be defined as the elapsed time from the enrollment to death from any cause. For surviving patients, follow-up will be censored at the date of last contact (or last date known to be alive). Follow-up for OS will occur every 12 weeks (±1 month) until death or withdrawal of consent from the study.

Secondary outcomes

• Progression-free survival (PFS) [up to 3 years]: Progression-free survival (PFS) will be defined as the elapsed time from the first date of study treatment until documented disease progression (as per mRECIST) or death from any cause, whichever is earlier. For patients who remain alive without progression, follow-up time will be censored at the date of last disease assessment.
• Adverse event rate [up to 3 years]: Adverse event rate will be defined as the rate of patients who developed adverse event.
• Distant metastasis-free survival [up to 3 years]: Progression-free survival (PFS) will be defined as the elapsed time from the first date of study treatment until documented distant metastasis (as per RECIST 1.1) or death from any cause, whichever is earlier. For patients who remain alive without progression, follow-up time will be censored at the date of last disease assessment .

Sex: All, ages: 18 Years to 75 Years

Inclusion Criteria:

1. The performance status of Eastern Cooperative Oncology Group (ECOG) must be 0-1
2. The diagnosis of primary hepatocellular carcinoma must be in line with the American Society for the study of liver diseases (AASLD) diagnostic criteria for hepatocellular carcinoma (HCC)
3. Child-Pugh score A or B;
4. Aged from 18 to 75 years;
5. Subjects voluntarily join the study, and signe informed consent;
6. No anti-tumor therapy was received；
7. Meet the following 4 characteristics: A. primary tumor diameter more than or equal to 10cm; B. no more than 3 HCC foci, and the maximum diameter is less than or equal to 5cm; C. with IIa, I or no portal vein tumor thrombus (Cheng's Classification)；D. the tumor could not be surgically removed
8. No extrahepatic metastases

Exclusion Criteria:

1. Abnormal coagulation function: PLT < 40×109/L, PTA < 40%;
2. Patients have the past history of liver cancer treatment, such as transplantation, resection, radiotherapy, chemotherapy and so on;
3. Patients participated in clinical trials of equipment or drugs (signed informed consent) within 4 weeks;
4. Patients accompany by ascites, hepatic encephalopathy and esophageal and gastric varices bleeding;
5. Any serious accompanying disease, which is expected to have an unknown, impact on the prognosis, include heart disease, inadequately controlled diabetes and psychiatric disorders;
6. Patients accompanied with other tumors or past medical history of malignancy;
7. Pregnant or lactating patients, all patients participating in this trial must adopt appropriate birth control measures during treatment;
8. Allergic to adriamycin chemotherapy drugs，contrast agent and lipiodol;
9. Patients have poor compliance.

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• Weijun Fan, M.D, Study chair, Sun Yat-sen University