The Effects of RFA in Combination With Second-line Chemotherapy and Bevacizumab on Unresectable CRLM

Inclusion Criteria:

1.CRLM patients with histopathological diagnosis. 2.Tumor progression after first-line therapy or intolerable adverse events occur;

1. The first-line therapy should be the standard regimen recommended by NCCN guideline.
2. Tumor progression indicates: progression occurs during the process or within three months after the final treatment of first-line therapy; progression occurs during the period of adjunctive therapy/neoadjuvant therapy or within six months after adjunctive therapy finished.
3. Prior treatment with bevacizumab or cetuximab is allowed. 3.Aged between 16-80 years old (16 and 80 years old are included), with no limitation of gender; 4.ECOG scores 0-1; 5.At least one measurable liver metastasis according to RECIST 1.1 criteria; 6.The liver metastasis is no larger than 50% of total liver lesions; 7.Determined as unresectable liver metastasis by the multidisciplinary team consisting of liver surgeons and medical oncologists;

1)R0 resection cannot be operated on liver metastases. 2)Hepatic artery or the branches of portal vein is invaded. 3)The three main hepatic veins are surrounded by liver metastases. 4)Extrahepatic metastases coexist. 8.Life expectancy is above three months; 9.With full appreciation, voluntary and a signed informed consent; 10.Vital organs with normal function:

1. Routine blood test: hemoglobin (HGB) 85g/L, platelet (PLT) 80/L, and neutrophils 1.5/L;
2. Normal coagulation function originally or after treatment (if exceeding reference level, whether it is still within normal range should be determined by researchers);
3. Total bilirubin(BIL) is 1.5 times higher than the upper normal limit, alanine aminotransferase (ALT) and aspartic transaminase (AST) are 5 times higher than the upper normal limit;
4. Urine protein ranges from - to +, and serum creatinine 1.5×ULN; 11.Negative pregnancy test results in women of childbearing age (7 days before RFA treatment), and effective contraceptive measures must be adopted until 6 m after the last treatment.

Exclusion Criteria:

1. Prior treatment with other clinically experimental drugs, systemic chemotherapy, immunotherapy or targeted therapy within 2 weeks before this trial;
2. Prior treatment on liver metastases with radiotherapy, hepatic arterial infusion chemotherapy, transcatheter hepatic arterial chemoembolization, cryoablation, microwave ablation or RFA within 2 weeks before this trial;
3. Abnormal coagulation function and with hemorrhagic tendency;
4. Damaged or infectious skin in the puncture or electrode sticking area;
5. Complicated by active hepatitis or hepatic failure;
6. Complicated by severe hypertension or hypertensive crisis (systolic pressure 180 mmHg and/or diastolic pressure 110 mmHg in a resting state);
7. Impaired cardiac function, manifested as left ventricular ejection fraction 50%, severe arrhythmia, unstable angina, history of myocardial infarction within 1 year before this trial, or congestive heart-failure in NYHA class III or IV;
8. History of stroke within 6 months;
9. History of other malignancies except for colorectal cancer within 5 years;
10. Abnormal medical or psychologic status that may hamper the ongoing trial or signing an informed consent;
11. No or limited legal capacity;
12. Pregnant or breast-feeding women;
13. Combined acute infection or human immunodeficiency virus (HIV) infection;
14. With contradictions for bevacizumab; 1)History of severe hemorrhage or hemoptysis 1 month before this trial 2)Urine protein 2+, and 24-hour urinary protein quantitative 2g 3)Allergy to bevacizumab or any active ingredients 4)Patients with surgery, major trauma or fracture within 4 weeks 5)Unhealed wounds, intestinal stomas or peptic ulcer
15. Treated with other experimental antineoplastic drugs.