Hepatocellular carcinoma (HCC) is the sixth prevalent malignancy worldwide. Although surgical excision is considered the standard treatment for resectable HCC, a high rate of postoperative recurrence was observed after partial hepatectomy, with a marginal recurrence rate up to 30%. Narrow margin resection may be the most appropriate procedure for centrally located HCC because the premise for survival is the conservation of more normal liver parenchyma. Unfortunately, narrow margin resection has been reported to contribute to poor survival outcomes. However, no (neo)adjuvant therapy before (or after) hepatectomy is generally considered to be effective in reducing post-operative recurrence.

Radiotherapy (RT) has been well used in many solid malignant tumors as an (neo)adjuvant to surgical treatment, including HCC. SBRT has shown encouraging rates of local control for HCC. Compared with standard fractionation radiation, SBRT can achieve more precise delivery of high-dose radiation beams to the lesion, obtaining a much smaller target volume. Meanwhile, it could be finished in a short period which can bring more convenience to patients. Recently, several study and randomized controlled trials revealed the survival benefit of adjuvant RT (IMRT and SBRT) in patients with HCC. However, there are still lack of exploration for the efficacy of neoadjuvant SBRT. This study is to analyze the safety of preoperative SBRT followed by hepatectomy for centrally located hepatocellular carcinoma.

Inclusion Criteria:

1. Aged ≥18 years;
2. Confirmed diagnosis of HCC. The diagnosis can be established radiographically by the criteria of the American Association for the Study of the Liver (AASLD), or by histologic diagnosis from the core biopsy;
3. Centrally located hepatocellular carcinoma and medically fit to undergo surgery as determined by the Multiple Disciplinary Team (MDT);
4. BCLC stage A
5. No imaging evidence of direct invasion of stomach, duodenum, small intestine, large intestine or diaphragm of the intrahepatic lesions to be treated with radiotherapy;
6. Child-Pugh class A and B7;
7. ECOG (Eastern Cooperative Oncology Group) performance status 0 or 1;
8. Willing to provide tissue from an excisional biopsy of a tumor lesion;
9. For patients with active HBV: HBV DNA < 2000 IU/mL during screening, and have initiated anti-HBV treatment at least 7 days prior to SBRT and willingness to continue anti-HBV treatment during the study;
10. Adequate organ and marrow function as defined below:

1)Marrow: absolute neutrophil count ≥1.5×109/L; platelets ≥50×109/L; hemoglobin ≥90g/L; 2)Liver: total bilirubin ≤3× institutional upper limit of normal (ULN); AST(aspartate aminotransferase) or ALT(alanine aminotransferase) ≤ 5× institutional ULN; albumin ≥29g/L; 3)Kidney: creatinine ≤ 1.5× institutional ULN or estimated glomerular filtration rate (GFR) ≥50 mL/min/1.73 m2 (according to the Cockcroft-Gault formula); 11. Women of childbearing potential must be willing to use a highly effective method of contraception for the course of the study through 30 days after radiotherapy. Female patient of childbearing potential should have a negative serum pregnancy test before 72h of her first treatment. Sexually active males must agree to use an adequate method of contraception starting with the treatment through 4 months after radiotherapy.

Exclusion Criteria:

1. Have received local or systemic treatments in the past, including but not limited to TACE, immunotherapy, targeted therapy, radiotherapy, radiofrequency therapy, etc.;
2. Severe bleeding tendency or coagulation dysfunction within the previous 6 months;
3. Extrahepatic metastasis;
4. Prior abdominal irradiation;
5. Any major surgery within 1 months prior to enrolment;
6. Known history of active Bacillus Tuberculosis (TB)
7. Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer.
8. Active infection requiring systemic therapy;
9. Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy;
10. Known psychiatric or substance abuse disorders ;
11. Pregnant or breastfeeding;
12. Known history of human immunodeficiency virus (HIV: HIV 1/2 antibodies);
13. Received a live vaccine within 30 days before radiotherapy.