Neoadjuvant Radiotherapy vs Surgery Alone for Resectable Hepatocellular Carcinoma With Tumor Thrombus


Key Points

  • The addition of neoadjuvant three-dimensional conformal radiotherapy improved overall survival vs hepatectomy alone.
  • Response to radiotherapy appeared to be associated with IL-6 expression.


In a Chinese study reported in the Journal of Clinical Oncology, Wei et al found that neoadjuvant three-dimensional conformal radiotherapy improved outcomes vs hepatectomy alone in patients with resectable hepatocellular carcinoma with portal vein tumor thrombus.

Study Details

In the multicenter trial, patients were randomly assigned between January 2016 and December 2017 to receive neoadjuvant three-dimensional conformal radiotherapy followed by hepatectomy (n = 82) or hepatectomy alone (n = 82). For radiotherapy, the planned total dose to the target volume was 18 Gy in 3 Gy fractions. Response was assessed using modified RECIST criteria. The primary endpoint was overall survival on intent-to-treat analysis. Interleukin-6 (IL-6) expression in serum before radiotherapy and in surgical specimens was assessed for correlation with response to radiotherapy.

Response and Survival

Partial remission was observed in 17 patients (20.7%) in the neoadjuvant radiotherapy group, with 58 (70.7%) having stable disease. Overall survival rates for the neoadjuvant radiotherapy group vs the hepatectomy alone group were 89.0% vs 81.7% at 6 months, 75.2% vs 43.1% at 12 months, 43.9% vs 16.7% at 18 months, and 27.4% vs 9.4% at 24 months (overall P < .001). Disease-free survival rates at these timepoints were 56.9% vs 42.1%, 33.0% vs 14.9%, 20.3% vs 5.0%, and 13.3% vs 3.3%, respectively (overall P < .001). On multivariate analysis, hazard ratios favoring the neoadjuvant radiotherapy group were 0.35 (P <.001) for overall survival and 0.45 (P < .001) for recurrence.

In the neoadjuvant radiotherapy group, nine patients developed contraindications to surgery after radiotherapy and underwent nonsurgical therapy, including two patients with grade 3 liver toxicity associated with radiotherapy. Surgical complication rates were similar in the two groups.

Increased expressions of IL-6 in preradiotherapy serum and tumor tissues were significantly associated with resistance to radiotherapy, with levels being higher in patients with stable disease vs partial response (P = .018) and higher in those with progressive disease vs stable disease or partial response (P = .047).

The investigators concluded, “For patients with resectable hepatocellular carcinoma and portal vein tumor thrombus, neoadjuvant radiotherapy provided significantly better postoperative survival outcomes than surgery alone. IL-6 may predict response to radiotherapy in these patients.”

Shuqun Cheng, MD, of the Department of Hepatic Surgery VI, Navy Military Medical University, Shanghai, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the National Key Basic Research Program 973 project, the Project of Shanghai Shenkang Hospital Development Center, the Key Project of the Natural Science Foundation of China, and others. For full disclosures of the study authors, visit

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