Neoadjuvant Three-Dimensional Conformal Radiotherapy for Resectable Hepatocellular Carcinoma With Portal Vein Tumor Thrombus: A Randomized, Open-Label, Multicenter Controlled Study

J Clin Oncol. 2019 Aug 20;37(24):2141-2151. doi: 10.1200/JCO.18.02184. Epub 2019 Jul 8.

Abstract

Purpose: To compare the survival outcomes of neoadjuvant three-dimensional conformal radiotherapy (RT) followed by hepatectomy with hepatectomy alone in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT).

Patients and methods: A randomized, multicenter controlled study was conducted from January 2016 to December 2017 in patients with resectable HCC and PVTT. Patients were randomly assigned to receive neoadjuvant RT followed by hepatectomy (n = 82) or hepatectomy alone (n = 82). The modified Response Evaluation Criteria in Solid Tumors (mRECIST) guidelines were used to evaluate the therapeutic effects of RT. The primary end point was overall survival. The expression of interleukin-6 (IL-6) in patients' serum before RT and in surgical specimens was correlated with response to RT.

Results: In the neoadjuvant RT group, 17 patients (20.7%) had partial remission. The overall survival rates for the neoadjuvant RT group at 6, 12, 18, and 24 months were 89.0%, 75.2%, 43.9%, and 27.4%, respectively, compared with 81.7%, 43.1%, 16.7%, and 9.4% in the surgery-alone group (P < .001). The corresponding disease-free survival rates were 56.9%, 33.0%, 20.3%, and 13.3% versus 42.1%, 14.9%, 5.0%, and 3.3% (P < .001). On multivariable Cox regression analyses, neoadjuvant RT significantly reduced HCC-related mortality and HCC recurrence rates compared with surgery alone (hazard ratios, 0.35 [95% CI, 0.23 to 0.54; P < .001] and 0.45 [95% CI, 0.31 to 0.64; P < .001]). Increased expressions of IL-6 in pre-RT serum and tumor tissues were significantly associated with resistance to RT.

Conclusion: For patients with resectable HCC and PVTT, neoadjuvant RT provided significantly better postoperative survival outcomes than surgery alone. IL-6 may predict response to RT in these patients.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Hepatocellular / radiotherapy*
  • Carcinoma, Hepatocellular / surgery
  • Female
  • Hepatectomy
  • Humans
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / blood
  • Liver Neoplasms / blood
  • Liver Neoplasms / radiotherapy*
  • Liver Neoplasms / surgery
  • Male
  • Middle Aged
  • Neoadjuvant Therapy
  • Portal Vein / pathology*
  • Predictive Value of Tests
  • Radiotherapy, Adjuvant
  • Radiotherapy, Conformal / adverse effects
  • Radiotherapy, Conformal / methods
  • Survival Rate
  • Treatment Outcome
  • Venous Thrombosis / blood
  • Venous Thrombosis / physiopathology*

Substances

  • IL6 protein, human
  • Interleukin-6

Associated data

  • ChiCTR/ChiCTR-INR-17012510