Clinical Benefits of Neoadjuvant Radiotherapy on the Postoperative Recurrence of Centrally Located Hepatocellular Carcinoma: A Real-World Evidence Based on Phase II Clinical Trial

OBJECTIVE: Although surgical resection is one of the most effective way to treat liver cancer, its efficacy and safety in treatment of centrally located hepatocellular carcinoma (HCC) remains elusive. Therefore, it is very important to find a comprehensive treatment mode, such as radical resection combined with neoadjuvant radiotherapy (neoRT). METHODS: The centrally located HCC patients who underwent radical resection from July 2015 to April 2021 were enrolled. According to whether the neoRT was implemented or not, these patients were allocated into neoadjuvant radiotherapy combined with liver resection (neoRT+LR) and liver resection alone (LR) group. The research method used propensity-score analysis and Cox proportional-hazards regression models. We generated an E-value to assess the sensitivity to unmeasured confounding. This study is a real-world, retrospective study based on phase II clinical trial. RESULTS: A total of 168 patients were enrolled, including 38 patients treating with neoRT+LR and 130 patients with LR. The 1-, 3-, 5-year disease free survival (DFS) rates were 74%, 55% and 39% in the neoRT+LR group, and 44%, 28%, and 24% in the LR group, respectively. Neoadjuvant radiotherapy was an independent prognostic factor for postoperative recurrence ([HR]0.42, 95% CI [0.25, 0.69]). There was significant association between neoRT+LR and longer disease-free survival (Match, [HR] 0.43, 95% CI [0.24, 0.76]; GenMatch, [HR] 0.32, 95% CI [0.23, 0.43]; Adjusted for propensity score, [HR] 0.41, 95% CI [0.23, 0.73]; Inverse probability weighting, [HR] 0.38, 95% CI [0.22, 0.65], respectively). DFS before and after matching analysis was statistically different in two groups (p-value=0.005, p-value=0.0024, respectively). Neoadjuvant radiotherapy can significantly reduce the postoperative early recurrence (p-value <0.05). E-value analysis suggested robustness to unmeasured confounding. CONCLUSION: Liver resection combined with neoadjuvant radiotherapy was effective and safe for treatment of centrally located HCC patients, which improved the prognosis of patients and reduced the incidence of early recurrence.