Neoadjuvant versus adjuvant radiotherapy for centrally located hepatocellular carcinoma: a propensity score matching study based on two prospective phase II trials

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Background: The prognosis of centrally located hepatocellular carcinoma (cl-HCC) was unsatisfactory when treated with surgery alone. Adjuvant radiotherapy (RT) and neoadjuvant radiotherapy have been reported to correlate with better disease-free survival (DFS) and overall survival (OS) in cl-HCC. Objectives: To compare the survival outcomes and safety of neoadjuvant intensity-modulated radiotherapy (Neo-IMRT) plus surgery with surgery plus adjuvant IMRT (Adj-IMRT) in patients with cl-HCC. Design: This was a retrospective cohort study. Methods: Data from previous prospective studies were analyzed. Propensity score matching (PSM) was used to balance the baseline characteristics between the Neo-IMRT group and the Adj-IMRT group. Results: Before PSM, the Neo-IMRT group had a higher proportion of larger tumor size (>5 cm), multiple nodes, and higher α-fetoprotein levels than the Adj-IMRT group (all p < 0.05). There were no significant differences in 5-year OS (69.1% for the Neo-IMRT group vs 72.2% for the Adj-IMRT group), DFS (41.0% for vs 51.6%), or recurrence pattern (all p > 0.05). The Neo-IMRT group had less leukopenia (50.0% vs 68.7%), more bilirubin increased (42.1% vs 22.4%), and wider surgical margins (median, 1.0 vs 0 cm; all p < 0.05). After PSM, 31 patients were matched in each group. The 5-year OS was 75.9% for the Neo-IMRT group and 66.3% for the Adj-IMRT group ( p = 0.532), and the 5-year DFS was 45.8% and 46.0% ( p = 0.970), respectively. There were no significant differences in recurrence pattern, radiation-related acute adverse events, operative variables, or postoperative complications, except that the Neo-IMRT group had wider surgical margins ( p < 0.001). Conclusion: Neo-IMRT plus surgery was as effective and safe as surgery plus Adj-IMRT for patients with cl-HCC. Further prospective trials are warranted to confirm the findings.

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