背景：手術作為超過米蘭標準的可切除 BCLC A/B 期肝細胞癌(HCC)的唯一根治性選擇，但療效仍不令人滿意。本研究旨在探討術前新輔助動脈灌注化療(TAI)聯合 FOLFOX 方案治療此類患者的療效和安全性。
Background:The efficacy of operation, as the only radical option for resectable BCLC stage A/B hepatocellular carcinoma (HCC) patients beyond Milan criteria, is still unsatisfactory. This study aimed to investigate to efficacy and safety of preoperative neoadjuvant transarterial infusion chemotherapy (TAI) with FOLFOX regimen for these patients.
方法：在這項多中心、前瞻性、3 期、隨機、開放標記、對照臨床試驗中，符合米蘭標準的可切除 BCLC A/B 期肝癌患者在肝切除前(1：1)隨機分為兩組，一組接受新輔助 TAI(NT 組)，另一組不接受任何新輔助治療直接手術(OP 組)。主要終點是總生存期(OS)，次要終點是無進展生存期(PFS)、無複發生存期(RFS)和安全性。
Methods:In this multi-center, prospective, phase 3, randomized, open-labeled, controlled clinical trial, resectable BCLC stage A/B HCC patients beyond Milan criteria were randomly assigned (1:1) before hepatectomy to receive either neoadjuvant TAI (NT group) or operation directly without any neoadjuvant treatment (OP group). The primary endpoint was overall survival (OS), the secondary endpoints are progression-free survival (PFS), recurrence free survival (RFS), and safety.
結果：自 2016 年 3 月至 2020 年 7 月，將來自 5 家中國醫院的 208 例患者隨機分為 NT 組(n=104)和 OP 組(n=104)。NT 組 99 例，OP 組 100 例納入療效和安全性分析。兩組患者的臨床病理特征基本一致。NT 組 1、2、3 年 OS 率分別為 92.9%、78.6%、63.5%，OP 組分別為 79.5%、62.0%、46.3%。NT 組 6 個月、12 個月、18 個月 PFS 率分別為 77.6%、50.4%、47.4%，OP組分別為 52.7%、42.8%、34.8%。NT 組的 OS 和 PFS 明顯優於 OP 組(p=0.016 和 0.017)。 NT 組 6 個月、12 個月、18 個月的 RFS 率分別為 63.8%、47.3%、47.3%，OP 組分別為 52.7%、42.8%、34.8%。兩組 RFS 差異無統計學意義(p=0.385)。NT 組無 3 級及以上嚴重 TAI 相關不良事件發生。兩組手術相關不良事件相似(p=0.300)。
Results:Between March, 2016 and July, 2020, 208 patients enrolled from five Chinese hospitals were randomly assigned to NT group (n=104) or OP group (n=104)， with 99 patients in NT group and 100 patients in OP group included in the efficacy and safety analysis. Clinicopathological characteristics were balanced between the two groups. The 1-, 2-, and 3-year OS rates for NT group were 92.9%, 78.6%, and 63.5%, and were 79.5%, 62.0%, and 46.3% for OP group, respectively. The 6-, 12-, and 18-month PFS rates for NT group were 77.6%, 50.4%, and 47.4%, and were 52.7%, 42.8%, and 34.8% for OP group, respectively. The OS and PFS were significantly better in NT group than in OP group (p=0.016 and 0.017, respectively). The 6-, 12-, and 18-month RFS rates for NT group were 63.8%, 47.3%, and 47.3%, and were 52.7%, 42.8%, and 34.8% for OP group, respectively. The RFS between the two group had no difference (p=0.385). No patients in NT group experienced grade 3 or more severe TAI related adverse events. The operation related adverse events were similar between two groups (p=0.300).
結論：肝切除術前新輔助 TAI 可能為超出米蘭標準的可切除 BCLC A/B 期肝癌患者帶來生存益處。
Conclusions:Neoadjuvant TAI before hepatectomy may bring survival benefits for resectable BCLC stage A/B HCC patients beyond Milan criteria.
