术后辅助酪氨酸激酶抑制剂联合抗 PD-1 抗体可改善具有高危复发因素的肝细胞癌的手术效果。

Postoperative adjuvant tyrosine kinase inhibitors combined with anti-PD-1 antibodies improves surgical outcomes for hepatocellular carcinoma with high-risk recurrent factors.

机构信息

Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Front Immunol. 2023 Jun 8;14:1202039. doi: 10.3389/fimmu.2023.1202039. eCollection 2023.

BACKGROUND

The clinical value of postoperative adjuvant therapy (PAT) for hepatocellular carcinoma (HCC) remains unclear. This study aimed to explore the effect of PAT with tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies on the surgical outcomes of HCC patients with high-risk recurrent factors (HRRFs).

METHODS

HCC patients who underwent radical hepatectomy at Tongji Hospital between January 2019 and December 2021 were retrospectively enrolled, and those with HRRFs were divided into PAT group and non-PAT group. Recurrence-free survival (RFS) and overall survival (OS) were compared between the two groups after propensity score matching (PSM). Prognostic factors associated with RFS and OS were determined by Cox regression analysis, and subgroup analysis was also conducted.

RESULTS

A total of 250 HCC patients were enrolled, and 47 pairs of patients with HRRFs in the PAT and non-PAT groups were matched through PSM. After PSM, the 1- and 2-year RFS rates in the two groups were 82.1% vs. 40.0% ( < 0.001) and 54.2% vs. 25.1% ( = 0.012), respectively. The corresponding 1- and 2-year OS rates were 95.4% vs. 69.8% ( = 0.001) and 84.3% vs. 55.5% ( = 0.014), respectively. Multivariable analyses indicated that PAT was an independent factor related to improving RFS and OS. Subgroup analysis demonstrated that HCC patients with tumor diameter > 5 cm, satellite nodules, or vascular invasion could significantly benefit from PAT in RFS and OS. Common grade 1-3 toxicities, such as pruritus (44.7%), hypertension (42.6%), dermatitis (34.0%), and proteinuria (31.9%) were observed, and no grade 4/5 toxicities or serious adverse events occurred in patients receiving PAT.

CONCLUSIONS

PAT with TKIs and anti-PD-1 antibodies could improve surgical outcomes for HCC patients with HRRFs.

背景

肝癌（HCC）术后辅助治疗（PAT）的临床价值仍不明确。本研究旨在探讨酪氨酸激酶抑制剂（TKI）和抗 PD-1 抗体的 PAT 对伴有高复发风险因素（HRRFs）的 HCC 患者手术结局的影响。

方法

回顾性纳入 2019 年 1 月至 2021 年 12 月在同济大学附属同济医院接受根治性肝切除术的 HCC 患者，将伴有 HRRFs 的患者分为 PAT 组和非 PAT 组。采用倾向性评分匹配（PSM）后比较两组患者的无复发生存率（RFS）和总生存率（OS）。采用 Cox 回归分析确定与 RFS 和 OS 相关的预后因素，并进行亚组分析。

结果

共纳入 250 例 HCC 患者，经 PSM 后在 PAT 和非 PAT 组中匹配了 47 对伴有 HRRFs 的患者。PSM 后，两组患者的 1 年和 2 年 RFS 率分别为 82.1%比 40.0%（<0.001）和 54.2%比 25.1%（=0.012），相应的 1 年和 2 年 OS 率分别为 95.4%比 69.8%（=0.001）和 84.3%比 55.5%（=0.014）。多变量分析表明，PAT 是改善 RFS 和 OS 的独立相关因素。亚组分析表明，肿瘤直径>5 cm、卫星结节或血管侵犯的 HCC 患者在 RFS 和 OS 中可从 PAT 中显著获益。观察到常见的 1-3 级毒性反应，如瘙痒（44.7%）、高血压（42.6%）、皮疹（34.0%）和蛋白尿（31.9%），接受 PAT 治疗的患者未发生 4/5 级毒性反应或严重不良事件。