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| 初始不可切除肝细胞癌行血管介入联合TKI及PD-1抑制剂转化治疗后序贯肝切除术的安全性和有效性研究 |
| 唐置鸿1,2△,袁度1,3△,许少伟1,3,庞清清1,4,赵桂霖1,3,韦猛1,2,吴飞翔1,2* |
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(1. 广西医科大学附属肿瘤医院肝胆胰脾外科, 南宁 530021;
2. 区域性高发肿瘤早期防治研究教育部重点实验室, 南宁 530021;
3. 广西医科大学肿瘤医学院肝胆胰脾外科, 南宁 530021;
4. 广西医科大学第四附属医院肿瘤科, 柳州 545005
△共同第一作者
*通信作者) |
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| 摘要: |
| 目的 探讨经血管介入治疗（包括肝动脉插管化疗栓塞术和肝动脉灌注化疗）联合酪氨酸激酶抑制剂（TKI）及程序性死亡受体1（PD-1）抑制剂在初始不可切除肝细胞癌转化治疗后序贯肝切除术患者中的围手术期安全性和预后影响因素。方法 回顾性分析2019年11月至2024年4月在广西医科大学附属肿瘤医院接受治疗的106例符合条件的肝细胞癌患者的临床资料，详细描述患者的围手术期相关参数和术后病理结果，并分析预后的影响因素。结果 转化治疗后序贯肝切除术的中位手术时间为240 min，中位出血量为200 mL。24例（22.6%）患者需要术中输血。术后不良反应发生率为49.1%（52/106），最常见的术后不良反应是肝功能衰竭（23例，21.7%）。1例（0.9%）患者在围手术期死亡，余105例患者的中位随访时间为14.7个月。随访期间有49例（46.2%）患者复发，其中早期复发（1年内）39例（36.8%），肝内复发33例（31.1%）。13例（12.3%）患者在随访期间死亡，中位无复发生存期为15.7个月，1年和2年无复发生存率分别为56.9%和40.3%。中位总生存期未达到，1年和2年总生存率分别为94.2%和85.3%。多因素Cox回归分析显示，达到完全病理缓解（HR＝0.410，95%CI 0.172～0.980，P＝0.045）、合并微血管侵犯（HR＝2.423，95%CI 1.269～4.625，P＝0.007）、存在卫星灶（HR＝1.916，95%CI 1.014～3.620，P＝0.045）和肿瘤多发（HR＝1.818，95%CI 1.012～3.241，P＝0.046）是术后复发的独立影响因素。结论 对于初始不可切除肝细胞癌患者，血管介入治疗联合TKI及PD-1抑制剂转化治疗后序贯肝切除术可能是一种不良反应可控且有效的治疗方式。 |
| 关键词: 肝肿瘤 不可切除肝细胞癌 转化治疗 肝切除术 预后 |
| DOI：10.16781/j.CN31-2187/R.20240424 |
| 投稿时间：2024-06-14修订日期：2025-01-08 |
| 基金项目:国家自然科学基金（82360537），区域性高发肿瘤早期防治研究教育部重点实验室项目（GKE-ZZ202309，GKE-ZZ202216，GKE-ZZ202129）． |
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| Safety and efficacy of sequential hepatectomy after conversion therapy using vascular intervention therapy combined with TKI and PD-1 inhibitors for initial unresectable hepatocellular carcinoma |
| TANG Zhihong1,2△,YUAN Du1,3△,XU Shaowei1,3,PANG Qingqing1,4,ZHAO Guilin1,3,WEI Meng1,2,WU Feixiang1,2* |
(1. Department of Hepatobiliary, Pancreatic and Splenic Surgery, Tumor Hospital Affiliated to Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China;
2. Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Ministry of Education, Nanning 530021, Guangxi Zhuang Autonomous Region, China;
3. Department of Hepatobiliary, Pancreatic and Splenic Surgery, College of Oncology, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China;
4. Department of Oncology, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou 545005, Guangxi Zhuang Autonomous Region, China
△Co-first authors.
* Corresponding author) |
| Abstract: |
| Objective To explore the perioperative safety and prognostic factors of sequential hepatectomy after conversion therapy using vascular interventional therapy (including transarterial chemoembolization and hepatic arterial infusion chemotherapy) combined with tyrosine kinase inhibitors (TKI) and programmed death-1 (PD-1) inhibitors in patients with initially unresectable hepatocellular carcinoma. Methods The clinical data of 106 eligible HCC patients treated in Tumor Hospital Affiliated to Guangxi Medical University from Nov. 2019 to Apr. 2024 were retrospectively analyzed. The perioperative parameters and postoperative pathological outcomes were described in detail, and factors influencing prognosis were analyzed. Results The median operative time for hepatectomy after conversion therapy was 240 min, with a median blood loss of 200 mL. Intraoperative blood transfusion was required in 24 (22.6%) patients. Postoperative adverse reactions occurred in 49.1% (52/106) of patients, with liver failure being the most common adverse reactions (23 patients, 21.7%). One (0.9%) patient died during the perioperative period, while the remaining 105 patients were followed up for a median duration of 14.7 months, during which 49 (46.2%) patients experienced recurrence. Among them, 39 (36.8%) cases experienced early recurrence (within 1 year), and 33 (31.1%) cases had intrahepatic recurrence. Thirteen (12.3%) patients died during follow-up. The median recurrence-free survival (RFS) was 15.7 months, with 1-year and 2-year RFS rates being 56.9% and 40.3%, respectively. The median overall survival (OS) was not reached, with 1-year and 2-year OS rates being 94.2% and 85.3%, respectively. Multivariate Cox regression analysis demonstrated that achieving complete pathological response (hazard ratio ［HR］ ＝0.410, 95% confidence interval ［CI］ 0.172-0.980, P＝0.045), presence of microvascular invasion (HR＝2.423, 95% CI 1.269-4.625, P＝0.007), satellite nodules (HR＝1.916, 95% CI 1.014-3.620, P＝0.045), and multiple tumors (HR＝1.818, 95% CI 1.012-3.241, P＝0.046) were independent factors associated with postoperative recurrence. Conclusion For patients with initially unresectable hepatocellular carcinoma, vascular interventional therapy combined with TKI and PD-1 inhibitors followed by sequential hepatectomy may be a feasible treatment strategy, with manageable adverse reactions and promising efficacy. |
| Key words: liver neoplasms unresectable hepatocellular carcinoma conversion therapy hepatectomy prognosis |
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