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中晚期肝细胞癌经肝动脉化疗栓塞治疗后无反应:放弃还是重复?

Lack of Response to Transarterial Chemoembolization for Intermediate-Stage Hepatocellular Carcinoma: Abandon or Repeat?

机构信息

From the Division of Interventional Ultrasound (S.C., M.K.), Cancer Center (S.C., M.K.), Department of Radiation Oncology (Z.P.), Clinical Trial Unit (Z.P., B.L., J.M.), Institute of Precision Medicine (Z.P., M.K.), Department of Interventional Oncology (Jiaping Li), Department of Radiology (S.F.), and Department of Liver Surgery (M.K.), The First Affiliated Hospital of Sun Yat-sen University, 58 Zhong Shan Road 2, Guangzhou, China 510080; Department of Hepatobiliary Surgery, Cancer Centre, Sun Yat-sen University, Guangzhou, China (Y.Z., M.C., R.G.); and Department of Liver Surgery, Dongguan People's Hospital, Dongguan, China (Jiali Li).

出版信息

Radiology. 2021 Mar;298(3):680-692. doi: 10.1148/radiol.2021202289. Epub 2021 Jan 19.

Abstract

Background Transarterial chemoembolization (TACE) is the standard treatment for intermediate-stage hepatocellular carcinoma (HCC). It is unknown whether conventional TACE (cTACE) should be continued or abandoned after initial nonresponse for intermediate-stage HCC. The optimal number of sessions before abandoning cTACE remains debated. Purpose To define the number of sessions that patients who do not respond to treatment (hereafter, nonresponders, with stable disease [SD] or progressive disease [PD]) should undergo before abandoning cTACE. Materials and Methods Patients with intermediate-stage HCC and Child-Pugh A liver function who underwent consecutive cTACE sessions between January 2005 and December 2012 were retrospectively included from three centers. Radiologic response rate to each session and its correlation with overall survival were evaluated. Response was assessed by modified Response Evaluation Criteria in Solid Tumors. A nomogram constructed by using tumor size, tumor capsule, and α-fetoprotein to predict patients who responded to treatment (hereafter, responders) was validated with sensitivity and specificity. Results This study evaluated 4154 patients (mean age, 58 years ± 6 [standard deviation]; 3777 men; primary cohort, 3442 patients [mean age, 58 years ± 6; 3129 men]; validation cohort, 712 patients [mean age, 58 years ± 7; 648 men]). Response rate to first cTACE was 35.6% (1227 of 3442, primary cohort) and 36.7% (261 of 712, validation cohort). For patients with SD who were nonresponders to first cTACE, the response rates after second cTACE were 46.1% (719 of 1560) and 48.4% (147 of 304); for patients with SD who were nonresponders to the second cTACE session, the response rates after the third cTACE session were 58.3% (591 of 1014) and 48.5% (98 of 202). For patients with SD who were nonresponders to third, fourth, and fifth cTACE sessions, response rates after fourth, fifth, and sixth cTACE sessions were less than 10%. All response rates in patients with PD who were nonresponders to the next cTACE were less than 5%. Responders to first, second, and third cTACE had higher 5-year overall survival than nonresponders (all < .001) but responders to the fourth cTACE did not ( = .21). The sensitivity and specificity of a nomogram predicted responders to third cTACE: 75.0% and 79.4% (internal validation) and 78.6% and 87.0% (external validation), respectively. Conclusion Three sessions were recommended before abandoning conventional transarterial embolization (cTACE) for intermediate-stage hepatocellular carcinoma. The nomogram developed in this study identified responders to third cTACE. © RSNA, 2021 See also the editorial by Georgiades in this issue.

摘要

背景 经动脉化疗栓塞术(TACE)是治疗中期肝细胞癌(HCC)的标准治疗方法。对于初始治疗无反应的中期 HCC,是继续还是放弃常规 TACE(cTACE)尚不清楚。放弃 cTACE 前的最佳治疗次数仍存在争议。目的 确定初始治疗无反应(即疾病稳定[SD]或疾病进展[PD]的无应答者)的患者在放弃 cTACE 前应接受多少次治疗。材料与方法 本研究回顾性纳入了 2005 年 1 月至 2012 年 12 月期间在三个中心连续接受 cTACE 治疗的中期 HCC 且 Child-Pugh A 级肝功能患者。评估了每次治疗的放射学反应率及其与总生存的相关性。使用实体瘤反应评估标准改良版评估反应。使用肿瘤大小、肿瘤包膜和甲胎蛋白构建的预测治疗应答者(即应答者)的列线图,通过敏感性和特异性进行了验证。结果 本研究共评估了 4154 例患者(平均年龄 58 岁±6[标准差];3777 例男性;主要队列 3442 例[平均年龄 58 岁±6;3129 例男性];验证队列 712 例[平均年龄 58 岁±7;648 例男性])。首次 cTACE 的反应率为 35.6%(3442 例中的 1227 例,主要队列)和 36.7%(712 例中的 261 例,验证队列)。对于首次 cTACE 无应答且为 SD 的患者,第二次 cTACE 后的反应率分别为 46.1%(1560 例中的 719 例)和 48.4%(304 例中的 147 例);对于第二次 cTACE 无应答且为 SD 的患者,第三次 cTACE 后的反应率分别为 58.3%(1014 例中的 591 例)和 48.5%(202 例中的 98 例)。对于 SD 且对第三、四和五次 cTACE 均无应答的患者,第四次、第五次和第六次 cTACE 后的反应率均低于 10%。所有对下一次 cTACE 无应答且 PD 的患者的反应率均低于 5%。首次、第二次和第三次 cTACE 有应答者的 5 年总生存率均高于无应答者(均<.001),但第四次 cTACE 有应答者的生存率则无差异( =.21)。预测第三次 cTACE 有应答者的列线图的敏感性和特异性分别为 75.0%和 79.4%(内部验证)和 78.6%和 87.0%(外部验证)。结论 对于中期肝细胞癌,建议在放弃常规经动脉栓塞术(cTACE)之前进行三次治疗。本研究构建的列线图可以识别出第三次 cTACE 的应答者。©RSNA,2021 另见本期 Georgiades 编辑的述评。

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