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本文引用的文献

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Pretreatment Heterogeneous Enhancement Pattern of Hepatocellular Carcinoma May Be a Useful New Predictor of Early Response to Lenvatinib and Overall Prognosis.肝细胞癌的治疗前异质性增强模式可能是乐伐替尼早期反应和总体预后的一种有用的新预测指标。
Liver Cancer. 2020 Jun;9(3):275-292. doi: 10.1159/000505190. Epub 2020 Feb 4.
2
A Changing Paradigm for the Treatment of Intermediate-Stage Hepatocellular Carcinoma: Asia-Pacific Primary Liver Cancer Expert Consensus Statements.中期肝细胞癌治疗模式的转变:亚太地区原发性肝癌专家共识声明
Liver Cancer. 2020 Jun;9(3):245-260. doi: 10.1159/000507370. Epub 2020 May 13.
3
F-Fluorodeoxyglucose Uptake in Hepatocellular Carcinoma as a Useful Predictor of an Extremely Rapid Response to Lenvatinib.氟代脱氧葡萄糖摄取在肝细胞癌中作为对乐伐替尼超快速反应的有用预测指标
Liver Cancer. 2020 Jan;9(1):84-92. doi: 10.1159/000503577. Epub 2019 Nov 13.
4
Randomised, multicentre prospective trial of transarterial chemoembolisation (TACE) plus sorafenib as compared with TACE alone in patients with hepatocellular carcinoma: TACTICS trial.随机、多中心前瞻性试验:比较经动脉化疗栓塞(TACE)联合索拉非尼与单纯 TACE 治疗肝细胞癌患者的疗效:TACTICS 试验。
Gut. 2020 Aug;69(8):1492-1501. doi: 10.1136/gutjnl-2019-318934. Epub 2019 Dec 4.
5
A New Treatment Option for Intermediate-Stage Hepatocellular Carcinoma with High Tumor Burden: Initial Lenvatinib Therapy with Subsequent Selective TACE.一种针对高肿瘤负荷中期肝细胞癌的新治疗选择:初始仑伐替尼治疗后序贯选择性经动脉化疗栓塞术
Liver Cancer. 2019 Oct;8(5):299-311. doi: 10.1159/000502905. Epub 2019 Sep 18.
6
Lenvatinib as an Initial Treatment in Patients with Intermediate-Stage Hepatocellular Carcinoma Beyond Up-To-Seven Criteria and Child-Pugh A Liver Function: A Proof-Of-Concept Study.乐伐替尼用于超出七项标准且肝功能为Child-Pugh A级的中期肝细胞癌患者的初始治疗:一项概念验证研究。
Cancers (Basel). 2019 Jul 31;11(8):1084. doi: 10.3390/cancers11081084.
7
Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial.瑞戈非尼治疗后索拉非尼治疗失败的晚期肝细胞癌患者的 Ramucirumab(REACH-2):一项随机、双盲、安慰剂对照、3 期临床试验。
Lancet Oncol. 2019 Feb;20(2):282-296. doi: 10.1016/S1470-2045(18)30937-9. Epub 2019 Jan 18.
8
Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial.乐伐替尼与索拉非尼用于不可切除肝细胞癌患者一线治疗的比较:一项随机、III 期非劣效性试验。
Lancet. 2018 Mar 24;391(10126):1163-1173. doi: 10.1016/S0140-6736(18)30207-1.
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Hepatocellular carcinoma.肝细胞癌。
Lancet. 2018 Mar 31;391(10127):1301-1314. doi: 10.1016/S0140-6736(18)30010-2. Epub 2018 Jan 5.
10
Hepatic Function during Repeated TACE Procedures and Prognosis after Introducing Sorafenib in Patients with Unresectable Hepatocellular Carcinoma: Multicenter Analysis.不可切除肝细胞癌患者重复经动脉化疗栓塞术期间的肝功能及引入索拉非尼后的预后:多中心分析
Dig Dis. 2017;35(6):602-610. doi: 10.1159/000480256. Epub 2017 Oct 17.

乐伐替尼-经动脉化疗栓塞序贯疗法作为晚期肝细胞癌乐伐替尼治疗进展期的有效治疗方法

Lenvatinib-Transarterial Chemoembolization Sequential Therapy as an Effective Treatment at Progression during Lenvatinib Therapy for Advanced Hepatocellular Carcinoma.

作者信息

Kawamura Yusuke, Kobayashi Masahiro, Shindoh Junichi, Kobayashi Yuta, Okubo Satoshi, Tominaga Licht, Kajiwara Akira, Kasuya Kayoko, Iritani Soichi, Fujiyama Shunichiro, Hosaka Tetsuya, Saitoh Satoshi, Sezaki Hitomi, Akuta Norio, Suzuki Fumitaka, Suzuki Yoshiyuki, Ikeda Kenji, Arase Yasuji, Hashimoto Masaji, Kozuka Tokuyo, Kumada Hiromitsu

机构信息

Department of Hepatology, Toranomon Hospital, Tokyo, Japan.

Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan.

出版信息

Liver Cancer. 2020 Dec;9(6):756-770. doi: 10.1159/000510299. Epub 2020 Oct 30.

DOI:10.1159/000510299
PMID:33442544
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7768146/
Abstract

BACKGROUND

The aims of this study were to evaluate the efficacy of additional treatment, especially lenvatinib-transarterial chemoembolization (TACE) sequential therapy, for unresectable hepatocellular carcinoma (HCC).

METHODS

Consecutive 56 patients who underwent lenvatinib treatment were reviewed. Oncological aggressiveness of tumor was estimated using a dynamic CT enhancement pattern classification, and clinical impact of subsequent treatment was investigated through analysis of progression-free survival (PFS), post-progression survival (PPS), and multivariate analysis of potential confounders for survival after progression during lenvatinib therapy.

RESULTS

Heterogeneous enhancement patterns ( and ), which are reportedly associated with higher oncological aggressiveness of HCC, were associated with better objective response to lenvatinib compared to homogeneous enhancement pattern () (86 and 85% vs. 53% in modified Response Evaluation Criteria in Solid Tumors), resulting in similar PFS ( = 0.313). Because of significantly worse PPS, overall survival of tumor was poor compared to or tumors ( = 0.009). However, subgroup of patients who achieved subsequent treatment showed significantly better PPS, regardless of CT enhancement pattern. Multivariate analysis confirmed that use of lenvatinib-TACE sequential treatment after progression during lenvatinib therapy was associated with better PPS (hazard ratio [HR], 0.08; 95% CI, 0.01-0.71; = 0.023), while enhancement pattern was correlated with worse PPS (HR, 2.92; 95% CI, 1.06-8.05; = 0.039).

CONCLUSION

Oncological aggressiveness of HCC estimated by CT enhancement pattern was predictive of PPS after progression during lenvatinib. Successful subsequent treatment with lenvatinib-TACE sequential therapy may offer survival benefit regardless of CT enhancement pattern of HCC.

摘要

背景

本研究旨在评估额外治疗,尤其是乐伐替尼-经动脉化疗栓塞术(TACE)序贯疗法,对不可切除肝细胞癌(HCC)的疗效。

方法

回顾了连续56例接受乐伐替尼治疗的患者。使用动态CT增强模式分类评估肿瘤的肿瘤侵袭性,并通过分析无进展生存期(PFS)、进展后生存期(PPS)以及乐伐替尼治疗期间进展后生存的潜在混杂因素的多变量分析来研究后续治疗的临床影响。

结果

据报道,与HCC较高肿瘤侵袭性相关的不均匀增强模式(和),与均匀增强模式()相比,对乐伐替尼的客观反应更好(实体瘤改良反应评估标准中分别为86%和85%对53%),导致PFS相似(P = 0.313)。由于PPS明显更差,肿瘤的总生存期比或肿瘤差(P = 0.009)。然而,接受后续治疗的患者亚组显示出明显更好的PPS,无论CT增强模式如何。多变量分析证实,乐伐替尼治疗期间进展后使用乐伐替尼-TACE序贯治疗与更好的PPS相关(风险比[HR],0.08;95%置信区间,0.01 - 0.71;P = 0.023),而增强模式与更差的PPS相关(HR,2.92;95%置信区间,1.06 - 8.05;P = 0.039)。

结论

通过CT增强模式评估的HCC肿瘤侵袭性可预测乐伐替尼治疗期间进展后的PPS。无论HCC的CT增强模式如何,乐伐替尼-TACE序贯疗法成功的后续治疗可能带来生存益处。