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尼伏鲁单抗治疗肝细胞癌患者的放射学反应:真实世界实践的多中心分析。

Radiological response to nivolumab in patients with hepatocellular carcinoma: A multicenter analysis of real-life practice.

机构信息

Barcelona Clinic Liver Cancer (BCLC) Group, Radiology Department, Hospital Clínic of Barcelona IDIBAPS, CIBERehd, Barcelona, Spain.

Barcelona Clínic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clínic of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain.

出版信息

Eur J Radiol. 2021 Feb;135:109484. doi: 10.1016/j.ejrad.2020.109484. Epub 2020 Dec 17.


DOI:10.1016/j.ejrad.2020.109484
PMID:33383399
Abstract

BACKGROUND AND AIMS: Immune-checkpoint inhibitors are effective in many advanced tumors. However, there is scarce information regarding the radiological response to these agents in hepatocellular carcinoma outside clinical trials. We aimed to describe the radiological response in a retrospective cohort of hepatocellular carcinoma patients treated with nivolumab and to analyze the radiological evolution according to tumor response at first post-treatment radiological assessment. METHODS: We reviewed pre-treatment and post-treatment images (CT or MRI) obtained at different time-points in patients with hepatocellular carcinoma treated with nivolumab outside clinical trials at seven Spanish centers, assessing the response according to RECIST 1.1 and iRECIST and registering atypical responses. We also analyzed the imaging findings on subsequent assessments according to tumor status on the first posttreatment imaging assessment. RESULTS: From the 118 patients with hepatocellular carcinoma treated with nivolumab, we finally analyzed data from 31 patients (71 % Child-Pugh A; 74 % BCLC-C). Median follow-up was 8.39 months [IQR 5.00-10.92]; median overall survival was 12.82 months (95 %CI 10.92-34.79). According to RECIST 1.1, the objective response rate was 16 % and according to iRECIST, the objective response rate was 22.6 %. Findings at the first post-treatment assessment varied, showing stable disease in 44.8 % of patients; findings during follow-up also varied widely, including 4 hyperprogressions and 3 pseudoprogressions. CONCLUSION: Imaging findings during nivolumab treatment are heterogeneous between and within patients. Progression of disease does not always signify treatment failure, and surrogate end-points may not reflect survival outcomes, making the management of hepatocellular carcinoma patients under immunotherapy challenging.

摘要

背景和目的:免疫检查点抑制剂在许多晚期肿瘤中具有疗效。然而,在临床试验之外,关于这些药物在肝细胞癌中的放射学反应的信息很少。我们旨在描述在接受纳武单抗治疗的肝细胞癌患者的回顾性队列中的放射学反应,并根据首次治疗后放射学评估时的肿瘤反应来分析放射学演变。

方法:我们在 7 家西班牙中心的临床试验之外,对接受纳武单抗治疗的肝细胞癌患者的治疗前和治疗后(CT 或 MRI)图像进行了回顾性分析,根据 RECIST 1.1 和 iRECIST 评估了反应,并记录了非典型反应。我们还根据首次治疗后影像学评估时肿瘤状态分析了后续评估的影像学发现。

结果:从 118 名接受纳武单抗治疗的肝细胞癌患者中,我们最终分析了 31 名患者的数据(71%的患者 Child-Pugh A;74%的患者 BCLC-C)。中位随访时间为 8.39 个月(IQR 5.00-10.92);中位总生存期为 12.82 个月(95%CI 10.92-34.79)。根据 RECIST 1.1,客观缓解率为 16%,根据 iRECIST,客观缓解率为 22.6%。首次治疗后评估的结果各不相同,显示 44.8%的患者为疾病稳定;随访期间的结果也差异很大,包括 4 例超进展和 3 例假性进展。

结论:在纳武单抗治疗期间,患者之间和患者内部的影像学发现具有异质性。疾病进展并不总是意味着治疗失败,替代终点可能无法反映生存结果,这使得免疫治疗下的肝细胞癌患者的管理具有挑战性。

相似文献

[1]
Radiological response to nivolumab in patients with hepatocellular carcinoma: A multicenter analysis of real-life practice.

Eur J Radiol. 2021-2

[2]
CheckMate 040 cohort 5: A phase I/II study of nivolumab in patients with advanced hepatocellular carcinoma and Child-Pugh B cirrhosis.

J Hepatol. 2021-9

[3]
Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial.

Lancet. 2017-4-20

[4]
Comparative assessment of standard and immune response criteria for evaluation of response to PD-1 monotherapy in unresectable HCC.

Abdom Radiol (NY). 2022-3

[5]
Local Tumor Control and Patient Outcome Using Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma: iRECIST as a Potential Substitute for Traditional Criteria.

AJR Am J Roentgenol. 2019-10-15

[6]
Feasibility and safety of nivolumab in advanced hepatocellular carcinoma: real-life experience from three German centers.

J Cancer Res Clin Oncol. 2018-10-29

[7]
CT imaging findings in patients with advanced hepatocellular carcinoma treated with sorafenib: Alternative response criteria (Choi, European Association for the Study of the Liver, and modified Response Evaluation Criteria in Solid Tumor (mRECIST)) versus RECIST 1.1.

Eur J Radiol. 2016-1

[8]
Post-registration experience of nivolumab in advanced hepatocellular carcinoma: an international study.

J Immunother Cancer. 2020-8

[9]
Comparison of Radiological Tumor Response Based on iRECIST and RECIST 1.1 in Metastatic Clear-Cell Renal Cell Carcinoma Patients Treated with Programmed Cell Death-1 Inhibitor Therapy.

Korean J Radiol. 2021-3

[10]
Comparison of RECIST and iRECIST criteria in patients with advanced lung cancer treated with nivolumab.

J Cancer Res Ther. 2023

引用本文的文献

[1]
Multiomics in silico analysis identifies TM4SF4 as a cell surface target in hepatocellular carcinoma.

PLoS One. 2025-2-25

[2]
Quantifying morphologic variations as an alternate to standard response criteria for unresectable primary liver tumors after checkpoint inhibition therapy.

Radiol Med. 2025-2

[3]
Tumor response assessment in hepatocellular carcinoma treated with immunotherapy: imaging biomarkers for clinical decision-making.

Eur Radiol. 2025-1

[4]
Systemic therapies in hepatocellular carcinoma: A revolution?

United European Gastroenterol J. 2024-3

[5]
Early variation of inflammatory indexes refines prognostic prediction in patients with hepatocellular carcinoma under systemic treatment.

Mol Clin Oncol. 2023-2-21

[6]
Assessment and Monitoring of Response to Systemic Treatment in Advanced Hepatocellular Carcinoma: Current Insights.

J Hepatocell Carcinoma. 2022-9-14

[7]
Immunotherapy for advanced hepatocellular carcinoma: From clinical trials to real-world data and future advances.

World J Clin Oncol. 2022-6-24

[8]
Systemic Therapy for Hepatocellular Carcinoma: Current Updates and Outlook.

J Hepatocell Carcinoma. 2022-3-30

[9]
Impact of COVID-19 crisis on medical care of patients with metastasized uro-oncologic disease under systemic cancer therapy: a multicenter study in German university hospitals.

World J Urol. 2022-2

[10]
Immunotherapies for hepatocellular carcinoma.

Nat Rev Clin Oncol. 2022-3

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