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表观扩散系数磁共振成像显示与不可切除肝内胆管癌联合靶向免疫治疗的早期进展相关。

Apparent Diffusion Coefficient MRI Shows Association With Early Progression of Unresectable Intrahepatic Cholangiocarcinoma With Combined Targeted-Immunotherapy.

作者信息

Sheng Ruofan, Sun Wei, Huang Xiaoyong, Jin Kaipu, Gao Shanshan, Zeng Mengsu, Wu Dong, Shi Guoming

机构信息

Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.

Department of Radiology, Xiamen Branch, Zhongshan Hospital, Fudan University, Fujian, 361006, China.

出版信息

J Magn Reson Imaging. 2023 Jan;57(1):275-284. doi: 10.1002/jmri.28214. Epub 2022 Apr 30.

Abstract

BACKGROUND

Most intrahepatic cholangiocarcinomas (ICCs) are diagnosed at advanced stage with an extremely poor prognosis. For these patients, combining targeted therapies and immunotherapy may have a promising therapeutic effect, and current Response Evaluation Criteria in Solid Tumors (RECIST) criteria have limited applicability.

PURPOSE

To investigate the associations between pretreatment MRI features and the efficacy of combined targeted-immunotherapy by estimating the risk of early progression (EP) in unresectable ICC, with special emphasis on diffusion-weighted imaging.

STUDY TYPE

Retrospective.

SUBJECTS

A total of 43 unresectable ICC patients (24 with EP [disease progression ≤12 months after treatment] and 19 with nonearly progression [NEP, disease progression >12 months]), who received first-line systemic therapy with lenvatinib plus PD1 antibody combination.

FIELD STRENGTH/SEQUENCE: The 0-T scanner, including T1- and T2-weighted imaging, diffusion-weighted imaging, and dynamic gadopentetate dimeglumine-enhanced imaging.

ASSESSMENT

Clinical characteristics and MR imaging features including apparent diffusion coefficient (ADC), as well as survival analysis of EP were evaluated.

STATISTICAL TESTS

Features between EP and NEP groups were compared by univariate analyses and multivariate logistic regression analysis. Diagnostic performance was analyzed by receiver operating characteristic curve. Univariate and multivariate Cox regression models were applied for survival analysis of EP. The progression-free survival (PFS) rates were estimated using the Kaplan-Meier analysis and compared by the log-rank test. The significance threshold was set at P < 0.05.

RESULTS

Tumor number, tumor margin, arterial peritumoral enhancement, lymphatic metastasis, and apparent diffusion coefficient (ADC) value were significantly different between EP and NEP groups. At multivariate logistic regression analysis, ADC was the only independent variable associated with EP (odds ratio = 0.012), with an area under the curve of 0.774 (optimal cutoff value was 1.028 × 10  mm /sec). Multivariate Cox regression model proved that ADC value (hazard ratio = 0.140) and ill-defined margin (hazard ratio = 2.784) were independent risk factors. ICCs with low ADC values showed shorter PFS than those with high values (χ  = 9.368).

DATA CONCLUSION

Pretreatment MRI features were associated with EP for unresectable ICC treated with combined targeted-immunotherapy, and decreased ADC value was an independent variable.

EVIDENCE LEVEL

3 TECHNICAL EFFICACY: Stage 4.

摘要

背景

大多数肝内胆管癌(ICC)在晚期被诊断出来,预后极差。对于这些患者,联合靶向治疗和免疫治疗可能具有良好的治疗效果,而目前的实体瘤疗效评价标准(RECIST)适用性有限。

目的

通过评估不可切除ICC早期进展(EP)的风险,研究治疗前MRI特征与联合靶向免疫治疗疗效之间的关联,特别强调扩散加权成像。

研究类型

回顾性研究。

研究对象

共43例不可切除的ICC患者(24例发生EP[治疗后疾病进展≤12个月],19例未发生早期进展[NEP,疾病进展>12个月]),接受了一线乐伐替尼联合PD1抗体的全身治疗。

场强/序列:3.0-T扫描仪,包括T1加权成像、T2加权成像、扩散加权成像和动态钆喷酸葡胺增强成像。

评估

评估临床特征和MR成像特征,包括表观扩散系数(ADC),以及对EP的生存分析。

统计检验

通过单因素分析和多因素逻辑回归分析比较EP组和NEP组之间的特征。通过受试者工作特征曲线分析诊断性能。应用单因素和多因素Cox回归模型对EP进行生存分析。采用Kaplan-Meier分析估计无进展生存期(PFS)率,并通过对数秩检验进行比较。显著性阈值设定为P<0.05。

结果

EP组和NEP组之间的肿瘤数量、肿瘤边缘、动脉期瘤周强化、淋巴结转移和表观扩散系数(ADC)值存在显著差异。在多因素逻辑回归分析中,ADC是与EP相关的唯一独立变量(比值比=0.012),曲线下面积为0.774(最佳截断值为1.028×10⁻³mm²/sec)。多因素Cox回归模型证明,ADC值(风险比=0.140)和边界不清(风险比=2.784)是独立的危险因素。ADC值低的ICC患者的PFS比高值患者短(χ²=9.368)。

数据结论

治疗前MRI特征与接受联合靶向免疫治疗的不可切除ICC的EP相关,ADC值降低是一个独立变量。

证据水平

3级。技术疗效:4级。

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