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基于非侵入性MRI成像特征预测肝细胞癌瘤内三级淋巴样结构成熟度:一项多中心回顾性研究

Noninvasive MRI imaging feature-based prediction of intratumoral tertiary lymphoid structure maturity in hepatocellular carcinoma: a multicenter retrospective study.

作者信息

Li Yiman, Chen Ying, Wu Zongqian, Shi Yuting, Li Mengsi, Cai Ping, Zhang Huarong, Liu Chen, Chen Wei, Li Qingrui, Li Xiaoming

机构信息

7T Magnetic Resonance Translational Medicine Research Center, Department of Radiology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China.

Department of Ultrasound, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China.

出版信息

Eur Radiol. 2025 Aug 6. doi: 10.1007/s00330-025-11902-9.

Abstract

OBJECTIVE

To develop a noninvasive MRI-based model for assessing intratumoral tertiary lymphoid structures (iTLSs) maturity in hepatocellular carcinoma (HCC) to guide therapeutic strategies.

MATERIALS AND METHODS

Retrospective analysis of 388 HCC patients from two centers included 338 in the training cohort and 50 in the external validation cohort. Patients were pathologically stratified into iTLSs-0 (n = 113), iTLSs-1 (n = 173), and iTLSs-2/3 (n = 32). External validation cohort included 20, 15, and 15 cases in each corresponding group. MRI features were analyzed using logistic regression to identify predictors of iTLSs maturity. The outcome cohort (n = 64) was used to assess the model's ability to identify candidates for tyrosine kinase inhibitors combined with immune checkpoint inhibitors (TKI-ICI) treatment. Nomogram performance was evaluated via area under the curve (AUC) with 95% confidence intervals (CIs).

RESULTS

iTLSs-1 exhibited lower intratumoral hemorrhage (p < 0.0001) and higher tumor in vein (p = 0.001) versus iTLSs-0 (AUC = 0.713, 95% CI: 0.661-0.764). iTLSs-2/3 showed higher complete capsule (p < 0.001), lower satellite nodules (p = 0.049), and lower intratumoral artery (p < 0.001) compared to iTLSs-1 (AUC = 0.750, 95% CI: 0.701-0.799). External validation confirmed generalizability (AUC = 0.750 and 0.764). The integrated nomogram demonstrated good calibration and potential clinical utility. A nomogram-based threshold (probability > 0.5) was used to stratify iTLSs, and the stratification effectively predicted iTLSs-2/3 patients who benefited from postoperative TKI-ICI treatment compared to iTLSs-0 and iTLSs-1 (p = 0.013 and 0.010).

CONCLUSION

MRI features effectively stratify iTLSs maturity in HCC, offering a noninvasive tool to personalize treatment.

KEY POINTS

Question Can preoperative MRI-based models assess intratumoral tertiary lymphoid structures maturity in hepatocellular carcinoma to guide tyrosine kinase inhibitors combined with immune checkpoint inhibitors treatment planning? Findings MRI-based intratumoral tertiary lymphoid structures stratification enables identification of hepatocellular carcinoma patients who may benefit from tyrosine kinase inhibitors combined with immune checkpoint inhibitors therapy. Clinical relevance This MRI-based model provides a preoperative tool to evaluate intratumoral tertiary lymphoid structures maturity in hepatocellular carcinoma, potentially guiding patient selection for tyrosine kinase inhibitor combined with immune checkpoint inhibitor treatment and supporting individualized therapeutic decision-making to improve outcomes.

摘要

目的

建立一种基于磁共振成像(MRI)的非侵入性模型,用于评估肝细胞癌(HCC)瘤内三级淋巴结构(iTLSs)的成熟度,以指导治疗策略。

材料与方法

对来自两个中心的388例HCC患者进行回顾性分析,其中训练队列338例,外部验证队列50例。患者在病理上分为iTLSs-0(n = 113)、iTLSs-1(n = 173)和iTLSs-2/3(n = 32)。外部验证队列在每个相应组中分别包括20、15和15例。使用逻辑回归分析MRI特征,以确定iTLSs成熟度的预测因素。结果队列(n = 64)用于评估该模型识别酪氨酸激酶抑制剂联合免疫检查点抑制剂(TKI-ICI)治疗候选者的能力。通过曲线下面积(AUC)及95%置信区间(CIs)评估列线图性能。

结果

与iTLSs-0相比,iTLSs-1表现出更低的瘤内出血(p < 0.0001)和更高的静脉内肿瘤(p = 0.001)(AUC = 0.713,95% CI:0.661 - 0.764)。与iTLSs-1相比,iTLSs-2/3表现出更高的完整包膜(p < 0.001)、更低的卫星结节(p = 0.049)和更低的瘤内动脉(p < 0.001)(AUC = 0.750,95% CI:0.701 - 0.799)。外部验证证实了其可推广性(AUC = 0.750和0.764)。综合列线图显示出良好的校准和潜在的临床实用性。基于列线图的阈值(概率>0.5)用于对iTLSs进行分层,与iTLSs-0和iTLSs-1相比,该分层有效地预测了从术后TKI-ICI治疗中获益的iTLSs-2/3患者(p = 0.013和0.010)。

结论

MRI特征可有效对HCC中的iTLSs成熟度进行分层,提供了一种用于个性化治疗的非侵入性工具。

关键点

问题基于术前MRI的模型能否评估肝细胞癌瘤内三级淋巴结构的成熟度,以指导酪氨酸激酶抑制剂联合免疫检查点抑制剂的治疗计划?发现基于MRI的瘤内三级淋巴结构分层能够识别可能从酪氨酸激酶抑制剂联合免疫检查点抑制剂治疗中获益的肝细胞癌患者。临床意义该基于MRI的模型提供了一种术前工具,用于评估肝细胞癌瘤内三级淋巴结构的成熟度,可能指导酪氨酸激酶抑制剂联合免疫检查点抑制剂治疗的患者选择,并支持个体化治疗决策以改善预后。

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