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一种用于评估胃癌微卫星不稳定性状态及其预后价值的非侵入性成像生物标志物的开发与外部验证:临床与定量CT成像特征的组合

Development and external validation of a non-invasive imaging biomarker to estimate the microsatellite instability status of gastric cancer and its prognostic value: The combination of clinical and quantitative CT-imaging features.

作者信息

Zhao Huiping, Gao Jianbo, Bai Biaosheng, Wang Rui, Yu Juan, Lu Hao, Cheng Ming, Liang Pan

机构信息

Department of CT, Shaanxi Provincial People's Hospital, No. 256, Youyi West Road, Xi'an 710068, Shaanxi Province, China.

Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China; Henan Key Laboratory of Image Diagnosis and Treatment for Digestive System Tumor & Henan International Joint Laboratory of Medical Imaging & Henan Engineering Laboratory of Tumor Imaging & Henan Key Laboratory of CT Imaging & Zhengzhou Key Laboratory of Medical Imaging Technology and Diagnosis, Zhengzhou 450052, Henan Province, China.

出版信息

Eur J Radiol. 2023 May;162:110719. doi: 10.1016/j.ejrad.2023.110719. Epub 2023 Jan 27.

Abstract

PURPOSE

Molecular testing for microsatellite instability (MSI) status plays a vital role in the clinical management of gastric cancer (GC). Nevertheless, challenges of routinely applied technology for MSI determination exist. This study aimed to develop and validate a non-invasive imaging biomarker for MSI assessment in GC and explore its prognostic value.

METHODS

We retrospectively recruited 396 GC patients with pretreatment CT images from a single center and a public database and divided them into an original cohort (n = 356) and an external validation cohort (n = 40). The SMOTE algorithm was used to generate a balanced training cohort (n = 192) and the independent radiomics model, clinical model, and radiomics-clinic combined model were constructed for determining MSI status. The models' discrimination, calibration, clinical usefulness, and prognosis significance were evaluated by AUC, calibration, decision curve analyses, and Kaplan-Meier curve analysis, respectively.

RESULTS

The radiomics-clinic combined model derived from clinical and quantitative CT-based "Radscore" exhibited the best discriminatory abilities of MSI status in all cohorts, with AUCs of 0.836 (95% CI, 0.780-0.893) in the training cohort, 0.834 (95% CI, 0.688-0.981) in the external validation cohort, and 0.750 (95% CI, 0.682-0.819) in the original cohort, respectively. Meanwhile, the combined model demonstrated goodness of fitness, higher clinical net benefits, and significant positive integrated discrimination improvement compared with any independent model. While it showed no significant overall survival- or progression-free survival-based risk stratification ability (p > 0.05).

CONCLUSIONS

The radiomics-clinic combined model could be a potential non-invasive biomarker for MSI status in GC, which help clinical decision-making, nevertheless, provided limited prognostic ability.

摘要

目的

微卫星不稳定性(MSI)状态的分子检测在胃癌(GC)的临床管理中起着至关重要的作用。然而,常规应用的MSI检测技术存在挑战。本研究旨在开发并验证一种用于GC中MSI评估的非侵入性成像生物标志物,并探索其预后价值。

方法

我们回顾性招募了来自单一中心和公共数据库的396例具有治疗前CT图像的GC患者,并将他们分为原始队列(n = 356)和外部验证队列(n = 40)。使用SMOTE算法生成一个平衡的训练队列(n = 192),并构建独立的放射组学模型、临床模型和放射组学 - 临床联合模型来确定MSI状态。分别通过AUC、校准、决策曲线分析和Kaplan - Meier曲线分析评估模型的鉴别能力、校准、临床实用性和预后意义。

结果

源自临床和基于定量CT的“Radscore”的放射组学 - 临床联合模型在所有队列中表现出对MSI状态的最佳鉴别能力,训练队列中的AUC为0.836(95%CI,0.780 - 0.893),外部验证队列中的AUC为0.834(95%CI,0.688 - 0.981),原始队列中的AUC为0.750(95%CI,0.682 - 0.819)。同时,与任何独立模型相比,联合模型显示出良好的拟合优度、更高的临床净效益和显著的阳性综合鉴别改善。然而,它在基于总生存期或无进展生存期的风险分层能力方面没有显著差异(p > 0.05)。

结论

放射组学 - 临床联合模型可能是GC中MSI状态的一种潜在非侵入性生物标志物,有助于临床决策,但其预后能力有限。

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