基于个体化影像组学特征筛选胃肠道间质瘤患者 KIT-11 基因突变型：一项回顾性多中心研究。

Personalized radiomics signature to screen for KIT-11 mutation genotypes among patients with gastrointestinal stromal tumors: a retrospective multicenter study.

机构信息

Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

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

出版信息

J Transl Med. 2023 Oct 16;21(1):726. doi: 10.1186/s12967-023-04520-w.

DOI:10.1186/s12967-023-04520-w

PMID:37845765

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10577986/

Abstract

OBJECTIVES

Gastrointestinal stromal tumors (GISTs) carrying different KIT exon 11 (KIT-11) mutations exhibit varying prognoses and responses to Imatinib. Herein, we aimed to determine whether computed tomography (CT) radiomics can accurately stratify KIT-11 mutation genotypes to benefit Imatinib therapy and GISTs monitoring.

METHODS

Overall, 1143 GISTs from 3 independent centers were separated into a training cohort (TC) or validation cohort (VC). In addition, the KIT-11 mutation genotype was classified into 4 categories: no KIT-11 mutation (K11-NM), point mutations or duplications (K11-PM/D), KIT-11 557/558 deletions (K11-557/558D), and KIT-11 deletion without codons 557/558 involvement (K11-D). Subsequently, radiomic signatures (RS) were generated based on the arterial phase of contrast CT, which were then developed as KIT-11 mutation predictors using 1408 quantitative image features and LASSO regression analysis, with further evaluation of its predictive capability.

RESULTS

The TC AUCs for K11-NM, K11-PM/D, K11-557/558D, and K11-D ranged from 0.848 (95% CI 0.812-0.884), 0.759 (95% CI 0.722-0.797), 0.956 (95% CI 0.938-0.974), and 0.876 (95% CI 0.844-0.908), whereas the VC AUCs ranged from 0.723 (95% CI 0.660-0.786), 0.688 (95% CI 0.643-0.732), 0.870 (95% CI 0.824-0.918), and 0.830 (95% CI 0.780-0.878). Macro-weighted AUCs for the KIT-11 mutant genotype ranged from 0.838 (95% CI 0.820-0.855) in the TC to 0.758 (95% CI 0.758-0.784) in VC. TC had an overall accuracy of 0.694 (95%CI 0.660-0.729) for RS-based predictions of the KIT-11 mutant genotype, whereas VC had an accuracy of 0.637 (95%CI 0.595-0.679).

CONCLUSIONS

CT radiomics signature exhibited good predictive performance in estimating the KIT-11 mutation genotype, especially in prediction of K11-557/558D genotype. RS-based classification of K11-NM, K11-557/558D, and K11-D patients may be an indication for choice of Imatinib therapy.

摘要

目的

携带不同 KIT 外显子 11（KIT-11）突变的胃肠道间质瘤（GIST）具有不同的预后和对伊马替尼的反应。在此，我们旨在确定计算机断层扫描（CT）放射组学是否可以准确分层 KIT-11 突变基因型，以受益于伊马替尼治疗和 GIST 监测。

方法

总体而言，来自 3 个独立中心的 1143 个 GIST 被分为训练队列（TC）或验证队列（VC）。此外，KIT-11 突变基因型分为 4 类：无 KIT-11 突变（K11-NM）、点突变或重复（K11-PM/D）、KIT-11 557/558 缺失（K11-557/558D）和无 557/558 密码子参与的 KIT-11 缺失（K11-D）。随后，基于对比 CT 的动脉期生成放射组学特征（RS），并使用 1408 个定量图像特征和 LASSO 回归分析将其开发为 KIT-11 突变预测因子，进一步评估其预测能力。

结果

TC 中 K11-NM、K11-PM/D、K11-557/558D 和 K11-D 的 AUC 范围分别为 0.848（95%CI 0.812-0.884）、0.759（95%CI 0.722-0.797）、0.956（95%CI 0.938-0.974）和 0.876（95%CI 0.844-0.908），而 VC 的 AUC 范围分别为 0.723（95%CI 0.660-0.786）、0.688（95%CI 0.643-0.732）、0.870（95%CI 0.824-0.918）和 0.830（95%CI 0.780-0.878）。KIT-11 突变基因型的宏观加权 AUC 范围分别为 TC 中的 0.838（95%CI 0.820-0.855）和 VC 中的 0.758（95%CI 0.758-0.784）。TC 中基于 RS 的 KIT-11 突变基因型预测的总体准确率为 0.694（95%CI 0.660-0.729），而 VC 的准确率为 0.637（95%CI 0.595-0.679）。