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新型放射组学特征作为局部晚期直肠癌的预后生物标志物

Novel radiomic signature as a prognostic biomarker for locally advanced rectal cancer.

作者信息

Meng Yankai, Zhang Yuchen, Dong Di, Li Chunming, Liang Xiao, Zhang Chongda, Wan Lijuan, Zhao Xinming, Xu Kai, Zhou Chunwu, Tian Jie, Zhang Hongmei

机构信息

Department of Radiology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China.

University of Electronic Science and Technology of China, Chengdu, Sichuan, P.R. China.

出版信息

J Magn Reson Imaging. 2018 Feb 13. doi: 10.1002/jmri.25968.

Abstract

BACKGROUND

Locally advanced rectal cancer (LARC) patient stratification by clinicoradiologic factors may yield variable results. Therefore, more efficient prognostic biomarkers are needed for improved risk stratification of LARC patients, personalized treatment, and prognostication.

PURPOSE/HYPOTHESIS: To compare the ability of a radiomic signature to predict disease-free survival (DFS) with that of a clinicoradiologic risk model in individual patients with LARC.

STUDY TYPE

Retrospective study.

POPULATION

In all, 108 consecutive patients (allocated to a training and validation set with a 1:1 ratio) with LARC treated with neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME).

FIELD STRENGTH/SEQUENCE: Axial 3D LAVA multienhanced MR sequence at 3T.

ASSESSMENT

ITK-SNAP software was used for manual segmentation of 3D pre-nCRT MR images. All manual tumor segmentations were performed by a gastrointestinal tract radiologist, and validated by a senior radiologist. The clinicoradiologic risk factors with potential prognostic outcomes were identified in univariate analysis based on the Cox regression model for the whole set. The results showed that ypT, ypN, EMVI, and MRF were potential clinicoradiologic risk factors. Interestingly, only ypN and MRF were identified as independent predictors in multivariate analysis based on the Cox regression model.

STATISTICAL TESTS

A radiomic signature based on 485 3D features was generated using the least absolute shrinkage and selection operator (LASSO) Cox regression model. The association of the radiomic signature with DFS was investigated by Kaplan-Meier survival curves. Survival curves were compared by the log-rank test. Three models were built and assessed for their predictive values, using the Harrell concordance index and integrated time-dependent area under the curve.

RESULTS

The novel radiomic signature stratified patients into low- and high-risk groups for DFS in the training set (hazard ratio [HR] = 6.83; P < 0.001), and was successfully validated in the validation set (HR = 2.92; P < 0.001). The model combining the radiomic signature and clinicoradiologic findings had the best performance (C index = 0.788, 95% confidence interval [CI] 0.72-0.86; integrated time-dependent area under the curve of 0.837 at 3 years).

DATA CONCLUSION

The novel radiomic signature could be used to predict DFS in patients with LARC. Furthermore, combining this radiomic signature with clinicoradiologic features significantly improved the ability to estimate DFS (P = 0.001, 0.005 in training set and in validation set, respectively), and may help guide individualized treatment in such patients.

LEVEL OF EVIDENCE

3 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2018.

摘要

背景

根据临床放射学因素对局部晚期直肠癌(LARC)患者进行分层可能会产生不同的结果。因此,需要更有效的预后生物标志物来改善LARC患者的风险分层、个性化治疗和预后评估。

目的/假设:比较放射组学特征与临床放射学风险模型对LARC个体患者无病生存期(DFS)的预测能力。

研究类型

回顾性研究。

研究对象

总共108例连续的LARC患者(按1:1比例分配到训练集和验证集),接受新辅助放化疗(nCRT)后行全直肠系膜切除术(TME)。

场强/序列:3T下的轴向3D LAVA多增强MR序列。

评估

使用ITK-SNAP软件对nCRT前的3D MR图像进行手动分割。所有手动肿瘤分割均由一位胃肠道放射科医生完成,并由一位资深放射科医生进行验证。基于Cox回归模型对整个数据集进行单变量分析,确定具有潜在预后结果的临床放射学危险因素。结果显示,ypT、ypN、EMVI和MRF是潜在的临床放射学危险因素。有趣的是,在基于Cox回归模型的多变量分析中,只有ypN和MRF被确定为独立预测因素。

统计检验

使用最小绝对收缩和选择算子(LASSO)Cox回归模型生成基于485个3D特征的放射组学特征。通过Kaplan-Meier生存曲线研究放射组学特征与DFS的关联。生存曲线通过对数秩检验进行比较。构建并评估三个模型的预测价值,使用Harrell一致性指数和曲线下综合时间依赖性面积。

结果

在训练集中,新的放射组学特征将患者分为DFS的低风险和高风险组(风险比[HR]=6.83;P<0.001),并在验证集中成功验证(HR=2.92;P<0.001)。结合放射组学特征和临床放射学结果的模型表现最佳(C指数=0.788,95%置信区间[CI]0.72-0.86;3年时曲线下综合时间依赖性面积为0.837)。

数据结论

新的放射组学特征可用于预测LARC患者的DFS。此外,将该放射组学特征与临床放射学特征相结合可显著提高估计DFS的能力(训练集和验证集中P分别为0.001、0.005),并可能有助于指导此类患者的个体化治疗。

证据水平

3 技术效能:5级 J.Magn.Reson.Imaging 2018。

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