Abstract

To recognize the epidermal growth factor receptor (EGFR) gene mutation status in lung adenocarcinoma (LADC) has become a prerequisite of deciding whether EGFR-tyrosine kinase inhibitor (EGFR-TKI) medicine can be used. Polymerase chain reaction assay or gene sequencing is for measuring EGFR status, however, the tissue samples by surgery or biopsy are required. We propose to develop deep learning models to recognize EGFR status by using radiomics features extracted from non-invasive CT images. Preoperative CT images, EGFR mutation status and clinical data have been collected in a cohort of 709 patients (the primary cohort) and an independent cohort of 205 patients. After 1,037 CT-based radiomics features are extracted from each lesion region, 784 discriminative features are selected for analysis and construct a feature mapping. One Squeeze-and-Excitation (SE) Convolutional Neural Network (SE-CNN) has been designed and trained to recognize EGFR status from the radiomics feature mapping. SE-CNN model is trained and validated by using 638 patients from the primary cohort, tested by using the rest 71 patients (the internal test cohort), and further tested by using the independent 205 patients (the external test cohort). Furthermore, SE-CNN model is compared with machine learning (ML) models using radiomics features, clinical features, and both features. EGFR(-) patients show the smaller age, higher odds of female, larger lesion volumes, and lower odds of subtype of acinar predominant adenocarcinoma (APA), compared with EGFR(+). The most discriminative features are for texture (614, 78.3%) and the features of first order of intensity (158, 20.1%) and the shape features (12, 1.5%) follow. SE-CNN model can recognize EGFR mutation status with an AUC of 0.910 and 0.841 for the internal and external test cohorts, respectively. It outperforms the CNN model without SE, the fine-tuned VGG16 and VGG19, three ML models, and the state-of-art models. Utilizing radiomics feature mapping extracted from non-invasive CT images, SE-CNN can precisely recognize EGFR mutation status of LADC patients. The proposed method combining radiomics features and deep leaning is superior to ML methods and can be expanded to other medical applications. The proposed SE-CNN model may help make decision on usage of EGFR-TKI medicine.

Highlights

  • Lung adenocarcinoma (LADC) is a type of common lung cancer [1]

  • LADC patients are divided into 8 different subtypes: acinar predominant adenocarcinoma (APA), micropapillary predominant adenocarcinoma (MPA), lepidic predominant adenocarcinoma (LPA), papillary predominant adenocarcinoma (PPA), solid predominant adenocarcinoma (SPA), invasive mucinous adenocarcinoma (IMA), minimally invasive adenocarcinoma (MIA), and adenocarcinoma in situ (AIS)

  • We find that compared with three machine learning models, SE-Convolutional Neural Network (CNN) model has an improvement in the ability of predicting EGFR(+)

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Summary

Introduction

Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) has become one significant target chemotherapy medicine for the treatment of the advanced LADC [2]. To know the mutation status of EGFR gene in LADC patients is a prerequisite of deciding whether EGFR-TKI can be used [3]. Polymerase chain reaction (PCR) assay or gene sequencing is the clinical method of measuring EGFR status, the tissue samples obtained by surgery or biopsy are required. The extensive intratumor heterogeneity may reduce the accuracy of EGFR gene measurement using the biopsy [4, 5]. Some patients may have inoperable LADC or the biopsy is not possible for the reason of patients’ endurance or willing or high economic cost. It is necessary to find a non-invasive method to predict EGFR mutation status

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