Abstract

ObjectivesTo develop and validate a radiomic feature-based nomogram for preoperative discriminating the epidermal growth factor receptor (EGFR) activating mutation from wild-type EGFR in non-small cell lung cancer (NSCLC) patients.MaterialA group of 301 NSCLC patients were retrospectively reviewed. The EGFR mutation status was determined by ARMS PCR analysis. All patients underwent nonenhanced CT before surgery. Radiomic features were extracted (GE healthcare). The maximum relevance minimum redundancy (mRMR) and LASSO, were used to select features. We incorporated the independent clinical features into the radiomic feature model and formed a joint model (i.e., the radiomic feature-based nomogram). The performance of the joint model was compared with that of the other two models.ResultsIn total, 396 radiomic features were extracted. A radiomic signature model comprising 9 selected features was established for discriminating patients with EGFR-activating mutations from wild-type EGFR. The radiomic score (Radscore) in the two groups was significantly different between patients with wild-type EGFR and EGFR-activating mutations (training cohort: P<0.0001; validation cohort: P=0.0061). Five clinical features were retained and contributed as the clinical feature model. Compared to the radiomic feature model alone, the nomogram incorporating the clinical features and Radscore exhibited improved sensitivity and discrimination for predicting EGFR-activating mutations (sensitivity: training cohort: 0.84, validation cohort: 0.76; AUC: training cohort: 0.81, validation cohort: 0.75). Decision curve analysis demonstrated that the nomogram was clinically useful and surpassed traditional clinical and radiomic features.ConclusionsThe joint model showed favorable performance in the individualized, noninvasive prediction of EGFR-activating mutations in NSCLC patients.

Highlights

  • With the development of molecular biology in cancer therapy, the treatment of non-small cell lung cancer (NSCLC) patients has become increasingly based on the patient’s clinical characteristics and tumor morphology and on individual mutational profiles [1]

  • Our results reveal that the combination of the repeatable, reproducible and low-cost CTderived radiomic signature and the clinical parameters can be used for evaluating the epidermal growth factor receptor (EGFR)-activating mutation status

  • Univariate analysis revealed that sex, smoking status, tumor volume, spiculation, air bronchogram, necrosis, Carcinoembryonic antigen (CEA), Squamous cell carcinoma (SCC), CYFRA21-1 and Neuron specific enolase (NSE) were significantly associated with EGFRactivating mutations

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Summary

Introduction

With the development of molecular biology in cancer therapy, the treatment of NSCLC patients has become increasingly based on the patient’s clinical characteristics and tumor morphology and on individual mutational profiles [1]. For advanced NSCLC patients with EGFRactivating mutations, treatment with EGFR tyrosine kinase inhibitors (EGFR TKIs), such as gefitinib and afatinib, has become the standard of care [3, 4]. Accumulating evidence suggests that EGFR TKIs can significantly prolong progression-free survival (PFS) compared to standard chemotherapy in this genetically distinct subset of patients [5, 6]. Clinical studies have suggested that 10% to 20% of all NSCLC biopsies are inadequate for molecular analysis because of a lack of either sufficient tumor cells or amplifiable DNA [7].

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