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Simple Summary  Multiple genetic mutations are associated with the outcomes of patients with non-small cell lung cancer (NSCLC) after using tyrosine kinase inhibitor, but the cost for detecting multiple genetic mutations is high. Few studies have investigated whether multiple genetic mutations can be simultaneously detected based on image features in patients with NSCLC. We developed a machine learning-derived radiomics approach that can simultaneously discriminate the presence of  EGFR ,  KRAS ,  ERBB2 , and  TP53  mutations on CT images in patients with NSCLC. These findings suggest that machine learning-derived radiomics may become a noninvasive and low-cost method to screen for multiple genetic mutations in patients with NSCLC before using next-generation sequencing tests, which can help to improve individualized targeted therapies.    Abstract  Purpose: To develop a machine learning-derived radiomics approach to simultaneously discriminate epidermal growth factor receptor ( EGFR ), Kirsten rat sarcoma viral oncogene ( KRAS ), Erb-B2 receptor tyrosine kinase 2 ( ERBB2 ), and tumor protein 53 ( TP53 ) genetic mutations in patients with non-small cell lung cancer (NSCLC). Methods: This study included consecutive patients from April 2018 to June 2020 who had histologically confirmed NSCLC, and underwent pre-surgical contrast-enhanced CT and post-surgical next-generation sequencing (NGS) tests to determine the presence of  EGFR ,  KRAS ,  ERBB2 , and  TP53  mutations. A dedicated radiomics analysis package extracted 1672 radiomic features in three dimensions. Discriminative models were established using the least absolute shrinkage and selection operator to determine the presence of  EGFR ,  KRAS ,  ERBB2 , and  TP53  mutations, based on radiomic features and relevant clinical factors. Results: In 134 patients (63.6 ± 8.9 years), the 20 most relevant radiomic features (13 for  KRAS ) to mutations were selected to construct models. The areas under the curve (AUCs) of the combined model (radiomic features and relevant clinical factors) for discriminating  EGFR, KRAS, ERBB2,  and  TP53  mutations were 0.78 (95% CI: 0.70–0.86), 0.81 (0.69–0.93), 0.87 (0.78–0.95), and 0.84 (0.78–0.91), respectively. In particular, the specificity to exclude  EGFR  mutations was 0.96 (0.87–0.99). The sensitivity to determine  KRAS ,  ERBB2 , and  TP53  mutations ranged from 0.82 (0.69–90) to 0.92 (0.62–0.99). Conclusions: Machine learning-derived 3D radiomics can simultaneously discriminate the presence of  EGFR ,  KRAS ,  ERBB2 , and  TP53  mutations in patients with NSCLC. This noninvasive and low-cost approach may be helpful in screening patients before invasive sampling and NGS testing.

cancers

Simultaneous Identification of EGFR,KRAS,ERBB2, and TP53 Mutations in Patients with Non-Small Cell Lung Cancer by Machine Learning-Derived Three-Dimensional Radiomics