Radiomics of metastatic brain tumor as a predictive image biomarker of progression-free survival in patients with non-small-cell lung cancer with brain metastasis receiving tyrosine kinase inhibitors

Abstract

Background and objective: Epidermal growth factor receptor (EGFR)–targeted tyrosine kinase inhibitors (TKIs) are the first-line therapy for EGFR-mutant non-small-cell lung cancer (NSCLC). Early prediction of treatment failure in patients with brain metastases treated with EGFR–TKIs may help in making decisions for systemic drug therapy or local brain tumor control. This study examined the predictive power of the radiomics of both brain metastasis tumors and primary lung tumors. We propose a deep learning based CoxCC model based on quantitative brain magnetic resonance imaging (MRI), a prognostic index and clinical data; the model can be used to predict progression-free survival (PFS) after EGFR–TKI therapy in advanced EGFR-mutant NSCLC. Methods: This retrospective single-center study included 271 patients receiving first-line EGFR–TKI targeted therapy in 2018–2019. Among them, 72 patients who had brain metastases before receiving first-line EGFR–TKI treatment. Three radiomic features were extracted from pretreatment brain MRI images. A CoxCC model for the progression risk stratification of EGFR–TKI treatment was proposed on the basis of MRI radiomics, clinical features, and a prognostic index. We performed time-dependent PFS predictions to evaluate the performance of the CoxCC model. Results: The CoxCC model based on a prognostic index, clinical features, and radiomic features of brain metastasis exhibited higher performance than clinical features combined with indexes previously proposed for determining the prognosis of brain metastasis, including recursive partitioning analysis, diagnostic-specific graded prognostic assessment, graded prognostic assessment for lung cancer using molecular markers (lung-molGPA), and modified lung-molGPA, with c-index values of 0.75, 0.67, 0.66, 0.65, and 0.65, respectively. The model achieved areas under the curve of 0.88, 0.73, 0.92, and 0.90 for predicting PFS at 3, 6, 9 and 12 months, respectively. PFS significantly differed between the high- and low-risk groups (p < 0.001). Conclusions: For patients with advanced-stage NSCLC with brain metastasis, MRI radiomics of brain metastases may predict PFS. The CoxCC model integrating brain metastasis radiomics, clinical features, and a prognostic index provided reliable multi-time-point PFS predictions for patients with advanced NSCLC and brain metastases receiving EGFR–TKI treatment.

Keywords

• Non-small-cell lung cancer with brain metastasis
• Epidermal growth factor receptor–tyrosine kinase inhibitors
• Treatment outcome prediction
• Radiomics
• Deep learning