Habitat-Based Radiomics for Predicting EGFR Mutations in Exon 19 and 21 From Brain Metastasis.

RATIONALE AND OBJECTIVES: To explore and externally validate habitat-based radiomics for preoperative prediction of epidermal growth factor receptor (EGFR) mutations in exon 19 and 21 from MRI imaging of non-small cell lung cancer (NSCLC)-originated brain metastasis (BM). METHODS: A total of 170, 62 and 61 patients from center 1, center 2 and center 3, respectively were included. All patients underwent contrast-enhanced T1-weighted (T1CE) and T2-weighted (T2W) MRI scans. Radiomics features were extracted from the tumor active (TA) and peritumoral edema (PE) regions in each MRI slice. The most important features were selected by the least absolute shrinkage and selection operator regression to develop radiomics signatures based on TA (RS-TA), PE (RS-PE) and their combination (RS-Com). Receiver operating characteristic (ROC) curve analysis was performed to access performance of radiomics models for both internal and external validation cohorts. RESULTS: 10, four and six most predictive features were identified to be strongly associated with the EGFR mutation status, exon 19 and exon 21, respectively. The RSs derived from the PE region outperformed those from the TA region for predicting the EGFR mutation, exon 19 and exon 21. The RS-Coms generated the highest performance in the primary training (AUCs, RS-EGFR-Com vs. RS-exon 19-Com vs. RS-exon 21-Com, 0.955 vs. 0.946 vs. 0.928), internal validation (AUCs, RS-EGFR-Com vs. RS-exon 19-Com vs. RS-exon 21-Com, 0.879 vs. 0.819 vs. 0.882), external validation 1 (AUCs, RS-EGFR-Com vs. RS-exon 19-Com vs. RS-exon 21-Com, 0.830 vs. 0.825 vs. 0.822), and external validation 2 (AUCs, RS-EGFR-Com vs. RS-exon 19-Com vs. RS-exon 21-Com, 0.812 vs. 0.818 vs. 0.800) cohort. CONCLUSION: The developed habitat-based radiomics model can be used to accurately predict the EGFR mutation subtypes, which may potentially guide personalized treatments for NSCLC patients with BM.

Brain-Tumor Interface-Based MRI Radiomics Models to Determine EGFR Mutation, Response to EGFR-TKI and T790M Resistance Mutation in Non-Small Cell Lung Carcinoma Brain Metastasis.

BACKGROUND: Preoperative assessment of epidermal growth factor receptor (EGFR) status, response to EGFR-tyrosine kinase inhibitors (TKI) and development of T790M mutation in non-small cell lung carcinoma (NSCLC) patients with brain metastases (BM) is important for clinical decision-making, while previous studies were only based on the whole BM. PURPOSE: To investigate values of brain-to-tumor interface (BTI) for determining the EGFR mutation, response to EGFR-TKI and T790M mutation. STUDY TYPE: Retrospective. POPULATION: Two hundred thirty patients from Hospital 1 (primary cohort) and 80 patients from Hospital 2 (external validation cohort) with BM and histological diagnosis of primary NSCLC, and with known EGFR status (biopsy) and T790M mutation status (gene sequencing). FIELD STRENGTH/SEQUENCE: Contrast-enhanced T1-weighted (T1CE) and T2-weighted (T2W) fast spin echo sequences at 3.0T MRI. ASSESSMENT: Treatment response to EGFR-TKI therapy was determined by the Response Evaluation Criteria in Solid Tumors. Radiomics features were extracted from the 4 mm thickness BTI and selected by least shrinkage and selection operator regression. The selected BTI features and volume of peritumoral edema (VPE) were combined to construct models using logistic regression. STATISTICAL TESTS: The performance of each radiomics model was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC). RESULTS: A total of 7, 3, and 3 features were strongly associated with the EGFR mutation status, response to EGFR-TKI and T790M mutation status, respectively. The developed models combining BTI features and VPE can improve the performance than those based on BTI features alone, generating AUCs of 0.814, 0.730, and 0.774 for determining the EGFR mutation, response to EGFR-TKI and T790M mutation, respectively, in the external validation cohort. DATA CONCLUSION: BTI features and VPE were associated with the EGFR mutation status, response to EGFR-TKI and T790M mutation status in NSCLC patients with BM. EVIDENCE LEVEL: 3 Technical Efficacy: Stage 2.

Radiomics for prediction of response to EGFR-TKI based on metastasis/brain parenchyma (M/BP)-interface.

PURPOSE: To evaluate the potential of subregional radiomics as a novel tumor marker in predicting epidermal growth factor receptor (EGFR) mutation status and response to EGFR-tyrosine kinase inhibitor (TKI) therapy in NSCLC patients with brain metastasis (BM). MATERIALS AND METHODS: We included 230 patients from center 1, and 80 patients were included from center 2 to form a primary and external validation cohort, respectively. Patients underwent contrast-enhanced T1-weighted and T2-weighted MRI scans before treatment. The individual- and population-level clustering was used to partition the peritumoral edema area (POA) into phenotypically consistent subregions. Radiomics features were calculated and selected from the tumor active area (TAA), POA and subregions, and used to develop models. Prediction values of each region were investigated and compared with receiver operating characteristic curves and Delong test. RESULTS: For predicting EGFR mutations, a multi-region combined model (EGFR-Fusion) was developed based on joint of the partitioned metastasis/brain parenchyma (M/BP)-interface and TAA, and generated the highest prediction performance in the training (AUC = 0.945, SEN = 0.878, SPE = 0.937), internal validation (AUC = 0.880, SEN = 0.733, SPE = 0.969), and external validation (AUC = 0.895, SEN = 0.875, SPE = 0.800) cohorts. For predicting response to EGFR-TKI, the developed multi-region combined model (TKI-Fusion) yielded predictive AUCs of 0.869 (SEN = 0.717, SPE = 0.884), 0.786 (SEN = 0.708, SPE = 0.818), and 0.802 (SEN = 0.750, SPE = 0.800) in the training, internal validation and external validation cohort, respectively. CONCLUSION: Our study revealed that complementary information regarding the EGFR status and response to EGFR-TKI can be provided by subregional radiomics. The proposed radiomics models may be new markers to guide treatment plans for NSCLC patients with BM.

Dual-modal imaging and photodynamic therapy using upconversion nanoparticles for tumor cells.

Here we synthesized silica-coated NaYF4:Yb,Tm@NaGdF4 nanoparticles with hypocrellin photosensitizers covalently incorporated inside the silica shells, combining dual modal imaging and photodynamic therapy (PDT) functions together. Under excitation at 980 nm, the tumor-targeting specificity of the as-prepared nanomaterials efficiently enhanced as folic acid (FA) was conjugated. The internalization of UCNPs@SiO2@hypocrellin A-FA in HeLa cells and HEK-293 cells was observed by confocal microscopy and in vitro magnetic resonance imaging (MRI), which demonstrated that the as-prepared nanocomposites have the ability to target folate receptor (FR) (+) cells. Moreover, magnetic resonance (MR) measurements also demonstrated that the as-prepared nanocomposites could be used as a contrast agent for MRI. All these results showed the feasibility and potential of the as-prepared nanocomposites for simultaneous imaging and PDT application.