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.

Preoperative MRI-Based Radiomics of Brain Metastasis to Assess T790M Resistance Mutation After EGFR-TKI Treatment in NSCLC.

BACKGROUND: Preoperative assessment of the acquired resistance T790M mutation in patients with metastatic non-small cell lung cancer (NSCLC) based on brain metastasis (BM) is important for early treatment decisions. PURPOSE: To investigate preoperative magnetic resonance imaging (MRI)-based radiomics for assessing T790M resistance mutation after epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) treatment in NSCLC patients with BM. STUDY TYPE: Retrospective. POPULATION: One hundred and ten primary NSCLC patients with pathologically confirmed BM and T790M mutation status assessment from two centers divided into primary training (N = 53), internal validation (N = 27), and external validation (N = 30) sets. FIELD STRENGTH/SEQUENCE: Contrast-enhanced T1-weighted (T1CE) and T2-weighted (T2W) fast spin echo sequences at 3.0 T. ASSESSMENT: Forty-five (40.9%) patients were T790M-positive and 65 (59.1%) patients were T790M-negative. The tumor active area (TAA) and peritumoral edema area (POA) of BM were delineated on pre-treatment T1CE and T2W images. Radiomics signatures were built based on features selected from TAA (RS-TAA), POA (RS-POA), and their combination (RS-Com) to assess the T790M resistance mutation after EGFR-TKI treatment. STATISTICAL TESTS: Receiver operating characteristic (ROC) curves were used to assess the capabilities of the developed RSs. The area under the ROC curves (AUC), sensitivity, and specificity were generated as comparison metrics. RESULTS: We identified two features (from TAA) and three features (from POA) that are highly associated with the T790M mutation status. The developed RS-TAA, RS-POA, and RS-Com showed good performance, with AUCs of 0.807, 0.807, and 0.864 in the internal validation, and 0.783, 0.814, and 0.860 in the external validation sets, respectively. DATA CONCLUSION: Pretreatment brain MRI of NSCLC patients with BM might effectively detect the T790M resistance mutation, with both TAA and POA having important values. The multi-region combined radiomics signature may have potential to be a new biomarker for assessing T790M mutation. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

PD-1 inhibitors plus oxaliplatin or cisplatin-based chemotherapy in first-line treatments for advanced gastric cancer: A network meta-analysis.

Background: Currently, there has been no direct comparison between programmed cell death protein 1 (PD-1) inhibitors plus different chemotherapy regimens in first-line treatments for advanced gastric cancer (AGC). This study performed a network meta-analysis (NMA) to evaluate the efficacy and safety of PD-1 inhibitors plus oxaliplatin- or cisplatin-based chemotherapy. Methods: PubMed, Embase, and the Cochrane Central Register were used to seek a series of phase III randomized controlled trials (RCTs) studying on first-line PD-1 inhibitors plus chemotherapy and phase III RCTs comparing first-line oxaliplatin and cisplatin-based chemotherapy for AGC to perform NMA. The main outcome was overall survival (OS) and other outcomes included progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (TRAEs). Results: Eight eligible RCTs involving 5723 patients were included. Compared with PD-1 inhibitors plus cisplatin-based chemotherapy, PD-1 inhibitors plus oxaliplatin-based chemotherapy could prolong the OS without statistical significance (hazard ratio [HR]: 0.82, 95% credible interval [CI]: 0.63-1.06). However, for patients with combined positive score (CPS) ≥ 1, PD-1 inhibitors plus oxaliplatin-based chemotherapy significantly prolonged the OS (HR: 0.75, 95% CI: 0.57-0.99). PFS in PD-1 inhibitors plus oxaliplatin-based chemotherapy was significantly longer than that in PD-1 inhibitors plus cisplatin-based chemotherapy (HR: 0.72, 95% CI: 0.53-0.99). Regarding safety, the incidence of ≥ 3 TRAEs was similar between PD-1 inhibitors plus oxaliplatin-based chemotherapy and PD-1 inhibitors plus cisplatin-based chemotherapy (RR: 0.86, 95% CI: 0.66-1.12). The surface under the cumulative ranking area curve (SUCRA) indicated that PD-1 inhibitors plus oxaliplatin-based chemotherapy ranked first for OS (97.7%), PFS (99.3%), and ORR (89.0%). For oxaliplatin-based regimens, there was no significant difference between nivolumab plus oxaliplatin-based chemotherapy and sintilimab plus oxaliplatin-based chemotherapy in terms of OS, PFS, ORR, and ≥3 TRAEs. Conclusion: Compared with PD-1 inhibitors plus cisplatin-based chemotherapy, PD-1 inhibitors plus oxaliplatin-based chemotherapy significantly prolonged PFS. Considering both efficacy and safety, PD-1 inhibitors plus oxaliplatin-based chemotherapy might be a better option in the first-line treatment for AGC.

Serum CA125 Level Is Associated with Diabetic Retinopathy in Chinese Patients with Type 2 Diabetes.

BACKGROUND: To investigate the association between serum carbohydrate antigen 125 (CA125) and the presence as well as severity of diabetes retinopathy (DR) in Chinese adult patients with type 2 diabetes. METHODS: A hospital-based cross-sectional study was conducted from February 2012 to November 2018. DR was assessed using Early Treatment Diabetic Retinopathy Study criteria. Vision-threatening DR (VTDR) was diagnosed if subjects had severe non-proliferative DR (NPDR), proliferative DR (PDR), or clinically significant macular edema (CSME). Multivariate logistic regression models were applied to explore the associations. RESULTS: Among the 2696 participants, the overall prevalence of DR was 25.1%, of which the prevalence of mild NPDR, moderate NPDR, and VTDR was 10.8%, 4.5%, and 9.9%, respectively. Serum CA125 level was significantly higher in participants with DR and increased with the severity of DR (P = 0.013). After accounting for age, gender, smoking, drinking, duration of diabetes, anti-diabetic agents use, systolic blood pressure, pulse pressure, weight, hemoglobin A1c and fasting plasma glucose levels, CA125 level was significantly associated with subjects in any-severity DR (odds ratio [OR] 1.006 [95% confidence interval CI: 1.002-1.010], P = 0.006) and VTDR (1.008 [1.003-1.013], P = 0.001). When CA125 was treated as categorized variables, the prevalence of VTDR might increase as improving CA125 quartiles (P value for trend = 0.017). CONCLUSION: In this study, serum CA125 level was associated with the presence and severity of DR in Chinese patients with type 2 diabetes. Further prospective studies should be warranted to validate the feasible role of CA125 as well as other biomarkers.

MicroRNA-1224 Inhibits Tumor Metastasis in Intestinal-Type Gastric Cancer by Directly Targeting FAK.

Intestinal-type gastric cancer (GC) of the Lauren classification system has specific epidemiological characteristics and carcinogenesis patterns. MicroRNAs (miRNAs) have prognostic significance, and some can be used as prognostic biomarkers in GC. In this study, we identified miR-1224 as a potential survival-related miRNA in intestinal-type GC patients by The Cancer Genome Atlas (TCGA) analysis. Using quantitative real-time PCR (qRT-PCR), we showed that the relative expression of miR-1224 was significantly decreased in intestinal-type GC tissues compared to matched adjacent normal mucosa tissues (p < 0.01). We found that high miR-1224 expression was associated with no lymph-node metastasis (p < 0.05) and good prognosis (p = 0.028) in 90 intestinal-type GC tissues. Transfection of intestinal-type GC cells with miR-1224 mimics showed that miR-1224 suppressed cell migration in vitro (wound healing assay and Transwell migration assay), whereas the transfection of cells with miR-1224 inhibitor promoted cell migration in vitro. miR-1224 also suppressed intestinal-type GC cell metastasis in a xenograft mouse model. Furthermore, bioinformatics, luciferase reporter, Western blotting, and immunohistochemistry (IHC) studies demonstrated that miR-1224 directly bound to the focal adhesion kinase (FAK) gene, and downregulated its expression, which decreased STAT3 and NF-κB signaling and subsequent the epithelial-to-mesenchymal transition (EMT). Repression of FAK is required for the miR-1224-mediated inhibition of cell migration in intestinal-type GC. The present study demonstrated that miR-1224 is downregulated in intestinal-type GC. miR-1224 inhibits the metastasis of intestinal-type GC by suppressing FAK-mediated activation of the STAT3 and NF-κB pathways, and subsequent EMT. miR-1224 could represent an important prognostic factor in intestinal-type GC.