BackgroundOsimertinib could effectively target epidermal growth factor receptor (EGFR) T790M resistance mutations in non‐small cell lung cancer (NSCLC), indicating that rebiopsy may be particularly important. However, the clinical benefit of repeat rebiopsy in T790M‐negative patients with NSCLC detected by the first rebiopsy is still unclear, and data on the efficacy and safety of osimertinib in patients with NSCLC who are T790M‐positive patients on a repeat rebiopsy remain rare.MethodsWe retrospectively collected the clinical data of advanced NSCLC patients with common EGFR mutation who were treated with 1/2‐generation (1/2G) EGFR–tyrosine kinase inhibitors (TKIs) in first‐line therapy in our center from January 2018 to December 2020. The detection rate of T790M by first and repeat rebiopsy was recorded, and we also analyzed the efficacy and safety of osimertinib for T790M‐positive patients.ResultsAmong 190 common EGFR‐mutant patients who received 1/2G EGFR–TKIs with advanced NSCLC in the first‐line treatment, 141 patients developed progressive disease. In total, 110 of 141 accepted the first rebiopsy, with a T790M prevalence of 50.9% (56/110). In total, 43 T790M‐positive patients who received osimertinib were included in first rebiopsy group. Of 54 T790M‐negative patients detected by the first rebiopsy, 28 underwent repeated rebiopsy in subsequent clinical treatment, and 10 (35.7%) T790M‐positive cases were confirmed. In total, eight T790M‐positive patients treated with osimertinib were included in repeat rebiopsy group. Overall, 66 (60%) of 110 patients acquired a T790M mutation. In patients with the T790M mutation discovered by the first and repeat rebiopsy, osimertinib resulted in median progression‐free survival of 7 (95% confidence interval [CI]: 5.3–8.7) and 6 (95% CI: 4.7–7.3) months, respectively (p = .656). The median overall survival since osimertinib initiation for T790M‐positive patients at first rebiopsy was 20 (95% CI: 15.1–24.9) months and 19 (95% CI: 16.9–21.1) months, for those at repeated rebiopsy (p = .888). Adverse events of grade 3 or higher were similar in the two groups (25.6% vs. 12.5%, p = .616). There was no treatment‐related death in the two groups.ConclusionsRepeat rebiopsy can increase the T790M mutation positivity rate. Osimertinib showed similar efficacy and safety in T790M‐positive patients whether detected by the first or repeat rebiopsy.
The treatment for squamous cell lung cancer (SqCLC) is limited, and the prognosis of SqCLC is poor. In this article, we aimed to analyze and identify immune-related cells and competition endogenous RNA (ceRNA) that influence the prognosis of SqCLC. SqCLC and lung adenocarcinoma data were downloaded from TCGA-GDC. A total of 22 types of immune cell fractions were estimated using CIBERSORT. R software was used to identify any significantly different transcriptome data, including mRNA, LncRNA, and miRNA. The univariate cox regression method was applied to screen for prognosis-related lncRNA, miRNA, mRNA and tumor-infiltrating immune cells. There were 504 patients included in this study. There was a higher proportion of memory activated CD4+ T cells and CD8+ T cells in younger women. Follicular helper T (Tfh) cells were predictive of a good prognosis and reflected immune activation in SqCLC. The SFTA1P/NKX2-1-AS1, hsa-mir-503, GREM2 ceRNA axes and NKX2-1-AS1, hsa-mir-96, PROK2 ceRNA axes were found to be important for the immune function, pathogenesis, and prognosis of SqCLC. Collectively, the immune-related ceRNA and tumor-infiltrating immune cells in SqCLC are likely important determinants of SqCLC pathogenesis, prognosis, and immune status.
Extrachromosomal circular DNA (eccDNA) is gaining substantial attention in basic and clinical research for its contribution to tumor heterogeneity, biogenesis, and evolution. However, its presence and molecular features in peripheral blood from cancer patients are poorly understood. Here, we demonstrated the existence of eccDNA molecules in cancer patients’ plasma using atomic-force microscopy and high throughput sequencing technology. We then developed a method named ScanTecc (Screening cancer Types with cell-free eccDNA) that integrates cell-free circular DNA sequencing and machine learning approaches for cancer patient screening and classification. We applied ScanTecc on a total of 413 patients with multiple types of human primary cancers and 52 healthy individuals and found a significantly greater number and more extended size of eccDNAs in patients’ peripheral blood. ScanTecc accurately distinguished cancer patients (including early stages I and II) from healthy individuals with an overall prediction rate of 0.85 and identified distinct cancer types with an overall prediction rate of 0.84. Our study provides evidence for a non-invasive approach potentially applicable for early detection of cancer patients in clinics.
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