Potential biomarkers of primary resistance to first- and second-generation EGFR-TKIs in non-small-cell lung cancer: a real-world study

Therapeutic Advances in Medical Oncology, Journal Year: 2025, Volume and Issue: 17

Published: April 1, 2025

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) significantly improve the prognosis of EGFR-sensitive mutant non-small-cell lung cancer (NSCLC). However, mechanisms underlying primary resistance to EGFR-TKIs remain unclear. This study aimed explore biomarkers associated with first- and second-generation EGFR-TKIs. Primary was defined as disease progression within 90 days (3 months) treatment in patients adenocarcinoma without any evidence objective response. Retrospective, single-center study. retrospectively screened NSCLC who received at Hunan Cancer Hospital from January 2018 December 2022. According pre-determined clinical outcomes, we divided into sensitivity groups. Only sufficient samples that passed quality control were included this Tumor tissue paired peripheral blood collected before subjected next-generation sequencing using an 825-gene panel. In addition, tumor analyzed for programmed cell death ligand 1 (PD-L1) expression. A total 70 enrolled study, 35 each resistant sensitive Patients exon 4 mutations TP53 gene had shorter progression-free survival (PFS) overall (OS) compared those mutation. PTPRD TACC3 mutation frequencies substantially higher group PFS OS. Furthermore, exhibited levels PD-L1 The potential are highly heterogeneous. Combining some somatic variants affecting function high expression may contribute resistance.

Language: Английский

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Imaging bridges pathology and radiology

Journal of Pathology Informatics, Journal Year: 2023, Volume and Issue: 14, P. 100298 - 100298

Published: Jan. 1, 2023

In recent years, medical disciplines have moved closer together and rigid borders been increasingly dissolved. The synergetic advantage of combining multiple is particularly important for radiology, nuclear medicine, pathology to perform integrative diagnostics. this review, we discuss how subdisciplines can be reintegrated in the future using state-of-the-art methods digitization, data science, machine learning. Integration made possible by digitalization radiological images, as well pathological images. 3D histology become a valuable tool, not only integration into images but also visualization cellular interactions, so-called connectomes. human pathology, it has recently image calculate movements contacts immunostained cells fresh tissue explants. Recording movement living cell proving informative makes study dynamic connectomes diagnosis lymphoid tissue. By applying computational including science learning, new perspectives analyzing understanding diseases possible.

Language: Английский

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Afatinib and Dacomitinib Efficacy, Safety, Progression Patterns, and Resistance Mechanisms in Patients with Non-Small Cell Lung Cancer Carrying Uncommon EGFR Mutations: A Comparative Cohort Study in China (AFANDA Study)

Cancers, Journal Year: 2022, Volume and Issue: 14(21), P. 5307 - 5307

Published: Oct. 28, 2022

(1) Background: Afatinib has been approved for patients with non-small cell lung cancer (NSCLC) carrying major uncommon epidermal growth factor receptor gene (EGFR) mutations. Dacomitinib, another second-generation tyrosine kinase inhibitor, also shown promising potential EGFR However, no comparative study conducted. (2) Methods: Two cohorts were employed: the AFANDA cohort, an ambispective cohort including 121 mutations admitted to two tertiary hospitals in China, and external validation afatinib (ex-AC), extracted from Uncommon Mutations Database (N = 1140). The was divided into (AC) a dacomitinib (DC) internal exploration. Objective response rate (ORR), progression-free survival (PFS), adverse events (AEs) assessed comparison. Progression patterns resistance mechanisms explored. (3) Results: In total, 286 advanced NSCLC treated or enrolled, 79 (44 DC, 35 AC) 207 ex-AC. exploration, ORR of DC significantly higher than that AC (60.5 vs. 26.7%, p 0.008), but there significant difference median PFS between (12.0 months 10.0 months, 0.305). Multivariate analysis confirmed independent favorable effect on (hazard ratio (HR), 1.909; 0.047). validation, multivariate prognostic role (HR, 1.953; 0.029). Propensity score matching superiority over terms both univariate analyses. Toxicity profiling suggested more G1 (p 0.006), fewer G3 0.036) AEs AC. revealed incidence intracranial progression (50 21.1%, 0.002). Drug indicated occurrence T790M (11.8 15.4%, 0.772). (4) Conclusions: Compared afatinib, demonstrated activity manageable toxicity different

Language: Английский

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Patterns of progression on first line osimertinib in patients with EGFR mutation-positive advanced non-small cell lung cancer (NSCLC): A Swiss cohort study

Lung Cancer, Journal Year: 2023, Volume and Issue: 187, P. 107427 - 107427

Published: Nov. 22, 2023

Language: Английский

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Uncommon de novo EGFRT790M-Mutant NSCLC characterized with unique genetic Features: Clinical response and acquired resistance to the third-generation EGFR-TKIs treatment

Lung Cancer, Journal Year: 2024, Volume and Issue: 190, P. 107528 - 107528

Published: March 2, 2024

Language: Английский

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