Stratifying risk in oligoprogressive EGFR-mutated non-small cell lung cancer (NSCLC): The role of liquid biopsy.

Background: EGFR-TKIs have markedly enhanced outcomes for non-small cell lung cancer (NSCLC) patients, but resistance development is virtually inevitable. In the context of oligoprogressive disease (OPD), local treatments can target resistant clones while EGFR-TKIs maintain systemic control, potentially extending the duration of therapy. However, identifying patients who benefit from this combined approach remains unclear.

Alectinib in combination with bevacizumab as first-line treatment in ALK-rearranged non-small cell lung cancer (ALEK-B): a single-arm, phase 2 trial.

Up to 25% of patients with ALK-rearranged non-small cell lung cancer (NSCLC) experience disease progression within the first year of targeted therapy. This phase 2 trial investigates whether combining alectinib with bevacizumab can delay resistance mechanisms in advanced ALK-rearranged NSCLC. ALEK-B was an open-label, single-arm, single-center phase 2 trial (NCT03779191) evaluating alectinib (600 mg BID) and bevacizumab (15 mg/kg) in patients with advanced ALK-rearranged NSCLC confirmed by next-generation sequencing.

Liquid biopsy in clinical outcomes and detection of T790M mutation in metastatic non-small cell lung cancer after progression to EGFR-TKI.

BACKGROUNDLiquid biopsy (LB) is used to detect epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) and has been demonstrated to have prognostic and predictive value.OBJECTIVETo associate the rates of and T790M mutations detected by LB during disease progression after first- or second-generation EGFR-TKIs with clinical characteristics and survival outcomes.METHODSFrom January 2018 to December 2021, 295 patients with advanced EGFR mutant (EGFRm) NSCLC treated with first- or second-generation EGFR-TKIs were retrospectively analyzed.

Impact of Concurrent Genomic Alterations on Clinical Outcomes in Patients With ALK-Rearranged NSCLC.

Introduction: ALK tyrosine kinase inhibitors have exhibited promising activity against advanced ALK-rearranged NSCLC. However, co-occurring genetic alterations, such as CDKN2A/B or TP53, may negatively affect the efficacy of targeted therapies.

Methods: From December 2017 to December 2022, this study cohort analyzed next-generation sequencing data of 116 patients with metastatic ALK-rearranged NSCLC from five Latin American cancer centers.

A high number of co-occurring genomic alterations detected by NGS is associated with worse clinical outcomes in advanced EGFR-mutant lung adenocarcinoma: Data from LATAM population.

Background: Co-occurring genomic alterations identified downstream main oncogenic drivers have become more evident since the introduction of next-generation sequencing (NGS) analyses at diagnosis and progression. Emerging evidence has stated that co-occurring genomic alterations at diagnosis might represent de novo and primary resistance mechanisms to tyrosine kinase inhibitors (TKIs) in advanced EGFR-mutant (EGFRm) non-small lung cancer (NSCLC). In this study, we assessed the prognostic role of co-occurring genomic alterations in advanced EGFRm NSCLC.

Modifying factors of PD-L1 expression on tumor cells in advanced non-small-cell lung cancer.

Background: Programmed death ligand-1 (PD-L1) expression predicts immunotherapy utility in nononcogenic addictive lung adenocarcinoma (ADC). However, its reproducibility and reliability may be compromised outside clinical trials. This study aimed to evaluate factors associated with PD-L1 expression in lung ADC.

Association of Lung Adenocarcinoma Subtypes According to the IASLC/ATS/ERS Classification and Programmed Cell Death Ligand 1 (PD-L1) Expression in Tumor Cells.

Programmed cell death-ligand 1 (PD-L1) protein expression is one of the most extensively studied biomarkers in patients with non-small cell lung cancer (NSCLC). However, there is scarce information regarding its association with distinct adenocarcinoma subtypes. This study evaluated the frequency of PD-L1 expression according to the IASLC/ATS/ERS classification and other relevant histological and clinical features.

Clinicopathological and Prognostic Significance of CD47 Expression in Lung Neuroendocrine Tumors.

Background: Lung neuroendocrine tumors account for approximately 15% of all lung cancer cases. LNET are subdivided into typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small-cell lung cancer (SCLC). The Ki-67 index has been used for decades to evaluate mitotic counts however, the role of Ki-67 as a biomarker for assessing prognosis and guiding therapy in metastatic LNET still lacks feasible clinical validation.

Cell-Free Circulating Tumor DNA Improves Standard Genotyping of Non-Small-Cell Lung Cancer and Increases Detection of Targetable Alterations in a Selected Hispanic Cohort.

Background: Several studies have shown that the non-small-cell lung cancer (NSCLC) genomic background among Hispanics differs from other populations. The finding of low-frequency genomic alterations in cell-free DNA (cfDNA) can increase diagnostic accuracy and could improve treatment in NSCLC.

Methods: Data from 54 Hispanic patients with advanced NSCLC with high clinical suspicion for ALK, EGFR, and ROS1 mutations were collected (including young age, female sex, and non-smokers).

Response rate of patients with baseline brain metastases from recently diagnosed non-small cell lung cancer receiving radiotherapy according to EGFR, ALK and KRAS mutation status.

Background: Previous studies have identified that patients with EGFR mutations tend to have better responses to targeted therapy, as well as chemotherapy; however, the effect of genetic alterations in terms of radiotherapy (RT)-related outcomes has not been fully assessed. We studied the impact of common non-small cell lung cancer (NSCLC) genetic alterations (EGFR, ALK and KRAS) in relation to objective response rate (ORR) to RT in patients with brain metastases.

Methods: From 2009-2015, 153 patients with an available genotyping status were treated with whole-brain irradiation (WBI) before receiving systemic therapy.

Association between CD47 expression, clinical characteristics and prognosis in patients with advanced non-small cell lung cancer.

Objective: CD47 is an antiphagocytic molecule that contributes to tumor cell resistance in host immune surveillance. CD47 overexpression correlated with tumor progression and shorter survival in lung cancer. However, the expression and functional significance of CD47 in Non-Small Cell Lung Cancer (NSCLC) has not been completely understood.

Effect of Metformin Plus Tyrosine Kinase Inhibitors Compared With Tyrosine Kinase Inhibitors Alone in Patients With Epidermal Growth Factor Receptor-Mutated Lung Adenocarcinoma: A Phase 2 Randomized Clinical Trial.

Importance: Metformin hydrochloride is emerging as a repurposed anticancer drug. Preclinical and retrospective studies have shown that it improves outcomes across a wide variety of neoplasms, including lung cancer. Particularly, evidence is accumulating regarding the synergistic association between metformin and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs).

Molecular Epidemiology of ALK Rearrangements in Advanced Lung Adenocarcinoma in Latin America.

Objective: Latin American countries are heterogeneous in terms of lung cancer incidence and exposure to potential carcinogens. We evaluated the frequency and clinical characteristics of ALK rearrangements (ALKr) in Latin America.

Methods: A total of 5,130 lung cancer patients from 10 Latin American countries were screened for inclusion.

Response Assessment of Ga-DOTA-E-[c(RGDfK)] PET/CT in Lung Adenocarcinoma Patients Treated with Nintedanib Plus Docetaxel.

Nintedanib is an oral angiokinase inhibitor used as second-line treatment for non-small cell lung cancer. New radiotracers, such as Ga-DOTA-E-[c(RGDfK)], that target αβ integrin might have an impact as a noninvasive method for assessing angiogenesis inhibitors. From July 2011 through October 2015, 38 patients received second-line nintedanib plus docetaxel.

Reduction in Hepatocyte Growth Factor Serum Levels is Associated with Improved Prognosis in Advanced Lung Adenocarcinoma Patients Treated with Afatinib: a Phase II Trial.

Background: C-met and its ligand, hepatocyte growth factor (HGF) have been associated with the resistance mechanism of EGFR-TKIs. HGF was evaluated as a clinical-marker of response in NSCLC patients treated with afatinib.

Methods: Sixty-six patients with stage IIIB/IV lung adenocarcinoma and progression to any-line chemotherapy received afatinib 40 mg/day.

Diagnosis of EML4-ALK Translocation With FISH, Immunohistochemistry, and Real-time Polymerase Chain Reaction in Patients With Non-Small Cell Lung Cancer.

Objective: To assess anaplastic lymphoma kinase (ALK) rearrangement detection with immunohistochemistry (IHC) and real-time polymerase chain reaction (RT-qPCR) in comparison with fluorescence in situ hybridization (FISH).

Methods: Tumor tissue samples from 230 patients with advanced non-small cell lung cancer (NSCLC) were analyzed by FISH to detect ALK rearrangements. Additional IHC tests using 5A4 clone and RT-qPCR (variants 1 to 5) were performed in 63 and 48 patients, respectively.