2024 World Conference on Lung Cancer (WCLC) - Posters-P3.03H.04 Molecular and Clonal Evolution of Primary Lesions vs Brain Metastasis and Progressive Disease of EGFR Mutated Patients

P3.03H.04 Molecular and Clonal Evolution of Primary Lesions vs Brain Metastasis and Progressive Disease of EGFR Mutated Patients

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The study investigates the molecular and clonal evolution of primary lesions versus brain metastases in EGFR-mutated lung adenocarcinoma patients. The analysis involved 30 patients from Mexico, Colombia, Brazil, and Chile, with a majority being female and a median age of 55 years. The focus was on different mutational patterns in brain metastases compared to primary tumors.<br /><br />The study employed a retrospective cohort design across four Latin American countries. Patients included in this study either had brain metastases upon diagnosis or developed them later. Each patient underwent genomic profiling through Next-Generation Sequencing (NGS) on samples from primary lesions, predominant brain lesions, and either liquid biopsies or extracranial lesion tissue. These patients received treatment with Osimertinib and Stereotactic radiosurgery for brain lesions.<br /><br />Findings revealed that 90% had Central Nervous System (CNS) involvement at diagnosis. The median number of brain lesions was two. Molecular differences were observed between brain metastases and primary tumors, with certain metastasis clones also driving systemic progression. Nearly half of the patients exhibited exon 19 deletions, while others had L858R mutations. TP53 mutations were most frequent in primary lesions. Notably, brain metastases exhibited higher tumor mutational burden (TMB) than primary lesions. EGFR mutations were lost in 30% of patients between primary and CNS lesions.<br /><br />In brain metastases, PIK3CA/PTEN/AKT mutations were common, alongside other alterations like BRAF and RB1. Gene amplifications were present in 63% of patients, indicating genetic diversity in metastatic sites. Upon systemic progression, MET amplification and small-cell transformation were noted in some cases. Mutations initially found in brain metastases, like PIK3CA, reappeared in systemic disease in several patients. Overall, the study highlights the complexity of brain metastasis evolution and its potential impact on disease progression.

Asset Subtitle

Leonardo Rojas

Meta Tag

Speaker Leonardo Rojas

Topic Tumor Biology – Translational Biology

Keywords

EGFR-mutated

lung adenocarcinoma

brain metastases

molecular evolution

Next-Generation Sequencing

Osimertinib

Stereotactic radiosurgery

tumor mutational burden

PIK3CA mutations

genetic diversity