2023 World Conference on Lung Cancer (Posters)-P2.03. Clinical Impact of Genomic Characterization in Induced Oligometastatic Non-small Cell Lung Cancer

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This study investigated the clinical impact of genomic characterization in induced oligometastatic non-small cell lung cancer (NSCLC). The combination of systemic therapies and local consolidation therapy (LCT) has been shown to benefit patients with this type of cancer. The researchers enrolled patients with advanced NSCLC who received systemic therapy and were diagnosed with oligometastasis. Pulmonary tumor resection was performed, and the tumor tissues were collected for whole-exome sequencing. Mutational data from tumor tissues before systemic treatment were also collected. <br /><br />Out of the 17 patients included in the study, 14 had EGFR actionable alterations and received targeted therapy. One patient had EML4-ALK and received targeted therapy, and two patients received a combination of chemo-immunotherapy. After systemic therapy, the most frequently mutated genes were EGFR, TP53, PIK3CA, and MUC17. Somatic copy number gain was observed in specific regions. Acquired resistance alterations to targeted therapies were identified, including EGFR T790M, BRAF V600E, PIK3CA, CDK4 amplification, MET amplification, and MCL1 amplification.<br /><br />Intratumoral heterogeneity (ITH) was assessed in primary lesions of 16 patients, and it was found to be positively correlated with tumor mutation burden and tumor neoantigen burden. Patients with higher ITH had a reduced progression-free survival. The homologous recombination deficiency (HRD) status was also evaluated, and a positive correlation was found between HRDscore and the duration of systemic therapy. Patients with HRDscore less than 18 had a significantly reduced progression-free survival.<br /><br />The study concludes that resistance to targeted therapy, ITH, and genomic instability driven by HRD may contribute to the persistence and recurrence of oligometastatic lesions in advanced NSCLC. Increased ITH and HRD events were associated with inferior clinical outcomes. These findings can help improve treatment strategies for patients with oligometastatic NSCLC after LCT and after drug resistance.

Asset Subtitle

Rui Fu

Meta Tag

Speaker Rui Fu

Topic Metastatic NSCLC: Local Therapies

Keywords

genomic characterization

oligometastatic non-small cell lung cancer

systemic therapies

local consolidation therapy

advanced NSCLC

targeted therapy

somatic copy number gain

intratumoral heterogeneity

homologous recombination deficiency

genomic instability