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C. Alaez



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    P2.01 - Advanced NSCLC (ID 618)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P2.01-075 - Genomic Changes and Clinical Characteristics Associated with Wood-Smoke Exposure in Patients with Non-Small Cell Lung Cancer (ID 10324)

      09:00 - 09:00  |  Author(s): C. Alaez

      • Abstract
      • Slides

      Background:
      Chronic wood smoke exposure (WSE) is related to obstructive pulmonary disease and represents an increased risk of lung cancer. WSE is asociated with EGFR-mutations and low frequency of KRAS mutations. WSE signaling networks show better response to EGFR-TKIs, improving response rate and overall survival in NSCLC patients. Next-generation sequencing (NGS) has facilitated parallel analysis of multiple genes for treatment selection and monitoring response to treatment. We evaluated genomic alterations in patients with WSE based on tumor profiling by massive parallel sequencing.

      Method:
      52 patients with advanced lung cancer were evaluated. Fresh-frozen samples were used for DNA extraction with the Wizard Genomic DNA Purification Kit (Promega) including some formalin-fixed paraffin-embedded tissues (FFPE). The TruSeQ Cancer Panel (Illumina) was used for library construction in targeted sequencing of 48 genes spanning 212 amplicons in mutation hotspots.

      Result:
      WSE was more frequent in women (59% vs 41% p=0.038). We found diferent mutations in ATM (A1309H, G1679V, N1793I and T2749P), EGFR exon 7 (G288V), KDR (H267, Q1146S) and SMARCB1 (T72Q, G157A). WSE correlated with mutations in the genes KDR 89% vs. 11% (p=0.024), ATM 72% vs. 27% (p=0.040), SMARCB1 74% vs. 26% (p=0.020) and in exon 7 of EGFR 75% vs. 25% (p=0.034). Additionally, ATM mutations correlated with metastasis in CNS and bones 77% vs. 23% (p=0.006), also, patients with EGFR exon 7 presented major metastases in CNS and bones 67 vs. 33 % (p=0.084). SMARCB1 mutations were associated with worse overal survival (48 vs 5.6 months p=0.066). WSE patients carrying EGFR exon 7 mutations had better response showing either partial response or stable disease.

      Conclusion:
      Latin American patients of lung cancer and WSE present a distinctive mutation profile compared to non-WSE patients showing a positive correlation with KDR, ATM, EGFR exon 7, and SMARCB1 mutations. Figure 1



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