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Gonzalo Colmenarejo



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    EP1.01 - Advanced NSCLC (ID 150)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.01-07 - Definitive Results of a Clinical and Molecular Multicentric Characterization of Long-Term Survivors with Advanced Non-Small Cell Lung CancerĀ  (Now Available) (ID 1191)

      08:00 - 18:00  |  Author(s): Gonzalo Colmenarejo

      • Abstract
      • Slides

      Background

      Long survivors (LS) in non-small-cell lung cancer (NSCLC), defined as an overall survival (OS) greater than 2 years, are less than 10% in most series. Classical prognosis factors include stage, weight loss and ECOG, but more information is missing in the literature. Recently, EGFR, ALK and ROS 1 population (less than 20%) reach OS longer than 2 years. Immunotherapy has demonstrated very promising results with more LS compared to chemotherapy in first and second line setting. In this study, we focused in the analysis of LS patients with advanced NSCLC EGFR wt (wild type) and ALK nt (non-translocated), defined as those with OS greater than 36 months, in 7 hospitals in Madrid.

      Method

      In this serie, first of all, we will try to make a clinical, histopathological characterization collecting data from clinical reports according to a previously defined information. In a second step, we will carry out a genetic analysis of these patient samples comparing to an opposite extreme short survivors (SS) samples (OS less than 9 months). Initially, we used a NGS method of RNA-seq technology to identify differentiating profiles of gene expression between the two opposite populations. And finally, we confirmed this preliminary profile by RT-PCR in the rest of samples.

      Result

      Ninety-six patients were initially included. The majority were men, smokers or former with adenocarcinoma and ECOG 0- 1. We have obtained a differential transcriptome expression between samples from 6 LS and 6 SS, resulting 13 over-expressed and 42 down-expressed genes in LS comparing to SS transcriptome expression. Some of the genes involved in this initial profile belong to different cellular pathways: Secretin Receptor, Surfactant Protein, Trefoil Factor 1, Serpin Family, Ca-bindings Protein channel and Toll like Receptor family. Finally, we carried on by RT-PCR in 40 samples of SS and LS survivors and only four genes were significantly down-regulated in SS compared to LS in the multivariate analysis. These 4 genes were related to Surfactant Proteins: SFTPA1 (p = 0.023), SFTPA2 (p = 0.027), SFTPB (p = 0.02) and SFTPC (p = 0.047)

      Conclusion

      We present a sequential genetic analysis of a LS population with NSCLC EGFR wt (wild type) and ALK nt (non-translocated), obtaining a differential RNA seq- and RT-PCR gene profile based on different surfactant proteins expression. A further confirmation in a larger sample is ongoing.

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    P1.03 - Biology (ID 161)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Biology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.03-33 - Analysis of Lipid Metabolism Genes in Advanced Small Cell Lung Cancer (ID 2276)

      09:45 - 18:00  |  Author(s): Gonzalo Colmenarejo

      • Abstract

      Background

      Lung cancer is the leading cause of cancer death worldwide. Although most of the knowledge about metabolic dysregulation in cancer focuses on carbohydrates, the importance of alterations related to lipid metabolism is starting to be recognized. There is increasing data on lipid metabolism and non-small lung cancer, but much less is known about this in small cell lung cancer (SCLC). In order to improve our knowledge of these alterations we evaluated a genetic profile related to lipid metabolism and studied clinical outcomes

      Method

      We performed a retrospective analysis of 22 genes related to lipid metabolism in 37 tumoral tissue samples of SCLC patients and evaluated clinical features and outcomes. Advanced SCLC patients enrolled from November 1, 2008 through December 31, 2015 were included in this analysis. Clinical data were collected from medical records at the time of enrollment. The study was approved by an Ethics Comittee and all patients signed an Informed Consent form. We used formalin-fixed, paraffin- embedded tumor tissue. Samples were deparaffinated and total RNA was extracted. A Taq-Man Low Density Array (Applied Biosystems) was specifically designed and gene-expression assays were performed in a HT-7900 Fast Real time PCR. RT-StatMiner software was used to detect and determine the quality control and differential expression analyses of data.

      Result

      We included 37 patients, 73 % males and 27 % women, with a median age of 62. 29 patients (78%) had stage IV tumor and nearly all of them (92%) were treated with platinum- based chemotherapy. 11 % (4/37) received thoracic radiotherapy and 5% (2/37) received whole brain radiotherapy. 6 patients (16%) were on chronic treatment with metformin and 15 (40%) on statins. We performed a multivariable analysis and found that overexpression of two metabolic genes (a mitochondrial enzyme and a lipid metabolism regulator) led to longer overall survival. (HR 0.13 (0.04-0.42), p 0.0019, padjusted 0.04 and HR 0.11 (0.03-0.35) p 0.0006, padjusted 0.01, respectively).

      Conclusion

      These genes contribute to normal functioning and regulation of lipid metabolism and could be considered as potential prognostic biomarkers. There is no previous evidence of association between levels of expression of these genes and overall survival in SCLC. Validation in a larger series of patients is ongoing.