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Driver Mutations in Non-Small Cell Lung Cancer: Utility of Liquid Biopsy

Received: 8 August 2022    Accepted: 29 August 2022    Published: 5 September 2022
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Abstract

Non-small Cell Lung Cancer (NSCLC) has become the most prominent example demonstrating the importance of targeted therapy in cancer treatment. Up to 25% of patients with non-squamous NSCLC (nsNSCLC) harbor driver mutations which are responsible for the malignancy. For these patients, oral targeted drugs directed against the mutated gene yield better outcomes than chemotherapy or immunotherapy. Consequently, assessing the tumor for driver mutations has become standard of care in managing nsNSCLC. However, in 20% of lung cancer patients, the tissue biopsy is either unobtainable or insufficient to assay. In these circumstances, analyzing circulating tumor DNA (ctDNA) or circulating tumor cells (CTCs) from the blood can reveal the driver mutations. A prospective study was conducted with Biocept, to evaluate the clinical utility of a single gene assay using ctDNA and CTCs in patients with advanced NSCLC. Here, we report the comparison between biomarker expression of the tumor tissue and liquid biopsy of matched samples of 40 unique patients. Methods: Matched liquid biopsy and tumor tissue was analyzed from forty unique patients with stage III and IV NSCLC for EGFR, KRAS, BRAF, ALK, and ROS-1. Tissue was analyzed by Next Generation Sequencing (NGS), whereas peripheral blood samples for liquid biopsy was analyzed using circulating tumor DNA (ctDNA) for EGFR, KRAS, and BRAF mutations, and circulating tumor cells (CTCs) for ALK and ROS-1 mutations. Results: 80% of the patients (32/40) received both tissue biopsy and liquid biopsy analysis. The concordance between EGFR, KRAS, BRAF, ALK and ROS-1 between tumor tissue and liquid biopsy was 86%. Furthermore, liquid biopsy demonstrated a higher rate of conclusive results compared to tissue biopsy and led to a change in treatment for in 4 of the 40 patients. Conclusion: This works suggests that tissue and liquid biopsy can be complementary, and liquid biopsy can inform the course of treatment when a tissue biopsy is not available.

Published in International Journal of Biomedical Engineering and Clinical Science (Volume 8, Issue 3)
DOI 10.11648/j.ijbecs.20220803.12
Page(s) 33-39
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Non-small Cell Lung Cancer, Liquid Biopsy, Cell-Free Tumor DNA, Circulating Tumor Cells, Driver Mutations

References
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Cite This Article
  • APA Style

    Andrew Friday, Khaled Alhamad, Gene Grant Finley, Robin Raquel Rodriguez, Herman Lo, et al. (2022). Driver Mutations in Non-Small Cell Lung Cancer: Utility of Liquid Biopsy. International Journal of Biomedical Engineering and Clinical Science, 8(3), 33-39. https://doi.org/10.11648/j.ijbecs.20220803.12

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    ACS Style

    Andrew Friday; Khaled Alhamad; Gene Grant Finley; Robin Raquel Rodriguez; Herman Lo, et al. Driver Mutations in Non-Small Cell Lung Cancer: Utility of Liquid Biopsy. Int. J. Biomed. Eng. Clin. Sci. 2022, 8(3), 33-39. doi: 10.11648/j.ijbecs.20220803.12

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    AMA Style

    Andrew Friday, Khaled Alhamad, Gene Grant Finley, Robin Raquel Rodriguez, Herman Lo, et al. Driver Mutations in Non-Small Cell Lung Cancer: Utility of Liquid Biopsy. Int J Biomed Eng Clin Sci. 2022;8(3):33-39. doi: 10.11648/j.ijbecs.20220803.12

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  • @article{10.11648/j.ijbecs.20220803.12,
      author = {Andrew Friday and Khaled Alhamad and Gene Grant Finley and Robin Raquel Rodriguez and Herman Lo and Aaron Weidman and Zachary Otaibi and Ashish Sethi and Suneera Bhatia},
      title = {Driver Mutations in Non-Small Cell Lung Cancer: Utility of Liquid Biopsy},
      journal = {International Journal of Biomedical Engineering and Clinical Science},
      volume = {8},
      number = {3},
      pages = {33-39},
      doi = {10.11648/j.ijbecs.20220803.12},
      url = {https://doi.org/10.11648/j.ijbecs.20220803.12},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijbecs.20220803.12},
      abstract = {Non-small Cell Lung Cancer (NSCLC) has become the most prominent example demonstrating the importance of targeted therapy in cancer treatment. Up to 25% of patients with non-squamous NSCLC (nsNSCLC) harbor driver mutations which are responsible for the malignancy. For these patients, oral targeted drugs directed against the mutated gene yield better outcomes than chemotherapy or immunotherapy. Consequently, assessing the tumor for driver mutations has become standard of care in managing nsNSCLC. However, in 20% of lung cancer patients, the tissue biopsy is either unobtainable or insufficient to assay. In these circumstances, analyzing circulating tumor DNA (ctDNA) or circulating tumor cells (CTCs) from the blood can reveal the driver mutations. A prospective study was conducted with Biocept, to evaluate the clinical utility of a single gene assay using ctDNA and CTCs in patients with advanced NSCLC. Here, we report the comparison between biomarker expression of the tumor tissue and liquid biopsy of matched samples of 40 unique patients. Methods: Matched liquid biopsy and tumor tissue was analyzed from forty unique patients with stage III and IV NSCLC for EGFR, KRAS, BRAF, ALK, and ROS-1. Tissue was analyzed by Next Generation Sequencing (NGS), whereas peripheral blood samples for liquid biopsy was analyzed using circulating tumor DNA (ctDNA) for EGFR, KRAS, and BRAF mutations, and circulating tumor cells (CTCs) for ALK and ROS-1 mutations. Results: 80% of the patients (32/40) received both tissue biopsy and liquid biopsy analysis. The concordance between EGFR, KRAS, BRAF, ALK and ROS-1 between tumor tissue and liquid biopsy was 86%. Furthermore, liquid biopsy demonstrated a higher rate of conclusive results compared to tissue biopsy and led to a change in treatment for in 4 of the 40 patients. Conclusion: This works suggests that tissue and liquid biopsy can be complementary, and liquid biopsy can inform the course of treatment when a tissue biopsy is not available.},
     year = {2022}
    }
    

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  • TY  - JOUR
    T1  - Driver Mutations in Non-Small Cell Lung Cancer: Utility of Liquid Biopsy
    AU  - Andrew Friday
    AU  - Khaled Alhamad
    AU  - Gene Grant Finley
    AU  - Robin Raquel Rodriguez
    AU  - Herman Lo
    AU  - Aaron Weidman
    AU  - Zachary Otaibi
    AU  - Ashish Sethi
    AU  - Suneera Bhatia
    Y1  - 2022/09/05
    PY  - 2022
    N1  - https://doi.org/10.11648/j.ijbecs.20220803.12
    DO  - 10.11648/j.ijbecs.20220803.12
    T2  - International Journal of Biomedical Engineering and Clinical Science
    JF  - International Journal of Biomedical Engineering and Clinical Science
    JO  - International Journal of Biomedical Engineering and Clinical Science
    SP  - 33
    EP  - 39
    PB  - Science Publishing Group
    SN  - 2472-1301
    UR  - https://doi.org/10.11648/j.ijbecs.20220803.12
    AB  - Non-small Cell Lung Cancer (NSCLC) has become the most prominent example demonstrating the importance of targeted therapy in cancer treatment. Up to 25% of patients with non-squamous NSCLC (nsNSCLC) harbor driver mutations which are responsible for the malignancy. For these patients, oral targeted drugs directed against the mutated gene yield better outcomes than chemotherapy or immunotherapy. Consequently, assessing the tumor for driver mutations has become standard of care in managing nsNSCLC. However, in 20% of lung cancer patients, the tissue biopsy is either unobtainable or insufficient to assay. In these circumstances, analyzing circulating tumor DNA (ctDNA) or circulating tumor cells (CTCs) from the blood can reveal the driver mutations. A prospective study was conducted with Biocept, to evaluate the clinical utility of a single gene assay using ctDNA and CTCs in patients with advanced NSCLC. Here, we report the comparison between biomarker expression of the tumor tissue and liquid biopsy of matched samples of 40 unique patients. Methods: Matched liquid biopsy and tumor tissue was analyzed from forty unique patients with stage III and IV NSCLC for EGFR, KRAS, BRAF, ALK, and ROS-1. Tissue was analyzed by Next Generation Sequencing (NGS), whereas peripheral blood samples for liquid biopsy was analyzed using circulating tumor DNA (ctDNA) for EGFR, KRAS, and BRAF mutations, and circulating tumor cells (CTCs) for ALK and ROS-1 mutations. Results: 80% of the patients (32/40) received both tissue biopsy and liquid biopsy analysis. The concordance between EGFR, KRAS, BRAF, ALK and ROS-1 between tumor tissue and liquid biopsy was 86%. Furthermore, liquid biopsy demonstrated a higher rate of conclusive results compared to tissue biopsy and led to a change in treatment for in 4 of the 40 patients. Conclusion: This works suggests that tissue and liquid biopsy can be complementary, and liquid biopsy can inform the course of treatment when a tissue biopsy is not available.
    VL  - 8
    IS  - 3
    ER  - 

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Author Information
  • Department of Medical Oncology, Allegheny General Hospital, Pittsburgh, United States

  • Department of Internal Medicine, Allegheny General Hospital, Pittsburgh, United States

  • Department of Medical Oncology, Allegheny General Hospital, Pittsburgh, United States

  • Department of Medical Oncology, Allegheny General Hospital, Pittsburgh, United States

  • Department of Medical Oncology, Allegheny General Hospital, Pittsburgh, United States

  • Vital Department, Highmark Health, Pittsburgh, United States

  • Department of Medical Oncology, Allegheny General Hospital, Pittsburgh, United States

  • Department of Medical Oncology, Allegheny General Hospital, Pittsburgh, United States

  • Vital Department, Highmark Health, Pittsburgh, United States

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