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Table of Contents
LETTER TO EDITOR
Year : 2020  |  Volume : 3  |  Issue : 1  |  Page : 142-143

Liquid biopsy in non-small-cell lung cancer: Ready for prime time?


Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India

Date of Submission05-Jan-2020
Date of Acceptance06-Jan-2020
Date of Web Publication24-Feb-2020

Correspondence Address:
Ullas Batra
Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/CRST.CRST_9_20

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How to cite this article:
Sharma M, Joga S, Batra U. Liquid biopsy in non-small-cell lung cancer: Ready for prime time?. Cancer Res Stat Treat 2020;3:142-3

How to cite this URL:
Sharma M, Joga S, Batra U. Liquid biopsy in non-small-cell lung cancer: Ready for prime time?. Cancer Res Stat Treat [serial online] 2020 [cited 2020 Mar 30];3:142-3. Available from: http://www.crstonline.com/text.asp?2020/3/1/142/279151



The treatment of lung cancer has undergone a paradigm shift in the last decade, with the advent of biomarker testing and subsequent treatment with targeted therapies. Lung cancer can indeed be called the poster child of personalized medicine. However, personalized therapy requires biopsy and tissue acquisition, and biomarker testing is still a problem in lung cancer. The reasons for this include lack of trained radiologists/pulmonologists, inaccessible lesions, poor performance status of patient, and lack of availability of biomarker testing facilities in various parts of India. Thus, tissue remains an issue in the management of lung cancer.

In the last couple of years, liquid biopsy is fast emerging as an alternative option to tissue biopsy. It has the potential advantages of being less invasive, overcomes tumor heterogeneity, and can be used to monitor tumor response and also to detect resistance earlier than the conventional radiological imaging modalities. In addition, results from various trials confirm the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) when used in EGFR-mutant patients detected by liquid biopsy.[1],[2],[3],[4]

Hence, should liquid biopsy replace tissue biopsy in the management of lung cancer? The results from the article published in this Journal[5] and the accompanying editorial[6] would like us to believe so. However, in our opinion, the following points need consideration before rolling out the red carpet.

  1. To begin with, the ideal source of liquid biopsy (circulating tumor deoxyribonucleic acid [DNA], circulating tumor cells, exosomes, platelets, micro-ribonucleic acid) has not been ascertained yet
  2. It is not clear whether the tumor releases DNA by necrosis or apoptosis. The amount of DNA released also depends on the stage of the disease
  3. There is still a lack of clarity about the method used to detect biomarkers in the liquid biopsy (droplet digital polymerase chain reaction [ddPCR] vs. next-generation sequencing vs. real-time polymerase chain reaction)
  4. Most of the commonly used assays check for only common mutations, and hence, rare mutations can be missed if only liquid biopsy is used
  5. Although the sensitivity of assays like ddPCR is high, their specificity is only 70%.[7] In simpler terms, this implies that a positive result can be used to start TKIs, but a negative result must be confirmed by tissue biopsy
  6. Liquid biopsy has no role in the management of wild-type patients as yet
  7. Last but not the least, liquid biopsy is at present approved to detect primary and secondary EGFR mutations. It is still not approved to start TKIs based on ALK/ROS/BRAF mutations detected on the liquid biopsy.


Based on the above, we opine that although liquid biopsy is a promising tool in the management of lung cancer, at present it is a work in progress and not yet ready for prime time in lung cancer. Its role at present is limited to detecting T790M mutation as a resistance mechanism and detecting primary EGFR mutations only when tissue biopsy is not available. All efforts however must be made to obtain tissue biopsy, and liquid biopsy must be considered supplementary to tissue biopsy and not its alternative.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Reck M, Hagiwara K, Han B, Tjulandin S, Grohé C, Yokoi T, et al. ctDNA determination of EGFR mutation status in European and Japanese patients with advanced NSCLC: The ASSESS Study. J Thorac Oncol 2016;11:1682-9.  Back to cited text no. 1
    
2.
Karachaliou N, Mayo-de las Casas C, Queralt C, de Aguirre I, Melloni B, Cardenal F, et al. Association of EGFR L858R mutation in circulating free DNA with survival in the EURTAC Trial. JAMA Oncol 2015;1:149-57.  Back to cited text no. 2
    
3.
Gray JE, Okamoto I, Sriuranpong V, Vansteenkiste J, Imamura F, Lee JS, et al. Tissue and plasma EGFR mutation analysis in the FLAURA Trial: Osimertinib versus comparator EGFR tyrosine kinase inhibitor as first-line treatment in patients with EGFR-mutated advanced non-small cell lung cancer. Clin Cancer Res 2019;25:6644-52.  Back to cited text no. 3
    
4.
Rajendra A, Noronha V, Joshi A, Patil VM, Menon N, Prabhash K. Epidermal growth factor receptor-mutated non-small-cell lung cancer: A primer on contemporary management. Cancer Res Stat Treat 2019;2:36-53.  Back to cited text no. 4
  [Full text]  
5.
Pandey A, Dutt S, Singh A, Kumar A, Singh S. Outcomes with liquid biopsy to determine the EGFR mutation status in poor performance status, biopsy-ineligible, advanced NSCLC patients. Cancer Res Stat Treat 2019;2:197-203.  Back to cited text no. 5
  [Full text]  
6.
Choughule A, D'Souza H. Liquid biopsy in lung cancer-hope or hype? Cancer Res Stat Treat 2019;2:221-3.  Back to cited text no. 6
  [Full text]  
7.
Zhang R, Chen B, Tong X, Wang Y, Wang C, Jin J, et al. Diagnostic accuracy of droplet digital PCR for detection of EGFR T790M mutation in circulating tumor DNA. Cancer Manag Res 2018;10:1209-18.  Back to cited text no. 7
    




 

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