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LETTER TO EDITOR
Year : 2020  |  Volume : 3  |  Issue : 1  |  Page : 140-141

EGFR mutation in non-small cell lung cancer by liquid biopsy when solid not feasible


Department of Integrated Oncopathology, Metropolis Healthcare Ltd, Mumbai, Maharashtra, India

Date of Submission31-Dec-2019
Date of Acceptance08-Jan-2020
Date of Web Publication24-Feb-2020

Correspondence Address:
Kirti Chadha
Unit No. 409 to 416, 4th Floor, Commercial Building A, Kohinoor City, Near Kohinoor Mall, Kirol Road, Kurla-W, Mumbai - 400 070, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/CRST.CRST_126_19

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How to cite this article:
Chadha K, Vinarkar S, Chheda P. EGFR mutation in non-small cell lung cancer by liquid biopsy when solid not feasible. Cancer Res Stat Treat 2020;3:140-1

How to cite this URL:
Chadha K, Vinarkar S, Chheda P. EGFR mutation in non-small cell lung cancer by liquid biopsy when solid not feasible. Cancer Res Stat Treat [serial online] 2020 [cited 2020 Apr 4];3:140-1. Available from: http://www.crstonline.com/text.asp?2020/3/1/140/279084



Pandey et al. using an advanced technology (digital droplet polymerase chain reaction [ddPCR]), bring out a very practical solution for a frequently encountered problem in the article “Outcomes with liquid biopsy to determine the EGFR mutation status in poor performance status, biopsy ineligible, advanced non-small cell lung cancer (NSCLC) patients.”[1] The updated IASLC guidelines have already factored the role of liquid biopsy in detecting actionable EGFR mutations in NSCLC.[2] The accompanying editorial and review of the literature on liquid biopsy ctDNA EGFR mutation not only highlights its concordance with tissue EGFR mutation but also emphasizes its importance in the early detection of resistant mutation in patients receiving tyrosine kinase inhibitor (TKI) therapy.[3],[4] The authors have very well clinically correlated and utilized the advantage of noninvasive liquid biopsy as an upfront modality instead of tissue biopsy for detecting EGFR mutations in poor performance, older, and biopsy-ineligible metastatic NSCLC patients.

ddPCR is a sensitive, cost-effective, rapid, less laborious technique for the detection of very minute quantities of EGFR mutations in the ctDNA from plasma and we concur with the author based on our own experience of the past 1 year with ddPCR and ctDNA EGFR mutation detection. One does though have to be careful about preanalytical factors-immediate separation and storage of plasma or use of special tubes to stabilize nucleated-cells to minimize contamination of genomic DNA. Extraction of ctDNA from at least 3 mL plasma using validated extraction kit to obtain sufficient input DNA to enable detection of >1000 wild-type copies on ddPCR is a critical factor for reliable patient results.[5] We were able to yield successful ddPCR results in 80% of specimens analyzed. For 20% of cases, we had to do repeat specimen collection because the blood samples were received 24–48 h postcollection.

In addition to detection, ctDNA EGFR serial monitoring is also easily performed due to liquid biopsy being noninvasive, this aids follow-up and predicting response to treatment with the early detection of relapse due to emerging resistant secondary mutation T790M. The therapy can then be modified to incorporate new generation TKIs like osimertinib.[4],[6] The authors may continue to follow-up this small cohort of patients with ctDNA EGFR exon 19 del and exon 21 L858R mutation by serial monitoring of liquid biopsy to detect emerging T790M-resistant mutation just as they were followed for a median duration of 14 months poststarting of first-line TKI therapy.

However, CAP and AMP guidelines recommend that ctDNA EGFR mutation-negative patients should undergo tissue-based EGFR mutation analysis as the sensitivity of ctDNA is only 70%.[2] This has been highlighted by the authors also, hence, FFPE EGFR mutation should have been attempted in all 12 cases (5 cases where the patient had initially refused biopsy, 2 cases where cytology was received, and 5 cases where tissue was inadequate for molecular analysis) as ctDNA EGFR mutation was negative.

Saarenheimo et al.[7] also outlined liquid biopsy application in detecting other actionable gene mutations in NSCLC apart from EGFR as well as predicted the future utility of liquid biopsy in the diagnosis of lung cancer and detecting tumor mutation burden. Liquid biopsy is an alternative to painful tissue biopsy and will help evolve the targeted precision medicine not only in lung cancers but also in other malignancies.

We strongly support the article and recommend ctDNA mutation analysis by liquid biopsy in advanced NSCLC patients where repeat biopsy is not an option.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
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. 1
  [Full text]  
2.
Lindeman NI, Cagle PT, Aisner DL, Arcila ME, Beasley MB, Bernicker EH, et al. Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors: Guideline from the College of American Pathologists, the International Association for the Study of Lung Cancer and the Association for Molecular Pathology. Arch Pathol Lab Med 2018;142:321-46.  Back to cited text no. 2
    
3.
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. 3
  [Full text]  
4.
Zhang C, Wei B, Li P, Yang K, Wang Z, Ma J, et al. Prognostic value of plasma EGFR ctDNA in NSCLC patients treated with EGFR-TKIs. PLoS One 2017;12:e0173524.  Back to cited text no. 4
    
5.
Garcia J, Dusserre E, Cheynet V, Bringuier PP, Brengle-Pesce K, Wozny AS, et al. Evaluation of pre-analytical conditions and comparison of the performance of several digital PCR assays for the detection of major EGFR mutations in circulating DNA from non-small cell lung cancers: The CIRCAN_0 study. Oncotarget 2017;8:87980-96.  Back to cited text no. 5
    
6.
Wu YL, Sequist LV, Hu CP, Feng J, Lu S, Huang Y, et al. EGFR mutation detection in circulating cell-free DNA of lung adenocarcinoma patients: Analysis of LUX-Lung 3 and 6. Br J Cancer 2017;116:175-85.  Back to cited text no. 6
    
7.
Saarenheimo J, Eigeliene N, Andersen H, Tiirola M, Jekunen A. The value of liquid biopsies for guiding therapy decisions in non-small cell lung cancer. Front Oncol 2019;9:129.  Back to cited text no. 7
    




 

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