We thank Bennett et al. for their correspondence, in which they suggest that our case report [
[1]
] may cause undue alarm in non-small cell lung cancer (NSCLC) patients who have been
genotyped by polymerase chain reaction (PCR)-based assays alone. Our intention is
not to cause unwarranted concern but to stress to clinicians the limitations of PCR-based
genotyping. Indeed, when PCR-based assays do identify an actionable genetic alteration,
their benefit is proven. However, the issue is when such assays are reported as “negative”
and the inability to differentiate false negatives from true negatives. Given the
paucity of NSCLC tissue, we argue to do the best test first: next-generation sequencing
(NGS). Bennett et al. reference their work which analysed the NGS reports of 2796 UK NSCLC patients over
a 3-year period. This study found that 12% of driver EGFR mutations detected in this population would have been missed by commercial EGFR PCR assays [
- O'Sullivan H.
- d'Arienzo P.D.
- Yousaf N.
- Cui W.
- Popat S.
Inadequacy of PCR genotyping in advanced non-small cell lung cancer: EGFR L747_A755delinsSS
exon 19 deletion is not detected by the real-time PCR Idylla™ EGFR mutation test but
is detected by ctDNA next generation sequencing and responds to osimertinib.
Eur J Cancer. 2022; 166 (Oxford, England : 1990): 38-40
[2]
]. We wonder whether this is an acceptable false-negative rate for EGFR.- Moore D.A.
- Balbi K.
- Ingham A.
- Hendrik-Tobias A.
- Bennett P.
Analysis of a large cohort of non-small cell lung cancers submitted for somatic variant
analysis demonstrates that targeted next-generation sequencing is fit for purpose
as a molecular diagnostic assay in routine practice.
J Clin Pathol. 2018; 71: 1001
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References
- Inadequacy of PCR genotyping in advanced non-small cell lung cancer: EGFR L747_A755delinsSS exon 19 deletion is not detected by the real-time PCR Idylla™ EGFR mutation test but is detected by ctDNA next generation sequencing and responds to osimertinib.Eur J Cancer. 2022; 166 (Oxford, England : 1990): 38-40
- Analysis of a large cohort of non-small cell lung cancers submitted for somatic variant analysis demonstrates that targeted next-generation sequencing is fit for purpose as a molecular diagnostic assay in routine practice.J Clin Pathol. 2018; 71: 1001
- Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.Ann Oncol : Off J Euro Soc Med Oncol. 2018; 29: iv192-iv237
- EGFR testing patterns and detection of EGFR exon 20 insertions in the United States.JTO Clinic Res Rep. 2022; 3: 100285
- The 2021 WHO classification of lung tumors: impact of advances since 2015.J Thorac Oncol. 2022; 17 (official publication of the International Association for the Study of Lung Cancer): 362-387
- FP07.12 underdiagnosis of EGFR exon 20 insertion mutation variants: estimates from NGS-based real-world datasets.J Thorac Oncol. 2021; 16: S208-S209
- A pilot of Blood-First diagnostic cell free DNA (cfDNA) next generation sequencing (NGS) in patients with suspected advanced lung cancer (Amsterdam, Netherlands).Lung Cancer. 2022; 165: 34-42
- Plasma genotyping at the time of diagnostic tissue biopsy decreases time-to-treatment in patients with advanced NSCLC-results from a prospective pilot study.JTO Clinic Res Rep. 2022; 3: 100301
Article info
Publication history
Published online: August 07, 2022
Accepted:
June 17,
2022
Received:
June 16,
2022
Identification
Copyright
© 2022 Elsevier Ltd. All rights reserved.
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- Re: Inadequacy of PCR genotyping in advanced non-small cell lung cancer: EGFR L747_A755delinsSS Exon 19 deletion is not detected by the real-time PCR IdyllaTM EGFR mutation test but is detected by ctDNA NGS and responds to osimertinibEuropean Journal of CancerVol. 174
- PreviewWhilst not disagreeing with much of the factual content in the recently published letter by O'Sullivan et al. [1], we feel that their article fails to consider relevance in a wider clinical context whilst making unjustifiable comments/recommendations on the basis of a single (n = 1) and also atypical case report.
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- Inadequacy of PCR genotyping in advanced non-small cell lung cancer: EGFR L747_A755delinsSS exon 19 deletion is not detected by the real-time PCR Idylla™ EGFR mutation test but is detected by ctDNA next generation sequencing and responds to osimertinibEuropean Journal of CancerVol. 166
- PreviewActivating alterations in EGFR occur in 5–60% of non–-small cell lung cancer (NSCLC), contingent on ethnicity. Exon 19 deletions and exon 21 L858R mutations account for approximately 85% of tier 1 EGFR variants [1,2]. EGFR tyrosine kinase inhibitors are the recommended first-line treatment, yielding durable responses [3].
- Full-Text
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