Detection of EGFR mutations in plasma and biopsies from non-small cell lung cancer patients by allele-specific PCR assays

Weber, Britta; Meldgaard, Peter; Hager, Henrik; Wu, Lin; Wen, Wei; Tsai, Julie; Khalil, Azza Ahmed; Nexø, Ebba; Sørensen, Boe Sandahl

doi:10.1186/1471-2407-14-294

Cited by 139 publications

(108 citation statements)

References 13 publications

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“…A total of 2 mL of blood was used for cfDNA extraction using the cobas cell-free DNA Purification Kit (in development; ref. 22). The cfDNA was eluted in 100 mL, 75 mL…”

Section: Biomarker Analysismentioning

confidence: 99%

Detection and Dynamic Changes of EGFR Mutations from Circulating Tumor DNA as a Predictor of Survival Outcomes in NSCLC Patients Treated with First-line Intercalated Erlotinib and Chemotherapy

Mok

Lee

et al. 2015

Clinical Cancer Research

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430

357

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Purpose: Blood-based circulating-free (cf) tumor DNA may be an alternative to tissue-based EGFR mutation testing in NSCLC. This exploratory analysis compares matched tumor and blood samples from the FASTACT-2 study.Experimental Design: Patients were randomized to receive six cycles of gemcitabine/platinum plus sequential erlotinib or placebo. EGFR mutation testing was performed using the cobas tissue test and the cobas blood test (in development). Blood samples at baseline, cycle 3, and progression were assessed for blood test detection rate, sensitivity, and specificity; concordance with matched tumor analysis (n ¼ 238), and correlation with progression-free survival (PFS) and overall survival (OS).Results: Concordance between tissue and blood tests was 88%, with blood test sensitivity of 75% and a specificity of 96%. Median PFS was 13.1 versus 6.0 months for erlotinib and placebo, respectively, for those with baseline EGFR mut þ cfDNA [HR, 0.22; 95% confidence intervals (CI), 0.14-0.33, P < Conclusions: Blood-based EGFR mutation analysis is relatively sensitive and highly specific. Dynamic changes in cfDNA EGFR mutation status relative to baseline may predict clinical outcomes.

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“…A total of 2 mL of blood was used for cfDNA extraction using the cobas cell-free DNA Purification Kit (in development; ref. 22). The cfDNA was eluted in 100 mL, 75 mL…”

Section: Biomarker Analysismentioning

confidence: 99%

Detection and Dynamic Changes of EGFR Mutations from Circulating Tumor DNA as a Predictor of Survival Outcomes in NSCLC Patients Treated with First-line Intercalated Erlotinib and Chemotherapy

Mok

Lee

et al. 2015

Clinical Cancer Research

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430

357

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“…ctDNA can be used to identify resistance to TKIs [126][127][128][129][130][131][132][133][134][135]. Weber et al [136] demonstrated a concordance rate of 90% (179/199) for EGFR mutations between biopsy tissue and ctDNA (plasma) before EGFR TKIs. These authors identified EGFR mutations in the plasma not identified in the biopsy, probably related to sampling issues or heterogeneity [136].…”

Section: Doi: 101159/000487440mentioning

confidence: 99%

Heterogeneity in Lung Cancer

2018

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Lung cancer diagnosis is a challenge since it is also one of the most frequently diagnosed cancers. Diagnostic challenges are deeply related to the development of personalized therapy and molecular and precise histological characterizations of lung cancer. When addressing these features, it is very important to acknowledge the issue of tumour heterogeneity, as it imposes several questions. First of all, lung cancer is a very heterogeneous disease, at a cellular and histological level. Cellular and histological heterogeneity are addressed with emphasis on the diagnosis, pre-neoplastic lesions, and cell origin, trying to contribute to a better knowledge of carcinogenesis. Molecular intra-tumour and inter-tumour heterogeneity are also addressed as temporal heterogeneity. Lung cancer heterogeneity has implications in pathogenesis understanding, diagnosis, selection of tissue for molecular diagnosis, as well as therapeutic decision. The understanding of tumour heterogeneity is crucial and we must be aware of the implications and future developments regarding this field.

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“…By contrast, tumor regression correlates to decreased ctDNA burden in cfDNA. With regard to specific genetic alterations, one clear example is the clinical utility of the detection of EGFR mutations in the cfDNA of NSCLC patients treated with gefitinib (25) or erlotinib (26). EGFR mutations have also been shown to be of prognostic and predictive value, and patients with an activating mutation in EGFR in cfDNA have been reported to respond significantly better to TKIs (27).…”

Section: Circulating Free Dna (Cfdna) As Prognostic and Monitoring Tementioning

confidence: 99%

KRAS mutations in the circulating free DNA (cfDNA) of non-small cell lung cancer (NSCLC) patients

Garzón¹,

Villatoro²,

Teixidó³

et al. 2016

Transl. Lung Cancer Res.

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Detection of EGFR mutations in plasma and biopsies from non-small cell lung cancer patients by allele-specific PCR assays

Cited by 139 publications

References 13 publications

Detection and Dynamic Changes of EGFR Mutations from Circulating Tumor DNA as a Predictor of Survival Outcomes in NSCLC Patients Treated with First-line Intercalated Erlotinib and Chemotherapy

Detection and Dynamic Changes of EGFR Mutations from Circulating Tumor DNA as a Predictor of Survival Outcomes in NSCLC Patients Treated with First-line Intercalated Erlotinib and Chemotherapy

Heterogeneity in Lung Cancer

KRAS mutations in the circulating free DNA (cfDNA) of non-small cell lung cancer (NSCLC) patients

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