EGFR circulating tumour DNA testing: identification of predictors of ctDNA detection and implications for survival outcomes
| العنوان: | EGFR circulating tumour DNA testing: identification of predictors of ctDNA detection and implications for survival outcomes |
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| المؤلفون: | Alexandra Pender, Aly Karsan, Selina Wong, Elaine Law, Amadea Kristanti, Janessa Laskin, Sean D. Young, Tracy Tucker, Cheryl Ho, Curtis Hughesman, Ian Bosdet, Kelly McNeil, Stephen Yip |
| المصدر: | Transl Lung Cancer Res |
| بيانات النشر: | AME Publishing Company, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Oncology, medicine.medical_specialty, business.industry, medicine.medical_treatment, Resistance mutation, medicine.disease, Dna testing, Targeted therapy, 03 medical and health sciences, T790M, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Baseline characteristics, Internal medicine, Medicine, Original Article, Osimertinib, business, Lung cancer, Progressive disease |
| الوصف: | Background EGFR T790M testing is the standard of care for activating EGFR mutation (EGFRm) non-small cell lung cancer (NSCLC) progressing on 1st/2nd generation TKIs to select patients for osimertinib. Despite sensitive assays, detection of circulating tumour deoxyribonucleic acid (ctDNA) is variable and influenced by clinical factors. The number and location of sites of progressive disease at time of testing were reviewed to explore the effect on EGFR ctDNA detection. The prognostic value of EGFR ctDNA detection on survival outcomes was assessed. Methods Following extraction of cell-free DNA from plasma using the QIAamp Circulating Nucleic Acid Kit, custom droplet digital polymerase chair reaction (ddPCR) assays were used to assess EGFR ctDNA using the Bio-Rad QX200 system. The ddPCR assay has a limit of detection of ≤0.15% variant allele fraction. Baseline characteristics and imaging reports at time of EGFR ctDNA testing were reviewed retrospectively for a 1 year period. Results The study included 177 patients who had an EGFR ctDNA test. Liver (aOR 3.13) or bone (aOR 2.76) progression or 3-5 sites of progression (aOR 2.22) were predictive of EGFR ctDNA detection. The median OS from first ctDNA test after multiple testing iterations was 12.3 m undetectable EGFR ctDNA, 7.6 m for original EGFR mutation only and 24.1 m with T790M (P=0.001). Conclusions Patients with liver or bone progression and 3-5 progressing sites are more likely to have informative EGFR ctDNA testing. Detection of EGFR ctDNA is a negative prognostic indicator in the absence of a T790M resistance mutation, potentially reflecting the disease burden in the absence of targeted therapy options. |
| تدمد: | 2226-4477 2218-6751 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ce6e27762dba579f9b5d82ae64bacb05 https://doi.org/10.21037/tlcr-19-581 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....ce6e27762dba579f9b5d82ae64bacb05 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22264477 22186751 |
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