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Article ; Online: Predictive significance of circulating tumor DNA against patients with T790M-positive EGFR-mutant NSCLC receiving osimertinib

Ou Yamaguchi / Norimitsu Kasahara / Hiroshi Soda / Hisao Imai / Ichiro Naruse / Hiroyuki Yamaguchi / Miki Itai / Kohei Taguchi / Megumi Uchida / Noriaki Sunaga / Toshitaka Maeno / Koichi Minato / Hiromi Tomono / Daiki Ogawara / Hiroshi Mukae / Yu Miura / Ayako Shiono / Atsuto Mouri / Hiroshi Kagamu /
Kyoichi Kaira

Scientific Reports, Vol 13, Iss 1, Pp 1-

2023  Volume 10

Abstract: Abstract Circulating tumor DNA (ctDNA) provides molecular information on tumor heterogeneity. The prognostic usefulness of ctDNA after first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are limited. Therefore, the ... ...

Abstract Abstract Circulating tumor DNA (ctDNA) provides molecular information on tumor heterogeneity. The prognostic usefulness of ctDNA after first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are limited. Therefore, the present study evaluated ctDNA during osimertinib administration as a second-line or more setting to identify the relationship between EGFR mutation levels and outcomes in patients with advanced non-small cell lung cancer (NSCLC). Forty patients with EGFR T790M-positive NSCLC receiving osimertinib after prior EGFR-TKI treatment were registered. Plasma samples were collected at osimertinib pretreatment, after 1 month of treatment, and at the time of progressive disease (PD). ctDNA analysis was performed by digital polymerase chain reaction. The detection rate of copy numbers of exon 19 deletion, L858R, and T790M in plasma samples was significantly lower 1 month after osimertinib than at pretreatment, and significantly higher at PD than at 1 month, whereas that of C797S was significantly higher at PD than at 1 month. No statistically significant difference was observed in the copy numbers of exon 19 deletion, L858R, T790M, and C797S between complete response or partial response and stable disease or PD. The detection of T790M at PD after osimertinib initiation was a significant independent prognostic factor for predicting shorter prognosis, and the presence of major EGFR mutations at pretreatment and PD was closely linked to worse survival after osimertinib initiation. Molecular testing based on ctDNA is helpful for predicting outcomes of osimertinib treatment in T790M-positive NSCLC after previous EGFR-TKI treatment.
Keywords Medicine ; R ; Science ; Q
Subject code 616
Language English
Publishing date 2023-11-01T00:00:00Z
Publisher Nature Portfolio
Document type Article ; Online
Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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