Onkológia 5/2020

Circulating tumor DNA in non-small cell lung cancer patients with epidermal growth factor receptor mutations

TKIs are standard of care of lung adenocarcinoma with driver mutations. The detection of genetic alterations of DNA is based on molecular genetics analysis of tumor cells or circulating tumor DNA (ctDNA). The most frequent targetable genetic alterations are activating mutations of EGFR gene. Deletion 19 has the best prognostic outcome of EGFR mutations with TKI treatment. The most frequent mechanism of acquired resistance to first- and second-generation TKI is resistant mutation T790M. ctDNA is non-invasive EGFR detection option at the time of diagnosis and progression in real clinical practice. Implementation of high-sensitive methods (ddPCR, BEAMing) will increase clinical importance of ctDNA. ctDNA tracking during TKI treatment enables assessment of treatment response, early detection of tumor biology changes, real-time resistance evolution assessment. The persistance of activating EGFR mutations in ctDNA is independent predictor of poor outcome (PFS, OS). ctDNA tracking will enable even more precise optimisation of targeted treatment or its combination with IO or CIT.

Keywords: TKIs are standard of care of lung adenocarcinoma with driver mutations. The detection of genetic alterations of DNA is based on molecular genetics analysis of tumor cells or circulating tumor DNA (ctDNA). The most frequent targetable genetic alterations are activating mutations of EGFR gene. Deletion 19 has the best prognostic outcome of EGFR mutations with TKI treatment. The most frequent mechanism of acquired resistance to first- and second-generation TKI is resistant mutation T790M. ctDNA is non-invasive EGFR detection option at the time of diagnosis and progression in real clinical practice. Implementation of high-sensitive methods (ddPCR, BEAMing) will increase clinical importance of ctDNA. ctDNA tracking during TKI treatment enables assessment of treatment response, early detection of tumor biology changes, real-time resistance evolution assessment. The persistance of activating EGFR mutations in ctDNA is independent predictor of poor outcome (PFS, OS). ctDNA tracking will enable even more precise optimisation of targeted treatment or its combination with IO or CIT.