Abstract
Long-lasting success in lung cancer therapy using tyrosine kinase inhibitors (TKIs) is rare since the tumors develop resistance due to the occurrence of molecularly altered subclones. The aim of this study was to monitor tumors over time based on the quantity of mutant plasma DNA and to identify early indications for therapy response and tumor progression. Serial plasma samples from lung adenocarcinoma patients treated with TKIs were used to quantify EGFR and KRAS mutations in circulating DNA by digital PCR. Mutant DNA levels were compared with the courses of responses to treatment with TKIs, conventional chemotherapy, radiotherapy, or combinations thereof. Variations in plasma DNA mutation levels over time were found in 15 patients. We categorize three major courses: First, signs of therapy response are associated with a fast clearing of plasma DNA mutations within a few days. Second, periods of stable disease are accompanied by either absence of mutations or fluctuation at low levels. Finally, dramatic increase of mutational load is followed by rapid tumor progression and poor patient survival. In summary, the serial assessment of EGFR mutations in the plasma of NSCLC patients allows conclusions about controlled disease and tumor progression earlier than currently available methods.
Highlights
TNM non smoker cT4 cN0 cM1b fmr. smoker; 35 pys cT4 cN3 cM1b fmr. smoker; 35 pys cT2b cN2 cM1a cur. smoker; 20 pys cT4 cN2 cM1b fmr. smoker cT2A cN0 cM1b non smoker pT1 pN1 pM0 R0 fmr. smoker; 28 pys pT3 pN9 pM1a R0 non smoker cT2A cN1 cM1b non smoker cT4 cN2 cM1a non smoker cT3-4 cN3 cM1b non smoker cT2-3 cN2 cM1a cur. smoker; 25 pys cT1a cN2 cM1b non smoker pT1B pN1 pM0 R0 fmr. smoker; 2 pys cT4 cN3 cM1b non smoker pT4 pN2 cM0 R1 cur. smoker; 43 pys cT4 cN3 cM1b
We describe the analysis of serial plasma DNA samples from 16 Non small cell lung cancer (NSCLC) patients under tyrosine kinase inhibitors (TKIs) therapy
In accordance with previous reports[11,16,20,29,30], we demonstrate that serial mutation analysis of cfDNA in plasma is feasible for therapy monitoring
Summary
TNM non smoker cT4 cN0 cM1b fmr. smoker; 35 pys cT4 cN3 cM1b fmr. smoker; 35 pys cT2b cN2 cM1a cur. smoker; 20 pys cT4 cN2 cM1b fmr. smoker cT2A cN0 cM1b non smoker pT1 pN1 pM0 R0 fmr. smoker; 28 pys pT3 pN9 pM1a R0 non smoker cT2A cN1 cM1b non smoker cT4 cN2 cM1a non smoker cT3-4 cN3 cM1b non smoker cT2-3 cN2 cM1a cur. smoker; 25 pys cT1a cN2 cM1b non smoker pT1B pN1 pM0 R0 fmr. smoker; 2 pys cT4 cN3 cM1b non smoker pT4 pN2 cM0 R1 cur. smoker; 43 pys cT4 cN3 cM1b. Smoker cT2A cN0 cM1b non smoker pT1 pN1 pM0 R0 fmr. Smoker; 25 pys cT1a cN2 cM1b non smoker pT1B pN1 pM0 R0 fmr. Smoker; 2 pys cT4 cN3 cM1b non smoker pT4 pN2 cM0 R1 cur. We describe the analysis of serial plasma DNA samples from 16 NSCLC patients under TKI therapy. We quantified prominent mutations in EGFR and KRAS genes in cell free DNA using digital PCR assays and compared these to the clinical progression data of the same patients. The aim of the study was to derive patterns of mutant plasma DNA courses over time and to evaluate the potential of this liquid biopsy approach for monitoring tumor disease and predicting therapy response
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