RESUMO
BACKGROUND Clinical monitoring of EGFR-positive NSCLC patients is important to gauge treatment response. The current study addresses the usage of circulating tumor DNA (ctDNA) as a prognostic marker during treatment of first-generation TKIs. MATERIAL AND METHODS Serial samplings of peripheral blood from 200 EGFR-positive NSCLC patients were taken. Baseline ctDNA quantification was conducted by digital droplet PCR before TKI treatment was administered and compared to primary biopsies. Thereafter blood sampling at different treatment cycles were measured and assessed for its prognostic and predictive value. RESULTS ctDNA was successfully detected in a number of patients and overall concordance rate was 84%. Importantly, we observed a strong correlation to ctDNA increase with disease progression using radiographic scans. In addition to survival analysis, we noted patients with the largest ctDNA variations had worst outcome. A significant number of EGFR patients during treatment developed a secondary mutation T790M and this cohort had worst survival outcome as well. CONCLUSIONS Our study demonstrated a highly associative relation of ctDNA to NSCLC patients during treatment that can be utilized to gauge treatment response. CtDNA is an attractive means compared with conventional core needle biopsies and presents new methods for accurately profiling NSCLC disease progression.
Assuntos
DNA Tumoral Circulante/análise , Genes erbB-1/genética , Inibidores de Proteínas Quinases/farmacologia , Idoso , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos/genética , Receptores ErbB/genética , Feminino , Humanos , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , Análise de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: Monitoring of key markers for lung cancer detection and tracking of acquired drug resistance is critical for the management of the disease. We aim to ascertain the value of monitoring both total cell free DNA concentrations and mutant EGFR DNA content within diverse groups of individuals most vulnerable to the disease. METHODS: We proposed longitudinal monitoring of circulating DNA using digital PCR. Circulating DNA present in peripheral blood can be obtained non-invasively and provide timely disease status update. 25 heavy smokers and 50 patients undergoing TKI therapy were recruited. Peripheral blood specimens were taken at different time points and their circulating DNA were analyzed and quantified. RESULTS: Significant higher concentrations of total cell free DNA were detected when compared with healthy high-risk individuals. Levels were stable throughout the treatment cycles, which makes it potentially a useful tool for patient stratification. Concurrent mutant T790M DNA detection of lung cancer patients at baseline achieved 82 % concordance with matched tissue analysis. Samples initially negative for the T790M gene mutation that became positive during treatment were corroborated with a repeat biopsy. The results showed its usefulness for serial monitoring. CONCLUSION: Monitoring of circulating DNA addresses the need for disease detection and shows the ability to capture the dynamic changes of the disease.