Dynamic circulating tumor DNA quantificaton for the individualization of non-small-cell lung cancer patients treatment

Background: Liquid biopsy has evolved from being a promising line to becoming a validated approach for biomarker testing. However, its utility for individualization of therapy has been scarcely reported. In this study, we show how monitoring levels of EGFR mutation in plasma can be useful for the in...

Descripción completa

Detalles Bibliográficos
Autores: Provencio Pulla, Mariano, Torrente, María, Calvo de Juan, Virginia, Gutiérrez, Lourdes, Pérez-Callejo, David, Pérez-Barrios, Clara, Barquín, Miguel, Royuela Vicente, Ana, Rodríguez-Alfonso, Begoña, Sotelo, Miguel, Cruz-Bermúdez, Juan Luis, Méndez, Miriam, Cruz-Bermúdez, Alberto, Romero, Atocha
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/681155
Acceso en línea:http://hdl.handle.net/10486/681155
https://dx.doi.org/10.18632/oncotarget.20016
Access Level:acceso abierto
Palabra clave:cfDNA
TKI
Personalized medicine
Lung cancer
Liquid biopsy
Medicina
Descripción
Sumario:Background: Liquid biopsy has evolved from being a promising line to becoming a validated approach for biomarker testing. However, its utility for individualization of therapy has been scarcely reported. In this study, we show how monitoring levels of EGFR mutation in plasma can be useful for the individualization of treatment. Results: Longitudinal EGFR mutation levels in plasma always correlated with tumor response ascertained by RECIST criteria. Moreover, decreasing EGFR mutation levels were detected in all patients benefiting from locoregional radiotherapy, whereas the opposite occurred when a patient progressed soon after radiotherapy treatment. Similarly, increasing EGFR mutation levels anticipated disease progression after TKI dose reduction, discontinuation of treatment, or reduced bioavailability due to drug interactions. In addition, EGFR mutation levels were useful to monitor treatment outcome of new therapies and constituted a decisive factor when the clinical situation of the patient did not correlate with responses ascertained by radiologist. Finally, our results indicate that cancer associated body fluids (pleural, pericardial or cerebrospinal fluid) are certainly a suitable source for biomarker testing that can extend EGFR mutation detection to biofluids other than blood. Materials and Methods: A total of 180 serial plasma samples from 18 non-smallcell lung cancer patients who carried an activating EGFR mutation were investigated by digital PCR. Conclusions: Monitoring levels of EGFR mutation in plasma allows resolving doubts that frequently arise in daily clinical practice and constitutes a major step towards achieving personalized medicine