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

2017; Impact Journals LLC; Volume: 8; Issue: 36 Linguagem: Inglês

10.18632/oncotarget.20016

1949-2553

Mariano Provencio, María Torrente, V. Blázquez Calvo, Lourdes Gutiérrez, David Pérez-Callejo, Clara Pérez-Barrios, Miguel Barquín, Ana Royuela, B. Rodríguez Alfonso, Miguel J. Sotelo, Juan Luis Cruz Bermúdez, Míriam Méndez, Alberto Cruz‐Bermúdez, Atocha Romero,

Cancer Cells and Metastasis

// Mariano Provencio 1 , María Torrente 1 , Virgina Calvo 1 , Lourdes Gutiérrez 1 , David Pérez-Callejo 1 , Clara Pérez-Barrios 2 , Miguel Barquín 2 , Ana Royuela 3 , Begoña Rodriguez-Alfonso 4 , Miguel Sotelo 5 , Juan Luis Cruz-Bermúdez 6 , Miriam Mendez 1 , Alberto Cruz-Bermúdez 1 and Atocha Romero 1, 2 1 Medical Oncology Department, Hospital Universitario Puerta de Hierro-Majadahonda, Majadahonda, Spain 2 Molecular Oncology Laboratory, Biomedical Sciences Research Institute, Hospital Universitario Puerta de Hierro-Majadahonda, Majadahonda, Spain 3 Biostatistics Department, Biomedical Sciences Research Institute, Hospital Universitario Puerta de Hierro-Majadahonda, Majadahonda, Spain 4 Nuclear Medicine Department, Hospital Universitario Puerta de Hierro-Majadahonda, Majadahonda, Spain 5 Medical Oncology Department, Hospital Infanta Cristina, Parla, Spain 6 Information Technologies Department, Hospital Universidad Politécnica de Madrid, Madrid, Spain Correspondence to: Mariano Provencio, email: mariano.provencio@salud.madrid.org Atocha Romero, email: atocha10@hotmail.com Keywords: cfDNA, TKI, personalized medicine, lung cancer, liquid biopsy Received: June 06, 2017 Accepted: July 25, 2017 Published: August 07, 2017 ABSTRACT 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-small-cell 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.