Research Papers:

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

Mariano Provencio _, María Torrente, Virgina Calvo, Lourdes Gutiérrez, David Pérez-Callejo, Clara Pérez-Barrios, Miguel Barquín, Ana Royuela, Begoña Rodriguez-Alfonso, Miguel Sotelo, Juan Luis Cruz-Bermúdez, Miriam Mendez, Alberto Cruz-Bermúdez and Atocha Romero

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Oncotarget. 2017; 8:60291-60298. https://doi.org/10.18632/oncotarget.20016

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Mariano Provencio1, María Torrente1, Virgina Calvo1, Lourdes Gutiérrez1, David Pérez-Callejo1, Clara Pérez-Barrios2, Miguel Barquín2, Ana Royuela3, Begoña Rodriguez-Alfonso4, Miguel Sotelo5, Juan Luis Cruz-Bermúdez6, Miriam Mendez1, Alberto Cruz-Bermúdez1 and Atocha Romero1,2

1Medical Oncology Department, Hospital Universitario Puerta de Hierro-Majadahonda, Majadahonda, Spain

2Molecular Oncology Laboratory, Biomedical Sciences Research Institute, Hospital Universitario Puerta de Hierro-Majadahonda, Majadahonda, Spain

3Biostatistics Department, Biomedical Sciences Research Institute, Hospital Universitario Puerta de Hierro-Majadahonda, Majadahonda, Spain

4Nuclear Medicine Department, Hospital Universitario Puerta de Hierro-Majadahonda, Majadahonda, Spain

5Medical Oncology Department, Hospital Infanta Cristina, Parla, Spain

6Information Technologies Department, Hospital Universidad Politécnica de Madrid, Madrid, Spain

Correspondence to:

Mariano Provencio, email: [email protected]

Atocha Romero, email: [email protected]

Keywords: cfDNA, TKI, personalized medicine, lung cancer, liquid biopsy

Received: June 06, 2017     Accepted: July 25, 2017     Published: August 07, 2017


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.

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