Research Papers:

Prognostic value of quantitative ctDNA levels in non small cell lung cancer patients

Mariano Provencio _, María Torrente, Virginia Calvo, David Pérez-Callejo, Lourdes Gutiérrez, Fernando Franco, Clara Pérez-Barrios, Miguel Barquín, Ana Royuela, Francisco García-García, Coralia Bueno, Aranzazu Garcia-Grande, Carlos Camps, Bartomeu Massuti, Eduardo Sotomayor and Atocha Romero

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Oncotarget. 2018; 9:488-494. https://doi.org/10.18632/oncotarget.22470

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Mariano Provencio1, María Torrente1, Virginia Calvo1, David Pérez-Callejo1, Lourdes Gutiérrez1, Fernando Franco1, Clara Pérez-Barrios2, Miguel Barquín2, Ana Royuela3, Francisco García-García4, Coralia Bueno5, Aranzazu Garcia-Grande6, Carlos Camps7, Bartomeu Massuti8, Eduardo Sotomayor9 and Atocha Romero1,2

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

2Liquid Biopsy Laboratory, Biomedical Sciences Research Institute Puerta de Hierro-Majadahonda University Hospital, Majadahonda, Spain

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

4Computational Genomics, Centro de Investigación Príncipe Felipe, Valencia, Spain

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

6Cytometry Unit, Biomedical Sciences Research Institute Puerta de Hierro-Majadahonda, Spain

7Medical Oncology Department, Hospital General de Valencia, CIBERONC Network, Valencia, Spain

8Medical Oncology Department, Hospital Universitario de Alicante, Alicante, Spain

9George Washington Cancer Center, Washington D.C., United States of America

Correspondence to:

Mariano Provencio, email: [email protected]

Atocha Romero, email: [email protected]

Keywords: ctDNA, non-small cell lung cancer, tyrosine kinase inhibitor, EGFR

Received: June 15, 2017     Accepted: September 30, 2017     Published: November 16, 2017


Background: Circulating tumor DNA (ctDNA) levels correlate well with tumor bulk. In this paper we aim to estimate the prognostic value of the dynamic quantification of ctDNA levels.

Materials and Methods: A total of 251 serial plasma samples from 41 non-small-cell lung cancer patients who carried an activating EGFR mutation were analysed by digital PCR. For survival analysis, ctDNA levels were computed as a time-dependent covariate.

Results: Dynamic ctDNA measurements had prognostic significance (hazard ratio for overall survival and progression free survival according to p.T790M mutant allele frequency; 2.676 and 2.71 respectively; P < 0.05). In the same way, patients with p.T790M-negative or unchanging or decreasing plasma levels of sensitizing EGFR mutation were 12 and 4.8 times more likely to maintain response or stable disease, respectively, than patients in which the opposite occurred (P < 0.05).On average, the p.T790M mutation was detected in plasma 51 days before the assessment of progression disease by CT-scan. Finally, ctDNA outperformed CTCs for assessing tumor progression (P = 0.021).

Conclusions: The appearance or increase in a unit of the p.T790M allele frequency almost triples the risk of death and progression. This information can be used to design clinical trials aiming to estimate whether T790M positive patients should start second line treatment based on molecular data rather than imaging data.

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