Dynamic circulating tumor DNA quantificaton for the individualization of non-small-cell lung cancer patients treatment
EntityUAM. Departamento de Medicina
10.18632/oncotarget.20016Oncotarget 8.36 (2017): 60291-60298
Funded byThis study was supported by Carlos III Institute of Health, Spanish Ministry of Science and Innovation, and European Regional Development Fund (grant number: PI16/01818 and PIE14/00064), A Romero is supported by Joan Rodés fellowship (grant number: JR14/00017) and CP pre-doctoral studies are supported by Jose Luís Castaño Foundation
ProjectGobierno de España. PI16/01818; Gobierno de España. PIE14/00064
SubjectscfDNA; TKI; Personalized medicine; Lung cancer; Liquid biopsy; Medicina
Rights© 2017 Provencio et al.
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
Google Scholar:Provencio, Mariano - Torrente, María - Calvo, Virginia - Gutiérrez, Lourdes - Pérez-Callejo, David - Pérez-Barrios, Clara - Barquín, Miguel - Royuela Vicente, Ana - Rodríguez-Alfonso, Begoña - Sotelo, Miguel - Cruz-Bermúdez, Juan Luis - Mendez, Miriam - Cruz-Bermúdez, Alberto - Romero, Atocha
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Concordance between circulating tumor cells and clinical status during follow-up in anaplastic lymphoma kinase (ALK) non-small-cell lung cancer patients Provencio, Mariano; Pérez-Callejo, David; Torrente, María; Martín, Paloma; Calvo, Virginia; Gutiérrez, Lourdes; Franco, Fernando; Coronado, María José; Cruz-Bermúdez, Juan Luis; Martín Ruiz-Valdepeñas, Asunción; Cruz-Bermúdez, Alberto; Sánchez-Beato, Margarita; Romero, Atocha; García-Grande, Aránzazu
Pérez-Callejo, David; Zurutuza, Lorea; Royuela Vicente, Ana; Torrente, María; Núñez, Beatriz; Calvo, Virginia; Méndez, Miriam; Franco, Fernando; Brenes, María Auxiliadora; Sánchez, Juan Cristobal; Provencio, Mariano
KRAS p.G12C mutation occurs in 1% of EGFR-mutated advanced non-small-cell lung cancer patients progressing on a first-line treatment with a tyrosine kinase inhibitor Serna-Blasco, R.; Sánchez-Herrero, E.; Sanz-Moreno, S.; Rodriguez-Festa, A.; García-Veros, E.; Casarrubios, M.; Sierra-Rodero, B.; Laza-Briviesca, R.; Cruz-Bermúdez, A.; Mielgo-Rubio, X.; Sánchez-Hernández, A.; Uribelarrea, E. A.; Calvo de Juan, Virginia; Romero, A.; Provencio Pulla, Mariano