Prognostic value of quantitative ctDNA levels in non small cell lung cancer patients
Por:
Provencio, M, Torrente, M, Calvo, V, Perez-Callejo, D, Gutierrez, L, Franco, F, Perez-Barrios, C, Barquin, M, Royuela, A, Garcia-Garcia, F, Bueno, C, Garcia-Grande, A, Camps, C, Massuti, B, Sotomayor, E and Romero, A
Publicada:
2 ene 2018
Categoría:
Oncology
Resumen:
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.
Filiaciones:
Provencio, M:
Hosp Univ Puerta Hierro Majadahonda, Med Oncol Dept, Majadahonda, Spain
Torrente, M:
Hosp Univ Puerta Hierro Majadahonda, Med Oncol Dept, Majadahonda, Spain
Calvo, V:
Hosp Univ Puerta Hierro Majadahonda, Med Oncol Dept, Majadahonda, Spain
Perez-Callejo, D:
Hosp Univ Puerta Hierro Majadahonda, Med Oncol Dept, Majadahonda, Spain
Gutierrez, L:
Hosp Univ Puerta Hierro Majadahonda, Med Oncol Dept, Majadahonda, Spain
Franco, F:
Hosp Univ Puerta Hierro Majadahonda, Med Oncol Dept, Majadahonda, Spain
Perez-Barrios, C:
Puerta Hierro Majadahonda Univ Hosp, Biomed Sci Res Inst, Liquid Biopsy Lab, Majadahonda, Spain
Barquin, M:
Puerta Hierro Majadahonda Univ Hosp, Biomed Sci Res Inst, Liquid Biopsy Lab, Majadahonda, Spain
Royuela, A:
Puerta Hierro Majadahonda Univ Hosp, Biomed Sci Res Inst, Biost Dept, Majadahonda, Spain
:
Ctr Invest Principe Felipe, Computat Genom, Valencia, Spain
Bueno, C:
Hosp Infanta Cristina, Med Oncol Dept, Parla, Spain
Garcia-Grande, A:
Puerta Hierro Majadahonda, Biomed Sci Res Inst, Cytometry Unit, Majadahonda, Spain
Camps, C:
Hosp Gen Valencia, CIBERONC Network, Med Oncol Dept, Valencia, Spain
Massuti, B:
Hosp Univ Alicante, Med Oncol Dept, Alicante, Spain
Sotomayor, E:
George Washington Canc Ctr, Washington, DC USA
Romero, A:
Hosp Univ Puerta Hierro Majadahonda, Med Oncol Dept, Majadahonda, Spain
Puerta Hierro Majadahonda Univ Hosp, Biomed Sci Res Inst, Liquid Biopsy Lab, Majadahonda, Spain
Green Published, gold, Green Submitted
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