Estudio de mutaciones de EGFR y KRAS en ADN circulante en pacientes afectos de cáncer de pulmón de célula no pequeña

Abstract

Molecular profiling of the tumor has become a crucial procedure in the management of patients with lung cancer. Although the analysis of the tumor tissue is considered the gold standard for the molecular profiling, this approach has some limitations, such as the absence of the required amount of tissue or the inability to capture the tumor heterogeneity. The use of liquid biopsy may help to overcome these limitations._x000D_ _x000D_ In this work we analyze the ability of the liquid biopsy to detect EGFR or KRAS mutations in plasma. Using liquid biopsy, we detected EGFR mutations in 83% of cases (100% in cases with extrathoracic metastases) and in 82% of mutated KRAS cases (96% in cases with more than one metastatic location). Furthermore, our work demonstrates the ability of the analysis of the circulating mutational load dynamics to predict the response or progression well in advance. In the EGFR mutated cases, the dynamics of the mutational load allowed predicting the response in 83% of the cases and the progression in 89% with a median advance of 38 and 80 days respectively. In the cases with KRAS mutations, the radiological response and progression prediction rate was 93% and 63%, respectively, with a median lead time of 33 and 50 days. _x000D_ _x000D_ On the other hand, in both EGFR and KRAS mutated cases, progression-free survival was significantly higher in cases in which, after starting treatment, the mutations became undetectable in circulating tumor DNA. _x000D_ _x000D_ In summary, our work demonstrates, in a routine clinical practice setting, the utility of liquid biopsy for the management of patients with lung cancer.

Date of Award	28 Jan 2021
Original language	Spanish
Supervisor	David Benaiges Boix (Tutor)