The characteristics of the course of the disease in lung adenocarcinoma in relation to activating mutations of the gene for epidermal growth factor receptor.

摘要

Introduction Treatment of lung adenocarcinoma is nowadays increasingly tailored to the individual patient due to new discoveries in the field of molecular biology and new targeted drugs. Among the most studied is the receptor for epidermal growth factor (EGFR), wherein the activating mutations allow the treatment with the new targeted drugs.;Aim, objectives and hypothesis The purpose of this study was to determine whether there are differences between patients with lung adenocarcinoma, harboring activating mutations in the gene for epidermal growth factor receptor and those without them. Our interest were sites of metastases at diagnosis and their occurrence during the course of the disease, type of treatment, time to disease progression and survival.;Our hypothesis was that patients with activating EGFR mutations hold a different pattern of metastatic spread already at the time of diagnosis. According to our clinical experience and previously scarce published data, we assumed that those patients have more metastases in the central nervous system (CNS) and bone. It is important for these types of metastases to be discovered early, since we have the possibility to combine several types of therapy, and use the best possible treatment.;Methods Our research was a type of observational population study, partly retrospective partly prospective. Among patients with non-small cell lung cancer, tested for activating EGFR mutations in the years 2010 and 2011, we selected patients with lung adenocarcinoma and reviewed their medical records and monitored their treatment by October 2013.;Results Among the 629 patients with lung adenocarcinoma 137 (21.8%) patients had activating EGFR mutations. More patients with EGFR mutations were women and non-smokers, there were also more patients with metastatic stage of the disease, though not statistically significant.;In those patients who developed metastases, time to development of metastases to specific organs was different according to EGFR status. Metastases to CNS (25.8 vs. 11.8 months), lung (25.9 vs. 9.9 months) and pleura (20.6 vs. 9.9 months) developed significantly later in EGFR mutated patients than in non-mutated.;Survival after the development of metastases was significantly longer for EGFR mutated patients with bone (10.8 vs. 2.9 months), lung (26.3 vs. 5.2 months) and pleural metastases (7.2 vs. 2.7 months) as compared to patients without EGFR mutations.;Median overall survival (mOS) of all patients was 16.0 months, significantly longer for EGFR-positive (32.7 months) than for EGFR negative patients (13.7 months).;Patients with sensitizing EGFR mutations (L858R substitution and exon 19 deletions) had significantly longer mOS than those harboring other type of mutations, 34.4 and 17.4 months, respectively (p = 0.05).;Patients with metastases only to one organ system, which had EGFR mutations, lived significantly longer than those without mutations (29.1 vs. 11.2 months, p < 0.001). Even patients with metastases in two or more organ systems, who had EGFR mutations lived significantly longer than those without mutations (18.7 vs. 6.1 months, p < 0.001).;Conclusions Patients with EGFR mutations had significantly more metastases in the bones and lungs already at the time of diagnosis and marginally significantly more in the CNS. During the course of the disease, patients with EGFR mutations developed more new metastases to pleura, but there was no difference between EGFR mutated and non-mutated tumors in other organs.;Patients with EGFR-mutated tumors developed metastases in the central nervous system, lungs and pleura later than wild-type patients, while no distinction based on EGFR status has been recorded for progression to other organs.;Median overall survival (mOS) of patients with EGFR mutations was significantly longer than for patients without mutations, regardless of the stage of the disease, location and number of metastases. Patients with EGFR mutations L858R and deletion 19 had longer mOS than patients with other type of mutations.;In half of the patients with lung adenocarcinoma, harboring activating EGFR mutations, we can expect metastases to bone. For patients who had not performed PET/CT as a part of diagnostic tests for the disease stage determination, therefore, in spite of the known disseminated stage, bone scintigraphy is justified already as a part of diagnostic procedures at diagnosis.;There were more EGFR mutated than non mutated patients with CNS metastases at diagnosis, and significantly more at any time during the course of the disease and the treatment. As the time to CNS disease dissemination and survival for EGFR mutated patients as compared to non-mutated is significantly longer if treated appropriately, careful diagnostic procedures for prognosis and treatment of disease is warranted in these patients. (Abstract shortened by UMI.).