Linear endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has proven useful for staging lung cancer. The objective of this thesis is to assess the usefulness of this technique not only in lung cancer staging but also as a diagnostic tool in patients with mediastinal disease, and the possibility of detecting epidermal growth factor receptor (EGFR) mutations in samples obtained through this technique in patients with lung adenocarcinoma or non small cell lung cancer (NSCLC). The safety of the technique and the decrease in the need for mediastinoscopy were also assessed. This thesis is based on three studies, which are: - Garcia-Olivé I, Monsó E, Andreo F, et al. Sensitivity of linear endobronchial ultrasonography and guided transbronchial needle aspiration for the identification of nodal metastasis in lung cancer staging. Ultrasound in Medicine and Biology 2009;35:1271-77. - Garcia-Olivé I, Valverde EX, Andreo F et al. La ultrasonografía endobronquial lineal como instrumento de diagnóstico inicial en el paciente con ocupación mediastínica. Arch Bronconeumol 2009;45:266-70. - Garcia-Olivé I, Monsó E, F Andreo F, et al. Endobronchial ultrasound-guided transbronchial needle aspiration for identifying EGFR mutations. Eur Resp J 2010;35:391-5. The aim of the first study was to determine the sensitivity of EBUS-TBNA in lung cancer staging. Short- and long-axis node diameters were measured during EBUS in patients referred for lung cancer staging and sensitivities for the identification of nodal malignancy at TBNA determined. Three hundred fifteen real-time EBUS-guided TBNA nodal sampling procedures were performed in 161 patients and in 87 of them, N2/N3 metastasis was confirmed (50.9%), eliminating the need for mediastinoscopy. The median (interquartile range [IQR]) short-axis diameters of the sampled mediastinal and lobar nodes were 11 (8–15) and 8 (7–12) mm, respectively. TBNA provided satisfactory samples from 269 nodes (85.4%) and a sensitivity of 100% for the identification of malignant TBNA samples was reached for a short-axis diameter cut-off of 5mmand a short- to long-axis ratio of 0.5. The probability of malignancy was over 90% for nodes with a short-axis diameter .20 mm and 55% for round nodes (short- to long-axis ratio of 1). In 18 out of 50 patients with a normal mediastinal computed tomography (CT) scan, EBUS identified enlarged nodes in the mediastinum (36%), mainly in the subcarinal region and confirmed mediastinal malignancy in 5 (10%). Real-time EBUS-guided TBNA obtains satisfactory node samples in almost 90% of cases and improves the identification of enlarged nodes in patients with a normal mediastinum at CT. If sampling all nodes with a short-axis diameter of >5 mm and a short- to long-axis ratio >0.5, a sensitivity of 100% for the cytological identification of malignant nodes can be expected. The aim of the second study was to assess the usefulness of this diagnostic tool in patients with indications of mediastinal disease that could not be diagnosed by non invasive methods or white light bronchoscopy. All patients undergoing linear EBUS for the diagnosis of mediastinal masses and/or adenopathy at our endoscopy unit were included in the study. Diagnoses obtained by linear EBUS or any surgical technique performed alter a non diagnostic EBUS were considered as final. In the study population of 128 patients with a mean (SD) age of 62.0 (11.2) years, a total of 294 TBNAs were performed on 12 masses and 282 nodes. Satisfactory samples were obtained in 11cases (91.7%) from masses and in 233 cases (82.6%) from nodes. Linear EBUS was diagnostic, obviating the need for mediastinoscopy in 115 patients (diagnostic sensitivity, 89.8%). The technique confirmed the diagnosis in 85 of the 94 patients with cancer (90.4%), in 8 of the 10 patients with tuberculosis (80.0%), and in the 5 patients with sarcoidosis. The usefulness EBUS for the detection of EGFR mutations in cells recovered from malignant mediastinal nodes in patients with NSCLC was assessed in the third article. All patients with lung adenocarcinoma or NSCLC referred for staging with EBUS were included. Nodes with a short-axis diameter of 5 mm were sampled, and genomic DNA from metastatic tumour cells was obtained for analysis of exons 19 and 21. The impact of sampling on management was assessed. EGFR gene analysis of the EBUS-TBNA sample was feasible in 26 (72.2%) out of the 36 patients with lymph node metastasis. Somatic mutations of the EGFR gene were detected in tissue obtained through EBUS-TBNA in two (10%) out of 20 patients with metastasic lung adenocarcinoma, eliminating the need for mediastinoscopy in these patients. Malignant tissue samples obtained by EBUS-TBNA from patients with nodal metastasis of NSCLC are suitable for the detection of EGFR mutations in most cases, and this technique demonstrates mutated neoplastic cells in a tenth of patients with adenocarcinoma. No complications related to the procedure developed during its performance or in the following 48 hours in any of the patients included in any of the three studies. To conclude, EBUS-TBNA has shown to be useful and safe in detecting metastatic mediastinal and/or hilar lymph nodes in patients with lung cancer, even in those with radiologically normal mediastinum. It can also be useful as a diagnostic tool in other mediastinal diseases. It is possible to detect EGFR gene mutations in samples obtained with this technique from patients with NSCLC.
|Date of Award||14 Oct 2010|
|Supervisor||Eduard Monso Molas (Director) & Juan Ruiz Manzano (Director)|