Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Multiple Pulmonary Nodules

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

The bronchovideoscope will be used together with an assisted image-guided bronchoscopic navigation software system called LungPoint®, to view lungs in a real time 3D manner.

Olympus Ultrathin Bronchofibervideoscope (XP260F)

Pyng Lee, MD

The study aims to determine if there are defining EBUS and confocal endoscopy features as well as exhaled alveolar gas VOC that can discriminate malignant pulmonary nodules or masses from benign etiology, thereby obviating unnecessary thoracotomy. Directly sampled alveolar gas VOC from patients with lung cancer will be compared against exhaled breath VOC for signature compounds that may complement CT in screening the population at risk.

AIMS

1. To improve diagnostic yield of pulmonary nodule or mass by using combined approach of navigation bronchoscopy and EBUS.
2. To determine if characteristic features of EBUS and confocal microendoscopy exist as well as VOC patterns in alveolar and exhaled gas that can aid in discriminating malignant pulmonary nodule or mass from benign etiology by correlating with pathology.
3. To identify VOC patterns specific for lung cancer by correlating VOC from directly sampled alveolar gas and exhaled breath with pathology. Exhaled breath VOC signature may complement CT in screening population at risk.

Evaluating the Pulmonary Nodule With Imaging and Biomarkers

National University Hospital, Singapore

Digestive System Diseases

Rare Diseases

Esophageal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

Minimally Invasive Echo-Endoscopic Lymph Node Evaluation and Biopsy

Endoscopic Ultrasound (EUS)

Minimally Invasive Echo-Bronchoscopic Lymph Node Evaluation and Biopsy

Endobronchial Ultrasound (EBUS)

Moishe Liberman, MD, PhD

The purpose of this study is determine if performing endobronchial ultrasound (EBUS) in addition to standard endoscopic ultrasound (EUS) can increase the precision and accuracy of staging esophageal cancer in comparison to EUS alone. The expectation is that EBUS can be used to biopsy lymph nodes that: (1) because of their position in the mediastinum would be inaccessible to EUS, or (2) would be inaccessible due to their position behind the esophageal tumor.

1. Problem:

   Endoscopic ultrasound techniques are becoming more and more popular. The safety of these technologies has been demonstrated on multiple occasions. These minimally invasive trans-luminal techniques do not require general anesthesia and can be performed, rapidly, accurately and at low cost. Endobronchial ultrasound (EBUS) has been used by pulmonologists and thoracic surgeons primarily for the staging, diagnosis and management of lung cancer. Its efficacy and safety has been demonstrated in multiple studies.

   EBUS is not currently utilized by most centers in the staging of esophageal cancer. To date, no study has explored the possible use of EBUS for peritumoral lymph node biopsy, nor for biopsy of any suspicious mediastinal lymph nodes, not accessible by EUS. At Notre Dame Hospital, Centre Hospitalier de L'Universite de Montreal, all patients diagnosed with esophageal cancer undergo complete EUS staging followed by EBUS during the same procedure, in order to examine all the lymph nodes near or far from the primary tumor amenable to EBUS guided trans-bronchial biopsy. This is important because it allows physicians to bypass the primary tumor and pass through the normal (non-cancerous) bronchial wall, eliminating any chances of tumoral contamination of the sample. In addition, this also provides a much more complete mediastinal staging as it allows biopsy of a population of lymph nodes non-accessible to EUS biopsy. Thus far, we have performed EBUS in six patients with esophageal cancer with upstaging of the N stage of the tumor in two of these patients (33%). There have been no morbidities and all patients have been discharged home on the day of the procedure. EBUS was therefore able to change the treatment strategy, without adding any morbidity, discomfort or additional procedural time for two out of six patients.

   The proposed project will be the first study ever to evaluate the impact of EBUS on esophageal cancer staging as well as on the choice of therapy. This study consists of a prospective cohort study with no placebo group, all patients will have EBUS and stages obtained with and without EBUS will be compared as well as changes to the treatment plan based on EBUS staging.
2. Objectives:

   * Examine the impact of adding EBUS to the gold standard work-up on esophageal cancer staging.
   * Examine the impact of adding EBUS to the gold standard work-up on the treatment plan for patients newly diagnosed with esophageal cancer.
3. Methodology:

   The study consists of a prospective cohort study. Each patient will serve as his/her own control. All patients currently undergoing esophageal cancer staging in the Division of Thoracic Surgery at the CHUM will be approached for enrolment into the study.

   EUS followed by EBUS will be performed during the EUS staging procedure. The order of procedures for all patients is as follows: (1) Flexible Esophagoscopy with endoluminal biopsy, (2) Radial EUS for T staging (3) Linear EUS for lymph node biopsy and N staging, (4) Flexible Bronchoscopy for evaluation of the left mainstem bronchus for tumor invasion, (5) Linear EBUS for trans-tracheal and trans-bronchial lymph node biopsy.

   All FNA samples will be evaluated using standard methods by cytopathologists at the CHUM. Results will be evaluated for: (A) positivity, (B) negativity (no tumor cells, positive lymphocytes), (C) inadequacy (no tumor cells, no lymphocytes). A minimum of two passes will be performed into each lymph node.

   Patients will be discharged on the same day, as their procedure. Results will be discussed with them in a follow-up clinic appointment with their thoracic surgeon within 3 weeks of the procedure. Any procedure-related morbidity will be documented in the post-procedural period as well as at their follow-up appointment.
4. Expected Results:

We believe that by adding EBUS to the gold standard work up and staging of esophageal cancer, we can make a significant difference in esophageal cancer staging. This may also significantly change the choice of therapy.

Endobronchial Ultrasound (EBUS) for Nodal Staging in Esophageal Cancer

C.E.T.O.C. - CHUM Endoscopic Tracheobronchial and Oesophageal Center

Marcel and Rolande Gosselin Chair in Thoracic Surgical Oncology

Fonds de la Recherche en Santé du Québec

Centre de Recherche du Centre Hospitalier de l'Université de Montréal

Centre hospitalier de l'Université de Montréal (CHUM)

Carcinoma, Non-Small-Cell Lung

Routine gene testing of EGFR, ROS1 and ALK will be performed on those diagnosed with nonsquamous NSCLC.

Routine gene testing was performed in those diagnosed with nonsquamous NSCLC. NGS will be performed on these that have adequate rest tissues.

For those diagnosed with nonsquamous NSCLC, routine gene testing including EGFR, ROS1 and ALK will be performed.

Routine gene testing

For those diagnosed with nonsquamous NSCLC and have done routine gene testing, NGS will be perform on those that have adequate rest tissues.

Next-generation sequencing

Jiayuan Sun, MD,PhD

The objective of the study was to compare the value of routine gene testing and next-generation sequencing (NGS) in detecting gene mutations of small specimens obtained by endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) and get the knowledge of how many EBUS-TBNA samples were adequate for NGS.

Some gene mutations can direct individualized treatment. The routine gene testing of EGFR, ROS1 and ALK is direct sequencing, Reverse transcription quantitative real-time polymerase chain reaction (RT-QPCR) and fluorescent in situ hybridization (FISH) or immunohistochemistry (IHC). Next-generation sequencing (NGS) is a new technique, which is more sensitive than routine techniques. So we decided to compare the value of gene testing between routine method and NGS in EBUS-TBNA specimens and get the knowledge of how many EBUS-TBNA samples were adequate for NGS.

The study was designed as a prospective and single center study. Seventy patients will be enrolled into the study and the clinical data of the patients, including his smoke history, cancer history, occupation exposure and so on, will be collected and recorded in a case report form. For the patients recruited in the study, the lymph nodes suspected to be malignant will be obtained by EBUS-TBNA. Samples will be sent to Pathology Department of Shanghai Chest Hospital and will be processed with paraffin-embedded, and for those diagnosed with nonsquamous NSCLC, routine gene testing of EGFR, ROS1 and ALK will be performed. And the rest tissues will be extracted with DNA and performed gene mutations using NGS for these qualified DNA samples.

Mutation Detection of EBUS-TBNA Specimens Using NGS

Mutation Detection of Small Specimens Obtained by Endobronchial Ultrasound Transbronchial Needle Aspiration in Advanced Nonsquamous Non-small Cell Lung Cancer Using Next-generation Sequencing

Jiayuan Sun

Director, Endoscope Department, Shanghai Chest Hospital

Carcinoma

Carcinoma, Bronchogenic

Bronchial Neoplasms

Minimally invasive technique to stage lung cancers

Endobronchial ultrasound (EBUS)

Traditional surgical method to stage lung cancers

Mediastinoscopy

Sang-Won Um, MD

Accurate staging of the mediastinum is essential to evaluate prognosis in non-small cell lung cancer and to devise an appropriate treatment plan. Mediastinal staging by surgical techniques (mainly cervical mediastinoscopy) is considered to be the gold standard, although surgical staging is invasive, requires general anesthesia, and is subject to potential serious complications. Endobronchial ultrasound (EBUS)-transbronchial needle aspiration (TBNA) is a new modality for the evaluation of mediastinal and hilar lymph node metastasis from lung cancer. Compared to other diagnostic methods, EBUS-TBNA is a real-time procedure that enables multiple biopsies with high-quality histologic cores under local anesthesia. However, there have been few data on the head-to-head comparisons of mediastinoscopy and EBUS-TBNA. The aim of this prospective study is to determine the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of EBUS-TBNA and mediastinoscopy in identifying N2 and N3 lymph node for patients with non-small cell lung cancer.

Endobronchial Ultrasound- Transbronchial Needle Aspiration (EBUS-TBNA) Versus Mediastinoscopy for Mediastinal Lymph Node Staging of Non-small Cell Lung Cancer (NSCLC)

A Prospective Trial of Endobronchial Ultrasound- Transbronchial Needle Aspiration Compared to Mediastinoscopy for Mediastinal Lymph Node Staging of Non-small Cell Lung Cancer

Samsung Medical Center

Assistant Professor

Presence of trained cytotechnologist providing on-site cytopathology feedback to bronchoscopist

Absence of trained cytotechnologist providing on-site cytopathology feedback to bronchoscopist

Standard of care EBUS will include presence of trained cytotechnologist providing on-site cytopathology feedback to bronchoscopist during the procedure

ROSE (presence of cytotech)

Standard of care EBUS will NOT include presence of trained cytotechnologist providing on-site cytopathology feedback to bronchoscopist during the procedure

NO-ROSE (absence of cytotech)

Lonny Yarmus, DO, MBA

This research study is being done to compare two ways to conduct bronchoscopic biopsy of lymph nodes and other structures in the chest (i.e. the presence or absence of an on-site cytotechnologist performing a limited microscopic evaluation to provide non-binding feedback on specimen adequacy in real time during the procedure).

Endobronchial ultrasound (EBUS) is a highly safe and effective bronchoscopic procedure that can achieve diagnostic yields of over 90% for lung cancer - similar to those with the more-invasive surgical mediastinoscopy - with EBUS enjoying the advantage of a near 0% complication rate in several large studies. This has led to EBUS becoming the procedure of choice for mediastinal staging of lung cancer. Increasingly, bronchoscopists are being asked to perform EBUS not only for lung cancer staging but also for tissue acquisition for molecular markers to assess for mutations that can be treated with biologic therapy. However, a frequently encountered clinical scenario is that while an EBUS is diagnostic for lung cancer, it is non-diagnostic for molecular testing because of an insufficient amount of tissue material being collected. According to multiple studies, the "molecular yield" for EBUS in lung cancer can range from 74-82%. These studies have not specifically looked at adequacy of biomarkers, which could be distinctly different considering that evaluation of biomarkers requires more tissue for next generation sequencing (NGS). Currently, Johns Hopkins Hospital uses NGS as standard of care for identifying mutations associated with malignant cells. NGS analysis, which is usually reported as a percentage of cells that express one of many biomarkers currently being tested as standard of care, is performed via immunohistochemistry (IHC), necessitating the presence of a sufficiently cellular material with \>100 tumor cells for reliable quantitative characterization. To the investigator's knowledge, the rates of NGS biomarker sufficiency have not been prospectively analyzed to date.

Rapid on-site evaluation (ROSE) is an optional step during EBUS bronchoscopy in which an on-site cytotechnologist performs a limited microscopic evaluation to provide non-binding feedback on specimen adequacy in real time during the procedure. The cytotechnologist can also aid specimen processing e.g. through creation of a "tissue clot" in addition to use of the more standard liquid-based medium. At Johns Hopkins, EBUS procedures are routinely performed both with and without ROSE since the presence or absence of ROSE during EBUS has not been shown to impact diagnostic yield or procedural safety. However, its impact on NGS biomarker sufficiency has not been tested to the investigator's knowledge.

This study aims to investigate whether ROSE can impact NGS biomarker sufficiency by assisting the bronchoscopist in obtaining adequate tissue from the appropriate site. The hypothesis is that ROSE will decrease the rate of insufficient tumor tissue to permit NGS biomarker testing.

Single-center non-blinded randomized controlled trial (presence or absence of trained cytotechnologist providing on-site cytopathology feedback to bronchoscopist).

blinding not possible given nature of intervention

ROSE for Improved Molecular Marker Testing Via EBUS

Rapid Onsite Cytopathologic Evaluation for Improved Molecular Marker Testing Via Endobronchial Ultrasound Bronchoscopy - A Randomized Controlled Trial

percentage of NGS biomarker testing attempts that were successful due to sufficient tissue

percentage of other ancillary testing attempts such as next generation sequencing that were successful due to sufficient tissue

Number of targets (including lymph node stations, other lesions) sampled per EBUS

For the ROSE arm only: Number of passes taken from the target site

Number of secondary procedures performed (such as radial EBUS, navigational bronchoscopy)

Need for repeat EBUS or another procedure due to non-diagnostic or insufficient sample during a 30-day follow up period (binary value: yes/no)

Procedural complications observed during a one-week follow up period

AstraZeneca

Johns Hopkins University

Cervical Mediastinoscopy

The gold standard techniques to assess the extent of disease and decide on therapy for patients with lung cancer consists of cervical mediastinoscopy, which is a surgical procedure which entails an incision in the neck and the removal of lymph nodes from around the airway. Endobronchial ultrasound (EBUS) and endoscopic ultrasound (EUS) are new, non-surgical techniques that have been available for the past several years and are proving invaluable in lung cancer evaluation. These techniques are minimally invasive and can be performed without surgery.

To date, there have been no head-to-head studies on the same group of patients using both the old and new techniques. The study will consist of a study which compares traditional staging techniques in lung cancer patients to new, less invasive techniques.

The significance of the proposed project is tremendous. If the new strategies prove to be equivalent (or superior) to traditional techniques, these techniques will be considered the new gold-standard tests. This will change the way lung cancer is evaluated. An equivalent or superior result will also significantly impact on patient care, cost and morbidity due to the speed, convenience and lack of operating room requirement as well as the lack of general anesthesia.

1. Problem:

   The gold standard techniques to stage and diagnose the mediastinum in patients with lung cancer consist of cervical mediastinoscopy (CM). CT, PET and PET-CT scans have improved the radiological staging of the mediastinum; however these techniques are unable to provide a tissue diagnosis and are inaccurate. Endobronchial ultrasound (EBUS) and endoscopic ultrasound (EUS) have been available for the past few years and are proving invaluable in the diagnosis and staging of the mediastinum. These techniques rely on imaging of mediastinal lymph nodes (LN) through the airway (EBUS) and the esophagus (EUS) using miniaturized ultrasound probes mounted on the tip of flexible bronchoscopes (EBUS) and esophagoscopes (EUS). Once a LN is visualized and identified using either of these techniques, a needle is passed through the airway (EBUS) or esophageal (EUS) wall into the LN and biopsies are performed. These minimally invasive trans-luminal techniques do not require general anesthesia and can be performed safely, rapidly, accurately and at low cost.

   Due to the cost, inconvenience and risks associated with traditional surgical mediastinal diagnosis and staging, many physicians are foregoing tissue diagnosis of the mediastinum, resulting in incomplete pre-operative staging for patients. The endoscopic techniques are quickly replacing traditional techniques in some centers; however, when replacing a gold standard test with a new modality, one must first prove equivalence in safety and efficacy. Until such a study is completed, we do not have compelling data to be able to offer these techniques as equivalent alternatives to patients. The proposed project will be the first head-to-head comparison of both endobronchial (EBUS) and endoscopic ultrasound (EUS) in addition to transluminal biopsy with gold standard invasive surgical staging techniques in the diagnosis and staging of NSCLC.
2. Objectives:

   * Define and compare the sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratio and accuracies between traditional and minimally invasive mediastinal diagnostic and staging techniques for lung cancer.
   * Compare morbidity, convenience, cost and efficiencies between traditional and minimally invasive diagnostic strategies.
   * Examine the impact on decisions regarding changes in treatment plans (neoadjuvant chemoradiotherapy, prevention of thoracotomy) based on minimally invasive mediastinal staging compared to conventional staging strategies.
3. Methodology:

   The study design consists of a prospective comparison of diagnostic test findings on a consecutive case series with each subject serving as his or her own control. In order to do this, we will enroll N subjects (N=166), and will subject each of the subjects to K procedures (K=3). One of those procedures, the "traditional" one (K-1), is considered to be the gold standard for comparison. We will compare the diagnostic findings from the K-2 and K-3 alternative procedures (EBUS and EUS, respectively) with the gold standard across the N subjects. We will compare them singly and in combination with the gold standard. All patients with a new or suspected diagnosis of lung cancer will be prospectively enrolled in the study. All patients will undergo standard mediastinal staging, EBUS and EUS in the operating room, during one procedure. Patients will be included in the study if they meet one of the following criteria: (A) Lung lesion with mediastinal lymphadenopathy and/or positive PET scan in the mediastinum, (B) Lung lesion without mediastinal lymphadenopathy or positive PET scan in the mediastinum. Sample size has been calculated to be 166 patients.

   Results of traditional staging techniques will be considered as the "gold standard" tests for mediastinal diagnosis and staging. These tests will be used as the standard to which other modalities and combinations of modalities are compared. Data will be collected and analyzed as a whole (all patients with mediastinal LN sampling) and separately based on pre-biopsy diagnosis, post-biopsy diagnosis, mediastinal LN size (CT scan), LN station and PET avidity. Sensitivity, specificity, positive and negative predictive values, likelihood ratios and accuracies will be calculated and used to compare EUS and EBUS (transluminal strategy) to traditional staging, EUS to EBUS, EUS to traditional staging and EBUS to traditional staging. Subanalysis based on pre-biopsy patient and imaging (CT and PET) characteristics as well as ultrasound imaging characteristics during biopsy will be used to develop predictive models for minimally invasive mediastinal diagnosis, in order to better define patients at increased or decreased likelihood of successful diagnosis using these techniques. ROC curves will be constructed and used to discriminate results between diagnostic tests.

   The primary focus of this project and the hypothesis for which the sample size calculations were designed around is whether or not minimally invasive trans-luminal mediastinal LN biopsy is as accurate as traditional "gold standard" techniques in the diagnosis and staging of the mediastinum. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy will be calculated for both strategies (minimally invasive and traditional) and compared. Receiver operating curves will be used to compare the two strategies at differing sensitivity and 1-specificity values. Relative operating characteristic curves will be used to compare the two strategies at different true positive and false positive rates. The study is estimated to be completed in three years. Sample size calculation has determined that 166 patients are required for the study. The thoracic surgery division at the CHUM estimates that accrual will be approximately 1.5 patients per week (6 patients/month).
4. Expected Results:

We expect to find that minimally invasive mediastinal LN staging and diagnosis is not only equivalent in terms of accuracy to traditional staging strategies, but is actually superior. This superiority is possible, secondary to the additional LN basins accessible via these techniques.

Minimally Invasive, Diagnosis and Staging of Lung Cancer

Minimally Invasive, Trans-Luminal Diagnosis and Staging of Lung Cancer: A Prospective Head-to-Head Comparison With Traditional Gold Standard Diagnostic Techniques

Define and compare the sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratio and accuriacies between traditional and minimally invasive mediastinal diagnostic and staging techniques for lung cancer.

Compare morbidity, convenience, cost and efficiencies between traditional and minimally invasive diagnostic strategies.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Evaluating the Pulmonary Nodule With Imaging and Biomarkers	NCT01739881	Lung Cancer	Olympus Ultrath...	21 Years -	National University Hospital, Singapore
Endobronchial Ultrasound (EBUS) for Nodal Staging in Esophageal Cancer	NCT01038544	Esophageal Canc...	Endoscopic Ultr... Endobronchial U...	18 Years -	Centre hospitalier de l'Université de Montréal (CHUM)
Mutation Detection of EBUS-TBNA Specimens Using NGS	NCT02420405	Lung Cancer	Routine gene te... Next-generation...	18 Years - 80 Years	Shanghai Chest Hospital
Endobronchial Ultrasound- Transbronchial Needle Aspiration (EBUS-TBNA) Versus Mediastinoscopy for Mediastinal Lymph Node Staging of Non-small Cell Lung Cancer (NSCLC)	NCT01079520	Carcinoma, Non-...	Endobronchial u... Mediastinoscopy	18 Years -	Samsung Medical Center
ROSE for Improved Molecular Marker Testing Via EBUS	NCT04945317	Non-small Cell ...	ROSE (presence ... NO-ROSE (absenc...	18 Years -	Johns Hopkins University
Evaluating the Pulmonary Nodule With Imaging and Biomarkers	NCT01739881	Lung Cancer	Olympus Ultrath...	21 Years -	National University Hospital, Singapore
Endobronchial Ultrasound (EBUS) for Nodal Staging in Esophageal Cancer	NCT01038544	Esophageal Canc...	Endoscopic Ultr... Endobronchial U...	18 Years -	Centre hospitalier de l'Université de Montréal (CHUM)
Minimally Invasive, Diagnosis and Staging of Lung Cancer	NCT01011595	Lung Cancer	Cervical Medias... Endobronchial U... Endoscopic Ultr...	18 Years -	Centre hospitalier de l'Université de Montréal (CHUM)
Minimally Invasive, Diagnosis and Staging of Lung Cancer	NCT01011595	Lung Cancer	Cervical Medias... Endobronchial U... Endoscopic Ultr...	18 Years -	Centre hospitalier de l'Université de Montréal (CHUM)

Spots Global Cancer Trial Database for endobronchial ultrasound (ebus)