ROSE for Improved Molecular Marker Testing Via EBUS

Study Overview
=================
Brief Summary
-----------------
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).

Detailed Description
-----------------
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.

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

Conditions
-----------------
Non-small Cell Lung Cancer (NSCLC)

Intervention / Treatment
-----------------
* Other: ROSE (presence of cytotech)
* Other: NO-ROSE (absence of cytotech)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Inpatients or outpatients >18 years old Capable of informed consent Known or suspected non-small cell lung cancer (NSCLC) Referred to the interventional pulmonary team at Johns Hopkins Hospital (JHH), Johns Hopkins Bayview Medical Center (JHBMC), or other participating sites for tissue sampling of a hilar/mediastinal lymph node or another lesion accessible by convex-probe (CP) EBUS Exclusion Criteria: Refuse participation Standard contraindications to EBUS and bronchoscopy in general: bleeding disorders, antiplatelet or anticoagulant usage, high fraction of inspired oxygen (FiO2) requirement, and clinical instability Pregnant women Cytotechnologist not available at the time of screening, enrollment, or randomization

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Single-center non-blinded randomized controlled trial (presence or absence of trained cytotechnologist providing on-site cytopathology feedback to bronchoscopist).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: ROSE arm<br>Presence of trained cytotechnologist providing on-site cytopathology feedback to bronchoscopist | Other: ROSE (presence of cytotech)<br>* Standard of care EBUS will include presence of trained cytotechnologist providing on-site cytopathology feedback to bronchoscopist during the procedure<br>|
| Other: NO-ROSE arm<br>Absence of trained cytotechnologist providing on-site cytopathology feedback to bronchoscopist | Other: NO-ROSE (absence of cytotech)<br>* Standard of care EBUS will NOT include presence of trained cytotechnologist providing on-site cytopathology feedback to bronchoscopist during the procedure<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NGS biomarker sufficiency | percentage of NGS biomarker testing attempts that were successful due to sufficient tissue | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Molecular yield | percentage of other ancillary testing attempts such as next generation sequencing that were successful due to sufficient tissue | Baseline | 
| Number of targets | Number of targets (including lymph node stations, other lesions) sampled per EBUS | Baseline | 
| Number of passes | For the ROSE arm only: Number of passes taken from the target site | Baseline | 
| Number of secondary procedures | Number of secondary procedures performed (such as radial EBUS, navigational bronchoscopy) | Baseline | 
| Need for repeat EBUS or another procedure | 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) | Within 30 days of procedure | 
| Procedure time | Procedure time (measured in minutes) | Baseline | 
| Procedural complications | Procedural complications observed during a one-week follow up period | Within 7 days of the procedure | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Endobronchial ultrasound (EBUS), Rapid on-site evaluation (ROSE)