ROSE for Improved Molecular Marker Testing Via EBUS (ROSE/NoROSE)

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

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).

Study Overview

• Status: Enrolling by invitation
• Conditions: Non-small Cell Lung Cancer (NSCLC)
• Intervention / Treatment: Other: ROSE (presence of cytotech) & tissue clot sample; Other: NO-ROSE (absence of cytotech) & tissue clot sample; Other: ROSE (presence of cytotech) & liquid prep; Other: NO-ROSE (absence of cytotech) & liquid prep

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.

• Study Type: Interventional
• Enrollment (Estimated): 349
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Medicine
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins Bayview Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • The Medical University of South Carolina (MUSC)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: ROSE clot arm; Presence of trained cytotechnologist providing on-site cytopathology feedback to bronchoscopist. Sample prepared as tissue clot.	Other: ROSE (presence of cytotech) & tissue clot sample; Standard of care EBUS will include presence of trained cytotechnologist providing on-site cytopathology feedback to bronchoscopist during the procedure. Sample is a tissue clot.
Other: NO-ROSE clot arm; Absence of trained cytotechnologist providing on-site cytopathology feedback to bronchoscopist. Sample prepared as tissue clot.	Other: NO-ROSE (absence of cytotech) & tissue clot sample; Standard of care EBUS will NOT include presence of trained cytotechnologist providing on-site cytopathology feedback to bronchoscopist during the procedure. Sample is a tissue clot.
Other: ROSE liquid arm; Presence of trained cytotechnologist providing on-site cytopathology feedback to bronchoscopist. Sample prepared as liquid.	Other: ROSE (presence of cytotech) & liquid prep; Standard of care EBUS will include presence of trained cytotechnologist providing on-site cytopathology feedback to bronchoscopist during the procedure. Sample is liquid.
Other: NO-ROSE liquid arm; Absence of trained cytotechnologist providing on-site cytopathology feedback to bronchoscopist. Sample prepared as	Other: NO-ROSE (absence of cytotech) & liquid prep; Standard of care EBUS will NOT include presence of trained cytotechnologist providing on-site cytopathology feedback to bronchoscopist during the procedure. Sample is liquid.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of NGS biomarker testing attempts	NGS biomarker sufficiency - percentage of NGS biomarker testing attempts that were successful due to sufficient tissue	within 60 days of procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Level of Programmed Cell Death Protein 1 (PD-1)	PD-1 sufficiency - amount of the protein "Programmed Cell Death Protein 1" (PD-1) expressed on immune cells = 500 cells/20% cellularity	within 60 days of procedure
Number of targets	Number of targets (including lymph node stations, other lesions) sampled per EBUS	During Procedure
Number of passes (ROSE arms only)	Number of passes taken from the target site	During Procedure
Number of secondary procedures	Number of secondary procedures performed (such as radial EBUS, navigational bronchoscopy)	During Procedure
Procedure time	Procedure time (measured in minutes)	During Procedure
Number of Procedural complications	Procedural complications observed during a one-week follow up period	Within 7 days of the procedure

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: AstraZeneca
• Investigators: Principal Investigator: Lonny Yarmus, DO, MBA, Johns Hopkins University

Publications and helpful links

General Publications

• Annema JT, van Meerbeeck JP, Rintoul RC, Dooms C, Deschepper E, Dekkers OM, De Leyn P, Braun J, Carroll NR, Praet M, de Ryck F, Vansteenkiste J, Vermassen F, Versteegh MI, Veselic M, Nicholson AG, Rabe KF, Tournoy KG. Mediastinoscopy vs endosonography for mediastinal nodal staging of lung cancer: a randomized trial. JAMA. 2010 Nov 24;304(20):2245-52. doi: 10.1001/jama.2010.1705.
• Varela-Lema L, Fernandez-Villar A, Ruano-Ravina A. Effectiveness and safety of endobronchial ultrasound-transbronchial needle aspiration: a systematic review. Eur Respir J. 2009 May;33(5):1156-64. doi: 10.1183/09031936.00097908.
• Anantham D, Koh MS, Ernst A. Endobronchial ultrasound. Respir Med. 2009 Oct;103(10):1406-14. doi: 10.1016/j.rmed.2009.04.010. Epub 2009 May 15.
• Silvestri GA, Gonzalez AV, Jantz MA, Margolis ML, Gould MK, Tanoue LT, Harris LJ, Detterbeck FC. Methods for staging non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013 May;143(5 Suppl):e211S-e250S. doi: 10.1378/chest.12-2355.
• Sakakibara R, Inamura K, Tambo Y, Ninomiya H, Kitazono S, Yanagitani N, Horiike A, Ohyanagi F, Matsuura Y, Nakao M, Mun M, Okumura S, Inase N, Nishio M, Motoi N, Ishikawa Y. EBUS-TBNA as a Promising Method for the Evaluation of Tumor PD-L1 Expression in Lung Cancer. Clin Lung Cancer. 2017 Sep;18(5):527-534.e1. doi: 10.1016/j.cllc.2016.12.002. Epub 2016 Dec 22.
• Oezkan F, Khan A, Zarogoulidis P, Hohenforst-Schmidt W, Theegarten D, Yasufuku K, Nakajima T, Freitag L, Darwiche K. Efficient utilization of EBUS-TBNA samples for both diagnosis and molecular analyses. Onco Targets Ther. 2014 Nov 10;7:2061-5. doi: 10.2147/OTT.S72974. eCollection 2014.
• Jurado J, Saqi A, Maxfield R, Newmark A, Lavelle M, Bacchetta M, Gorenstein L, Dovidio F, Ginsburg ME, Sonett J, Bulman W. The efficacy of EBUS-guided transbronchial needle aspiration for molecular testing in lung adenocarcinoma. Ann Thorac Surg. 2013 Oct;96(4):1196-1202. doi: 10.1016/j.athoracsur.2013.05.066. Epub 2013 Aug 21.
• Yung RC, Otell S, Illei P, Clark DP, Feller-Kopman D, Yarmus L, Askin F, Gabrielson E, Li QK. Improvement of cellularity on cell block preparations using the so-called tissue coagulum clot method during endobronchial ultrasound-guided transbronchial fine-needle aspiration. Cancer Cytopathol. 2012 Jun 25;120(3):185-95. doi: 10.1002/cncy.20199. Epub 2011 Dec 5.
• Oki M, Saka H, Kitagawa C, Kogure Y, Murata N, Adachi T, Ando M. Rapid on-site cytologic evaluation during endobronchial ultrasound-guided transbronchial needle aspiration for diagnosing lung cancer: a randomized study. Respiration. 2013;85(6):486-92. doi: 10.1159/000346987. Epub 2013 Apr 3.

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: June 22, 2021
• First Submitted That Met QC Criteria: June 22, 2021
• First Posted (Actual): June 30, 2021

Study Record Updates

• Last Update Posted (Estimated): December 17, 2025
• Last Update Submitted That Met QC Criteria: December 9, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Endobronchial ultrasound (EBUS); Rapid on-site evaluation (ROSE)
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Anti-Infective Agents; Antifungal Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Enzyme Inhibitors; Steroid Synthesis Inhibitors; Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Anti-Infective Agents, Local; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; 14-alpha Demethylase Inhibitors; Clotrimazole; Miconazole
• Other Study ID Numbers: IRB00162151

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No