The Canada Lymph Node Score Project: A Crossover Trial

NCT ID: NCT04342377

Last Updated: 2022-07-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-30
• Study Completion Date: 2022-06-30

Brief Summary

Before deciding on treatment for patients with lung cancer, a critical step in the investigation is finding out whether the lymph nodes in the chest contain cancer cells. This is accomplished with a biopsy of the lymph nodes through the airway wall, known as Endobronchial Ultrasound-guided Transbronchial Needle Aspiration. Guidelines require that every single lymph node in the chest be biopsied through a process called Systematic Sampling. However, emerging data suggests that the lymph nodes that appear benign on imaging and ultrasound do not need a biopsy. A proposed alternative to the inefficient Systematic Sampling is the simplified Selective Targeted Sampling of the lymph nodes, whereby only lymph nodes that look malignant are biopsied. This trial will evaluate the simplified Selective Targeted Sampling of lymph nodes and compare it to Systematic Sampling to see whether it is equally as effective in staging lung cancer.

Detailed Description

Treatment decisions in Non-Small Lung Cancer (NSCLC) are reliant on a thorough staging process that includes imaging with Computed Tomography (CT), Positron Emission Tomography (PET) and Systematic Sampling (SS) of mediastinal lymph nodes (LNs) by Endobronchial Ultrasound Transbronchial Needle Aspiration (EBUS-TBNA). Collectively, the results of these staging procedures dictate whether patients will be treated with surgery, radiation and/or chemotherapy. Current guidelines for SS through EBUS-TBNA mandate the biopsy of at least 3 mediastinal LN stations (4R, 4L and 7) in the chest, even if they appear normal on CT and PET scan. Despite improvements in diagnostic techniques and safety, LN biopsies remain onerous for the patient and costly to our healthcare system. SS is also unreliable, yielding inconclusive pathology results in 42.14% of cases, especially for Triple Normal LNs, which are LNs that appear normal on PET, and CT, and EBUS. In fact, SS results in mostly negative or inconclusive biopsies for Triple Normal LNs, which may be due in part to their very low probability (< 6%) of malignancy. As such, the researchers have proposed to replace the onerous and unreliable process of SS by a simpler Selective Targeted Sampling (STS) staging process. In STS, Triple Normal LNs will not be biopsied, due to the very high negative predictive value (NPV) of malignancy. STS follows the simple notion that only LNs that have the potential to be malignant should be biopsied, whereas LNs which are very likely benign (i.e. Triple Normal LNs) should not be biopsied.

Conditions

Lung Cancer; Non Small Cell Lung Cancer; Non-small Cell Lung Cancer Stage I; Non-small Cell Lung Cancer Stage II

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Selective Targeted Sampling

During patients' Endobronchial Ultrasound (EBUS) procedure, they will first undergo:

Selective Targeted Sampling - endosonographic assessment of at least 3 mediastinal lymph node stations (4R, 4L, and 7) using the four criteria of the Canada Lymph Node Score (predictor of nodal disease during Endobronchial Ultrasound). Each lymph node will be assigned a CLNS ranging from 0 to 4. Triple Normal lymph nodes will be defined as those that appear normal on CT (diameter < 1 cm), AND normal on PET (SUV < 2.5), AND normal on EBUS (CLNS < 2). Lymph nodes that are found to be Triple Normal will be marked as "Not for Biopsy", whereas all other lymph nodes will be biopsied.

Group Type: EXPERIMENTAL

Selective Targeted Sampling

Intervention Type: DIAGNOSTIC_TEST

Mediastinal lymph nodes are assessed with the CLNS, and only those appearing malignant with the score are biopsied. Triple Normal lymph nodes (normal appearing on PET, CT and EBUS) are not biopsied.

Systematic Sampling

Upon completion of Systematic Targeted Sampling, all patients will crossover and receive the standard of care:

Systematic Sampling - all lymph nodes previously marked as "Not for Biopsy" will be biopsied.

At the conclusion of the EBUS procedure, all nodal stations would have been sampled as is mandated by current guidelines.

Group Type: ACTIVE_COMPARATOR

Systematic Sampling

Intervention Type: DIAGNOSTIC_TEST

All examined mediastinal lymph nodes are biopsied, regardless of whether they appear normal during PET, CT and EBUS.

Interventions

Selective Targeted Sampling

Mediastinal lymph nodes are assessed with the CLNS, and only those appearing malignant with the score are biopsied. Triple Normal lymph nodes (normal appearing on PET, CT and EBUS) are not biopsied.

Intervention Type: DIAGNOSTIC_TEST

Systematic Sampling

All examined mediastinal lymph nodes are biopsied, regardless of whether they appear normal during PET, CT and EBUS.

Intervention Type: DIAGNOSTIC_TEST

Other Intervention Names

STS; SS

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18 years
• Both CT and PET scans completed prior to EBUS
• Suspected or confirmed NSCLC requiring mediastinal staging
• cN0-cN1 as indicated by CT and PET scans

Exclusion Criteria

• Patients with cN0 disease AND peripheral tumors AND tumor < 2 cm in diameter, as they do not require mediastinal staging
• Evidence of cN2 disease or higher on CT and PET scans

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Health Sciences Centre, Winnipeg, Manitoba

OTHER

Sponsor Role: collaborator

Royal Alexandra Hospital

OTHER

Sponsor Role: collaborator

Toronto General Hospital

OTHER

Sponsor Role: collaborator

Centre hospitalier de l'Université de Montréal (CHUM)

OTHER

Sponsor Role: collaborator

McGill University Health Centre/Research Institute of the McGill University Health Centre

OTHER

Sponsor Role: collaborator

St. Joseph's Healthcare Hamilton

OTHER

Sponsor Role: lead

Responsible Party

Wael Hanna

Lead Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Waël C Hanna, MDCM, MBA, FRCSC

Role: PRINCIPAL_INVESTIGATOR

McMaster University

Locations

Royal Alexandra Hospital

Edmonton, Alberta, Canada

Health Sciences Centre

Winnipeg, Manitoba, Canada

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, Canada

McMaster University

Hamilton, Ontario, Canada

Toronto General Hospital

Toronto, Ontario, Canada

CHUM Endoscopic Tracheo-bronchial and Oesophageal Center

Montreal, Quebec, Canada

MUHC Interventional Pulmonology Department

Montreal, Quebec, Canada

Countries

Canada

Other Identifiers

clns_10696

Identifier Type: -

Identifier Source: org_study_id