The Canada Lymph Node Score: A Feasibility Randomized Controlled Trial (CLNS)

Routine Systematic Sampling vs. Targeted Sampling of Mediastinal Lymph Nodes Prior to Lung Cancer Treatment: A Feasibility Randomized Controlled Trial

For patients diagnosed with early stage Non-Small Cell Lung Cancer (NSCLC) on preoperative computerized tomography (CT) and positron emission tomography (PET) scans, surgical resection is usually the preferred method of treatment. However, to be eligible for surgery, current guidelines require that the cancer has not spread to the lymph nodes in the chest cavity. To evaluate these lymph nodes, the standard of care is to undergo an endobronchial ultrasound (EBUS) procedure, where all the visible lymph nodes in the chest are biopsied (sampled) with a needle. Unfortunately, these biopsies are often inconclusive, especially in patients who have no evidence of mediastinal lymph node spread on pre-operative imaging. Currently, the standard of care mandates that inconclusive biopsies should be repeated, either through another EBUS, or through more invasive procedures. Repeat inconclusive biopsies are oftentimes inconclusive as well; leading to a vicious cycle of inconclusive results, a delay in treatment, morbidity for the patient, and increased costs to the healthcare system. To circumvent this issue, the investigators have developed, validated and published a 4-point score, the Canada Lymph Node Score (CLNS), which uses four features observed during EBUS to predict whether the cancer has spread to the lymph nodes or not. Research has demonstrated that lymph nodes which appear benign on both CT and PET scan that also have a CLNS of ≤1/4 are almost certainly benign. As such, it is believed that these "triple normal" lymph do not require biopsy (or repeat biopsy).

The investigators are challenging the current standard of care in lung cancer, which mandates that all the lymph nodes in the chest need to be biopsied (i.e. Systematic Sampling) before surgery, by proposing that triple normal lymph nodes can be omitted, and only those with cancer potential should be biopsied (i.e. Targeted Sampling).To prove this hypothesis, a randomized controlled trial comparing Systematic Sampling to Targeted Sampling is required. A feasibility trial is proposed to determine whether this large-scale randomized trial will be possible.

Study Overview

• Status: Completed
• Conditions: Non Small Cell Lung Cancer
• Intervention / Treatment: Diagnostic test: Systematic Sampling; Diagnostic test: Selective Targeted Sampling

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • St. Joseph's Healthcare Hamilton

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Referred to have EBUS for staging of confirmed or suspected NSCLC
• Completed both a CT and PET scans
• cN0-cN1 disease indicated on CT and PET scans

Exclusion Criteria:

• Patients with cN0 disease, peripheral tumours and tumours < 2 cm in diameter (they do not require staging)
• Evidence of cN2 disease or higher on CT and PET scan

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Systematic Sampling; Patients will undergo systematic sampling of lymph node stations in the mediastinum with a minimum sampling of 3 stations: 4R, 4L and 7, as is the standard of care. Other stations may be included at the endoscopist's discretion. CLNS is not used for this arm.	Diagnostic test: Systematic Sampling; Following routine biopsy of lymph nodes, patients with proven malignant mediastinal lymph nodes will be referred for chemoradiation and patients with proven benign mediastinal lymph nodes will undergo surgical resection as per standard of care guidelines. Final pathology from the resected specimen will be considered the gold standard for analysis of sensitivity and specificity.; Other Names: Routine Mediastinal Staging; SS
Experimental: Selective Targeted Sampling; Patients will first undergo endosonographic assessment of 3 mediastinal lymph node stations (i.e. 4R, 4L, and 7) using the four criteria of the CLNS. Lymph node stations that exhibit a CLNS >1/4 will be biopsied as is standard of care. Lymph node stations with CLNS ≤ 1/4 will be marked as "not requiring biopsy" but will be biopsied nevertheless, so that there is no deviation from the standard of care. Other stations may be included at the endoscopist's discretion.	Diagnostic test: Selective Targeted Sampling; After CLNS assessment, patients with proven malignant mediastinal lymph nodes will be referred for chemoradiation and patients with proven benign mediastinal lymph nodes will undergo surgical resection as per standard of care guidelines. Final pathology from the resected specimen will be considered the gold standard for analysis of sensitivity and specificity.; Other Names: STS; CLNS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recruitment Rate	Minimum acceptable recruitment rate is 70%	1 Year
Procedure Length	Calculated in minutes. Recorded for both treatment arms.	1 Day
Diagnostic Accuracy	The proportion of patients in whom the treatment (CLNS or biopsy) yielded the same diagnosis as the pathology report out of the total number of patients that have received the treatment. Recorded for both treatment arms.	1 Year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of Each Possible CLNS	The CLNS has five possible scores: 0/4, 1/4, 2/4, 3/4 and 4/4. The number of lymph nodes with each score will be recorded for the Experimental Arm (Targeted Sampling).	1 Year
Frequency of Biopsies	Number of times lymph nodes had to be sampled with a transbronchial needle per EBUS procedure. Recorded for both treatment arms.	1 Year
Percent of Inconclusive Biopsies	Number of biopsies that provided an inconclusive diagnosis out of total number of biopsies obtained. Recorded for each treatment arm.	1 Year
Adverse Events	Number of AEs has classified by the Ottawa TM&M System	1 Year
Accrual Period	Duration of time to reach sample size	1 Year

Collaborators and Investigators

• Sponsor: St. Joseph's Healthcare Hamilton
• Collaborators: McMaster University
• Investigators: Principal Investigator: Waël C Hanna, MDCM, MBA, FRCSC, St. Joseph's Healthcare Hamilton / McMaster University

Publications and helpful links

General Publications

• Sullivan KA, Farrokhyar F, Leontiadis GI, Patel YS, Churchill IF, Hylton DA, Xie F, Seely AJE, Spicer J, Kidane B, Turner SR, Yasufuku K, Hanna WC. Routine systematic sampling versus targeted sampling during endobronchial ultrasound: A randomized feasibility trial. J Thorac Cardiovasc Surg. 2022 Jul;164(1):254-261.e1. doi: 10.1016/j.jtcvs.2021.11.062. Epub 2021 Dec 4.

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2019
• Primary Completion (Actual): March 2, 2020
• Study Completion (Actual): June 8, 2020

Study Registration Dates

• First Submitted: February 19, 2019
• First Submitted That Met QC Criteria: February 27, 2019
• First Posted (Actual): March 1, 2019

Study Record Updates

• Last Update Posted (Actual): June 16, 2020
• Last Update Submitted That Met QC Criteria: June 12, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Feasibility; Randomized Controlled Trial; Diagnostic Imaging; Endobronchial Ultrasound; Clinical N0-N1 Disease
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms
• Other Study ID Numbers: sjhhclns_5829

Drug and device information, study documents

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