The Canada Lymph Node Score: A Feasibility Randomized Controlled Trial

NCT03859349 | Completed

• 1 other identifier: sjhhclns_5829
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Non Small Cell Lung Cancer

Keywords

Endobronchial Ultrasound; Diagnostic Imaging; Feasibility; Randomized Controlled Trial; Clinical N0-N1 Disease

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (5)

• Prevalence of Each Possible CLNS

  1 Year

• Frequency of Biopsies

  1 Year

• Percent of Inconclusive Biopsies

  1 Year

• Adverse Events

  1 Year

• Accrual Period

  1 Year

Study Arms (2)

Systematic Sampling

ACTIVE COMPARATOR

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

Selective Targeted Sampling

EXPERIMENTAL

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

Interventions

Selective Targeted Sampling DIAGNOSTIC_TEST

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.

Also known as: STS, CLNS

Selective Targeted Sampling

Systematic Sampling DIAGNOSTIC_TEST

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.

Also known as: Routine Mediastinal Staging, SS

Systematic Sampling

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• St. Joseph's Healthcare Hamilton: lead
• McMaster University: collaborator

Study Sites (1)

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, L8N 4A6, Canada

Location

Related Publications (1)

• 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.

  PMID: 35031139 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Waël C Hanna, MDCM, MBA, FRCSC

  St. Joseph's Healthcare Hamilton / McMaster University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Trial participants will remain blinded to their randomized treatment. Additionally, the biostatistician performing the analysis will be blinded as to which intervention arm participants were allocated to, as the group allocations will be coded as Group A and Group B. Provided this is an endoscopic trial, endoscopist blinding will not be feasible. Nonetheless, all patients deemed surgical candidates after EBUS will have their pathology compared to EBUS staging in order to ensure appropriate diagnosis. Pathologists performing such pathology report will be blinded to which intervention arm participants are allocated to.
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Endoscopy Services, Thoracic Surgeon

Model Details: All participants who provide consent for participation and who fulfil eligibility criteria will be randomized with a unique randomization sequence derived from the random permuted block design (with blocks of varying sizes) in a 1:1 ratio. Participants will randomized to either Systematic Sampling (Control) or Targeted Sampling (Experimental).

Study Record Dates

• First Submitted: February 19, 2019
• First Posted: March 1, 2019
• Study Start: May 6, 2019
• Primary Completion: March 2, 2020
• Study Completion: June 8, 2020
• Last Updated: June 16, 2020

Record last verified: 2020-06

Locations

CA (1)