Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

minimally invasive technique to perform pleural evaluation, pleural biopsy and pleurodesis

Cervical mediastinoscopy

Vicky Thiffault, RN, CCRP

Moishe Liberman, MD, PhD

Pasquale Ferraro, MD

André Duranceau, MD

Although thoracic NOTES may not be ready for human trials, a new minimally invasive technique to access the pleural cavity and perform pleural, pulmonary and mediastinal procedures would be possible. Cervical Video Assisted Thoracoscopic Surgery (C-VATS) is a technique that borrows from traditional VATS procedures, from cervical mediastinoscopy, and from flexible endoscopy. All of these procedures are very familiar to the thoracic surgeon.

The current feasibility and safety study examines C-VATS as a method of evaluating, biopsying and performing pleurodesis in patients with pleural disease and or effusion.

Hypothesis: C-VATS is a feasible and safe method of entering the pleural space in order to perform pleural evaluation, pleural biopsy and pleurodesis in patients with pleural disease and/or pleural effusions.

Objectives: Evaluate the safety and feasibility of C-VATS in patients with pleural disease.

Design: Prospective, cohort, feasibility and safety study.

Methods: Patients referred to all thoracic surgeons in the Division of Thoracic Surgery at the CHUM Notre Dame campus for the diagnosis or treatment of pleural based diseases will be screened for enrolment. The investigators plan to recruit 10 patients in this initial study. Eligible patients will be consented by one of the thoracic surgeons at the CHUM.

All procedures will be performing in the operating room at the CHUM Notre Dame Hospital. All patients will be admitted prior to their procedure and treated on the post-operative thoracic surgery ward using standard post-VATS procedural treatments. All cause, as well as procedure specific morbidity will be recorded by the study investigators on the day of the procedure, every day in hospital until discharge and at 1 week, 4 weeks and 12 weeks post procedure.

Cervical Video Assisted Thoracoscopic Surgery (C-VATS)

Cervical Video Assisted Thoracoscopic Surgery (C-VATS)Using a Flexible Endoscope for Thoracoscopy

Intra-operative mortality In-hospital mortality 30-day mortality

Centre hospitalier de l'Université de Montréal (CHUM)

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

This group will undergo cervical mediastinoscopy before surgery to stage their lung cancer (procedure decided by the surgeon).

This group will undergo endobronchial ultrasound before surgery to stage their lung cancer (procedure decided by the surgeon).

Donna E Maziak, MD, MSc

This study will compare two different methods of staging lung cancer to determine whether endobronchial ultrasound (EBUS) staging of mediastinal lymph nodes will provide good diagnostic yield in detecting lung cancer, when compared to current methods of a staging bronchoscopy and cervical mediastinoscopy.

Evaluation of Endobronchial Ultrasound (EBUS) for Staging Lung Cancer

Lung cancer staging (assessed by either cervical mediastinoscopy or EBUS) will be compared both pre-op and post-op.

Ottawa Hospital Research Institute

Cervical Mediastinoscopy

Minimally Invasive Echo-Bronchoscopic Lymph Node Evaluation and Biopsy

Endobronchial Ultrasound (EBUS)

Minimally Invasive Echo-Endoscopic Lymph Node Evaluation and Biopsy

Endoscopic Ultrasound (EUS)

The gold standard techniques to assess the extent of disease and decide on therapy for patients with lung cancer consists of cervical mediastinoscopy, which is a surgical procedure which entails an incision in the neck and the removal of lymph nodes from around the airway. Endobronchial ultrasound (EBUS) and endoscopic ultrasound (EUS) are new, non-surgical techniques that have been available for the past several years and are proving invaluable in lung cancer evaluation. These techniques are minimally invasive and can be performed without surgery.

To date, there have been no head-to-head studies on the same group of patients using both the old and new techniques. The study will consist of a study which compares traditional staging techniques in lung cancer patients to new, less invasive techniques.

The significance of the proposed project is tremendous. If the new strategies prove to be equivalent (or superior) to traditional techniques, these techniques will be considered the new gold-standard tests. This will change the way lung cancer is evaluated. An equivalent or superior result will also significantly impact on patient care, cost and morbidity due to the speed, convenience and lack of operating room requirement as well as the lack of general anesthesia.

1. Problem:

   The gold standard techniques to stage and diagnose the mediastinum in patients with lung cancer consist of cervical mediastinoscopy (CM). CT, PET and PET-CT scans have improved the radiological staging of the mediastinum; however these techniques are unable to provide a tissue diagnosis and are inaccurate. Endobronchial ultrasound (EBUS) and endoscopic ultrasound (EUS) have been available for the past few years and are proving invaluable in the diagnosis and staging of the mediastinum. These techniques rely on imaging of mediastinal lymph nodes (LN) through the airway (EBUS) and the esophagus (EUS) using miniaturized ultrasound probes mounted on the tip of flexible bronchoscopes (EBUS) and esophagoscopes (EUS). Once a LN is visualized and identified using either of these techniques, a needle is passed through the airway (EBUS) or esophageal (EUS) wall into the LN and biopsies are performed. These minimally invasive trans-luminal techniques do not require general anesthesia and can be performed safely, rapidly, accurately and at low cost.

   Due to the cost, inconvenience and risks associated with traditional surgical mediastinal diagnosis and staging, many physicians are foregoing tissue diagnosis of the mediastinum, resulting in incomplete pre-operative staging for patients. The endoscopic techniques are quickly replacing traditional techniques in some centers; however, when replacing a gold standard test with a new modality, one must first prove equivalence in safety and efficacy. Until such a study is completed, we do not have compelling data to be able to offer these techniques as equivalent alternatives to patients. The proposed project will be the first head-to-head comparison of both endobronchial (EBUS) and endoscopic ultrasound (EUS) in addition to transluminal biopsy with gold standard invasive surgical staging techniques in the diagnosis and staging of NSCLC.
2. Objectives:

   * Define and compare the sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratio and accuracies between traditional and minimally invasive mediastinal diagnostic and staging techniques for lung cancer.
   * Compare morbidity, convenience, cost and efficiencies between traditional and minimally invasive diagnostic strategies.
   * Examine the impact on decisions regarding changes in treatment plans (neoadjuvant chemoradiotherapy, prevention of thoracotomy) based on minimally invasive mediastinal staging compared to conventional staging strategies.
3. Methodology:

   The study design consists of a prospective comparison of diagnostic test findings on a consecutive case series with each subject serving as his or her own control. In order to do this, we will enroll N subjects (N=166), and will subject each of the subjects to K procedures (K=3). One of those procedures, the "traditional" one (K-1), is considered to be the gold standard for comparison. We will compare the diagnostic findings from the K-2 and K-3 alternative procedures (EBUS and EUS, respectively) with the gold standard across the N subjects. We will compare them singly and in combination with the gold standard. All patients with a new or suspected diagnosis of lung cancer will be prospectively enrolled in the study. All patients will undergo standard mediastinal staging, EBUS and EUS in the operating room, during one procedure. Patients will be included in the study if they meet one of the following criteria: (A) Lung lesion with mediastinal lymphadenopathy and/or positive PET scan in the mediastinum, (B) Lung lesion without mediastinal lymphadenopathy or positive PET scan in the mediastinum. Sample size has been calculated to be 166 patients.

   Results of traditional staging techniques will be considered as the "gold standard" tests for mediastinal diagnosis and staging. These tests will be used as the standard to which other modalities and combinations of modalities are compared. Data will be collected and analyzed as a whole (all patients with mediastinal LN sampling) and separately based on pre-biopsy diagnosis, post-biopsy diagnosis, mediastinal LN size (CT scan), LN station and PET avidity. Sensitivity, specificity, positive and negative predictive values, likelihood ratios and accuracies will be calculated and used to compare EUS and EBUS (transluminal strategy) to traditional staging, EUS to EBUS, EUS to traditional staging and EBUS to traditional staging. Subanalysis based on pre-biopsy patient and imaging (CT and PET) characteristics as well as ultrasound imaging characteristics during biopsy will be used to develop predictive models for minimally invasive mediastinal diagnosis, in order to better define patients at increased or decreased likelihood of successful diagnosis using these techniques. ROC curves will be constructed and used to discriminate results between diagnostic tests.

   The primary focus of this project and the hypothesis for which the sample size calculations were designed around is whether or not minimally invasive trans-luminal mediastinal LN biopsy is as accurate as traditional "gold standard" techniques in the diagnosis and staging of the mediastinum. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy will be calculated for both strategies (minimally invasive and traditional) and compared. Receiver operating curves will be used to compare the two strategies at differing sensitivity and 1-specificity values. Relative operating characteristic curves will be used to compare the two strategies at different true positive and false positive rates. The study is estimated to be completed in three years. Sample size calculation has determined that 166 patients are required for the study. The thoracic surgery division at the CHUM estimates that accrual will be approximately 1.5 patients per week (6 patients/month).
4. Expected Results:

We expect to find that minimally invasive mediastinal LN staging and diagnosis is not only equivalent in terms of accuracy to traditional staging strategies, but is actually superior. This superiority is possible, secondary to the additional LN basins accessible via these techniques.

Minimally Invasive, Diagnosis and Staging of Lung Cancer

Minimally Invasive, Trans-Luminal Diagnosis and Staging of Lung Cancer: A Prospective Head-to-Head Comparison With Traditional Gold Standard Diagnostic Techniques

Define and compare the sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratio and accuriacies between traditional and minimally invasive mediastinal diagnostic and staging techniques for lung cancer.

Compare morbidity, convenience, cost and efficiencies between traditional and minimally invasive diagnostic strategies.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Cervical Video Assisted Thoracoscopic Surgery (C-VATS)	NCT01440244	Lung Cancer	Cervical medias...	18 Years -	Centre hospitalier de l'Université de Montréal (CHUM)
Evaluation of Endobronchial Ultrasound (EBUS) for Staging Lung Cancer	NCT01799980	Lung Cancer		18 Years -	Ottawa Hospital Research Institute
Cervical Video Assisted Thoracoscopic Surgery (C-VATS)	NCT01440244	Lung Cancer	Cervical medias...	18 Years -	Centre hospitalier de l'Université de Montréal (CHUM)
Evaluation of Endobronchial Ultrasound (EBUS) for Staging Lung Cancer	NCT01799980	Lung Cancer		18 Years -	Ottawa Hospital Research Institute
Minimally Invasive, Diagnosis and Staging of Lung Cancer	NCT01011595	Lung Cancer	Cervical Medias... Endobronchial U... Endoscopic Ultr...	18 Years -	Centre hospitalier de l'Université de Montréal (CHUM)
Minimally Invasive, Diagnosis and Staging of Lung Cancer	NCT01011595	Lung Cancer	Cervical Medias... Endobronchial U... Endoscopic Ultr...	18 Years -	Centre hospitalier de l'Université de Montréal (CHUM)

Spots Global Cancer Trial Database for cervical mediastinoscopy