The Value of Surgical Mediastinal Staging in Clinical N1 Lung Cancer (ASTER3)

• ClinicalTrials.gov Identifier: NCT02222194
• Recruitment Status: Completed
• First Posted: August 21, 2014
• Last Update Posted: July 25, 2017
• Sponsor: Johnny Moons
• Information provided by (Responsible Party): Johnny Moons, University Hospital, Gasthuisberg

Study Description

Brief Summary:

In case of PET or CT based cN1 (suspected) NSCLC, ESTS guidelines propose mediastinal staging by echo-endoscopy OR mediastinoscopy. Recent data show a sensitivity of less than 50% for echo-endoscopy to detect N2 disease in cN1 NSCLC patients, while prevalence of mediastinal nodal disease was 24% (unpublished data Aster II).2 The investigators plan to perform a prospective multicentric observational study to measure the sensitivity of mediastinal staging by video-assisted mediastinoscopy (VAM) in cN1 operable and resectable (suspected) NSCLC patients.

Condition or disease
Non Small Cell Lung Cancer

Detailed Description:

Few reports in the literature evaluated the final pathological stage distribution of patients with resectable and operable non-small cell lung cancer (NSCLC) with clinical stage cN1. These retrospective series demonstrated that patients with computed tomography (CT) based cN1 often had clinically occult mediastinal lymph node metastases (N2/3 disease). Hishida et al. reported that 30% of 143 patients with cN1 were diagnosed N2/3 by mediastinoscopy3. Watanabe et al. reported that 37% of 168 patients with cN1 were diagnosed N2/3 by mediastinoscopy 4. Adding FDG-positron emission tomography (PET) to CT might enable the detection of N2/3 disease among these cN1 patients, but negative PET findings do not necessarily exclude N2/3 disease. Kim et al reported that 19,2 % of 99 patients with cN1, in whom cN2 was ruled out by PET-CT scan, were found to have pathologic N2 disease at pulmonary resection with mediastinal lymph node dissection.5 In conclusion, 20-30% of patients with cN1 nodes on imaging, and normal sized FDG-negative mediastinal lymph nodes on CT and PET have malignant involvement in their mediastinal nodes.

The ACCP guidelines state that invasive preoperative mediastinal staging should be performed in these cN1 patients 6. The updated ESTS guidelines recommend mediastinal staging by echo-endoscopic or mediastinoscopy.1 Non-randomized trials suggested the potential of linear endosonography for mediastinal staging 7-9. However, the patients with cN1 disease form only a minority in these studies. A recently performed prospective ASTER 2 trial (N=100) showed a sensitivity of echo-endoscopic for mediastinal staging of 38% (ITT analysis), while the prevalence of mediastinal nodal disease was 24% (unpublished data Aster 2) 2. The conclusion made by ASTER 2 is that a negative endosonography must be followed by a VAM. However, the investigators consider such double approach not cost-effective in a setting with N2 prevalence <30%. Therefore, it seems reasonable to perform a VAM instead of an endosonography in cN1 patients, which is one of the proposed strategies in the recent ESTS guidelines.1 However, there is no prospective study to date that assessed the sensitivity, NPV and accuracy of VAM in a well-defined group of cN1 patients.

Several publications have demonstrated a lobe-specific mediastinal nodal drainage for upper versus lower lobe NSCLC. Shapiro et al conclude that in early lung cancer, including cN1 disease, lobe-specific mediastinal dissection is warranted 10. However, in this study the only patient with a positive subcarinal node, upper lobe tumour, and negative superior mediastinal nodes had positive N1 nodes. To the investigators knowledge there is no study focussing on mediastinal nodal dissemination patterns in cN1 patients.

Study Design

• Study Type: Observational
• Actual Enrollment: 105 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Assessment of Surgical Mediastinal sTaging in cN1 Lung canceR
• Study Start Date: August 2014
• Actual Primary Completion Date: March 2017
• Actual Study Completion Date: May 30, 2017

Groups and Cohorts

Group/Cohort

VAM; Patients with operable and resectable cT1-2-selected T3 cN1cM0 NSCLC undergo VAM for mediastinal lymph node staging. After VAM, patients without tissue proof of N2/3 disease at surgical staging undergo a VATS or thoracotomy with systematic lymph node dissection during the same anaesthesia or at a later stage. Sensitivity, NPV and accuracy of staging with VAM will be calculated. Provided N2 lymph node metastases are proven by VAM the patient goes off study protocol and can further be assessed/treated according to local clinical practice.

Outcome Measures

Primary Outcome Measures :

1. Sensitivity of VAM [ Time Frame: at surgery (VAM) ]
   Sensitivity (%) of surgical mediastinal staging by video-assisted mediastinoscopy in clinical N1; true positives (TP) = cN1 and pN1 - false negatives (FP) = cN1 and pN2/3; sensitivity is calculated as TP / (TP+FN)

Secondary Outcome Measures :

1. Prevalence of N2/3 disease after VAM [ Time Frame: at surgery (VAM) ]
   % of patients with cN1 disease who show pN2/3 disease after VAM

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 90 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Probability Sample

Study Population

Patients with operable and resectable cT1-2- selectedT3 cN1 (suspected) NSCLC. (selected T3 = intraparenchymal tumour >7cm or T3 chest wall or T3 additional nodule, excluding mediastinal invasion or invasion of the main bronchus < 2cm from the carina)

Criteria

Inclusion Criteria:

(Suspected) NSCLC Medical operable and surgical resectable cT1, cT2 selected cT3 (i.e. intraparenchymal tumour >7cm, T3 chest wall, or T3 based on additional nodule in the lobe of the primary tumour) cN1 based on CT or PET 18 years or older Informed Consent

Exclusion Criteria:

History of mediastinoscopy No integrated FDG PET/CT available No videomediastinoscopy available EBUS/EUS for mediastinal staging of present N1 disease cN2: mediastinal nodes enlarged on CT or Pet positive invasion of mediastinal pleura invasion of phrenic nerve invasion of parietal pericardium tumour in main bronchus less than 2cm form the main carina cT4 cM1 former therapy for lung cancer (chemotherapy, radiotherapy, surgery) technical contraindication for videomediastinoscopy ( eg extreme kyphosis, cutaneous tracheostomy, extreme goiter) pregnancy inability to consent

Contacts and Locations

Locations

Belgium

University Hospital Leuven

Leuven, Belgium, 3000

France

Aix-Marseille University & Hospitals System of Marseille (AP-HM)

Marseille, France, 13915

Germany

ELK Berlin Chest Hospital

Berlin, Germany, 13125

Albert-Ludwigs-University Freiburg

Freiburg, Germany, 79106

Katholisches Klinikum Koblenz

Koblenz, Germany, 56073

Katholisches Klinikum, Thoraxchirurgie

Koblenz, Germany, 56073

Spain

Hospital Universitari Mutua Terrassa

Barcelona, Spain, 08017

Hospital Clinic; Barcelona University

Barcelona, Spain, 08036

Switzerland

University Hospital, Division of Thoracic Surgery

Zurich, Switzerland, 8091

Turkey

Istanbul University, Cerrahpasa Medical Faculty

Istanbul, Turkey, 81080

Sponsors and Collaborators

Johnny Moons

Investigators

• Study Director: Herbert Decaluwé, MD; Universitaire Ziekenhuizen Leuven

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Decaluwé H, Dooms C, D'Journo XB, Call S, Sanchez D, Haager B, Beelen R, Kara V, Klikovits T, Aigner C, Tournoy K, Zahin M, Moons J, Brioude G, Trujillo JC, Klepetko W, Turna A, Passlick B, Molins L, Rami-Porta R, Thomas P, Leyn P. Mediastinal staging by videomediastinoscopy in clinical N1 non-small cell lung cancer: a prospective multicentre study. Eur Respir J. 2017 Dec 21;50(6). pii: 1701493. doi: 10.1183/13993003.01493-2017. Print 2017 Dec.

• Responsible Party: Johnny Moons, Data Manager / Clinical Trial Coordinator, University Hospital, Gasthuisberg
• ClinicalTrials.gov Identifier: NCT02222194
• Other Study ID Numbers: ASTER 3
• First Posted: August 21, 2014
• Last Update Posted: July 25, 2017
• Last Verified: July 2017

Keywords provided by Johnny Moons, University Hospital, Gasthuisberg:

Lung cancer; Surgery; Videomediastinoscopy

Additional relevant MeSH terms:

Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases