Molecular Signature From Tumor to Lymph Nodes

Recruiting

• Conditions: Stage IIIA-cN2; Node Tumor Tissue Available; Lung Cancer; Operated With Curative Intent; Primary Tumor Tissue Available

• Registration Number: NCT04677205
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

Mediastinal lymph node (LN) involvement (N2) in non-small cell lung cancer (NSCLC) concerns 15% of resectable tumors and is associated with a poor prognosis and an overall survival reaching 9 to 49%. Literature fails to provide any definitive consensus regarding the management of these patients, except for the platinum-based doublet chemotherapy. The N2 involvement remains a matter of debate because of its not yet well-classified heterogeneity. Regarding anatomy, the Mountain and Dresler's regional LN classification for lung cancer staging remains the reference. Different studies classified IIIA-N2 disease into 4 groups, in addition to the skip-N2 phenomenon: minimal-N2, N2 single station, N2 multiple stations, and bulky-N2. Other subgroups were recently proposed for the 8th edition of the TNM: N2a1 - single station skip, N2a2 - single station non-skip, N2b - multiple stations.

The French National Cancer Institute (INCa) proposed guidelines, but in case of cN2 staging without mediastinal infiltration, guidelines remained imprecise ("resectability should be discussed for each case") and suggested surgery first, or induction chemotherapy, or concomitant chemoradiation.

Thus, optimal management of cIIIA-N2 remains controversial but complete tumor resection can be related to long-term survival in some patients, including 10 years after surgery \[1\]. In this situation, the identification of markers that will help select IIIA-N2 patients who will benefit from surgical resection is mandatory.

Detailed Description

We planned a comprehensive molecular characterization of tumors and lymph nodes to evaluate the impact of molecular signatures and molecular heterogeneity on disease-free survival after surgery in IIIA-N2 NSCLC patients. Identification of specific molecular profiles in primary tumors and evolution profiles in nodes might provide clues to the potential risk of metastatic evolution and trigger specific management.

For patients included prospectively, we planned to analyze cell free circulating tumor DNA (ctDNA) as prognostic marker. Because multiple biopsies are not always available in care settings, ctDNA could also be analyzed as a surrogate marker of molecular heterogeneity. Next generation sequencing (NGS) that was validated in our lab to screen ctDNA using a specific bio-informatics workflow allows accurate and cost effective ctDNA screening

Study Timeline

• Study First Submitted: 2020-12-15
• Study First Submitted QC: 2020-12-15
• Study First Posted: 2020-12-21
• Study Start: 2021-03-30
• Status Verified: 2023-01
• Last Update Submitted: 2023-01-06
• Last Update Posted: 2023-01-09
• Primary Completion: 2023-11
• Study Completion: 2027-11

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• Adult patient, men and women age >18 years
• Patients operated with a curative intent for an IIIA-cN2 NSCLC
• Social security affiliation
• Written informed consent for patient included in part 2 (prospective) or not opposing the use of this data for patient included in part 1 (retrospective)

Exclusion Criteria

• Patient with T4, R1 or R2 surgical resection, sublobar resection, no radical lymphadenectomy
• Patient under protectives measures
• Pregnancy or breast-feeding

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
3-year disease-free survival	3 years	To identify a molecular signature based on a comprehensive molecular analysis at genomic and transcriptomic levels linked to 3-year disease-free survival in resected IIIA-N2 NSCLC.

Secondary Outcome Measures

Name	Time	Method
5-year disease-free survival	5 years	To identify a molecular signature based on a comprehensive molecular analysis at genomic and transcriptomic levels linked to 5-year disease-free survival in resected IIIA-N2 NSCLC.
pathological architectural patterns WHO 2015 classification	5 years	To evaluate the impact of the pathological architectural patterns WHO 2015 classification on the 5-year cancer-specific survival and the 5-year overall survival
ctDNA	3 years	To assess ctDNA prognostic impact, before and after surgery.
anatomical lymphatic spread	at the end of molecular analyses	To identify tumor molecular patterns associated with specific anatomical lymphatic spread subgroups.

Trial Locations

Locations (12)

Hegp-Aphp; 🇫🇷 Paris, France

Hôpital Européen Georges-Pompidou; 🇫🇷 Paris, France

Hôpital du Haut-Lévêque, CHU de Bordeaux; 🇫🇷 Bordeaux, France

Hôpital Militaire Percy; 🇫🇷 Clamart, France

Hôpital Nord; 🇫🇷 Marseille, France

Hôpital Pasteur, CHU de Nice; 🇫🇷 Nice, France

Hôpital Pontchaillou, CHU de Rennes; 🇫🇷 Rennes, France

Hôpital Cochin; 🇫🇷 Paris, France

Hôpital Bichat; 🇫🇷 Paris, France

Hôpitaux universitaires de Strasbourg; 🇫🇷 Strasbourg, France

CHRU de Tours; 🇫🇷 Tours, France

Hôpital Larrey, CHU de Toulouse; 🇫🇷 Toulouse, France