Official Title
Molecular Signature From Tumor to Lymph Nodes: How to Identify the Right Candidate for IIIA-N2 Lung Cancer Surgery?
Brief Title
Molecular Signature From Tumor to Lymph Nodes
Protocol ID
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 Period
Enrollment Count
200 participants
Eligibility Criteria
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
Filters
Lung Cancer
Stage IIIA-cN2
Operated With Curative Intent
Primary Tumor Tissue Available
Node Tumor Tissue Available
RECRUITING
ADULT
OLDER_ADULT