Molecular Signature From Tumor to Lymph Nodes: How to Identify the Right Candidate for IIIA-N2 Lung Cancer Surgery?
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 200
- 试验地点
- 12
- 主要终点
- 3-year disease-free survival
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •Patient with T4, R1 or R2 surgical resection, sublobar resection, no radical lymphadenectomy
- •Patient under protectives measures
- •Pregnancy or breast-feeding
结局指标
主要结局
3-year disease-free survival
时间窗: 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.
次要结局
- 5-year disease-free survival(5 years)
- pathological architectural patterns WHO 2015 classification(5 years)
- ctDNA(3 years)
- anatomical lymphatic spread(at the end of molecular analyses)