Pathophysiological Mechanisms Involved in the Pronostic and Evolution of Non-Small Cell Lung Cancer (NSCLC) at All Stages of the Disease (EMA)

University Hospital of Bordeaux

Status

Begins enrollment in 1 month

Conditions

Non Small Cell Lung Cancer

Treatments

Biological: Biological sampling

Study type

Observational

Funder types

Other

Identifiers

NCT07470476

CHUBX 2024/108

Details and patient eligibility

About

This single-center observational cohort study conducted at Bordeaux University Hospital aims to establish a structured clinico-biological platform in non-small cell lung cancer (NSCLC) to investigate the biological mechanisms involved in tumor initiation, progression, and relapse across all disease stages (I-IV).

A total of 150 consecutive adult patients with histologically or cytologically confirmed NSCLC will be included over a 3-year period. Tumor samples will undergo translational analyses. These biological data will be correlated with pseudonymized clinical data collected from medical records and the institutional clinical data warehouse.

The primary objective is to characterize the molecular, metabolic, and immune mechanisms associated with tumor progression and recurrence in NSCLC.

The central hypothesis is that integrating comprehensive clinical data with in-depth molecular and immunological analyses of tumor tissues will identify biologically distinct patterns associated with disease evolution, therapeutic resistance, and prognosis. Such integrated clinico-biological signatures may improve patient stratification and contribute to the identification of novel biomarkers and therapeutic targets in NSCLC.

Full description

Lung cancer remains one of the leading causes of cancer-related mortality worldwide. Despite major therapeutic advances over the past two decades, including targeted therapies and immune checkpoint inhibitors, long-term survival remains limited for a substantial proportion of patients. Although five-year survival has improved compared to the early 2000s, prognosis remains heterogeneous and largely dependent on tumor biology, stage at diagnosis, molecular alterations, and host-related factors.

Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancers and represents a biologically heterogeneous group of diseases. Tumor progression and resistance to therapy are driven by complex interactions between tumor cells, the tumor microenvironment, immune components, and host-related factors such as aging, smoking exposure, and chronic inflammatory lung diseases including chronic obstructive pulmonary disease (COPD).

A deeper understanding of these mechanisms is required to:

Identify biomarkers associated with tumor progression and relapse
Better predict therapeutic response and resistance
Develop innovative diagnostic and therapeutic strategies

Bordeaux University Hospital is a regional referral center managing approximately 300-400 lung cancer patients annually. The institution hosts multiple academic research laboratories with expertise in tumor biology, immunology, thoracic diseases, and molecular oncology. This study aims to create a structured translational research continuum integrating clinical care and laboratory research.

Clinical data will be extracted from:

The institutional clinical data warehouse
Electronic medical records

Data collected will include:

Demographics and smoking history
Comorbidities (including COPD and other lung diseases)
Tumor histology and molecular characteristics
TNM staging
Treatment modalities (surgery, radiotherapy, systemic therapies)
Treatment response and toxicity
Recurrence, progression, and survival outcomes Clinical data will be pseudonymized and recorded in a dedicated REDCap electronic case report form hosted at Bordeaux University Hospital.

Clinico-biological correlation analyses will make it possible to define :

Response in study patients and evaluation of the impact of the different biological factors on treatment response, assessed according to RECIST 1.1 criteria
Prognostic analyses may also be performed on overall survival (time between inclusion and death/loss to follow-up) and progression-free survival (time between inclusion and progression/loss to follow-up/death)
Survival of patients in the cohort (overall survival, progression-free survival)
Response rate of patients in the cohort according to treatment
Factors statistically associated with survival using univariate then multivariate Cox analysis
Treatment tolerance (descriptive analysis)
List of pathways involved in resistance processes, and description of newly identified therapeutic targets for the different treatments
Validation of the functional involvement of proteins/pathways in in vitro models

Biological Samples and Translational Analyses Tumor samples consist of formalin-fixed paraffin-embedded (FFPE) biopsy or surgical specimens stored at the institutional Biological Resource Center.

Samples will undergo translational analyses in partner academic laboratories, including:

Molecular characterization of tumor cells
Metabolic profiling
Characterization of the tumor immune microenvironment
Evaluation of immunosuppressive pathways
Analysis of secretome-related functions
Identification of aging-related biological signatures

After analysis, biological data will be securely transferred to the coordinating center and correlated with clinical variables.

All samples and associated data will be pseudonymized in accordance with applicable data protection regulations.

Enrollment

150 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Adult patients
NSCLC treated at the Bordeaux University Hospital.
TNM stage between I to IV
Patient affiliated with or beneficiary of a social security scheme.
Non opposition

Exclusion criteria

Patients with small cell lung cancer.
History of any other malignancy other than NSCLC within 1 years prior to screening. except for non-melanoma skin cancers, in situ cancers, or low-risk prostate cancer
Pregnant or breastfeeding women.
Patients with a medical or psychiatric condition or illness that compromises their ability to understand the information or participate in the study.
Individuals subject to legal protection measures (legal guardianship, trusteeship or curatorship).
Individuals deprived of their liberty by judicial or administrative decision.
Individuals who are unable to give their consent.
Patients who are in a period of exclusion following another study or who have participated in another interventional study involving a medicinal product within 30 days prior to entry into the protocol or who are participating in another clinical study.