Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| ID-RCB 2021-A01024-37 | Other Identifier | ANSM | |
| ARI 20-0446 | Other Grant/Funding Number | University Hospital, Toulouse |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Lung cancer screening is based on low dose CT scan (LDCT), a highly sensitive but poorly specific tool.
Complementary specific approaches are thus strongly needed, among which cell-free DNA (cfDNA) genotyping has been proven highly specific but of low sensitivity (25 to 50% for stage I diseases) due to inconstant tumor shed. Tumor biopsy is thus often required and radial endobronchial ultrasound (rEBUS) bronchoscopy is a minimally invasive approach (<3% complications) but of limited sensitivity in cases of nodules < 20 mm.
The investigators hypothesized that methylation analysis on cfDNA floating in supernatant derived from rEBUS specimens could improve rEBUS sensitivity
Tumor biopsy is often required to characterize indeterminate nodules. Radial endobronchial ultrasound (rEBUS) bronchoscopy is often used due to a low rate of complications but its sensitivity is limited for small nodules.
The investigators hypothesized that methylation analysis on cfDNA floating in supernatant derived from rEBUS specimens could improve rEBUS sensitivity.
The primary outcome of this pilot, diagnostic validation, monocentric study is the sensitivity of targeted (9 genes panel) methylation analysis on supernatant cfDNA to detect a malignant nodule.
Secondary outcomes include the comparison of supernatant to pathology and plasma cfDNA methylation analysis.
Specificity, negative predictive value (NPV), positive predictive value (PPV) of targeted (9 genes panel) methylation analysis on supernatant cfDNA to detect a malignant nodule will be analyzed.
60 patients planned for a rEBUS bronchoscopy for one, two or three < 20 mm nodule, without mediastinal or extra thoracic lesions (cT1N0M0) will be included.
The day of the rEBUS bronchoscopy, 2 7.5 mL blood samples are collected. rEBUS samples' supernatant, usually discarded, is saved.
Cell free DNA is extracted from these biological specimens at the Laboratory of Oncological Medical Biology (LBMO) in Toulouse University Cancer Institute and tested for methylation (targeted analysis on 9 genes).
The patients will be followed for one year to obtain a final diagnosis and correlate it with tissue, nodule supernatant and plasma methylation analyses.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| blood sampling | Experimental | blood sample (2 tubes of 7.5 mL of blood = 15 mL) during the preoperative check-up on the day of the ultrasound-bronchoscopy in order to compare the sensitivity of the analysis of free circulating DNA present in the supernatant of pulmonary nodules less than 20 mm samples taken under ultrasound-bronchoscopy to that present in the plasma |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Blood samples | Biological | Patients will be taken from an additional blood sample (2 tubes of 7.5 mL of blood = 15 mL) during the preoperative check-up on the day of the ultrasound-bronchoscopy in order to compare the sensitivity of the analysis of free circulating DNA present in the supernatant of pulmonary nodules less than 20 mm samples taken under ultrasound-bronchoscopy to that present in the plasma. |
| Measure | Description | Time Frame |
|---|---|---|
| Sensitivity of targeted (9 genes panel) methylation analysis on supernatant cfDNA to detect a malignant nodule will be evaluated. | Promoter methylation rates of the 9 targeted genes in the free circulating DNA of the endoscopic samples supernatant is obtained by quantitative Polymerase Chain Reaction (PCR) of bisulfite-treated DNA fragments from the cytological samples supernatant after DNA concentration and separation by size at the Centre of Cancer Research of Toulouse (CRCT). These analyses will be performed blinded to the clinical data and the histopathology result of the lung nodule. | 1st day (D0) of patients' inclusion, on morning of their ultrasound-bronchoscopy |
| Measure | Description | Time Frame |
|---|---|---|
| Comparison of supernatant to pathology and plasma cfDNA methylation analysis. Specificity, negative predictive value (NPV), positive predictive value (PPV) of targeted (9 genes panel) methylation analysis on supernatant cfDNA to detect a malignant nodule | Methylation profiles of free circulating DNA from plasma obtained after centrifugation of blood samples will be obtained by the same method as described for analysis of cytopunction's supernatant methylation profile. These analyses will be performed blinded to the clinical data and the histopathology result of the lung nodule. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Valentin HELUAIN, MD | Contact | +33567771439 | +33 | heluain.v@chu-toulouse.fr |
| Name | Affiliation | Role |
|---|---|---|
| Valentin HELUAIN, MD | University Hospital, Toulouse | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Toulouse University Hospital | Recruiting | Toulouse | Occitanie | 31300 | France |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D008175 | Lung Neoplasms |
| ID | Term |
|---|---|
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
Not provided
Not provided
| ID | Term |
|---|---|
| D001800 | Blood Specimen Collection |
| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| 1st day (D0) of patients' inclusion, on morning of their ultrasound-bronchoscopy |
| D008171 |
| Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |