Evaluation of NETs in Patients With Solid Cancers Associated With a High Risk of Venous Thromboembolic Events

Evaluation of Neutrophil Extracellular Traps (NETs) by Flow Cytometry in Patients With Solid Cancers Associated With a High Risk of Venous Thromboembolic Events

Venous Thromboembolic Events (ETVs) are the second leading cause of death (9.2% of causes of death) in cancer patients after tumor progression (1). Indeed, cancer is associated with a 4 to 7-fold risk of ETV during chemotherapy (2). This complication is observed in 20% of cancer patients (3), and is sometimes an inaugural manifestation of cancer. This risk is particularly increased during the first 3 months after cancer diagnosis (4).

A biomarker correlated with the occurrence of ETVs would make it possible to target patients at high risk of thrombosis who could benefit from primary thromboprophylaxis, thus avoiding the complications, particularly haemorrhagic, and the additional costs associated with the long-term diagnostic and therapeutic management of ETVs. The investigator has implemented in the laboratory an innovative approach to the detection and quantification of circulating NETs by flow cytometry (FCM) allowing the routine determination of NETs. Therefore the investigator propose to assess NETs by CMF in a cohort of cancer patients with a very high risk of ETVs (pancreatic cancer, gastric cancer and colon cancer).

The NETs will be detected and quantified by CMF on the remaining EDTA tube collected to perform the blood count (NFS), using the method in place in the laboratory, adapted from the method initially described by Gavillet et al. The analyses will be carried out on a Fortessa LSR cytometer (Becton Dickinson), the antibodies used are specific to NET components: citrullinated H3 anti-histone in indirect labelling coupled APC, PE myeloperoxidase and Hoescht 34580 as DNA marker. The level will be measured in NETs/µL of whole blood as a function of the white blood cell count (Sysmex XN-3000). In parallel, other parameters associated with ETV risk will be evaluated: NFS on Sysmex-XN PLC, D-dimers, FVIII and MP. The assays of PM, D-dimers and FVIII will be performed specifically as part of the project, the other parameters will be measured as part of routine patient management and will not result in any additional constraints or costs. Biomarker assays will be performed at the time of cancer diagnosis on the EDTA and citrate tubes collected for NFS and TP/TCA respectively as part of routine care.

Inclusion Criteria:

• Male or Female over 18 years of age (≥18),
• Patient with pancreatic, gastric or colorectal cancer,
• Patient with a high risk of ETV,
• Patient on the first line of treatment or relapsing after a period of complete remission,
• Patient affiliated to a social security system or CMU.

Exclusion Criteria:

• Patient who has had an ETV in the 3 months prior to inclusion,
• Patient with a life expectancy of less than 3 months,
• Patient with an anticoagulation placement,
• Known pregnant or breastfeeding woman,
• Patient under guardianship or curatorship.