A New Clinic-Genetic Risk Score for Predicting Venous Thromboembolic Events in Cancer Patient
Condition: Cancer-associated Thrombosis; Genetic Predisposition
MeSH terms: Thrombosis; Genetic Predisposition to Disease
Study type: Observational

Summary: 
      Venous thromboembolism (VTE) is a common disease in cancer patients and one of the major
      causes of cancer-associated mortality. Risk for developing VTE increases when cancer patients
      are receiving chemotherapy. Current risk scores for predicting cancer-associated VTE in
      ambulatory patients had low/moderate discrimination and clinical sensitivity. These models
      use clinical and biochemical parameters of the patient.

      In the development of VTE genetics play a relevant role. The product Thrombo inCode (TiC)
      assess VTE risk prediction by using a combination of a genetic risk score (GRS) and clinical
      parameters from the patient. The investigators hypothesized that the GRS included in TiC
      combined with clinical parameter some of them associated with cancer could be better
      predicted by TiC than by current risk scores (Khorana score).

      After publishing the primary results in 2018, we have expanded the GRS in a external
      validation cohort adding gliomas and biliary tract tumors. Also we have incorporated the
      assessment of D-dimer in order to improve the predictive capability.
    

Detailed description: 
      The working hypothesis of this study establishes that the risk of cancer patients suffering a
      thromboembolic event is conditioned by individual genomic factors. The genes to be analyzed
      have clearly demonstrated their relationship with thromboembolic disease in other clinical
      contexts. This study is considered the initiation of a field of research in genomic risk
      markers indicating a risk of thrombosis in cancer patients. The ultimate goal of the study is
      to establish a clinic-genomic score for selecting patients with a high risk of suffering
      thrombotic events who can benefit from guided thromboprophylaxis. Its secondary goal is to
      prevent the adverse effects of ineffective therapies in other patients (low-risk patients not
      requiring an anti-thrombotic prophylaxis).

      The aim is to demonstrate the link between the clinic-genetic profile and the risk of
      suffering thromboembolic events in the group of cancer patients. The working hypothesis
      establishes that cancer patients who develop thrombotic events will have a higher score for
      the thrombosis risk clinic-genetic profile than cancer patients not developing thromboembolic
      events. The second aim is to analyze whether the thrombosis clinic-genetic risk score
      improves the detection of patients at risk of suffering a thromboembolic event compared to
      the Khorana predictive model routinely used (Khorana score).

      Current validations ongoing:

      An external retrospective validation adding 250 patients more and including D-dimer and other
      types of high-risk neoplasm.

      An external prospective validation (second ONCOTRHROMB12-01 cohort 2) adding 450 patients
      more and including D-dimer and other types of high-risk neoplasm.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        The study will include patients diagnosed with colorectal, esophago-gastric, biliary tract,
        pancreas or lung cancer who have not previously been treated with chemotherapy or
        chemotherapy and radiation therapy and are candidate for chemotherapy in outpatient setting
      
Biospecimen description: 
      EDTA Blood sample
    
Keywords: Venous thrombosis; Cancer; Risk Model Assessment; Genomic