Vascular Fingerprint Validation Study

Study Overview
=================
Brief Summary
-----------------
The vascular fingerprint is a simple selection tool to identify testicular cancer patients with a high risk of arterial cardiovascular events during and in the first year after cisplatin chemotherapy. Eventually, this selection method allows a relative small randomized intervention study with i.e. LMWH during chemotherapy to prove the effectiveness and safety in lowering the chance of an arterial cardiovascular event.

Detailed Description
-----------------
Since the introduction of cisplatin in the late seventies (1), the prognosis of metastatic testicular cancer patients has dramatically improved, with long-term survival rates of 80-90% (2). However, cure rates are compromised by the increased risk of cardiovascular events (3-5). Approximately 1-5% of the patients with metastatic testicular cancer develop arterial cardiovascular events during or shortly after cisplatin- and bleomycin containing chemotherapy (3-7). Arterial cardiovascular events include ischemic stroke and myocardial infarction. These arterial events are a source of serious treatment-induced morbidity and mortality as recently clearly confirmed by Fung (8). No established standard prophylaxis is available. There is an unmet need to have the possibility to identify high risk patients before start of chemotherapy in whom prophylactic anti-coagulant treatment may prevent events (9). An identification tool could maximize the benefit of an intervention without introducing too much unnecessary harm: preventive interventions also carry risk. Recent data from the investigators' cancer center showed that before chemotherapy 22% of the metastatic cancer patients had ≥3 of the following 5 traditional cardiovascular risk factors present (high risk vascular fingerprint, figure 1): overweight, smoking, hypertension, dyslipidemia and impaired blood glucose. These patients had an increased risk to develop arterial events during or early after chemotherapy: 19% of the patients with a high risk vascular fingerprint developed an arterial cardiovascular event whereas only 2% of the patients with ≤2 risk factors developed an event . The vascular fingerprint seems an easy method to identify which metastatic testicular cancer patients are at a high risk for early arterial events and who may benefit from prophylaxis with for example low molecular weight heparins (LMWHs). To be used in the clinic these data need to be confirmed in an independent cohort.

Official Title
-----------------
Vascular Fingerprint to Identify Patients at Risk for Arterial Cardiovascular Events Within the First Year After Start of Cisplatin-based Chemotherapy for Testicular Cancer: a Validation Study

Conditions
-----------------
Testicular Cancer

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of metastatic TC and an indication to start with first-line cisplatin-based chemotherapy for metastatic TC Classified into IGCCCG good or intermediate prognosis group Younger than 50 years of age at start of chemotherapy Signed informed consent Exclusion Criteria: History of previous cardiovascular disease Retroperitoneal mass > 5 cm Indication for anticoagulant therapy at start of chemotherapy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------
What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Development of arterial cardiovascular events | Primary outcome is development of arterial cardiovascular events within the first year after start of chemotherapy. Events taken into account are: myocardial infarction (WHO ICD-10 I20-I25), ischemic cerebrovascular accidents (WHO ICD-10 I63-I66 and G45) or infarction in other specific organ systems (WHO ICD-10 K76.3, K55, D73.5, M62.2, N28.0) | first year after start of chemotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | first year after start of chemotherapy | 
| Response to testicular cancer treatment (no evidence of disease / relapse / no response to treatment) |  | first year after start of chemotherapy | 
| Development of venous thromboembolic events (VTE) (WHO ICD-10 I26, I80-82) |  | first year after start of chemotherapy |