Screening for Occult Malignancy in Patients With Unprovoked Venous Thromboembolism

Study Overview
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Brief Summary
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Venous thromboembolism (VTE) can be the earliest sign of cancer. Identifying occult cancers at the time of VTE diagnosis may lead to significant improvement of patients' care. This is also an upmost issue for patients who want to know if an underlying cancer might have triggered the VTE. An individual patient-level data meta-analysis (IPDMA) supports extensive screening strategies for occult cancer especially based on FDG PET/CT, and suggests that the best target population for cancer screening would be patients with unprovoked VTE older than 50 years of age (6.7% in patients aged 50 years or more vs. 1.0% in patients of less than 50 years (OR: 7.1, 95% CI: 3.1 to 16%).

Detailed Description
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The identification of subgroups of patients at high risk of cancer might enable more efficient screening strategies for early detection of cancer. Venous thromboembolism (VTE) can be the first manifestation of an occult cancer. All tumor sites may be involved. In an individual patient-level data meta-analysis (IPDMA), it was reported a 1-year prevalence of occult cancer of 5.2% (95%CI 4.1-6.5) among patients presenting with unprovoked VTE. Two recent multicenter randomized controlled trials (e.g. SOME (Canada) and MVTEP (France) trials) failed to demonstrate that extensive cancer screening strategies diagnosed more cancers, more early stage tumors, or improved cancer-related mortality in comparison with a more limited screening strategy. However, the main limitation of these studies was the twice lower than expected overall incidence of occult cancer diagnosis in unselected patients with unprovoked VTE, which limited the statistical power. In the IPDMA, it was also reported that the 1-year period prevalence of occult cancer was 7-fold higher in patients aged ≥ 50 (6.8%; 95%CI 5.6-8.3) as compared with those < 50 years (1.0%; 95%CI 0.5-2.3). Moreover, in the MVTEP trial, the incidence of missed cancers over a 2-years follow-up period was significantly lower in patients randomized to a 18F-Fluorodeoxyglucose Positron Emission/Computed Tomography (FDG-PET/CT) screening strategy. Thus, the most promising diagnostic modality for occult cancer screening seems to be FDG-PET/CT. FDG-PET/CT which allows a one-stop whole-body imaging, is routinely used for the diagnosis, staging and restaging of various cancers. The MVTEP2 Trial seeks to determine if among higher risk patients (≥ 50 year-old) with a first unprovoked VTE, a cancer screening strategy including a FDG-PET/CT decreases the number of missed occult cancers detected over a 1-year follow-up period as compared with a limited screening alone.

Official Title
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Screening for Occult Malignancy Using 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG PET/CT) in Patients With Unprovoked Venous Thromboembolism

Conditions
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Embolism and Thrombosis

Intervention / Treatment
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* Diagnostic Test: Limited cancer screening
* Diagnostic Test: Limited cancer screening + FDG PET/CT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 50 years or older with a new diagnosis of first unprovoked proximal deep vein thrombosis (DVT) and/or pulmonary embolism (PE) will be eligible to participate into the study. Unprovoked VTE is defined as the absence of any of the following predisposing factors: active malignancy (known malignancy, progressive and/or treated during the last 5 years) except for adequately treated basal or squamous cell carcinoma; Patients whose state of health suggests the presence of cancer at the time of diagnosis of VTE cannot be included in the protocol recent (less than 3 months) paralysis, paresis or plaster immobilization of the lower extremities; recently bedridden for period of 3 or more days, or major surgery, within the previous 12 weeks requiring general or regional anaesthesia; previous unprovoked VTE; known thrombophilia (hereditary or acquired) Exclusion Criteria: Patients will be excluded from the study if they have any of the following criteria: Refusal or inability to provide informed consent; Hypersensitivity to 18F-FDG or any of the excipients according to the product monograph; Unavailable to follow-up. VTE while on anticoagulation (e.g apixaban, rivaroxaban, edoxaban, dabigatran, warfarin)

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Limited cancer screening<br>Limited screening alone. | Diagnostic Test: Limited cancer screening<br>* The limited cancer screening will include: 1) a complete medical history and physical examination; 2) complete blood count; 3) liver function tests (AST, ALT, ALP, bilirubin); and 4) chest X-ray. In women, a breast examination, Pap smear/pelvic examination (if < 70 years old and previously sexually active) and mammogram will be performed, if not conducted in last year. In men, similarly, prostate examination and PSA testing will be performed, if not conducted in the last year. All patients will undergo colon cancer screening as per local practice.<br>|
| Experimental: Limited cancer screening + FDG PET/CT<br>Limited screening + FDG PET/CT | Diagnostic Test: Limited cancer screening + FDG PET/CT<br>* The limited cancer screening (as described above) in combination with a FDG PET/CT.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occult cancer missed by screening strategies | Occult cancer missed by cancer screening defined as proven cancer diagnosed (either biopsy proven cancer or cancer diagnosis approved by adjudication committee in the absence of biopsy proven cancer) from the time of cancer screening completion to the end of the 1-year follow-up period, and not detected at the time of screening. In other words, missed means the number of new cancers diagnosed in patients considered not to have cancer after having completed the assigned cancer screening strategy (i.e false negative results of screening strategies). | At 1 year of follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occult cancer diagnosed by screening strategies | The proportion of patients with a new cancer diagnosis after completion of the initial allocated screening strategy. | At 1 month | 
| Early vs Adanced-stage cancers | The proportion of early-stage (T1-2N0M0) as per the World Health Organization TNM classification system) versus advanced-stage tumors at initial screening and during follow-up. | At 1 year of follow-up | 
| Cancer-related mortality | Cancer-related mortality during a 5-year follow-up period. | At 5 years of follow-up | 
| Cost effectiveness analysis | Additional cost per additional cancer detected. | At 1 year of follow-up | 
| Recurrent VTE | Rate of recurrent VTE | At 1 year of follow-up | 
| Decision aid to assist patients in the decision of cancer screening | Development of a decision aid to assist patients in the decision of cancer screening | At 1 year of follow-up | 
| Additional tests | The proportion of patients receiving additional tests following each strategy | At 1 year of follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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venous thrombosis, pulmonary embolism, screening, occult cancer