Screening for Occult Malignancy in Patients With Idiopathic Venous Thromboembolism (SOME)

Screening for Occult Malignancy in Patients With Idiopathic Venous Thromboembolism: an Open Randomized Controlled Trial Using a Comprehensive Abdomen/Pelvis Computed Tomography

Blood clots in leg veins (deep vein thrombosis) or lung arteries (pulmonary embolism) that happen for no reason (i.e. unexplained) are both called "unprovoked venous thromboembolism" (VTE). These unexplained blood clots can be the first symptom of cancer. Up to 10% of patients with unexplained blood clots will be diagnosed with cancer within one year of their blood clot diagnosis.

These cancers can be found anywhere in the body although the relationship appears stronger with the pancreas, ovary and liver. Cancer testing in patients with blood clots is controversial. There is presently a wide variety of expert opinions and practices. Previous studies showed that a limited cancer screen including a medical history, physical examination, basic blood work and chest X-ray, will find about 90% of cancers. More recent and better designed studies showed that the limited cancer screen misses many cancers and needs to be improved. More extensive cancer testing may find more cancers but is potentially uncomfortable for patients, costs a lot of money and involves a lot of people.

The "comprehensive computed tomography" is less uncomfortable, inexpensive, radiological test made to find many cancers at once. Thus, the scientific question to be asked is: Does a "comprehensive computed tomography" miss less cancers than a limited cancer screen in patients with blood clots?

The main goal of this study is to find out if a "comprehensive computed tomography" misses less cancers than a limited cancer screen in patients with unexplained blood clots.

The second goal of the study is 1) to find out if a "comprehensive computed tomography" finds more "curable" cancers than the limited cancer screen; 2) to find out if the patients diagnosed with cancer are still alive and cancer-free after one year (i.e. the patients with curable cancer were treated and are doing well); 3) to prove that a negative "comprehensive computed tomography" means that the patient will not have cancer and; 4) to find out if a "comprehensive computed tomography" is well tolerated and safe for patients.

Study Overview

• Status: Completed
• Conditions: Deep Vein Thrombosis; Venous Thromboembolism; Pulmonary Embolism
• Intervention / Treatment: Other: Limited Malignancy Screening; Device: Comprehensive computed tomography of the abdomen/pelvis

• Study Type: Interventional
• Enrollment (Actual): 862
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada
      • St. Boniface Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada
      • Capital Health Centre for Research
  • Ontario
    • Hamilton, Ontario, Canada
      • St. Joseph's Healthcare Hamilton
    • London, Ontario, Canada
      • London Health Sciences Center
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital
  • Quebec
    • Montreal, Quebec, Canada
      • Montreal General Hospital
    • Montreal, Quebec, Canada
      • Sir Mortimer B. Davis Jewish General Hospital
    • Montreal, Quebec, Canada
      • Sacre-Coeur Hospital
    • Montreal, Quebec, Canada
      • St. Mary's Hospital Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with a new diagnosis of unprovoked proximal deep vein thrombosis (DVT) 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:

    1. known active cancer;
    2. recent (less than 3 months) paralysis, paresis or plaster immobilization of the lower extremities;
    3. recently bedridden for period of 3 or more days, or major surgery, within the previous 12 weeks requiring general or regional anaesthesia;
    4. previous unprovoked VTE;
    5. known thrombophilia (hereditary or acquired)
  • Proximal DVT is defined as a non-compressibility of any vein segment from the common femoral vein to the trifurcation of the popliteal vein or a persistent intra-luminal filling defect of the iliac, common femoral, superficial femoral or popliteal veins on contrast venography.

  • Pulmonary embolism is defined as:

    1. patients with a high/intermediate pre-test probability (Wells' model > 4) + high probability V/Q scan;
    2. positive pulmonary angiogram; or
    3. spiral CT demonstrating intraluminal filling defect in a vessel larger than a segmental artery

Exclusion Criteria:

Patients will be excluded from the study if they have any of the following criteria:

• Age < 18 years-old;
• Refusal or inability to provide informed consent;
• Greater than 21 days post diagnosis of idiopathic VTE
• Index VTE event of UEDVT or unusual site DVT
• Diagnosis of SSPE in the absence of above or below knee DVT
• Allergy to contrast media;
• Creatinine clearance < 60 ml/min;
• Claustrophobia or agoraphobia;
• Weight > 130 kg;
• Diagnosis of ulcerative colitis; and
• Diagnosis of glaucoma
• Current pregnancy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Limited Malignancy Screening	Other: Limited Malignancy Screening; 1) A complete medical history and physical examination; 2) complete blood count; 3) liver function tests (AST, ALT, ALP, bilirubin, LDH); 4) renal function test (creatinine); 5) chest X-ray (if not performed in the past year) In women, a pap smear/pelvic examination (if > 18 and < 70 years old and not performed during the past year),a mammogram (> 50 years old) will be performed if not conducted in last year. Similarly for men, prostate examination +/- PSA testing (>40 years old) will be performed if not conducted in the past year.
Experimental: Extensive Malignancy Screening; Limited screen as described above in combination with comprehensive computed tomography of the abdomen/pelvis	Device: Comprehensive computed tomography of the abdomen/pelvis; Virtual colonoscopy and gastroscopy, a biphasic enhanced CT for hepatoma and renal cell carcinoma, parenchymal pancreatogram with minimum intensity projection (MinIP) reformation for pancreatic carcinoma, and finally uniphasic enhanced CT of distended bladder for bladder and ovarian carcinomas.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Previously undiagnosed malignancy "missed" by malignancy screening defined as biopsy proven tissue diagnosis of malignancy diagnosed from the time of malignancy screening completion to the end of the 1 year follow-up period.	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall mortality	1 year
Recurrent VTE	1 year
Early malignancy: T1-2N0M0 as per the World Health Organization TNM classification system	1 year
QALYs gained	1 year
Incremental cost-effectiveness ratio	1 year
Adverse events with cCT	1 year

Collaborators and Investigators

• Sponsor: Ottawa Hospital Research Institute
• Investigators: Principal Investigator: Marc Carrier, MD MSc FRCPC, The Ottawa Hospital Research Institute

Publications and helpful links

General Publications

• Robertson L, Broderick C, Yeoh SE, Stansby G. Effect of testing for cancer on cancer- or venous thromboembolism (VTE)-related mortality and morbidity in people with unprovoked VTE. Cochrane Database Syst Rev. 2021 Oct 1;10(10):CD010837. doi: 10.1002/14651858.CD010837.pub5.
• Carrier M, Le Gal G, Wells PS, Fergusson D, Ramsay T, Rodger MA. Systematic review: the Trousseau syndrome revisited: should we screen extensively for cancer in patients with venous thromboembolism? Ann Intern Med. 2008 Sep 2;149(5):323-33. doi: 10.7326/0003-4819-149-5-200809020-00007.
• Carrier M, Lazo-Langner A, Shivakumar S, Tagalakis V, Zarychanski R, Solymoss S, Routhier N, Douketis J, Danovitch K, Lee AY, Le Gal G, Wells PS, Corsi DJ, Ramsay T, Coyle D, Chagnon I, Kassam Z, Tao H, Rodger MA; SOME Investigators. Screening for Occult Cancer in Unprovoked Venous Thromboembolism. N Engl J Med. 2015 Aug 20;373(8):697-704. doi: 10.1056/NEJMoa1506623. Epub 2015 Jun 22.
• Ihaddadene R, Corsi DJ, Lazo-Langner A, Shivakumar S, Zarychanski R, Tagalakis V, Solymoss S, Routhier N, Douketis J, Le Gal G, Carrier M. Risk factors predictive of occult cancer detection in patients with unprovoked venous thromboembolism. Blood. 2016 Apr 21;127(16):2035-7. doi: 10.1182/blood-2015-11-682963. Epub 2016 Jan 27.

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: October 14, 2008
• First Submitted That Met QC Criteria: October 15, 2008
• First Posted (Estimate): October 16, 2008

Study Record Updates

• Last Update Posted (Estimate): July 7, 2015
• Last Update Submitted That Met QC Criteria: July 2, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: Cancer; Screening
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; Thrombosis; Venous Thrombosis; Thromboembolism; Venous Thromboembolism; Pulmonary Embolism
• Other Study ID Numbers: 2004723-01H