Rationale: Venous thromboembolism (VTE), the term comprising deep venous thrombosis and pulmonary embolism, is a frequent complication of cancer, and is the second cause of death among these patients. Even when they have no overt thrombosis, cancer patients present a series of alterations in their blood, indicative of chronic activation of coagulation – this is known as ‘hypercoagulability’. This can be detected by laboratory tests that measure thrombosis markers in the circulation.
In a healthy subject, unexplained thrombosis or persistently abnormal results in these tests may suggest a hidden tumor, not yet diagnosed. In patients who already have cancer, test results are increasingly altered with more advanced disease. The level of hypercoagulability therefore correlates with a worse prognosis.
These considerations lay the foundation for this Italian multicenter prospective study, referred to as HYPERCAN.
Objectives: The HYPERCAN study aims to identify markers of thrombosis which could make an early diagnosis of cancer in healthy subjects and indicate the prognosis in tumor patients.
To date about 9,500 blood donors have been enrolled as healthy subjects, and about 3,900 subjects with four different types of tumor – breast, colorectal, gastric, lung. The preliminary findings of the study are promising, demonstrating a relationship between specific thrombosis biomarkers, measured at the time of enrolment of the cancer patients, and their different outcomes.
Despite these original observations, however, some fundamental research questions are still open on the utility of thrombosis biomarkers in the diagnosis and management of tumors.
Study design: HYPERCAN is an Italian translational, prospective and multicenter project, based on two closely linked research plans.
Plan 1 “Thrombosis markers as a tool for predicting tumor risk”
Levels of activation of coagulation will be measured in a cohort of 15,000 male or female blood donors, aged from 30-70 years, in the Province of Bergamo. All will be asked to complete a questionnaire on their lifestyle, including their socio-economic status, physical exercise, medical history, use of drugs, dietary habits, and risk factors for cancer and cardiovascular diseases. These blood donors will be followed for at least five years, and checked for cancer every six months. Their plasma will be analyzed for a case-control study of coagulation factors. Hemostatic markers will be analyzed by the Hemostasis and Thrombosis Laboratory, In the Department of Immunohematology and Transfusion Medicine.
Plan 2 “Thrombosis markers in cancer patients and relation to prognosis”: A prospective cohort of 5000 patients with a new diagnosis of the following tumors will be enrolled: breast, lung, and non-small-cell lung cancer, (NSCLC), colorectal and gastric. These patients will be enrolled by the four main hospitals in the Province of Bergamo (Ospedale Papa Giovanni XXIII, Bergamo, Policlinico San Marco, Gruppo San Donato, Zingonia, Ospedale di Treviglio-Caravaggio, Ospedale Bolognini di Seriate) and the main Italian tumor institutes (IRCCS, Istituto Nazionale dei Tumori, Milan, Istituto Clinico Humanitas, Rozzano (Milan), Ospedale San Filippo Neri/San Giovanni, Rome, and Istituto Nazionale Tumori, Bari). Blood samples taken at enrolment and at the intervals scheduled during the follow-up, will be tested for thrombosis biomarkers, and for the routine serum tumor markers.
Laboratory results will be collected in parallel with the clinical data and entered in a dedicated eCRF system.
Expected results: The aim is to identify the most promising blood biomarkers for use in a risk model which, for the first time, will make an early tumor diagnosis or identify the people at greatest risk of the disease. As part of this project we established the independent predictive D-dimer value for tumor diagnosis.
We also hope to confirm in blood donors the effects of lifestyle factors important for the risk of cancer, or protection against it.
Plan 2 does not aim to find tools for diagnosis (which already exist) but is designed to identify biomarkers of hemostasis that will cast light on the likely course of the disease and could help direct clinical-oncological decisions.
Preliminary findings so far are promising and have led to the detection of biomarkers to forecast overall survival, the progression of the disease, relapse, and VTE. As the size of the study sample is close enough to the number initially established, we hope to be able to confirm these preliminary data on completion of the study.
Impact on cancer: The study could provide data useful for developing new tools for early diagnosis of cancer and forecasting its progression. The assays scheduled have all been done on peripheral blood samples, available for translational research.
This is particularly important for early cancers and resected tumors, to identify risk factors for recurrent disease.
The VTE forecasts will be useful for calculating this risk in individual patients, and prescribing preventive measures.