A Predictive Score for Arterial Thrombosis Associated With Cancer. The Prospective COMPASS- Arterial Cancer Associated Thrombosis Study

Cancer is associated with an increased incidence of thrombosis and thromboembolic events are one of the leading causes of morbidity and mortality in this population. The main consideration has been given to venous thromboembolic events (VTEs); arterial thrombotic events (ATEs) have more recently been recognized to precede cancer diagnosis and/or follow it as a serious complication. Thus, while plausible, the relationship between cancer and arterial thrombosis is less well established than for VTE.

The heightened risk for VTEs in outpatients who receive anticancer treatment has been extensively investigated and associated to the histological type of the malignancies, the stage of the disease, the time since cancer diagnosis and the expanding armamentarium of chemotherapeutic agents. Patients' intrinsic risk factors and particularly, the presence of cardiovascular risk factors and personal history of VTE, as well as other underlying comorbidities (i.e. recent hospitalization for acute medical illness, acquired or hereditary thrombophilia, autoimmune disease) are determinant clinical predictors for VTE and have been included to the most recent risk assessment models (RAMs) for patients with common solid tumors (i.e. breast, lung, ovarian or colon cancers) or hematological malignancies (i.e. lymphoma). In specific, the COMPASS-CAT (Comparison of Methods for thromboembolic risk assessment with clinical Perceptions and AwareneSS in real life patients-Cancer Associated Thrombosis) and ThroLy (Thrombosis Lymphoma) scores are derived from prospective multicentric observational studies specifically designed to evaluate the clinical relevance of predictors related to cancer characteristics, patients' intrinsic risk factors and anticancer treatment related risk factors. The COMPASS-CAT score for VTE is applicable to cancer patients at any time after anticancer therapy initiation providing a global evaluation of VTE risk, feasible in real life conditions of medical oncology practice. This score been externally validated in about 4000 patients and showed similar accuracy, sensitivity and specificity as compared to the ones reported in the initial derivation study. Thus, the methodological design applied in the COMPASS-CAT study (prospective multicenter observational study with symptomatic and documented end point of thrombosis and elaboration of an extensive CRF including all known cancer related and patient- related risk factors for thrombosis) leads to an accurate RAM.

Taking into consideration that clinical research in the field of risk assessment tools in cancer associated arterial thrombosis is delayed compared to the respective in cancer associated VTE, we sought to undertake the COMPASS-ARTeCAT (Comparison of Methods for thromboembolic risk assessment with clinical Perceptions and AwareneSS in real life patients- Arterial Cancer Associated Thrombosis) study aiming to identify the most clinically relevant clinical predictors of arterial thrombosis in ambulatory patients with specific types of cancer who are going to start or have already started anticancer treatment. The COMPASS-ARTeCAT study will be a multicenter, prospective, longitudinal, non-interventional study undertaken in patients suffering from specific solid cancers or hematological malignancies and will derive to a new RAM for identification of patients at risk for arterial thrombosis which will be applicable during patients' journey in the oncological context.

Materials and methods Study Design and Participants. This study is an investigator-initiated multinational, prospective, and non-interventional trial. Ambulatory cancer patients, with histologically confirmed solid cancer (breast, lung, gastric, colorectal, pancreatic, ovarian, prostate, or bladder cancer) or specific hematologic malignancy (Hodgkin and non-Hodgkin lymphoma or multiple myeloma), will be recruited and followed from January 2021 to January 2023. Patients diagnosed with multiple primary cancers during the study period will be assigned to the cancer type diagnosed first. The specific site definitions for cancer cohorts will be based on the International Classification of Diseases (ICD) for Oncology, third edition, site recode classification to identify the cancer population. Consecutive patients from the ambulatory anticancer clinics will be assessed for eligibility. Patients with: (a) age younger than 18 years, (b) life expectancy less than 3 months, (c) ongoing pregnancy, (d) recent (≤3 months) arterial thromboembolism and/or (e) major psychiatric disorder will be excluded from the study.

Patients at assessment for eligibility in the study will be receiving or will be scheduled to receive the recommended anticancer treatments according to the institutional practices. At the follow-up visits, at 3, 6, 12 and 24 months after inclusion, patients will be interviewed and clinical records will be analyzed regarding the occurrence of symptomatic arterial thrombosis, bleeding episodes, disease evolution, and anticancer treatments. During the study, investigators will be free to decide for antiplatelet and/or anticoagulation therapy according to local clinical practice and individual perception of the thrombotic risk. All patients enrolled in the study will provide written informed consent. The study protocol will be approved by the institutional review boards or ethics committees of all participating institutions.