Utility of the Khorana and the new-Vienna CATS prediction scores in cancer patients of the HYPERCAN cohort.

BACKGROUND: Risk assessment models (RAMs) are relevant approaches to identify cancer outpatients at high risk of venous thromboembolism (VTE). Among the proposed RAMs, the Khorana (KRS) and the new-Vienna CATS risk scores have been externally validated in ambulatory patients with cancer. OBJECTIVES: To test KRS and new-Vienna CATS scores in 6-month VTE prediction and mortality in a large prospective cohort of metastatic cancer outpatients during chemotherapy. PATIENTS/METHODS: Newly diagnosed patients with metastatic non-small cell lung, colorectal, gastric, or breast cancers were analyzed (n = 1286). The cumulative incidence of objectively confirmed VTE was estimated with death as a competing risk and multivariate Fine and Gray regression. RESULTS: Within 6 months, 120 VTE events (9.7%) occurred. The KRS and the new-Vienna CATS scores showed comparable c-stat. Stratification by KRS provided VTE cumulative incidences of 6.2%, 11.4%, and 11.5% in the low-, intermediate-, and high-risk categories, respectively (p = ns), and of 8.5% vs. 11.8% (p = ns) in the low- vs. high-risk group by the single 2-point cut-off value stratification. Using a pre-defined 60-point cut-off by the new-Vienna CATS score, 6.6% and 12.2% cumulative incidences were obtained in the low- and high-risk groups, respectively (p < 0.001). Furthermore, having a KRS ≥2 = or a new-Vienna CATS score >60 points was also an independent risk factor for mortality. CONCLUSION: In our cohort, the 2 RAMs showed a comparable discriminating potential; however, after the application of cut-off values, the new-Vienna CATS score provided statistically significant stratification for VTE. Both RAMs proved to be effective in identifying patients at increased risk of mortality.

Thrombin generation predicts early recurrence in breast cancer patients.

BACKGROUND: Cancer patients present with a hypercoagulable state often associated with poor disease prognosis. OBJECTIVES: This study aims to evaluate whether thrombin generation (TG), a global coagulation test, may be a useful tool to improve the identification of patients at high risk of early disease recurrence (ie, E-DR within 2 years) after breast cancer surgery. PATIENTS/METHODS: A cohort of 522 newly diagnosed patients with surgically resected high-risk breast cancer were enrolled in the ongoing prospective HYPERCAN study. TG potential was measured in plasma samples collected before starting systemic chemotherapy. Significant predictive hemostatic and clinic-pathological parameters were identified in the derivation cohort by Cox regression analysis. A risk prognostic score for E-DR was generated in the derivation and tested in the validation cohort. RESULTS: After a median observation period of 3.4 years, DR occurred in 51 patients, 28 of whom were E-DR. E-DR subjects presented with the highest TG values as compared to both late-DR (from 2 to 5 years) and no relapse subjects (P < .01). Multivariate analysis in the derivation cohort identified TG, mastectomy, triple negative and Luminal B HER2-neg molecular subtypes as significant independent predictors for E-DR, which were utilized to generate a risk assessment score. In the derivation and validation cohorts, E-DR rates were 2.3% and 0% in the low-risk, 10.1% and 6.3% in the intermediate-risk, and 18.2% and 16.7%, in the high-risk categories, respectively. CONCLUSIONS: Inclusion of TG in a risk-assessment model for E-DR significantly helps the identification of operated breast cancer patients at high risk of very early relapse.

Thrombotic biomarkers for risk prediction of malignant disease recurrence in patients with early stage breast cancer.

In cancer patients, hypercoagulability is a common finding. It has been associated with an increased risk of venous thromboembolism, but also to tumor proliferation and progression. In this prospective study of a large cohort of breast cancer patients, we aimed to evaluate whether pre-chemotherapy abnormalities in hemostatic biomarkers levels: (i) are associated with breast cancer-specific clinico-pathological features; and (ii) can predict for disease recurrence. D-dimer, fibrinogen, prothrombin fragment 1+2, and FVIIa/antithrombin levels were measured in 701 early-stage resected breast cancer patients candidate to adjuvant chemotherapy and prospectively enrolled in the HYPERCAN study. Significant prognostic parameters for disease recurrence were identified by Cox regression multivariate analysis and used for generating a risk assessment model. Pre-chemotherapy D-dimer, fibrinogen, and pro-thrombin fragment 1+2 levels were significantly associated with tumor size and lymph node metastasis. After 3.4 years of follow up, 71 patients experienced a recurrence. Cox multivariate analysis identified prothrombin fragment 1+2, tumor size, and Luminal B HER2-negative or triple negative molecular subtypes as independent risk factors for disease recurrence. Based on these variables, we generated a risk assessment model that significantly differentiated patients at low- and high-risk of recurrence (cumulative incidence: 6.2 vs 20.7%; Hazard Ratio=3.5; P<0.001). Our prospective clinical and laboratory data from the HYPERCAN study were crucial for generating a scoring model for assessing risk of disease recurrence in resected breast cancer patients, candidate to systemic chemotherapy. This finding stimulates future investigations addressing the role of plasma prothrombin fragment 1+2 in the management of breast cancer patients to provide the rationale for new therapeutic strategies. (The HYPERCAN study is registered at clinicaltrials.gov identifier 02622815).