Hypercoagulation screening as an innovative tool for risk assessment, early diagnosis and prognosis in cancer: the HYPERCAN study

Falanga, Anna; Santoro, Armando; Labianca, Roberto; Braud, Filippo de; Gasparini, Giampietro; D’Alessio, Andrea; Barni, Sandro; Iacoviello, Licia; Barcella, Luca; Brevi, S.; Gamba, Sara; Giaccherini, Cinzia; Marchetti, Marina; Milesi, V.; Piras, Francesca; Rio, Francesca; Russo, Laura; Tartari, Carmen J; Tessarolo, Serena; Verzeroli, Cristina; Vignoli, Alfonso; Donati, Maria Benedetta; Masci, Giovanna; Nardozza, Angelo; Tondini, Carlo; Mandalà, Mario; Merelli, Barbara; Celio, Luigi; Martinetti, Antonia; Maria, Ilaria De; Meoni, Guido; Minelli, Mauro; Sarmiento, Roberta; Tarantini, Paola; Oliva, Nadia; Ghilardi, Mara; Malighetti, Paolo; Spinelli, Daniele; Sampietro, Giuseppe

doi:10.1016/s0049-3848(16)30099-8

Cited by 29 publications

(31 citation statements)

References 12 publications

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“…The Vienna Cancer and Thrombosis Study (CATS) and the HYPERCAN study proposed TG as a marker of the hypercoagulable profile in patients with cancer [ 8 , 9 ]. However, both studies encompass patients with mixed cancer diagnoses.…”

Section: Discussionmentioning

confidence: 99%

“…Thrombin is a key factor in coagulation activation [ 7 ], and its generation has been widely studied to unravel the mechanisms of cancer-associated VTE. Thrombin generation (TG), as determined by the calibrated automated thrombogram (CAT) assay, has recently gained interest as a biomarker of disease aggressiveness as well as VTE risk in cancer [ 8 , 9 ]. Cancer-associated hypercoagulability may in part be explained by the activation of tissue factor (TF), which is the main initiator of coagulation [ 6 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

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Coagulation biomarkers and prediction of venous thromboembolism and survival in small cell lung cancer: A sub-study of RASTEN - A randomized trial with low molecular weight heparin

et al. 2018

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Coagulation activation and venous thromboembolism (VTE) are hallmarks of cancer; however, there is an unmet need of improved biomarkers for individualized anticoagulant treatment. The present sub-study of the RASTEN trial was designed to explore the role of coagulation biomarkers in predicting VTE risk and outcome in a homogenous cancer patient population. RASTEN is a multicenter, randomized phase-3 trial investigating the survival effect of low molecular weight heparin enoxaparin when added to standard treatment in newly diagnosed small cell lung cancer (SCLC) patients. Plasma collected at baseline, during treatment, and at follow-up was used in this ad hoc sub-study (N = 242). Systemic coagulation was assessed using four assays reflecting various facets of the coagulation system: Total tissue factor (TF); extracellular vesicle associated TF (EV-TF); procoagulant phospholipids (PPL); and thrombin generation (TG). We found small variations of biomarker levels between baseline, during treatment and at follow-up, and appeared independent on low molecular weight heparin treatment. Overall, none of the measured biomarkers at any time-point did significantly associate with VTE incidence, although increased total TF at baseline showed significant association in control patients not receiving low molecular weight heparin (P = 0.03). Increased TG-Peak was significantly associated with decreased overall survival (OS; P = 0.03), especially in patients with extensive disease. Low baseline EV-TF predicted a worse survival in the low molecular weight heparin as compared with the control group (HR 1.42; 95% CI 1.04–1.95; P = 0.03; P for interaction = 0.12). We conclude that the value of the analyzed coagulation biomarkers for the prediction of VTE risk was very limited in SCLC patients. The associations between TG-Peak and EV-TF with patient survival and response to low molecular weight heparin therapy, respectively, warrant further studies on the role of coagulation activation in SCLC aggressiveness.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Coagulation biomarkers and prediction of venous thromboembolism and survival in small cell lung cancer: A sub-study of RASTEN - A randomized trial with low molecular weight heparin

et al. 2018

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“…The process of cancer growth and dissemination may interact with the hemostatic system in two ways: on one hand coagulation/fibrinolysis proteins may influence tumor progression and dissemination by different pathways, 4,5,17 and on the other hand, thrombosis and hemorrhagic events occur more frequently in cancer patients. 18,19 Concerning fibrinolytic components, several studies have shown that elevated levels of the key enzymes of the fibrinolytic system are predictors of poor patient outcome.…”

Section: Discussionmentioning

confidence: 99%

“…[2][3][4][5]20,21 Moreover, it is recognized that the hemostatic system is activated in the majority of cancer patients. 8,17 On the other hand, in the last few decades, several studies have underlined the role of the hemostatic and fibrinolytic systems in the pathogenesis of several cardiovascular diseases. [22][23][24][25] In particular, thrombosis and impaired fibrinolysis are among the major events underlying the occurrence of coronary artery disease (CAD).…”

Section: Discussionmentioning

confidence: 99%

Tissue Plasminogen Activator Levels and Risk of Breast Cancer in a Case–Cohort Study on Italian Women: Results from the Moli-sani Study

et al. 2020

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Background Elevated levels of key enzymes of the fibrinolytic system, such as tissue plasminogen activator (tPA), are reported as predictors of poor outcome in cancer patients. Limited information is available about their potential predictive value for breast cancer (BC) risk in the general population. Aim We examined the association of tPA levels with BC risk in a case–cohort study including women from the prospective Moli-sani cohort. Methods A sample of 710 women (mean age: 54.6 ± 12.1 years) was selected as a subcohort and compared with 84 BC cases, in a median follow-up of 4.2 years. Incident cases of BC were validated through medical records. tPA plasma levels were measured using an enzyme-linked immunosorbent assay kit. Hazard ratio (HR) and 95% confidence interval (CI), adjusted for relevant covariates, were estimated by a Cox regression model using the Prentice method. Results Compared with the lowest quartile (<4.9 ng/mL), women in the highest quartile of tPA (>11.2 ng/mL) had increased risk of BC (HRIVvsI: 2.20, 95% CI: 1.13–4.28) after adjusted for age, smoking, education, menopause, and residence. Further adjustment for biochemical markers did not modify this association. The risk of BC increased by 34% for each increase in 1 standard deviation of log-transformed tPA levels (p = 0.046). Elevated levels of tPA were associated mainly with estrogen-receptor-positive BC (2.08, 95% CI: 1.18–3.66). Conclusion Higher levels of tPA, reported to predict cardiovascular risk, are a potential biomarker for BC risk, supporting the hypothesis of a “common soil” linking the pathogenic mechanisms of hormone-dependent tumors and cardiovascular disease.

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“…The study included adult women with high-risk surgically treated breast cancer (stage I-II-III according to the American Joint Committee on Cancer [AJCC] 31 ) enrolled from March 2012 to December 2015 in the ongoing, Italian, multicenter, prospective HYPERCAN study 32,33 (see Appendix 1 for participating centers).…”

Section: Study Design and Populationmentioning

confidence: 99%

Thrombin generation predicts early recurrence in breast cancer patients

Marchetti

Giaccherini

Masci

et al. 2020

Journal of Thrombosis and Haemostasis

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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.

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Hypercoagulation screening as an innovative tool for risk assessment, early diagnosis and prognosis in cancer: the HYPERCAN study

Cited by 29 publications

References 12 publications

Coagulation biomarkers and prediction of venous thromboembolism and survival in small cell lung cancer: A sub-study of RASTEN - A randomized trial with low molecular weight heparin

Coagulation biomarkers and prediction of venous thromboembolism and survival in small cell lung cancer: A sub-study of RASTEN - A randomized trial with low molecular weight heparin

Tissue Plasminogen Activator Levels and Risk of Breast Cancer in a Case–Cohort Study on Italian Women: Results from the Moli-sani Study

Thrombin generation predicts early recurrence in breast cancer patients

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