scholarly journals Biomarkers of Haemostasis and Occurrence of Venous Thromboembolism Are Associated with Disease Progression and Poor Prognosis in Patients with Pancreatic Cancer

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 7-8
Author(s):  
Florian Moik ◽  
Gerald Prager ◽  
Sarah Wiedemann ◽  
Florian Posch ◽  
Ingrid Pabinger ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Disease Progression ◽  
Poor Prognosis ◽  
Palliative Chemotherapy ◽  
Stage Iv ◽  
Therapy Response ◽  
Competing Risk Analysis ◽  
Landmark Analyses ◽  
Pai 1 ◽  
D Dimer

Background: Patients with pancreatic cancer have a high risk for venous thromboembolism (VTE). Activation of haemostasis has been suggested to contribute to the progression of cancer and its metastatic spread. However, clinical data to support the contribution of activation of haemostasis to disease progression are scarce. Our aim was to evaluate the association biomarkers indicating activation of haemostasis and/or hypercoagulability and of VTE occurrence with survival and therapy response in patients with pancreatic cancer. Methods: Within a prospective, observational cohort study (Vienna Cancer and Thrombosis Study, CATS), we evaluated the subgroup of patients with pancreatic cancer (n=145). Levels of a comprehensive panel of haemostatic biomarkers (D-dimer, prothrombin fragment 1+2, fibrinogen, factor VIII, plasminogen activator inhibitor 1 (PAI-1), soluble (s)P-selectin, peak thrombin generation, endogenous thrombin potential) were measured at baseline. Differences in levels of haemostatic biomarkers between disease stages were tested for statistical significance by Kruskal-Wallis-test. The association of biomarker levels with overall survival (OS) and therapy response (progression-free survival (PFS) and radiological disease control rate; sub-cohort of patient initiating palliative chemotherapy, n=95) was analysed by multivariable Cox regression, adjusting for disease stage, grade, sex, age, ECOG, VTE (as time-dependent covariable) and vascular infiltration or compression by the primary tumour. Cumulative incidence of VTE was estimated in competing risk analysis, considering death as competing outcome event. The impact of VTE on OS and PFS was evaluated by multi-state modelling, adjusting for stage, grade, sex, age, ECOG and vascular involvement. Results: We observed higher baseline levels of biomarkers according to increasing stage of disease for D-dimer (stage I/II: median 1.25 µg/ml [interquartile range (IQR): 0.65-2.10]; stage III: 1.41 µg/ml [IQR: 0.65-2.24]; stage IV: 1.68 µg/ml [IQR: 0.98-3.82], p=0.035), and sP-selectin (stage I/II: median 34.2 ng/ml [IQR: 26.8-43.1]; stage III: 37.6 ng/ml [IQR: 31.4-49.1]; stage IV: 38.8 ng/ml [IQR:32.9-51.5], p=0.033). Higher levels of D-dimer, PAI-1 and sP-selectin were associated with shorter OS in multivariable analysis (hazard ratio (HR) for death per doubling: 1.33 [95% confidence interval (CI): 1.08-1.66], 1.25 [95% CI: 1.08-1.45, and 1.42 [95% CI: 1.00-2.01] (Figure 1). In the subgroup of patients initiating palliative chemotherapy, pre-therapeutic levels of D-dimer predicted for shorter PFS (HR for disease progression per double: 1.29 [95% CI: 1.03-1.61]) and a decreased probability for radiological therapy response (odds ratio to achieve radiological disease control per double: 0.61 [95% CI: 0.38-0.99]). Cumulative incidence estimates of VTE in competing risk analysis at 3, 6, 12, and 24 months were 9.0% [95% CI: 5.0-14.3], 13.1% [95% CI: 8.2-19.1], 16.6% [95% CI: 11.1-23.1], and 19.5% [95% CI: 13.4-26.2], respectively. The occurrence of VTE was associated with an immediate increase in risk of death (transition hazard ratio, (THR): 2.37 [95% CI: 1.47-3.84]) and early disease progression (THR: 2.34 [95% CI: 1.50-3.66]), which prevailed upon multivariable adjustment. In landmark analyses, median OS and PFS after VTE were 5.5 months [95% CI: 2.2-6.5] and 3.0 months [95% CI: 1.5-3.9] compared to 13.4 months [95% CI: 9.7-16.6] and 7.5 months [95% CI: 5.9-9.8] in those without VTE (Mantel-Byar: both p<0.001). Figure 2 displays landmark analyses of OS and PFS according to occurrence of VTE within the first 3 months of observation. Conclusion: Occurrence of VTE, activation of haemostasis and hypercoagulability, as indicated by elevated levels of D-dimer, PAI-1 and sP-selectin are associated with poor prognosis and D-dimer predicts for unfavourable response to palliative chemotherapy in patients with pancreatic cancer. Disclosures No relevant conflicts of interest to declare.

Hemostatic Biomarkers and Venous Thromboembolism Are Associated With Mortality and Response to Chemotherapy in Patients With Pancreatic Cancer

2021 ◽  
Author(s):  
Florian Moik ◽  
Gerald Prager ◽  
Johannes Thaler ◽  
Florian Posch ◽  
Sarah Wiedemann ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tissue Factor ◽  
Palliative Chemotherapy ◽  
Cox Regression ◽  
Extracellular Vesicle ◽  
Hazard Ratio ◽  
Factor Activity ◽  
Tissue Factor Activity ◽  
Pai 1 ◽  
D Dimer

Objective: Pancreatic cancer activates coagulation and increases risk of venous thromboembolism (VTE). We aimed at characterizing the association of hemostatic biomarkers and VTE with mortality and chemotherapy response. Approach and Results: Pancreatic cancer patients (n=145) were included in a prospective, observational cohort study (CATS [Vienna Cancer and Thrombosis Study]). Hemostatic biomarkers (D-dimer, extracellular vesicle–tissue factor activity, prothrombin fragment 1+2, fibrinogen, factor VIII, PAI-1 [plasminogen activator inhibitor 1], sP-selectin [soluble P-selectin], thrombin generation assay) were measured at inclusion. The impact of VTE on overall survival/progression-free survival (OS/PFS) was evaluated by multistate modeling. The association of biomarkers with OS was analyzed by Cox-regression and with PFS and disease control rate in patients initiating palliative chemotherapy (n=95) by Cox-regression and logistic regression. Multivariable analysis included stage, grade, sex, age, performance status, VTE (time-dependent), vascular infiltration/compression, and tumor marker levels (carbohydrate-antigen 19-9, carcinoembryonic antigen). VTE occurrence was associated with shorter OS (transition hazard ratio, 3.40 [95% CI, 2.05–5.64]) and shorter PFS (transition hazard ratio, 2.10 [1.16–3.79]). Median post-VTE OS/PFS in months was 5.5 [2.2–6.5] and 3.0 [1.5–3.9], compared with 13.4 [9.7–16.6] and 7.5 [5.9–9.8] in patients without VTE (both P <0.001). D-dimer, extracellular vesicle–tissue factor activity, PAI-1, and sP-selectin were associated with increased mortality (hazard ratio per doubling, 1.27 [1.00–1.61]; 1.63 [1.14–2.36]; 1.25 [1.06–1.47]; 1.52 [1.05–2.20]). In patients initiating palliative chemotherapy, higher D-dimer predicted shorter PFS (hazard ratio per doubling, 1.27 [1.01–1.60]) and lower disease control rate (odds ratio per doubling, 0.59 [0.36–0.98]). Conclusions: VTE diagnosis is associated with shorter OS and PFS. Higher baseline levels of D-dimer, extracellular vesicle–tissue factor activity, PAI-1, and sP-selectin were independently prognostic for increased mortality, and D-dimer predicted response to palliative chemotherapy.

scholarly journals Systemic Inflammation and Activation of Haemostasis Predict Poor Prognosis and Response to Chemotherapy in Patients with Advanced Lung Cancer

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1619
Author(s):  
Florian Moik ◽  
Sabine Zöchbauer-Müller ◽  
Florian Posch ◽  
Ingrid Pabinger ◽  
Cihan Ay
Keyword(s):  
Lung Cancer ◽  
Systemic Inflammation ◽  
Poor Prognosis ◽  
Prognostic Model ◽  
Prognostic Score ◽  
Therapy Response ◽  
Advanced Lung Cancer ◽  
Lymphocyte Ratio ◽  
Response To Chemotherapy ◽  
D Dimer

Systemic inflammation and activation of haemostasis are common in patients with lung cancer. Both conditions support tumour growth and metastasis. Therefore, inflammatory and haemostatic biomarkers might be useful for prediction of survival and therapy response. Patients with unresectable/metastatic lung cancer initiating 1st-line chemotherapy (n = 277, 83% non-small cell lung cancer) were followed in a prospective observational cohort study. A comprehensive panel of haemostatic biomarkers (D-dimer, prothrombin fragment 1+2, soluble P-selectin, fibrinogen, coagulation factor VIII, peak thrombin generation), blood count parameters (haemoglobin, leucocytes, thrombocytes) and inflammatory markers (neutrophil-lymphocyte ratio, lymphocyte-monocyte ratio, platelet-lymphocyte ratio, C-reactive protein) were measured at baseline. We assessed the association of biomarkers with mortality, progression-free-survival (PFS) and disease-control-rate (DCR). A biomarker-based prognostic model was derived. Selected inflammatory and haemostatic biomarkers were strong and independent predictors of mortality and therapy response. The strongest predictors (D-dimer, LMR, CRP) were incorporated in a unified biomarker-based prognostic model (1-year overall-survival (OS) by risk-quartiles: 79%, 69%, 51%, 24%; 2-year-OS: 53%, 36%, 23%, 8%; log-rank p < 0.001). The biomarker-based model further predicted shorter PFS and lower DCR. In conclusion, inflammatory and haemostatic biomarkers predict poor prognosis and treatment-response in patients with advanced lung cancer. A biomarker-based prognostic score efficiently predicts mortality and disease progression beyond clinical characteristics.

scholarly journals Umbilical mass as the sole presenting symptom of pancreatic cancer: a case report

2004 ◽  
Vol 59 (4) ◽  
pp. 198-202 ◽  
Author(s):  
Fábio Crescentini ◽  
Fernanda Deutsch ◽  
Carlos Walter Sobrado ◽  
Sérgio de Araújo
Keyword(s):  
Pancreatic Cancer ◽  
Poor Prognosis ◽  
Palliative Chemotherapy ◽  
Advanced Disease ◽  
Immunohistochemical Analysis ◽  
Abdominal Discomfort ◽  
Clinical Suspicion ◽  
Clinical Staging ◽  
Metastatic Involvement ◽  
Sister Mary Joseph

Umbilical nodes are rare. The metastatic involvement of the region was first described in 1846. Sister Mary Joseph was the first observer to establish the correlation between carcinomas and umbilical nodes. The umbilical node may be the sole presenting sign of cancer and is usually associated with advanced disease and poor prognosis. A 64-year-old woman, previously healthy, presented vague abdominal discomfort and a hard umbilical nodule for 1 week, which was first diagnosed as an incarcerated umbilical hernia. She underwent a new clinical assessment and biopsy. After immunohistochemical analysis and computerized tomography, she was diagnosed with pancreatic cancer. The clinical staging showed advanced disease with distant metastasis. She received palliative chemotherapy. After 8 months, she was alive in poor clinical condition. Clinical suspicion should lead to a careful additional evaluation whenever an umbilical nodule presents with malignant signs.

Prognostic model for survival in patients with advanced pancreatic cancer receiving palliative chemotherapy.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 248-248
Author(s):  
Yu Uneno ◽  
Tadayuki Kou ◽  
Masashi Kanai ◽  
Michio Yamamoto ◽  
Peng Xue ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Poor Prognosis ◽  
Prognostic Model ◽  
Palliative Chemotherapy ◽  
Cox Regression ◽  
Advanced Pancreatic Cancer ◽  
Prognostic Index ◽  
Prognostic Models

248 Background: The prognosis of patients with advanced pancreatic cancer (APC) is extremely poor. Several clinical and laboratory factors have been known to be associated with prognosis of APC patients. However, there are few clinically available prognostic models predicting survival in APC patients receiving palliative chemotherapy. Methods: To construct a prognostic model to predict survival in APC patients receiving palliative chemotherapy, we analyzed the clinical data from 306 consecutive patients with pathologically confirmed APC who received palliative chemotherapy. We selected six independent prognostic factors which remained independent prognostic factors after multivariate analysis. Thereafter, we rounded the regression coefficient (β) for each independent prognostic factor derived from the Cox regression equation (HR = eβ) and developed a prognostic index (PI). Results: Developed prognostic index (PI) was as follows: PI = 2 (if performance status score 2–3) + 1 (if metastatic disease) + 1 (if initially unresectable disease) + 1 (if carcinoembryonic antigen level ≥5.0 ng/ml) + 1 (if carbohydrate antigen 19-9 level ≥1000 U/ml) + 2 (if neutrophil–lymphocyte ratio ≥5). The patients were classified into three prognostic groups: favorable (PI 0–1, n = 73), intermediate (PI 2–3, n = 145), and poor prognosis (PI 4–8, n = 88). The median overall survival for each prognostic group was 16.5, 12.3 and 6.2 months, respectively, and the 1-year survival rates were 67.3%, 51.3%, and 19.1%, respectively (P < 0.01). The c index of the model was 0.658. This model was well calibrated to predict 1-year survival, in which overestimation (2.4% and 0.2% in the favorable and poor prognosis groups, respectively) and underestimation (3.6% in the intermediate prognosis group) were observed. Conclusions: This prognostic model based on readily available clinical factors would help clinicians in estimating the overall survival in APC patients receiving palliative chemotherapy.

scholarly journals Lung Metastases in Patients with Stage IV Pancreatic Cancer: Prevalence, Risk Factors, and Survival Impact

2019 ◽  
Vol 8 (9) ◽  
pp. 1402 ◽  
Author(s):  
Liu ◽  
Hung ◽  
Hsueh ◽  
Chang ◽  
Chen ◽  
...  
Keyword(s):  
Risk Factors ◽  
Pancreatic Cancer ◽  
Multivariate Analysis ◽  
Palliative Chemotherapy ◽  
Lung Metastases ◽  
Stage Iv ◽  
Survival Outcome ◽  
Entire Cohort ◽  
Isolated Lung ◽  
The Impact

The aim of this study was to evaluate the prevalence, the clinicopathological variables associated with probability of lung metastases, and the impact of lung metastases on survival outcome in patients with stage IV pancreatic cancer (PC) treated with palliative chemotherapy. A total of 654 patients with stage IV PC who underwent palliative chemotherapy from 2010–2016 were retrospectively enrolled in this study. Possible clinical variables associated with lung metastases and survival outcome were examined by univariate and multivariate analysis. Lung metastases were detected in 15.0% (3.4% with isolated lung metastases and 11.6% with synchronic metastases to lung and other organs). Female gender, poorly differentiated tumor grade, and large primary tumor size were independent risk factor in multivariate analysis. The median overall survival (OS) time was 6.5 months in the entire cohort, while the median OS was 11.8, 6.9, 7.7, 10.1, and 5.0 months for patients with isolated lung, isolated liver, isolated peritoneum, isolated distant lymph nodes, and multiple sites metastases, respectively. Isolated lung metastases were a better prognosticator for OS in univariate and multivariate analysis. This study utilized real-world clinical practice data to assess the prevalence, risk factors, and survival impact of lung metastases in patients with stage IV pancreatic cancer.

Predictors of venous thromboembolic complications in patients with pancreatic cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16220-e16220
Author(s):  
Oksana V. Katelnitskaya ◽  
Oleg I. Kit ◽  
Elena M. Frantsiyants ◽  
Yuriy A. Gevorkyan ◽  
Oleg Yu. Kaymakchi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
High Risk ◽  
Venous Thrombosis ◽  
Clinical Characteristics ◽  
Stage Iv ◽  
Distant Metastases ◽  
Underlying Disease ◽  
Ductal Adenocarcinoma ◽  
Tumor Type ◽  
D Dimer

e16220 Background: Patients with pancreatic cancer are at high risk for venous thrombosis. Thrombotic episodes are most often recorded at the tumor diagnosis, surgical treatment and chemotherapy courses, or the disease recurrence. This complication postpones the beginning of treatment of the underlying disease and increases the mortality rate of cancer patients. The purpose of the study was to reveal the relationship between clinical characteristics and disorders of hemostasis indicators in patients with pancreatic cancer, and to identify predictors of venous thrombosis. Methods: 246 patients diagnosed with pancreatic cancer were recruited in 2019. The most common histological tumor type was pancreatic ductal adenocarcinoma (91.9%). The most common tumor site was the head of the pancreas (68.3%). Almost half of the patients were initially diagnosed with stage IV cancer (TanyNanyM1). Surgery was performed in 28% of patients. VTEC incidence during the 12-month follow-up period was 15.4%. Results: Analysis of the clinical characteristics and initial hemostasis parameters in patients with and without venous thrombosis revealed that the risk of thrombosis was higher in patients with larger tumors and the presence of distant metastases. High levels of D-dimers at diagnosis doubled the risk of venous thrombosis during antitumor treatment. Conclusions: The most significant predictors of venous thrombosis in patients with pancreatic cancer are tumor size, stage IV, and initially high levels of D-dimer. The study of hemostasis indicators at the stage of diagnosis of pancreatic cancer (D-dimer) can help to identify patients with a high risk of VTEC, for whom anticoagulant prophylaxis with a low hemorrhagic risk is advisable.

One Month Follow-up of Haemostatic Variables in Patients Undergoing Aortocoronary Bypass Surgery

1995 ◽  
Vol 73 (03) ◽  
pp. 356-361 ◽  
Author(s):  
L Mannucci ◽  
P S Gerometta ◽  
L Mussoni ◽  
C Antona ◽  
A Parolari ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Bypass Surgery ◽  
Fibrinolytic System ◽  
Aortocoronary Bypass ◽  
Protamine Sulphate ◽  
Aortocoronary Bypass Surgery ◽  
Intraoperative Period ◽  
Pai 1 ◽  
D Dimer

SummaryIt is already known that activation of the coagulation and fibrinolytic system occurs in patients undergoing cardiopulmonary bypass (CPB). We have thus studied twenty patients (10 treated with aprotinin during CPB and 10 untreated) both during the intraoperative period and during thirty days follow up. In untreated patients D-dimer levels increased 4-fold during CPB and the levels were above baseline for the whole follow up (p<0.0001). D-dimer levels were reduced in aprotinin treated patients in comparison to untreated patients (p = 0.0172); levels then gradually increased to the values of the untreated patients over the following 24 h later and remained higher during the thirty day follow up. The behavior of haemostatic variables in the 24 h after CPB did not vary between untreated and aprotinin treated patients. In particular, five minutes after protamine sulphate administration, levels of F1 + 2 and TAT rose significantly (p = 0.0054, p = 0.0022 respectively), whereas fibrinogen significantly decreased (p<0.0001) and PAI-1 antigen levels were reduced. Two days after CPB the concentrations of F1 + 2 and TAT lowered, whereas fibrinogen and PAI-1 antigen levels increased. On the 5th, 8th and 30th days after CPB, F1 + 2 and TAT levels remained higher than those reported at baseline in both groups of patients, whereas fibrinogen levels increased over basal levels in aprotinin treated patients only.Thus, in addition to the activation of the coagulation and fibrinolytic system occurring during the intraoperative period, in patients undergoing CPB, there are alterations of haemostatic variables up to thirty days from surgery.

Aktivierungs- und Umsatzmarker der Hämostase im Verlauf der akuten tiefen Beinyenenthrombose

1995 ◽  
Vol 15 (02) ◽  
pp. 87-91 ◽  
Author(s):  
Ch. Burstein ◽  
S. Bitter ◽  
M. Kundt ◽  
M. Freund ◽  
O. Anders
Keyword(s):  
Thrombolytische Therapie ◽  
Pai 1 ◽  
D Dimer

ZusammenfassungIn einer prospektiven Untersuchung wurde das Verhalten von Thrombin-Antithrombin-lll-(TAT-)Komplex, D-Dimer, Plasminogenaktivator-lnhibitor-1 (PAI-1) und weiteren Parametern der Hämostase bei 50 Patienten mit spontaner tiefer Beinvenenthrombose bei Stellung der Diagnose während der initialen Behandlung und bei der ambulanten Kontrolle untersucht: 37 Patienten erhielten eine thrombolytische Therapie, davon 31 Patienten mit Streptokinase in ultrahoher Dosierung (UHSK) und sechs Patienten mit Urokinase; 13 Patienten wurden mit einer Heparininfusion behandelt.Im Vergleich zu den Patienten mit einer Heparintherapie führte die thrombolytische Therapie zu einem Anstieg von TAT (p <0,05), D-Dimer (p <0,01) und von PAI-1 (p <0,05). Bei vier Patienten trat eine Rethrombose nach Thrombolyse auf. Nach fibrinolytischer Therapie wurde eine Aktivierung der Gerinnung und eine erhöhte Aktivität von PAI-1 nachgewiesen, die für die Entstehung einer Rethrombose von Bedeutung sein können.

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