Pre-Chemotherapy Levels of Hemostatic Biomarkers and Prediction of Prognosis in Newly Diagnosed Metastatic Cancer Patients from the Hypercan Study

Abstract Introduction Patients with cancer commonly present with laboratory evidence of hypercoagulability. The HYPERCAN study (ClinicalTrials.gov, ID# NCT02622815) is an ongoing Italian prospective, multicenter, observational study, evaluating the predictive value of thrombotic markers for early cancer diagnosis in healthy subjects and for cancer prognosis and venous thromboembolism in patients with newly diagnosed cancer disease (Thromb Res, 2016). In this analysis of the HYPERCAN study, in a subcohort of consecutive patients with newly diagnosed metastatic non-small cell lung (NSCL) or gastrointestinal (GI) cancers, we aimed to assess whether the pre-chemotherapy levels of thrombotic biomarkers may be predictive of early disease progression (EDP, i.e. within 6 months) and early deaths (i.e. within 1 year). Methods The study cohort included 401 patients [median age: 65 (34-88) years] with metastatic NSCL (n=241) or GI (n=160) cancer. Clinical data were recorded at enrollment and during follow-up visits, disease progression being monitored by imaging. Fibrinogen (Clauss method, IL Werfen, Italy), d-dimer (immuneturbidimetric assay, IL Werfen, Italy), and thrombin generation (TG) potential (CAT assay, Stago, France) were measured in plasma samples collected at patient enrollment, before starting any curative chemotherapy and from a control group of 108 healthy subjects. The study protocol is approved by the local Ethics Committee. Informed written consent is obtained from all study subjects. Data are expressed as median (5th-95th percentile). Results Significantly higher plasma levels of fibrinogen, D-dimer and TG potential were observed in the cohort of cancer patients compared to healthy controls (p<0.01). Among cancer types, fibrinogen levels were significantly greater in NSCL as compared to GI cancer patients [479 (258-934) vs 402 (220-668) mg/dl), p<0.001]. After two year follow up, the cumulative incidence of EDP was 31% (CI 95% 27-36). Of interest, patients with EDP (n=125) vs those without EDP were characterized by significantly (p<0.05) greater pre-chemotherapy levels of leucocytes [9.1 (5.6-21.4) vs 8.4 (4.6-18.2) x109/L], platelets [305 (131-586) vs 283 (148-513) x109/L], fibrinogen [475 (290-913) vs 421 (226-814) mg/dl], and TG endogenous thrombin potential (ETP) [1,919 (1,137-3,086) vs 1,752 (1,264-2,559) nM*min]. In GI cancer, but not in lung cancer patients, multivariate Cox regression analysis according to site of primary tumor identified d-dimer and TG ETP plasma levels, together with GI cancer diagnosis, as independent risk factors for EDP. Concerning mortality, after two year follow-up, the cumulative incidence of overall survival at one year was 63% (CI 95% 58-67), early deaths = 37%. The group of patients who deceased during the first year (n=145) showed significantly (p<0.01) higher leucocyte count [9.7 (5.4-21.6) vs 8 (4.6-16.1) x109/L], plasma fibrinogen [486 (250-846) vs 402 (223-816) mg/dl] and d-dimer [515 (97-3,174) vs 286 (55-1,456) ng/ml] levels. In GI cancer, multivariate Cox regression analysis identified d-dimer and TG ETP plasma levels, leucocytes and platelet counts, and GI cancer diagnosis, as independent risk factors for mortality within 1 year. Differently, none of the hemostatic biomarkers were predictive for mortality in NSCL cancer patients. Conclusions The current analysis of prospectively collected data shows the utility of detecting circulating thrombotic biomarkers in specific cancer types. In particular, in GI metastatic cancer, the levels of D-dimer and TG before starting chemotherapy, together with having a GI cancer, could predict EDP (within 6 months) and early deaths (within 12 months). This was not the case for NSCL cancer. Currently, new tests involving other coagulation biomarkers are ongoing and will be evaluated. Project funded by AIRC "5xMILLE" n. 12237 grant from the "Italian Association for Cancer Research (AIRC)". * On behalf of the HYPERCAN investigators. Disclosures No relevant conflicts of interest to declare.

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Thrombin Generation and D-Dimer Significantly Predict for Early Disease Progression and Mortality in Patients with Gastrointestinal Cancer

Blood ◽

10.1182/blood-2020-136631 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 32-32

Author(s):

Marina Pesenti ◽

Marina Marchetti ◽

Cinzia Giaccherini ◽

Cristina Verzeroli ◽

Laura Russo ◽

...

Keyword(s):

Disease Progression ◽

Cancer Patients ◽

Cancer Diagnosis ◽

Cox Regression ◽

Newly Diagnosed ◽

Early Disease ◽

Gi Cancer ◽

Independent Risk Factors ◽

Ecog Ps ◽

D Dimer

Background: Abnormalities of laboratory coagulation tests are common in cancer patients, underlying a subclinical hypercoagulable state. Due to the reciprocal interaction between coagulation and cancer, the biomarkers of hemostatic system activation are under evaluation as a tool for predicting cancer outcomes, disease progression, and mortality. Aim: In this analysis of a prospective cohort of patients with newly diagnosed metastatic gastro-intestinal (GI) cancer, we wanted to evaluate whether the pre-chemotherapy abnormalities of hemostatic biomarkers may predict for early-disease progression (E-DP), i.e. within 6 months from cancer diagnosis, and for 1-year overall survival (1-year OS). Methods: The study cohort included 304 newly diagnosed metastatic GI cancer patients, candidate to chemotherapy associated or not with immunotherapy, enrolled from March 2012 to March 2019 in the HYPERCAN study (ClinicalTrials.gov, ID# NCT02622815), an ongoing Italian prospective, multicenter, observational study; 191 healthy subjects acted as a control group. At diagnosis, before starting any curative chemotherapy, plasma samples were collected and tested for the following hypercoagulation biomarkers: D-dimer and fibrinogen by an automated coagulometer analyzer (ACL TOP500, Werfen Group), and prothrombin fragment 1+2 (F1+2) by ELISA (Siemens). In addition, thrombin generation (TG) potential was evaluated by Calibrated Automated Thrombogram (CAT) assay at 5 pM tissue factor and endogenous thrombin potential (TG ETP) and TG peak were analyzed. Clinical data [i.e. age, sex, BMI, ECOG Performance Status (ECOG-PS), relevant comorbidies] and the hemochromocytometric parameters were recorded at enrollment, whereas E-DP was clinically monitored every 3 chemotherapy cycles and during follow-up. Results: A cohort of 304 (205M/99F) metastatic GI cancer patients (206 colorectal and 98 gastric cancers) with a median age of 66 years (min-max: 29-85) was available for analysis. At enrollment, patients presented with a hypercoagulable state, as shown by significantly higher (p<0.001) plasma levels of D-dimer, fibrinogen and F1+2, and significantly higher (p<0.01) TG peak and TG ETP values than controls. After 6 months from the start of chemotherapy, E-DP had occurred in 80 patients, providing a cumulative incidence of 29.6% (CI 95% 24.1-35.1). E-DP subjects had significantly (p<0.05) higher baseline D-dimer levels and TG ETP value than non-E-DP patients. Correlation analyses showed that pre-chemotherapy fibrinogen (β = -0.127; p=0.048), D-dimer (β = -0.198; p=0.002) and TG ETP (β = -0.133; p=0.034) levels were significantly and inversely associated with time to E-DP. By Multivariate Cox regression analysis, gastric cancer diagnosis (HR=1.546), pre-chemotherapy D-dimer (HR=1.001) and TG ETP values (HR=1.001) were identified as independent risk factors for E-DP. After 1 year from the start of chemotherapy, 228 patients were dead and the OS was 66.6% (CI 95% 61.3-71.9). Patients who died within 1 year showed higher baseline D-dimer, F1+2, fibrinogen, TG peak and TG ETP values compared to the remaining subjects. Multivariate Cox regression identified independent risk factors for 1-year OS the followings: gastric cancer diagnosis (HR=2.237), D-Dimer (HR=1.001) and TG ETP (HR=1.001) levels, white blood cell count (HR=1.094), ECOG-PS>1 (HR=3.858), and chemotherapy plus immunotherapy treatment (HR=2.274). Conclusion: Our results show that, in newly diagnosed metastatic gastrointestinal cancer patients, before the start of antitumor treatment, a procoagulant state exists. Among the different hemostatic parameters evaluated, D-dimer and TG ETP appear as candidate biomarkers to predict for 6-month DP and 1-year OS. In particular, in this setting, the role of TG as a prognostic biomarker emerges for the first time in a large prospective cohort of GI cancer patients. Project funded by "5xMILLE" n. 12237 grant from the "Italian Association for Cancer Research (AIRC)" Disclosures Santoro: Bristol-Myers Squibb, SERVIER, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Sanofi, ArQule: Consultancy; Arqule, Sanofi: Consultancy; Takeda, Roche, Abbvie, Amgen, Celgene, AstraZeneca, ArQule, Lilly, Sandoz, Novartis, Bristol-Myers Squibb, Servier, Gilead Sciences, Pfizer, Eisai, Bayer, MSD: Speakers Bureau; Takeda, Roche, Abbvie, Amgen, Celgene, AstraZeneca, ArQule, Lilly, Sandoz, Novartis, Bristol-Myers Squibb, Servier, Gilead Sciences, Pfizer, Eisai, Bayer, MSD: Speakers Bureau; Bristol Myers Squibb, Servier, Gilead, Pfizer, Eisai, Bayer, MSD: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb, SERVIER, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Sanofi, ArQule: Consultancy, Speakers Bureau; Bristol-Myers Squibb, SERVIER, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Sanofi, ArQule: Consultancy.

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D-dimer daily continuous tendency predicts the short-term prognosis for COVID-19 independently: A retrospective study from Northeast China

Clinical Hemorheology and Microcirculation ◽

10.3233/ch-201071 ◽

2021 ◽

pp. 1-9

Author(s):

Yinting Xing ◽

Wei Yang ◽

Yingyu Jin ◽

Chao Wang ◽

Xiuru Guan

Keyword(s):

Cox Regression ◽

Short Term ◽

Cox Regression Analysis ◽

Prognosis Group ◽

The Difference ◽

Group B ◽

The Relationship ◽

Worse Prognosis ◽

D Dimer

BACKGROUND AND OBJECTIVE: To study whether D-dimer daily continuous tendency could predict the short-term prognosis of COVID-19. PATIENTS AND METHODES: According to the short-term prognosis, 81 COVID-19 patients were divided into two groups, one of worse prognosis (Group W) and the other of better prognosis (Group B). The slope of D-dimer linear regression during hospitalization (SLOPE) was calculated as an indicator of D-dimer daily continuous tendency. The SLOPE difference between Group W and Group B was compared. The difference between the discharge results and the 3-month follow-up results was also compared. COX regression analysis was used to analyze the relationship between SLOPE and short-term prognosis of COVID-19. RESULTS: There were 16 patients in Group W and 65 patients in Group B. Group W had more critical proportion (p < 0.0001), indicating that the symptoms of its patients were more severe during hospitalization. ARDS, the most visible cause of worse prognosis, accounted for up to 68.75%, and many symptoms merged and resulted in worse prognosis. The D-dimer levels of Group W not only were significantly higher (p < 0.0001), but also showed an increasing trend. In addition, the D-dimer levels at discharge were significantly higher than those at follow-up (p = 0.0261), and the mean difference was as high as 0.7474. SLOPE significantly correlated with the short-term prognosis of COVID-19 independently (RR: 1.687, 95% CI: 1.345–2.116, P < 0.0001). The worst prognosis occurred most likely during the first month after COVID-19 diagnosis. CONCLUSION: Our study found that D-dimer daily continuous tendency independently correlates with worse prognosis and can be used as an independent predictor of the short-term prognosis for COVID-19.

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The influence of obesity on tumor recurrence in vulvar cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e17130 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e17130-e17130 ◽

Cited By ~ 1

Author(s):

Rüdiger Klapdor ◽

Peter Hillemanns ◽

Linn Lena Woelber ◽

Julia Kathrin Jueckstock ◽

Felix Hilpert ◽

...

Keyword(s):

Cancer Patients ◽

Vulvar Cancer ◽

Cox Regression ◽

Univariate Analysis ◽

Disease Free Survival ◽

Tumor Grade ◽

Tumor Stage ◽

Tumor Diameter ◽

Cox Regression Analysis

e17130 Background: Obesity is associated with worse patients’ survival in several cancer entities. Vulvar cancer as well as obesity show increasing incidence over the last years. The influence of obesity on prognosis of vulvar cancer patients is not clear. However, knowledge about this may have consequences on prevention, treatment, and follow-up. Methods: This is an analysis of the large AGO-CaRE-1 study. Patients suffering from squamous cell vulvar cancer (UICC stage IB and higher), treated in 29 cancer centers between 1998 and 2008, were categorized in a database, in order to analyze treatment patterns and prognostic factors in a retrospective setting. Results: In total, 849 patients with documented height and weight were divided into two groups depending on their body mass index (BMI, < 30 vs. ≥30 kg/m²). There was no difference in the baseline variables (age, tumor diameter, depth of infiltration, tumor stage, nodal invasion, tumor grade) between both groups (p > 0.05). However, we identified differences regarding ECOG status and preexistent comorbidities (cardiovascular, dementia) towards healthier patients with BMI < 30 kg/m². Treatment variables (R0 resection, chemotherapy, radiotherapy, continuation of adjuvant therapy) did not differ (p > 0.05). Patients with BMI ≥30 kg/m² underwent radical vulvectomy more often (61.1 % vs. 51.8%, p = 0.042). During follow-up, there was a higher recurrence rate in the group having a BMI ≥30 kg/m² (43.4%, vs. 28.3%, p < 0.01) due to an increased rate of local recurrences (33.3% vs. 18.5%, p < 0.01). The rate of groin and distant recurrences was similar between both groups (p > 0.05). Noteworthy, we observed a significantly shorter disease free survival (DSF) of the obese patients in univariate analysis (HR 1.362, 95%CI 1.093-1.696, p = 0.006). Even in multivariate Cox-regression analysis including age, ECOG, tumor stage, type of surgery, nodal invasion, tumor grade, and comorbidities patients with BMI ≥30 kg/m² had a significantly shorter DFS (HR 1.811, 95%CI 1.005-3.262, p = 0.048). Conclusions: In this first large study about the association between obesity and prognosis of vulvar cancer patients, we observed that a BMI ≥30kg/m² was associated with shorter DFS, mainly attributed to a higher risk for local recurrence.

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Measurement of Thrombin Generation Is a Positive Predictive Biomarker of V enous Thromboembolism (VTE) in Metastatic Cancer Patients Enrolled in the Hypercan Study

Blood ◽

10.1182/blood.v126.23.654.654 ◽

2015 ◽

Vol 126 (23) ◽

pp. 654-654 ◽

Cited By ~ 2

Author(s):

Anna Falanga ◽

Marina Marchetti ◽

Cristina Verzeroli ◽

Cinzia Giaccherini ◽

Giovanna Masci ◽

...

Keyword(s):

Cancer Patients ◽

Healthy Subjects ◽

Metastatic Cancer ◽

Breast Cancer Patients ◽

Vein Thrombosis ◽

Kaplan Meier ◽

Cancer Types ◽

D Dimer

Abstract Introduction The HYPERCAN study is an ongoing prospective Italian multicenter trial (Thromb.Res. 2014, Suppl 2, 182), designed to evaluate the role of laboratory hypercoagulation screening to predict early diagnosis (in healthy subjects), or prognosis and response to therapy in patients with either limited or metastatic cancers. Four cancer types are included, i.e. non-small cell lung [NSCL], gastric, colorectal, and breast cancers. The occurrence of clinically manifest VTE events, confirmed by objective diagnostic tests, is also recorded. Patients are followed up for 5 years or death. Aim In a group of patients with metastatic cancer enrolled in the HYPERCAN program, we wanted to evaluate the role of thrombin generation assay (TG), fibrinogen, and D-dimer levels in predicting the occurrence of VTE in the follow up. Methods As of June 2015, overall 831 patients with metastatic cancer have been enrolled. According to protocol, blood samples from these patients are collected at enrollment (baseline), after 3 and 6 chemotherapy cycles, and at end of treatment, or earlier if cancer disease progression. We measured the levels of TG, fibrinogen, and D-dimer in the baseline citrated plasma samples from the first 281 patients enrolled into the study (158 M/123 F; median age 64 years, range 32-84; NSCL = 56.2%, gastric = 11.1%, colorectal = 14.6%, breast = 18.1%). TG was measured by the Calibrated automated thrombogram (CAT assay, STAGO, France) at 5pM TF and results expressed as endogenous thrombin potential (ETP), fibrinogen and D-dimer were measured by commercial assays (Q.F.A. Thrombin; D-dimer HS; Werfen, Italy). Cut-off values were established by ROC curves; Kaplan Meier analysis was performed to define the VTE risk. Results Overall the patient baseline ETP values as well as the fibrinogen and D-Dimer levels were significantly greater than those of a control group of healthy subjects (p<0.0001). Among the cancer types, ETP values were highest in patients with NSCL cancer, and lowest in those with gastric cancer (1899±517 nM*min vs 1622±550 nM*min; p=0.024). D-dimer and fibrinogen levels were greatest in gastric (801±186 ng/ml) and NSCL (484±190 mg/dl) cancers, respectively, and were both lowest in breast cancer patients. After a median follow up of 473 days, overall 37 VTE events were recorded in 36 patients: 16 pulmonary embolism (PE), 16 deep vein thrombosis (DVT), 3 superficial vein thrombosis, and 1 PE + DVT. Of these events, 69% occurred in NSCL, 17% in colon, 8.5% in gastric, and 5.5% in breast cancer patients. Median time to VTE was 5 months from enrollment, >80% of VTE developed during chemotherapy. Baseline ETP levels were significantly higher in patients with VTE than in patients without VTE (2020±618 nM*min vs 1799±467 nM*min; p=0.017). Univariate analysis (Kaplan-Meier) showed that patients with ETP>1750 nM*min had about 3-fold higher risk of developing VTE than those with ETP<1750 nM*min (HR:2.841, 95% CI 1.42-5.69 p=0.002). ETP predictive value remained significant by multivariate analysis after correction for age, gender, and tumor site (HR: 2.341, 95% CI 1.15-4.75, p=0.019). Differently, the baseline levels of D-dimer and fibrinogen did not significantly predict for VTE. Conclusions These results reveal that ETP is a valuable marker in predicting VTE in metastatic cancer patients, therefore it can help to optimize the identification of the high risk subjects, which remains an important challenge and may improve the design of interventional studies of efficacy and safety of primary thromboprophylaxis in cancer patients during chemotherapy. Project funded by AIRC "5xMILLE" n. 12237 grant from the "Italian Association for Cancer Research (AIRC)". Disclosures Santoro: Celgene: Research Funding.

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Chronic Diseases among Older Cancer Survivors

Journal of Cancer Epidemiology ◽

10.1155/2012/206414 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 17

Author(s):

Laura Deckx ◽

Marjan van den Akker ◽

Job Metsemakers ◽

André Knottnerus ◽

François Schellevis ◽

...

Keyword(s):

Colorectal Cancer ◽

Venous Thrombosis ◽

Cancer Patients ◽

Chronic Diseases ◽

Cancer Diagnosis ◽

Cox Regression ◽

Cox Regression Analysis ◽

Older Cancer Patients ◽

After Cancer ◽

Colorectal Cancer Patients

Objective. To compare the occurrence of pre-existing and subsequent comorbidity among older cancer patients (≥60years) with older non-cancer patients.Material and Methods. Each cancer patient (n=3835, mean age 72) was matched with four non-cancer patients in terms of age, sex, and practice. The occurrence of chronic diseases was assessed cross-sectionally (lifetime prevalence at time of diagnosis) and longitudinally (incidence after diagnosis) for all cancer patients and for breast, prostate, and colorectal cancer patients separately. Cancer and non-cancer patients were compared using logistic and Cox regression analysis.Results. The occurrence of the most common pre-existing and incident chronic diseases was largely similar in cancer and non-cancer patients, except for pre-existing COPD (OR 1.21, 95% CI 1.06–1.37) and subsequent venous thrombosis in the first two years after cancer diagnosis (HR 4.20, 95% CI 2.74–6.44), which were significantly more frequent (P<0.01) among older cancer compared to non-cancer patients.Conclusion. The frequency of multimorbidity in older cancer patients is high. However, apart from COPD and venous thrombosis, the incidence of chronic diseases in older cancer patients is similar compared to non-cancer patients of the same age, sex, and practice.

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Thrombotic Risk Assessment in a Prospective Cohort of Newly Diagnosed Ambulatory Cancer Patients Candidate to Chemotherapy

Blood ◽

10.1182/blood-2019-129901 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3642-3642

Author(s):

Anna Falanga ◽

Cristina Verzeroli ◽

Marina Marchetti ◽

Cinzia Giaccherini ◽

Laura Russo ◽

...

Keyword(s):

Risk Assessment ◽

High Risk ◽

Cancer Patients ◽

Cumulative Incidence ◽

Prospective Cohort ◽

Tumor Site ◽

Newly Diagnosed ◽

Thrombotic Risk ◽

D Dimer

Introduction: The occurrence of venous thromboembolism (VTE) during chemotherapy may result in treatment delays with unfavorable effects on cancer outcome, therefore VTE prevention is a relevant issue. Current guidelines recommend primary thromboprophylaxis in select high-risk cancer outpatients undergoing chemotherapy. Hence, the use of risk assessment models involving both clinical and biological parameters is increasingly important. In this analysis, in a large prospective cohort of patients with newly diagnosed metastatic non-small cell lung (NSCLC), colorectal (CRC), gastric (GC) or breast (BC) cancers, we assessed whether pre-chemotherapy levels of thrombotic biomarkers may help to stratify patients at different risk levels of VTE during the first 6 months of anti-tumor therapy. Methods: The study cohort included patients with advanced cancer enrolled from January 2012 to December 2017 in the HYPERCAN study (ClinicalTrials.gov, ID# NCT02622815), an ongoing Italian prospective, multicenter, observational study (Falanga et al, Thromb Res 2016). Clinical data and blood samples were collected at enrollment and during scheduled follow-up visits. Baseline plasma levels of fibrinogen (Clauss method), d-dimer (immunoturbidimetric assay), prothrombin fragment F1+2 (ELISA), FVIIa-AT (ELISA) and thrombin generation (TG, CAT assay) were measured. The study protocol was approved by the local Ethics Committee. Informed written consent was obtained from all study subjects. The outcome measure of the current analysis is the time to the occurrence of first symptomatic and/or incidental VTE, objectively confirmed. Results: A cohort of 922 patients [median age: 66 (30-92) years] with metastatic NSCLC (n=416), CRC (n=262), GC (n=105) and BC (n=139) was available for analysis. After a median follow-up of 327 days (range 44-1,548), VTE occurred in 122 (76 M/46 F) patients [median age 64 y (range 40-85)] providing a cumulative incidence of 19.7% (CI 95%: 16-23). According to tumor site, VTE frequency was: NSCLC (n= 64, 15.3%) > CRC (n= 38, 14.5%) > GC (n= 12, 11.4%) > BC (n= 8, 5.7%). Biomarkers' analysis of baseline plasma samples from 598 patients showed significantly higher levels of fibrinogen, d-dimer and TG in the cancer cohort compared to healthy control subjects (p<0.01). NSCLC patients had significantly (p<0.001) higher levels of d-dimer compared to CRC and BC patients, and of fibrinogen (p<0.001) compared to CRC, BC and GC patients. Cumulative incidence of VTE at 6 months was 10% (CI 95% 8-12). In particular, patients who had VTE in 6 months presented with significantly higher pre-chemotherapy levels of D-Dimer than VTE-free subjects (p<0.05). Cox-multivariate analysis identified as independent risk factors for VTE, high d-dimer (HR: 2.1, CI 95% 1.2 - 3.7; p=0.008), high peak of TG (HR: 1.8, CI 95% 0.99 - 3.2; p=0.052), and site of primary tumor (non-BC vs BC) (HR: 3.3, CI 95% 1.01 - 10.5; p=0.048). A score for VTE prediction was created with these variables and three risk categories (low, intermediate, and high) were generated. The cumulative incidence of VTE at 6 months in each risk category was 3.9%, 9.8%, and 19%, respectively (low vs high HR: 2.36 p=0.005; intermediate vs high HR 2.16 p=0.006). Differently, the application of the Khorana score failed to identify high risk patients. Conclusions: Our prospective study in a large cohort of metastatic cancer patients shows the high burden of VTE during the first 6 months of chemotherapy. Furthermore, laboratory data from this analysis enable us to create a risk scoring system based on d-dimer and TG together with tumor site, that significantly identifies patients at the highest VTE risk. Further investigation are worth to externally validate this score for clinical use. Project funded by AIRC "5xMILLE multiunit extension program" n. 12237 grant from the "Italian Association for Cancer Research (AIRC)". Disclosures Santoro: Eisai: Consultancy, Speakers Bureau; Novartis: Speakers Bureau; MSD: Speakers Bureau; Servier: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; BMS: Consultancy; Abb-Vie: Speakers Bureau; Roche: Speakers Bureau; Bayer: Consultancy, Speakers Bureau; AstraZeneca: Speakers Bureau; BMS: Speakers Bureau; Amgen: Speakers Bureau; Celgene: Speakers Bureau; Lilly: Speakers Bureau; Arqule: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Sandoz: Speakers Bureau; Takeda: Speakers Bureau.

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Effects of the Timing of Venous Thromboembolic Events on Survival of Patients with Uterine Cancer

Blood ◽

10.1182/blood.v124.21.1534.1534 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1534-1534

Author(s):

Heera Remasankar ◽

Xiao Zhou ◽

Saroj Vadhan-Raj

Keyword(s):

Survival Time ◽

Cancer Patients ◽

Cancer Diagnosis ◽

Uterine Cancer ◽

Hazard Ratio ◽

Newly Diagnosed ◽

Venous Thromboembolic ◽

Uterine Cancers ◽

The Impact

Abstract Background: Cancer patients are at high risk for venous thromboembolic event (VTE), and the occurrence of VTE can affect the prognosis. However, it is unclear if the timing of VTE can influence the prognosis. The purpose of this study was to evaluate the incidence and impact of the timing of VTE (early vs late) on the survival of patients with uterine cancers. Methods: A retrospective cohort study was conducted. The study population included all uterine cancer patients who had newly diagnosed episode of VTE from January 1st 2006 to December 31st2007 at MD Anderson Cancer Center. Medical records of these patients were reviewed for cancer diagnosis, patient demographics, metastasis, date of diagnosis of VTE, type of VTE, the site of VTE, and any recurrences during the follow up period of 2 years since the first VTE. Clinical and laboratory parameters predictive for survival were also reviewed. All VTE episodes, including symptomatic as well as incidental VTEs were confirmed by the radiological studies using CT ANGIO, CT scan, Doppler compression ultrasound or V/Q perfusion scans. The survival time was defined as the time from the date of cancer diagnosis to the date of death, or to the date of last follow up. Survival analysis was conducted using Kaplan-Meier method and Cox proportional hazard models. Results: Of the 2151 patients with newly diagnosed VTEs within the 2 years study period, 33 patients were found to have uterine cancers. The median age was 60 years (range 41-84 years). Among all the primary VTEs, 42% were pulmonary embolus (PE); 45% were deep vein thrombosis (DVT), and 12% were concurrent PE/DVT (diagnosed on the same day). The median time of VTE from the date of cancer diagnosis was 8 months (range 0 - 88 months). The majority of these VTE events (55%) were found to occur within 1 year from the date of cancer diagnosis. A total of 8 patients had 10 recurrent episodes of VTE (2 patients had 2 recurrent VTE episodes) during the follow up period. The median survival time was 33 months (range 2.6-121.6 months); 82% of these patients had a metastatic disease. Multivariate proportional hazards model showed that the diagnosis of VTE within 6 months from the cancer diagnosis [Hazard ratio: 3.8, 95% CI (1.1-12.9), p=0.03] and the presence of baseline white blood cell (WBC) count of greater than 11,000/uL [Hazard ratio: 3.5, 95% CI (1.0-12.2), p=0.045] were statistically significant independent predictors for 2 year survival adjusting for age, presence of central venous catheter (CVC), and the baseline platelet count of greater than 350,000/uL. Conclusion: These findings suggest that the timing of VTE is an important indicator of prognosis in patients with uterine cancer; patients who had VTE within 6 months from cancer diagnosis had a shorter 2 year survival. Future larger studies may better define the impact of timing of VTE on survival of patients with Uterine Cancers. Disclosures No relevant conflicts of interest to declare.

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Development and validation of a nomogram to predict synchronous lung metastases in patients with ovarian cancer: a large cohort study

Bioscience Reports ◽

10.1042/bsr20203089 ◽

2020 ◽

Vol 40 (11) ◽

Author(s):

Yufei Yuan ◽

Fanfan Guo ◽

Ruoran Wang ◽

Yidan Zhang ◽

Guiqin Bai

Keyword(s):

Ovarian Cancer ◽

Overall Survival ◽

Cancer Patients ◽

Lung Metastasis ◽

Cox Regression ◽

Lung Metastases ◽

Newly Diagnosed ◽

Discriminative Ability ◽

Factors Affecting ◽

Cox Regression Analysis

Abstract Purpose: Lung metastasis is an independent risk factor affecting the prognosis of ovarian cancer patients. We developed and validated a nomogram to predict the risk of synchronous lung metastases in newly diagnosed ovarian cancer patients. Methods: Data of ovarian cancer patients from the Surveillance, Epidemiology, and Final Results (SEER) database between 2010 and 2015 were retrospectively collected. The model nomogram was built on the basis of logistic regression. The consistency index (C-index) was used to evaluate the discernment of the synchronous lung metastasis nomogram. Calibration plots were drawn to analyze the consistency between the observed probability and predicted probability of synchronous lung metastases. The Kaplan–Meier method was used to estimate overall survival rate, and influencing factors were included in multivariate Cox regression analysis (P<0.05) to determine the independent prognostic factors of synchronous lung metastases. Results: Overall, 16059 eligible patients were randomly divided into training (n=11242) and validation cohorts (n=4817). AJCC T, N stage, bone metastases, brain metastases, and liver metastases were evaluated as predictors of synchronous lung metastases. Finally, a nomogram was constructed. The nomogram based on independent predictors was calibrated and showed good discriminative ability. Mixed histological types, chemotherapy, and primary site surgery were factors affecting the overall survival of patients with synchronous lung metastases. Conclusion: The clinical prediction model has high accuracy and can be used to predict lung metastasis risk in newly diagnosed ovarian cancer patients, which can guide the treatment of patients with synchronous lung metastases.

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Markers of Coagulation and Angiogenesis Can Serve As Surrogate Biomarkers for Disease Activity and Survival in Cancer Patients

Blood ◽

10.1182/blood.v128.22.4992.4992 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4992-4992

Author(s):

Elina Angelova Beleva ◽

Tanya Deneva ◽

Veselin Popov ◽

Janet G. Grudeva

Keyword(s):

Cancer Patients ◽

Tissue Factor ◽

Plasma Levels ◽

Cox Regression ◽

Conflicts Of Interest ◽

Predictive Biomarkers ◽

Metastatic Progression ◽

Elevated Plasma ◽

Urokinase Plasminogen Activator Receptor ◽

Cox Regression Analysis

Abstract Based on observations of the link between hemostatic system and malignancy it is plausible to consider that plasma coagulation factors could serve as easily accessible markers for detection of malignant state and monitoring of cancer patients. Therefore, we hypothesized that tissue factor (TF), angiopoietin-2 (Ang-2) and soluble urokinase plasminogen activator receptor (suPAR) might perform as diagnostic and predictive biomarkers for the presence of malignancy as well as for the development of cancer-related events: metastatic progression and death. To analyze their performance TF-associated microparticle activity (MPTF), tissue factor antigen (TFAg), Ang-2 and suPAR were determined in 128 cancer patients with various cancer types receiving chemotherapy by sequential measurements (up to four times) at prespecified time points incorporated into interim and end-of-treatment analysis. MPTF activity was measured with Zymuphen MPTF kit, TFAg, suPAR and ANG-2 were quantitated by ELISA. Patients were followed up for progression free survival (PFS) from therapy initiation until occurrence of a combined event defined as either metastatic progression or death. In order to determine the predictive ability of hemostatic biomarkers for a PFS event Log-rank (Mantel-Cox) test was applied. ROC analysis was used to determine the cut off values for detection of an event, cut off values were transformed into binary variables and Kaplan-Meier curves were constructed. Cox regression analysis was applied to explore quantitatively the effect on the risk of progression. Results: Cut off values for the occurrence of an event were MPTF < 0.5 pg/ml (AUC 0.591), TFAg (√ pg/ml) > 8.28 (AUC 0.603), Ang-2 > 302.3 pg/ml (AUC 0.615) and suPAR (√ pg/ml) > 2.83. Shortened PFS was associated with decreased MPTF procoagulant activity and elevated plasma levels of TFAg, Ang-2, suPAR. As significant predictors for PFS were determined only TFAg (RR 4.57, p=0.038), Ang-2 (RR 2.138, p=0.031) and suPAR (RR 2.238, p=0.049). Conclusion: TFAg, Ang-2 and suPAR might be identified as significant adverse predictors of metastatic progression or death in cancer patients and risk is increased with elevated plasma levels. Disclosures No relevant conflicts of interest to declare.

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Effect of discharge to subacute rehabilitation (SAR) on hospitalized patients with progressive gastrointestinal (GI) cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.26_suppl.41 ◽

2016 ◽

Vol 34 (26_suppl) ◽

pp. 41-41

Author(s):

Andrew S. Epstein ◽

Anjali V. Desai ◽

Leonard Saltz

Keyword(s):

Cancer Patients ◽

Metastatic Cancer ◽

Cancer Center ◽

Low Grade ◽

First Line ◽

First Line Therapy ◽

Gi Cancer ◽

History Of ◽

Chemotherapy Patients

41 Background: SAR may be an alternative when hospice is declined. However, the outcomes of discharges to SAR in cancer patients with progressive (chemotherapy-refractory) disease are not known. We examined the characteristics and outcomes of patients with debility from progressive metastatic GI cancer who were discharged to SAR after an admission to our center. Methods: An institutional electronic database was queried to identify patients of the GI medical oncology service of Memorial Sloan Kettering Cancer Center who had been discharged to a SAR facility. Patient exclusion criteria were: incomplete follow-up, non-metastatic cancer, low grade neuroendocrine tumors, patients receiving first-line chemotherapy or with newly diagnosed cancer awaiting planned chemotherapy, patients off treatment with a remote history of metastatic cancer, and a primary admitting diagnosis representing an acute complication of cancer treatment. Results: From 2008-2014, 22 patients meeting criteria were identified. Median overall survival from the time of discharge to SAR was 0.8 months (range 0.2-5.2 months). Of the 22 patients, 7 (32%) died at the SAR. Twelve (55%) and 19 (86%) died within 1 and 3 months of discharge to SAR, respectively. For 7 patients (32%), documentation indicated that hospice, instead of SAR, had been recommended by clinicians but declined by family. Nine patients (41%) ultimately were transitioned to hospice within 3 months of discharge to SAR. Eight (36%) were readmitted to hospital within 1 month of discharge to SAR. Two (9%) were able to follow up with their medical oncologist for an outpatient appointment after discharge to SAR. None of the 22 patients received further chemotherapy after discharge to SAR. Conclusions: SAR is not a productive alternative to hospice in hospice-eligible patients with GI malignancies.In patients with metastatic GI cancers whose diseases had progressed beyond first-line therapy and who were hospitalized for reasons other than acute reversible toxicity, discharges to SAR were not associated with either prolonged survival or resumption of chemotherapy. These data can help inform decisions and establish goals of care in advanced GI cancer patients.

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