Predicting Venous Thromboembolism Recurrence Risk in Patients with Cancer: A Validation Study

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 394-394
Author(s):  
Martha L Louzada ◽  
Gauruv Bose ◽  
Andrew Cheung ◽  
Benjamin H Chin-Yee ◽  
Simon Wells ◽  
...  

Abstract Abstract 394 Background: Long-term low molecular weight heparin (LMWH) is the current standard for treatment of venous thromboembolism (VTE) in cancer patients. Whether treatment strategies should vary according to individual risk of VTE recurrence remains unknown. We have derived a clinical prediction rule that stratifies VTE recurrence risk in patients with cancer-associated VTE. The derivation model includes 4 independent predictors (sex, primary tumor site, stage and prior VTE). The score sum ranges between −3 and +3 points. Patients with a score ≤ 0 had low risk (≤4.5%) for recurrence and patients with a score above 1 had a high risk (≥ 19%) for VTE recurrence. Subsequently, we applied and validated the rule in an independent set of 819 patients from 2 randomized controlled trials comparing LMWH to warfarin for VTE treatment in cancer patients. In the current study we aim to externally validate our clinical prediction rule with an independent population of patients with cancer-associated VTE followed at the Thrombosis clinics of two tertiary Canadian centres. Methods: We conducted a retrospective cohort study of patients with cancer and VTE diagnosed and/or followed at the Thrombosis Clinic of the Victoria Hospital (London, Canada) from January 2006 to December 2010; and the Thrombosis Unit of the Ottawa Hospital (Ottawa, Canada) from January 2009 to December 2011. We included data from adult patients with active malignancy and objectively diagnosed acute pulmonary embolism (PE) or deep venous thrombosis (DVT) of the lower extremity (above knee), upper extremity and neck veins, or unusual site thrombosis. The primary outcome measure was VTE recurrence during the first six months of anticoagulation. Results: 353 patients fulfilled our inclusion criteria and were included in the study. There were 149 males, and the overall population had a median age of 64 years (range: 18 – 95). One hundred and twenty-three patients had lower extremity DVT, 93 had PE and 57 had both. The remaining 80 patients had either upper extremity/neck DVT (n = 55) or unusual site thrombosis (n = 25). 77 patients had a prior history of VTE. The most common primary tumour site was gastrointestinal, followed by the lung. Of the 304 patients with solid tumours, 230 (75.7%%) had TNM greater than I. Two hundred and ninety-three (83.0%) patients were treated with longterm low molecular weight heparin (LMWH) only and 60 (17.0%) with warfarin (VKA). VTE recurrence occurred in 44 of 353 patients (12.4%). When we evaluated VTE recurrence risk per site, there was no significant difference: London 13 of 90 and Ottawa 31 of 263 [RR=1.23 (95%CI= 0.671 – 2.237; p=0. 507)]. In addition, there was no significant benefit with the use of LMWH (37 of 293) over VKA (7 of 60) in the risk of recurrence [RR=0.92 (95%CI= 0.433 – 1.973; p= 0.8379)]. When we applied our clinical prediction rule (Table 1) in the entire study population, recurrent VTE occurred in 12 of 204 (5.8%) patients stratified as low risk probability and in 32 of 149 (21.4%) patients stratified as high risk probability (Table 2). Conclusions: Our prediction rule has been adequately validated to now be used in prospective trials of treatment. Future trials evaluating novel treatment strategies for high risk patients are warranted. Disclosures: No relevant conflicts of interest to declare.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 475-475 ◽  
Author(s):  
Martha L Louzada ◽  
Alejandro Lazo-Langner ◽  
Vi Dao ◽  
Jerry Zhang ◽  
Michael J. Kovacs ◽  
...  

Abstract Abstract 475 Background: Current guidelines suggest that all cancer patients with venous thromboembolism be treated with long-term low molecular weight heparin (LMWH). However, whether treatment strategies should vary according to patient and malignancy characteristics, in particular whether patients with low risk of VTE recurrence can be identified, remains unknown. Methods: We performed a single centre retrospective cohort study conducted at the Thrombosis Unit of the Ottawa Hospital. The charts of patients with cancer and VTE followed from 2002 to 2004 and from 2007 to 2008 were reviewed to assess the feasibility of derivation of a clinical prediction rule that stratifies VTE recurrence risk in patients with cancer—associated venous thrombosis through identification and evaluation of characteristics of malignancy and other clinical characteristics. We analysed only the patients who had a recurrent VTE within the first 6 months of anticoagulation. A univariate analysis determined the strength of association between each potential predictor and VTE recurrence. All potential predictor variables (p<0.25) were evaluated in a logistic regression model. Result: Of 543 patients 55 (10.1%) presented with a VTE recurrence during the first 6 months of anticoagulation. At VTE recurrence 19 (9.5%) patients were using VKA and 36 (10.5%) patients were using LMWH. The relative risk for VTE recurrence was not significantly different between patients who used VKA or LMWH [RR= 1. 13 (95%CI, 0.743 – 1.711; p= 0.565)]. A multivariate analysis suggested that gender, primary tumour site, tumour stage and history of prior VTE were significant variables to include in the clinical prediction rule. The final model included female gender, lung cancer and prior history of VTE as increasing risk and breast cancer and stage I disease as lowering risk. Patients with a score equal or less than 0 have low risk (4.5%) for VTE recurrence and this represented 48% of our patients. Patients with a score equal or above 1 have high risk (> 19%) for VTE recurrence (Tables 1 and 2). Conclusion: We were able to derive a simple and easy scoring system that stratifies patients with cancer-associated thrombosis into low or high risk of recurrent VTE. Future prospective validation of the model is warranted and may be very relevant to better tailor anticoagulation treatment in this heterogeneous population. Disclosure: No relevant conflicts of interest to declare.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1052-1052
Author(s):  
Carolyn J. Owen ◽  
Steve Doucette ◽  
Philip S. Wells

Abstract Background: The diagnosis of DVT can be made by determining pretest probability of disease and using this information in combination with DD testing and ultrasound imaging. A number of studies have evaluated the use of clinical probability but this literature has not been summarized. Purpose: To systematically review trials that evaluated DVT prevalence using clinical prediction rules either with or without DD for the diagnosis of DVT. Data Sources: English and French language studies were identified from a MEDLINE search from 1990 to March 2004 and were supplemented by a review of all relevant bibliographies. Study Selection: Prospective management studies of symptomatic outpatients with suspected DVT in which patients were followed for a minimum of 3 months were selected. Clinical prediction rules had to be employed prior to DD and diagnostic tests. Studies were excluded if patients with a history of prior DVT were enrolled or if insufficient information was presented to calculate the prevalence of DVT for each of the 3 clinical probability estimates (low, moderate and high risk). Data Extraction: Two reviewers assessed each study for inclusion/exclusion criteria and collected data on prevalence and on sensitivity, specificity and likelihood ratios of DD in each of the 3 clinical probability estimates (low, moderate and high risk). Data Synthesis: 14 management studies involving a clinical prediction model in the diagnosis of DVT in over 8000 patients were included, of which 11 utilized DD in the diagnostic algorithm. All studies employed the same clinical prediction rule. The inverse variance weighted average prevalence of DVT in the low, moderate and high probability subgroups were 4.9% (95% CI= 4.2% to 5.7%), 17.4% (95% CI= 16.2% to 18.8%), and 53.6% (95% CI= 51.1% to 56.2%), respectively. The overall weighted prevalence was 18.3% (95% CI= 17.4% to 19.2%). The sensitivity of DD for the diagnosis of DVT in the low, moderate and high probability subgroups were 90.4% (95% CI= 84.7% to 94.2%), 92.0 % (95% CI= 89.1% to 94.2%), 93.6% (95% CI= 91.2% to 94.3%); and the specificities were 69.9% (95% CI= 68.0% to 71.8%), 52.4% (95% CI= 49.8% to 55.0%), and 43.2% (95% CI= 38.8% to 47.6%), respectively. The Mantel-Haenszel pooled estimates for diagnostic odds ratios (DOR) were 17.4 (95%CI=10.4–29.1), 10.2 (95% CI=7.1–14.6), and 10.1 (95% CI=6.9–14.9) in low, moderate and high groups respectively. Conclusion: Accurate estimates of the prevalence of DVT can be achieved using the same clinical prediction rule. Using this rule, it is unlikely that low probability patients have a DVT probability of more than 5%. Specificity of the DD seems to have clinically relevant differences depending on pretest probability but the DORs (which incorporate sensitivity and specificity) are similar. The data suggest that DVT can be excluded if patients are low probability even when DDs of lower sensitivity are employed and that DD testing has lower utility in high probability patients since false positives are common.


2017 ◽  
Vol 117 (08) ◽  
pp. 1630-1636 ◽  
Author(s):  
Adriano Alatri ◽  
Lucia Mazzolai ◽  
Carme Font ◽  
Alfonso Tafur ◽  
Reina Valle ◽  
...  

SummaryTreatment of patients with cancer-associated venous thromboembolism (VTE) remains a major challenge. The modified Ottawa score is a clinical prediction rule evaluating the risk of VTE recurrences during the first six months of anticoagulant treatment in patients with cancer-related VTE. We aimed to validate the Ottawa score using data from the RIETE registry. A total of 11,123 cancer patients with VTE were included in the analysis. According to modified Ottawa score, 2,343 (21%) were categorised at low risk for VTE recurrences, 4,525 (41%) at intermediate risk, and 4,255 (38%) at high risk. Overall, 477 episodes of VTE recurrences were recorded during the course of anticoagulant therapy, with an incidence rate for low, intermediate, and high risk groups of 6.88% (95% CI 5.31–8.77), 11.8% (95% CI 10.1–13.6), and 21.3% (95% CI 18.8–24.1) patient-years, respectively. Overall mortality had an incidence rate of 21.1% (95% CI 18.2–24.3), 79.4% (95% CI: 74.9–84.1), and 134.7% (95% CI: 128.3–141.4) patient-years, respectively. The accuracy and discriminating power of the modified Ottawa score for VTE recurrence was modest, with low sensitivity, specificity and positive predictive value, and a C-statistics of 0.58 (95% CI: 0.56–0.61). In our analysis, the modified Ottawa score did not accurately predict VTE recurrence among patients with cancer-associated thrombosis, thus hindering its use in clinical practice. It is time to define a new score including other clinical predictors.


2010 ◽  
Vol 45 (1) ◽  
pp. 67-74 ◽  
Author(s):  
Gary B. Wilkerson ◽  
J. Todd Bullard ◽  
David W. Bartal

Abstract Context: Excessive fat mass clearly has adverse effects on metabolic processes that can ultimately lead to the development of chronic disease. Early identification of high-risk status may facilitate referral for definitive diagnostic tests and implementation of interventions to reduce cardiometabolic risk. Objective: To document the prevalence of metabolic syndrome among collegiate football players and to develop a clinical prediction rule that does not require blood analysis to identify players who may possess a high level of cardiometabolic risk. Design: Cross-sectional cohort study. Setting: University athletic training research laboratory. Patients or Other Participants: Sixty-two National Collegiate Athletic Association Division I Football Championship Subdivision football players (age  =  19.9 ± 1.2 years, height  =  182.6 ± 6.1 cm, mass  =  97.4 ± 18.3 kg). Main Outcome Measure(s): Anthropometric characteristics associated with body fat, isokinetic quadriceps strength, and biometric indicators associated with metabolic syndrome were measured. Participants were classified as high risk or low risk for future development of type 2 diabetes and cardiovascular disease. Results: The prevalence of metabolic syndrome in the cohort was 19% (12 of 62), and 79% (49 of 62) of the players exceeded the threshold for 1 or more of its 5 components. A 4-factor clinical prediction rule that classified individuals on the basis of waist circumference, blood pressure, quadriceps strength, and ethnic category had 92% sensitivity (95% confidence interval  =  65%, 99%) and 76% specificity (95% confidence interval  =  63%, 86%) for discrimination of high-risk or low-risk status. Conclusions: The risk for developing type 2 diabetes and cardiovascular disease appears to be exceptionally high among collegiate football players. A lack of race-specific criteria for the diagnosis of metabolic syndrome almost certainly contributes to an underestimation of the true level of cardiometabolic risk for African American collegiate football players.


2000 ◽  
Vol 18 (5) ◽  
pp. 1012-1012 ◽  
Author(s):  
Robert J. Klaassen ◽  
T. Robin Goodman ◽  
Ba Pham ◽  
John J. Doyle

PURPOSE: To prospectively derive and validate a clinical prediction rule to allow a more tailored approach to the management of pediatric oncology outpatients presenting with fever and neutropenia. PATIENTS AND METHODS: The clinical prediction rule was derived over a 1-year period and then validated over the following 8 months in a new set of fever and neutropenia episodes. Patients were excluded if they presented with comorbidity or an abnormal chest x-ray (CXR). RESULTS: Significant bacterial infection (SBI; defined as any blood or urine culture positive for bacteria, interstitial or lobar consolidation on CXR, or unexpected death from infection) was documented in 43 of the 227 episodes. Multivariate analysis found four significant factors: bone marrow disease, general appearance unwell on initial examination, monocyte count less than 0.1 × 109/L, and peak oral or oral equivalent temperature greater than 39°C. Only the monocyte count contributed to determining a low-risk group, excluding SBI with 84% sensitivity (95% confidence interval [CI], 61% to 100%), 42% specificity (95% CI, 38% to 46%), and a negative predictive value of 92% (95% CI, 76% to 100%). If the monocyte count was ≥ 0.1 × 109/L at the time of presentation (low risk), the incidences of SBI and bacteremia were 8% and 5%, respectively, versus 25% and 17% in the high-risk group. When validated in a new population of 136 episodes of fever and neutropenia, the incidences of SBI and bacteremia in the low-risk group were 12% and 5%, respectively, and 25% and 19% in the high-risk group. CONCLUSION: Pediatric oncology outpatients with fever and neutropenia who present with an initial monocyte count of ≥ 0.1 × 109/L and do not have comorbidity or an abnormal CXR at the time of presentation are at lower risk for SBI and can be considered for less aggressive initial therapy.


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