Validation of A Clinical Prediction Rule for Risk Stratification of Recurrent Venous Thromboembolism In Patients with Cancer-Associated Venous Thromboembolism

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4209-4209
Author(s):  
Martha L Louzada ◽  
Marc Carrier ◽  
Alejandro Lazo-Langner ◽  
Vi Dao ◽  
Jerry Zhang ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
High Risk ◽  
Prediction Rule ◽  
Recurrence Risk ◽  
Low Risk ◽  
Tnm Stage ◽  
Stage I ◽  
Risk Of Recurrence ◽  
Patients With Cancer ◽  
Recurrent Venous Thromboembolism

Abstract Abstract 4209 Background: The risk of recurrent venous thromboembolism (VTE) in patients with cancer-associated VTE, remains high even with the use of low molecular weight heparin (LMWH). However, due to the heterogeneity of the disease it is probable that recurrence risk varies widely. We have developed a prediction rule to classify risk of recurrence in the first 6 months of treatment: + 1 is scored for each of female gender, lung cancer and prior VTE and – 1 is scored for breast cancer and – 2 for TNM stage 1 disease. With a score of ≤ 0, 4.5% of patients recur (this represented 48% of the patient populations), and > 0, 19.7% recur. The rule was derived in a retrospective cohort study of patients followed at the Thrombosis unit of the Ottawa hospital and requires validation. Methods: We applied our rule in a new set of 819 consecutive patients with cancer-associated VTE from 2 multicentre randomized controlled trials comparing LMWH with vitamin K antagonists (VKA) (ClotCant group). In these studies the stage of disease was not separated by exact TNM classification, rather patients were classified as stage I, II (no metastasis) versus III, IV (metastasis). As such, we redid our derivation model with stage I and II grouped together, which gave this variable a score of – 1. This resulted in a prediction rule which gave a recurrence risk that no longer clearly dichotomized risk; rather gave a low, intermediate, and high risk groups. As in our derivation study, we evaluated patients' risk of recurrence regardless of type of anticoagulant use (VKA or LMWH). Results: Of 819 patients, 86 (10.5%) presented with a VTE recurrence during the anticoagulation period. When we applied our derivation rule in this population, we were able to demonstrate a significant difference in VTE recurrence risk dependent on gender, primary tumour site, stage and history of prior VTE. Patients with a score < 0 have low risk (5.1%) for VTE recurrence and this represented 19% of the patient population; patients with a score of 0 had a intermediate risk (9.8%) and this represented 42% of patients; a score ≥ 1 was high risk (13.9%), occurring in 38% of the population. Dichotomizing the results gave a recurrence risk of 8% in patients with a score ≤ 0 and a 15.2% recurrence risk with a score > 0. Conclusion: the validation dataset suggests reproducibility of our model. The dichotomized score is less discriminatory than our original model suggesting an advantage to classifying patients tumour stage as TNM stage I versus stage II, III and IV. Unfortunately, we could not test this hypothesis with the ClotCant dataset. Our model appears to differentiate risk for recurrence and should be utilized in treatment trials: attempting novel treatment strategies in high risk patients since LMWH alone does not seem to be enough; and using the less costly typical “LMWH followed by oral anticoagulants” in the low risk population to evaluate whether VKA can be as safe and effective as long term LMWH. Disclosures: Lee: Eisai: Research Funding; Sanofi Aventis: Consultancy, Honoraria; Leo Pharma: Consultancy; Pfizer: Consultancy, Honoraria; Bayer: Honoraria; Boehringer Ingelheim: Consultancy, Honoraria, Speakers Bureau.

Development of A Clinical Prediction Rule for Risk Stratification of Recurrent Venous Thromboembolism In Patients with Cancer-Associated Venous Thromboembolism

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 475-475 ◽  
Author(s):  
Martha L Louzada ◽  
Alejandro Lazo-Langner ◽  
Vi Dao ◽  
Jerry Zhang ◽  
Michael J. Kovacs ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
High Risk ◽  
Prediction Rule ◽  
Clinical Prediction Rule ◽  
Low Risk ◽  
Clinical Prediction ◽  
Potential Predictor ◽  
Patients With Cancer ◽  
History Of ◽  
Recurrent Vte

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.

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 ◽  
...  
Keyword(s):  
High Risk ◽  
Low Molecular Weight Heparin ◽  
Treatment Strategies ◽  
Prediction Rule ◽  
Clinical Prediction Rule ◽  
Recurrence Risk ◽  
Low Molecular Weight ◽  
Clinical Prediction ◽  
Unusual Site ◽  
Patients With Cancer

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.

Predictive ability of modified Ottawa score for recurrence in patients with cancer-associated venous thromboembolisms: from the COMMAND VTE Registry

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Y Nishimoto ◽  
Y Yamashita ◽  
T Morimoto ◽  
S Saga ◽  
Y Sato ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Group ◽  
Anticoagulation Therapy ◽  
Predictive Performance ◽  
High Risk Group ◽  
Low Risk ◽  
Intermediate Risk ◽  
Risk Of Recurrence ◽  
Patients With Cancer ◽  
Discriminating Power

Abstract Background/Introduction Patients with cancer-associated venous thromboembolisms (VTEs) have a markedly higher risk of recurrence as well as bleeding, compared to those without, leading to difficulty in achieving a good risk-to-benefit balance with anticoagulation therapy. Thus, the assessment of the risk of recurrence in an individual patient is essential. The modified Ottawa score has been developed to predict the risk of recurrence in patients with cancer-associated VTEs during anticoagulation therapy, however, the validity of the score is still controversial. Purpose We aimed to evaluate the utility and limitations of the modified Ottawa score in the risk stratification of recurrent VTEs in patients with cancer-associated VTEs. Methods The COMMAND VTE Registry is a multicenter retrospective registry enrolling 3027 consecutive patients with acute symptomatic VTEs among 29 Japanese centers between January 2010 and August 2014. The present study population consisted of 614 cancer-associated VTE patients with anticoagulation therapy beyond 10 days after the diagnosis, who were divided into 3 groups; High-risk group with a modified Ottawa score ≥1, Intermediate-risk group with a score = 0, and Low-risk group with a score ≤−1. To evaluate the discriminating power of the modified Ottawa score for recurrence, we described the receiver operating characteristic curve with a C-statistic, and evaluated the positive likelihood ratio as the predictive performance of the score for recurrence in each subgroup. Results The high-risk group accounted for 202 patients (33%), intermediate-risk group for 269 (44%), and low-risk group for 143 (23%). During the first 6 months of anticoagulation therapy, recurrent VTEs occurred in 39 patients. The cumulative incidence of recurrent VTEs substantially increased in the higher risk categories by the modified Ottawa score (High-risk group: 13.6%, Intermediate-risk group: 5.9%, and Low-risk group: 3.0%, Log-rank P=0.02) (Figure 1). The discriminating power of the score was modest with a C-statistic of 0.63 (95% CI 0.55–0.71). The positive likelihood ratios as the predictive performance of the score were 1.71 in the high-risk group, 0.81 in the intermediate-risk group, and 0.42 in the low-risk group. Women and patients with prior VTEs had numerically higher cumulative 6-month incidences of recurrent VTEs compared with those without, while patients with lung cancer, breast cancer, and without metastasis had numerically lower cumulative 6-month incidences of recurrent VTEs. Depending on the presence or absence of each score component, the risks of recurrence seemed to differ in the low-, intermediate-, and high-risk groups. Conclusions The risks of recurrence in patients with cancer-associated VTEs substantially increased in the higher risk categories by using the modified Ottawa score, but the discriminating power of the score for recurrence was modest with a widely variable impact of each score component on recurrence. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Research Institute for Production Development, Mitsubishi Tanabe Pharma Corporation

Failure of the Ottawa Score to Predict the Risk of Recurrent Venous Thromboembolism in Cancer Patients: The Prospective PREDICARE Cohort Study

2021 ◽  
Author(s):  
Philippe Girard ◽  
Silvy LAPORTE ◽  
Céline Chapelle ◽  
Nicolas Falvo ◽  
Lionel Falchero ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
High Risk ◽  
Cancer Patients ◽  
Risk Groups ◽  
Therapeutic Implications ◽  
Patients With Cancer ◽  
Risk Of Death ◽  
C Statistic ◽  
Recurrent Venous Thromboembolism ◽  
Recurrent Vte

Introduction: Recurrent venous thromboembolism (VTE) despite curative anticoagulation is frequent in patients with cancer. Identifying patients with a high risk of recurrence could have therapeutic implications. A prospective study was designed to validate the Ottawa risk score of recurrent VTE in cancer patients. Methods: In a prospective multicenter observational cohort, adult cancer patients with a recent diagnosis of symptomatic or incidental lower limb deep vein thrombosis or pulmonary embolism were treated with tinzaparin for 6 months. The primary endpoint was the recurrence of symptomatic or asymptomatic VTE within the first 6 months of treatment. All clinical events were centrally reviewed and adjudicated. Time-to-event outcomes were estimated by the Kalbfleisch and Prentice method to take into account the competing risk of death. A C-statistic value >0.70 was needed to validate the Ottawa score. Results: A total of 409 patients were included and analyzed on an intention-to-treat basis. Median age was 68 years, 60.4% of patients had PE, VTE was symptomatic in 271 patients (66.3%). The main primary sites were lung (31.3%), digestive tract (18.3%) and breast (13.9%) cancers. The Ottawa score was high (≥1) in 58% of patients. The 6-month cumulative incidence of recurrent VTE was 7.3% (95% confidence interval [CI]: 4.9-11.1) overall, and 5.0% (95%CI: 2.3-10.8) vs 9.1% (95%CI: 6.1-13.6) in the Ottawa low vs high risk groups, respectively. The C-statistic value was 0.60 (95%CI: 0.55-0.65). Conclusion: In this prospective cohort of patients with cancer receiving tinzaparin for VTE, the Ottawa score failed to accurately predict recurrent VTE.

Changing Paradigms in Breast Cancer Management: Introducing Molecular Genetics into the Treatment Algorithm

2008 ◽  
Vol 74 (10) ◽  
pp. 887-890 ◽  
Author(s):  
Jessica A. Rayhanabad ◽  
L. Andrew Difronzo ◽  
Phillip I. Haigh ◽  
Lina Romero
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Molecular Genetics ◽  
Risk Group ◽  
Recurrence Risk ◽  
Low Risk ◽  
Oncotype Dx ◽  
Risk Of Recurrence ◽  
Cancer Management ◽  
Gene Assay

Advances in molecular genetics aimed at individualizing breast cancer treatment have been validated. We examined the use of gene assays predictive of distant recurrence in breast cancer and their impact on adjuvant treatment. A retrospective chart review of 58 T1/T2, node-negative, estrogen-receptor positive breast cancer patients that underwent Oncotype DX gene assay testing between January and December 2006 was performed. We compared treatment received after gene assay evaluation to treatment based on National Comprehensive Cancer Network guidelines. Patients were grouped using these recommendations: Low-risk group (T1a/T1b), no chemotherapy; High-risk group (T1c/T2), chemotherapy. Oncotype DX recommendations are as follows: Low recurrence risk, no chemotherapy; high recurrence risk, chemotherapy. A change in management was defined as chemotherapy for T1a/T1b disease and no chemotherapy for T1c/T2 disease. Two T1a/T1b patients had high risk of recurrence per gene assay scores and were treated with chemotherapy (P < 0.05). Eighteen T1c/T2 patients had low recurrence risk scores; 13 (72%) were spared chemotherapy. The recurrence score increased the number of patients classified as low risk of recurrence by 12 per cent and downstaged 63 per cent of high-risk patients (P < 0.003). Gene assay results changed management in 15 of 58 (26%) patients (P < 0.05). The use of gene assays allowed us to better tailor treatment in a significant number of our patients.

scholarly journals Identification of Patients with Unprovoked Venous Thromboembolism and a Low Risk of Recurrence Estimated By the Vienna Prediction Model: A Prospective Cohort Management Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 775-775
Author(s):  
Sabine Eichinger ◽  
Lisbeth Eischer ◽  
Hana Šinkovec ◽  
Paul Gressenberger ◽  
Thomas Gary ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Prospective Cohort ◽  
Cumulative Risk ◽  
Recurrence Risk ◽  
Low Risk ◽  
Study Group ◽  
Risk Of Recurrence ◽  
One Year ◽  
D Dimer

Abstract Introduction: Patients with unprovoked venous thromboembolism (VTE) have a high recurrence risk, and, according to guidelines, should receive extended oral anticoagulation (OAC). OAC prevents recurrence in most patients but may cause major bleeding. Patients with a low recurrence risk could therefore benefit from limited OAC duration. The Vienna prediction model (VPM) estimates the recurrence risk of patients with a first unprovoked deep vein thrombosis (DVT) of the leg and/or pulmonary embolism (PE) based on the patient's sex, site of index VTE and D-Dimer measured after stopping OAC (Eichinger et al., Circulation 2010). In a prospective cohort management study, we evaluated whether the VPM can identify patients with an unprovoked VTE at low recurrence risk. Methods: The study was performed between January 2013 and May 2021 at two tertiary Austrian hospitals. Patients &gt;18 years with a first symptomatic DVT of the leg and/or symptomatic PE were eligible. The diagnosis of VTE was established by compression ultrasonography (CUS), spiral computed tomography, or lung scanning. We excluded patients with previous VTE, VTE provoked by a temporary risk factor including surgery, trauma, pregnancy, immobilisation, or female hormone intake, with cancer, OAC duration longer than 7 months or OAC for reasons other than VTE. OAC was discontinued 3 to 7 months after VTE diagnosis. D-Dimer was measured by a quantitative assay 3 weeks later and the probability of recurrence was estimated by the VPM. In patients with &lt;180 risk points (corresponding to a predicted one-year recurrence risk of &lt;4.4%), OAC was not resumed. CUS of both legs was performed at the time of discontinuation of OAC for reference baseline imaging in case of suspected recurrence. Patients were seen after 3, 12 and 24 months or at recurrence. Patients with a high recurrence risk (&gt;180 VPM risk points) were excluded and their management was left to the discretion of their local practitioner. The main outcome measure was independently adjudicated recurrence of symptomatic DVT of the leg and/or symptomatic PE. The study was approved by the local ethics committees and all patients gave written informed consent. Statistical analysis: Baseline characteristics of patients were described by median and interquartile range (IQR) or by absolute frequency and percentage. The cumulative risk of recurrent VTE after discontinuation of OAC was estimated using the Kaplan-Meier method. Recurrence risk was also predicted with the VPM for each patient, and predictions were averaged over the study group. Results: Of 818 eligible patients, 520 (65%) had a risk score of &lt;180 points and were classified as being at low risk of recurrence. They were included in the study and did not resume OAC. Their median age was 52 (42-65) years, and 289 (56%) were men. 226 (43%) patients had PE, 206 (40%) proximal and 88 (17%) distal DVT as index VTE. Median duration of anticoagulation was 3.9 (3.3-5.7) months, and the median time of follow-up was 23.9 (23.8, 23.9) months. Ten (1.9%) patients were lost to follow-up.52 patients (of which 30 were male) had non-fatal recurrent VTE (5.8 events per 100 patient-years, 95% CI 4.4-7.7). 28 (54%) patients had PE, 17 (33%) proximal and 7 (13%) distal DVT at recurrence. The cumulative risk of recurrence at one and two years was 5.2% (95% CI 3.2-7.2) and 11.2% (95% CI 8.3-14), respectively (Figure 1). The corresponding predicted recurrence risk for the study group was 4% and 7%, respectively. Conclusion: The VPM identifies patients with unprovoked VTE at low risk of recurrence. Applying the VPM refines risk stratification which could facilitate treatment decisions on the duration of OAC for patients and physicians. The model was well calibrated at one year. The apparent underestimation of the recurrence risk at two years could be countered by recalibration. Figure 1 Figure 1. Disclosures Eichinger: Takeda: Speakers Bureau; Daiichi-Sankyo: Speakers Bureau; BMS: Speakers Bureau; Bayer: Speakers Bureau; Pfizer: Speakers Bureau; Boehringer-Ingelheim: Speakers Bureau; CSL Behring: Speakers Bureau.

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