Cancer-associated Pulmonary Embolism Research Articles

Home Treatment for Active Cancer Patients With Low-Risk Pulmonary Embolism - A Predetermined Companion Report From the ONCO PE Trial.

Patients with appropriately selected low-risk pulmonary embolism (PE) can be treated at home, although it has been controversial whether applies to patients with cancer, who are considered not to be at low risk.Methods and Results: The current predetermined companion report from the ONCO PE trial evaluated the 3-month clinical outcomes of patients with home treatment and those with in-hospital treatment. The ONCO PE trial was a multicenter, randomized clinical trial among 32 institutions in Japan investigating the optimal duration of rivaroxaban treatment in cancer-associated PE patients with a score of 1 using the simplified version of the Pulmonary Embolism Severity Index (sPESI). Among 178 study patients, there were 66 (37%) in the home treatment group and 112 (63%) in the in-hospital treatment group. The primary endpoint of a composite of PE-related death, recurrent venous thromboembolism (VTE) and major bleeding occurred in 3 patients (4.6% [0.0-9.6%]) in the home treatment group and in 2 patients (1.8% [0.0-4.3%]) in the in-hospital treatment group. In the home treatment group, there were no cases of PE-related death or recurrent VTE, but major bleeding occurred in 3 patients (4.6% [0.0-9.6%]), and 2 patients (3.0% [0.0-7.2%]) required hospitalization due to bleeding events. Active cancer patients with PE of sPESI score=1 could be potential candidates for home treatment.

Outpatient management of cancer-associated pulmonary embolism: A post-hoc analysis from the HOME-PE trial

IntroductionCancer-related pulmonary embolism (PE) is associated with poor prognosis. Some decision rules identifying patients eligible for home treatment categorize cancer patients at high risk of complications, precluding home treatment. We sought to assess the effectiveness and the safety of outpatient management of patients with low-risk cancer-associated PE. MethodsIn the HOME-PE trial, hemodynamically stable patients with symptomatic PE were randomized to either triaging with Hestia criteria or sPESI score. We analyzed 3 groups of low-risk PE patients: 47 with active cancer treated at home (group 1), 691 without active cancer treated at home (group 2), and 33 with active cancer as the only sPESI criterion qualifying them for hospitalization (group 3). The main outcome was the composite of recurrent venous thromboembolism, major bleeding, and all-cause death within 30 days after randomization. ResultsPatients treated at home had composite outcome rates of 4.3 % (2/47) for those with cancer vs. 1.0 % (7/691) for those without (odds ratio (OR) 4.98, 95%CI 1.15–21.49). Patients with cancer had rates of complications of 4.3 % when treated at home vs. 3.0 % (1/33) when hospitalized (OR 1.19, 95%CI 0.15–9.47). In multivariable analysis, active cancer was associated with an increased risk of complications for patients treated at home (OR 7.95; 95%CI 1.48–42.82). For patients with active cancer, home treatment was not associated with the primary outcome (OR 1.19, 95%CI 0.15–9.74). ConclusionsAmong patients treated at home, active cancer was a risk factor for complications, but among patients with active cancer, home treatment was not associated with adverse outcomes.

Pulmonary embolism in cancer patients. Effectiveness of vitamin K antagonists and direct oral anticoagulants in long-term therapy.

Patients with cancer are prone to develop pulmonary embolism (PE) in the course of cancer-associated thrombosis. These patients have increased risk of both recurrent venous thromboembolism and major bleeding. Pulmonary embolism treatment in the cancer patient group is challenging. Selection of anticoagulants, duration of anticoagulation, decision of adjuvant therapy, and adjustment of the regimen in special situations are the major problems that need to be considered in the treatment of cancer-associated PE. Current first line treatment in long-term therapy following an episode of PE is low molecular weight heparin (LMWH), with direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) listed as viable alternatives. This study aims to explore long-term oral anticoagulation therapy for cancer patients. Both VKAs and DOACs are compared to LMWH, which serves as a gold standard in anticoagulation therapy for cancer patients and has proven to be effective.

Intensify Standardized Anticoagulation for Cancer-associated Pulmonary Embolism: From Single-center Real-world Data

Pulmonary embolism (PE) is a significant contributor to mortality in patients with cancer. Although anticoagulation serves as the cornerstone of treatment for cancer-associated PE, it has not been emphasized in real-world settings. The aim of this study was to examine the impact of suboptimal anticoagulant treatment on the prognosis of cancer-associated PE. A cohort of 356 individuals newly diagnosed with acute PE were enrolled. The primary outcome of the study was recurrent venous thromboembolism (VTE), and the secondary outcomes were all-cause mortality and major bleeding (consisting of a reduction in the hemoglobin level by at least 20 g/L, transfusion of at least 2 units of blood, or symptomatic bleeding in a critical area or organ or fatal bleeding). Of the total participants, 156 (43.8%) were diagnosed with cancer. A comparison between the cancer and noncancer groups revealed that patients with cancer were more frequently asymptomatic (41.0% vs 4.5%; P < 0.001), less likely to have right ventricular dysfunction (4.5% vs 14.0%; P=0.001), received less anticoagulant treatment during hospitalization (85.3% vs 98.5%; P < 0.001), and had a shorter duration of anticoagulation (5.02 [7.40] months vs 14.19 [10.65] months; P < 0.001). In addition, patients with cancer were found to be at a higher risk of recurrent VTE (17.3% vs 4.0%; P < 0.001) and all-cause mortality (23.7% vs 10.5%; P=0.001). Multiple Cox regression analysis indicated that discontinuation of anticoagulation at 3 months was a significant risk factor for recurrent VTE in the cancer group (HR, 15.815; 95% CI, 3.047-82.079; P=0.001). The brief duration of anticoagulation therapy and elevated likelihood of recurrent VTE serve as cautionary indicators for the need to enhance awareness of standardized anticoagulant treatment for cancer-associated PE. The ultimate goal is to enhance patient prognosis and quality of life.

Comorbidities and high in-hospital mortality of cancer-associated pulmonary embolism: findings from a real-world registry study.

Comorbidities and high in-hospital mortality of cancer-associated pulmonary embolism: findings from a real-world registry study.

Prediction of serious complications in patients with pulmonary thromboembolism and solid cancer: Validation of the EPIPHANY Index in a prospective cohort of patients from the PERSEO study.

There is currently no validated score capable of classifying cancer-associated pulmonary embolism (PE) in its full spectrum of severity. This study has validated the EPIPHANY Index, a new tool to predict serious complications in cancer patients with suspected or unsuspected PE. The PERSEO Study prospectively recruited individuals with PE and active cancer or receiving antineoplastic therapy from 22 Spanish hospitals. The estimation of the relative frequency θ of complications based on the EPIPHANY Index categories was made using the Bayesian alternative for the binomial test. A total of 900 patients, who were diagnosed with PE between October 2017 and January 2020, were enrolled. The rate of serious complications at 15 days was 11.8%, 95% highest density interval [HDI], 9.8-14.1%. Of the EPIPHANY low-risk patients, 2.4% (95% HDI, 0.8-4.6%) had serious complications, as did 5.5% (95% HDI, 2.9-8.7%) of the moderate-risk participants and 21.0% (95% HDI, 17.0-24.0%) of those with high-risk episodes. The EPIPHANY Index was associated with overall survival (OS) in patients with different risk levels: median OS was 16.5, 14.4, and 4.4 months for those at low, intermediate, and high risk, respectively. Both the EPIPHANY Index and the Hestia criteria exhibited greater negative predictive value and a lower negative likelihood ratio than the remaining models. The incidence of bleeding at 6 months was 6.2% (95% HDI, 2.9-9.5%) in low/moderate-risk vs 12.7% (95% HDI, 10.1-15.4%) in high-risk (p-value = 0.037) episodes. Of the outpatients, serious complications at 15 days were recorded in 2.1% (95% HDI, 0.7-4.0%) of the cases with EPIPHANY low/intermediate-risk vs 5.3% (95% HDI, 1.7-11.8%) in high-risk cases. We have validated the EPIPHANY Index in patients with incidental or symptomatic cancer-related PE. This model can contribute to standardize decision-making in a scenario lacking quality evidence.

Performance Status and Long-Term Outcomes in Cancer-Associated Pulmonary Embolism: Insights From the Hokusai-VTE Cancer Study

BackgroundPerformance status (PS) is a reliable prognostic tool for overall survival in patients with cancer-associated pulmonary embolism (PE). However, its association with venous thromboembolism (VTE) recurrence and bleeding remains unclear. ObjectivesThe aim of this study was to investigate whether PS at the time of PE diagnosis and its course during follow-up are linked to VTE-related outcomes. MethodsIn this post hoc analysis of the Hokusai-VTE Cancer study, multivariable survival analysis was used to examine the association of PS with anticoagulation discontinuation and the composite primary outcome of VTE recurrence or major bleeding in patients with cancer-associated PE. PS was assessed using the Eastern Cooperative Oncology Group (ECOG) scale at baseline and at predefined study follow-up visits. ResultsOverall, 652 patients with cancer-associated PE were included. During 12-month follow-up, PS worsened in 317 of 642 patients (49.4%) with complete ECOG data at the end of follow-up. Those with worse ECOG values over follow-up were more likely to discontinue anticoagulation for any reason apart from death (adjusted HR: 1.59; 95% CI: 1.31-1.93). The composite primary outcome occurred in 57 of 500 patients with baseline ECOG status 0 or 1 and in 32 of 152 patients with ECOG status 2 (cumulative incidence at 12 months 10.7% [95% CI: 8.2%-13.9%] vs 14.4% [95% CI: 9.7%-21.3%]). Worse ECOG values during follow-up were associated with greater risk for the composite outcome (adjusted HR: 2.13; 95% CI: 1.24-3.67). ConclusionsECOG PS is a valuable indicator for predicting VTE-related outcomes and may inform decision making regarding anticoagulation during follow-up in patients with cancer-associated PE.

Increased risk of long-term mortality following pulmonary embolism in Denmark, 2000–2020: a nationwide trend study

Abstract Background New diagnostics and treatment regimens have been introduced in the last 20 years which may have influenced the prognosis of pulmonary embolism (PE). However, there is a lack of studies investigating temporal trend in short- and long-term mortality following PE in different subgroups. Purpose We aimed to investigate temporal trends in short- and long-term mortality following PE according to age, sex, and cancer status. Method This study was based on data from Danish national registries. All patients with a first-time inpatient hospital diagnosis of PE between the 1st of January 2000 through 3rd of December 2020 were included in the study. Mortality was calculated as the proportion of patients who died within 30 days and 31–365 days, respectively, and were presented with 95% confidence intervals (CI), and additionally stratified into categories of age groups (18–39, 40–59, 60–79, and 80–100 years), sex (male/female) and cancer status (no cancer/cancer). Cancer was defined as a cancer diagnosis registered within 6 months prior to the PE diagnosis. Results In total 62,750 patients had a first-time PE during the study period. The mean age of the study population was 68.3 years (sd), and 32,617 (51.9%) were women and 18,719 (29.83%) of patients had cancer. The 30-day mortality for age groups, sex, and cancer status decreased during the study period 2000–2020 (Figure 1A). The 31–365-day mortality for age group 40–59 years increased from 5.7% [95% CI: 3.7–8.5] in 2000 to 9.5% [95% CI: 7.5–11.9] in 2019. Age group 80–100 years increased from 18.5% [95% CI: 14.8–22.8] in 2000 to 23.5% [95% CI: 21.0–26.2] in 2019. No temporal differences were observed for age groups 18–39 and 60–79 years. Mortality for cancer-associated PE increased from 24.8% [95% CI: 19.8–30.6] in 2000 to 29.9% [95% CI: 27.4–32.4] in 2019 (Figure 1B). Conclusion Despite overall mortality following PE has improved, our data suggest that short-term mortality following pulmonary embolism has improved considerably while long-term mortality were increased. Future studies should assess whether this phenomenon is due to a different patient risk profile (e.g. cancer) or lack of longer term care (e.g. rehabilitation program, withdrawal of antithrombotic treatment). Funding Acknowledgement Type of funding sources: None.

Pulmonary Embolism in the Cancer Associated Thrombosis Landscape.

In cancer patients, pulmonary embolism (PE) is the second leading cause of death after the cancer itself, most likely because of difficulties in diagnosing the disease due to its nonclassical presentation. The risk of PE recurrence and possibly the case-fatality rate depends on whether the patient presents a symptomatic PE, an unsuspected PE, a subsegmental PE, or a catheter-related PE. Choosing the best therapeutic option is challenging and should consider the risk of both the recurrence of thrombosis and the occurrence of bleeding. The purpose of this review is to provide an overview of the clinical characteristics and the treatment of cancer-associated PE, which could benefit clinicians to better manage the deadliest form of thrombosis associated with cancer. After a brief presentation of the epidemiological data, we will present the current attitude towards the diagnosis and the management of cancer patients with PE. Finally, we will discuss the perspectives of how the medical community can improve the management of this severe medical condition.

Optimal reperfusion strategy in acute high-risk pulmonary embolism requiring extracorporeal membrane oxygenation support: a systematic review and meta-analysis.

The optimal pulmonary revascularisation strategy in high-risk pulmonary embolism (PE) requiring implantation of extracorporeal membrane oxygenation (ECMO) remains controversial. We conducted a systematic review and meta-analysis of evidence comparing mechanical embolectomy and other strategies, including systemic thrombolysis, catheter-directed thrombolysis or ECMO as stand-alone therapy, with regard to mortality and bleeding outcomes. We identified 835 studies, 17 of which were included, comprising 327 PE patients. Overall, 32.4% were treated with mechanical pulmonary reperfusion (of whom 85.9% had surgical embolectomy), while 67.6% received other strategies. The mortality rate was 22.6% in the mechanical reperfusion group and 42.8% in the "other strategies" group. The pooled odds ratio for mortality with mechanical reperfusion was 0.439 (95% CI 0.237-0.816) (p=0.009; I2=35.2%) versus other reperfusion strategies and 0.368 (95% CI 0.185-0.733) (p=0.004; I2=32.9%) for surgical embolectomy versus thrombolysis. The rate of bleeding in patients under ECMO was 22.2% in the mechanical reperfusion group and 19.1% in the "other strategies" group (OR 1.27, 95% CI 0.54-2.96; I2=7.7%). The meta-regression model did not identify any relationship between the covariates "more than one pulmonary reperfusion therapy", "ECMO implantation before pulmonary reperfusion therapy", "clinical presentation of PE" or "cancer-associated PE" and the associated outcomes. The results of the present meta-analysis and meta-regression suggest that mechanical reperfusion, notably by surgical embolectomy, may yield favourable results regardless of the timing of ECMO implantation in the reperfusion timeline, independent of thrombolysis administration or cardiac arrest presentation.

Genomic profiling identifies somatic mutations predicting thromboembolic risk in patients with solid tumors

Venous thromboembolism (VTE) associated with cancer (CAT) is a well-described complication of cancer and a leading cause of death in patients with cancer. The purpose of this study was to assess potential associations of molecular signatures with CAT, including tumor-specific mutations and the presence of clonal hematopoiesis. We analyzed deep-coverage targeted DNA-sequencing data of >14 000 solid tumor samples using the Memorial Sloan Kettering–Integrated Mutation Profiling of Actionable Cancer Targets platform to identify somatic alterations associated with VTE. End point was defined as the first instance of cancer-associated pulmonary embolism and/or proximal/distal lower extremity deep vein thrombosis. Cause-specific Cox proportional hazards regression was used, adjusting for pertinent clinical covariates. Of 11 695 evaluable individuals, 72% had metastatic disease at time of analysis. Tumor-specific mutations in KRAS (hazard ratio [HR], 1.34; 95% confidence interval (CI), 1.09-1.64; adjusted P = .08), STK11 (HR, 2.12; 95% CI, 1.55-2.89; adjusted P < .001), KEAP1 (HR, 1.84; 95% CI, 1.21-2.79; adjusted P = .07), CTNNB1 (HR, 1.73; 95% CI, 1.15-2.60; adjusted P = .09), CDKN2B (HR, 1.45; 95% CI, 1.13-1.85; adjusted P = .07), and MET (HR, 1.83; 95% CI, 1.15-2.92; adjusted P = .09) were associated with a significantly increased risk of CAT independent of tumor type. Mutations in SETD2 were associated with a decreased risk of CAT (HR, 0.35; 95% CI, 0.16-0.79; adjusted P = .09). The presence of clonal hematopoiesis was not associated with an increased VTE rate. This is the first large-scale analysis to elucidate tumor-specific genomic events associated with CAT. Somatic tumor mutations of STK11, KRAS, CTNNB1, KEAP1, CDKN2B, and MET were associated with an increased risk of VTE in patients with solid tumors. Further analysis is needed to validate these findings and identify additional molecular signatures unique to individual tumor types.

Optimizing management of the oncological patient with pulmonary embolism: Validation of the epiphany index—PERSEO study.

12085 Background: EPIPHANY is the first algorithm to predict serious complications in both suspected and unsuspected cancer-associated pulmonary embolism (PE), overcoming limitations of previous models. Methods: PERSEO is a prospective multicenter study. We recruited cancer patients with both incidental and symptomatic PE treated between Oct. 2017 and Dec. 2019. The primary aim was to determine the percentage of serious complications in patients at low predicted risk, with at least 3% accuracy. We also compared the predictive parameters of EPIPHANY with other available scores for prediction 15-day serious complications and 30-day mortality. Results: Cohort includes 831 patients (men, 58.6%; median age, 66 years). Most frequent tumors were lung (27.1%), colorectal (19%) and breast (7.8%). 78.6% had stage IV disease, and 77.6% were receiving antineoplastic treatment. EPIPHANY classified 27%, 24% and 49% of patients as low, medium and high risk, respectively. The rate of 15-day serious complications increased significantly across these prognostic categories: 2.67 (95% CI 0.6 - 4.8), 8.9% (95% CI 0.5 - 12.8), and 25.9% (95% CI 21.7 - 30.2), for low, intermediate, and high risk patients, respectively (p&lt;0.001, linear-by-linear test). In comparison with other validated scores, EPIPHANY has a higher negative predictive value, lower negative likelihood-ratio, and comparable sensitivity (Table). Conclusions: The EPIPHANY index is able to identify a subgroup of patients with cancer-associated pulmonary embolism at very low risk of serious complications or short-term mortality, with potential implications for decision making. [Table: see text]

Lymphoma-Associated Pulmonary Embolism Burden in Hospital Admissions in the United States

Background: Cancer-associated pulmonary embolism (PE) is a common condition that increases morbidity and mortality among cancer patients. Lymphoma has one of the highest rates of venous thromboembolism in cancer patients. The National Inpatient Sample (NIS) Healthcare Cost and Utilization Project (HCUP) includes the largest all-payer inpatient hospital care data in the United States and therefore may represent a significant sample of clinically relevant pulmonary embolism in lymphoma patients. Methods: We utilized the NIS-HCUP database to extract the following data on hospitalizations from 2002 to 2014. We included in our analysis ICD-9 codes for acute PE as a primary or secondary diagnosis of admission and excluded iatrogenic, septic, chronic PE and PE related to obstetrical conditions. We divided our primary population of yielded weighted frequencies i.e. acute PE admissions into two groups: a group with lymphoma as a comorbid condition using Elixhauser comorbidity measures and a group without lymphoma. We identified baseline characteristics of each group including median age on admission, gender and race breakdown as well as common comorbidities' prevalence using Elixhauser comorbidity measures. We ran the analysis for the median length of stay, total charges, mortality scores, readmit scores and inpatient mortality using SAS software, version 9.4 (SAS Institute, Cary, North Carolina). Continuous variables were tested using Wilcoxon two-sample test. Results: We identified a total of 3,293,040 admissions of acute PE in the database from 2002 to 2014, with 98.5% (3,242,571) of the admissions in patients without lymphoma vs. 1.5% (50,469) in patients with lymphoma as a comorbidity. The breakdown of race was comparable across the two groups with the Caucasian race being predominant in lymphoma and non-lymphoma groups at 77.3% vs. 74.2% respectively [Table 1]. Male gender constituted the majority in the lymphoma group at 53.6% in contrast to the non-lymphoma group where female gender was the majority at 53.6%. [Table 2]. While median age on admission was higher in the lymphoma group compared with the non-lymphoma group (68.7 vs. 65 years respectively) , the prevalence of common comorbidities such as hypertension, paralysis, renal failure, heart failure, diabetes mellitus with and without complications were comparable across the two groups except for obesity prevalence which was higher in the non-lymphoma group. [Table 2] Median length of stay was marginally but significantly higher in the lymphoma group at 5.4 days (95% CI 5.33-5.53) vs. 4.96 (95% CI 4.95-4.97) days in the non-lymphoma group (p&lt;0.001); as were the readmission scores with a median readmission score of 30 (95% CI 29.65-30.24) vs. 14 (95% CI 13.99-14.08) for lymphoma and non-lymphoma groups, respectively (p&lt;0.001). We observed that total charges of hospitalization were significantly higher in the lymphoma group with a median of 31,899 US dollars (USD) per hospitalization (95% CI 31,174 - 32,622) compared with 27,784 USD (95% CI 27,704 - 27,864) in the non-lymphoma group. Ultimately, all-cause inpatient mortality was higher in the lymphoma group at 10.4% vs. 7.3% in the non-lymphoma group (Odds ratio 1.46, 95% CI 1.43-1.51, P-value &lt;0.0001). Median mortality score was also significantly higher in the lymphoma group at 13.15 (95% CI 12.6-13.6) vs. 5.53 (95% CI 5.50-5.55) in the non-lymphoma group (p&lt;0.001). Conclusion: Lymphoma was a comorbid diagnosis in 1.5% of patients admitted to the hospital with acute PE between 2002 and 2014 in the NIS-HCUP database. While the median age in the lymphoma group was higher, the prevalence of clinically significant comorbidities was comparable or higher in the non-lymphoma group. Lymphoma was associated with increased all-cause inpatient mortality in patients admitted with acute PE despite the study's limitation of not excluding other cancer patients from the control non-lymphoma group. Patients in the lymphoma group also had a higher risk of readmission in addition to having higher total charges per hospitalization and increased the length of stay. Efforts should continue to better prevent and treat pulmonary embolism in the lymphoma population. Disclosures No relevant conflicts of interest to declare.

Extended Mutational Profiling By MSK-IMPACTTM Identifies Mutations Predicting Thromboembolic Risk in Patients with Solid Tumor Malignancy

Background: Cancer-associated thrombosis (CAT) is a leading cause of death in cancer patients after cancer itself. Risk factors for CAT include tumor type/stage, body mass index (BMI), blood cell counts and chemotherapy exposure. These factors form the basis of prediction algorithms for CAT risk, including most notably the Khorana Risk Score. However, significant limitations exist with these currently-available risk prediction models. Emerging data suggest that a tumor's molecular profile can impact venous thromboembolism (VTE) risk. Mutations of ALK, EGFR, IDH1, ROS1, and KRAS for example have been shown to modulate the risk of CAT; however, these studies were limited by the number of mutations and specific tumor types analyzed. We hypothesized that extended molecular testing in a large patient cohort would allow for improved detection of molecular signatures associated with CAT. We analyzed deep-coverage targeted sequencing data (up to 341 genes) of tumor samples from 11,776 cancer patients to identify gene mutations associated with VTE. Methods: Adult patients with any solid tumor diagnosis who had their tumors sequenced using MSK-IMPACT from 1/2014 to 12/2016 were retrospectively assessed for CAT events using redundant algorithmic methods and individual chart reviews. The endpoint was defined as the first instance of cancer-associated pulmonary embolism and/or proximal/distal lower extremity deep vein thrombosis (DVT). An episode of upper extremity DVT was considered a competing event. The observation period was limited to 365 days after IMPACT blood control sampling. Cause-specific Cox proportional hazards regression was used to test for an association between gene and CAT risk, adjusting for clinical covariates including age, cancer type, cytotoxic chemotherapy (time-dependent), anticoagulant use, stage (metastatic/non-metastatic) and prior history of VTE. Separate multivariate models evaluated the association for the 60 most frequently-mutated genes identified, along with ALK, MET, ROS1 which were included based on existing literature suggesting an effect on VTE risk. Final p-values were adjusted for false discovery using the Benjamini-Hochberg procedure, and the threshold for statistical significance was set at 0.10. Patients with multiple cancer diagnoses were excluded. Results: Out of 11,776 individuals we observed 727 CAT events (6.2% of cohort). The most commonly represented tumor types were lung (18%), breast (15%) and colorectal cancer (10%); see Figure for a breakdown of CAT incidence by tumor type. Most (72%) of patients were metastatic at time of IMPACT testing and 4% were on anticoagulation therapy. Statistically significant predictors of CAT included cytotoxic chemotherapy (HR 1.61 [1.37-1.9]; p&amp;lt;0.001), history of VTE preceding cancer diagnosis (HR 2.48 [1.62-3.79]; p&amp;lt;0.001), and presence of metastatic disease (HR 2.48 [1.94-3.16]; p&amp;lt;0.001). Molecular profiling of tumors revealed STK11 (HR 1.93 [1.42-2.64]; adjusted p=0.002), KRAS (HR 1.42 [1.17-1.72]; adjusted p=0.012), KEAP1 (HR 1.78 [1.18-2.69]; adjusted p=0.095), and MET (HR 1.8 [1.17-2.78]; adjusted p=0.095) somatic mutations were associated with a significant increase in the risk of CAT, independent of tumor type. However, it should be noted that a majority of these genes were specific to lung cancer highlighting the prevalence of this tumor type within the IMPACT cohort. Additionally, the presence of IDH1 mutations in primary brain tumors correlated with a decreased risk of CAT in comparison to wild-type IDH1 (HR 0.34 [0.16-0.69]; adjusted p=0.068), consistent with previous studies. See Table for an extended report of regression coefficients. Conclusions: This work is the first large-scale analysis to elucidate cancer-specific genomic determinants of CAT. Using a large patient cohort, we found that somatic tumor mutations in STK11, KRAS, IDH1, KEAP1, and MET modulate the risk of venous thromboembolism in solid tumor patients. Further analysis is needed to validate these findings and identify additional molecular signatures unique to individual tumor types. We hope these findings will ultimately translate into improved risk stratification for patients at risk of CAT. Disclosures Mones: Janssen: Research Funding. Iyengar:Puma Biotechnology: Consultancy; Novartis: Consultancy. Hyman:AstraZeneca: Consultancy, Research Funding; Fount: Consultancy, Equity Ownership; Pfizer: Consultancy; Chugai Pharma: Consultancy; Loxo Oncology: Research Funding; Boehringer Ingelheim: Consultancy; Bayer Pharmaceuticals: Consultancy, Research Funding; Genentech / Roche: Consultancy; PUMA Biotechnology: Research Funding; CytomX Therapeutics: Consultancy. Park:Merck: Research Funding; Parker Institute for Cancer Immunotherapy: Research Funding; Astellas: Research Funding; Ipsen: Consultancy. Khorana:Bayer: Consultancy; Janssen: Consultancy; Sanofi: Consultancy; Pfizer: Consultancy. Soff:Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Dova: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees. Mantha:Medical Case Management Group: Consultancy; MJH Live Events: Other: Give CME talk; Heidell, Pittoni, Murphy &amp; Bach, LLP: Consultancy; Daboia Consulting LLC: Equity Ownership; Janssen: Research Funding.

1771P - Performance of the ‘4S rule’ to predict short-term outcomes in cancer outpatients with unsuspected pulmonary embolism

BackgroundThe diagnosis of incidental or unsuspected pulmonary embolism (PE) in cancer outpatients undergoing scheduled CT-scans is a challenge in daily oncological practice. The aim of this study was to assess the performance of the ‘4S rule’ (Setting, Suspicion, Signs and Symptoms) as a PE risk-assessment model in this setting. MethodsWe assessed consecutive patients with cancer-associated PE from an ongoing multicenter observational registry (2005-2018). Patients were classified as presenting ‘Truly asymptomatic unsuspected PE’ (TAUPE) according to the ‘4S rule’ (EurRespir J 2017;49(1):1600282 and EurRespir J 2017;49(1):1602225) that includes the following variables: (1) outpatient Setting at PE diagnosis; (2) no Suspicion of PE; (3) vital Signs within normal limits including blood pressure >100mmHg, heart rate <100 per minute and oxygen saturation >95%; and (4) absence of PE Symptoms. Short-term outcome measures included: all-cause and PE-related mortality within 30 days after the index PE. ResultsWe evaluated a total of 617 patients (61.6% male; median age 65+11.4 years) including 207 (33%) with TAUPE, 284 (47%) with ‘acute suspected PE’ and 126 (20%) with ‘unsuspected PE with symptoms’. Most patients (79%) had metastatic cancer and nearly half (47%) were on chemotherapy. The PE was incidentally found in 54% of the cohort. The most frequent tumors were: 32% lung, 14% colorectal, 13% urological, and 12% upper gastrointestinal. All-cause 30-day mortality occurred in 95 patients (15% of the cohort) and 12 cases presented PE-related mortality (2% of the cohort). Patients with TAUPE had lower all-cause 30-day mortality compared to non-TAUPE cases (3% vs. 22%; p<0.0001). PE-related 30-day mortality occurred in 0 patients with TAUPE and in 12 (3%) non-TAUPE patients (0% vs. 3%; p=0.013). ConclusionsShort-term mortality in patients with cancer-associated PE is high. Cancer outpatients with TAUPE according to the 4S rule criteria (33% in the cohort) were identified as a low-risk group of all-cause and PE-related short-term mortality. These findings may help to develop PE risk-assessment models in this setting. Legal entity responsible for the studyHospital Clinic de Barcelona. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Effect of post-filter anticoagulation on mortality in patients with cancer-associated pulmonary embolism.

Malignancy is associated with an increased risk of venous thromboembolism. Inferior vena cava filters are a viable alternative when anticoagulation is infeasible because of the risk of bleeding. Although the current guidelines recommend that all patients with a vena cava filter be treated with anticoagulation treatment when the risk of bleeding is reduced, studies concerning the role of concomitant anticoagulation after vena cava filter insertion in high-risk patients are scarce. Since many cancer patients suffer from a high risk of hemorrhagic complications, we aimed to determine the effect of post-filter anticoagulation on mortality in patients with a malignant solid tumor. A retrospective cohort study of patients with pulmonary embolism was performed between January 2010 and May 2016. Patients with a solid tumor and vena cava filter inserted because of pulmonary embolism were included. Using Cox proportional hazards model, the prognostic effect of clinical variables was analyzed. A total of 180 patients were analyzed, with 143 patients receiving and 37 patients not receiving post-filter anticoagulation treatment. Mortality was not significantly different between the two groups. The presence of metastatic cancer and that of pancreatobiliary cancer were significant risk factors for mortality. However, post-filter anticoagulation did not show significant effect on mortality regardless of the stage of cancer. In patients with cancer-associated pulmonary embolism, the effect of post-filter anticoagulation on mortality may not be critical, especially in patients with a short life expectancy.

Validation of the EPIPHANY index for predicting risk of serious complications in cancer patients with incidental pulmonary embolism.

The EPIPHANY index was developed to classify cancer associated pulmonary embolism (PE) into different risk categories using decision tree modeling. In this study, we tried to externally validate this index in a distinct group of patients solely composed of incidental PE (IPE). A retrospective study of patients diagnosed with IPE in two Emergency Departments in the USA and South Korea from 2013 to 2014 was performed. The primary outcome was the occurrence of a serious medical complication within 15days of presentation to ED. Thirty-day complication was the secondary outcome. Cumulative hazard curves for each prognostic category were drawn to show the change in hazards over time. A total of 258 patients with IPE were included (193 from MD Anderson Cancer Center and 65 from Asan Medical Center). Serious complication within 15days occurred in 23 (8.9%) patients. The risk of overall 15-day and 30-day serious complications increased with each category (low, intermediate, and high risk: 3.4, 8.9, and 23.8%, P = 0.033; 6.9, 9.5, and 33.3%, P = 0.011). Cumulative hazard curves for each prognostic category were drawn and the survival functions factored by prognostic categories were significantly different over 15days (P = 0.015) and 30days (P = 0.001). Our study suggests the EPIPHANY index could be a useful adjunct tool in risk stratification of cancer patients with IPE.

Short- and long-term mortality after pulmonary embolism in patients with and without cancer.

Pulmonary embolism (PE) is a major cause of mortality and morbidity. It is known that the risk of death varies by provoking factors; however, it is unknown if the risk of death persists beyond the initial diagnosis among patients with cancer-associated and non-cancer provoked patients. In this study, we aimed to investigate the effect of cancer on overall, short- and long-term mortality in a cohort of consecutive incident PE patients. Using administrative databases, we identified all incident cases of PE between 2004 and 2012 in Alberta, Canada. Cases were stratified by provoking factors (i.e. unprovoked, provoked, and cancer-associated). A multivariate Cox survival model was used to estimate the hazard ratios of short- and long-term death. We identified 8641 patients with PE, among which 42.2% were unprovoked, 37.9% were provoked and 19.9% were cancer-associated. The 1-year and 5-year survival probabilities were 60% (95% CI: 57-64%) and 39% (95% CI: 36-43%) in patients with cancer-associated PE, 93% (95% CI: 92-94%) and 80% (95% CI: 78-81%) in provoked PE, and 94% (95% CI: 93-95%) and 85% (95% CI: 83-87%) in unprovoked PE, respectively. Compared to patients with unprovoked events, both short-term and long-term survival in patients with cancer-associated PE have a higher observed risk of all-cause mortality in all age groups ( p<0.001). In contrast, patients with provoked events had a similar short- and long-term all-cause mortality. While PE has a significant mortality in all risk groups, patients with cancer have a higher risk of short-term mortality compared to patients with unprovoked PE.

Outcomes after inferior vena cava filter placement in cancer patients diagnosed with pulmonary embolism: risk for recurrent venous thromboembolism.

Venous thromboembolism (VTE) is a common complication in cancer patients and anticoagulation (AC) remains the standard of care for treatment. Inferior vena cava (IVC) filters may also used to reduce the risk of pulmonary embolism, either alone or in addition to AC. Although widely used, data are limited on the safety and efficacy of IVC filters in cancer patients. We performed a retrospective review of outcomes after IVC filter insertion in a database of 1270 consecutive patients with cancer-associated pulmonary embolism (PE) at our institution between 2008 and 2009. Outcomes measured included rate of all recurrent VTE, recurrent PE, and overall survival within 12months. 317 (25%) of the 1270 patients with PE had IVC filters placed within 30days of the index PE event or prior to the index PE in the setting of prior DVT. Patients with IVC filters had markedly lower overall survival (7.3months) than the non-IVC filter patients (13.2months). Filter patients also had a lower rate of AC use at time of initial PE. There was a trend towards higher recurrent VTE in patients with IVC filters (11.9%) compared to non-filter patients (7.7%), but this was not significant (p = 0.086). The risk of recurrent PE was similar between the IVC filter cohort (3.5%) and non-filter group (3.5%, p = 0.99). Cancer patients receiving IVC filters had a similar risk of recurrent PE, but a trend towards more overall recurrent VTE. The filter patients had poorer overall survival, which may reflect a poorer cancer prognosis, and had greater contraindication to AC; therefore these patients likely had a higher inherent risk for recurrent VTE. A prospective study would be helpful for further clarification on the partial reduction in the recurrent PE risk by IVC filter placement in cancer patients.

1481P - Outpatient management of cancer-associated pulmonary embolism (PE): analysis of lung carcinoma (LC) cohort from the Epiphany study

1481P - Outpatient management of cancer-associated pulmonary embolism (PE): analysis of lung carcinoma (LC) cohort from the Epiphany study