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PURPOSE To conduct an update of the ASCO venous thromboembolism (VTE) guideline. METHODS After publication of potentially practice-changing clinical trials, identified through ASCO's signals approach to updating, an updated systematic review was performed for two guideline questions: perioperative thromboprophylaxis and treatment of VTE. PubMed and the Cochrane Library were searched for randomized controlled trials (RCTs) published between November 1, 2018, and June 6, 2022. RESULTS Five RCTs provided information that contributed to changes to the 2019 recommendations. Two RCTs addressed direct factor Xa inhibitors (either rivaroxaban or apixaban) for extended thromboprophylaxis after surgery. Each of these postoperative trials had important limitations but suggested that these two oral anticoagulants are safe and effective in the settings studied. An additional three RCTs addressed apixaban in the setting of VTE treatment. Apixaban was effective in reducing the risk of recurrent VTE, with a low risk of major bleeding. RECOMMENDATIONS Apixaban and rivaroxaban were added as options for extended pharmacologic thromboprophylaxis after cancer surgery, with a weak strength of recommendation. Apixaban was also added as an option for the treatment of VTE, with high quality of evidence and a strong recommendation. Additional information is available at www.asco.org/supportive-care-guidelines .

Cancer-associated thrombosis, with the incidence rising over the years, is associated with significant morbidity and mortality in patients with cancer. Recent advances in the treatment of cancer-associated venous thromboembolism (VTE) include the introduction of direct oral anticoagulants (DOACs), which provide a more convenient and effective option than low-molecular-weight heparin (LMWH). Nonetheless, important unmet needs remain including an increased risk of bleeding in certain patient subgroups such as those with gastroesophageal cancer, concerns about drug-drug interactions, and management of patients with severe renal impairment. Although DOACs are more convenient than LMWH, persistence can decline over time. Factor XI inhibitors have potential safety advantages over DOACs because factor XI appears to be essential for thrombosis but not hemostasis. In phase II trials, some factor XI inhibitors were superior to enoxaparin for the prevention of VTE after knee replacement surgery without increasing the risk of bleeding. Ongoing trials are assessing the efficacy and safety of factor XI inhibitors for the treatment of cancer-associated VTE. ispartof: ONCOLOGIST vol:28 issue:7 ispartof: location:England status: Published online

Purpose:Dickkopf-1 (DKK1) modulates Wnt signaling, promoting tumor growth, metastasis, and immunosuppression. High DKK1 expression has been detected in various tumor types—including biliary tract cancer (BTC)—and is associated with poor prognosis. DKN-01—a humanized mAb targeting DKK1—was evaluated in a phase I multicenter study in combination with gemcitabine and cisplatin in patients with unresectable or metastatic BTC with no prior systemic therapy for advanced disease.Patients and Methods:This study included a dose-escalation phase assessing DKN-01 at two dose levels (150 mg and 300 mg) combined with gemcitabine (1,000 mg/m2) and cisplatin (25 mg/m2) followed by dose expansion. Primary endpoints evaluated safety and tolerability; secondary endpoints evaluated efficacy, pharmacokinetics, and circulating biomarkers.Results:Fifty-one patients with intrahepatic cholangiocarcinoma (63%), extrahepatic cholangiocarcinoma (8%), and gallbladder cancer (29%) were enrolled. No dose-limiting toxicities were seen, and the expansion phase proceeded with DKN-01 300 mg (N = 47). The most frequent grade 3/4 treatment-emergent adverse events included neutropenia (60%), thrombocytopenia (34%), and anemia (23%). The objective response rate was 21.3% and median progression-free survival was 8.7 months (95% confidence interval, 5.4–10.3 months). Better outcomes were associated with biomarkers of angiogenesis inhibition (increased sVEGFR1 and lower VEGF-C) and reduced inflammation (lower IL6 and decreased TNFα).Conclusions:DKN-01 300 mg was well tolerated in this combination but did not appear to have additional activity beyond historically reported efficacy with gemcitabine/cisplatin alone. Exploratory pharmacokinetic and biomarker data indicate potential antiangiogenic and immunomodulatory activity of DKN-01/chemotherapy and the need for increased dose/intensity. A study with DKN-01 600 mg in combination with a PD-1 inhibitor in BTC is ongoing.

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Lymph nodes with acellular mucin harvested from treated colorectal cancers (CRC) are staged as pN0. However, there is variability among pathologists while reporting the pN stage when acellular mucin is found within nodes of untreated CRCs. While the UICC guidelines suggest staging them as pN1, the AJCC and CAP do not offer any recommendations. In order to characterize their clinicopathologic features and outcome, we compared 16 untreated CRCs (study group; mean age: 68 years) harboring nodes with acellular mucin with 34 pN0 and 25 pN1 untreated CRC controls. All tumors were unifocal; 12 (75%) were right-sided lesions. Most cases (75%) showed one node with acellular mucin (range: 1-3). MMR-deficient tumors were significantly more common in the study group (83%) compared to pN0 (33%; p = 0.006) and pN1 controls (8%; p0.001). The overall survival of study group patients was closer to pN0 compared to pN1 controls; however, this difference was not statistically significant. In conclusion, untreated CRC that harbor acellular mucin within lymph nodes commonly present as right-sided, MMR-deficient tumors in older women that show a non-mucinous phenotype. While the limited number of cases precludes us from making any formal recommendations about staging, we suggest that the finding of acellular mucin in a node should prompt evaluation of deeper levels (with or without cytokeratin immunohistochemistry) and submission of all pericolonic fat for additional lymph node harvest. Whether acellular mucin in nodes of untreated CRCs is related to the indolent biology of the disease, a robust local immune response or MMR deficiency requires further investigation.

OBJECTIVES To identify drivers of time from diagnosis to treatment (TTT) of surgically resected early stage non-small cell lung cancer (NSCLC) and determine the effect of TTT on post-resection survival. SUMMARY BACKGROUND DATA Large database studies that lack relevant comorbidity data have identified longer TTT as a driver of worse overall survival. METHODS From 1/1/2014-4/1/2018, 599 patients underwent lung resection for clinical stage I and II NSCLC. Random forest classification, regression, and survival were used to estimate likelihood of TTT=0 (tissue diagnosis obtained at surgery), > 0 (diagnosis obtained pre-resection), and effect of TTT on all-cause mortality. RESULTS Patients with TTT > 0 (n=413) had median TTT of 42 days [25-75th percentile: 27-59 days]. Patients with TTT=0 (n=186) had smaller tumors and higher percent predicted forced expiratory volume in one second (FEV1%). Patients with history of stroke, oncology consultation, invasive mediastinal staging, low and high extremes of FEV1% had longer TTT. Higher clinical stage, lack of preoperative stress test, anemia, older age, lower FEV1% and diffusion lung capacity, larger tumor size, and longer TTT were the most important predictors of all-cause mortality. One- and five-year overall survival decreased when TTT was longer than 50 days. CONCLUSION Preoperative physiologic workup and multidisciplinary evaluation were the predominant drivers of longer TTT. Patients with TTT=0 have more favorable presentation and should be considered in TTT analyses for early stage lung cancer populations. The time needed to clinically stage and optimize patients for resection is not deleterious to overall survival until resection is performed after 50 days from diagnosis.

Key Points Cleaved HK is observed in many patients with cancer, suggesting activation of the contact system.EVs from cancer cell lines or patients with cancer express polyphosphate, bind and activate FXII, and are prothrombotic., Visual Abstract, Extracellular vesicles (EV) have been implicated in diverse biological processes, including intracellular communication, transport of nucleic acids, and regulation of vascular function. Levels of EVs are elevated in cancer, and studies suggest that EV may stimulate thrombosis in patients with cancer through expression of tissue factor. However, limited data also implicate EV in the activation of the contact pathway of coagulation through activation of factor XII (FXII) to FXIIa. To better define the ability of EV to initiate contact activation, we compared the ability of EV derived from different cancer cell lines to activate FXII. EV from all cell lines activated FXII, with those derived from pancreatic and lung cancer cell lines demonstrating the most potent activity. Concordant with the activation of FXII, EV induced the cleavage of high molecular weight kininogen (HK) to cleaved kininogen. We also observed that EVs from patients with cancer stimulated FXII activation and HK cleavage. To define the mechanisms of FXII activation by EV, EV were treated with calf intestinal alkaline phosphatase or Escherichia coli exopolyphosphatase to degrade polyphosphate; this treatment blocked binding of FXII to EVs and the ability of EV to mediate FXII activation. In vivo, EV induced pulmonary thrombosis in wild-type mice, with protection conferred by a deficiency in FXII, HK, or prekallikrein. Moreover, pretreatment of EVs with calf intestinal alkaline phosphatase inhibited their prothrombotic effect. These results indicate that polyphosphate mediates the binding of contact factors to EV and that EV-associated polyphosphate may contribute to the prothrombotic effects of EV in cancer.

Metastatic renal cell carcinoma (mRCC) is associated with a high risk of thromboembolism (TE). We investigated whether immunotherapy (IO) increases the hypercoagulable state in this high-risk population. Patients with mRCC treated with IO between 1 January 2015 and 31 December 2019 at the Cleveland Clinic were identified. Cumulative incidence analysis calculated TE rates over time and Gray’s test determined differences in TE rates among groups. The Kaplan–Meier method estimated survival, while Cox proportional hazard regression evaluated the impact of TE on OS. Of 351 patients, 75% were men with clear cell mRCC (81%) and International Metastatic Renal Cell Carcinoma (IMDC) intermediate- to poor-risk disease (77%). Patients received single-agent IO (52%), doublet IO (31%), or IO with non-IO therapy (17%). The median number of IO doses was 8 (range 1–81). At a median follow-up of 12.8 months, 12% of patients (n = 43) had a TE event (venous n = 37 [11%], arterial n = 6 [2%]). The cumulative TE incidence at 6 months was 4.4% (95% confidence interval [CI] 2.6–6.9) and 9.8% (95% CI 6.8–13.4) at 12 months. No factors, including IMDC or Khorana score, were identified to predict TE development. Seventy-two percent of TE resulted in hospitalization (9% TE-related mortality and 21% TE-related dose delay). TE (p

Background The incidence of colorectal cancer (CRC) in patients under age 50 is rising for unclear reasons. We examined the effects of socioeconomic factors on outcomes for patients with early‐onset CRC compared to late‐onset CRC. Methods Patients with CRC from 2004 to 2015 in the National Cancer Database were included and categorized by age (under or over 50 years). Differences in demographic and socioeconomic factors, disease characteristics, and survival outcomes between early‐onset versus late‐onset CRC patients were assessed by Chi‐squared test and Cox models. Results The study population included 1,061,204 patients, 108,058 (10.2%) of whom were under age 50. The proportion of patients diagnosed under age 50 increased over time: 9.4% in 2004–2006, 10.1% in 2007–2009, 10.5% in 2010–2012, and 10.7% in 2013–2015 (p, Patients with early‐onset colorectal cancer are more likely to be Black or Hispanic and to present with stage 4 cancer. Within the subgroup of early‐onset CRC patients with private insurance, Black patients had worse OS compared to White patients, even in communities with higher income and education status.

Cancer patients have an increased risk of developing venous thrombosis. The implementation of a cancer associated thrombosis clinic can be instrumental for the prevention, early recognition, and management of venous thromboembolism in this vulnerable population. Cancer thrombosis clinics rely on a multidisciplinary approach to care and require standardization along with a dedicated team of healthcare professionals. Cancer thrombosis clinics have the potential to improve patient outcomes and lower healthcare expenditure. Herein, we describe a successful model of a cancer thrombosis clinic and highlight the potential impact on clinical outcomes.

Cancer patients have an increased risk of developing venous thrombosis. The implementation of a cancer associated thrombosis clinic can be instrumental for the prevention, early recognition, and management of venous thromboembolism in this vulnerable population. Cancer thrombosis clinics rely on a multidisciplinary approach to care and require standardization along with a dedicated team of healthcare professionals. Cancer thrombosis clinics have the potential to improve patient outcomes and lower healthcare expenditure. Herein, we describe a successful model of a cancer thrombosis clinic and highlight the potential impact on clinical outcomes.

Although venous thromboembolism (VTE) is an important treatment and disease-related complication in myeloma, a validated risk prediction model including disease-specific variables such as cytogenetics or tumor burden is lacking. The aim of this study was to develop a new risk prediction model for VTE in the context of modern antimyeloma therapy. All consecutive patients diagnosed at the Cleveland Clinic between 2008 and 2018 and with available data on baseline candidate risk factors constituted the derivation cohort. The primary outcome was VTE (deep venous thrombosis/pulmonary embolism) within 1 year of treatment initiation. A multivariable model was used, and weights were derived from subdistribution hazard ratios to construct a risk score. The model was validated both by internal bootstrap validation and in an external validation cohort. The derivation cohort consisted of 783 patients. A 5-component risk prediction tool, named the PRISM score, was developed, including the following variables: prior VTE, prior surgery, immunomodulatory drug use, abnormal metaphase cytogenetics, and Black race. The c-statistic of the model was 0.622 (95% confidence interval [CI], 0.567-0.674). The model stratified patients into low, intermediate, and high risk, with 12-month cumulative VTE incidence of 2.7%, 10.8%, and 36.5%, respectively. Risk of VTE increased significantly with increasing score in both the derivation and the external validation data sets, with a subdistribution hazard ratio per 1-point increase of 1.28 (95% CI, 1.19-1.39; P < .001) and 1.23 (95% CI, 1.07-1.41; P = .004) respectively. Although the PRISM score can guide clinicians in identifying patients at a high risk of VTE, additional external validation is necessary for incorporation into routine clinical practice.

COVID‐19 continues to dominate the health‐care burden in the twenty‐first century. While health‐care professionals around the world try their best to minimize the mortality from this pandemic, we also continue to battle the high mortality from different types of cancer. For the hemostasis and thrombosis specialist, these two conditions present some unusual similarities including the high rate of thrombosis and marked elevation of D‐dimers. In this forum article, we discuss these similarities and provide some considerations for future research and therapeutic trials.

Hospitalized medically ill patients with cancer are at increased risk of both venous thromboembolism and bleeding. The safety and efficacy of extended thromboprophylaxis in patients with cancer are unclear. We conducted a systematic review and meta-analysis of the literature using of MEDLINE, EMBASE, and the Cochrane CENTRAL databases to identify cancer subgroups enrolled in randomized controlled trials evaluating extended thromboprophylaxis following hospitalization. The primary outcomes were symptomatic and incidental venous thromboembolic events and hemorrhage (major hemorrhage and clinically relevant nonmajor bleeding). Four randomized controlled trials reported the outcomes of extended thromboprophylaxis in 3655 medically ill patients with active or history of cancer. The rates of venous thromboembolic events were similar between the extended-duration and standard-duration groups (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.61-1.18; I2 = 0%). However, major and clinically relevant nonmajor bleeding occurred significantly more frequently in the extended-duration thromboprophylaxis group (OR, 2.10; 95% CI, 1.33-3.35; I2 = 8%). Extended thromboprophylaxis in hospitalized medically ill patients with cancer was not associated with a reduced rate of venous thromboembolic events but was associated with increased risk of hemorrhage. This study protocol was registered on PROSPERO as #CRD42020209333.

Objectives We retrospectively examined the venous thromboembolism (VTE) events diagnosed in the Prophylaxis of High-Risk Ambulatory Cancer Patients Study (PHACS), a multi-center randomized trial, to assess the value of screening vascular imaging for the diagnosis of incidental VTE in high-risk cancer patients. Methods A total of 117 asymptomatic cancer patients with a Khorana score ≥3 starting a new systemic chemotherapy regimen were enrolled in a prospective randomized control trial. Patients underwent baseline venous ultrasound (US) of the lower extremities (LEs) and screening contrast-enhanced chest computed tomography (CT). Those without preexisting VTE were then randomized into observation or dalteparin prophylaxis groups and were screened with serial US every 4 weeks for up to 12 weeks and imaged with contrast-enhanced chest CT at 12 weeks. Any additional imaging performed during the study period was also evaluated for VTE. Results Baseline prevalence of incidental VTE was 9% (n = 10) with 58% percent of VTEs diagnosed by screening US. Incidence of VTE in the randomized phase of the trial was 16% (n = 16) with 21% (n = 10) of patients in the control arm and 12% (n = 6) of patients in the dalteparin arm developing VTE, a non-significant 9% absolute risk reduction (HR = 0.69, 95% CI 0.23-1.89). Sixty-nine percent of these patients were asymptomatic with 31% of patients diagnosed by screening US. Conclusions Adding screening US to routine oncologic surveillance CT in high-risk ambulatory cancer patients with a Khorana score ≥3 can lead to increased VTE detection, with potential for decreased morbidity, mortality, and health care spending.

INTRODUCTION Thromboembolism (TE) is common in patients with non-small cell lung cancer (NSCLC) and is associated with worse outcomes. Recent advances in the understanding of NSCLC have led to the identification of molecular subtypes such as anaplastic lymphocyte kinase (ALK) and epidermal growth factor receptor (EGFR) mutations. The association of these subtypes with risk of TE has not been fully explored. METHODS We conducted a retrospective cohort study of consecutive NSCLC patients seen at the Cleveland Clinic from July 2002 through July 2017 for whom molecular classification and follow-up were available. TE events included deep vein thrombosis (DVT), pulmonary embolism (PE), visceral vein thrombosis (VVT), and arterial events. TE-free survival and overall survival rates for each of the molecular subtypes (wild-type, ALK-mutant, and EGFR-mutant) were estimated by the Kaplan-Meier method. Cox proportional hazard regression analysis was used to identify factors associated with the endpoints TE and overall survival. TE was analyzed as a conditional, time-dependent covariate to assess its impact with respect to overall survival. RESULTS The study population consisted of 461 patients. Approximately half were females (n = 263, 57%) and 58% (n = 270) were older than 65 years. TE occurred in 98 of 461 patients (21.3%) during a median follow-up of 33.1 months. The highest cumulative rates of TE were observed in patients with ALK-mutant NSCLC (N = 20/46, 43.5%) followed by patients with EGFR-mutant cancers (N = 35/165, 21.2%) and wild-type cancers (N = 43/250, 17.2%) P

Background: Immune checkpoint inhibitors with or without chemotherapy form the backbone of treatment for patients with advanced NSCLC without an actionable driver mutation. Emerging literature shows that ICIs increase the risk of venous thromboembolism (VTE), which is a major cause of death in patients with NSCLC. The mechanism is yet to be elucidated but is likely secondary to inflammation. Since chemotherapy is immunosuppressive, we sought to understand if the addition of chemotherapy to ICIs impacted the incidence of VTEs. Methods: We performed a retrospective cohort study to evaluate thromboembolic outcomes in patients diagnosed with advanced NSCLC between 2012 and 2018 and treated with either ICIs or chemo immunotherapy at Cleveland Clinic Foundation. Diagnosis of thrombotic events (TE) (arterial/deep vein thrombosis and/or pulmonary embolism) was confirmed by imaging. Overall survival (OS) was estimated by Kaplan-Meier and compared using log rank test. Odds of developing TE was estimated and compared between ICI and ChemoIO groups, using Fisher's Exact Test. Results: A total of 367 NSCLC patients (242 pts on ICI only and 125 pts on ChemoIO regimen), were identified with a median age 65 years ( range 58-72), 52% were men, 82% white, 85.3% smokers, 91.8% had ECOG ≤2, 73 % had adenocarcinoma and 18% had squamous cell carcinoma, 34% with brain metastasis and the distribution of PDL1expression was as follows- 0.05). Conclusion: Rates of TE were high in patients with advanced NSCLC who received ICI therapy, but no different if treated with ICIs alone or ChemoIO. Further studies to better understand the pathophysiology of TE in patients treated with ICIs might allow us to identify subgroups of patients that are at the highest risk for TEs. Citation Format: Doaa Attia, Ran Zhao, Alok A. Khorana, Prandya Patil. Risk of thromboembolism in patients with non-small lung cancer (NSCLC) treated with immune check point inhibitors (ICIs) versus chemoimmunotherapy (ChemoIO) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3217.

Background: Venous thromboembolism (VTE) is a common complication among patients with cancer. Patients with cancer and VTE are at a markedly increased risk for morbidity and mortality. Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in their decisions about the prevention and treatment of VTE in patients with cancer. Methods: ASH formed a multidisciplinary guideline panel balanced to minimize potential bias from conflicts of interest. The guideline development process was supported by updated or new systematic evidence reviews. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess evidence and make recommendations. Results: Recommendations address mechanical and pharmacological prophylaxis in hospitalized medical patients with cancer, those undergoing a surgical procedure, and ambulatory patients receiving cancer chemotherapy. The recommendations also address the use of anticoagulation for the initial, short-term, and long-term treatment of VTE in patients with cancer. Conclusions: Strong recommendations include not using thromboprophylaxis in ambulatory patients receiving cancer chemotherapy at low risk of VTE and to use low-molecular-weight heparin (LMWH) for initial treatment of VTE in patients with cancer. Conditional recommendations include using thromboprophylaxis in hospitalized medical patients with cancer, LMWH or fondaparinux for surgical patients with cancer, LMWH or direct oral anticoagulants (DOAC) in ambulatory patients with cancer receiving systemic therapy at high risk of VTE and LMWH or DOAC for initial treatment of VTE, DOAC for the short-term treatment of VTE, and LMWH or DOAC for the long-term treatment of VTE in patients with cancer.

As a result of the coronavirus disease 2019 pandemic, the International Society on Thrombosis and Haemostasis (ISTH), like many societies around the world, canceled their in‐person hematology congress planned for Milan, Italy, in July 2020. As a result, the first virtual ISTH congress in the organisation’s 51‐year history was delivered, inviting free registration from across the globe. As part of the social media support, marketing, and scientific dissemination efforts for the virtual congress, the ISTH assembled a group of official Twitter Ambassadors, which represented the broad and diverse ISTH community. Ambassadors were tasked to tweet daily throughout the congress and to share their commentary on the hematology research being presented with the “#ISTH2020” hashtag. Ambassadors were also supported by Twitter activities from the two official ISTH‐affiliated journals: the Journal of Thrombosis and Haemostasis (JTH) and Research and Practice in Thrombosis and Haemostasis (RPTH). In this forum and through the Twitter ambassadors’ lens, we present the Twitter Ambassadors’ experience, reflect on the impact of social media on the ISTH 2020 congress, and share this experience with the wider scientific community. Specifically, we report on the role of Twitter communication for virtual meetings, discuss the pros and cons of the virtual congress, and offer Twitter‐related recommendations for future virtual or blended congresses. We conclude that the ISTH Twitter Ambassador program broadened social media engagement and offers a novel route to improve social connectivity in the virtual research congress setting.

Aims Patients with cancer are at high risk of venous thromboembolism (VTE), which entails a high economic burden. The risk of cancer-associated VTE can be assessed using the Khorana score (KS), a validated VTE risk prediction algorithm. This study compared healthcare costs associated with different KS in a population of patients newly diagnosed with cancer. Methods The Optum® Clinformatics® DataMart database (01/01/2012-09/30/2017) was used to select adult patients with ≥1 hospitalization or ≥2 outpatient claims with a cancer diagnosis (index date) initiated on systemic therapy or radiation therapy. Patients were classified in mutually exclusive cohorts based on KS (i.e., KS =0, 1, 2 or ≥3). The observation period spanned from index to the earliest among end of data availability, death, end of insurance coverage, or 12 months. Results In total 6,194 patients (KS =0: 2,488; KS =1: 2,125; KS =2: 1,074; KS ≥3: 507) were included. On average, patients were aged 68 years, 48-52% were female, and the Quan-Charlson comorbidity index ranged between 1.1 and 1.4. Over the observation period, all-cause total healthcare costs per patient per month (PPPM) were $8,826 (KS =0), $11,598 (KS =1), $14,028 (KS =2), and $16,211 (KS ≥3). Using the KS =0 cohort as reference, adjusted PPPM costs were $2,506, $4,775, and $6,452 higher in the KS =1, KS =2 cohort, and KS ≥3 cohorts, respectively. Hospitalization and outpatient costs were the main drivers of these differences. Similar results were found for VTE-related costs, which represented 4-11% of the total all-cause cost difference between KS cohorts. Limitations Residual confounders; results may not be generalized to patients with other insurance plans or those who received treatments other than systemic therapy or radiation therapy. Conclusions This real-world analysis found that cancer patients at higher risk of VTE (based on KS) incurred significantly greater all-cause and VTE-related healthcare costs compared with cancer patients at lower risk of VTE.

Venous and arterial thromboembolism are prevalent, highly burdensome, and associated with risk of worse outcomes for patients with cancer. Risk for venous thromboembolism (VTE) varies widely across specific cancer subpopulations. The ability to predict risk of cancer-associated VTE is critical because an optimal thromboprophylaxis strategy is best achieved by targeting high-risk patients with cancer and avoiding prophylaxis in patients with cancer at low risk for VTE. A validated risk tool for solid tumors has been available for a decade. Newer tools have focused on specific populations, such as patients with multiple myeloma. Emerging studies continue to optimize risk prediction approaches in patients with cancer. Recent randomized trials have specifically addressed risk-adapted thromboprophylaxis using direct oral anticoagulants, and revised guidelines have included these new data to formulate recommendations for outpatient thromboprophylaxis. Implementation science approaches to enhance use of outpatient prophylaxis in the context of these guideline changes are under way. However, major knowledge gaps remain, including a lack of data for inpatient thromboprophylaxis in the cancer setting and a lack of formal tools for identifying risk of bleeding. This review describes optimal approaches to risk prediction and patient selection for primary pharmacologic thromboprophylaxis of cancer-associated VTE, addresses barriers to implementing these practices, and highlights strategies to overcome them. Implications for Practice Risk for venous thromboembolism (VTE) varies widely among patients with cancer. Individual risk can be determined using validated approaches. Inpatient and postsurgical thromboprophylaxis is more widely accepted. However, most patients with cancer develop VTE in the outpatient setting. Recent randomized trials have demonstrated benefit to risk-adapted outpatient thromboprophylaxis. High-risk patients may therefore be considered for outpatient thromboprophylaxis as recommended by recently updated guidelines. System-wide implementation approaches are necessary to improve compliance with prophylaxis.