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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 associated thrombosis (CAT) is a common complication among patients with active malignancy. • Cancer associated thrombosis (CAT) clinics can improve patient outcomes by targeting patients at high risk of VTE. • CAT clinics can provide standardized outpatient care for acute VTE management in the majority of ambulatory cancer patients • CAT clinics can aid in implementing current guidelines recommendations for primary VTE prophylaxis. [ABSTRACT FROM AUTHOR]

Background: The Khorana score (KS) clinical algorithm is used to predict VTE risk in cancer patients. The study objective was to evaluate VTE and survival rates among patients newly diagnosed with cancer and stratified by KS in a real‐world population. Methods: Data from the Optum® Clinformatics® DataMart database between 01/01/2012–09/30/2017 was used to identify adults with ≥ 1 hospitalization or ≥ 2 outpatient claims with a cancer diagnosis (index date). Only patients who were initiated on chemotherapy or radiation therapy were included. Patients were classified based on KS (KS = 0, 1, 2 or ≥ 3). Time‐to‐first VTE and survival were evaluated from the index date to the earliest among end of data availability or insurance coverage, death, or 12 months post‐index using Kaplan‐Meier (KM) analyses. Results: A total of 2,488 (KS = 0); 2,125 (KS = 1), 1,074 (KS = 2), and 507 (KS ≥ 3) cancer patients were included. The 12‐month KM rates of VTE were 3.1%, 5.4%, 7.9%, and 14.9% (associated median time to VTE of 2.7, 3.0, 1.4, and 1.7 months) among KS = 0, 1, 2, and ≥ 3 cohorts, respectively. Corresponding adjusted hazard ratios (95% CIs) relative to the KS = 0 cohort were 1.72 (1.25‐2.38), 2.46 (1.73‐3.50), and 4.99 (3.40‐7.31) for the KS = 1, 2, and ≥ 3 cohorts, respectively (all P <.001). Regardless of KS, patients with VTE had significantly lower survival rates than those without. Conclusions: This real‐world claims‐based cohort study of newly diagnosed cancer patients showed significantly higher rates of VTE with increased KS, confirming its predictive ability. Moreover, VTE was associated with lower survival rates within each KS cohort. [ABSTRACT FROM AUTHOR]

Purpose: Anticoagulant therapy for at least 3-6 months is currently recommended for treatment of venous thromboembolism (VTE) in patients with cancer, but the optimal duration of treatment is unknown. This study examines the association between the duration of anticoagulation treatment and VTE recurrence in cancer patients.Methods: The Humana claims database was used to identify newly diagnosed cancer patients who had their first VTE diagnosis between January 1, 2013, and May 31, 2015, and initiated injectable or oral anticoagulant therapy. Follow-up was calculated from the index treatment initiation to the end of eligibility or end of data (June 2015). VTE recurrence was defined as a hospitalization with a primary diagnosis of VTE. Cox proportional hazards models were used to evaluate the risk of VTE recurrence by duration of therapy in patients who discontinued therapy.Results: The study included 1158 patients. Compared to patients treated for 0 to 3 months, VTE recurrences were significantly lower among patients treated for 3 to 6, or over 6 months. After adjustment for baseline characteristics, patients treated for 3 to 6 months (HR [95%CI], 0.53; 0.37-0.76) and more than 6 months (HR [95%CI], 0.48; 0.34-0.68) were still significantly less likely to have VTE recurrences compared to patients treated for 0 to 3 months (both p < 0.01). Findings were similar using a VTE event definition that included outpatient visits.Conclusions: Among newly diagnosed cancer patients with VTE, anticoagulant therapy lasting more than 3 months was associated with a lower risk of VTE recurrence. [ABSTRACT FROM AUTHOR]

Venous thromboembolism (VTE) is a common complication of cancer occurring in up to one-fifth of cancer patients. The risk of VTE, which includes deep venous thrombosis (DVT) and pulmonary embolism (PE), is increased up to seven-fold in patients with cancer. While the indications and contraindications to treatment for VTE patients with cancer parallel to those patients without cancer, the treatment of VTE is challenging for cancer patients who are three-fold more likely to have VTE recurrence than patients without cancer and who are also at increased risk of bleeding. While anticoagulant therapy is recommended for most cancer patients with VTE, some patients may benefit from alternative interventions, such as thrombolysis, thromboembolectomy, or placement of an inferior vena cava (IVC) filter. Recent data support the use of direct oral anticoagulants (DOACs) for treatment of cancer-associated VTE in select cancer patients and for primary prevention of thromboembolism in high-risk cancer patients. Individualized decision-making, keeping in consideration the patient's risk for thrombotic and bleeding events is essential. [ABSTRACT FROM AUTHOR]

The article offers information on the evidence-based clinical practice guidelines on potentially curable pancreatic cancer. It mention the guideline update adds a modified dose of Folfirinox to the postoperative treatment options for patients with resected pancreatic adenocarcinoma; and also mentions that the eligible patients for the trial were adult patients up to 79 years old with histologically proven pancreatic ductal adenocarcinoma.

Background: Delays in time to treatment initiation (TTI) for new cancer diagnoses cause patient distress and may adversely affect outcomes. We investigated trends in TTI for common solid tumors treated with curative intent, determinants of increased TTI and association with overall survival. Methods and findings: We utilized prospective data from the National Cancer Database for newly diagnosed United States patients with early-stage breast, prostate, lung, colorectal, renal and pancreas cancers from 2004–13. TTI was defined as days from diagnosis to first treatment (surgery, systemic or radiation therapy). Negative binomial regression and Cox proportional hazard models were used for analysis. The study population of 3,672,561 patients included breast (N = 1,368,024), prostate (N = 944,246), colorectal (N = 662,094), non-small cell lung (N = 363,863), renal (N = 262,915) and pancreas (N = 71,419) cancers. Median TTI increased from 21 to 29 days (P<0.001). Aside from year of diagnosis, determinants of increased TTI included care at academic center, race, education, prior history of cancer, transfer of facility, comorbidities and age. Increased TTI was associated with worsened survival for stages I and II breast, lung, renal and pancreas cancers, and stage I colorectal cancers, with hazard ratios ranging from 1.005 (95% confidence intervals [CI] 1.002–1.008) to 1.030 (95% CI 1.025–1.035) per week of increased TTI. Conclusions: TTI has lengthened significantly and is associated with absolute increased risk of mortality ranging from 1.2–3.2% per week in curative settings such as early-stage breast, lung, renal and pancreas cancers. Studies of interventions to ease navigation and reduce barriers are warranted to diminish potential harm to patients. [ABSTRACT FROM AUTHOR]

Some chemotherapy medications, in particular those that are used to treat a blood cancer called multiple myeloma, put patients at higher risk for thrombosis, and patients receiving these medications will also be prescribed preventive anticoagulants. Patients with arterial thrombosis often receive the same treatment with anticoagulant medications as patients with VTE. For patients with more severe bleeding, anticoagulants are typically stopped until the patient is felt to be safe to be resumed on treatment. These CVCs can cause DVT in the arm or neck veins.[5] Despite that, most patients with cancer and CVCs will never have a catheter-related thrombosis, so preventive anticoagulants are not recommended. [Extracted from the article]

Current guidelines recommend that patients with cancer be assessed for venous thromboembolism(VTE) risk at the time of chemotherapy initiation and periodically thereafter. Rates of VTE vary substantially among cancer patients. Multiple clinical factors contribute to VTE risk, including the primary site of cancer, extent of disease, interventions including major surgery, hospitalization, and systemic therapy. However, risk of VTE cannot reliably be predicted based on a single risk factor or biomarker. Within the last decade, risk assessment scores have been developed in cancer patients to more reliably predict thromboembolic events. This review provides an overview of evidence supporting the use of such tools for both primary and recurrent cancer-associated VTE. Potential applications of risk assessment tools as well as current knowledge gaps are outlined. [ABSTRACT FROM AUTHOR]

Purpose The EINSTEIN-Extension trial showed that an extended rivaroxaban treatment significantly reduced the risk for venous thromboembolic (VTE) recurrence. The present study assessed the risk for VTE recurrence and major bleeding associated with extended rivaroxaban treatment in a clinical practice setting among patients with VTE. Methods A retrospective study was conducted using claims data from February 2011 to April 2015. It included adult patients who initiated rivaroxaban therapy within 7 days after their first VTE and who continuously used rivaroxaban for at least 3 months (index date: end of initial 3-month treatment). Categorized into discontinued and continued cohorts, patients were followed up from the index date until the end of continuous treatment (continued cohort) or end of data or reinitiation of oral anticoagulant therapy (discontinued cohort). Using inverse probability of treatment weights controlling for confounders, adjusted Kaplan-Meier rates of recurrent VTE and major bleeding events were compared. Findings The analysis showed that, compared with the discontinued cohort (n = 1,536), the continued cohort (n = 5,933) had a significantly lower VTE recurrence rate after an additional 3 months (0.70% vs 1.70%), 6 months (1.41% vs 2.34%), 9 months (1.82% vs 3.01%), and 12 months (1.97% vs 3.01%) of treatment (all, p < 0.05). The difference in the cumulative event rates for major bleeding was not statistically significant. Similar results were obtained in an analysis among patients with VTE receiving rivaroxaban for ≥6 months. Implications Our results suggest that, in clinical practice settings, patients with VTE who continued rivaroxaban therapy after the initial 3- or 6-month treatment period had a significantly lower risk for VTE recurrence without a statistically significant increased risk for major bleeding. [ABSTRACT FROM AUTHOR]

The article presents a February 2017 clinical practice guideline update summary released by the American Society of Clinical Oncology (ASCO) which aimed to provide oncologists and other clinicians with current evidence on potentially curable pancreatic cancer. The guideline includes target population and audience, methods and updated recommendations.

Background Ambulatory cancer patients at high-risk for venous thromboembolism (VTE) can be identified using a validated risk score (Khorana score). We evaluated the benefit of outpatient thromboprophylaxis with dalteparin in high-risk patients in a multicenter randomized study. Methods Cancer patients with Khorana score ≥ 3 starting a new systemic regimen were screened for VTE and if negative randomized to dalteparin 5000 units daily or observation for 12 weeks. Subjects were screened with lower extremity ultrasounds every 4 weeks on study and with chest CT at 12 weeks. The primary efficacy endpoint was all VTE over 12 weeks and primary safety endpoint was clinically relevant bleeding events over 13 weeks. The study was terminated early due to low accrual. Results Of 117 enrolled patients, 10 (8.5%) had VTE on baseline screening and were not randomized. Of 98 randomized patients, VTE occurred in 12% (N = 6/50) of patients on dalteparin and 21% (N = 10/48) on observation (hazard ratio, HR 0.69, 95% CI 0.23–1.89). Major bleeding was similar (N = 1) in each arm but clinically relevant bleeding was higher in dalteparin arm (N = 7 versus 1 on observation) (HR = 7.0, 95% CI 1.2–131.6). There was no difference in overall survival. Conclusions Thromboprophylaxis is associated with a non-significantly reduced risk of VTE and significantly increased risk of clinically relevant bleeding in this underpowered study. The Khorana score successfully identifies patients with high incidence of VTE both at baseline and during treatment. Future studies should continue to focus on risk-adapted approaches to reduce the burden of VTE in cancer. Trial registration clinicaltrials.gov identifier: NCT00876915 [ABSTRACT FROM AUTHOR]

This Arts and Medicine feature offers an appreciation of mid-20th century novelist, essayist, memoirist, and civil rights activist James Baldwin and argues for his continuing relevance to medicine and society at large. [ABSTRACT FROM AUTHOR]

Introduction Venous thromboembolism (VTE) is a common complication of cancer. Clinical practice guidelines recommend low-molecular-weight heparin (LMWH) for treatment of cancer-associated VTE, but it is unclear how frequently these are followed. This study assessed anticoagulation treatment patterns for VTE in newly diagnosed cancer patients in the United States. Materials and methods MarketScan® claims records of more than 80 million insured members between January 1, 2009 and July 31, 2014 were retrospectively analyzed. Subjects were included if they were 18 years of age or older, and had a diagnosis of cancer (9 solid tumor types) and VTE. Data were included for LMWH, warfarin, and other anticoagulants (fondaparinux and direct oral anticoagulants [DOACs]). Patients with anticoagulant treatment prior to cancer diagnosis were excluded. Results VTE developed in 6.2% of cancer patients (median, 181 days after cancer diagnosis). VTE rates were highest for pancreatic (17.5%) and lung (12.6%) cancer and lowest for breast (4.2%) and prostate (4.1%) cancer. For patients for whom outpatient prescription data were available, warfarin was most commonly used (50.0%), followed by LMWH (40.0%) and other anticoagulants (10.0%). Over 6 months, 13% of patients who initiated injectable anticoagulants remained on them compared with 30% of those who initiated oral anticoagulants. More patients switched from LMWH to warfarin and other anticoagulants (44%) versus those who switched from warfarin (28%). Conclusions Warfarin was the most utilized anticoagulant for cancer-associated VTE despite guideline recommendations for LMWH. More patients remained on oral versus injectable agents, which may be related to self-injection burden and costs. [ABSTRACT FROM AUTHOR]

Patients with active malignancy are well-known to be at higher risk for venous thromboembolism (VTE). However, the risk of VTE varies considerably between patients and in the same patient over the natural history of their malignancy. Multiple clinical risk factors including primary site of cancer, use of systemic therapy including novel targeted agents, surgery, and hospitalization are known to increase the risk of VTE. Multiple candidate biomarkers including tissue factor, D-dimer, and soluble P-selectin have been identified. However, risk cannot be reliably predicted based on single risk factors or biomarkers. A risk assessment score has been validated in multiple populations and can identify patients at high risk for cancer-associated VTE. This review discusses the risk factors, predictive biomarkers, and new guidelines, which recommend risk assessment of VTE for all cancer patients. Potential applications of risk assessment, including targeted thromboprophylaxis, are also identified in this review. [ABSTRACT FROM AUTHOR]

Abstract: Background: Tissue factor (TF), the physiologic initiator of coagulation, is over-expressed in pancreatic cancer, and is associated with a pro-coagulant and pro-angiogenic state. We hypothesized that in patients with pancreaticobiliary cancers (PBC), elevated circulating microparticle-associated TF (MP-TF) activity would be associated with thrombosis and worsened survival. Patients and Methods: Clinical data and plasma were obtained for consecutive patients with PBC seen at Roswell Park Cancer Institute from 2005-08. MP-TF activity levels were measured using a TF-dependent FXa generation assay. Results: The study population comprised 117 patients, including pancreatic (n=80), biliary (n=34) or unknown primary histologically consistent with PBC (n=3). Of these, 52 patients (44.5%) experienced thromboembolism, including pulmonary embolism (n=15), deep venous thrombosis (n=21) and other arterial or venous events (n=32). Mean TF was 2.15 (range 0.17- 31.01) pg/mL. Median survival was 98.5days for MP-TF activity ≥2.5pg/mL versus 231days for MP-TF activity<2.5pg/mL (p<0.0001). In multivariate analysis, elevated MP-TF activity was associated with both VTE (OR 1.4, 95% CI 1.1-1.6) and mortality (HR 2.5, 95% CI 1.4-4.5). Conclusions: Elevated circulating MP-TF activity is associated with thrombosis and worsened survival in patients with PBC. MP-TF activity as a prognostic biomarker warrants further prospective evaluation. [Copyright &y& Elsevier]

BACKGROUND: Recent studies suggest that thromboprophylaxis is beneficial in preventing venous thromboembolism (VTE) in cancer outpatients, but this is not widely adopted because of incomplete understanding of the contemporary incidence of VTE and concerns about bleeding. Therefore, the authors examined the incidence and predictors of VTE in ambulatory patients with bladder, colorectal, lung, ovary, pancreas, or gastric cancers. METHODS: Data were extracted from a large health care claims database of commercially insured patients in the United States between 2004 and 2009. Demographic and clinical characteristics of the cancer cohort (N = 17,284) and an age/sex-matched, noncancer control cohort were evaluated. VTE incidence was recorded during a 3-month to 12-month follow-up period after the initiation of chemotherapy. Multivariate analyses were conducted to identify independent predictors of VTE and bleeding. RESULTS: The mean age of the study population was 64 years, and 51% of patients were women. VTE occurred in 12.6% of the cancer cohort (n = 2170) over 12 months after the initiation of chemotherapy versus 1.4% of controls (n = 237; P < .0001); incidence ranged by cancer type from 19.2% (pancreatic cancer) to 8.2% (bladder cancer). Predictors of VTE included type of cancer, comorbidities (Charlson Comorbidity Index score or obesity), and commonly used specific antineoplastic or supportive care agents (cisplatin, bevacizumab, and erythropoietin). CONCLUSIONS: This large, contemporary, real-world analysis confirmed high rates of VTE in select patients with solid tumors and suggested that the incidence of VTE is high in the real-world setting. Awareness of the benefits of targeted thromboprophylaxis may result in a clinically significant reduction in the burden of VTE in this population. Cancer 2013. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

Abstract: Background: Leukocytosis has been associated with thrombosis and mortality in cancer patients. We explored the association of leukocytosis with venous thromboembolism (VTE) and early mortality in cancer patients initiating chemotherapy. Methods: Data from a prospective, multicenter observational study of treatment-related complications in 4,405 ambulatory cancer patients initiating chemotherapy was used for this analysis. The association of leukocytosis, VTE and mortality during the course of chemotherapy was evaluated in univariate and multivariate analysis. Results: Ninety-three patients (2.1%) developed VTE and 134 (3%) died over a median follow up of 75days (range 0-384). Of 4391 patients with available baseline white blood cell (WBC) count, 561 (12.8%) had elevated pretreatment leukocyte counts, defined as WBC > 11×109 cells/L. VTE occurred in 25 of 561 patients (4.5%) with baseline leukocytosis compared to 68 of 3830 (1.8%) with WBC ≤ 11×109 cells/L (P<0.0001). Baseline leukocytosis was associated with VTE by multivariate analysis as well (HR 2.1, 95% confidence interval 1.3-3.4, p=0.003). Forty one patients (7.3%) with leukocytosis died compared to 92 (2.4%) with WBC ≤ 11×109 cells/L (P<0.0001). Baseline leukocytosis was associated with early mortality by multivariate analysis as well (HR 2.2, 95% confidence interval 1.5-3.3, p<0.0001). Mortality was greatest in patients with both leukocytosis and VTE. In multivariate analysis several factors were predictive of leukocytosis. Conclusions: Elevated WBC, particularly neutrophils, is strongly associated with increased risk of VTE and mortality in cancer patients receiving systemic chemotherapy. Further studies are needed to elicit the mechanisms involved. [Copyright &y& Elsevier]

Abstract: Venous thromboembolism (VTE) is a frequent complication of malignancy, and its incidence has increased markedly in recent years. VTE itself can directly lead to patient mortality, and is the second leading cause of death in patients with cancer. Furthermore, emerging data suggest that activation of coagulation in malignancy is integrally linked with tumor biology, particularly with angiogenesis. The development of the clinical hypercoagulable state is also linked with adverse prognosis in patients with cancer, including patients receiving systemic chemotherapy. This review focuses on the clinical evidence documenting a link between VTE and adverse short-term and long-term prognosis in patients with cancer. [Copyright &y& Elsevier]

Objective: Docetaxel and capecitabine are active agents in advanced gastric and gastroesophageal (GE) carcinomas. This multi-institutional phase II trial evaluates the combination of docetaxel and capecitabine as first- or second-line treatment in patients with advanced gastric and GE adenocarcinomas. Methods: Patients who had received 1 or no prior chemotherapy regimens were eligible. The chemotherapy regimen consisted of a 21-day cycle with docetaxel 30 mg/m2 administered on days 1 and 8 and capecitabine 825 mg/m2 administered twice daily on days 1–14. The primary end point of the study was overall survival (OS). Results: Forty patients were enrolled in the study; 39 received treatment and were evaluable for response and toxicity. The median patient age was 61 years (range 21–84); 8 patients had received prior chemotherapy in the advanced or metastatic setting. Grade 3/4 adverse events occurred in 15 patients (38%), including diarrhea in 5 patients (13%) and hand-foot syndrome in 5 patients (13%). The overall response rate was 32% [95% confidence interval (CI) 16.7–51.4]. The median time to progression and OS were 3.4 months (95% CI 2.7–5.8) and 10.7 months (95% CI 6.1–12.1), respectively. Conclusions: The regimen of docetaxel and capecitabine is a well-tolerated, easily administered and active outpatient regimen for advanced gastric and GE adenocarcinoma. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article presents a retrospective cohort study which examines the association of blood transfusions, thrombosis and mortality in hospitalized patients with cancer in the U.S. In the study, 70,542 patients received at least one red blood cell (RBC) transfusion while 15,237 underwent at least one platelet transfusion. It states that 7.2% of the patients developed venous thromboembolism and 5.2% obtained arterial thromboembolism. Researchers found that both RBC and platelet transfusions are linked with increased risks of venous and arterial thrombotic events and mortality to cancer patients.

Simple Summary: Patients with cancer commonly develop blood clots, which can cause issues including hospitalizations and complications and can affect cancer treatments. Cancer therapies can be one of the reasons for blood clots. A type of cancer therapy called "immune checkpoint inhibitors" has been used more and more often in recent years for different types of cancer. Recent reports revealed an increasing concern of blood clots related to immune checkpoint inhibitors. In this review, we will summarize data from the available studies and discuss the rates, risk factors, prevention, and treatment strategies for blood clots related to immune checkpoint inhibitors. Thromboembolism is a common complication in patients with cancer and is associated with significant morbidity and mortality. Anticancer treatment is a known risk factor of cancer-associated thrombosis. Immune checkpoint inhibitors have become a mainstay of treatment in various cancers. Both venous and arterial thrombosis have been increasingly reported as adverse events associated with immune checkpoint inhibitors in recent studies, with a cumulative incidence of venous thrombosis to be 5–8% at 6 months and over 10% at 12 months. Additionally, rates of approximately 1–5% for arterial thrombosis were reported at 12 months. Data also showed an association of thromboembolism with adverse survival. Many pertinent clinical questions in this population deserve further investigation, including the risks of thrombosis associated with immune checkpoint inhibitors as compared to those with traditional systemic therapy, associated risk factors, and the optimal prevention and treatment strategies. In this review, we synthesize data from available literature, provide relevant information for clinicians and potential future directions for research. [ABSTRACT FROM AUTHOR]

A personal narrative is presented which relates the author's experience of his first night on call at a hospital in New York state after arriving from India three weeks into the start of his residency.

The article presents a study which investigated the frequency, risk factors and trends associated with venous thromboembolism (VTE) among hospitalized cancer patients. The authors conclude that VTE, particularly pulmonary embolism, is an increasingly frequent complication of hospitalization in cancer patients.

The article presents a study which evaluated the impact of anticoagulants on survival and safety in cancer patients without venous thromboembolism. A comprehensive systematic literature examination of randomized controlled trials (RCT) was performed without language restrictions through May 2006 with subsequent updates to the end of 2006. The study found that anticoagulation significantly decreased 1-year overall mortality with a relative risk (RR) of 0.905.

Keywords: cancer; thrombosis; venous thromboembolism (VTE) EN cancer thrombosis venous thromboembolism (VTE) 208 209 2 06/19/20 20200601 NES 200601 The association between cancer and thrombosis has been known for at least a century. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO Clinical Practice Guideline Update. [Extracted from the article]

In this narrative medicine essay, a hematologist/oncologist and a nurse practitioner couple tell of a terrifying change in the behavior of their intellectually challenged son and of the physician who discovered the cause. [ABSTRACT FROM AUTHOR]

Angiogenesis is important for pancreatic cancer progression, but its role in predicting response to therapy is not known. We investigated the association of various angiogenic factors and intratumoral microvessel density (IMD) with adjuvant therapy and survival in resected pancreatic cancer. Tissue cores from a multi-institutional retrospective series of resected patients were used to build a pancreatic cancer tissue microarray. Vascular endothelial growth factor (VEGF), platelet-derived endothelial cell growth factor (PD-ECGF), CD31 (for IMD), and DPC4 expression were determined using immunohistochemistry. Expression of VEGF and PD-ECGF, both proangiogenic factors, was observed in 70 (56%) and 75 (59%) of 124 tumors, respectively. Expression of DPC4, an angiogenesis inhibitor, was observed in 59 of 124 (48%) tumors. VEGF expression correlated significantly with increased IMD (P =.03), as did loss of antiangiogenic DPC4 (P =.05). PD-ECGF expression did not correlate with IMD. Use of adjuvant therapy was associated with increased survival in patients with VEGF-positive tumors (18.8 [treated] versus 11.2 [untreated] months; hazard ratio [HR]=0.38, 95% confidence interval [CI], 0.19–0.76; P =.005), but not in patients with VEGF-negative tumors. Similarly, improved survival was observed in patients with high IMD (16.3 [treated] versus 11.2 [untreated] months; HR=0.44, 95% CI, 0.23–0.87; P =.02) and in patients with loss of DPC4 (20.3 [treated] versus 11.2 [untreated] months; HR=0.31, 95% CI, 0.14–0.67; P =.002), but not in those with low IMD or normal DPC4 expression. VEGF (stimulator) and DPC4 (inhibitor) are important regulators of pancreatic tumor angiogenesis and predictive of benefit from adjuvant therapy. Adjuvant therapy may have both antiangiogenic and cytotoxic effects. Addition of anti-VEGF agents to adjuvant regimens may further improve outcomes. [Copyright &y& Elsevier]

The article is the narrative of the author regarding one of his patients, K.W. KW. suffers from metastatic rectal cancer, and he has been his sometime oncologist over the past six months. His cancer was metastatic when first diagnosed, and his initial surgery was complicated by a wound infection. This took several courses of antibiotics and several weeks of nursing care provided by his foster son, to heal. K.W's condition improved, but only to an intermittently awake state. Health care providers and researchers should be equally humanists and scientists.

Thromboembolic disease is a common complication of pancreatic cancer and is causally associated with the generation of an intrinsic hypercoagulable state. Pancreatic-cancer cells activate platelets and express several procoagulant factors, including tissue factor and thrombin. The activation of coagulation is not simply an epiphenomenon, but might also be related to enhanced tumour growth and angiogenesis. Clinical manifestations of thromboembolic disease in pancreatic cancer include deep venous thrombosis, pulmonary embolism, disseminated intravascular coagulation, portal vein thrombosis, and arterial thromboembolism. Reported incidences of disease range from 17% to 57%. Treatment options include warfarin and low-molecular-weight heparins. Studies over the past decade suggest that long-term use of these heparins in both primary and secondary prevention of venous thromboembolic disease improves outcomes in comparison with warfarin. Further research is needed to understand better the morbidity and mortality associated with this disease in pancreatic cancer and to optimise strategies of prevention and treatment. [Copyright &y& Elsevier]

Presents the story of a physician who is about to be married. Challenges faced by the physician in his daily life; Difficulties faced by the doctor in getting a dying patient to sign a Do-not-resuscitate orders form.

Aims: Interferon-gamma (IFN-g) has been shown to upregulate MHC class I and II expression, and to promote generation of specific antitumor immune responses. We hypothesized that intratumoral administration of an IFN-γ gene transfer vector facilitates its enhanced local production and may activate effector cells locally. We conducted a phase I dose-escalation study of a replication-deficient adenovirus-interferon-gamma construct (TG1041) to determine safety and tolerability of intratumoral administration, in advanced or locally recurrent melanoma. Methods: Patients were enrolled at four successive dose levels: 10[SUP7] infectious units (iu) (n =3), 10[SUP8] iu (n =3), 10[SUP9]iu (n =3), and 10[SUP10]iu (n =2) per injection per week for 3 weeks. TG1041 was injected in the same tumor nodule weekly in each patient. Safety, toxicity, local and distant tumor responses and biologic correlates were evaluated. Results: A total of 11 patients were enrolled and received the planned three injections per cycle. One patient with stable disease received a second cycle of treatment. A maximum tolerated dose was not reached in this study. No grade 4 toxicities were observed. Two grade 3 toxicities, fever and deep venous thrombosis were observed in one patient. The most frequently reported toxicities were grade 1 pain and redness at the injected site (n =8), and grade 1 fatigue (n =5) patients. Clinical changes observed at the local injected tumor site included erythema (n =5), a minor decrease in size of the injected lesion (n =5) and significant central necrosis by histopathology (n =1). Systemic effects included stable disease in one patient. Correlative studies did not reveal evidence of immunologic activity. Conclusion: Weekly intratumoral administration of TG1041 appears to be safe and well tolerated in patients with advanced melanoma. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article about the American College of Chest Physicians' evidence-based clinical practice guidelines on antithrombotic therapy and thrombosis prevention in the February 2012 issue.

Patients with treatment-naïve mRCC are treated with IO-based regimens, usually a combination of either IO/IO or IO/TKI. Both IO and TKI therapies are associated with an increased risk of thromboembolism, however, there are no head-to-head trials comparing IO/IO to IO/TKI regimens. Our study did not show a significant difference in the rate of TE between patients treated with IO/IO or IO/TKI. Background: Most patients with treatment-naïve metastatic renal cell carcinoma (mRCC) receive combination-based immunotherapy with either 2 immune-oncology checkpoint inhibitors (IO/IO) or an IO agent in combination with a vascular endothelial growth factor receptor (VEGF-R) tyrosine kinase inhibitor (IO/TKI). The rates of thromboembolism (TE) in these cohorts are not clear ly descr ibed and can potentially impact decision-making between IO/IO and IO/TKI. Methods: We conducted a retrospective investigation of patients with treatment-naïve mRCC treated with IO-based combinations between January 2015 and April 2021 at the Cleveland Clinic. TE events, including venous and arterial, were identified in each group. Competing risk regression was done to identify factors associated with the development of TE following therapy, with all-cause mortality treated as a competing event. Results: Of 180 patients identified, 77 (43%) received IO/TKI and 103 (57%) received IO/IO. Median age was 65 years, 75% were male, and 80% had clear cell histology. Baseline characteristics were similar between the 2 groups. At a median follow-up of 22.0 months, 10.0% of all patients had a TE. The one-year incidence of TE was 8.1% (95% CI: 3.3%-15.8%) with IO/TKI and 9.8% (95% CI: 5.0%-16.5%) with IO/IO and was not significantly different between the 2 groups (HR 0.89, 95% CI: 0.35%-2.28%). Occurrence of TE was associated with decreased overall survival regardless of IO/IO or IO/TKI therapy (HR 2.80, 95% CI: 1.57-5.02). There was no difference in incidence of TE based on patient age, gender, prior history of TE, International Metastatic Renal Cell Carcinoma (IMDC) risk group, or Khorana score. Conclusions: Incidence of TE is similar between IO/IO and IO/TKI regimens in treatment-naïve mRCC and is also associated with decreased overall survival. While risk of TE may not guide decision-making in choice of front-line mRCC therapy, careful attention should be given to the high risk of TE in this population. [ABSTRACT FROM AUTHOR]

Background: Postacute sequelae of COVID-19 (PASC), also referred to as "Long COVID", sometimes follows COVID-19, a disease caused by SARS-CoV-2. Although SARS-CoV-2 is well known to promote a prothrombotic state, less is known about the thrombosis risk in PASC. Our objective was to evaluate platelet function and thrombotic potential in patients following recovery from SARS-CoV-2, but with clear symptoms of patients with PASC. Methods: patients with PASC and matched healthy controls were enrolled in the study on average 15 months after documented SARS-CoV-2 infection. Platelet activation was evaluated by light transmission aggregometry (LTA) and flow cytometry in response to platelet surface receptor agonists. Thrombosis in platelet-deplete plasma was evaluated by Factor Xa activity. A microfluidics system assessed thrombosis in whole blood under shear stress conditions. Results: A mild increase in platelet aggregation in patients with PASC through the thromboxane receptor was observed, and platelet activation through the glycoprotein VI (GPVI) receptor was decreased in patients with PASC compared to age- and sex-matched healthy controls. Thrombosis under shear conditions as well as Factor Xa activity were reduced in patients with PASC. Plasma from patients with PASC was an extremely potent activator of washed, healthy platelets – a phenomenon not observed when stimulating healthy platelets after incubation with plasma from healthy individuals. Conclusions: patients with PASC show dysregulated responses in platelets and coagulation in plasma, likely caused by a circulating molecule that promotes thrombosis. A hitherto undescribed protective response appears to exist in patients with PASC to counterbalance ongoing thrombosis that is common to SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Deleterious effects of environmental exposures may contribute to the rising incidence of early-onset colorectal cancer (eoCRC). We assessed the metabolomic differences between patients with eoCRC, average-onset CRC (aoCRC), and non-CRC controls, to understand pathogenic mechanisms. Patients with stage I–IV CRC and non-CRC controls were categorized based on age ≤ 50 years (eoCRC or young non-CRC controls) or ≥ 60 years (aoCRC or older non-CRC controls). Differential metabolite abundance and metabolic pathway analyses were performed on plasma samples. Multivariate Cox proportional hazards modeling was used for survival analyses. All P values were adjusted for multiple testing (false discovery rate, FDR P < 0.15 considered significant). The study population comprised 170 patients with CRC (66 eoCRC and 104 aoCRC) and 49 non-CRC controls (34 young and 15 older). Citrate was differentially abundant in aoCRC vs. eoCRC in adjusted analysis (Odds Ratio = 21.8, FDR P = 0.04). Metabolic pathways altered in patients with aoCRC versus eoCRC included arginine biosynthesis, FDR P = 0.02; glyoxylate and dicarboxylate metabolism, FDR P = 0.005; citrate cycle, FDR P = 0.04; alanine, aspartate, and glutamate metabolism, FDR P = 0.01; glycine, serine, and threonine metabolism, FDR P = 0.14; and amino-acid t-RNA biosynthesis, FDR P = 0.01. 4-hydroxyhippuric acid was significantly associated with overall survival in all patients with CRC (Hazards ratio, HR = 0.4, 95% CI 0.3–0.7, FDR P = 0.05). We identified several unique metabolic alterations, particularly the significant differential abundance of citrate in aoCRC versus eoCRC. Arginine biosynthesis was the most enriched by the differentially altered metabolites. The findings hold promise in developing strategies for early detection and novel therapies. [ABSTRACT FROM AUTHOR]

A reply to a letter to the editor in response to the article "Tinzaparin vs Warfarin for Acute Venous Thromboembolism," that was published in a previous issue of the journal is presented.

The author reflects on the diagnostic workup of cancer patients after their unprovoked clot. Topics discussed by the author include the emergence of femoral-vein thrombosis, the significance of early cancer diagnosis, and the insufficiency of evidence on the effectiveness of undiagnosed cancer testing.

Cancer-associated venous thromboembolism (VTE) has major consequences for patients, including morbidity and risk of mortality. However, there is substantial variation in risk depending on a multitude of clinical risk factors and many cancer patients are at low risk for VTE. This critical concept of risk variation has led to efforts to identify patients at high or low risk for developing VTE. Our research group and others have focused on understanding and predicting risk of cancer-associated VTE. This narrative review describe research efforts conducted over the past decade, beginning with the 2008 publication of the first validated risk assessment tool in this setting. We describe current applications of the “Khorana score” including identification of high- and low-risk patients, selecting and excluding patients for thromboprophylaxis and screening high-risk patients for early detection of VTE. New approaches to risk prediction including precision medicine and next-generation sequencing are discussed. Finally, we offer suggestions on improving the field of risk prediction in this setting in the near future. [ABSTRACT FROM AUTHOR]

In this issue of Blood, Warkentin et al describe a novel clinical syndrome of warfarin-associated severe venous limb ischemia occurring in a series of 10 patients with malignancy after initiating treatment of deep venous thrombosis. Patients in this series also demonstrated a decline in platelet counts after stopping heparin, warfarin-associated supratherapeutic international normalized ratios (INRs), and evidence of persistent thrombin generation despite anticoagulation.1 [ABSTRACT FROM AUTHOR]

The article discusses the decision taken by a physician for treatment of patient. Topics discussed include the recommendations of health screening for diagnosis of patient disease, increasing awareness in families for patient disease and advice on chemotherapy for cancer treatment. It also informs about the recommendations of ultrasound and radiology for diagnosis of disease.

Objectives: Tissue factor overexpression is associated with tumor progression, venous thromboembolism, and worsened survival in patients with cancer. Tissue factor and activated factor VII (FVIIa) complex may contribute to tumor invasiveness by promoting cell migration and angiogenesis. The study objective was to evaluate safety, pharmacokinetics, and efficacy of PCI-27483, a selective FVIIa inhibitor. Methods: This was an open-label, multicenter phase 2 trial of patients with advanced pancreatic cancer. Part A of the study was an intrapatient dose escalation lead-in portion in patients concurrently receiving gemcitabine, and in part B, patients were randomized 1: 1 to the recommended phase 2 dose combination PCI-27483–gemcitabine versus gemcitabine alone. Results: Target international normalized ratio (between 2.0–3.0) was achieved following PCI-27483 treatment. Overall safety of PCI-27483–gemcitabine (n = 26) was similar to gemcitabine alone (n = 16), with a higher incidence of mostly low-grade bleeding events (65% vs. 19%). Progression-free survival (PFS) and overall survival (OS) were not significantly different between patients treated with PCI-27483–gemcitabine (PFS: 3.7 months, OS: 5.7 months) and those treated with gemcitabine alone (PFS: 1.9 months, OS: 5.6 months). Conclusions: Targeted inhibition of the coagulation cascade was achieved by administering PCI-27483. PCI-27483–gemcitabine was well tolerated, but superiority to single agent gemcitabine was not demonstrated. [ABSTRACT FROM AUTHOR]

The article offers information on evaluating susceptibility to pancreatic cancer. It mentions the provisional clinical opinion (PCO) is intended to offer timely clinical direction to American Society of Clinical Oncology (ASCO's) oncologists and other health care providers; and also mentions estimates suggest that up to 10 percent of all pancreatic adenocarcinoma cases are familial, and pathogenic germline variants in specific genes have been associated with lifetime risks of pancreatic cancer.

Cancer-associated thrombosis leads to morbidity and mortality in cancer patients. We sought to ascertain awareness of venous thromboembolism (VTE) and receptiveness to thromboprophylaxis amongst ambulatory cancer patients. In all 190 patients completed the survey over a three-week period. Of these, 100 patients (53%) reported unawareness of the increased risk of thrombosis with malignancy. Of the examined patients, 161 (86%) were willing to use oral anticoagulant for prophylaxis, and 86 (46%) were willing to perform daily anticoagulant injections. This study reveals an alarming lack of knowledge amongst patients regarding the increased risk of thrombosis. Informed patients are willing to use prophylaxis, if its effectiveness is established. [ABSTRACT FROM AUTHOR]