We recently proposed a scale for assessment of patient-relevant functional limitations following an episode of venous thromboembolism (VTE). Further development of this post-VTE functional status ...(PVFS) scale is still needed.
Guided by the input of VTE experts and patients, we refined the PVFS scale and its accompanying manual, and attempted to acquire broad consensus on its use.
A Delphi analysis was performed involving 53 international VTE experts with diverse scientific and clinical backgrounds. In this process, the number of scale grades of the originally proposed PVFS scale was reduced and descriptions of the grades were improved. After these changes, a consensus was reached on the number/definitions of the grades, and method/timing of the scale assessment. The relevance and potential impact of the scale was confirmed in three focus groups totaling 18 VTE patients, who suggested additional changes to the manual, but not to the scale itself. Using the improved manual, the κ-statistics between PVFS scale self-reporting and its assessment via the structured interview was 0.75 (95%CI 0.58–1.0), and 1.0 (95%CI 0.83–1.0) between independent raters of the recorded interview of 16 focus groups members.
We improved the PVFS scale and demonstrated broad consensus on its relevance, optimal grades, and methods of assessing among international VTE experts and patients. The interobserver agreement of scale grade assignment was shown to be good-to-excellent. The PVFS scale may become an important outcome measure of functional impairment for quality of patient care and in future VTE trials.
•Functional limitations are frequent after venous thromboembolism (VTE).•We evaluated the previously proposed post-VTE functional status scale (PVFS scale).•After modifications, 53 VTE experts reached consensus on all scale aspects.•The goal and use of the scale were fully endorsed by patient focus groups.•Interobserver agreement of PVFS scale assessment was shown to be good to excellent.
Patients with cancer may be at high risk of adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed a cohort of patients with cancer and coronavirus ...2019 (COVID-19) reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies.
Patients with active or historical cancer and a laboratory-confirmed SARS-CoV-2 diagnosis recorded between 17 March and 18 November 2020 were included. The primary outcome was COVID-19 severity measured on an ordinal scale (uncomplicated, hospitalized, admitted to intensive care unit, mechanically ventilated, died within 30 days). Multivariable regression models included demographics, cancer status, anticancer therapy and timing, COVID-19-directed therapies, and laboratory measurements (among hospitalized patients).
A total of 4966 patients were included (median age 66 years, 51% female, 50% non-Hispanic white); 2872 (58%) were hospitalized and 695 (14%) died; 61% had cancer that was present, diagnosed, or treated within the year prior to COVID-19 diagnosis. Older age, male sex, obesity, cardiovascular and pulmonary comorbidities, renal disease, diabetes mellitus, non-Hispanic black race, Hispanic ethnicity, worse Eastern Cooperative Oncology Group performance status, recent cytotoxic chemotherapy, and hematologic malignancy were associated with higher COVID-19 severity. Among hospitalized patients, low or high absolute lymphocyte count; high absolute neutrophil count; low platelet count; abnormal creatinine; troponin; lactate dehydrogenase; and C-reactive protein were associated with higher COVID-19 severity. Patients diagnosed early in the COVID-19 pandemic (January-April 2020) had worse outcomes than those diagnosed later. Specific anticancer therapies (e.g. R-CHOP, platinum combined with etoposide, and DNA methyltransferase inhibitors) were associated with high 30-day all-cause mortality.
Clinical factors (e.g. older age, hematological malignancy, recent chemotherapy) and laboratory measurements were associated with poor outcomes among patients with cancer and COVID-19. Although further studies are needed, caution may be required in utilizing particular anticancer therapies.
NCT04354701
•Among 4966 patients with COVID-19 and a history of or active cancer, 58% were hospitalized and 14% died within 30 days.•Older age, male sex, obesity, comorbidities, non-Hispanic black race, and Hispanic ethnicity were associated with higher COVID-19 severity.•Worse performance status, hematologic malignancy, and recent cytotoxic chemotherapy were associated with more severe COVID-19.•Low or high absolute lymphocyte count, high absolute neutrophil count, low platelets, abnormal creatinine, troponin, lactate dehydrogenase, or C-reactive protein were associated with more severe COVID-19.•Specific anticancer therapies were associated with high 30-day all-cause mortality.
Venous thromboembolism (VTE) is a common cause of morbidity and mortality in patients with cancer. Compared with the general population, cancer patients with VTE have higher rates of both VTE ...recurrence and bleeding. While low molecular weight heparin (LMWH) has been the mainstay of treatment for cancer-associated VTE for over a decade, direct oral anticoagulants (DOACs) have recently emerged as a new therapeutic option due to their ease of administration and because they do not require laboratory monitoring. Several large randomized clinical trials have been performed or are ongoing at the time of writing, comparing DOACs with LMWH in this population. Three of these trials have thus far been published and suggest that DOACs are a reasonable alternative to LMWH for management of cancer-associated VTE. Despite the advantages offered by DOACs, these agents may not be appropriate for certain patient groups owing to increased risk of bleeding, organ compromise, extremes of weight, and other issues. Finally, data are emerging suggesting that DOACs may be useful for primary thromboprophylaxis in cancer patients in conjunction with validated risk assessment scores. In this evidence-based review, data for the use of DOACs to treat cancer-associated VTE will be examined, focusing on efficacy, safety, and timing of treatment. Guidance on choosing the optimal anticoagulant for a given patient is also offered.
Pulmonary embolism (PE) is a major cause of morbidity and mortality worldwide. In the United States alone, it is estimated that up to 100,000 PE-related deaths occur each year. While anticoagulant ...therapy is highly effective in reducing the risk of mortality in the majority of patients, advanced therapeutics are required in certain high-risk scenarios, such as in the setting of massive PE with haemodynamic compromise where urgent reperfusion therapy is strongly recommended. Conversely, patients with low-risk PE can often be safely managed with anticoagulant therapy alone and without the requirement of advanced therapies or for hospital admission. The optimal approach to management is less clear among patients with intermediate risk PE. In this setting, there is limited data to guide decision-making regarding the role of more aggressive treatment strategies and the competing risks are significant. The Pulmonary Embolism Response Team (PERT) model of care was developed in 2012 in order to support rapid clinical decision-making in the setting of complex acute PE. The PERT draws on expertise across multiple disciplines and provides a framework for timely access to advanced therapeutics when indicated based on consensus decision. The PERT model of PE care has expanded internationally and has led to operational streamlining in PE management through enhanced communication. Registry data suggest that the introduction of the PERT system is associated with an increased use of advanced techniques, such as catheter-directed thrombolysis without a concomitant increase in bleeding complications, although data from randomized trials are lacking. International guidelines have supported the concept of formalizing pathways of engagement between multidisciplinary colleagues. In the absence of randomised trial data, the model of care provided by PERT appears to represent the most effective means of optimizing communication strategies between specialist colleagues to collaborate in the care of individual patients, particularly in scenarios where patients present with complex care needs and where the balance of risks may be difficult to determine.
Central venous catheters (CVCs) are commonly used in oncology patients. Up to 50% of CVCs are complicated by thrombosis within the catheter or the blood vessel. These thrombi are the result of local ...tissue damage, the catheter itself, and the thrombophilia of cancer. Frequent flushes with saline or heparin may reduce the frequency of catheter dysfunction but do not reduce the rate of deep venous thrombosis (DVT) in the catheterized blood vessel. Efforts to use prophylactic heparin or warfarin to reduce catheter-related DVT have not been rewarding.
Personalizing non-small-cell lung cancer (NSCLC) therapy toward oncogene addicted pathway inhibition is effective. Hence, the ability to determine a more comprehensive genotype for each case is ...becoming essential to optimal cancer care.
We developed a multiplexed PCR-based assay (SNaPshot) to simultaneously identify >50 mutations in several key NSCLC genes. SNaPshot and FISH for ALK translocations were integrated into routine practice as Clinical Laboratory Improvement Amendments-certified tests. Here, we present analyses of the first 589 patients referred for genotyping.
Pathologic prescreening identified 552 (95%) tumors with sufficient tissue for SNaPshot; 51% had ≥1 mutation identified, most commonly in KRAS (24%), EGFR (13%), PIK3CA (4%) and translocations involving ALK (5%). Unanticipated mutations were observed at lower frequencies in IDH and β-catenin. We observed several associations between genotypes and clinical characteristics, including increased PIK3CA mutations in squamous cell cancers. Genotyping distinguished multiple primary cancers from metastatic disease and steered 78 (22%) of the 353 patients with advanced disease toward a genotype-directed targeted therapy.
Broad genotyping can be efficiently incorporated into an NSCLC clinic and has great utility in influencing treatment decisions and directing patients toward relevant clinical trials. As more targeted therapies are developed, such multiplexed molecular testing will become a standard part of practice.
Data on patients with COVID-19 who have cancer are lacking. Here we characterise the outcomes of a cohort of patients with cancer and COVID-19 and identify potential prognostic factors for mortality ...and severe illness.
In this cohort study, we collected de-identified data on patients with active or previous malignancy, aged 18 years and older, with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from the USA, Canada, and Spain from the COVID-19 and Cancer Consortium (CCC19) database for whom baseline data were added between March 17 and April 16, 2020. We collected data on baseline clinical conditions, medications, cancer diagnosis and treatment, and COVID-19 disease course. The primary endpoint was all-cause mortality within 30 days of diagnosis of COVID-19. We assessed the association between the outcome and potential prognostic variables using logistic regression analyses, partially adjusted for age, sex, smoking status, and obesity. This study is registered with ClinicalTrials.gov, NCT04354701, and is ongoing.
Of 1035 records entered into the CCC19 database during the study period, 928 patients met inclusion criteria for our analysis. Median age was 66 years (IQR 57–76), 279 (30%) were aged 75 years or older, and 468 (50%) patients were male. The most prevalent malignancies were breast (191 21%) and prostate (152 16%). 366 (39%) patients were on active anticancer treatment, and 396 (43%) had active (measurable) cancer. At analysis (May 7, 2020), 121 (13%) patients had died. In logistic regression analysis, independent factors associated with increased 30-day mortality, after partial adjustment, were: increased age (per 10 years; partially adjusted odds ratio 1·84, 95% CI 1·53–2·21), male sex (1·63, 1·07–2·48), smoking status (former smoker vs never smoked: 1·60, 1·03–2·47), number of comorbidities (two vs none: 4·50, 1·33–15·28), Eastern Cooperative Oncology Group performance status of 2 or higher (status of 2 vs 0 or 1: 3·89, 2·11–7·18), active cancer (progressing vs remission: 5·20, 2·77–9·77), and receipt of azithromycin plus hydroxychloroquine (vs treatment with neither: 2·93, 1·79–4·79; confounding by indication cannot be excluded). Compared with residence in the US-Northeast, residence in Canada (0·24, 0·07–0·84) or the US-Midwest (0·50, 0·28–0·90) were associated with decreased 30-day all-cause mortality. Race and ethnicity, obesity status, cancer type, type of anticancer therapy, and recent surgery were not associated with mortality.
Among patients with cancer and COVID-19, 30-day all-cause mortality was high and associated with general risk factors and risk factors unique to patients with cancer. Longer follow-up is needed to better understand the effect of COVID-19 on outcomes in patients with cancer, including the ability to continue specific cancer treatments.
American Cancer Society, National Institutes of Health, and Hope Foundation for Cancer Research.
Pulmonary embolism (PE) is common and management is based on risk stratification. The significance of clot location in submassive and massive PE is unclear. Data from a prospectively gathered ...database of submassive and massive PE were used for analysis. Available data included patient presentation, diagnostics, treatment, and outcome. Comparisons were made according to clot location: central or peripheral. A multivariable model was used for composite outcome of death or right ventricular (RV) strain at 90 days. Among 269 patients, there were no significant demographic differences between patients with peripheral and central PE. Peripheral PE was more likely to present with hypotension (46.4% vs 32.6%; p = 0.02), but central PE was more likely to have RV strain on echocardiography (76.7% vs 57.7%, p <0.001) and computed tomography (58.1% vs 32.0%, p <0.0001). Peripheral PE was more likely to receive anticoagulation as the only form of therapy (69.1% vs 55.8%; p = 0.03), and central PE was more likely to receive catheter-directed therapies (18.3% vs 3.3%; p <0.001). Nonetheless, peripheral PE had higher 30- and 90-day all-cause mortality (18.5% vs 9.3%; p = 0.03; 25.9% vs 13.5%; p = 0.02, respectively). In a multivariable analysis, the only independent predictor of death or RV strain at 90 days was increased age (odds radio 1.35, CI 1.06 to 1.72 per 10 years). Specifically, neither clot location nor treatment was associated with patient outcomes. In conclusion, in this cohort of patients with submassive and massive PE, clot location was associated with treatment patterns but not patient outcomes to 90 days. Reevaluation of practice is thus warranted.
Background
Hospitalized patients with COVID‐19 have increased risks of venous (VTE) and arterial thromboembolism (ATE). Active cancer diagnosis and treatment are well‐known risk factors; however, a ...risk assessment model (RAM) for VTE in patients with both cancer and COVID‐19 is lacking.
Objectives
To assess the incidence of and risk factors for thrombosis in hospitalized patients with cancer and COVID‐19.
Methods
Among patients with cancer in the COVID‐19 and Cancer Consortium registry (CCC19) cohort study, we assessed the incidence of VTE and ATE within 90 days of COVID‐19–associated hospitalization. A multivariable logistic regression model specifically for VTE was built using a priori determined clinical risk factors. A simplified RAM was derived and internally validated using bootstrap.
Results
From March 17, 2020 to November 30, 2020, 2804 hospitalized patients were analyzed. The incidence of VTE and ATE was 7.6% and 3.9%, respectively. The incidence of VTE, but not ATE, was higher in patients receiving recent anti‐cancer therapy. A simplified RAM for VTE was derived and named CoVID‐TE (Cancer subtype high to very‐high risk by original Khorana score +1, VTE history +2, ICU admission +2, D‐dimer elevation +1, recent systemic anti‐cancer Therapy +1, and non‐Hispanic Ethnicity +1). The RAM stratified patients into two cohorts (low‐risk, 0–2 points, n = 1423 vs. high‐risk, 3+ points, n = 1034) where VTE occurred in 4.1% low‐risk and 11.3% high‐risk patients (c statistic 0.67, 95% confidence interval 0.63–0.71). The RAM performed similarly well in subgroups of patients not on anticoagulant prior to admission and moderately ill patients not requiring direct ICU admission.
Conclusions
Hospitalized patients with cancer and COVID‐19 have elevated thrombotic risks. The CoVID‐TE RAM for VTE prediction may help real‐time data‐driven decisions in this vulnerable population.
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