Risk of recurrent venous thromboembolism in patients with autoimmune diseases: data from the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) registry.

Autoimmune disease is a risk factor for first incident venous thromboembolism (VTE). However, data on the risk of recurrent VTE in people with autoimmune disease is sparse. We explored the risk of recurrent VTE using the RIETE registry, comparing people with autoimmune disease (n = 1305) to those without (n = 50608). Overall rates were 6.5 and 5.1 recurrent VTE/100 years for patients with autoimmune disease vs controls, respectively. After adjustment for sex and unprovoked/provoked VTE yielded an adjusted hazard ratio of 1.29 (95%CI 1.03-1.62). The analysis was limited by short median follow up time (161 days overall), precluding definitive conclusions on recurrent VTE risks.

A Pragmatic Study Evaluating NEPA Versus Aprepitant for Prevention of Chemotherapy-Induced Nausea and Vomiting in Patients Receiving Moderately Emetogenic Chemotherapy.

BACKGROUND: Neurokinin (NK) 1 receptor antagonists (RAs), administered in combination with a 5-hydroxytryptamine-3 (5-HT3 ) RA and dexamethasone (DEX), have demonstrated clear improvements in chemotherapy-induced nausea and vomiting (CINV) prevention over a 5-HT3 RA plus DEX. However, studies comparing the NK1 RAs in the class are lacking. A fixed combination of a highly selective NK1 RA, netupitant, and the 5-HT3 RA, palonosetron (NEPA), simultaneously targets two critical antiemetic pathways, thereby offering a simple convenient antiemetic with long-lasting protection from CINV. This study is the first head-to-head NK1 RA comparative study in patients receiving anthracycline cyclophosphamide (AC) and non-AC moderately emetogenic chemotherapy (MEC). MATERIALS AND METHODS: This was a pragmatic, multicenter, randomized, single-cycle, open-label, prospective study designed to demonstrate noninferiority of single-dose NEPA to a 3-day aprepitant regimen in preventing CINV in chemotherapy-naive patients receiving AC/non-AC MEC in a real-life setting. The primary efficacy endpoint was complete response (no emesis/no rescue) during the overall (0-120 hour) phase. Noninferiority was achieved if the lower limit of the 95% confidence interval (CI) of the difference between NEPA and the aprepitant group was greater than the noninferiority margin set at -10%. RESULTS: Noninferiority of NEPA versus aprepitant was demonstrated (risk difference 9.2%; 95% CI, -2.3% to 20.7%); the overall complete response rate was numerically higher for NEPA (64.9%) than aprepitant (54.1%). Secondary endpoints also revealed numerically higher rates for NEPA than aprepitant. CONCLUSION: This pragmatic study in patients with cancer receiving AC and non-AC MEC revealed that a single dose of oral NEPA plus DEX was at least as effective as a 3-day aprepitant regimen, with indication of a potential efficacy benefit for NEPA. IMPLICATIONS FOR PRACTICE: In the absence of comparative neurokinin 1 (NK1 ) receptor antagonist (RA) studies, guideline committees and clinicians consider NK1 RA agents to be interchangeable and equivalent. This is the first head-to-head study comparing one NK1 RA (oral netupitant/palonosetron [NEPA]) versus another (aprepitant) in patients receiving anthracycline cyclophosphamide (AC) and non-AC moderately emetogenic chemotherapy. Noninferiority of NEPA versus the aprepitant regimen was demonstrated; the overall complete response (no emesis and no rescue use) rate was numerically higher for NEPA (65%) than aprepitant (54%). As a single-dose combination antiemetic, NEPA not only simplifies dosing but may offer a potential efficacy benefit over the current standard-of-care.

Role of supportive care in improving the quality of life and reducing unscheduled hospital care in patients with metastatic breast cancer.

BACKGROUND: Metastatic breast cancer (MBC) patients experience long survival and report poorer quality of life than localized breast cancer patients. Comprehensive supportive care (CSC) has been shown to improve the quality of life (QoL) of MBC. The respective part of each support care has not been fully examined, and little is known about whether meeting patients' needs is accompanied by decreased unscheduled hospital care (UHC). METHODS: This prospective monocentric study included women who started a new treatment line for MBC between January 2018 and December 2018. The endpoints were factors associated with UHC and QoL (SF36) at month 12. RESULTS: 100 patients were offered CSC, 78 were included (21 refusals, 1 no MBC). CSC was provided to 60 patients: pain (43%), psychological (37%), kinesitherapy (30%), social assistance (22%), esthetic (18%), nutrition (18%), massage (13%), and none (10%). CSC rate was not statistically different among patients with (58%) and without UHD (49%). Factors associated with a decrease of UHC were age > 65 years (p = 0.01), no previous treatment for MBC (p = 0.0001) with a trend for the lack of CSC (p = 0.054). Among the 8 domains of the SF36 scale, only health change perception was improved (p = 0.01) and its predictive factors were treatment carried out as planned (p = 0.0004), pain care (p = 0.003), and lack of MBC progression (p = 0.0035). CONCLUSION: CSC can improve QoL in MBC. Painful patients might benefit more from CSC. UHC did not decrease for patients receiving CSC as expected possibly because of their important needs for clinical care.

Dalteparin or vitamin K antagonists to prevent recurrent venous thromboembolism in cancer patients: a patient-level economic analysis for France and Austria.

BACKGROUND: International guidelines recommend extended duration secondary prophylaxis in cancer patients who develop primary venous thromboembolism (VTE). Agent selection is guided in part by one large randomized trial (i.e., CLOT; Lee et al., N Engl J Med 349:146-53, 2003) which demonstrated that dalteparin reduced the relative risk of recurrence by 52% compared with oral vitamin K antagonists (VKA; HR = 0.48, 95% CI, 0.30 to 0.77). In a subgroup analysis from that same trial, patients with renal impairment also derived benefit with dalteparin (VTE rates = 3% vs. 17%; p = 0.011). To measure the economic value of secondary VTE prophylaxis with dalteparin, a patient-level pharmacoeconomic analysis was conducted from the Austrian and French healthcare system perspectives. METHODS: Chapter 1 Healthcare resource use collected during the CLOT trial was extracted and converted into direct cost estimates. Incremental cost differences between the dalteparin and VKA groups were then combined with health state utilities to measure the cost per quality-adjusted life year (QALY) gained. RESULTS: The dalteparin group had significantly higher costs than the VKA group in both countries (Austria: dalteparin = €2687 vs. VKA = €2012; France: dalteparin = €2053 vs. VKA = €1352: p < 0.001). However, when the incremental costs were combined with the utility gain, dalteparin had a cost of €6600 and €4900 per QALY gained in Austria and France, respectively. The analyses in patients with renal impairment suggested an even better economic profile, with the cost per QALY gained being less than €4000 in both countries. CONCLUSIONS: Secondary prophylaxis with dalteparin is a cost-effective alternative to VKA for the prevention of recurrent VTE in patients with cancer.

International clinical practice guidelines including guidance for direct oral anticoagulants in the treatment and prophylaxis of venous thromboembolism in patients with cancer.

Venous thromboembolism (VTE) is the second leading cause of death in patients with cancer. These patients are at an increased risk of developing VTE and are more likely to have a recurrence of VTE and bleeding while taking anticoagulants. Management of VTE in patients with cancer is a major therapeutic challenge and remains suboptimal worldwide. In 2013, the International Initiative on Thrombosis and Cancer (ITAC-CME), established to reduce the global burden of VTE in patients with cancer, published international guidelines for the treatment and prophylaxis of VTE and central venous catheter-associated thrombosis. The rapid global adoption of direct oral anticoagulants for management of VTE in patients with cancer is an emerging treatment trend that needs to be addressed based on the current level of evidence. In this Review, we provide an update of the ITAC-CME consensus recommendations based on a systematic review of the literature ranked according to the Grading of Recommendations Assessment, Development, and Evaluation scale. These guidelines aim to address in-hospital and outpatient cancer-associated VTE in specific subgroups of patients with cancer.

Impact of venous thromboembolism on the natural history of pancreatic adenocarcinoma.

BACKGROUND: Few studies have analyzed the effect of venous thromboembolism (VTE) events on the prognosis of pancreatic cancer, but their results were conflicting. The present study was undertaken to determine the effect of VTE on pancreatic adenocarcinoma (PA) outcomes. METHODS: All consecutive patients diagnosed with PA from May 2004 to January 2012 in a single oncology center were retrospectively studied. Clinical, radiological and histological data at time of diagnosis or within the first 3 months after surgery, including the presence (+) or absence (-) of VTE were collected. VTE was defined as radiological evidence of either pulmonary embolism (PE), deep venous thrombosis without infection or catheter-related thrombosis. PA with and without PE was compared for survival using the Kaplan-Meier method to estimate overall survival. RESULTS: Among 162 PA patients with a median follow-up of 15 (3-92) months after diagnosis, 28 demonstrated VTE (+). PA patients with and without PE were similar for age, American Society of Anesthesiologist score, body mass index, and history of treatment. The distribution of cancer stages was similar between the two groups VTE (+) and VTE (-). The median duration of survival was significantly worse in the VTE (+) group vs VTE (-) (12 vs 18 months, P=0.010). In multivariate analysis, the presence of VTE and surgical treatment were independent prognostic factors for overall survival. CONCLUSION: VTE (+) at time of diagnosis or within the first 3 months after surgery during treatment is an independent factor of poor prognosis in PA.

Treatment of cancer-associated venous thromboembolism in patients under palliative care.

Many patients with cancer require palliative care at some stage and the vast majority of people followed in palliative care are cancer patients. Patients with cancer are at high risk of venous thromboembolism (VTE), and this is particularly true during the advanced palliative phase when mobility is limited or absent. Patients with cancer in palliative cancer are at higher bleeding risk compared to non-cancer patients. Decisions to treat VTE or withhold anticoagulation for these patients have proven to be difficult and depend largely on an individual clinician's judgment. For this reason, we have developed a consensus proposal for appropriate management of cancer-associated thromboembolism (CAT) in patients in palliative care, which is presented in this article. The proposal was informed by the recent scientific literature retrieved through a systematic literature review. In cancer patients in advanced palliative care, the benefit-risk ratio of anticoagulation seems unfavourable with a higher haemorrhagic risk than the benefit associated with prevention of CAT recurrence and, above all, in the absence of any benefit on quality of life. For this reason, we recommend that patients should be prescribed anticoagulants on a case-by-case basis. The choice of whether to treat, and with which type of treatment, should take into account anticipated life expectancy and patient preferences, as well as clinical factors such as the estimated bleeding risk, the type of VTE experienced and the time since the VTE event.

Central venous catheter associated upper extremity deep vein thrombosis in cancer patients: Diagnosis and therapeutic management.

Catheter-related thrombosis (CRT) is a relatively frequent and potentially fatal complication arising in patients with cancer who require a central catheter placement for intravenous treatment. In everyday practice, CRT remains a challenge for management; despite its frequency and its negative clinical impact, few data are available concerning diagnosis and treatment of CRT. In particular, no diagnostic studies or clinical trials have been published that included exclusively patients with cancer and a central venous catheter (CVC). For this reason, many questions regarding optimal management of CRT remain unanswered. Due to the paucity of high-grade evidence regarding CRT in cancer patients, guidelines are derived from upper extremity DVT studies for diagnosis, and from those for lower limb DVT for treatment. This article addresses the issues of diagnosis and management of CRT through a review of the available literature and makes a number of proposals based on the available evidence. In symptomatic patients, venous ultrasound is the most appropriate choice for first-line diagnostic imaging of CRT because it is noninvasive, and its diagnostic performance is high (which is not the case in asymptomatic patients). In the absence of direct comparative clinical trials, we suggest treating patients with CRT with a therapeutic dose of either a LMWH or a direct oral factor Xa inhibitor, with or without a loading dose. These anticoagulants should be given for a total of at least three months, including at least one month after catheter removal following initiation of therapy.

Cetuximab versus methotrexate in first-line treatment of older, frail patients with inoperable recurrent or metastatic head and neck cancer (ELAN UNFIT): a randomised, open-label, phase 3 trial.

BACKGROUND: At present, there is no established standard treatment for frail older patients with recurrent or metastatic head and neck squamous cell carcinoma. We aimed to compare the efficacy and safety of cetuximab to those of methotrexate (the reference regimen) in this population. METHODS: This randomised, open-label, phase 3 trial was done at 20 hospitals in France. Patients aged 70 years or older, assessed as frail by the ELAN Geriatric Evaluation, with recurrent or metastatic head and neck squamous cell carcinoma in the first-line setting and with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 were eligible for inclusion. Patients were randomly assigned (1:1) to receive cetuximab 500 mg/m2 intravenously every 2 weeks or methotrexate 40 mg/m2 intravenously every week, with minimisation by ECOG performance status, type of disease evolution, Charlson Comorbidity Index score, serum albumin concentration, and geriatrician consultation. To avoid deterministic minimisation and assure allocation concealment, patients were allocated with a probability of 0·80 to the treatment that most reduced the imbalance. Treatment was continued until disease progression or unacceptable toxicity, whichever occurred first. The primary endpoint was failure-free survival (defined as the time from randomisation to disease progression, death, discontinuation of treatment, or loss of 2 or more points on the Activities in Daily Living scale, whichever occurred first) and was analysed in the intention-to-treat population. 151 failures expected out of 164 patients were required to detect a hazard ratio (HR) of 0·625 with 0·05 alpha error, with 80% power. A futility interim analysis was planned when approximately 80 failures were observed, based on failure-free survival. Safety analyses included all patients who received at least one dose of the study drug. This study is registered on ClinicalTrials.gov (NCT01884623) and was stopped for futility after the interim analysis. FINDINGS: Between Nov 7, 2013, and April 23, 2018, 82 patients were enrolled (41 to the cetuximab group and 41 to the methotrexate group); 60 (73%) were male, 37 (45%) were aged 80 years or older, 35 (43%) had an ECOG performance status of 2, and 36 (44%) had metastatic disease. Enrolment was stopped for futility at the interim analysis. At the final analysis, median follow-up was 43·3 months (IQR 30·8-52·1). At data cutoff, all 82 patients had failure; failure-free survival did not differ significantly between the groups (median 1·4 months [95% CI 1·0-2·1] in the cetuximab group vs 1·9 months [1·1-2·6] in the methotrexate group; adjusted HR 1·03 [95% CI 0·66-1·61], p=0·89). The frequency of patients who had grade 3 or worse adverse events was 63% (26 of 41) in the cetuximab group and 73% (30 of 41) in the methotrexate group. The most common grade 3-4 adverse events in the cetuximab group were fatigue (four [10%] of 41 patients), lung infection (four [10%]), and rash acneiform (four [10%]), and those in the methotrexate group were fatigue (nine [22%] of 41), increased gamma-glutamyltransferase (seven [17%]), natraemia disorder (four [10%]), anaemia (four [10%]), leukopenia (four [10%]), and neutropenia (four [10%]). The frequency of patients who had serious adverse events was 44% (18 of 41) in the cetuximab group and 39% (16 of 41) in the methotrexate group. Four patients presented with a fatal adverse event in the cetuximab group (sepsis, decreased level of consciousness, pulmonary oedema, and death of unknown cause) as did two patients in the methotrexate group (dyspnoea and death of unknown cause). INTERPRETATION: The study showed no improvement in failure-free survival with cetuximab versus methotrexate. Patients with an ECOG performance status of 2 did not benefit from these systemic therapies. New treatment options including immunotherapy should be explored in frail older patients with recurrent or metastatic head and neck squamous cell carcinoma, after an initial geriatric evaluation, such as the ELAN Geriatric Evaluation. FUNDING: French programme PAIR-VADS 2011 (sponsored by the National Cancer Institute, the Fondation ARC and the Ligue Contre le Cancer), GEMLUC, GEFLUC, and Merck Santé. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Adapted EXTREME regimen in the first-line treatment of fit, older patients with recurrent or metastatic head and neck squamous cell carcinoma (ELAN-FIT): a multicentre, single-arm, phase 2 trial.

BACKGROUND: A standard treatment for fit, older patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) is yet to be established. In the previous EXTREME trial, few older patients were included. We aimed to evaluate the efficacy and tolerance of an adapted EXTREME regimen in fit, older patients with recurrent or metastatic HNSCC. METHODS: This single-arm, phase 2 study was done at 22 centres in France. Eligible patients were aged 70 years or older and assessed as not frail (fit) using the ELAN Geriatric Evaluation (EGE) and had recurrent or metastatic HNSCC in the first-line setting that was not eligible for local therapy (surgery or radiotherapy), and an Eastern Cooperative Oncology Group performance status of 0-1. The adapted EXTREME regimen consisted of six cycles of fluorouracil 4000 mg/m2 on days 1-4, carboplatin with an area under the curve of 5 on day 1, and cetuximab on days 1, 8, and 15 (400 mg/m2 on cycle 1-day 1, and 250 mg/m2 subsequently), all intravenously, with cycles starting every 21 days. In patients with disease control after two to six cycles, cetuximab 500 mg/m2 was continued once every 2 weeks as maintenance therapy until disease progression or unacceptable toxicity. Granulocyte colony-stimulating factor was systematically administered and erythropoietin was recommended during chemotherapy. The study was based on the two-stage Bryant and Day design, combining efficacy and toxicity endpoints. The primary efficacy endpoint was objective response rate at week 12 after the start of treatment, assessed by central review (with an unacceptable rate of ≤15%). The primary toxicity endpoint was morbidity, defined as grade 4-5 adverse events, or cutaneous rash (grade ≥3) that required cetuximab to be discontinued, during the chemotherapy phase, or a decrease in functional autonomy (Activities of Daily Living score decrease ≥2 points from baseline) at 1 month after the end of chemotherapy (with an unacceptable morbidity rate of >40%). Analysis of the coprimary endpoints, and of safety in the chemotherapy phase, was based on the per-protocol population, defined as eligible patients who received at least one cycle of the adapted EXTREME regimen. Safety in the maintenance phase was assessed in all patients who received at least one dose of cetuximab as maintenance therapy. The study is registered with ClinicalTrials.gov, NCT01864772, and is completed. FINDINGS: Between Sept 27, 2013, and June 20, 2018, 85 patients were enrolled, of whom 78 were in the per-protocol population. 66 (85%) patients were male and 12 (15%) were female, and the median age was 75 years (IQR 72-79). The median number of chemotherapy cycles received was five (IQR 3-6). Objective response at week 12 was observed in 31 patients (40% [95% CI 30-51]) and morbidity events were observed in 24 patients (31% [22-42]). No fatal adverse events occurred. Four patients presented with a decrease in functional autonomy 1 month after the end of chemotherapy versus baseline. During chemotherapy, the most common grade 3-4 adverse events were haematological events (leukopenia [22 patients; 28%], neutropenia [20; 26%], thrombocytopenia [15; 19%], and anaemia [12; 15%]), oral mucositis (14; 18%), fatigue (11; 14%), rash acneiform (ten; 13%), and hypomagnesaemia (nine; 12%). Among 44 patients who received cetuximab during the maintenance phase, the most common grade 3-4 adverse events were hypomagnesaemia (six patients; 14%) and acneiform rash (six; 14%). INTERPRETATION: The study met its primary objectives on objective response and morbidity, and showed overall survival to be as good as in younger patients treated with standard regimens, indicating that the adapted EXTREME regimen could be used in older patients with recurrent or metastatic HNSCC who are deemed fit with use of a geriatric evaluation tool adapted to patients with head and neck cancer, such as the EGE. FUNDING: French programme PAIR-VADS 2011 (sponsored by the National Cancer Institute, the Fondation ARC, and the Ligue Contre le Cancer), Sandoz, GEFLUC, and GEMLUC. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Three-Month Outcomes in Cancer Patients with Superficial or Deep Vein Thrombosis in the Lower Limbs: Results from the RIETE Registry.

BACKGROUND: The clinical characteristics and outcomes of cancer patients with lower-limb isolated superficial vein thrombosis (SVT) have not been consistently evaluated. METHODS: We used data in the RIETE registry to compare the clinical characteristics and 90-day outcomes for patients with: (1) active cancer and lower-limb SVT; (2) active cancer and lower-limb deep vein thrombosis (DVT); (3) lower-limb SVT without cancer. The primary outcomes included subsequent symptomatic SVT, DVT or pulmonary embolism (PE). Secondary outcomes were major bleeding and death. RESULTS: From March 2015 to April 2021, there were 110 patients with cancer and SVT, 1695 with cancer and DVT, and 1030 with SVT but no cancer. Most patients in all subgroups (93%, 99% and 96%, respectively) received anticoagulants, while those with SVT received lower daily doses of low-molecular-weight heparin (114 ± 58, 163 ± 44, and 106 ± 50 IU/kg, respectively). During the first 90 days, 101 patients (3.6%) developed subsequent VTE (PE 47, DVT 41, SVT 13), whereas 72 (2.5%) had major bleeding and 282 (9.9%) died. Among the three groups, 90-day events were, respectively: VTE at rates of 7.3%, 4.0% and 2.4%; major bleeding at rates of 2.7%, 3.9% and 0.3%; mortality at rates of 8.2%, 16% and 0.3%. Between D90 and D180, only one SVT recurrence and one death occurred in SVT cancer patients. In multivariable analysis, cancer was associated with subsequent VTE (HR = 2.04; 1.15-3.62), while initial presentation as SVT or DVT were not associated with a different risk. CONCLUSIONS: The risk for subsequent VTE (including symptomatic SVT, DVT or PE) was similar in cancer patients with isolated SVT than in those with isolated DVT.

Non-compliance with end-of-life parenteral nutrition prescription recommendations: retrospective study of 1,260 cancer patients.

BACKGROUND: Cancer patients near end of life (EOL) often suffer malnourishment and cachexia. In these patients, the prescription of parenteral nutrition (PN) remains highly controversial. Guidelines state that nutritional support does not improve quality of life in dying patients. We aimed to assess the compliance with international recommendations about PN prescription in advanced cancer, identify factors associated with PN at EOL and to evaluate the risk of blood stream infections (BSI). METHODS: Retrospective analysis of data from medical records of patients who died in 2013, 2015, 2017 and 2019 in a cancer center. RESULTS: One thousand two hundred and sixty patients with advanced cancer were included. PN was prescribed in 574 (45.6%) patients, the mean duration of PN was 10±9.7 days. Patients with a severe malnutrition [odds ratio (OR) =2.36; 95% confidence interval (CI): 1.42-4.02], a malignant bowel obstruction (MBO) (OR =2.25; 95% CI: 1.44-3.56), a length of hospitalization >12 days (OR =2.21; 95% CI: 1.67-2.94), a body mass index (BMI) <22.14 kg/m2 (OR =2.02; 95% CI: 1.52-2.67), an antitumor treatment (OR =1.58; 95% CI: 1.14-2.20) were more frequently prescribed a PN. BSI was diagnosed in 113 patients (9%) and was more frequent in patients receiving a PN (13% vs. 6%; OR =2.01; 95% CI: 1.18-3.54). CONCLUSIONS: International guidelines on PN in EOL cancer patients are poorly applied in the studied settings. Factors associated with the use of PN were low BMI, severe malnutrition, antitumor treatment, increased length of hospitalization. These findings argue for the use of a survival estimation tool and a multidisciplinary integrative care intervention when considering PN.

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

INTRODUCTION: Recurrent venous thromboembolism (VTE) despite curative anticoagulation is frequent in patients with cancer. Identifying patients with a high risk of recurrence could have therapeutic implications. A prospective study was designed to validate the Ottawa risk score of recurrent VTE in cancer patients. METHODS: In a prospective multicenter observational cohort, adult cancer patients with a recent diagnosis of symptomatic or incidental lower limb deep vein thrombosis or pulmonary embolism (PE) were treated with tinzaparin for 6 months. The primary endpoint was the recurrence of symptomatic or asymptomatic VTE within the first 6 months of treatment. All clinical events were centrally reviewed and adjudicated. Time-to-event outcomes were estimated by the Kalbfleisch and Prentice method to take into account the competing risk of death. A C-statistic value of > 0.70 was needed to validate the Ottawa score. RESULTS: A total of 409 patients were included and analyzed on an intention-to-treat basis. Median age was 68 years, 60.4% of patients had PE, and VTE was symptomatic in 271 patients (66.3%). The main primary sites were lung (31.3%), lower digestive tract (14.4%), and breast (13.9%) cancers. The Ottawa score was high (≥ 1) in 58% of patients. The 6-month cumulative incidence of recurrent VTE was 7.3% (95% confidence interval [CI]: 4.9-11.1) overall, and 5.0% (95% CI: 2.3-10.8) versus 9.1% (95%CI: 6.1-13.6) in the Ottawa low versus high risk groups, respectively. The C-statistic value was 0.60 (95% CI: 0.55-0.65). CONCLUSION: In this prospective cohort of patients with cancer receiving tinzaparin for VTE, the Ottawa score failed to accurately predict recurrent VTE.

Fever and deep venous thrombosis. Findings from the RIETE registry.

Fever is a presenting sign in some patients with acute deep venous thrombosis (DVT), but its influence on outcome has not been thoroughly investigated. RIETE is an ongoing, international, observational registry of consecutive patients with symptomatic, objectively confirmed, acute venous thromboembolism. The aim of the present study was to assess the prevalence of fever in patients with acute DVT, and to compare their outcome during the first month of therapy, according to the presence or absence of fever. As of September 2009, 14,480 patients with symptomatic DVT have been enrolled in RIETE. Of these, 707 (4.9%) had fever at presentation. During the 30-day study period, 448 patients (3.1%) died, 171 (1.2%) developed DVT recurrences, 376 (2.6%) had pulmonary embolism, and 384 (2.6%) had a major bleeding. Patients initially presenting with fever had a higher mortality (5.8% vs. 2.9%; odds ratio: 2.6; 95% CI 1.9-3.5) than those without fever. Among the causes of death, pulmonary embolism (0.7% vs. 0.1%) and infection (1.1% vs. 0.3%) were significantly more common in patients presenting with fever. Multivariate analysis confirmed that DVT patients with fever had an increased mortality (hazard ratio: 2.00; 95% CI 1.44-2.77) irrespectively of the patient's age, body weight, and risk factors for VTE. Fever is not uncommon in patients with DVT, and carries a worse outcome.

[Patients treated with palbociclib and endocrine therapy for metastatic breast cancer: Can we predict the occurrence of severe early hematological toxicity?] / Patients sous palbociclib et hormonothérapie pour un cancer du sein métastatique : peut-on prédire la survenue d'une hématotoxicité précoce et sévère ?

INTRODUCTION: The addition of palbociclib to endocrine therapy has been shown to improve progression free survival in hormone receptor positive metastatic breast cancer patients. This cyclin CDK4/6 inhibitor could expose patients to a grade 3-4 hematological toxicity, leading to treatment discontinuation or treatment interruption that is potentially associated with a lack of efficiency. The aim of this study was to identify predictive factors of severe early hematotoxicity (ESHT). METHODS: This retrospective cohort study included patients who started palbociclib in the Institut Sainte Catherine between December 1, 2016 and January 1, 2019 for the treatment of metastatic breast cancer. Individual data and hematological toxicity were collected from electronic medical records. ESHT was defined as the occurrence, during the first 3 cycles, of grade 4 or grade 3 hematological toxicity requiring palbociclib dose reduction. RESULTS: In total, 181 patients (180 females) were included; median age was 67 years. Forty-six patients (25.4%) experienced an ESHT. Predictive factors of ESHT in multivariate analysis were a performance status (PS) of 2 or more (P=0.024) and an history of radiotherapy of bone metastasis in the previous year (P=0.003). Before palbociclib initiation, a neutrophil count below 3.37g/L was predictive of ESHT with a sensibility of 76% and a specificity of 71%. CONCLUSIONS: ECOG PS, bone radiotherapy within the year and low baseline neutrophils count are associated with ESHT in palbociclib-treated metastatic breast cancer patients. These elements could be useful for a careful monitoring leading to adapted therapy.

Venous thromboembolism associated with central venous catheters in patients with cancer: From pathophysiology to thromboprophylaxis, areas for future studies.

Symptomatic catheter related thrombosis (CRT) occurs in 4%-8% of cancer patients. The mean incidence of CRT, detected either by echography or Doppler ranges between 12 and 14% with a high negative predictive value of about 95%, allowing the subsequent occurrence of CRT (symptomatic and asymptomatic) to be safely excluded. Despite its frequency and its medico-economic consequences, no thromboprophylaxis has been validated to date. In most patients, CRT occurs immediately after catheter insertion, most often within the first week and almost all within the first month after insertion. Meta analyses show a reduction of asymptomatic and symptomatic CRT incidence by about 55%-60% using either vitamin K antagonists or low molecular weight heparins without an increased risk of major bleeding. This pharmacological prophylaxis is only effective when started before the central venous catheter insertion at prophylactic doses and thereafter continued at subtherapeutic doses. Since no population at high risk of CRT has been identified, this review focuses on pathophysiology, epidemiology and clinical supportive data that could lead to a new CRT prophylaxis strategy.

[Low-molecular-weight heparins for cancer-associated thromboembolism: What place in 2019?] / Héparines de bas poids moléculaires dans la maladie thromboembolique veineuse liée au cancer : quelle place en 2019 ?

According to international clinical practice guidelines, low-molecular-weight heparins are advocate for the treatment and the prevention of cancer associated thrombosis. Direct oral anticoagulants recently introduced represent an alternative to vitamin K antagonists and low-molecular-weight heparins since their use doesn't require coagulation monitoring or daily subcutaneous injections. Recent studies comparing direct oral anticoagulants and low-molecular-weight heparins have shown a trend towards a reduction of venous thromboembolism events of direct oral anticoagulants but an increased risk of major bleeding. Recent French inter-group recommendations on the treatment of venous thromboembolism in cancer patients, favor low molecular weight heparins over direct oral anticoagulants as curative agents. In the light of recent studies, the objective of this review is to re-evaluate the place of low-molecular-weight heparins in the management of patents with cancer-associated thrombosis and to focus on the recent updates of international guidelines.

Identification of factors associated with aggressive end-of-life antitumour treatment: retrospective study of 1282 patients with cancer.

OBJECTIVE: Antitumour treatment in the last 2 weeks of death (ATT-W2) and a new regimen of ATT within 30 days of death (NATT-M1) are considered as aggressive end-of-life (EOL) care. We aimed to assess factors associated with inappropriate use of antitumour treatment (ATT) at EOL. METHODS: Data of patients with cancer who died in 2013, 2015, 2017 and 2019 in a single for-profit cancer centre were retrospectively analysed. ATT was divided into chemotherapy (CT), oral targeted therapy (OTT), hormonotherapy and immunotherapy (IMT). RESULTS: A total of 1282 patients were included. NATT-M1 was given to 197 (15.37%) patients, and 167 (13.03%) had an ATT-W2. Patients with a performance status of <2 and treated with CT had more both ATT- W2 (OR=2.45, 95% CI 1.65 to 3.65, and OR=10.29, 95% CI 4.70 to 22.6, respectively) and NATT-M1 (OR=2.01, 95% CI 1.40 to 2.90, and OR=8.41, 95% CI 4.46 to 15.86). Predictive factors of a higher rate of ATT-W2 were treatment with OTT (OR=19.08, 95% CI 7.12 to 51.07), follow-up by a medical oncologist (OR=1.49, 95% CI 1.03 to 2.17), miscellaneous cancer (OR=3.50, 95% CI 1.13 to 10.85) and length of hospital stay before death of <13 days (OR=1.92, 95% CI 1.32 to 2.79). Urinary tract and male genital cancers received less ATT-W2 (OR=0.38, 95% CI 0.16 to 0.89, and OR=0.40, 95% CI 0.16 to 0.99) and patients treated by IMT or with age <69 years more NATT-M1 (OR=19.21, 95% CI 7.55 to 48.8, and OR=1.69, 95% CI 1.20 to 2.37). Patients followed up by the palliative care team (PCT) had fewer ATT-W2 and NATT-M1 (OR=0.49, 95% CI 0.35 to 0.71, and OR=0.42, 95% CI 0.30 to 0.58). CONCLUSIONS: Most recent ATT and access to a PCT follow-up are the two most important potentially modifiable factors associated with aggressive EOL in patients with cancer. Early integrated palliative oncology care could help to decrease futile ATT at EOL.

Venous Thromboembolism in Patients With Autoimmune Disorders: Findings From the RIETE Registry.

Patients with autoimmune disorders are at an increased risk of venous thromboembolism (VTE), but this association has not been consistently evaluated. We used the RIETE (Registro Informatizado Enfermedad Trombo Embólica) database to compare the rates of VTE recurrences, major bleeding, and death during the course of anticoagulation, according to the presence or absence of autoimmune disorders. Of 71 625 patients with VTE recruited in February 2018, 1800 (2.5%) had autoimmune disorders. Median duration of anticoagulant therapy was slightly longer in patients with autoimmune disorders (median, 190 vs 182 days; P = .001). On multivariable analysis, patients with autoimmune disorders had a similar risk of VTE recurrences (hazard ratio [HR]: 0.93; 95% confidence interval [CI]: 0.68-1.27) or major bleeding (HR: 1.07; 95% CI: 0.82-1.40) and a lower risk to die (HR: 0.66; 95% CI: 0.54-0.81) than those without autoimmune disorders. Patients with giant cell arteritis had the highest rates of major bleeding (8.6 events per 100 patient-years) and the lowest rate of recurrences (zero). In other subgroups, the rates of both events were more balanced. During anticoagulation, patients with or without autoimmune disorders had similar rates of VTE recurrences or major bleeding. However, there were some differences between subgroups of patients with autoimmune disorders.