ABSTRACT


Recently, cancer-related venous thromboembolism (VTE) has been termed "cancer-associated thrombosis (CAT)" and is the focus of current research. We retrospectively investigated the efficacy of a single-drug approach with edoxaban for the treatment of non-acute CAT. Thirty-two non-acute CAT patients who received edoxaban were analyzed. The primary endpoint of this analysis was the thrombus disappearance rate at the first evaluation. Secondary endpoints included progression/recurrence of VTE, major bleeding, and D-dimer levels. The thrombus disappearance rate was 62.5%. Therefore, the null hypothesis for the primary endpoint (thrombus disappearance rate of ≤32.0%) was rejected (p = 0.00038) based on the rate of the previous study as the historical control. Recurrent VTE and major bleeding occurred in two patients each. After the start of treatment with edoxaban, a significant difference in D-dimer levels was observed (p = 0.00655). We demonstrated that a single-drug approach with edoxaban is a potential treatment option for non-acute CAT.


PMID:32605234 | DOI:10.3390/cancers12071711

20:05

PubMed articles on: Cardio-Oncology

Remote Ischemic Preconditioning Ameliorates Anthracycline-induced Cardiotoxicity and Preserves Mitochondrial Integrity


Galán-Arriola C, et al. Cardiovasc Res 2020.


ABSTRACT


AIMS: Anthracycline-induced cardiotoxicity (AIC) is a serious adverse effect among cancer patients. A central mechanism of AIC is irreversible mitochondrial damage. Despite major efforts, there are currently no effective therapies able to prevent AIC.


METHODS AND RESULTS: Forty Large-White pigs were included. In Study 1, 20 pigs were randomized 1:1 to remote ischemic pre-conditioning (RIPC, 3 cycles of 5 min leg ischemia followed by 5 min reperfusion) or no pretreatment. RIPC was performed immediately before each intracoronary doxorubicin injections (0.45 mg/kg) given at weeks 0, 2, 4, 6, and 8. A group of 10 pigs with no exposure to doxorubicin served as healthy controls. Pigs underwent serial cardiac magnetic resonance (CMR) exams at baseline and at weeks 6, 8, 12, and 16, being sacrifice after that. In study 2, 10 new pigs received 3 doxorubicin injections (with/out preceding RIPC) and were sacrificed at week 6.In Study 1, LVEF depression was blunted animals receiving RIPC before doxorubicin (RIPC-Doxo), which had a significantly higher LVEF at week 16 than doxorubicin treated pigs that received no pretreatment (Untreated-Doxo) (41.5±9.1% vs 32.5±8.7%, p = 0.04). It was mainly due to conserved regional contractile function. In Study 2, transmission electron microscopy (TEM) at week 6 showed fragmented mitochondria with severe morphological abnormalities in Untreated-Doxo pigs, together with upregulation of fission and autophagy proteins. At the end of the 16-week Study 1 protocol, TEM revealed overt mitochondrial fragmentation with structural fragmentation in Untreated-Doxo pigs, whereas interstitial fibrosis was less severe in RIPC+Doxo pigs.


CONCLUSION: In a translatable large animal model of AIC, RIPC applied immediately before each doxorubicin injection resulted in preserved cardiac contractility with significantly higher long-term LVEF and less cardiac fibrosis. RIPC prevented mitochondrial fragmentation and dysregulated autophagy from AIC early stages. RIPC is a promising intervention for testing in clinical trials in AIC.


TRANSLATIONAL PERSPECTIVE: Serial cardiac magnetic resonance (CMR) evaluation of a highly translatable large animal model of anthracycline-induced cardiotoxicity (AIC) shows that cumulative exposure to doxorubicin results in significantly reduced LVEF and extensive mitochondrial fragmentation. Remote ischemic preconditioning (RIPC) applied before each doxorubicin cycle preserved cardiac contractility and LVEF in long-term CMR exams. RIPC prevented doxorubicin-induced irreversible mitochondrial fragmentation and dysregulated autophagy. RIPC is as an attractive strategy for testing in clinical trials in AIC.


PMID:32597960 | DOI:10.1093/cvr/cvaa181

20:06

PubMed articles on: Cancer & VTE/PE

Practice patterns for extended venous thromboembolism chemoprophylaxis among urologic oncologists after radical cystectomy


Dall CP, et al. Urol Oncol 2020.


ABSTRACT


INTRODUCTION: Extended outpatient chemoprophylaxis (ECP) following radical cystectomy (RC) for bladder cancer is proven to reduce rates of venous thromboembolism (VTE). While ECP is commonly performed with enoxaparin, its cost-effectiveness and adherence rate has been called into question. Data from orthopedic literature suggest that ECP with direct oral anticoagulants (DOACs) may be as effective in VTE prevention as enoxaparin in patients undergoing joint surgery. Our goal is to determine how urologic oncologists employ ECP following RC.


METHODS: Members of the Society of Urologic Oncology were surveyed on practice patterns for the use of ECP after RC. Specific questions were asked regarding the use of inpatient and outpatient VTE prophylaxis, as well as perceived barriers to DOACs and enoxaparin.


RESULTS: There were 121 of 878 (13.8%) respondents and the majority were in academic practices (83%). Most respondents had at least 5 years of experience and performed greater than 10 cystectomies annually. Almost all participants utilized inpatient (97%) and extended (80%) chemoprophylaxis for VTE prevention. Of those who elected for ECP, almost all (96%) used enoxaparin. Only 3 respondents (3%) prescribed oral agents such as rivaroxaban (2) or warfarin (1). Among those using enoxaparin, financial-specific barriers to treatment such as lack of insurance coverage (38%), inability to afford the medication (51%), and need for additional insurance authorization (44%) were reported. Poor patient adherence and refusal to perform injections were reported by 20% and 18% of respondents, respectively. Among the 23 physicians who did not use ECP, cost (39%) and delivery method (26%) were cited as barriers to treatment.


CONCLUSIONS: The majority of surveyed urologic oncologists are prescribing subcutaneous enoxaparin ECP following RC. Poor patient adherence due to self-injections and financial barriers were frequently reported and represent a possible opportunity for the use of oral anticoagulants in the post-operative setting. These data will be used in the development of a proposed clinical trial of a DOAC in the post-RC setting.


PMID:32616422 | DOI:10.1016/j.urolonc.2020.05.030

20:06

PubMed articles on: Cardio-Oncology

Cardio-toxicity among patients with sarcoma: a cardio-oncology registry


Shamai S, et al. BMC Cancer 2020.


ABSTRACT


BACKGROUND: Chemotherapy induced cardio-toxicity has been recognized as a serious side effect since the first introduction to anthracyclines (ANT). Cardio-toxicity among patients with breast cancer is well studied but the impact on patients with sarcoma is limited, even though they are exposed to higher ANT doses. The commonly used term for cardio-toxicity is cancer therapeutics related cardiac dysfunction (CTRCD), defined as a left ventricular ejection fraction (LVEF) reduction of > 10%, to a value below 53%. The aim of our study was to estimate the prevalence of CTRCD in patients diagnosed with sarcoma and to describe the baseline risk factors and echocardiography parameters among that population.


METHODS: Data were collected as part of the Israel Cardio-Oncology Registry (ICOR), enrolling all patients evaluated in the cardio-oncology clinic at our institution. The registry was approved by the local ethics committee and is registered in clinicaltrials.gov (Identifier: NCT02818517). All sarcoma patients were enrolled and divided into two groups - CTRCD group vs. non-CTRCD group.


RESULTS: Among 43 consecutive patients, 6 (14%) developed CTRCD. Baseline cardiac risk factors were more frequent among the non-CTRCD group. Elevated left ventricular end systolic diameter and reduced Global Longitudinal Strain were observed among the CTRCD group. During follow-up, 2 (33%) patients died in the CTRCD group vs. 3 (8.1%) patients in the non-CTRCD group.


CONCLUSIONS: CTRCD is an important concern among patients with sarcoma, regardless of baseline risk factors. Echocardiography parameters may provide an early diagnosis of cardio-toxicity.


PMID:32605637 | PMC:PMC7325299 | DOI:10.1186/s12885-020-07104-9

20:06

PubMed articles on: Cardio-Oncology

Real-time three-dimensional echocardiography predicts cardiotoxicity induced by postoperative chemotherapy in breast cancer patients


Zhou F, et al. World J Clin Cases 2020.


ABSTRACT


BACKGROUND: The anthracycline chemotherapeutic drugs are cardiotoxic. Studies have found some indicators related to cardiotoxicity. However, there is currently no accurate indicator that can predict cardiac toxicity early.


AIM: To explore the diagnostic value of real-time three-dimensional echocardiography (RT3DE) in predicting cardiac toxicity in breast cancer patients undergoing chemotherapy.


METHODS: Female breast cancer patients who underwent radical mastectomy and postoperative chemotherapy at the Affiliated Hanzhou First People's Hospital, Zhejiang University School of Medicine were recruited. All patients were routinely administered with chemotherapy for four cycles (T1-T4) after surgery. Two-dimensional (2D) echocardiography, RT3DE, and serological examinations were performed after each cycle of chemotherapy. Patients were divided into a toxic group and a non-toxic group based on whether patients had Δ left ventricular ejection fraction > 10% after one year of chemotherapy. Repeated measurement analysis of variance was used to compare the changes in 2D echocardiographic indicators, serological indicators, and RT3DE indicators before and after chemotherapy. Multivariate logistic regression was used to identify independent predictive indicators for cardiac toxicity in postoperative chemotherapy patients. Receiver operating characteristics (ROC) curve analysis was performed to analyze the diagnostic value of potential indicators in the diagnosis of cardiotoxicity.


RESULTS: A total of 107 female breast cancer patients were included in the study. T4 maximum peak velocity in early diastole (E peak)/mitral annulus lateral tissue Doppler (e' peak) (E/e'), serological indicators [T4 cardiac troponin I (cTnI) and T4 pro-brain natriuretic peptide (Pro-BNP)], T3 minimum left atrial volume (LAV), T4 LAVmin, T3 LAV before the start of the P wave (LAVprep), and T4 LAVprep in the toxicity group were significantly higher than those in the non-toxic group. Multivariate logistic regression found that T4 cTnI, T4 Pro-BNP, T3 LAVmin, T4 LAVmin, T3 LAVprep, and T4 LAVprep had potential predictive value for cardiac toxicity (P 0.05). ROC results showed that T4 LAVmin had the highest accuracy for diagnosing cardiac toxicity [area under the curve (AUC) =0.947; sensitivity =78.57%; specificity =94.62%], followed by T4 LAVprep (AUC =0.899; sensitivity =100%; specificity =66.67%). The accuracies of LAVprep and LAVprep in predicting cardiac toxicity were higher than those of T3 LAVmin and T3 LAVprep.


CONCLUSION: RT3DE of left atrial volume can be used to predict the cardiotoxicity caused by chemotherapy, and it is expected to guide the clinical adjustment of dose and schedule in time.


PMID:32607331 | PMC:PMC7322441 | DOI:10.12998/wjcc.v8.i12.2542

20:06

PubMed articles on: Cancer & VTE/PE

Resection of recurrent hepatocellular carcinoma with thrombi in the inferior vena cava, right atrium, and phrenic vein: a report of three cases


Tomita K, et al. World J Surg Oncol 2020.

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