ABSTRACT

OBJECTIVE: To investigate the association between stages of QTc prolongation and the risk of cardiac events among patients on TKIs.

METHODS: This was a retrospective cohort study performed at an academic tertiary care center of cancer patients who were taking TKIs or not taking TKIs. Patients with two recorded ECGs between January 1, 2009, and December 31, 2019, were selected from an electronic database. The QTc duration > 450ms was determined as prolonged. The association between QTc prolongation progression and events of cardiovascular disease were compared.

RESULTS: This study included a total of 451 patients with 41.2% of patients taking TKIs. During a median follow up period of 3.1 years, 49.5% subjects developed CVD and 5.4% subjects suffered cardiac death in patient using TKIs (n = 186); the corresponding rates are 64.2% and 1.2% for patients not on TKIs (n = 265), respectively. Among patient on TKIs, 4.8% of subjects developed stroke, 20.4% of subjects suffered from heart failure (HF) and 24.2% of subjects had myocardial infarction (MI); corresponding incidence are 6.8%, 26.8% and 30.6% in non-TKIs. When patients were regrouped to TKIs versus non-TKIs with and without diabetes, there was no significant difference in the incidence of cardiac events among all groups. Adjusted Cox proportional hazards models were applied to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). There is a significant increased risk of HF events (HR, 95% CI: 2.12, 1.36-3.32) and MI events (HR, 95% CI: 1.78, 1.16-2.73) during the 1st visit. There are also trends for an increased incidence of cardiac adverse events associated with QTc prolongation among patient with QTc > 450ms, however the difference is not statistically significant. Increased cardiac adverse events in patients with QTc prolongation were reproduced during the 2nd visit and the incidence of heart failure was significantly associated with QTc prolongation(HR, 95% CI: 2.94, 1.73-5.0).

CONCLUSION: There is a significant increased QTc prolongation in patients taking TKIs. QTc prolongation caused by TKIs is associated with an increased risk of cardiac events.

PMID:37208762 | PMC:PMC10197472 | DOI:10.1186/s40959-023-00178-x

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PubMed articles on: Cardio-Oncology

Cardiac toxicities in multiple myeloma: an updated and a deeper look into the effect of different medications and novel therapies

Blood Cancer J. 2023 May 19;13(1):83. doi: 10.1038/s41408-023-00849-z.

ABSTRACT

With the continuous improvement in survival of cancer patients, including those with multiple myeloma, related to the novel treatment agents and therapeutic approaches, the probability for patients to develop cardiovascular disease has significantly increased, especially in elderly patients and those with additional risk factors. Multiple myeloma is indeed a disease of the elderly population and so these patients are, solely by age, at an increased risk of cardiovascular disease. Risk factors for these events can be patient-, disease- and/or therapy-related, and they have been shown to adversely impact survival. Cardiovascular events affect around 7.5% of patients with multiple myeloma and the risk for different toxicities has considerably varied across trials depending on patients' characteristics and treatment utilized. High grade cardiac toxicity has been reported with immunomodulatory drugs (odds ratio [OR] around 2), proteasome inhibitors (OR 1.67-2.68 depending on the specific agent, and generally higher with carfilzomib), as well as other agents. Cardiac arrhythmias have also been reported with various therapies and drug interaction plays a significant role in that setting. Comprehensive cardiac evaluation before, during and after various anti-myeloma therapy is recommended and the incorporation of surveillance strategies allows early detection and management resulting in improved outcomes of these patients. Multidisciplinary interaction including hematologists and cardio-oncologists is critical for optimal patient care.

PMID:37208317 | PMC:PMC10199017 | DOI:10.1038/s41408-023-00849-z

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PubMed articles on: Cancer & VTE/PE

Thrombosis in the Neonatal Intensive Care Unit

Neoreviews. 2023 Jun 1;24(6):e356-e369. doi: 10.1542/neo.24-6-e356.

ABSTRACT

Neonates, particularly critically ill and premature infants, have one of the highest risks of thromboembolic complications, particularly venous thromboembolism (VTE), in the pediatric population. Recent data suggest that the incidence of VTE has significantly increased in neonates over the last few decades. Critically ill and premature infants exhibit multiple risk factors that place them at a high risk for thromboembolic events including developmental hemostasis, propensity to infections, and frequent need for central venous access. The clinical presentation, diagnostic modalities, and treatment strategies for thromboembolic complications in neonates vary based on several factors, including the etiology of the thromboembolic event, the anatomic site affected, and the patient's underlying comorbidities. Although guidelines for management are available, they are mostly based on consensus recommendations and on extrapolation from adult data due to a lack of high-quality data in the neonatal population. Current guidelines recommend anticoagulation for specific scenarios. More studies are necessary to elucidate optimal management strategies for newborns with thromboembolic complications.

PMID:37258498 | DOI:10.1542/neo.24-6-e356

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PubMed articles on: Cancer & VTE/PE

Disparities in the Outcomes of Acute Pulmonary Embolism in Hospitalized Patients with Hematologic Malignancy and Solid Tumor

Int Heart J. 2023;64(3):432-441. doi: 10.1536/ihj.22-704.

ABSTRACT

This study aimed to compare the clinical burden and healthcare utilization outcomes of hematologic versus solid malignancies in patients hospitalized with acute pulmonary embolism (PE). This population-based, retrospective study extracted and analyzed the discharge data from the 2016-2018 US National Inpatient Sample (NIS) of hospitalized patients with a primary diagnosis of acute PE and a subsequent diagnosis of hematologic malignancies or solid tumors. Prolonged length-of-stay (LOS) was defined as ≥75th percentile LOS of the study cohort. Unfavorable discharge was defined as discharged to nursing home or long-term facility. Univariate and multivariate regression analyses were conducted to determine associations between cancer type, presence of unstable PE, and in-hospital outcomes in acute PE patients. Patients with acute PE with solid tumors had higher rates of in-hospital deaths and unfavorable discharge than those with hematologic malignancies (6.4% versus 3.2%, P < 0.001; 14.0% versus 11.2%, P = 0.01, respectively). Acute PE patients with hematologic malignancies had a lower risk of in-hospital death (aOR: 0.43, 95% CI: 0.31-0.60), unfavorable discharge (aOR: 0.76, 95% CI: 0.63-0.92), and prolonged LOS (aOR: 0.83, 95% CI: 0.71-0.98) than those with solid tumors. Stratified analysis showed that male patients aged <60

PMID:37258119 | DOI:10.1536/ihj.22-704

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PubMed articles on: Cancer & VTE/PE

Risk Factors of Venous Thromboembolic Disease in Cancer Patients Treated with Immune Checkpoint Inhibitor

Thromb Haemost. 2023 May 31. doi: 10.1055/s-0043-1769609. Online ahead of print.

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the management of cancers. The risk factors and pathophysiological mechanisms of venous thromboembolic events (VTEs) of this new therapeutic class are still to be specified.

METHODS: The included patients had to have cancer and should be treated with ICI. Data analyzed included demographic data, biological data, and immune-related adverse events (IRAEs). We studied the prevalence of VTEs and the factors associated with VTEs.

RESULTS: Of 374 patients on ICI, over a median follow-up period of 15.2 months, the number of VTE was 50 (13.4%). The majority of patients were treated for metastatic melanoma or nonsmall cell lung cancer. There was no difference in prevalence or survival between cancer types. Patients with combined therapy composed of nivolumab and ipilimumab had higher 1-year cumulative VTE occurrence (29.3% [95% confidence interval [CI]: 9.7; 44.6]) than patients with pembrolizumab (14.9%, [95%CI: 2.5; 25.8], p= 0.03) or nivolumab (9.1%, [95% CI: 5.0; 12.9], p< 0.01). The presence of IRAE was associated with a higher risk of VTE occurrence compared with patients without any IRAE (1-year VTE cumulative incidence: 17.42% [95% CI: 9.5; 24.65] vs. 9.46% [95% CI: 5.18; 13.55], p= 0.04). There was a higher risk of VTE in patients treated with the combination of nivolumab and ipilimumab (adjusted subdistribution hazard ratio [SHR]: 3.71 [95% CI: 1.74; 7.90], p< 0.001) and in patients with IRAE (adjusted SHR: 2.14 [95% CI: 1.22; 3.75], p< 0.01).

CONCLUSION: The prevalence of VTE was 14.2% under ICIs. IRAE and combine treatment of nivolumab and ipilimumab were associated with VTE. The pathophysiological mechanisms are multiple and complex with a possible link to aberrant activation of the immune system.

PMID:37257835 | DOI:10.1055/s-0043-1769609

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PubMed articles on: Cancer & VTE/PE

A systemic review and meta-analysis of Aflibercept plus FOLFIRI regimen as a second-line treatment for metastatic colorectal cancer: A PRISMA compliant pooled analysis of randomized controlled trials and single arm studies to assess efficacy and safety

Crit Rev Oncol Hematol. 2023 May 29:104034. doi: 10.1016/j.critrevonc.2023.104034. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Aflibercept; a decoy receptor for vascular endothelial growth factors (VEGFs) and placental growth factor (PLGF), in combination with FOLFIRI (leucovorin calcium, fluorouracil, irinotecan hydrochloride) chemotherapy regime, was FDA approved in 2012 as second-line salvage chemotherapy for metastatic colorectal cancer (mCRC). This is the first systematic review, and meta-analysis-based evidence to determine the efficacy and safety of Aflibercept plus FOLFIRI regimen pooling randomized controlled trials and single-arm studies.

METHOD: PubMed, Cochrane library, Embase, and Clinical trial.gov were systematically searched for published randomized controlled trials, single-arm studies, and national patient programs on aflibercept plus FOLFIRI chemotherapy for the treatment of mCRC till 11/10/2022.

RESULT: Ten studies met the inclusion criteria comprising 1075 patients for efficacy studies and 2027 patients for safety studies. The pooled prevalences were 18% (95% CI, 5%-37%, p = 0.00) for 12m PFS and 61% (95% CI, 53% - 68%, p = 0.00) for 12m OS. The pooled prevalences were 69% (95% CI, 55% - 82%, p = 0.00) for any grade 3-4 toxicities, 10% (95% CI, 5% - 16%, p = 0.00) for grade 3-4 diarrhea, 13% (95% CI, 5% - 24%, p = 0.00) for grade 3-4 hypertension, 31% (95% CI, 22% - 40%, p = 0.00) for grade 3-4 neutropenia and 5% (95% CI, 2% - 7%, p = 0.00) for grade 3-4 venous thromboembolic event.

CONCLUSION: Our meta-analysis shows that the aflibercept plus FOLFIRI combination shows better survival efficacies however; it is also associated with more high-grade adverse events.

PMID:37257732 | DOI:10.1016/j.critrevonc.2023.104034

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PubMed articles on: Cancer & VTE/PE

Thrombotic Risk Assessment in Patients with Lymphoid Neoplasm seen at the Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra State

West Afr J Med. 2023 May 27;40(5):533-540. ABSTRACTBACKGROUND: Venous thromboembolism (VTE) is a cause of increased morbidity and mortality in cancer patients. VTE is the second leading cause of death in cancer patients. Risk assessment models have been developed to identify patients at risk of VTE for thromboprophylaxis. Risk scores of patients in our environment have not been adequately investigated.

OBJECTIVE: The study evaluates the association of thrombotic risk assessment scores (using the modified Khorana risk assessment tool) and soluble P-selectin levels with thrombotic events in patients with lymphoid cancer.

METHODS: This is a comparative cross-sectional study conducted at Nnamdi Azikiwe University Teaching Hospital (NAUTH, Nnewi, Anambra State). Forty-five patients with lymphoid malignancy and 45 apparently healthy subjects participated in the study. The modified Khorana risk assessment score was used to assess cancer-associated thrombotic risk. Blood sample was collected for soluble P-selectin estimation. Data were analyzed with SPSS version 23.

RESULTS: The age of subjects with lymphoid neoplasm and controls were 49.1±15.8 years, and 49.6±11.1 years respectively (p = 0.548). Subjects with lymphoid neoplasm consist of 26 (57.8%) males and 19 (42.2%) females while the controls consist of 25 (55.6%) males and 20 (44.4%) females. Non-Hodgkin's lymphoma was the most frequent of lymphoid neoplasm (18, 40.0%), followed by multiple myeloma (10, 22%), CLL (9, 20%), ALL (6, 13.0%) and Hodgkin's lymphoma (2, 4.0%). Thirty-five (77.8%) subjects with lymphoid neoplasm had intermediate risk scores and 10 (22.2%) had high-risk scores. Nineteen (42.2%) of the controls had intermediate risk and 26 (57.8%) low risk. The differences in proportion were statistically significant (p < 0.001). The median (IQR) levels of soluble P-selectin were significantly higher in patients with lymphoid neoplasm (12.2 vs. 7.0ng/mL, p <0.001).

CONCLUSION: Lymphoid malignancy is associated with relatively higher thrombotic risk scores, sP-selectin levels, and venous thromboembolic events.

CONTEXTE: La thromboembolie veineuse (TEV) est une cause de morbidité et de mortalité accrues chez les patients atteints de cancer. La TEV est la deuxième cause de décès chez les patients atteints de cancer. Des modèles d’évaluation des risques ont été mis au point pour identifier les patients présentant un risque de TEV en vue d’une thromboprophylaxie. Les scores de risque des patients dans notre environnement n’ont pas été étudiés de manière adéquate.

OBJECTIF: L’étude évalue l’association des scores d’évaluation du risque thrombotique (en utilisant l’outil modifié d’évaluation du risque de Khorana) et des niveaux de P-sélectine soluble avec les événements thrombotiques chez les patients atteints d’un cancer lymphoïde.

MÉTHODES: Il s’agit d’une étude transversale comparative menée au Nnamdi Azikiwe University Teaching Hospital (NAUTH, Nnewi, État d’Anambra). Quarante-cinq patients atteints d’un cancer lymphoïde et 45 sujets apparemment sains ont participé à l’étude. Le score modifié d’évaluation du risque de Khorana a été utilisé pour évaluer le risque thrombotique associé au cancer. Un échantillon de sang a été prélevé pour l’estimation de la P-sélectine soluble. Les données ont été analysées avec SPSS version 23.

RÉSULTATS: L’âge des sujets atteints de néoplasme lymphoïde et des témoins était respectivement de 49,1±15,8 ans et 49,6±11,1 ans (p = 0,548). Les sujets atteints de néoplasme lymphoïde sont 26 (57,8 %) hommes et 19 (42,2 %) femmes, tandis que l[...]

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PubMed articles on: Cancer & VTE/PE

Evaluation of Patient Characteristics Linked to Major Bleeding Events in Patients Prescribed Direct Oral Anticoagulants

Clin Appl Thromb Hemost. 2023 Jan-Dec;29:10760296231172765. doi: 10.1177/10760296231172765.

ABSTRACT

INTRODUCTION: Direct oral anticoagulants (DOACs) demonstrated similar efficacy and lower risk of intracranial hemorrhage than warfarin in patients with atrial fibrillation and venous thromboembolism. Given the lack of data identifying risk factors in patients who bled while on a DOAC, we sought to investigate these characteristics.

MATERIALS AND METHODS: This retrospective chart review was approved by the Mass General Brigham Institutional Review Board and assessed patients who experienced bleeding events while on DOAC therapy from 6/1/2015 to 7/1/2020. Patient characteristics were evaluated, including age, sex, body mass index (BMI), renal function, concomitant therapies, and baseline comorbidities.

RESULTS: Eighty-seven patients were included for analysis, with a median age of 75.8 years. Most patients were female (51.7%) and 24 (27.6%) had a BMI >30. At time-of-event, 21 patients (24.1%) had acute kidney injury. Thirty-three patients (37.9%) were on concomitant antiplatelet therapy (APT), with 31 (35.6%) on single APT and 2 on dual APT. Pertinent comorbidities included hypertension (74.7%), ischemic cerebrovascular accident (28.7%), thyroid abnormality (23.0%), active cancer (14.9%), and anemia (13.8%). Eleven patients (12.6%) had a prior bleeding event. Most patients were on apixaban (69.0%) for the indication of stroke prevention in nonvalvular atrial fibrillation/flutter (72.4%). FDA-approved dosing was used in most patients (92.0%), and all deviations reflected underdosing. Most bleeding events were defined as major (95.4%), occurred at a critical organ site (72.4%), and developed spontaneously (58.6%).

CONCLUSIONS: These data provide insight into characteristics of patients who experience bleeding events while on DOAC therapy. Understanding these potential risk factors may optimize the safe use of these agents.

PMID:37246422 | DOI:10.1177/10760296231172765

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PubMed articles on: Cancer & VTE/PE

Hypercoagulability State Combined with Post-Treatment Hypofibrinolysis in Invasive Breast Cancer: A Seven-Year Follow-Up Evaluating Disease-Free and Overall Survival

Life (Basel). 2023 Apr 28;13(5):1106. doi: 10.3390/life13051106.

ABSTRACT

(1) Background: Cancer treatment, including chemotherapy, endocrine therapy, targeted therapy and radiotherapy, has been identified as an important independent risk factor for venous thromboembolism in cancer patients. The aim of the study was to evaluate the effect of adjuvant therapy on the coagulation and fibrinolysis components in invasive breast cancer. (2) Methods: Tissue factor pathway inhibitor (TFPI), tissue factor (TF), tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) antigen (concentration) and TFPI and TF activities were examined in the blood samples of 60 breast cancer patients treated by adjuvant chemotherapy, endocrine therapy, radiotherapy and immunotherapy. Blood samples were taken 24 h before primary surgery and 8 months after tumour removal surgery. (3) Results: Adjuvant therapy administrated to breast cancer patients significantly increased the concentration of plasma TF, the PAI-1 antigen and also the activity of TFPI and TF, but significantly decreased the level of the t-PA antigen. Combined chemotherapy and endocrine therapy, but not monotherapy, has an important effect on haemostatic biomarker levels. (4) Conclusions: Breast cancer patients receiving adjuvant therapy have an elevated risk of developing a hypercoagulability and hypofibrinolysis state leading to venous thromboembolism.

PMID:37240751 | PMC:PMC10222121 | DOI:10.3390/life13051106

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PubMed articles on: Cancer & VTE/PE

Phase 1 study of GSK3368715, a type I PRMT inhibitor, in patients with advanced solid tumors

Br J Cancer. 2023 May 26. doi: 10.1038/s41416-023-02276-0. Online ahead of print.

ABSTRACT

BACKGROUND: GSK3368715, a first-in-class, reversible inhibitor of type I protein methyltransferases (PRMTs) demonstrated anticancer activity in preclinical studies. This Phase 1 study (NCT03666988) evaluated safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of GSK3368715 in adults with advanced-stage solid tumors.

METHODS: In part 1, escalating doses of oral once-daily GSK3368715 (50, 100, and 200 mg) were evaluated. Enrollment was paused at 200 mg following a higher-than-expected incidence of thromboembolic events (TEEs) among the first 19 participants, resuming under a protocol amendment starting at 100 mg. Part 2 (to evaluate preliminary efficacy) was not initiated.

RESULTS: Dose-limiting toxicities were reported in 3/12 (25%) patients at 200 mg. Nine of 31 (29%) patients across dose groups experienced 12 TEEs (8 grade 3 events and 1 grade 5 pulmonary embolism). Best response achieved was stable disease, occurring in 9/31 (29%) patients. Following single and repeat dosing, GSK3368715 maximum plasma concentration was reached within 1 h post dosing. Target engagement was observed in the blood, but was modest and variable in tumor biopsies at 100 mg.

CONCLUSION: Based on higher-than-expected incidence of TEEs, limited target engagement at lower doses, and lack of observed clinical efficacy, a risk/benefit analysis led to early study termination.

TRIAL REGISTRATION NUMBER: NCT03666988.

PMID:37237172 | DOI:10.1038/s41416-023-02276-0

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PubMed articles on: Cancer & VTE/PE

Spray Cryotherapy for Benign Large Airway Stenosis: A Multicenter Retrospective Cohort Study of Safety and Practice Patterns

J Bronchology Interv Pulmonol. 2023 May 29. doi: 10.1097/LBR.0000000000000930. Online ahead of print.