1/24/26
1/21/26
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
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 | PMC:PMC10233572 | DOI:10.1177/10760296231172765
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PubMed articles on: Cancer & VTE/PE
Safety Profile and Effectiveness of Rivaroxaban for Patients With Venous Thromboembolism in Japan - Results From Post-Marketing Surveillance (XASSENT)
Circ J. 2023 May 27. doi: 10.1253/circj.CJ-23-0104. Online ahead of print.
ABSTRACT
BACKGROUND: The incidence of venous thromboembolism (VTE; pulmonary embolism [PE] and/or deep vein thrombosis [DVT]) in Japan is increasing, but relatively small numbers of patients from Japan have been included in studies investigating rivaroxaban (a direct factor Xa inhibitor) for the treatment of VTE and preventing its recurrence.Methods and Results: An open-label, prospective, observational study (XASSENT [NCT02558465]) investigated the safety profile and effectiveness of rivaroxaban for ≤2 years in the treatment of VTE and prevention of its recurrence in Japanese clinical practice. Primary outcomes were major bleeding and symptomatic recurrent VTE. Statistical analyses were exploratory and descriptive. Overall, 2,540 patients were enrolled (safety analysis population [SAP], n=2,387; effectiveness analysis population [EAP], n=2,386). In the SAP, >80% of patients received the approved rivaroxaban dose, the mean (standard deviation) age was 66.6 (15.0) years, ≈74% were >50 kg, and 43% had a creatinine clearance ≥80 mL/min. PE+DVT, PE only, and DVT only were reported in 42%, 8%, and 50% of patients, respectively, and active cancer in 17% of patients. Major bleeding was reported in 69 patients (2.89%; 3.60%/patient-year; SAP) and symptomatic PE/DVT recurrence in 26 patients (1.09%; 1.36%/patient-year; EAP) during the treatment period.
CONCLUSIONS: XASSENT provided information on the expected proportions of bleeding and VTE recurrence during rivaroxaban treatment in Japanese clinical practice; no new concerns of safety or effectiveness were found.
PMID:37245989 | DOI:10.1253/circj.CJ-23-0104
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PubMed articles on: Cancer & VTE/PE
Venous thromboembolism secondary to hospitalization for COVID-19: patient management and long-term outcomes
Res Pract Thromb Haemost. 2023 May;7(4):100167. doi: 10.1016/j.rpth.2023.100167. Epub 2023 Apr 26.
ABSTRACT
BACKGROUND: Venous thromboembolism (VTE) is a complication of COVID-19 in hospitalized patients. Little information is available on long-term outcomes of VTE in this population.
OBJECTIVES: We aimed to compare the characteristics, management strategies, and long-term clinical outcomes between patients with COVID-19-associated VTE and patients with VTE provoked by hospitalization for other acute medical illnesses.
METHODS: This is an observational cohort study, with a prospective cohort of 278 patients with COVID-19-associated VTE enrolled between 2020 and 2021 and a comparison cohort of 300 patients without COVID-19 enrolled in the ongoing START2-Register between 2018 and 2020. Exclusion criteria included age <18<3
RESULTS: Patients with VTE secondary to COVID-19 had more frequent pulmonary embolism without deep vein thrombosis than controls (83.1% vs 46.2%, P<.001),P<.001),P<.001).P= 0.9) and the proportion of patients who discontinued anticoagulation (78.0% and 75.0%, P= 0.4) were similar between the 2 groups. Thrombotic event rates after discontinuation were 1.5 and 2.6 per 100 patient-years, respectively (P = 0.4).
CONCLUSION: The risk of recurrent thrombotic events in patients with COVID-19-associated VTE is low and similar to the risk observed in patients with VTE secondary to hospitalization for other medical diseases.
PMID:37229314 | PMC:PMC10131739 | DOI:10.1016/j.rpth.2023.100167
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PubMed articles on: Cancer & VTE/PE
Pulmonary embolism complicated by tamponade revealing metastatic lung cancer in a woman pregnant with twin: about a case report
Ann Med Surg (Lond). 2023 Apr 7;85(5):1966-1970. doi: 10.1097/MS9.0000000000000516. eCollection 2023 May.
ABSTRACT
Background:As a new drug delivery and embolization system, drug-eluted bronchial artery chemoembolization (DEB-BACE) can not only embolize the tumor blood supply artery but also load chemotherapy drugs and slowly release them into the local environment. Bevacizumab (BEV) combined with chemotherapy drugs has attained significant achievements in the first-line treatment of advanced non-squamous non-small cell lung cancer (NSCLC). The role of BEV-loaded DEB-BACE combined with immunotherapy and targeted therapy in patients with lung adenocarcinoma (LUAD) is unclear. This study was designed to evaluate the efficacy and safety of bevacizumab-loaded CalliSpheres® bronchial arterial chemoembolization combined with immunotherapy and targeted therapy in patients with lung adenocarcinoma. Methods:Nine patients with LUAD who received BEV-loaded CalliSpheres® BACE combined with immunotherapy and targeted therapy from 1 Jan 2021 to Dec 2021 were included in this study. The primary endpoint was the disease control rate (DCR) and the objective response rate (ORR). The secondary endpoints were the overall survival rates (OS) at 6 months and 12 months. The tumor response was evaluated according to the mRECIST standard. Safety was assessed by the occurrences of adverse events and the severity of the adverse events. Results:All patients received CalliSpheres® BACE loaded with BEV (200 mg) in combination with immunotherapy and targeted therapy. A total of nine patients received the BACE procedures 20 times, four of them received a third session of BACE, three underwent a second session of DEB-BACE, and two underwent one cycle of DEB-BACE. Partial response and stable disease were found in seven (77.8%), and two (22.2%) patients, respectively, 1 month after the last multimodal treatment. The ORR at 1, 3, 6, and 12 months was 77.8%, 66.7%, 44.4%, and 33.3%, respectively, while the DCR was 100%, 77.8%, 44.4%, and 33.3%, respectively. The OS rates at 6-and 12-month were 77.8% and 66.7%, respectively. There were no serious adverse events. Conclusion:BEV-loaded CalliSpheres® transcatheter bronchial arterial chemoembolization combined with immunotherapy and targeted therapy is a promising and well-tolerated treatment for patients with lung adenocarcinoma.
PMID:37284322 | PMC:PMC10239861 | DOI:10.3389/fphar.2023.1170344
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PubMed articles on: Cancer & VTE/PE
Prognosis of incidental pulmonary embolism vs. symptomatic pulmonary embolism in cancer patients: a single-center retrospective cohort study in China
Thromb J. 2023 Jun 6;21(1):64. doi: 10.1186/s12959-023-00502-6.
ABSTRACT
BACKGROUND: The incidence of incidental pulmonary embolism (IPE) has greatly increased, but its clinical characteristics and outcomes are still controversial. This study aimed to compare the clinical characteristics and outcomes between cancer patients with IPE and patients with symptomatic pulmonary embolism (SPE).
PATIENTS/METHODS: Clinical data of 180 consecutive patients with cancer complicated with pulmonary embolism admitted to Beijing Cancer Hospital from July 2011 to December 2019 were retrospectively collected and analysed. General characteristics, diagnosis time of pulmonary embolism (PE), location of PE, concurrent deep venous thrombosis, anticoagulant treatment, impact of PE on anti-tumor treatment, recurrent venous thromboembolism, rate of bleeding after anticoagulation therapy, survival and risk factors of IPE were compared with SPE.
RESULTS: Of 180 patients, 88 (49%) had IPEs and 92 (51%) had SPEs. Patients with IPE and SPE did not differ in age, sex, tumor type, or tumor stage. Median diagnosis times of IPE and SPE after cancer were 108 (45, 432) days and 90 (7, 383) days, respectively. Compared to SPE, IPE tended to be central (44% versus 26%; P < 0.001), isolated (31.8% versus 0.0%; P < 0.001), and unilateral (67.1% versus 12.8%; P < 0.00). The rate of bleeding after anticoagulation therapy did not differ between IPE and SPE. Patients with IPE had a better prognosis than patients with SPE in terms of 30-, and 90-day mortality, as well as overall survival after diagnosis of PE (median: 314.5 vs. 192.0 days, log-rank P = 0.004) and cancer (median: 630.0 vs. 450.5 days, log-rank P = 0.018). SPE (compared to IPE) was an independent risk factor for poor survival after diagnosis of PE in multivariate analysis (hazard ratio [HR] = 1.564, 95% confidence interval [CI]: 1.008-2.425, p = 0.046).
CONCLUSIONS: IPE accounts for nearly one half of PE cases among Chinese cancer patients. With active anticoagulation treatment, IPE is expected to achieve better survival rates than SPE.
PMID:37280671 | PMC:PMC10245445 | DOI:10.1186/s12959-023-00502-6
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PubMed articles on: Cancer & VTE/PE
Tissue factor (coagulation factor III): a potential double-edge molecule to be targeted and re-targeted toward cancer
Biomark Res. 2023 Jun 6;11(1):60. doi: 10.1186/s40364-023-00504-6.
ABSTRACT
Tissue factor (TF) is a protein that plays a critical role in blood clotting, but recent research has also shown its involvement in cancer development and progression. Herein, we provide an overview of the structure of TF and its involvement in signaling pathways that promote cancer cell proliferation and survival, such as the PI3K/AKT and MAPK pathways. TF overexpression is associated with increased tumor aggressiveness and poor prognosis in various cancers. The review also explores TF's role in promoting cancer cell metastasis, angiogenesis, and venous thromboembolism (VTE). Of note, various TF-targeted therapies, including monoclonal antibodies, small molecule inhibitors, and immunotherapies have been developed, and preclinical and clinical studies demonstrating the efficacy of these therapies in various cancer types are now being evaluated. The potential for re-targeting TF toward cancer cells using TF-conjugated nanoparticles, which have shown promising results in preclinical studies is another intriguing approach in the path of cancer treatment. Although there are still many challenges, TF could possibly be a potential molecule to be used for further cancer therapy as some TF-targeted therapies like Seagen and Genmab's tisotumab vedotin have gained FDA approval for treatment of cervical cancer. Overall, based on the overviewed studies, this review article provides an in-depth overview of the crucial role that TF plays in cancer development and progression, and emphasizes the potential of TF-targeted and re-targeted therapies as potential approaches for the treatment of cancer.
PMID:37280670 | PMC:PMC10242999 | DOI:10.1186/s40364-023-00504-6
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PubMed articles on: Cancer & VTE/PE
Direct Oral Anticoagulants for Cancer-Associated Venous Thromboembolism
Curr Oncol Rep. 2023 Jun 6. doi: 10.1007/s11912-023-01428-y. Online ahead of print.
ABSTRACT
PURPOSE OF REVIEW: To present the randomized controlled trial (RCT) evidence and highlight the areas of uncertainty regarding direct oral anticoagulants (DOAC) for cancer-associated venous thromboembolism (CAT).
RECENT FINDINGS: In the last years, four RCTs have shown that rivaroxaban, edoxaban, and apixaban are at least as effective as low-molecular-weight heparin (LMWH) for the treatment of both incidental and symptomatic CAT. On the other hand, these drugs increase the risk of major gastrointestinal bleeding in patients with cancer at this site. Another two RCTs have demonstrated that apixaban and rivaroxaban also prevent CAT in subjects at intermediate-to-high risk commencing chemotherapy, albeit at the price of higher likelihood of bleeding. By contrast, data are limited about the use DOAC in individuals with intracranial tumors or concomitant thrombocytopenia. It is also possible that some anticancer agents heighten the effects of DOAC via pharmacokinetic interactions, up to making their effectiveness-safety profile unfavorable. Leveraging the results of the aforementioned RCTS, current guidelines recommend DOAC as the anticoagulants of choice for CAT treatment and, in selected cases, prevention. However, the benefit of DOAC is less defined in specific patient subgroups, in which the choice of DOAC over LMWH should be carefully pondered.
PMID:37278934 | DOI:10.1007/s11912-023-01428-y
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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:People with cancer experience high rates of venous thromboembolism (VTE). Additionally, risk of subsequent cancer is increased in people experiencing their first VTE. The causal mechanisms underlying this association are not completely understood, and it is unknown whether VTE is itself a risk factor for cancer. Methods:We used data from large genome-wide association study meta-analyses to perform bi-directional Mendelian randomisation analyses to estimate causal associations between genetically-proxied lifetime risk of VTE and risk of 18 different cancers. Results:We found no conclusive evidence that genetically-proxied lifetime risk of VTE was causally associated with an increased incidence of cancer, or vice-versa. We observed an association between VTE and pancreatic cancer risk (odds ratio for pancreatic cancer 1.23 (95% confidence interval 1.08 - 1.40) per log-odds increase in risk of VTE, P =0.002). However, sensitivity analyses revealed this association was predominantly driven by a variant proxying non-O blood group, with inadequate evidence from Mendelian randomisation to suggest a causal relationship. Conclusions:These findings do not support the hypothesis that genetically-proxied lifetime risk of VTE is a cause of cancer. Existing observational epidemiological associations between VTE and cancer are therefore more likely to be driven by pathophysiological changes which occur in the setting of active cancer and anti-cancer treatments. Further work is required to explore and synthesise evidence for these mechanisms.
KEY MESSAGES: 1) There is strong observational evidence that active cancer is associated with venous thromboembolism.2) It is currently unknown whether venous thromboembolism is a risk factor for cancer.3) We applied a bi-directional Mendelian randomisation framework to appraise the causal relationships between genetically-proxied risk of venous thromboembolism and 18 different cancers.4) Overall, there was no clear evidence from Mendelian randomisation that lifetime-elevated risk of venous thromboembolism is causally associated with an increased risk of cancer, or visa versa.
PMID:37292802 | PMC:PMC10246038 | DOI:10.1101/2023.05.16.23289792
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PubMed articles on: Cancer & VTE/PE
Stroke Recurrence in Embolic Stroke of Undetermined Source Without Atrial Fibrillation on Invasive Cardiac Monitoring
Heart Lung Circ. 2023 Jun 6:S1443-9506(23)00514-0. doi: 10.1016/j.hlc.2023.05.010. Online ahead of print.
ABSTRACT
BACKGROUND: More than half of patients with embolic stroke of undetermined source (ESUS) suffer from recurrent ischaemic stroke, despite the absence of atrial fibrillation (AF) on invasive cardiac monitoring (ICM). This study investigated the predictors and prognosis of recurrent stroke in ESUS without AF on ICM.
METHOD: This prospective study included patients with ESUS at two tertiary hospitals from 2015 to 2021 who underwent comprehensive neurological imaging, transthoracic echocardiography, and inpatient continuous electrographic monitoring for ≥48 hours prior to ICM for definitive exclusion of AF. Recurrent ischaemic stroke, all-cause mortality, and functional outcome by the modified Rankin scale (mRS) at 3 months were evaluated in patients without AF.
RESULTS: Of 185 consecutive patients with ESUS, AF was not detected in 163 (88%) patients (age 62±12 years, 76% men, 25% prior stroke, median time to ICM insertion 26 [7, 123] days), and stroke recurred in 24 (15%) patients. Stroke recurrences were predominantly ESUS (88%), within the first 2 years (75%), and involved a different vascular territory from qualifying ESUS (58%). Pre-existing cancer was the only independent predictor of recurrent stroke (adjusted hazard ratio [AHR] 5.43, 95% CI 1.43-20.64), recurrent ESUS (AHR 5.67, 95% CI 1.15-21.21), and higher mRS score at 3 months (ß 1.27, 95% CI 0.23-2.42). All-cause mortality occurred in 17 (10%) patients. Adjusting for age, cancer, and mRS category (≥3 vs <3),
CONCLUSIONS: Patients with recurrent ESUS are a high-risk subgroup. Studies elucidating optimal diagnostic and treatment strategies in non-AF-related ESUS are urgently required.
PMID:37291002 | DOI:10.1016/j.hlc.2023.05.010
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PubMed articles on: Cancer & VTE/PE
Dynamic Patterns and Persistence of Anticoagulation Therapy in Patients with Venous Thromboembolism in South Korea: A Nationwide Cohort Study
Thromb Haemost. 2023 Jun 7. doi: 10.1055/a-2107-0815. Online ahead of print.
ABSTRACT
Background Venous thromboembolism (VTE) is associated with increased morbidity, mortality, and healthcare expenditure. However, the comprehensive utilization of anticoagulation therapy in patients with VTE, especially regarding active cancer, in real-world practice remains unclear. Objective To describe the prescription, persistence, and patterns of anticoagulation therapy among patients with VTE stratified according to active cancer. Methods Using Korean nationwide claims data, we identified an incident, treatment-naïve cohort of patients with VTE from 2013 to 2019 and classified them according to the presence/absence of active cancer. We explored the secular trends, treatment patterns (e.g., discontinuation, interruption, and switch), and persistence of anticoagulation therapy. Results There were 48,504 and 7,255 patients without and with active cancer, respectively. NOACs were the most common anticoagulant in both groups (65.1% and 57.9%, respectively). The prescription of non-vitamin K antagonist oral anticoagulants (NOACs) increased steeply over time, regardless of active cancer, whereas parenteral anticoagulants (PACs) plateaued and warfarin decreased sharply. A heterogeneous pattern was observed between the groups without and with active cancer (3-month persistence was 60.8%, 62.9%, 57.2%, and 3.4%, respectively; 6-month persistence was 42.3%, 33.5%, 25.9%, and 1.2% vs. 9.9%). Median duration of continuous anticoagulant therapy for warfarin, NOAC, and PAC were 183, 147, and 3 days in non-active cancer patients, and 121, 117, and 44 days in active cancer patients. Conclusion Our findings suggest that there were substantial differences in persistence, patterns, and patient characteristics of anticoagulant therapy based on index anticoagulant and active cancer.
PMID:37285903 | DOI:10.1055/a-2107-0815
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PubMed articles on: Cancer & VTE/PE
Congenital hepatic hemangioma: an unusual case report of pulmonary hypertension
BMC Pediatr. 2023 Jun 7;23(1):284. doi: 10.1186/s12887-023-04096-w.
ABSTRACT
BACKGROUND: Pulmonary hypertension (PH) in newborns is a rare but serious condition that often requires immediate intervention and quick diagnosis of the correct etiology to prevent mortality. Congenital hepatic hemangioma (CHH) is an example of an extrathoracic etiology of PH.
CASE PRESENTATION: Herein, we report the case of a newborn with a giant liver hemangioma, who presented with an early onset of PH and was successfully treated with intra-arterial embolization.
CONCLUSIONS: This case illustrates the importance of suspicion and prompt evaluation of CHH and related systemic arteriovenous shunts among infants with unexplained PH.
PMID:37286954 | PMC:PMC10245545 | DOI:10.1186/s12887-023-04096-w
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PubMed articles on: Cancer & VTE/PE
Bevacizumab loaded CalliSpheres® bronchial arterial chemoembolization combined with immunotherapy and targeted therapy for advanced lung adenocarcinoma
Front Pharmacol. 2023 May 22;14:1170344. doi: 10.3389/fphar.2023.1170344. eCollection 2023.
ABSTRACT
PURPOSE OF REVIEW: To present the randomized controlled trial (RCT) evidence and highlight the areas of uncertainty regarding direct oral anticoagulants (DOAC) for cancer-associated venous thromboembolism (CAT).
RECENT FINDINGS: In the last years, four RCTs have shown that rivaroxaban, edoxaban, and apixaban are at least as effective as low-molecular-weight heparin (LMWH) for the treatment of both incidental and symptomatic CAT. On the other hand, these drugs increase the risk of major gastrointestinal bleeding in patients with cancer at this site. Another two RCTs have demonstrated that apixaban and rivaroxaban also prevent CAT in subjects at intermediate-to-high risk commencing chemotherapy, albeit at the price of higher likelihood of bleeding. By contrast, data are limited about the use DOAC in individuals with intracranial tumors or concomitant thrombocytopenia. It is also possible that some anticancer agents heighten the effects of DOAC via pharmacokinetic interactions, up to making their effectiveness-safety profile unfavorable. Leveraging the results of the aforementioned RCTS, current guidelines recommend DOAC as the anticoagulants of choice for CAT treatment and, in selected cases, prevention. However, the benefit of DOAC is less defined in specific patient subgroups, in which the choice of DOAC over LMWH should be carefully pondered.
PMID:37278934 | DOI:10.1007/s11912-023-01428-y
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PubMed articles on: Cardio-Oncology
Cardiac Mechanical Performance Assessment at Different Levels of Exercise in Childhood Acute Lymphoblastic Leukemia Survivors
J Pediatr Hematol Oncol. 2023 May 16. doi: 10.1097/MPH.0000000000002682. Online ahead of print.
ABSTRACT
BACKGROUND: There is a shortage of relevant studies interested in cardiac mechanical performance. Thus, it is clinically relevant to study the impact of cancer treatments on survivors' cardiac mechanical performance to improve our knowledge. The first objective of this study is to assess survivors' cardiac mechanical performance during a cardiopulmonary exercise test (CPET) using both ventricular-arterial coupling (VAC) and cardiac work efficiency (CWE) from cardiac magnetic resonance (CMR) acquisitions. The second objective is to assess the impact of doxorubicin and dexrazoxane (DEX) treatments.
METHODS: A total of 63 childhood acute lymphoblastic leukemia survivors underwent a CMR at rest on a 3T magnetic resonance imaging system, followed by a CPET on ergocycle. The CircAdapt model was used to study cardiac mechanical performance. At different levels of exercise, arterial elastance, end-systolic elastance, VAC, and CWE were estimated.
RESULTS: We observed significant differences between the different levels of exercise for both VAC (P<0.0001)
CONCLUSIONS: This study reveals that the combination of CPET, CMR acquisitions and CircAdapt model was sensitive enough to observe slight changes in the assessment of VAC and CWE parameters. Our study contributes to improving survivors' follow-up and detection of cardiac problems induced by doxorubicin-related cardiotoxicity.
PMID:37278566 | DOI:10.1097/MPH.0000000000002682
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PubMed articles on: Cardio-Oncology
Late-stage diagnosis of carcinoid heart disease due to lack of access to health care
Cardiooncology. 2023 Jun 5;9(1):28. doi: 10.1186/s40959-023-00176-z.
ABSTRACT
Carcinoid syndrome (CS) is a unique constellation of symptoms caused by release of vasoactive substances from neuroendocrine tumors (Pandit et al., StatPearls, 2022). Neuroendocrine tumors are rare with an annual incidence of 2 in 100,000 people (Ram et al., 46:21-27, 2019). Up to 50% of patients with these tumors will develop carcinoid syndrome, which is characterized by symptoms caused by elevated levels of serotonin and most commonly include fatigue, flushing, wheezing, and non-specific gastrointestinal symptoms such as diarrhea and malabsorption (Pandit et al., StatPearls, 2022) (Fox et.al., 90:1224-1228, 2004). Over time, patients with carcinoid syndrome can develop carcinoid heart disease (CHD). CHD refers to the cardiac complications that occur when the vasoactive substances, such as serotonin, tachykinins, and prostaglandins, secreted from the carcinoid tumors. These complications most commonly include valvular abnormalities, but can also present as coronary artery damage, arrhythmias or direct myocardial injury (Ram et al., 46:21-27, 2019). While CHD is not typically an initial feature of carcinoid syndrome, it does eventually occur in up to 70% of patients with carcinoid tumors (Ram et al., 46:21-27, 2019) (Jin et.al., 146:65-73, 2021) (Macfie et.al., 224:665-669, 2022). CHD is associated with significant morbidity and mortality due to the risk of progressive heart failure (Bober et.al., 14:1179546820968101, 2020). In this case, we describe a 35-year-old Hispanic woman in South Texas with undiagnosed carcinoid syndrome for over 10 years that eventually progressed to severe CHD. In this patient's case, we emphasize how lack of access to healthcare resulted in delay of diagnosis, appropriate treatment, and worsened prognosis in this young patient.
PMID:37277819 | PMC:PMC10240769 | DOI:10.1186/s40959-023-00176-z
C
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PubMed articles on: Cancer & VTE/PE
COVID-19 related acute necrotizing encephalopathy presenting in the early postoperative period
Arch Clin Cases. 2023 Jun 7;10(2):78-85. doi: 10.22551/2023.39.1002.10246. eCollection 2023.
ABSTRACT
Besides respiratory and gastrointestinal symptoms, SARS-CoV-2 also has potential neurotropic effects. Acute hemorrhagic necrotizing encephalopathy is a rare complication of Covid-19. This article presents a case of an 81-year-old female, fully vaccinated, who underwent laparoscopic transhiatal esophagectomy due to gastroesophageal junction cancer. In the early postoperative period, the patient developed persistent fever accompanied by acute quadriplegia, impaired consciousness, and no signs of respiratory distress. Imaging with Computed Tomography and Magnetic Resonance revealed multiple bilateral lesions both in gray and white matter, as well as pulmonary embolism. Covid-19 infection was added to the differential diagnosis three weeks later, after other possible causes were excluded. The molecular test obtained at that time for coronavirus was negative. However, the high clinical suspicion index led to Covid-19 antibody testing (IgG and IgA), which confirmed the diagnosis. The patient was treated with corticosteroids with noticeable clinical improvement. She was discharged to a rehabilitation center. Six months later, the patient was in good general condition, although a neurological deficit was still present. This case indicates the significance of a high clinical suspicion index, based on a combination of clinical manifestations and neuroimaging, and the confirmation of the diagnosis with molecular and antibody testing. Constant awareness of a possible Covid-19 infection among hospitalized patients is mandatory.
PMID:37293685 | PMC:PMC10246599 | DOI:10.22551/2023.39.1002.10246
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PubMed articles on: Cancer & VTE/PE
Incidence and risk factors for venous thromboembolism in patients with ovarian cancer during neoadjuvant chemotherapy: a meta-analysis
Am J Cancer Res. 2023 May 15;13(5):2126-2134. eCollection 2023.
ABSTRACT
In recent years, there has been increasing recognition of the relationship between neoadjuvant chemotherapy (NACT) in ovarian cancer and the incidence rate of venous thromboembolism (VTE). Some studies have suggested that NACT may be associated with a high risk of VTE in patients with ovarian cancer. To investigate this, we conducted a systematic review and meta-analysis of the incidence of VTE during NACT and its associated risk factors. We searched PubMed, Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and the International Standard Randomized Controlled Trial Number Register (ISRCTN) from their inception to September 15, 2022. We calculated the incidence of VTE as the event rate (%) and used logistic regression analysis to investigate pooled VTE rates. Risk factors for VTE were presented as odds ratios (ORs), and pooled ORs was estimated using the inverse variance method. We reported pooled effect estimates with 95% confidence intervals (CIs). Our review included 7 cohort studies with 1244 participants. Meta-analysis of these studies revealed a pooled VTE rate of 13% during NACT (1224 participants; 95% CI, 9%-17%), with body mass index identified as a risk factor for VTE during NACT in 3 of the included studies (633 participants; OR, 1.76; 95% CI, 1.13-2.76).
PMID:37293158 | PMC:PMC10244120
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PubMed articles on: Cancer & VTE/PE
Causal relationships between risk of venous thromboembolism and 18 cancers: a bidirectional Mendelian randomisation analysis
medRxiv. 2023 May 18:2023.05.16.23289792. doi: 10.1101/2023.05.16.23289792. Preprint.
ABSTRACT
Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the management of aggressive hematologic malignancies. However, its role in patients with lymphoma and cardiac metastasis or cardiomyopathy remains undefined due to potentially life-threatening complications such as ventricular rupture, cardiac tamponade, and circulatory failure. We present a case series of patients with lymphoma and cardiomyopathy or cardiac metastasis managed with chimeric antigen receptor T-cell therapy. (Level of Difficulty: Advanced.).
PMID:37283829 | PMC:PMC10240233 | DOI:10.1016/j.jaccas.2023.101840
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PubMed articles on: Cardio-Oncology
Informatics tools to implement late cardiovascular risk prediction modeling for population management of high-risk childhood cancer survivors
Pediatr Blood Cancer. 2023 Jun 7:e30474. doi: 10.1002/pbc.30474. Online ahead of print.
ABSTRACT
BACKGROUND: Clinical informatics tools to integrate data from multiple sources have the potential to catalyze population health management of childhood cancer survivors at high risk for late heart failure through the implementation of previously validated risk calculators.
METHODS: The Oklahoma cohort (n = 365) harnessed data elements from Passport for Care (PFC), and the Duke cohort (n = 274) employed informatics methods to automatically extract chemotherapy exposures from electronic health record (EHR) data for survivors 18 years old and younger at diagnosis. The Childhood Cancer Survivor Study (CCSS) late cardiovascular risk calculator was implemented, and risk groups for heart failure were compared to the Children's Oncology Group (COG) and the International Guidelines Harmonization Group (IGHG) recommendations. Analysis within the Oklahoma cohort assessed disparities in guideline-adherent care.
RESULTS: The Oklahoma and Duke cohorts both observed good overall concordance between the CCSS and COG risk groups for late heart failure, with weighted kappa statistics of .70 and .75, respectively. Low-risk groups showed excellent concordance (kappa > .9). Moderate and high-risk groups showed moderate concordance (kappa .44-.60). In the Oklahoma cohort, adolescents at diagnosis were significantly less likely to receive guideline-adherent echocardiogram surveillance compared with survivors younger than 13 years old at diagnosis (odds ratio [OD] 0.22; 95% confidence interval [CI]: 0.10-0.49).
CONCLUSIONS: Clinical informatics tools represent a feasible approach to leverage discrete treatment-related data elements from PFC or the EHR to successfully implement previously validated late cardiovascular risk prediction models on a population health level. Concordance of CCSS, COG, and IGHG risk groups using real-world data informs current guidelines and identifies inequities in guideline-adherent care.
PMID:37283294 | DOI:10.1002/pbc.30474
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PubMed articles on: Cardio-Oncology
Myocardial bridge in a patient with castration-resistant metastatic prostate cancer treated with enzalutamide
J Oncol Pharm Pract. 2023 Jun 6:10781552231180599. doi: 10.1177/10781552231180599. Online ahead of print.
ABSTRACT
INTRODUCTION: Myocardial bridge is a morphological anomaly of the heart characterised by the presence of a myocardial segment above a coronary artery, which results in a higher risk of cardiovascular events. In patients with prostate cancer treated with androgen receptor-targeted agents, a higher risk of cardiotoxicity was observed.
CASE REPORT: An 88 years old man with metastatic castration-resistant prostate cancer in treatment with enzalutamide, denosumab, and triptorelin presented to our attention complaining dyspnoea and angina pectoris.
MANAGEMENT AND OUTCOME: Blood examinations revealed normal Troponin I levels. Transthoracic echocardiography revealed no signs of acute myocardial ischaemia. The treadmill stress test revealed S-T tract under levelling in V4-V6 with a very slow resolution. Coronary angiography identified a myocardial bridge in the medium tract of the interventricular anterior artery. Due to these findings, ranolazine and simvastatin were started and, after multidisciplinary assessment, we decided to continue the treatment with enzalutamide. At the first follow-up visit echocardiography found out the cardiological reports stability and no therapy changes were performed. During follow-up visit cardiological revaluation showed reports stability and no therapy changes were performed.
DISCUSSION: Due to the high prevalence of prostate cancer in elderly patients at high cardiovascular risk and the increasing use of androgen receptor-targeted agent, a multidisciplinary approach is highly recommended to weigh survival benefits on toxicities. This case report may support the use of androgen receptor-targeted agent in elderly patients with controlled cardiovascular diseases, a population that is often excluded from randomised trials.
PMID:37282514 | DOI:10.1177/10781552231180599
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PubMed articles on: Cardio-Oncology
A Phase II Study of Neoadjuvant PLD/Cyclophosphamide and Sequential nab-Paclitaxel Plus Dual HER2 Blockade in HER2-Positive Breast Cancer
Oncologist. 2023 Jun 5:oyad160. doi: 10.1093/oncolo/oyad160. Online ahead of print.
ABSTRACT
BACKGROUND: Neoadjuvant trastuzumab/pertuzumab (HP) plus chemotherapy for HER2-positive breast cancer (BC) achieved promising efficacy. The additional cardiotoxicity still existed. Brecan study evaluated the efficacy and safety of neoadjuvant pegylated liposomal doxorubicin (PLD)/cyclophosphamide and sequential nab-paclitaxel based on HP (PLD/C/HP-nabP/HP).
PATIENTS AND METHODS: Brecan was a single-arm phase II study. Eligible patients with stages IIA-IIIC HER2-positive BC received 4 cycles of PLD, cyclophosphamide, and HP, followed by 4 cycles of nab-paclitaxel and HP. Definitive surgery was scheduled after 21 days for patients completing treatment or experiencing intolerable toxicity. The primary endpoint was the pathological complete response (pCR).
RESULTS: Between January 2020 and December 2021, 96 patients were enrolled. Ninety-five (99.0%) patients received 8 cycles of neoadjuvant therapy and all underwent surgery with 45 (46.9%) breast-conserving surgery and 51 (53.1%) mastectomy. The pCR was 80.2% (95%CI, 71.2%-87.0%). Four (4.2%) experienced left ventricular insufficiency with an absolute decline in LVEF (43%-49%). No congestive heart failure and ≥grade 3 cardiac toxicity occurred. The objective response rate was 85.4% (95%CI, 77.0%-91.1%), including 57 (59.4%) complete responses and 25 (26.0%) partial responses. The disease control rate was 99.0% (95%CI, 94.3%-99.8%). For overall safety, ≥grade 3 AEs occurred in 30 (31.3%) and mainly included neutropenia (30.2%) and asthenia (8.3%). No treatment-related deaths occurred. Notably, age of >30 (P = 0.01; OR = 5.086; 95%CI, 1.44-17.965) and HER2 IHC 3+ (P = 0.02; OR = 4.398; 95%CI, 1.286-15.002) were independent predictors for superior pCR (ClinicalTrials.gov Identifier NCT05346107).
CONCLUSION: Brecan study demonstrated the encouraging safety and efficacy of neoadjuvant PLD/C/HP-nabP/HP, suggesting a potential therapeutic option in HER2-positive BC.
PMID:37279780 | DOI:10.1093/oncolo/oyad160
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PubMed articles on: Cardio-Oncology
Direct Oral Anticoagulants for Cancer-Associated Venous Thromboembolism
Curr Oncol Rep. 2023 Jun 6. doi: 10.1007/s11912-023-01428-y. Online ahead of print.
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