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1/12/26

ABSTRACT

OBJECTIVE: To quantitatively analyze the cardiac magnetic resonance imaging (CMR) characteristics of chemotherapy-related cardiac dysfunction (CTRCD) and explore their prognostic value for major adverse cardiovascular events (MACE).

MATERIALS AND METHODS: A total of 145 patients (male:female = 76:69, mean age = 63.0 years) with cancer and heart failure who underwent CMR between January 2015 and January 2021 were included. CMR was performed using a 3T scanner (Siemens). Biventricular functions, native T1 T2, extracellular volume fraction (ECV) values, and late gadolinium enhancement (LGE) of the left ventricle (LV) were compared between those with and without CTRCD. These were compared between patients with mild-to-moderate CTRCD and those with severe CTRCD. Cox proportional hazard regression analysis was used to evaluate the association between the CMR parameters and MACE occurrence during follow-up in the CTRCD patients.

RESULTS: Among 145 patients, 61 had CTRCD and 84 did not have CTRCD. Native T1, ECV, and T2 were significantly higher in the CTRCD group (1336.9 ms, 32.5%, and 44.7 ms, respectively) than those in the non-CTRCD group (1303.4 ms, 30.5%, and 42.0 ms, respectively; P= 0.013, 0.010, and < 0.001, respectively). They were not significantly different between patients with mild-to-moderate and severe CTRCD. Indexed LV mass was significantly smaller in the CTRCD group (65.0 g/m² vs. 78.9 g/m²; P< 0.001). According to the multivariable Cox regression analysis, T2 (hazard ratio [HR]: 1.14, 95% confidence interval [CI]: 1.01-1.27; P= 0.028) and quantified LGE (HR: 1.07, 95% CI: 1.01-1.13; P= 0.021) were independently associated with MACE in the CTRCD patients.

CONCLUSION: Quantitative parameters from CMR have the potential to evaluate myocardial changes in CTRCD. Increased T2 with reduced LV mass was demonstrated in CTRCD patients even before the development of severe cardiac dysfunction. T2 and quantified LGE may be independent prognostic factors for MACE in patients with CTRCD.

PMID:37634639 | DOI:10.3348/kjr.2023.0095

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PubMed articles on: Cardio-Oncology

Non-pegylated liposomal doxorubicin in older adjuvant early breast cancer patients: cardiac safety analysis and final results of the COLTONE study

Clin Exp Med. 2023 Aug 27. doi: 10.1007/s10238-023-01144-8. Online ahead of print.

ABSTRACT

AIMS: To explore the cardiac safety of adjuvant Non-Pegylated Liposomal Doxorubicin (NPL-DOX) plus Cyclophosphamide (CTX) followed by weekly Paclitaxel, in elderly women (≥ 65 years) with high-risk breast cancer. Previously, we described no symptomatic cardiac events within the first 12 months from starting treatment. We now reported the updated results after a median follow-up 76 months.

METHODS: The cardiac activity was evaluated with left ventricular ejection fraction (LVEF) echocardiograms assessments, before starting chemotherapy and every 6 months, until 30 months from baseline, then yearly for at least 5 years.

RESULTS: Forty-seven women were recruited by two Units of Medical Oncology (Ethics Committee authorization CESM-AOUP, 3203/2011; EudraCT identification number: 2010-024067-41, for Pisa and Pontedera Hospitals). An episode of grade 3 CHF (NCI-CTCAE, version 3.0) occurred after 18 months the beginning of chemotherapy. The echocardiograms assessments were performed comparing the LVEF values of each patient evaluated at fixed period of time, compared to baseline. We observed a slight changed in terms of mean values at 48, 60, 72 and 84 months. At these time points, a statistically significant reduction of - 3.2%, - 4.6%, - 6.4% and - 7.1%, respectively, was observed. However, LVEF remained above 50% without translation in any relevant clinical signs. No other cardiac significant episodes were reported. To this analysis, in 13 patients (28%) occurred disease relapse and, of them, 11 (23%) died due to metastatic disease. Eight patients died of cancer-unrelated causes.

CONCLUSIONS: The combination including NPL-DOX in elderly patients revealed low rate of cardiac toxic effects. Comparative trials are encouraged.

PMID:37634231 | DOI:10.1007/s10238-023-01144-8

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PubMed articles on: Cardio-Oncology

Carvedilol Phenocopies PGC-1α Overexpression to Alleviate Oxidative Stress, Mitochondrial Dysfunction and Prevent Doxorubicin-Induced Toxicity in Human iPSC-Derived Cardiomyocytes

Antioxidants (Basel). 2023 Aug 9;12(8):1585. doi: 10.3390/antiox12081585.

ABSTRACT

Doxorubicin (DOX), one of the most effective and widely used anticancer drugs, has the major limitation of cancer treatment-related cardiotoxicity (CTRTOX) in the clinic. Reactive oxygen species (ROS) generation and mitochondrial dysfunction are well-known consequences of DOX-induced injury to cardiomyocytes. This study aimed to explore the mitochondrial functional consequences and associated mechanisms of pretreatment with carvedilol, a ß-blocking agent known to exert protection against DOX toxicity. When disease modeling was performed using cultured rat cardiac muscle cells (H9c2 cells) and human iPSC-derived cardiomyocytes (iPSC-CMs), we found that prophylactic carvedilol mitigated not only the DOX-induced suppression of mitochondrial function but that the mitochondrial functional readout of carvedilol-pretreated cells mimicked the readout of cells overexpressing the major regulator of mitochondrial biogenesis, PGC-1α. Carvedilol pretreatment reduces mitochondrial oxidants, decreases cell death in both H9c2 cells and human iPSC-CM and maintains the cellular 'redox poise' as determined by sustained expression of the redox sensor Keap1 and prevention of DOX-induced Nrf2 nuclear translocation. These results indicate that, in addition to the already known ROS-scavenging effects, carvedilol has a hitherto unrecognized pro-reducing property against the oxidizing conditions induced by DOX treatment, the sequalae of DOX-induced mitochondrial dysfunction and compromised cell viability. The novel findings of our preclinical studies suggest future trial design of carvedilol prophylaxis, such as prescreening for redox state, might be an alternative strategy for preventing oxidative stress writ large in lieu of the current lack of clinical evidence for ROS-scavenging agents.

PMID:37627583 | PMC:PMC10451268 | DOI:10.3390/antiox12081585

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PubMed articles on: Cardio-Oncology

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PubMed articles on: Cardio-Oncology

Accelerated Atherosclerosis and Cardiovascular Toxicity Induced by Radiotherapy in Breast Cancer

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PubMed articles on: Cardio-Oncology

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Cardiotoxicity News

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PubMed articles on: Cancer & VTE/PE

Association of type of oral anticoagulation with risk of bleeding in 45,114 patients with venous thromboembolism during initial and extended treatment-A nationwide register-based study

J Intern Med. 2023 Aug 28. doi: 10.1111/joim.13712. Online ahead of print.

ABSTRACT

BACKGROUND: Safety data for different anticoagulant medications in venous thromboembolism (VTE) are scarce, in particular for extended treatment.

OBJECTIVES: To compare major bleeding rates depending on the choice of anticoagulation during initial (first 6 months) and extended treatment (6 months up to 5 years).

METHODS: A nationwide register-based study including cancer-free patients with a first-time VTE between 2014 and 2020. Cox proportional hazards models were used to compare bleeding rates.

RESULTS: We included 6558 patients on warfarin, 18,196 on rivaroxaban, and 19,498 on apixaban. At 6 months, 4750 (72.4%) remained on warfarin, 11,366 (62.5%) on rivaroxaban, and 11,940 (61.2%) on apixaban. During initial treatment, major bleeding rates were 3.86 (95% CI 3.14-4.58), 2.93 (2.55-3.31), and 1.95 (1.65-2.25) per 100 patient-years for warfarin, rivaroxaban, and apixaban, respectively, yielding adjusted hazard ratios (aHRs) of 0.89 (95% CI 0.71-1.12) for rivaroxaban versus warfarin, 0.55 (0.43-0.71) for apixaban versus warfarin, and 0.62 (0.50-0.76) for apixaban versus rivaroxaban. During extended treatment, major bleeding rates were 1.55 (1.19-1.91), 1.05 (0.85-1.26), and 0.96 (0.78-1.15) per 100 patient-years for warfarin, rivaroxaban, and apixaban, respectively, with aHRs of 0.72 (0.53-0.99) for rivaroxaban versus warfarin, 0.60 (0.44-0.82) for apixaban versus warfarin, and 0.85 (0.64-1.12) for apixaban versus rivaroxaban. Previous bleeding and increasing age were risk factors for bleeding both during initial and extended treatment.

CONCLUSION: Apixaban had a lower bleeding risk than warfarin or rivaroxaban during initial treatment. During extended treatment, bleeding risk was similar for apixaban and rivaroxaban, and higher with warfarin.

PMID:37641391 | DOI:10.1111/joim.13712

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PubMed articles on: Cancer & VTE/PE

Edoxaban for 12 Months Versus 3 Months in Cancer Patients With Isolated Distal Deep Vein Thrombosis (ONCO DVT study): An Open-label, Multicenter, Randomized Clinical Trial

Circulation. 2023 Aug 28. doi: 10.1161/CIRCULATIONAHA.123.066360. Online ahead of print.

ABSTRACT

Background:The optimal duration of anticoagulation therapy for isolated distal deep vein thrombosis (DVT) in patients with cancer is clinically relevant, but the evidence is lacking. The prolonged anticoagulation therapy could have a potential benefit for prevention of thrombotic events, however, it could also increase the risk of bleeding. Methods:In a multicenter, open-label, adjudicator-blinded, randomized clinical trial at 60 institutions in Japan, we randomly assigned cancer patients with isolated distal DVT, in a 1-to-1 ratio, to receive either a 12-month or 3-month edoxaban treatment. The primary endpoint was a composite of a symptomatic recurrent venous thromboembolism (VTE) or VTE-related death at 12 months. The major secondary endpoint was major bleeding at 12 months, according to the criteria of the International Society on Thrombosis and Hemostasis. The primary hypothesis was that a 12-month edoxaban treatment was superior to a 3-month edoxaban treatment with respect to the primary endpoint. Results:From April 2019 through June 2022, 604 patients were randomized, and after excluding 3 patients who withdrew consent, 601 patients were included in the intention-to-treat population: 296 patients in the 12-month edoxaban group and 305 patients in the 3-month edoxaban group. The mean age was 70.8 years, 28% of the patients were men, and 20% of the patients had symptoms of DVT at baseline. The primary endpoint of a symptomatic recurrent VTE event or VTE-related death occurred in 3 of the 296 patients (1.0%) in the 12-month edoxaban group and in 22 of the 305 (7.2%) in the 3-month edoxaban group (odds ratio, 0.13; 95% CI, 0.03 to 0.44). The major secondary endpoint of major bleeding occurred in 28 of the 296 patients (9.5%) in the 12-month edoxaban group and in 22 of the 305 (7.2%) in the 3-month edoxaban group (odds ratio, 1.34; 95% CI, 0.75 to 2.41). The prespecified subgroups did not affect the estimates on the primary endpoint. Conclusions:In cancer patients with isolated distal DVT, 12 months was superior to 3 months for an edoxaban treatment with respect to the composite outcome of a symptomatic recurrent VTE or VTE-related death.

PMID:37638968 | DOI:10.1161/CIRCULATIONAHA.123.066360

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PubMed articles on: Cancer & VTE/PE

Sternum Metastases: From Case-Identifying Strategy to Multidisciplinary Management

Diagnostics (Basel). 2023 Aug 17;13(16):2698. doi: 10.3390/diagnostics13162698. ABSTRACTWe aimed to overview the most recent data on sternal metastases from a multidisciplinary approach (diagnosis strategies, outcome, and histological reports). This narrative review based on a PubMed search (between January 2020 and 22 July 2023) using key words such as "sternal", "manubrium", and "metastasis" within the title and/or abstract only included original papers that specifically addressed secondary sternal spreading of cancer in adults, for a total of 48 original articles (14 studies and 34 single case reports). A prior unpublished case in point is also introduced (percutaneous incisional biopsy was used to address a 10 cm sternal tumour upon first admission on an apparently healthy male). The studies (n = 14) may be classified into one of three groups: studies addressing the incidence of bone metastases (including sternum) amid different primary cancers, such as prostate cancer (N = 122 with bone metastases, 83% of them with chest wall metastases), head and neck cancers (N = 3620, 0.8% with bone metastases, and 10.34% of this subgroup with sternum involvement); and glioblastoma (N = 92 with bone metastases, 37% of them with non-vertebral metastases, including the sternum); assessment cohorts, including breast cancer (N = 410; accuracy and sensitivity of PET/CT vs. bone scintigraphy is superior with concern to sternum spreading) and bone metastases of unknown origin (N = 83, including a subgroup with sternum metastases; some features of PET/CT help the differentiation with multiple myeloma); and cohorts with various therapeutic approaches, such as palliative arterial embolization (N = 10), thymic neuroendocrine neoplasia (1/5 detected with sternum metastases), survival rates for sternum metastases vs. non-sternum chest wall involvement (N = 87), oligo-metastatic (sternal) breast cancer (3 studies, N = 16 for all of them), oligo-metastatic head and neck cancer (N = 81), conformal radiotherapy (N = 24,215, including an analysis on sternum spreading), and EBRT followed by MR-HIFU (N = 6). Core data coming from the isolated case reports (N = 34) showed a female to male ratio of 1.6; the females' ages were between 34 and 80 (mean of 57.28) and the males' ages varied between 33 and 79 (average of 58.78) years. The originating tumour profile revealed that the most frequent types were mammary (N = 8, all females) and thyroid (N = 9, both women and men), followed by bladder (N = 3), lung (N = 2), and kidney (N = 2). There was also one case for each of the following: adenoid cystic carcinoma of the jaw, malignant melanoma, caecum MiNEN, a brain and an extracranial meningioma, tongue carcinoma, cholangiocarcinoma, osteosarcoma, and hepatocellular carcinoma. To our knowledge, this is the most complex and the largest analysis of prior published data within the time frame of our methods. These data open up new perspectives of this intricate, dynamic, and challenging domain of sternum metastases. Awareness is a mandatory factor since the patients may have a complex multidisciplinary medical and/or surgical background or they are admitted for the first time with this condition; thus, the convolute puzzle will start from this newly detected sternal lump. Abbreviations: N = number of patients; n = number of studies; PET/CT = positron emission tomography/computed tomography; EVRT = external beam radiotherapy; MR-HIFU = magnetic resonance-guided high-intensity focused ultrasound; MiNEN = mixed neuroendocrine-non-neuroendocrine tumour.

PMID:37627957 | PMC:PMC10453928 | DOI:10.3390/diagnostics13162698

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PubMed articles on: Cancer & VTE/PE

Venous thrombotic events and impact on outcomes in patients treated with first-line single-agent pembrolizumab in PD-L1 ≥ 50% advanced non small cell lung cancer

J Cancer Res Clin Oncol. 2023 Aug 25. doi: 10.1007/s00432-023-05321-w. Online ahead of print.

ABSTRACT

BACKGROUND: Few data are available on the impact of venous thrombotic events (VTE) in patients with metastatic non-small cell lung cancer (mNSCLC) treated with immunotherapy.

METHODS: This is a secondary analysis of the ESKEYP study, a national, retrospective, multicenter study that consecutively included all PD-L1 ≥ 50% mNSCLC patients who initiated first-line treatment with pembrolizumab monotherapy. From May 2017 to November 2019, 845 patients were included (from availability of pembrolizumab in this indication in France to the authorization of the combination with chemotherapy). Impact of VTE and patient characteristics were analyzed.

RESULTS: Of the 748 patients (88.5%) with available data, the incidence of VTE was 14.8% (111/748). At pembrolizumab initiation, Khorana score was ≥ 2 for 55.0% (61/111) of them. Recurrence of VTE was reported for 4 of the 111 patients and 5 had bleeding complications. Patients with VTE were significantly younger, had more frequently long-term corticosteroids treatment and more often liver metastases. Progression-free survival (PFS) was significantly shorter in patients with VTE compared to patients without VTE: 6.1 (95% CI 4.1-9.0) months vs. 8.3 (6.9-10.3) months (p = 0.03). VTE did not significantly impact overall survival (OS): 15.2 (10.0-24.7) months with VTE and 22.6 (18.4-29.8) months without VTE (p = 0.07). In multivariate analysis for PFS and OS, HRs for VTE were 1.3 (0.99-1.71), p = 0.06 and 1.32 (0.99-1.76), p = 0.05.

CONCLUSION: The incidence of VTE appears to be as high with in first-line immunotherapy as with chemotherapy in patients with mNSCLC, with in patient with VTE, a no significant trend for lower PFS and OS in multivariate analysis. more marked impact on PFS than on OS.

PMID:37626173 | DOI:10.1007/s00432-023-05321-w