ABSTRACT
INTRODUCTION: Sequential anti-PD-(L)1 followed by small targeted therapy use is associated with increased prevalence of adverse events (AEs) in non-small cell lung cancer (NSCLC). KRASG12C inhibitor sotorasib may trigger severe immune-mediated hepatotoxicity when used in sequence or in combination with anti-PD-(L)1. This study was designed to address whether sequential anti-PD-(L)1 and sotorasib therapy increases the risk of hepatotoxicity and other AEs.
METHODS: This is a multicenter, retrospective study of consecutive advanced KRASG12C-mutant NSCLC treated with sotorasib outside clinical trials in 16 French medical centers. Patient records were reviewed to identify sotorasib-related AEs (NCI-CTCAE v5.0). Grade 3 and higher AE was considered as severe. Sequence group was defined as patients who received an anti-PD-(L)1 as last line of treatment before sotorasib initiation and control group as patients who did not receive an anti-PD-(L)1 as last line of treatment before sotorasib initiation.
RESULTS: We identified 102 patients who received sotorasib, including 48 (47%) in sequence group and 54 (53%) in control group. Patients in control group received an anti-PD-(L)1 followed by at least one treatment regimen before sotorasib in 87% of the cases or did not receive an anti-PD-(L)1 at any time before sotorasib in 13% of the cases. Severe sotorasib-related AEs were significantly more frequent in sequence group compared to control group (50% vs 13%, p<0.001).<0.001).
CONCLUSIONS: Sequential anti-PD-(L)1 and sotorasib therapy is associated with a significantly increased risk of severe sotorasib-related hepatotoxicity and severe non-liver AEs. We suggest avoiding starting sotorasib within 30 days from the last anti-PD-(L)1 infusion.
PMID:37217096 | DOI:10.1016/j.jtho.2023.05.013
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PubMed articles on: Cardio-Oncology
Clinical Outcomes and Prognostic Factors of Patients With Early Malignant Melanoma in One Latin American Country: Results of the Epidemiological Registry of Malignant Melanoma in Colombia Study
JCO Glob Oncol. 2023 May;9:e2200377. doi: 10.1200/GO.22.00377.
ABSTRACT
To describe the population with early malignant melanoma, we performed a cohort study on the basis of the Epidemiological Registry of Malignant Melanoma in Colombia-Asociacion Colombiana de Hematologia y Oncologia. From January 2011 until December 2021, 759 patients were included; the average age was 66 years, 57% were women, acral lentiginous histology was found in 27.8% of patients, and the median follow-up was 36.5 months. The prognostic factors for overall survival in our population are Eastern Cooperative Oncology Group 3-4 (hazard ratio [HR], 13.8), stage III (HR, 5.07), received radiotherapy (HR, 3.38), ulceration on histology (HR, 2.68), chronic sun exposure (HR, 2.3), low income (HR, 2.04), previous local surgery (HR, 0.27), and have received adjuvant treatment (HR, 0.41).
PMID:37216624 | DOI:10.1200/GO.22.00377
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PubMed articles on: Cardio-Oncology
Assessment of left heart dysfunction to predict doxorubicin cardiotoxicity in children with lymphoma
Front Pediatr. 2023 May 5;11:1163664. doi: 10.3389/fped.2023.1163664. eCollection 2023.
ABSTRACT
OBJECTIVES: The objectives of this study were to assess the changes in the left myocardial function after chemotherapy for childhood lymphoma and observe the predictive or monitor value for cancer treatment-related cardiac dysfunction (CTRCD) by speckle-tracking echocardiography.
METHODS: A total of 23 children with histopathological diagnoses of lymphoma were included, with age-matched normal controls. Comparative analysis of clinical serological tests and left heart strain parameters in children with lymphoma, including left ventricular global longitudinal strain (LVGLS); global myocardial work (GMW) indices, which include global work index (GWI), global constructive work (GCW), global wasted work, and global work efficiency; and the LS of subendocardial, middle, and subepicardial layer myocardium during left ventricular systole were measured: left atrial strain of reservoir phase (LASr), left atrial strain of conduit phase (LAScd), and left atrial strain of contraction phase (LASct).
RESULTS: One-way ANOVA showed that GLS, GWI, GCW, LASr, and LAScd were closely associated with CTRCD and multivariate logistic regression analysis showed that GLS was the most sensitive predictor for detecting patients at lofty risk of anthracycline-related cardiotoxicity. Both before and after chemotherapy, GLS in the left ventricle showed a pattern of basal segment < middle segment < apical segment and subepicardial < middle < subendocardial layer (p < 0.05), and the degree of decrease also showed a regular pattern of epicardial layer < middle layer < subendocardial layer while the difference was not significant (p > 0.05). After chemotherapy, maximum flow rate in early mitral relaxation/left atrial systolic maximum flow rate (E/A) and left atrial volume index of each group were in the normal range, and the values of LASr, LAScd, and LASct slightly increased in the second cycle and decreased significantly in the fourth cycle after chemotherapy, reaching the lowest level; LASr and LAScd were positively correlated with GLS.
CONCLUSION: LVGLS is a more sensitive and earlier indicator to predict CTRCD compared with conventional echocardiography-related parameters and serological markers, and GLS of each myocardial layer showed a certain regularity. Left atrial strain can be used for early monitoring of cardiotoxicity in children with lymphoma after chemotherapy.
PMID:37215605 | PMC:PMC10196234 | DOI:10.3389/fped.2023.1163664
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PubMed articles on: Cardio-Oncology
Recurrent cardiotoxicity in a fluoropyrimidine treated cancer patient - case report and practical recommendations
Arch Clin Cases. 2023 May 18;10(2):55-60. doi: 10.22551/2023.39.1002.10241. eCollection 2023.
ABSTRACT
Fluoropyrimidines remain some of the most used chemotherapeutics, despite the appearance in the therapeutic arsenal of targeted therapy and immunotherapy. Fluropyrimidines related cardiotoxicity is an undesirable adverse event and affects almost 20% of patients. The mechanisms of fluoropyrimidine toxicity are closely related to deficient allelic variants of DPYD, but considering the low penetrance and interindividual variability, not all adverse reactions are explained by their presence. In this case, we report a patient with recurrent fluoropyrimidine toxicity without a deficient allelic variant and how this case was managed by the oncologist and cardiologist, considering the need to use fluoropyrimidine in the treatment.
PMID:37215066 | PMC:PMC10194170 | DOI:10.22551/2023.39.1002.10241
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PubMed articles on: Cardio-Oncology
Will nanomedicine become a good solution for the cardiotoxicity of chemotherapy drugs?
Front Pharmacol. 2023 May 4;14:1143361. doi: 10.3389/fphar.2023.1143361. eCollection 2023.
ABSTRACT
Cancer is one of the leading causes of death worldwide, and with the continuous development of life sciences and pharmaceutical technology, more and more antitumor drugs are being used in clinics to benefit cancer patients. However, the incidence of chemotherapy-induced cardiotoxicity has been continuously increasing, threatening patients' long-term survival. Cardio-oncology has become a research hot spot, and the combination of nanotechnology and biomedicine has brought about an unprecedented technological revolution. Nanomaterials have the potential to maximize the efficacy and reduce the side effects of chemotherapeutic drugs when used as their carriers, and several nano-formulations of frequently used chemotherapeutic drugs have already been approved for marketing. In this review, we summarize chemotherapeutic drugs that are highly associated with cardiotoxicity and evaluate the role of nano-delivery systems in reducing cardiotoxicity based on studies of their marketed or R&D nano-formulations. Some of the marketed chemotherapy drugs are combined with nano-delivery systems that can effectively deliver chemotherapy drugs to tumors and cannot easily penetrate the endothelial barrier of the heart, thus decreasing their distribution in the heart and reducing the cardiotoxicity to some extent. However, many chemotherapy nanomedicines that are marketed or in R&D have not received enough attention in determining their cardiotoxicity. In general, nanomedicine is an effective method to reduce the cardiotoxicity of traditional chemotherapy drugs. However, cardiovascular complications in cancer treatment are very complex diseases, requiring the application of multiple measures to achieve effective management and prevention.
PMID:37214453 | PMC:PMC10194942 | DOI:10.3389/fphar.2023.1143361
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PubMed articles on: Cardio-Oncology
Review of cardiovascular imaging in the Journal of Nuclear Cardiology 2022: positron emission tomography, computed tomography, and magnetic resonance
J Nucl Cardiol. 2023 May 19. doi: 10.1007/s12350-023-03283-7. Online ahead of print.
ABSTRACT
In 2022, the Journal of Nuclear Cardiology® published many excellent original research articles and editorials focusing on imaging in patients with cardiovascular disease. In this review of 2022, we summarize a selection of articles to provide a concise recap of major advancements in the field. In the first part of this 2-part series, we addressed publications pertaining to single-photon emission computed tomography. In this second part, we focus on positron emission tomography, cardiac computed tomography, and cardiac magnetic resonance. We specifically review advances in imaging of non-ischemic cardiomyopathy, cardio-oncology, infectious disease cardiac manifestations, atrial fibrillation, detection and prognostication of atherosclerosis, and technical improvements in the field. We hope that this review will be useful to readers as a reminder to articles they have seen during the year as well as ones they have missed.
PMID:37204688 | DOI:10.1007/s12350-023-03283-7
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PubMed articles on: Cardio-Oncology
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PubMed articles on: Cardio-Oncology
Association of atrial fibrillation and outcomes in patients undergoing bone marrow transplantation
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PubMed articles on: Cardio-Oncology
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PubMed articles on: Cardio-Oncology
Modelling cardiac mechanics in doxorubicin-induced cardiotoxicity following childhood acute lymphoblastic leukemia using a combination of cardiac magnetic resonance imaging, cardiopulmonary exercise testing and the CircAdapt model
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PubMed articles on: Cardio-Oncology
Quantitative assessment of radiotherapy-induced myocardial damage using MRI: a systematic review
Cardiooncology. 2023 May 18;9(1):24. doi: 10.1186/s40959-023-00175-0.
ABSTRACT
PURPOSE: To determine the role of magnetic resonance imaging (MRI)-based metrics to quantify myocardial toxicity following radiotherapy (RT) in human subjects through review of current literature.
METHODS: Twenty-one MRI studies published between 2011-2022 were identified from available databases. Patients received chest irradiation with/without other treatments for various malignancies including breast, lung, esophageal cancer, Hodgkin's, and non-Hodgkin's lymphoma. In 11 longitudinal studies, the sample size, mean heart dose, and follow-up times ranged from 10-81 patients, 2.0-13.9 Gy, and 0-24 months after RT (in addition to a pre-RT assessment), respectively. In 10 cross-sectional studies, the sample size, mean heart dose, and follow-up times ranged from 5-80 patients, 2.1-22.9 Gy, and 2-24 years from RT completion, respectively. Global metrics of left ventricle ejection fraction (LVEF) and mass/dimensions of cardiac chambers were recorded, along with global/regional values of T1/T2 signal, extracellular volume (ECV), late gadolinium enhancement (LGE), and circumferential/radial/longitudinal strain.
RESULTS: LVEF tended to decline at >20 years follow-up and in patients treated with older RT techniques. Changes in global strain were observed after shorter follow-up (13±2 months) for concurrent chemoradiotherapy. In concurrent treatments with longer follow-up (8.3 years), increases in left ventricle (LV) mass index were correlated with LV mean dose. In pediatric patients, increases in LV diastolic volume were correlated with heart/LV dose at 2 years post-RT. Regional changes were observed earlier post-RT. Dose-dependent responses were reported for several parameters, including: increased T1 signal in high-dose regions, a 0.136% increase of ECV per Gy, progressive increase of LGE with increasing dose at regions receiving >30 Gy, and correlation between increases in LV scarring volume and LV mean/V10/V25 Gy dose.
CONCLUSION: Global metrics only detected changes over longer follow-up, in older RT techniques, in concurrent treatments, and in pediatric patients. In contrast, regional measurements detected myocardial damage at shorter follow-up and in RT treatments without concurrent treatment and had greater potential for dose-dependent response. The early detection of regional changes suggests the importance of regional quantification of RT-induced myocardial toxicity at early stages, before damage becomes irreversible. Further works with homogeneous cohorts are required to examine this matter.
PMID:37202766 | PMC:PMC10193692 | DOI:10.1186/s40959-023-00175-0
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PubMed articles on: Cardio-Oncology
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Cardiotoxicity News
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.
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