Abstract
Radiation therapy is received by over half of all cancer patients. However, radiation doses may be constricted due to normal tissue side effects. In thoracic cancers, including breast and lung cancers, cardiac radiation is a major concern in treatment planning. There are currently no biomarkers of radiation-induced cardiotoxicity. Complex genetic modifiers can contribute to the risk of radiation-induced cardiotoxicities, yet these modifiers are largely unknown and poorly understood. We have previously reported the SS (Dahl salt-sensitive/Mcwi) rat strain is a highly sensitized model of radiation-induced cardiotoxicity compared to the more resistant Brown Norway (BN) rat strain. When rat chromosome 3 from the resistant BN rat strain is substituted into the SS background (SS.BN3 consomic), it significantly attenuates radiation-induced cardiotoxicity, demonstrating inherited genetic variants on rat chromosome 3 modify radiation sensitivity. Genes involved with mitochondrial function were differentially expressed in the hearts of SS and SS.BN3 rats 1 week after radiation. Here we further assessed differences in mitochondria-related genes between the sensitive SS and resistant SS.BN3 rats. We found mitochondrial-related gene expression differed in untreated hearts, while no differences in mitochondrial morphology were seen 1 week after localized heart radiation. At 12 weeks after localized cardiac radiation, differences in mitochondrial complex protein expression in the left ventricles were seen between the SS and SS.BN3 rats. These studies suggest that differences in mitochondrial gene expression caused by inherited genetic variants may contribute to differences in sensitivity to cardiac radiation.
PMID: 32195269 [PubMed]
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Administration of trastuzumab with heart irradiation induced acute cardiotoxicity in mice.
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Administration of trastuzumab with heart irradiation induced acute cardiotoxicity in mice.
Am J Cancer Res. 2020;10(2):536-544
Authors: Yi P, Li H, Fang Y, Su J, Xu C, Cao L, Li M, Chen J
Abstract
Cardiac toxicity is one of the major advese effect associated with thoracic irradiation. Breast cancer patients with human epidermal factor receptor-2 (Her-2) overexpression could be indicated for both radiation and anti-Her2 target therapy. We aimed to investigate the early detection of radiation and Trastuzumab (TRZ) induced acute cardiotoxicity in mice. In the present study, the heart of animal was subjected to irradiation (IR, 14 Gy/1 Fx), TRZ was intraperitonealy (i.p.) administrated to mice in 2 weeks (6 fractions). The IR plus TRZ group received heart IR after TRZ. We found that body weight of mouse in treatment groups reduced significantly as compared with that of mouse in control group (P<0.05).<0.05).<0.05;<0.05).
PMID: 32195025 [PubMed]
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Cardiotoxicity of radiation therapy in esophageal cancer.
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Cardiotoxicity of radiation therapy in esophageal cancer.
Rep Pract Oncol Radiother. 2020 May-Jun;25(3):318-322
Authors: Vošmik M, Hodek M, Buka D, Sýkorová P, Grepl J, Paluska P, Paulíková S, Sirák I
Abstract
With a development of radiotherapeutic techniques, availability of radiotherapy data on cardiotoxicity, and slowly improving esophageal cancer outcomes, an increasing emphasis is placed on the heart protection in radiation treated esophageal cancer patients. Radiation induced heart complications encompass mainly pericardial disease, cardiomyopathy, coronary artery atherosclerosis, valvular heart disease, and arrhythmias. The most frequent toxicity is pericardial effusion which is usually asymptomatic in the majority of patients. The use of modern radiotherapy techniques is expected to reduce the risk of cardiotoxicity, although this expectation has to be confirmed by clinical data.
PMID: 32194352 [PubMed]
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MicroRNAs in Cancer Treatment-Induced Cardiotoxicity.
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MicroRNAs in Cancer Treatment-Induced Cardiotoxicity.
Cancers (Basel). 2020 Mar 17;12(3):
Authors: Pellegrini L, Sileno S, D'Agostino M, Foglio E, Florio MC, Guzzanti V, Russo MA, Limana F, Magenta A
Abstract
Cancer treatment has made significant progress in the cure of different types of tumors. Nevertheless, its clinical use is limited by unwanted cardiotoxicity. Aside from the conventional chemotherapy approaches, even the most newly developed, i.e., molecularly targeted therapy and immunotherapy, exhibit a similar frequency and severity of toxicities that range from subclinical ventricular dysfunction to severe cardiomyopathy and, ultimately, congestive heart failure. Specific mechanisms leading to cardiotoxicity still remain to be elucidated. For instance, oxidative stress and DNA damage are considered key players in mediating cardiotoxicity in different treatments. microRNAs (miRNAs) act as key regulators in cell proliferation, cell death, apoptosis, and cell differentiation. Their dysregulation has been associated with adverse cardiac remodeling and toxicity. This review provides an overview of the cardiotoxicity induced by different oncologic treatments and potential miRNAs involved in this effect that could be used as possible therapeutic targets.
PMID: 32192047 [PubMed]
23 March 2020
15:11
Cardiotoxicity News
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T2 Mapping Identifies Early Anthracycline-Induced Cardiotoxicity in Elderly Patients With Cancer.
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T2 Mapping Identifies Early Anthracycline-Induced Cardiotoxicity in Elderly Patients With Cancer.
JACC Cardiovasc Imaging. 2020 Mar 13;:
Authors: Martin-Garcia A, Diaz-Pelaez E, Lopez-Corral L, Sanchez-Pablo C, Macias de Plasencia G, Galan-Arriola C, Sanchez-Gonzalez J, Cruz JJ, Ibanez B, Sanchez PL
PMID: 32199840 [PubMed - as supplied by publisher]
24 March 2020
12:29
Cardiotoxicity News
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Long-term cardiac outcomes of patients with HER2-positive breast cancer treated in the adjuvant lapatinib and/or trastuzumab Treatment Optimization Trial.
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Long-term cardiac outcomes of patients with HER2-positive breast cancer treated in the adjuvant lapatinib and/or trastuzumab Treatment Optimization Trial.
Br J Cancer. 2020 Mar 16;:
Authors: Eiger D, Pondé NF, Agbor-Tarh D, Moreno-Aspitia A, Piccart M, Hilbers FS, Werner O, Chumsri S, Dueck A, Kroep JR, Gomez H, Láng I, Rodeheffer RJ, Ewer MS, Suter T, de Azambuja E
Abstract
BACKGROUND: Cardiotoxicity is the most significant adverse event associated with trastuzumab (T), the main component of HER2-positive breast cancer (BC) treatment. Less is known about the cardiotoxicity of dual HER2 blockade with T plus lapatinib (L), although this regimen is used in the metastatic setting.
METHODS: This is a sub-analysis of the ALTTO trial comparing adjuvant treatment options for patients with early HER2-positive BC. Patients randomised to either T or concomitant T + L were eligible. Cardiac events (CEs) rates were compared according to treatment arm.
RESULTS: With 6.9 years of median follow-up (FU) and 4190 patients, CE were observed in 363 (8.6%): 166 (7.9%) of patient in T + L arm vs. 197 (9.3%) in T arm (OR = 0.85 [95% CI, 0.68-1.05]). During anti-HER2 treatment 270 CE (6.4%) occurred while 93 (2.2%) were during FU (median time to onset = 6.6 months [IQR = 3.4-11.7]). While 265 CEs were asymptomatic (73%), 94 were symptomatic (26%) and four were cardiac deaths (1%). Recovery was observed in 301 cases (83.8%). Identified cardiac risk factors were: baseline LVEF < 55%64%, OR 3.1 [95% CI 1.54-6.25]), diabetes mellitus (OR 1.85 [95% CI 1.25-2.75]), BMI > 30 kg/m2 (vs < 25 mg
CONCLUSIONS: Dual HER2 blockade with T + L is a safe regimen from a cardiac perspective, but cardiac-focused history for proper patient selection is crucial.
TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT00490139 (registration date: 22/06/2007); EudraCT Number: 2006-000562-36 (registration date: 04/05/2007); Sponsor Protocol Number: BIG2-06 /EGF106708/N063D.
PMID: 32203207 [PubMed - as supplied by publisher]
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Factors Influencing Adjuvant Chemotherapy and Trastuzumab Choice in Older Human Epidermal Growth Factor Receptor 2-positive Breast Cancer Patients.
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Factors Influencing Adjuvant Chemotherapy and Trastuzumab Choice in Older Human Epidermal Growth Factor Receptor 2-positive Breast Cancer Patients.
J Cancer. 2020;11(9):2602-2609
Authors: Fang Y, Wang Z, Wu J, Huang O, He J, Zhu L, Chen W, Li Y, Chen X, Shen K
Abstract
Objectives: This study aims to evaluate influence factors for adjuvant chemotherapy regimen choice on the basis of trastuzumab in older human epidermal growth factor receptor 2 (HER2)-positive breast cancer under multi-disciplinary team (MDT) modality. Materials and Methods: HER2-positive breast cancer patients aged ≥ 60 years who received breast cancer surgery between April 2013 and December 2017 in Shanghai Ruijin Hospital were retrospectively enrolled. Clinical and pathological features, MDT recommendations, administration of adjuvant treatment, cardiotoxicity, and disease outcome information were reviewed and analyzed. Results: A total of 222 older HER2-positive breast cancer patients were included and recommended to receive adjuvant chemotherapy plus trastuzumab therapy. Paclitaxel plus trastuzumab (PH, 41/222, 18.5%), docetaxel plus carboplatin and trastuzumab (TCH, 62/222, 27.9%), and antharcyclines plus cyclophosphamide followed by taxanes and trastuzumab (AC-TH, 119/222, 53.6%) were the three main regimens. Patients with T1a-b (P<0.001),<0.001),<0.001),<0.001)<0.001)
PMID: 32201530 [PubMed]
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Cancer therapy-induced cardiovascular toxicity: old/new problems and old drugs.
//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--journals.physiology.org-pb-assets-images-aps-pubmed-logo.gif Related Articles
Cancer therapy-induced cardiovascular toxicity: old/new problems and old drugs.
Am J Physiol Heart Circ Physiol. 2019 07 01;317(1):H164-H167
Authors: Beyer AM, Bonini MG, Moslehi J
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