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Pubblicazioni recenti - cardio-oncology
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Troponins and brain natriuretic peptides for the prediction of cardiotoxicity in cancer patients: a meta-analysis.
Eur J Heart Fail2019 Nov;():. doi: 10.1002/ejhf.1631.
Michel Lars, Mincu Raluca I, Mahabadi Amir A, Settelmeier Stephan, Al-Rashid Fadi, Rassaf Tienush, Totzeck Matthias,
Abstract
AIMS:
Cardiac biomarkers are a mainstay in diagnosis of cardiovascular disease but their role in cardio-oncology has not yet been systematically evaluated. This meta-analysis aims to determine whether cardiac troponins and (N-terminal pro) brain natriuretic peptide (BNP/NT-proBNP) predict cancer therapy-related left ventricular (LV) dysfunction.
METHODS AND RESULTS:
Scientific databases were searched for studies that assessed troponins or BNP/NT-proBNP in adult patients undergoing cancer therapy. Data from 61 trials with 5691 patients were included. Cancer therapy was associated with an increase in troponin levels [odds ratio (OR) 14.3, 95% confidence interval (CI) 6.0-34.1; n = 3049]. Patients with elevated troponins receiving chemotherapy or human epidermal growth factor receptor 2 inhibitor therapy were at higher risk for LV dysfunction (OR?11.9, 95% CI 4.4-32.1; n = 2163). Troponin had a negative predictive value of 93%. Mean BNP/NT-proBNP levels were increased in patients post-treatment (standardized mean difference 0.6, 95% CI 0.3-0.9; n = 912), but the available evidence did not consistently indicate prediction of LV dysfunction (OR 1.7, 95% CI 0.7-4.2; n = 197). ?-blocker and angiotensin-converting enzyme inhibitor therapy to mitigate cardiotoxicity during cancer therapy was associated with a decline in serum troponins (OR 4.1, 95% CI 1.7-9.8; n = 466).
CONCLUSION:
Elevated troponin levels predict LV dysfunction in patients receiving cancer therapy. Assessment of troponin levels may qualify as a screening test to identify patients who require referral to cardio-oncology units and benefit from preventive strategies. Further evidence is required for both biomarkers.
© 2019 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
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Association of Cardiac Resynchronization Therapy With Change in Left Ventricular Ejection Fraction in Patients With Chemotherapy-Induced Cardiomyopathy.
JAMA2019 11;322(18):1799-1805. doi: 10.1001/jama.2019.16658.
Singh Jagmeet P, Solomon Scott D, Fradley Michael G, Barac Ana, Kremer Kristina A, Beck Christopher A, Brown Mary W, McNitt Scott, Schleede Susan, Zareba Wojciech, Goldenberg Ilan, Kutyifa Valentina, ,
Abstract
Importance:
The incidence of chemotherapy-induced cardiomyopathy is increasing and is associated with poor clinical outcomes.
Objective:
To assess the association of cardiac resynchronization therapy (CRT) with improvement in cardiac function, as well as clinical improvement in patients with chemotherapy-induced cardiomyopathy.
Design, Setting, and Participants:
The Multicenter Automatic Defibrillator Implantation Trial-Chemotherapy-Induced Cardiomyopathy was an uncontrolled, prospective, cohort study conducted between November 21, 2014, and June 21, 2018, at 12 tertiary centers with cardio-oncology programs in the United States. Thirty patients were implanted with CRT owing to reduced left ventricular ejection fraction (LVEF?35%), New York Heart Association class II-IV heart failure symptoms, and wide QRS complex, with established chemotherapy-induced cardiomyopathy and were followed up for 6 months after CRT implantation. The date of final follow-up was February 6, 2019.
Exposures:
CRT implantation according to standard of care.
Main Outcomes and Measures:
The primary end point was change in LVEF from baseline to 6 months after initiating CRT. Secondary outcomes included all-cause mortality and change in left ventricular end-systolic volume and end-diastolic volume.
Results:
Among 30 patients who were enrolled (mean [SD] age, 64 [11] years; 26 women [87%]; 73% had a history of breast cancer; 20% had a history of lymphoma or leukemia), primary end point data were available for 26 patients and secondary end point data were available for 23 patients. Patients had nonischemic cardiomyopathy with left bundle branch block, median LVEF of 29%, and a mean QRS duration of 152 ms. Patients with CRT experienced a statistically significant improvement in mean LVEF at 6 months from 28% to 39% (difference, 10.6% [95% CI, 8.0%-13.3%]; P?
Conclusions and Relevance:
In this preliminary study of patients with chemotherapy-induced cardiomyopathy, CRT was associated with improvement in LVEF after 6 months. The findings are limited by the small sample size, short follow-up, and absence of a control group.
Trial Registration:
ClinicalTrials.gov Identifier: NCT02164721.
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Need for Multidisciplinary Research and Data-Driven Guidelines for the Cardiovascular Care of Patients With Cancer.
JAMA2019 11;322(18):1775-1776. doi: 10.1001/jama.2019.17415.
Meijers Wouter C, Moslehi Javid J,
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Pyroptosis: A new frontier in cancer.
Biomed Pharmacother2019 Nov;121():109595. doi: S0753-3322(19)35217-5.
Fang Yuan, Tian Shengwang, Pan Yutian, Li Wei, Wang Qiming, Tang Yu, Yu Tao, Wu Xi, Shi Yongkang, Ma Pei, Shu Yongqian,
Abstract
Pyroptosis is an inflammatory form of cell death triggered by certain inflammasomes, leading to the cleavage of gasdermin D (GSDMD) and activation of inactive cytokines like IL-18 and IL-1?. Pyroptosis has been reported to be closely associated to some diseases like atherosclerosis and diabetic nephropathy. Recently, some studies found that pyroptosis can influence the proliferation, invasion and metastasis of tumor, which regulated by some non-coding RNAs and other molecules. Hence, we provided an overview of morphological and molecular characteristics of pyroptosis. We also focus on mechanism of regulating pyroptosis in tumor cells as well as the potential roles of pyroptosis in cancer to explore potential diagnostic markers in cancers contributing to the prevention and treatment in cancers.
Copyright © 2019. Published by Elsevier Masson SAS.
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Comorbidities in chronic heart failure: An update from Italian Society of Cardiology (SIC) Working Group on Heart Failure.
Eur J Intern Med2019 Nov;():. doi: S0953-6205(19)30342-5.
Correale Michele, Paolillo Stefania, Mercurio Valentina, Limongelli Giuseppe, Barillà Francesco, Ruocco Gaetano, Palazzuoli Alberto, Scutinio Domenico, Lagioia Rocco, Lombardi Carolina, Lupi Laura, Magrì Damiano, Masarone Daniele, Pacileo Giuseppe, Scicchitano Pietro, Matteo Ciccone Marco, Parati Gianfranco, Tocchetti Carlo G, Nodari Savina,
Abstract
The increasing number of patients with heart failure HF and comorbidities is due to aging population and increase of life expectancy of patients with cardiovascular disease. Encouraging results derived by recent trials may suggest some comorbidities as new targets for new drugs, highlighting the need for a better understanding of the comorbidities' effects in HF patients and the need of a multidisciplinary approach for the management of chronic HF with comorbidities. We report a brief review about main cardiovascular and non-cardiovascular comorbidities in HF patients in order to update physicians and researchers engaged in the HF research or in "fight against heart failure."
Copyright © 2019 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
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Distinct IL-1?-responsive enhancers promote acute and coordinated changes in chromatin topology in a hierarchical manner.
EMBO J2019 Nov;():e101533. doi: 10.15252/embj.2019101533.
Weiterer Sinah-Sophia, Meier-Soelch Johanna, Georgomanolis Theodore, Mizi Athanasia, Beyerlein Anna, Weiser Hendrik, Brant Lilija, Mayr-Buro Christin, Jurida Liane, Beuerlein Knut, Müller Helmut, Weber Axel, Tenekeci Ulas, Dittrich-Breiholz Oliver, Bartkuhn Marek, Nist Andrea, Stiewe Thorsten, van IJcken Wilfred Fj, Riedlinger Tabea, Schmitz M Lienhard, Papantonis Argyris, Kracht Michael,
Abstract
How cytokine-driven changes in chromatin topology are converted into gene regulatory circuits during inflammation still remains unclear. Here, we show that interleukin (IL)-1? induces acute and widespread changes in chromatin accessibility via the TAK1 kinase and NF-?B at regions that are highly enriched for inflammatory disease-relevant SNPs. Two enhancers in the extended chemokine locus on human chromosome 4 regulate the IL-1?-inducible IL8 and CXCL1-3 genes. Both enhancers engage in dynamic spatial interactions with gene promoters in an IL-1?/TAK1-inducible manner. Microdeletions of p65-binding sites in either of the two enhancers impair NF-?B recruitment, suppress activation and biallelic transcription of the IL8/CXCL2 genes, and reshuffle higher-order chromatin interactions as judged by i4C interactome profiles. Notably, these findings support a dominant role of the IL8 "master" enhancer in the regulation of sustained IL-1? signaling, as well as for IL-8 and IL-6 secretion. CRISPR-guided transactivation of the IL8 locus or cross-TAD regulation by TNF?-responsive enhancers in a different model locus supports the existence of complex enhancer hierarchies in response to cytokine stimulation that prime and orchestrate proinflammatory chromatin responses downstream of NF-?B.
© 2019 The Authors. Published under the terms of the CC BY 4.0 license.
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Metabolic Imaging in Cardio-oncology.
J Cardiovasc Transl Res2019 Nov;():. doi: 10.1007/s12265-019-09927-9.
Tong Dan, Zaha Vlad G,
Abstract
Tremendous progress in cancer detection and therapy has improved survival. However, cardiovascular complications are a major source of morbidity in cancer survivors. Cardiotoxicity is currently defined by structural myocardial changes and cardiac injury biomarkers. In many instances, such changes are late and irreversible. Therefore, diagnostic modalities that can identify early alterations in potentially reversible biochemical and molecular signaling processes are of interest. This review is focused on emerging translational metabolic imaging modalities. We present in context relevant mitochondrial biology aspects that ground the development and application of these technologies for detection of cancer therapy-related cardiac dysfunction (CTRCD). The application of these modalities may improve the assessment of cardiovascular risk when anticancer treatments with a defined cardiometabolic toxic mechanism are to be used. Also, they may serve as screening tools for cardiotoxicity when novel lines of cancer therapies are applied.
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Heart failure and atrial tachyarrhythmia on abiraterone: A pharmacovigilance study.
Arch Cardiovasc Dis2019 Nov;():. doi: S1875-2136(19)30172-X.
Bretagne Marie, Lebrun-Vignes Bénédicte, Pariente Antoine, Shaffer Christian M, Malouf Gabriel G, Dureau Pauline, Potey Camille, Funck-Brentano Christian, Roden Dan M, Moslehi Javid J, Salem Joe-Elie,
Abstract
BACKGROUND:
Abiraterone and enzalutamide are recently-approved androgen deprivation therapies (ADTs) for metastatic prostate cancer, with unknown cardiac safety profiles. Abiraterone has a propensity to hypermineralocorticism on top of androgen deprivation, so might carry an additional risk for atrial tachyarrhythmia (AT) and heart failure (HF) compared with other ADTs.
AIM:
To determine if abiraterone was associated with an increased proportion of AT and HF reports among all suspected adverse drug reactions (ADRs) reported in several pharmacovigilance databases compared with enzalutamide, other ADTs and all other drugs.
METHODS:
In this observational retrospective pharmacovigilance study, we performed a disproportionality analysis of reports of suspected ADRs in men in the French pharmacovigilance database, the European pharmacovigilance database and the international pharmacovigilance database VigiBase, to evaluate the reporting odds ratios (RORs) of AT and HF for abiraterone compared with enzalutamide, other ADTs and all other drugs.
RESULTS:
In the 5,759,781 ADR reports in men in VigiBase, 55,070 pertained to ADTs. The RORs for AT for abiraterone versus enzalutamide, other ADTs and all other drugs were 4.1 (95% confidence interval 3.1-5.3), 3.7 (3-4.5) and 3.2 (2.7-3.7), respectively (P<0.0001 for all). The corresponding RORs for HF were 2.5 (2-3), 1.5 (1.3-1.7) and 2 (1.7-2.3), respectively (P<0.0001 for all). These results were concordant with the French and European pharmacovigilance databases. Mean times to AT and HF onset were shorter with abiraterone (5.2±0.8 and 4.5±0.6 months, respectively) versus other ADTs (13.3±3.2 and 9.2±1.1 months, respectively) (both P<0.05). Cases on abiraterone versus other ADTs were more frequently associated with at least two ADR terms, including AT, HF, hypokalaemia, hypertension and oedema (13.6% vs 6%; P<0.0001). For abiraterone, age, but not dose, was associated with reporting of AT and HF versus any other ADR.
CONCLUSIONS:
Compared with other ADTs, abiraterone was associated with higher reporting of AT and HF, associated with hypokalaemia, hypertension and oedema. These findings are consistent with the hypermineralocorticism induced by abiraterone, but not by other ADTs.
Copyright © 2019 Elsevier Masson SAS. All rights reserved.
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First experimental measurement of the effect of cardio-synchronous brain motion on the dose distribution during microbeam radiation therapy.
Med Phys2019 Nov;():. doi: 10.1002/mp.13899.
Duncan Mitchell, Donzelli Mattia, Pellicioli Paolo, Brauer-Krisch Elke, Davis Jeremy A, Lerch Michael L F, Rosenfeld Anatoly B, Petasecca Marco,
Abstract
PURPOSE:
Microbeam radiation therapy (MRT) is an emerging radiation oncology modality ideal for treating inoperable brain tumours. MRT employs quasi-parallel beams of low energy x-rays produced from modern synchrotrons. A tungsten-carbide multi-slit collimator (MSC) spatially fractionates the broad beam into rectangular beams. In this study the MSC creates beams 50µm wide ("peaks") separated by a centre-to-centre distance of 400µm ("valleys"). The peak to valley dose ratio (PVDR) is of critical importance to the efficacy of MRT. The underlying radiobiological advantage of MRT relies on high peak dose for tumour control and low valley dose for healthy tissue sparing. Cardio synchronous brain motion of the order 100-200 µm is comparable to microbeam width and spacing. The motion can have a detrimental effect on the PVDR, full-width at half maximum (FWHM) of the microbeams, and ultimately the dose distribution. We present the first experimental measurement of the effect of brain motion on MRT dose distribution. Dosimetry in MRT is difficult due to the high dose rate (up to 15-20kGy/s) and small field sizes.
METHODS:
A real time dosimetry system based on a single silicon strip detector (SSSD) has been developed with spatial resolution ~10µm. The SSSD was placed in a water equivalent phantom and scanned through the microbeam distribution. A monodirectional positioning stage reproduced brain motion during the acquisition. Microbeam profiles were reconstructed from the SSSD and compared with Geant4 simulation and radiochromic HD-V2 film.
RESULTS:
The SSSD is able to reconstruct dose profiles within 2µm compared to film. When brain motion is applied the SSSD shows two times increase in FWHM of profiles and 50% reduction in PVDR. This is confirmed by Geant4 and film data.
CONCLUSIONS:
Motion induced misalignment and distortion of microbeams at treatment delivery will result in a reduced PVDR and increased irradiation of additional healthy tissue compromising the radiobiological effectiveness of MRT. The SSSD was able to reconstruct dose profiles under motion conditions and predict similar effects on FWHM and PVDR as by the simulation. The SSSD is a simple to setup, real-time detector which can provide time-resolved high spatial resolution dosimetry of microbeams in MRT.
© 2019 American Association of Physicists in Medicine.
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Short length of hospitalization in patients with acute heart failure entails a high risk of readmission: True or false? Insights from the LOHRCA study.
Eur J Intern Med -
Increased reporting of fatal hepatitis associated with immune checkpoint inhibitors.
Eur J Cancer2019 Oct;123():112-115. doi: S0959-8049(19)30745-2.
Vozy Aurore, De Martin Eleonora, Johnson Douglas B, Lebrun-Vignes Bénédicte, Moslehi Javid J, Salem Joe-Elie,
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Electrophysiology Translational Considerations in Cardio-Oncology: QT and Beyond.
J Cardiovasc Transl Res2019 Oct;():. doi: 10.1007/s12265-019-09924-y.
Alomar Mohammed, Fradley Michael G,
Abstract
With improved screening and the advent of many novel therapeutics, patients with cancer are living longer and often surviving their disease. Cardiovascular complications have significant impact on both short- and long-term morbidity and mortality in these patients. While a great deal of attention has been paid to cardiomyopathy and heart failure, many other cardiotoxicities can occur, often at higher rates. Arrhythmias are a particularly common cardiovascular complication of cancer therapeutics and can range from benign to life threatening. Moreover, management of these rhythm disturbances can be challenging in cancer patients for various reasons including drug interactions, as well as underlying hematologic and metabolic disturbances. In this review, we describe the most common therapeutics associated with arrhythmias in cancer patients and provide a discussion about the potential basic and translational mechanisms leading to the development of the various rhythm disturbances which may help to guide prevention and treatment decisions. Clinicaltrials.gov Identifier: NCT02928497.
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MFP-Unet: A novel deep learning based approach for left ventricle segmentation in echocardiography.
Phys Med2019 Oct;67():58-69. doi: S1120-1797(19)30450-8.
Moradi Shakiba, Oghli Mostafa Ghelich, Alizadehasl Azin, Shiri Isaac, Oveisi Niki, Oveisi Mehrdad, Maleki Majid, Dhooge Jan,
Abstract
Segmentation of the Left ventricle (LV) is a crucial step for quantitative measurements such as area, volume, and ejection fraction. However, the automatic LV segmentation in 2D echocardiographic images is a challenging task due to ill-defined borders, and operator dependence issues (insufficient reproducibility). U-net, which is a well-known architecture in medical image segmentation, addressed this problem through an encoder-decoder path. Despite outstanding overall performance, U-net ignores the contribution of all semantic strengths in the segmentation procedure. In the present study, we have proposed a novel architecture to tackle this drawback. Feature maps in all levels of the decoder path of U-net are concatenated, their depths are equalized, and up-sampled to a fixed dimension. This stack of feature maps would be the input of the semantic segmentation layer. The performance of the proposed model was evaluated using two sets of echocardiographic images: one public dataset and one prepared dataset. The proposed network yielded significantly improved results when comparing with results from U-net, dilated U-net, Unet++, ACNN, SHG, and deeplabv3. An average Dice Metric (DM) of 0.953, Hausdorff Distance (HD) of 3.49, and Mean Absolute Distance (MAD) of 1.12 are achieved in the public dataset. The correlation graph, bland-altman analysis, and box plot showed a great agreement between automatic and manually calculated volume, area, and length.
Copyright © 2019 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.
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Ameliorative effect of rosiglitazone, a peroxisome proliferator gamma agonist on adriamycin-induced cardio toxicity via suppressing oxidative stress and apoptosis.
IUBMB Life2019 Oct;():. doi: 10.1002/iub.2190.
Zhang Lingling, Wu Ping, Zhang Luyan, SreeHarsha Nagaraja, Mishra Anurag, Su Xinyou,
Abstract
We investigated the rosiglitazone (RSG) effect on adriamycin (ADM)-induced cardio toxicity in experimental animals. Forty adult Wistar male rats were separated into four groups as follows: normal control; RSG (10 mg/kg)-treated; ADM (10 mg/kg)-administered; and ADM (10 mg/kg)?+?RSG (10 mg/kg)-treated. Serum lipid level, different biochemical biomarkers, histological analysis, and nuclear factor erythroid 2-related factor/heme oxygenase-1 (Nrf2/HO-1), Caspase 3, B-cell lymphoma 2 (Bcl-2), and Bax gene expression were assessed in serum and cardiac tissue samples. Our results show that RSG treatment in ADM-administered animals significantly diminished low-density lipoprotein cholesterol, triglyceride, and total cholesterol, and increases high-density lipoprotein cholesterol (HDL-c) in comparison with the ADM group. RSG treatment reduced the effect of ADM administration on cardiac dysfunction markers such as cardiac troponin T Creatine Kinase-MB, aspartate aminotransferase, and lactate dehydrogenase, showing the amelioration of cardio toxicity in ADM-administered rats. Additionally, RSG treatment significantly decreased the level of malondialdehyde and nitric oxide in cardiovascular tissue. RSG-treated rats in combination with ADM likewise showed a significant increase in reduced glutathione, superoxide dismutase, catalase content, and the activity of glutathione peroxidase (GPx) as compared with ADM group. Moreover, RSG treatment in ADM rats significantly increased an Nrf2 and HO-1 expression in comparison with ADM group. While in apoptosis parameters, RSG treatment in ADM rats significantly diminished a cleaved caspase-3 and Bax expression as well as expanded Bcl-2 expression when contrasted with ADM group of rats. In conclusion, RSG is capable of protecting heart toxicity in ADM-treated animals through defensive effects on oxidative stress and biochemical markers.
© 2019 International Union of Biochemistry and Molecular Biology.
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Dose to the cardio-pulmonary system and treatment-induced electrocardiogram abnormalities in locally advanced non-small cell lung cancer.
Clin Transl Radiat Oncol2019 Nov;19():96-102. doi: 10.1016/j.ctro.2019.09.003.
Hotca Alexandra, Thor Maria, Deasy Joseph O, Rimner Andreas,
Abstract
Introduction:
High dose radiotherapy (RT) has been associated with unexpectedly short survival times for locally advanced Non-Small Cell Lung Cancer (LA-NSCLC) patients. Here we tested the hypothesis that cardiac substructure dose is associated with electrocardiography (ECG) assessed abnormalities after RT for LA-NSCLC.
Materials and methods:
Pre- and post-RT ECGs were analyzed for 155 LA-NSCLC patients treated to a median of 64?Gy in 1.8-2.0?Gy fractions using intensity-modulated RT plus chemotherapy (concurrent/sequential: 64%/36%) between 2004 and 2014. ECG abnormalities were classified as new Arrhythmic, Ischemic/Pericardial, or Non-specific ( or ) events. Abnormalities were modeled as time to ECG events considering death a competing risk, and the variables considered for analysis were fractionation-corrected dose-volume metrics (?/??=?3?Gy) of ten cardio-pulmonary structures (aorta, heart, heart chambers, inferior and superior vena cava, lung, pulmonary artery) and 15 disease, patient and treatment characteristics. Each abnormality was modelled using bootstrapping and a candidate predictor was suggested by a median multiple testing-adjusted p-value ?0.05 across the 1000 generated samples. Forward-stepwise multivariate analysis was conducted in case of more than one candidate.
Results:
At a median of eight months post-RT, the rate of and was 66%, 35%, and 67%. Both and were associated with worse performance status (p?=?0.007, 0.03), while a higher superior vena cava minimum dose was associated with (p?=?0.002).
Conclusion:
This study suggests that higher radiation doses to the cardio-pulmonary system lead to non-specific ECG abnormalities. Reducing dose to this system, along with effective tumor control, is likely to decrease radiation-induced cardiac toxicity.
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[Benefits of physical activity for cancer patients].
Rev Prat2019 Apr;69(4):438-443.
Ancellin Raphaëlle,
Abstract
The prescription of physical activity for patients living with a long-term condition has been enshrined in legislation since 2016. The French National Cancer Institute published a literature review on the expected effects of physical activity in patients living with cancer. The benefits are prevention or correction of physical deconditioning, a preservation and/or a normalization of body composition, a reduction of cancerrelated fatigue, an overall quality-of-life improvement, the improvement of treatments tolerance and their medium and long-term effects, an increased life expectancy and a lower risk of cancer recurrence. These effects can be observed for a mixed physical activity program -cardio respiratory fitness and muscular strength-, with moderate to vigorous intensity activity, 30 minutes a day at least 5 days a week. The benefits are all the more important as physical activity starts early. Health professionals have an important part to play in helping patients engage in physical activity, with a regular even moderate practice which is always beneficial as compared with sedentary behaviors.
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Effects of imperatorin in the cardiovascular system and cancer.
Biomed Pharmacother2019 Oct;120():109401. doi: S0753-3322(19)33410-9.
Nasser M I, Zhu Shuoji, Hu Haiyan, Huang Huanlei, Guo Minghui, Zhu Ping,
Abstract
Patients with cancer survivors are at increased risk of cardiovascular disease(CVD). Cardio-oncology has developed as a new discipline with the advances in cancer treatment. There are many new challenges for the clinician and a new frontier for research and investigation. There is an urgent need for further study on the prevention of cardiovascular toxicity. Imperatorin (IMP) is a natural form of coumarin and extract from several plants with diver's pharmacokinetic effects, including antioxidant and anti-inflammatory properties. This review focus on the molecular mechanisms and pharmacological effects of Imperatorin maybe provide potential cancer and cardiovascular protection that targets IMP. Further studies are required to elucidate the entire spectrum of cytotoxic activities of these compounds to validate and expand their preclinical and clinical applications and to clarify the potential role of IMP.
Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.
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Pragmatic randomised clinical trial of proton versus photon therapy for patients with non-metastatic breast cancer: the Radiotherapy Comparative Effectiveness (RadComp) Consortium trial protocol.
BMJ Open2019 Oct;9(10):e025556. doi: 10.1136/bmjopen-2018-025556.
Bekelman Justin E, Lu Hien, Pugh Stephanie, Baker Kaysee, Berg Christine D, de Gonzalez Amy Berrington, Braunstein Lior Z, Bosch Walter, Chauhan Cynthia, Ellenberg Susan, Fang L Christine, Freedman Gary M, Hahn Elizabeth A, Haffty B G, Khan Atif J, Jimenez Rachel B, Kesslering Christy, Ky Bonnie, Lee Choonsik, Lu Hsiao-Ming, Mishra Mark V, Mullins C Daniel, Mutter Robert W, Nagda Suneel, Pankuch Mark, Powell Simon N, Prior Fred W, Schupak Karen, Taghian Alphonse G, Wilkinson J Ben, MacDonald Shannon M, Cahlon Oren, ,
Abstract
INTRODUCTION:
A broad range of stakeholders have called for randomised evidence on the potential clinical benefits and harms of proton therapy, a type of radiation therapy, for patients with breast cancer. Radiation therapy is an important component of curative treatment, reducing cancer recurrence and extending survival. Compared with photon therapy, the international treatment standard, proton therapy reduces incidental radiation to the heart. Our overall objective is to evaluate whether the differences between proton and photon therapy cardiac radiation dose distributions lead to meaningful reductions in cardiac morbidity and mortality after treatment for breast cancer.
METHODS:
We are conducting a large scale, multicentre pragmatic randomised clinical trial for patients with breast cancer who will be followed longitudinally for cardiovascular morbidity and mortality, health-related quality of life and cancer control outcomes. A total of 1278 patients with non-metastatic breast cancer will be randomly allocated to receive either photon or proton therapy. The primary outcomes are major cardiovascular events, defined as myocardial infarction, coronary revascularisation, cardiovascular death or hospitalisation for unstable angina, heart failure, valvular disease, arrhythmia or pericardial disease. Secondary endpoints are urgent or unanticipated outpatient or emergency room visits for heart failure, arrhythmia, valvular disease or pericardial disease. The Radiotherapy Comparative Effectiveness (RadComp) Clinical Events Centre will conduct centralised, blinded adjudication of primary outcome events.
ETHICS AND DISSEMINATION:
The RadComp trial has been approved by the institutional review boards of all participating sites. Recruitment began in February 2016. Current version of the protocol is A3, dated 08 November 2018. Dissemination plans include presentations at scientific conferences, scientific publications, stakeholder engagement efforts and presentation to the public via lay media outlets.
TRIAL REGISTRATION NUMBER:
NCT02603341.
© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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Coronary Artery Dose-Volume Parameters Predict Risk of Calcification After Radiation Therapy.
J Cardiovasc Imaging2019 Oct;27(4):268-279. doi: 10.4250/jcvi.2019.27.e38.
Milgrom Sarah A, Varghese Bibin, Gladish Gregory W, Choi Andrew D, Dong Wenli, Patel Zarana S, Chung Caroline C, Rao Arvind, Pinnix Chelsea C, Gunther Jillian R, Dabaja Bouthaina S, Lin Steven H, Hoffman Karen E, Huff Janice L, Slagowski Jordan, Abe Jun Ichi, Iliescu Cezar A, Banchs Jose, Yusuf Syed Wamique, Lopez-Mattei Juan C,
Abstract
BACKGROUND:
Radiation exposure increases the risk of coronary artery disease (CAD). We explored the association of CAD with coronary artery dose-volume parameters in patients treated with 3D-planned radiation therapy (RT).
METHODS:
Patients who received thoracic RT and were evaluated by cardiac computed tomography ? 1 year later were included. Demographic data and cardiac risk factors were retrospectively collected. Dosimetric data (mean heart dose, d, d, V - V?) were collected for the whole heart and for each coronary artery. A coronary artery calcium (CAC) Agatston score was calculated on a per-coronary basis and as a total score. Multivariable generalized linear mixed models were generated. The predicted probabilities were used for receiver operating characteristic analyses.
RESULTS:
Twenty patients with a median age of 53 years at the time of RT were included. Nine patients (45%) had ? 3/6 conventional cardiac risk factors. Patients received RT for breast cancer (10, 50%), lung cancer (6, 30%), or lymphoma/myeloma (4, 20%) with a median dose of 60 Gy. CAC scans were performed a median of 32 months after RT. CAC score was significantly associated with radiation dose and presence of diabetes. In a multivariable model adjusted for diabetes, segmental coronary artery dosimetric parameters (d, d, V??, V?? V??, V??, V??, and V?) were significantly associated with CAC score > 0. V?? had the highest area under the ROC curve (0.89, 95% confidence interval, 0.80-0.97).
CONCLUSIONS:
Coronary artery radiation exposure is strongly correlated with subsequent segmental CAC score. Coronary calcification may occur soon after RT and in individuals with conventional cardiac risk factors.
Copyright © 2019 Korean Society of Echocardiography.
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Outcomes following percutaneous coronary intervention in patients with cancer.
Int J Cardiol2019 Sep;():. doi: S0167-5273(19)32714-7.
Quintana Raymundo A, Monlezun Dominique J, Davogustto Giovanni, Saenz Humberto R, Lozano-Ruiz Francisco, Sueta Daisuke, Tsujita Kenichi, Landes Uri, Denktas Ali E, Alam Mahboob, Paniagua David, Addison Daniel, Jneid Hani,
Abstract
BACKGROUND:
Randomized clinical trials demonstrated the benefits of percutaneous coronary interventions (PCI) in diverse clinical settings. Patients with cancer were not routinely included in these studies.
METHODS/RESULTS:
Literature search of PubMed, Cochrane, Medline, SCOPUS, EMBASE, and ClinicalTrials was conducted to identify studies that assessed one-year all-cause, cardiovascular and non-cardiovascular mortality in patients with historical or active cancer. Using the random effects model, we computed risk ratios (RRs) and standardized mean differences and their 95% confidence intervals for the dichotomous and continuous measures and outcomes, respectively. Of 171 articles evaluated in total, 5 eligible studies were included in this meta-analysis. In total, 33,175 patients receiving PCI were analyzed, of whom 3323 patients had cancer and 29,852 no cancer history. Patients in the cancer group had greater all-cause mortality [RR 2.22 (1.51-3.26; p?
CONCLUSIONS:
Patients with cancer undergoing PCI have worse mid-term outcomes compared to non-cancer patients. Cancer patients should be managed by a multi-specialist team, in an effort to close the mortality gap.
Copyright © 2019 Elsevier B.V. All rights reserved.
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