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      Cardiovascular disease incidence after internal mammary chain irradiation and anthracycline-based chemotherapy for breast cancer

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          Abstract

          Background

          Improved breast cancer (BC) survival and evidence showing beneficial effects of internal mammary chain (IMC) irradiation underscore the importance of studying late cardiovascular effects of BC treatment.

          Methods

          We assessed cardiovascular disease (CVD) incidence in 14,645 Dutch BC patients aged <62 years, treated during 1970–2009. Analyses included proportional hazards models and general population comparisons.

          Results

          CVD rate-ratio for left-versus-right breast irradiation without IMC was 1.11 (95% CI 0.93–1.32). Compared to right-sided breast irradiation only, IMC irradiation (interquartile range mean heart doses 9–17 Gy) was associated with increases in CVD rate overall, ischaemic heart disease (IHD), heart failure (HF) and valvular heart disease (hazard ratios (HRs): 1.6–2.4). IHD risk remained increased until at least 20 years after treatment. Anthracycline-based chemotherapy was associated with an increased HF rate (HR = 4.18, 95% CI 3.07–5.69), emerging <5 years and remaining increased at least 10–15 years after treatment. IMC irradiation combined with anthracycline-based chemotherapy was associated with substantially increased HF rate (HR = 9.23 95% CI 6.01–14.18), compared to neither IMC irradiation nor anthracycline-based chemotherapy.

          Conclusions

          Women treated with anthracycline-based chemotherapy and IMC irradiation (in an older era) with considerable mean heart dose exposure have substantially increased incidence of several CVDs. Screening may be appropriate for some BC patient groups.

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          Most cited references23

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          Estimation of failure probabilities in the presence of competing risks: new representations of old estimators.

          A topic that has received attention in both the statistical and medical literature is the estimation of the probability of failure for endpoints that are subject to competing risks. Despite this, it is not uncommon to see the complement of the Kaplan-Meier estimate used in this setting and interpreted as the probability of failure. If one desires an estimate that can be interpreted in this way, however, the cumulative incidence estimate is the appropriate tool to use in such situations. We believe the more commonly seen representations of the Kaplan-Meier estimate and the cumulative incidence estimate do not lend themselves to easy explanation and understanding of this interpretation. We present, therefore, a representation of each estimate in a manner not ordinarily seen, each representation utilizing the concept of censored observations being 'redistributed to the right.' We feel these allow a more intuitive understanding of each estimate and therefore an appreciation of why the Kaplan-Meier method is inappropriate for estimation purposes in the presence of competing risks, while the cumulative incidence estimate is appropriate.
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            Prevention and Monitoring of Cardiac Dysfunction in Survivors of Adult Cancers: American Society of Clinical Oncology Clinical Practice Guideline.

            Purpose Cardiac dysfunction is a serious adverse effect of certain cancer-directed therapies that can interfere with the efficacy of treatment, decrease quality of life, or impact the actual survival of the patient with cancer. The purpose of this effort was to develop recommendations for prevention and monitoring of cardiac dysfunction in survivors of adult-onset cancers. Methods Recommendations were developed by an expert panel with multidisciplinary representation using a systematic review (1996 to 2016) of meta-analyses, randomized clinical trials, observational studies, and clinical experience. Study quality was assessed using established methods, per study design. The guideline recommendations were crafted in part using the Guidelines Into Decision Support methodology. Results A total of 104 studies met eligibility criteria and compose the evidentiary basis for the recommendations. The strength of the recommendations in these guidelines is based on the quality, amount, and consistency of the evidence and the balance between benefits and harms. Recommendations It is important for health care providers to initiate the discussion regarding the potential for cardiac dysfunction in individuals in whom the risk is sufficiently high before beginning therapy. Certain higher risk populations of survivors of cancer may benefit from prevention and screening strategies implemented during cancer-directed therapies. Clinical suspicion for cardiac disease should be high and threshold for cardiac evaluation should be low in any survivor who has received potentially cardiotoxic therapy. For certain higher risk survivors of cancer, routine surveillance with cardiac imaging may be warranted after completion of cancer-directed therapy, so that appropriate interventions can be initiated to halt or even reverse the progression of cardiac dysfunction.
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              Regional Nodal Irradiation in Early-Stage Breast Cancer.

              Most women with breast cancer who undergo breast-conserving surgery receive whole-breast irradiation. We examined whether the addition of regional nodal irradiation to whole-breast irradiation improved outcomes.
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                Author and article information

                Contributors
                +31 20 512 2483 , f.v.leeuwen@nki.nl
                Journal
                Br J Cancer
                Br. J. Cancer
                British Journal of Cancer
                Nature Publishing Group UK (London )
                0007-0920
                1532-1827
                1 August 2018
                1 August 2018
                14 August 2018
                : 119
                : 4
                : 408-418
                Affiliations
                [1 ]GRID grid.430814.a, Epidemiology, , Netherlands Cancer Institute, ; Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
                [2 ]ISNI 000000040459992X, GRID grid.5645.2, Department of Medical Oncology, , Erasmus MC - Cancer Institute, ; Groene Hilledijk 301, 3075 EA Rotterdam, The Netherlands
                [3 ]ISNI 0000 0000 9558 4598, GRID grid.4494.d, Medical Oncology, , University Medical Center Groningen, ; Hanzeplein 1, 9213 GZ Groningen, The Netherlands
                [4 ]ISNI 0000 0004 1936 8948, GRID grid.4991.5, Nuffield Department of Population Health, , University of Oxford, ; Old Road Campus, Oxford, OX3 7LF UK
                [5 ]ISNI 0000 0004 1936 8948, GRID grid.4991.5, Medical Research Council Population Health Research Unit, Nuffield Department of Population Health, , University of Oxford, ; Old Road Campus, Oxford, OX3 7LF UK
                [6 ]ISNI 000000040459992X, GRID grid.5645.2, Radiation Oncology, , Erasmus MC - Cancer Institute, ; Groene Hilledijk 301, 3075 EA Rotterdam, The Netherlands
                [7 ]GRID grid.430814.a, Medical Oncology, , Netherlands Cancer Institute, ; Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
                [8 ]GRID grid.430814.a, Surgery, , Netherlands Cancer Institute, ; Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
                [9 ]GRID grid.430814.a, Radiation Oncology, , Netherlands Cancer Institute, ; Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
                Article
                159
                10.1038/s41416-018-0159-x
                6133926
                30065254
                279ddc3c-faac-4d29-ae49-dc0470e555ae
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 9 November 2017
                : 14 April 2018
                : 7 June 2018
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100004622, KWF Kankerbestrijding (Dutch Cancer Society);
                Award ID: NKI 2008-3994
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/100003262, Pink Ribbons Project;
                Award ID: 2012.WO39.C143
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100000289, Cancer Research UK (CRUK);
                Award ID: C8225/A21133
                Award ID: MC_U137686858
                Award ID: C8225/A21133
                Award ID: MC_U137686858
                Award ID: C8225/A21133
                Award ID: MC_U137686858
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100000274, British Heart Foundation (BHF);
                Award ID: RE/13/1/30181
                Award ID: MC_U137686858
                Award ID: MC_U137686858
                Award ID: RE/13/1/30181
                Award ID: MC_U137686858
                Award Recipient :
                Categories
                Article
                Custom metadata
                © Cancer Research UK 2018

                Oncology & Radiotherapy
                breast cancer,epidemiology
                Oncology & Radiotherapy
                breast cancer, epidemiology

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