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09:59 CET
EU 1 - Cardiovascular effects after radiotherapy for breast cancer: the European MEDIRAD Project
EuroSafe Imaging Oncologic Imaging Cardiac Breast Physics in Medical Imaging
Wednesday, February 27, 08:30 - 10:00
Room: N
Type of session: EuroSafe Imaging Session
Topic: EuroSafe Imaging, Oncologic Imaging, Cardiac, Breast, Physics in Medical Imaging
Moderators: A. Crijns (Groningen/NL), G. Frija (Paris/FR)

A-0014
08:30
Chairpersons' introduction (part 1)
A. Crijns; Groningen/NL
Learning Objectives

1. To learn about major cardiovascular events after radiotherapy for breast cancer.
2. To understand the importance of assessing their relationship with radiation dose to cardiac substructures.
3. To appreciate the potential of imaging biomarkers for their early detection and their role in prevention strategies.

Abstract

Radiation-induced major cardiac events (MCEs) are becoming increasingly relevant for breast cancer (BC) patients, affecting the quality of life and increasing morbidity and mortality. Information regarding the relationship between radiation dose to cardiac substructures and MCEs and their early subclinical precursor cardiovascular effects is needed to develop preventive strategies for radiation-induced MCEs. In this session, current knowledge of dose-effect relationships will be discussed as well as which important information is still lacking. The European MEDIRAD project comprises a multicenter retrospective cohort study aiming at the development and external validation of prediction models for MCEs. In addition, a prospective multicenter study for identification of early subclinical cardiovascular effects with three different cardiac imaging modalities; echocardiography, cardiac MRI and cardiac CT is ongoing. We will present how the European MEDIRAD project provides the data needed for the development of individualised preventive strategies for radiation-induced MCEs. Finally, the technical issues of cardiac CT and MRI in detecting early subclinical morphological and/or functional cardiovascular effects will be discussed.

A-0015
08:33
Chairpersons' introduction (part 2)
G. Frija; Paris/FR
Learning Objectives

1. To learn about major cardiovascular events after radiotherapy for breast cancer.
2. To understand the importance of assessing their relationship with radiation dose to cardiac substructures.
3. To appreciate the potential of imaging biomarkers for their early detection and their role in prevention strategies.

Abstract

MEDIRAD (Implications of Medical Low Dose Radiation Exposure) is a multidisciplinary, cross-cutting project funded under the Euratom research and training programme 2014-2018 under grant agreement No. 662287. The four-year MEDIRAD project kicked off in June 2017 and is led by the European Institute for Biomedical Imaging Research (EIBIR). The consortium brings together a wide range of expertise, with 33 partners from 14 European countries, and involves research groups that focus on radiology, nuclear medicine, radiotherapy, dosimetry, epidemiology, biology, bioinformatics, modelling, radiation protection, and public health. MEDIRAD has three major operational objectives. Improving organ dose estimation and registration; evaluating and understanding the mechanisms of the effects of medical radiation exposure, focusing on two outcomes of public health relevance (cardiovascular effects of radiotherapy in breast cancer treatment and cancer risk following CT scanning of children and adolescents); and, developing science-based policy recommendations for the effective protection of patients, workers, and the general public. This session will focus on cardiovascular effects after radiotherapy for breast cancer and introduce the Early-Heart Study developed under work package 4 of the MEDIRAD project.

A-0016
08:36
Overview of dose-effect relationships and their use in strategies for prevention of cardiovascular effects after radiotherapy for breast cancer
A. Crijns; Groningen/NL
Learning Objectives

1. To learn about the increased risk of various major cardiac events after incidental exposure of the heart during breast radiotherapy.
2. To understand that multivariable prediction models are needed describing the relationship between radiation dose to cardiac substructures and (early) cardiovascular effects.
3. To appreciate the role of modern cardiac imaging techniques in providing detailed information regarding early cardiovascular effects after radiotherapy.

Abstract

Breast cancer (BC) radiotherapy leads to incidental cardiac irradiation, resulting in an increased risk of various major cardiac events (MCEs). The risk of a MCEs increases linearly by 7.4% per Gray of the mean heart dose. Recent studies have shown that MCEs may already appear within 5-10 years of radiotherapy. Due to an increased incidence of BC in Europe and a continuously improving survival rate, the prevalence of BC survivors at risk of MCEs is also growing. Information regarding the relationship between radiation dose to cardiac substructures and MCEs is scarce. Knowledge about early subclinical cardiovascular effects (ESCEs) induced by radiotherapy that eventually develop into MCEs is also largely lacking. We need this information to optimise radiation dose distributions as a primary preventive strategy. In addition, we need tools to identify BC patients -already treated with radiotherapy- who have a high risk of future treatment-related MCEs. These patients may benefit from secondary preventive strategies. Finally, information on potential targets for developing strategies to prevent or delay progression into clinically apparent is not currently available. The European MEDIRAD Project; Modern imaging techniques such as echocardiography, cardiac MRI and cardiac CT can be used to identify morphological and functional ESCEs, considered risk factors for developing MCEs. This information will provide better insight into the biological mechanisms of radiation-induced MCE and may provide potential targets for secondary prevention. In addition, by relating imaging-derived ESCEs and/or MCEs to local radiation dose, prediction models can be developed to optimise radiation planning techniques.

08:52
A-0017
08:57
Optimisation of multivariable prediction models for major cardiac events after radiotherapy for breast cancer
D. S. Spoor; Groningen/NL
Learning Objectives

1. To appreciate how the MEDIRAD-BRACE study will provide optimised multivariable prediction models for major cardiac events.
2. To learn that optimal prevention of radiation-induced major cardiac events requires early detection/imaging biomarkers.

Abstract

The relationship between radiation dose to the heart in breast cancer radiotherapy (RT) and various major cardiac events (MCEs) can be described with normal tissue complication probability (NTCP) models. Previous studies showed the predictive value of the mean heart dose (MHD) for the risk of acute coronary events (ACE). Recent studies suggest that the dose delivered to cardiac substructures, like the left ventricle, might be better predictors of MCEs. Furthermore, preliminary results of ongoing work suggest that radiation dose to coronary arteries, particularly the left anterior descending artery, may have superior predictive value. More accurate risk estimations for MCEs requires improved NTCP-models, which requires large retrospective cohort studies with sufficient length of follow-up to capture sufficient numbers of cardiac events.MEDIRAD-BRACE is an international multicenter retrospective cohort study. The study will include 7000 female breast cancer patients treated with primary surgery and postoperative RT treated from 2005 to 2014 and who were aged 40-75 years at a time of RT start. A test cohort of 5000 patients will be used to develop NTCP-models for MCEs, which will be validated using a validation cohort consisting of 2000 patients. The primary endpoint of the study is an ACE after completion of treatment, and secondary endpoint comprises other MCEs. The resulting models can be used to identify patients at increased risk for MCE, which allows for the development of primary and secondary preventive measures. Moreover, NTCP-models may be further improved by incorporating imaging-derived subclinical cardiac effects that precede MCE. This is studied in MEDIRAD-EARLY HEART.

09:13
A-0018
09:18
The MEDIRAD Early-Heart study
S. Jacob; Fontenay aux Roses/FR
Learning Objectives

1. To appreciate that there is already some information from cardiac imaging studies regarding early cardiovascular effects after breast cancer radiotherapy.
2. To learn how the MEDIRAD Early-Heart study will provide information regarding imaging biomarkers of early cardiovascular effects after radiotherapy for breast cancer.
3. To understand that cardiac imaging can provide clues for underlying mechanisms of radiation-induced major cardiac events.

Abstract

Radiotherapy (RT) plays a major role in breast cancer (BC) treatment. However, BC RT can lead to incidental irradiation of the heart, resulting in cardiac complications with an increased risk of various heart diseases arising many years after RT. Long before the onset of clinically significant late cardiac complications, subclinical cardiac changes may occur over months or years after RT that can be detected using anatomical and functional cardiac imaging. Therefore, detecting early signs of cardiotoxicity and determining the relationship between radiation dose to specific cardiac structures and subclinical cardiac changes is crucial for primary/secondary prevention. In the frame of the MEDIRAD European project, the EARLY-HEART study was launched in 2017. This five European centres prospective cohort study will include approximately 250 unilateral BC women aged 40-75 years treated with RT without chemotherapy and followed for two years. Baseline (before RT) and follow-up data (6 and 24 months after RT) include cardiac imaging measurements: myocardial deformation is evaluated with myocardial strain imaging (2D-speckle-tracking echocardiography); cardiac magnetic resonance imaging is performed to detect subtle changes in cardiac function and structure; cardiac computed tomography is performed to evaluate coronary artery lesions. Radiation exposure to cardiac structures based on 3D- dosimetry is precisely evaluated for all patients. Dose-response relationship will allow modelling radiation-induced occurrence and evolution of subclinical cardiac lesions to develop early cardiotoxicity prediction models. Based on emerging research in advanced imaging modalities, this study will allow enhanced detection and prediction of early radiotherapy-induced cardiotoxicity and patients’ care.

09:34
A-0019
09:39
Imaging biomarkers of cardiovascular effects of incidental cardiac radiation
E. Mousseaux; Paris/FR
Learning Objectives

1. To appreciate how radiation-induced coronary artery lesions can be studied by cardiac CT.
2. To understand how MRI can be used to evaluate myocardial tissues abnormalities induced by incidental cardiac radiation, including morphology, function and tissue abnormalities.

Abstract

Since Radiotherapy (RT) has been linked to cardiac diseases, detection of early signs of radiotherapy-induced cardiotoxicity (RTIC) is crucial and challenging for prevention. To identify and validate cardiac imaging biomarkers of RTIC arising within two years after breast cancer RT. CT and MRI will be done at baseline, and at RT+6 months (MRI), and RT+24 months (CT+MRI) during follow-up. By using MRI, in association to conventional ventricular function analysis of both ventricles, myocardial strain (deformation) will be quantified by studying cavity contours length changes (Δl/l°) during the cardiac cycle in each of four cardiac chambers. In addition, after myocardial T1 estimation of the left ventricle before and after gadolinium injection, derived indices of intra- and extra-cellular lesions will be calculated since RT is likely to modify components of these two compartments (cell destruction, inflammation and/or appearance of interstitial fibrosis). Cardiac CT will also be performed to evaluate coronary artery, valves and pericardium lesions by estimating local and global calcium score with a non-enhanced acquisition, and by subjectively analysed all these structures with enhanced acquisitions before and after RT. All analysis will be done in a core lab without knowledge of any possible clinical events that may occur and of information regarding the site of a tumour and RT procedures. Based on emerging results in CT and MRI to analyse sensitive biomarkers of cardiac lesions, hypotheses of the study are that early signs of RTIC could be detected to predict irreversible cardiotoxicity better and to improve patients’ care.

09:55
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