Breast Cancer (BC) is the most common malignancy affecting women worldwide [1]. Adjuvant radiation therapy (RT) of the breast plays a vital role in BC treatment and has been shown to improve overall survival [2]. Due to increased survivorship, the cardiac sequelae that develop due to BC treatments have become more apparent. Radiation therapy, a common BC treatment, exposes the heart to radiation due to its presence in the irradiation field. Although modern RT techniques aim to reduce cardiac radiation exposure, research suggests the persistence of cardiac damage. This scoping review aims to establish the types of cardiovascular disease (CVD) that manifest post‐RT, and create a timeline for early radiation‐induced cardiotoxicity detection and surveillance. A scoping review was conducted utilizing the methodology of the Preferred Reporting Items for Systematic reviews and Meta‐Analyses extension for Scoping Reviews (PRISMA‐Scr). A literature search was conducted on MEDLINE and EMBASE in Ovid on July 29th, 2021 for papers published from 1995 to July 2021. MeSH/EMTREE terms and keywords were used for the following concepts: Breast Cancer, Radiation Therapy, Cardiovascular, Treatment Outcomes. Search strategies were optimized for each database. After removing duplicates, 1341 papers were sent to title and abstract screening, of which 276 were sent to full‐text review. 160 studies were included for final data extraction. Agreement from two reviewers was required for an article to move to the next stage of screening. Eligibility criteria included primary clinical studies reporting a cardiovascular outcome of interest for patients who underwent BC RT. Even with modern radiotherapy techniques, patients who have undergone BC RT face an increased risk of the development of cardiovascular morbidities. In the long term, the risk of cardiac disease increases with an increase in mean heart radiation dose. Early‐detection studies reveal that changes in cardiac dysfunction can be detected early on, often characterized by a decline in left ventricular ejection fraction. With most RT‐induced cardiac sequelae manifesting years after RT exposure, studies with a shorter follow‐up period often report lower CVD risk. Articles produced contrasting results regarding whether breast cancer radiation laterality increases the risk of CVD, with many indicating no difference while others concluded those with left‐sided radiation therapy have an increased risk. Detection and surveillance, with a combination of both cardiac biomarkers and imaging, is critical at an early stage for all women who have undergone BC RT. With the majority of current surveillance techniques only detecting cardiovascular damage once it is too late, early detection is a critical prerequisite in improving cardiac sequelae prediction and prevention to ultimately improve breast cancer patients’ quality of life and care. [1] Sung et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin; 72...
Our purpose was to investigate the utility of 18 F-FDG PET/MRI and serial blood work to detect early inflammatory responses and cardiac functionality changes at 1 mo after radiation therapy (RT) in patients with left-sided breast cancer. Methods: Fifteen left-sided breast cancer patients who enrolled in the RICT-BREAST study underwent cardiac PET/MRI at baseline and 1 mo after standard RT. Eleven patients received deep-inspiration breath-hold RT, whereas the others received free-breathing RT. A list-mode 18 F-FDG PET scan with glucose suppression was acquired. Myocardial inflammation was quantified by the change in 18 F-FDG SUV mean (based on body weight) and analyzed on the basis of the myocardial tissue associated with the left anterior descending, left circumflex, or right coronary artery territories. MRI assessments, including left ventricular functional and extracellular volumes (ECVs), were extracted from T1 (before and during a constant infusion of gadolinium) and cine images, respectively, acquired simultaneously during the PET acquisition. Cardiac injury and inflammation biomarker measurements of high-sensitivity troponin T, high-sensitivity C-reactive protein, and erythrocyte sedimentation rate were measured at the 1-mo follow-up and compared with preirradiation values. Results: At the 1-mo follow-up, a significant increase (10%) in myocardial SUV mean in left anterior descending segments (P 5 0.04) and ECVs in slices at the apex (6%) and base (5%) was detected (P # 0.02). Further, a significant reduction in left ventricular stroke volume (27%) was seen (P , 0.02). No significant changes in any circulating biomarkers were seen at follow-up. Conclusion: Myocardial 18 F-FDG uptake and functional MRI, including stroke volume and ECVs, were sensitive to changes at 1 mo after breast cancer RT, with findings suggesting an acute cardiac inflammatory response to RT.
Purpose: To investigate the utility of hybrid 18FDG-PET/MRI and serial blood work to detect early inflammatory response and cardiac functionality changes at one-month post-radiation therapy (RT) in patients with left-sided breast cancer.Methods: Fifteen left-sided breast cancer patients enrolled in the RICT-BREAST study underwent hybrid PET/MRI cardiac imaging at baseline and one-month after standard RT. Eleven patients received deep-inspiration breath-hold RT, while others received free-breathing RT. A list-mode 18FDG/PET scan with glucose suppression was acquired. Myocardial inflammation was quantified by the change of mean 18FDG standard uptake and analyzed based on the coronary vascular territory (left anterior descending (LAD), left circumflex or right coronary artery).MR assessments, including LV functional and extracellular volume matrices (ECV), were extracted from T1 (pre and during-constant infusion of gadolinium) and cine images, respectively, acquired simultaneously during PET acquisition. Cardiac injury and inflammation biomarker measurements of hs-TnT, hs-CRP and erythrocyte sedimentation rate were compared at the 1-month follow-up in this study.Results: At one-month follow-up, a significant increase (10%) of 18FDG/PET myocardial uptake (meanSUVbw) in LAD segments (p=0.04) and ECV in slices at the apex (6%) and base (5%) were detected (p≤0.02). Further, a significant reduction of LV stroke volume (-7%) was seen (p <0.02). No significant changes in all circulating biomarkers at follow-up were shown. Conclusions: 18FDG/PET myocardial uptake and functional MR, including SV and ECV were sensitive to changes at one-month after breast cancer RT with findings suggesting an acute cardiac inflammatory response which is an important cardiotoxicity surrogate to RT. The clinical pilot study (NCT03748030, November 16, 2018) was approved by the Western University Human Research Ethics Board (HSREB ID 112991), funded by Lawson Strategic Research Fund (R19-292).
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