Cancer therapy-related cardiac dysfunction after radiation therapy for breast cancer: results from the BACCARAT cohort study
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SUBMITTER: Honaryar M
PROVIDER: S-EPMC11345963 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:BackgroundRadiotherapy (RT) for breast cancer presents a benefit in terms of reducing local recurrence and deaths resulting from breast cancer but it can lead to secondary effects due to the presence of neighboring cardiac normal tissues within the irradiation field. Breast RT has been shown to be associated with long-term increased risk of heart failure, coronary artery disease, myocardial infarction and finally cardiovascular death more than 10 years after RT. However, there is still a lack of knowledge for early cardiotoxicity induced by breast RT that can appear long before the onset of clinically significant cardiac events. Based on a 2-year follow-up prospective cohort of patients treated with breast RT, the BACCARAT (BreAst Cancer and CArdiotoxicity Induced by RAdioTherapy) study aims to enhance knowledge on detection and prediction of early subclinical cardiac dysfunction and lesions induced by breast RT and on biological mechanisms potentially involved, based on functional and anatomical cardiac imaging combined with simultaneous assessment of multiple circulating biomarkers and accurate heart dosimetry.Methods/designBACCARAT study consists in a monocentric prospective cohort study that will finally include 120 women treated with adjuvant 3D CRT for breast cancer, and followed for 2 years after RT. Women aged 50 to 70 years, treated for breast cancer and for whom adjuvant 3D CRT is indicated, without chemotherapy are eligible for the study. Baseline (before RT) and follow-up data include measurements of functional myocardial dysfunction including strain and strain rate based on 2D-speckle tracking echocardiography, anatomical coronary lesions including description of plaques in segments of coronary arteries based on Coronary computed tomography angiography, and a wide panel of circulating biomarkers. The absorbed dose is evaluated for the whole heart and its substructures, in particular the coronary arteries. Analysis on occurrence and evolution of subclinical cardiac lesions and biomarkers will be performed and completed with dose-response relationship. Multivariate model of normal tissue complication probability (NTCP) will also be proposed.DiscussionTools and results developed in the BACCARAT study should allow improving prediction and prevention of potential lesions to cardiac normal tissues surrounding tumors and ultimately enhance patients' care and quality of life.Trial registrationClinicalTrials.gov: NCT02605512.
| S-EPMC4823906 | biostudies-literature
Project description:BACKGROUND:Breast cancer (BC) radiotherapy (RT) can induce cardiotoxicity, with adverse events often observed many years after BC RT. Subclinical left ventricular (LV) dysfunction can be detected early after BC RT with global longitudinal strain (GLS) measurement based on 2D speckle-tracking echocardiography. This 6-month follow-up analysis from the BACCARAT prospective study aimed to investigate the association between cardiac radiation doses and subclinical LV dysfunction based on GLS reduction. METHODS:The patient study group consisted of 79 BC patients (64 left-sided BC, 15 right-sided BC) treated with RT without chemotherapy. Echocardiographic parameters, including GLS, were measured before RT and 6 months post-RT. The association between subclinical LV dysfunction, defined as GLS reduction > 10%, and radiation doses to whole heart and the LV were performed based on logistic regressions. Non-radiation factors associated with subclinical LV dysfunction including age, BMI, hypertension, hypercholesterolemia and endocrine therapy were considered for multivariate analyses. RESULTS:A mean decrease of 6% in GLS was observed (- 15.1% ± 3.2% at 6 months vs. - 16.1% ± 2.7% before RT, p = 0.01). For left-sided patients, mean heart and LV doses were 3.1 ± 1.3 Gy and 6.7 ± 3.4 Gy respectively. For right-sided patients, mean heart dose was 0.7 ± 0.5 Gy and median LV dose was 0.1 Gy. Associations between GLS reduction > 10% (37 patients) and mean doses to the heart and the LV as well as the V20 were observed in univariate analysis (Odds Ratio = 1.37[1.01-1.86], p = 0.04 for Dmean Heart; OR = 1.14 [1.01-1.28], p = 0.03 for Dmean LV; OR = 1.08 [1.01-1.14], p = 0.02 for LV V20). In multivariate analysis, these associations did not remain significant after adjustment for non-radiation factors. Further exploratory analysis allowed identifying a subgroup of patients (LV V20 > 15%) for whom a significant association with subclinical LV dysfunction was found (adjusted OR = 3.97 [1.01-15.70], p = 0.048). CONCLUSIONS:This analysis indicated that subclinical LV dysfunction defined as a GLS decrease > 10% is associated with cardiac doses, but adjustment for non-radiation factors such as endocrine therapy lead to no longer statistically significant relationships. However, LV dosimetry may be promising to identify high-risk subpopulations. Larger and longer follow-up studies are required to further investigate these associations. TRIAL REGISTRATION:ClinicalTrials.gov: NCT02605512, Registered 6 November 2015 - Retrospectively registered.
| S-EPMC6854785 | biostudies-literature
Project description:PurposeCardiac dysfunction as a result of anthracycline treatment is a major concern regarding the management of patient life after therapy. The aim of the present study was to determine the clinical characteristics of cancer patients at high risk of developing cancer therapy-related cardiac dysfunction (CTRCD), in order to improve the risk management for the appropriate treatment.MethodsThis is a single-center, retrospective study of patients with breast cancer who underwent anthracycline treatment and had regular consultations with cardiologists. To investigate the incidence of CTRCD and the risk factors related to its occurrence, left ventricular ejection fraction (LVEF), cardiac troponin I (TnI), and brain natriuretic peptide (BNP) were assessed in 177 patients at the start of anthracycline treatment, and again at 3, 6, 9, and 12 months.ResultsEight patients (4.5%) developed CTRCD (CTRCD group). The comparisons between the CTRCD group and those without CTRCD (non-CTRCD group) showed significant differences in pre-treatment cancer stage and neutrophil/lymphocyte ratio (NLR). Multivariate analysis showed a strong association between pre-treatment cancer stage, NLR, and type of anthracycline administered (epirubicin or doxorubicin).ConclusionHigh NLR, the more advanced stages of cancer, and doxorubicin administration were suggested as possible risk factors for the development of CTRCD. Special attention should be warranted for patients with any of these risk factors.
| S-EPMC11625689 | biostudies-literature
Project description: Not available
| S-EPMC11695210 | biostudies-literature
Project description:Background The risk of cardiac dysfunction for patients with prostate cancer undergoing androgen deprivation therapy (ADT) in the real-world setting remains unclear. Methods and Results A total of 1120 patients with prostate cancer and a baseline echocardiography scan were identified from Chang Gung Research Database between January 1, 2001 and December 31, 2019. Patients were treated with gonadotropin-releasing hormone agonist therapy, gonadotropin-releasing hormone antagonist therapy, or bilateral orchiectomy. Changes in left ventricular ejection fraction (LVEF) were further assessed in 421 patients using repeated measurements of LVEF before and during ADT treatment. The incidence of cancer therapy-related cardiac dysfunction (CT-RCD) was evaluated and defined as a ≥10% absolute decline in LVEF from baseline to a value of <53%. Among 421 patients undergoing ADT, LVEF declined from 66.3±11.3% to 62.5±13.6% (95% CI of mean difference: -5.0% to -2.7%) after a mean follow-up period of 1.6±0.8 years. CT-RCD occurred in 58 patients (13.7%) with a nadir LVEF of 40.3±9.1% after ADT. Lower baseline LVEF was significantly associated with CT-RCD (odds ratio, 1.07 [95% CI, 1.04-1.10]). The area under the curve of baseline LVEF for discriminating CT-RCD was 75.6%, with the corresponding optimal cutoff value of 64.5% (sensitivity, 79.3%; specificity, 67.2%). Conclusions ADT with gonadotropin-releasing hormone agonist therapy, gonadotropin-releasing hormone antagonist therapy, and bilateral orchiectomy were associated with an increased risk of CT-RCD in patients with prostate cancer. In addition, lower baseline LVEF was a significant predictor of CT-RCD in patients with prostate cancer undergoing treatment with ADT.
| S-EPMC10727237 | biostudies-literature
Project description:Anthracyclines are associated with cardiotoxic effects. Cardiovascular biomarkers may reflect myocardial injury, dysfunction, inflammation, and fibrosis and may precede and predict the development of left ventricular impairment. The aim of this study was to assess: (1) longitudinal change in circulating cardiovascular biomarkers, (2) the effect of metoprolol succinate and candesartan cilexetil on the biomarker response, and (3) the associations between on-treatment changes in biomarker concentrations and subsequent left ventricular dysfunction in patients with early breast cancer receiving anthracyclines. This report encompasses 121 women included in the 2×2 factorial, placebo-controlled, double-blind PRADA (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) trial with metoprolol and candesartan given concomitantly with anticancer therapy containing the anthracycline, epirubicin (total cumulative dose, 240-400 mg/m2). Cardiovascular magnetic resonance, echocardiography images, and circulating levels of biomarkers were obtained before and after anthracycline treatment. Cardiac troponins I and T, B-type natriuretic peptide, N-terminal pro-B-type natriuretic peptide, C-reactive protein, and galectin-3 increased during anthracycline therapy (all P<0.05). The troponin response was attenuated by metoprolol (P<0.05), but not candesartan. There was no association between change in biomarker concentrations and change in cardiac function during anthracycline therapy. Treatment with contemporary anthracycline doses for early breast cancer is associated with increase in circulating cardiovascular biomarkers. This increase is, however, not associated with early decline in ventricular function. Beta-blockade may attenuate early myocardial injury, but whether this attenuation translates into reduced risk of developing ventricular dysfunction in the long term remains unclear. URL: http://www.clinicaltrial.gov. Unique identifier: NCT01434134.
| S-EPMC5721750 | biostudies-literature
Project description:PurposeTo characterize the early changes in echocardiographically derived measures of cardiac function with contemporary radiation therapy (RT) in breast cancer and to determine the associations with radiation dose-volume metrics, including mean heart dose (MHD).Methods and materialsIn a prospective longitudinal cohort study of 86 patients with breast cancer treated with photon or proton thoracic RT, clinical and echocardiographic data were assessed at 3 time points: within 4 weeks before RT initiation (T0), within 3 days before 6 weeks after the end of RT (T1), and 5 to 9 months after RT completion (T2). Associations between MHD and echocardiographically derived measures of cardiac function were assessed using generalized estimating equations to define the acute (T0 to T1) and subacute (T0 to T2) changes in cardiac function.ResultsThe median estimates of MHD were 139 cGy (interquartile range, 99-249 cGy). In evaluating the acute changes in left ventricular ejection fraction (LVEF) from T0 to T1, and accounting for the time from RT, age, race, preexisting cardiovascular disease, and an interaction term with anthracycline or trastuzumab exposure and MHD, there was a modest decrease in LVEF of borderline significance (0.22%; 95% confidence interval [CI], -0.44% to 0.01%; P = .06) per 30-day interval for every 100 cGy increase of MHD. Similarly, there was a modest worsening in longitudinal strain (0.19%; 95% CI, -0.01% to 0.39%; P = .06) per 30-day interval for each 100 cGy increase in MHD. We did not find significant associations between MHD and changes in circumferential strain or diastolic function.ConclusionsWith modern radiation planning techniques, there are modest subclinical changes in measures of cardiac function in the short-term. Longer-term follow-up studies are needed to determine whether these early changes are associated with the development of overt cardiac disease.
| S-EPMC11237872 | biostudies-literature
Project description:BackgroundResults from numerous clinical trials have led to a consensus that moderately hypofractionated radiation therapy is the ideal postoperative irradiation treatment plan in patients with breast cancer (BC). However, there are specific situations such as chest wall (with or without breast reconstruction) and regional node irradiation that still face obstacles in its widespread use. There is a lack of evidence supporting the use of moderately hypofractionated irradiation from the Latin American context. This study aims to describe the profile and clinical outcomes of patients treated with moderate hypofractionation for both early-stage (Stage I and II) and locally advanced BC (Stage III) regardless of the type of surgery in a Brazilian Oncology Center.MethodsAll patients with non-metastatic BC who were treated with moderately hypofractionated schedules of 40Gy in 15 fractions or 42.4Gy in 16 fractions between 2010 to 2019 at Hospital Sírio-Libanês, Brazil were retrospectively analyzed. The rates of local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distance recurrence-free survival (DRFS) and overall survival (OS) were estimated. Acute and late toxicity profiles were accessed for the entire cohort.FindingsA total of 670 patients were included. The median age was 57 years and the median follow-up time was 31 months. Most of the patients had stage I and II breast cancer, and 81.6% underwent breast-conserving surgery. Of the 123 women who underwent mastectomy treatment, 29% (n = 37) had immediate reconstruction with implants and 28% (n = 35) with autologous tissue. Seventy-one per cent of the patients presented luminal subtype tumour and 84.3% received adjuvant hormonal therapy. Chemotherapy was administered to almost half of the patients and all 80 patients with Her-2 positive disease received trastuzumab-based systemic therapy. One-third of patients received regional node irradiation; boost was performed in 41.1% of treatments. The 5-year LRFS, RRFS, DRFS and OS was 95.6%, 97.6%,92.2% and 95.9%, respectively. Acute and late side effects profile were mild and only 2.9% of patients developed grade 3 dermatitis. Among patients with breast implants, 11.4% had capsular contracture.InterpretationIn this Brazilian institution experience, moderately hypofractionated irradiation to the breast, chest wall (with or without breast reconstruction), and regional lymph nodes was safe and with an acceptable toxicity profile.FundingNone.
| S-EPMC9903971 | biostudies-literature
Project description:Cardiac resynchronization therapy (CRT) with multipoint pacing and quadripolar lead implantation showed improvement in systolic function, reduction in left ventricular volumes, and improved functional capacity in a patient with cancer therapeutics-related cardiac dysfunction; this therapy could be a valid option in those cases where a suboptimal CRT response is expected.
| S-EPMC6552964 | biostudies-literature
Project description:PurposeWe evaluated the risk of cardiac mortality in older patients who receive adjuvant radiation therapy (RT) for stage I breast cancer to determine whether this risk persists in the modern era.Methods and materialsUsing the 2000 to 2015 Surveillance, Epidemiology, and End Results program data, we performed a population-based cohort study to evaluate the association between adjuvant breast RT, tumor laterality, and cardiac-specific survival (CSS) among patients 60 and older with stage I estrogen receptor positive breast cancer who received breast-conserving surgery and RT.ResultsAt a median follow-up of 6 years (range, 0-15.9 years), patients receiving RT for left-sided breast cancer demonstrated no difference in 5- and 10-year CSS compared with those with right-sided breast cancer (5 year 98.3% vs 98.2%, 10 year 94.3% vs 93.9%; log-rank P = .56). Cox proportional hazards regression analysis confirmed the lack of association of tumor laterality on adjusted 5-year CSS (hazard ratio [HR] = 0.96; 95% confidence interval [CI] = 0.87-1.06), breast-cancer specific survival (HR = 0.96; 95% CI = 0.85-1.09), and overall survival (HR = 0.98; 95% CI = 0.94-1.03). There was also no association of inner versus outer quadrant location on adjusted 5-year CSS for right-sided (HR = 1.06; 95% CI = 0.89-1.12) and left-sided breast cancer (HR = 0.95; 95% CI = 0.79-1.15).ConclusionsWith modern radiation therapy techniques, older patients who received left-sided RT for stage I estrogen-receptor positive breast cancer do not demonstrate an increased risk of cardiac mortality compared with patients with right-sided breast cancer. RT can be offered to older patients without concern for inducing cardiac-related death.
| S-EPMC8071719 | biostudies-literature