Radiation-induced Cardiac Toxicity Research Articles

Detection of radiation induced cardiotoxicity: Role of echocardiography and biomarkers.

We review the role of echocardiography and biomarkers in detection of radiation-induced cardiac toxicity (RICT). RICT is related to micro- and macrovascular damage which induce inflammation, endothelial dysfunction, accelerated atherosclerosis, myocyte degeneration and fibrosis. The process is cumulative dose to the heart and target volume dependent. Furthermore, the damage of the heart is frequently potentiated by the adjunctive chemotherapy. The clinical manifestations of RICT may acutely develop but most often become clinically apparent several years after irradiation. RICT clinical manifestation covers a wide spectrum of pathologies including pericarditis, coronary artery disease (CAD), myocardial infarction, valvular heart disease, rhythm abnormalities, and non-ischemic myocardial and conduction system damages. Echocardiography and cardiac markers are important diagnostic tools for the detection of RICT.

Advances in Preclinical Research Models of Radiation-Induced Cardiac Toxicity.

Radiation therapy (RT) is an important component of cancer therapy, with >50% of cancer patients receiving RT. As the number of cancer survivors increases, the short- and long-term side effects of cancer therapy are of growing concern. Side effects of RT for thoracic tumors, notably cardiac and pulmonary toxicities, can cause morbidity and mortality in long-term cancer survivors. An understanding of the biological pathways and mechanisms involved in normal tissue toxicity from RT will improve future cancer treatments by reducing the risk of long-term side effects. Many of these mechanistic studies are performed in animal models of radiation exposure. In this area of research, the use of small animal image-guided RT with treatment planning systems that allow more accurate dose determination has the potential to revolutionize knowledge of clinically relevant tumor and normal tissue radiobiology. However, there are still a number of challenges to overcome to optimize such radiation delivery, including dose verification and calibration, determination of doses received by adjacent normal tissues that can affect outcomes, and motion management and identifying variation in doses due to animal heterogeneity. In addition, recent studies have begun to determine how animal strain and sex affect normal tissue radiation injuries. This review article discusses the known and potential benefits and caveats of newer technologies and methods used for small animal radiation delivery, as well as how the choice of animal models, including variables such as species, strain, and age, can alter the severity of cardiac radiation toxicities and impact their clinical relevance.

P1355 Short-term cardiac side-effects from radiotherapy in women with breast cancer

Abstract Introduction Breast cancer radiotherapy provides an apparent benefit for long-term survival and local recurrence rate. However, there is still much concern about the early and late radiation-induced cardiac toxicity. Therefore, various radiotherapy techniques have been developed to reduce the cardiopulmonary radiation doses in patients with left-sided breast cancer, who are at particular risk of developing post-radiation cardiac injury. Aim We sought to investigate the early effect of radiotherapy on left (LV) and right ventricular (RV) function in females subjected to this treatment. Methods Fifty left-sided breast cancer patients , who underwent adjuvant radiotherapy between May 2017 and May 2018 were included in the study. Forty-nine enrollees were initially treated with breast conserving surgery, and 1 - with mastectomy and axillary lymph node resection. Adjuvant radiotherapy was carefully planned to minimize the radiation side effects and 37 patient received radiotherapy with deep inspiration breath hold technique and 13 patients with free breathing technique. In most cases (n = 33), 3D conformal tangential field radiation therapy was applied, 13 patients received radiotherapy with dynamic-Rapid-Arc technique with additional 3D fields, and 4 patients underwent radiotherapy only with Rapid-Arc technique. Before surgery and 3 months after radiotherapy, echocardiography with measurement of conventional cardiac function parameters, as well as LV and RV longitudinal deformation analysis by speckle tracking technique was performed, and venous blood for biomarkers - galectin-3 reflecting myocardial fibrosis and NT-proBNP was sampled. Results At a mean follow-up of 97 ± 19 days , there were no significant changes in any of the studied cardiac systolic or diastolic function parameters (Table). There were no relationships between the change in LV longitudinal strain at follow-up and type of radiotherapy, as well as type of radiotherapy gating (both R = 0.02, p = 0.90). Similarly, no analogous associations were demonstrated for RV longitudinal strain (R = 0.02, p = 0.88, and R = 0.04, p = 0.77, respectively). No significant changes were found post radiotherapy in serum galectin-3 (7.2 ± 2.6 ng/ml vs. 6.8 ± 2.5 ng/ml; p = 0.58) and NT-proBNP (83 ± 68 pg/ml vs. 84 ± 54 pg/ml; p = 0.90). Conclusions Breast cancer radiotherapy with the use of contemporary planning techniques shows an excellent early cardiac safety. Abstract P1355 Figure.

Effects of Radiotherapy in Coronary Artery Disease.

This review describes the effects of radiotherapy (RT) on coronary artery disease, its mechanisms, and clinical and laboratory evidence and discusses ways to minimize radiation-induced coronary atherosclerosis. Radiation-induced cardiac toxicity is known in patients undergoing thoracic RT. One of the damages occurs in the coronary arteries, with accelerated atherosclerosis manifesting decades later. There is clinical and laboratory evidence of coronary damage in retrospective studies, systematic reviews, and meta-analyses. Clinical studies have shown that RT cardiotoxicity occurs decades after radiation, regardless of chemotherapy, and may occur earlier in patients with pre-existing risk factors or disease. The pathogenesis of radiation-induced coronary artery disease is complex and multifactorial, including endothelial dysfunction, altered vascular tone, hemostatic imbalance, and inflammatory activation. Some factors are responsible, such as mean heart dose, RT chest site, patient position, techniques, and breathing maneuvers. There are approaches to reduce radiation-induced cardiac toxicity. Among them, besides the mentioned factors, metformin and anti-inflammatory agents can minimize coronary damage, with impact on morbidity and mortality.

Effect of Radiation Doses to the Heart on Survival for Stereotactic Ablative Radiotherapy for Early-stage Non–Small-cell Lung Cancer: An Artificial Neural Network Approach

IntroductionThe cardiac radiation dose is an important predictor of cardiac toxicity and overall survival (OS) for patients with locally advanced non–small-cell lung cancer (NSCLC). However, radiation-induced cardiac toxicity among patients with early-stage NSCLC who have undergone stereotactic ablative radiotherapy (SABR) has been less well-characterized. Our objective was to assess the associations between cardiac radiation dosimetry and OS in patients with early-stage NSCLC undergoing SABR. Materials and MethodsFrom 2009 to 2014, 153 patients with early-stage NSCLC had undergone SABR at a single institution. The maximum dose, mean dose, V10Gy, V25Gy, and V50Gy to 15 cardiac substructures and the whole heart were analyzed for their association with OS using the Kaplan-Meier method. An artificial neural network (ANN) analysis was performed to modulate confounding behaviors of dosimetric variables to predict for OS. ResultsA total of 112 patients were included in the present analysis. The right ventricle (RV) V10Gy most negatively predicted for OS, such that patients who had received a RV V10Gy dose < 4% had significantly longer OS than patients who had received a RV V10Gy does > 4% (5.3 years vs. 2.4 years). On ANN analysis, 74 input features, including cardiac dosimetry parameters, predicted for survival with a test accuracy of 64.7%. A repeat ANN analysis using dosimetry to dose neutral structure confirmed the predictive power of cardiac dosimetry. ConclusionCardiac dosimetry to subvolumes of the heart was associated with decreased OS in patients with early-stage NSCLC undergoing SABR. These data support the importance of minimizing the radiation dose to cardiac substructures. Further prioritizing the heart as an organ at risk might be warranted. Additionally, cardiac follow-up should be considered.

Dose to the cardio-pulmonary system and treatment-induced electrocardiogram abnormalities in locally advanced non-small cell lung cancer

IntroductionHigh 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 methodsPre- 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 (AΔECG, I/PΔECG, or NSΔECG) 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 (α/β = 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. ResultsAt a median of eight months post-RT, the rate of AΔECG, I/PΔECG, and NSΔECG was 66%, 35%, and 67%. Both AΔECG and I/PΔECG were associated with worse performance status (p = 0.007, 0.03), while a higher superior vena cava minimum dose was associated with NSΔECG (p = 0.002). ConclusionThis 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.

Metformin Reduces Radiation-Induced Cardiac Toxicity Risk in Patients Having Diabetes and Breast Cancer: Results from the Taiwan National Cohort and Basic Research

Background: To analyze the effects of metformin in reducing radiation-induced cardiac toxicity (RICT) risk during adjuvant radiotherapy (RT) after surgery for early-stage breast cancer among diabetic women. Methods: A retrospective national cohort study was conducted using the Taiwan Cancer Registry of 2004-2014. This study included 6,993 diabetic women with early-stage breast cancer who received adjuvant breast RT. An inverse probability of treatment weighting (IPTW) Cox hazards model was used to estimate metformin effects on the occurrence of major heart events. To investigate the effects of Metformin on the cardio-protective, primary culture of human cardiomyocytes were first used as the radiation induced cardiac toxicity experimental model. We also compared RICT in cardiac tissue specimens obtained from irradiated (10 Gy/shot) C57BL/6 mice with or without metformin administration. Results: Among diabetic women with breast cancer status post-surgery under adjuvant breast RT, 2,062 were prescribed metformin and 4,931 were not prescribed metformin. Cox proportional hazard regression analysis, with adjustment using IPTW, indicated that metformin use during adjuvant breast RT significantly reduces the risk of major heart events (adjusted hazard ratio [aHR], 0.789; 95% confidence interval [CI], 0.645-0.965; p = 0.021). The basic research results demonstrated that RT significantly reduced mitochondria membrane potential; meanwhile, metformin co-treatment significantly rescued the death of mitochondria in Human cardiomyocytes. In vivo, metformin administration attenuated RT-induced fibrosis in cardiac tissues. Conclusion: Our results suggest that metformin use during adjuvant breast RT was associated with reduced RICT risk in diabetic women with early-stage breast cancer. Funding Statement: Taipei Medical University and Wan Fang Hospital Declaration of Interests: The authors have no potential conflicts of interest to declare. Ethics Approval Statement: Our protocols were reviewed and approved by the Institutional Review Board of Taipei Medical University (TMU-JIRB No. 201712019).

Circulating microRNAs as biomarkers of radiation-induced cardiac toxicity in non-small-cell lung cancer.

Radiation-induced cardiac toxicity (RICT) is an increasingly well-appreciated source of morbidity and mortality in patients receiving thoracic radiotherapy (RT). Currently available methods to predict RICT are suboptimal. We investigated circulating microRNAs (c-miRNAs) as potential biomarkers of RICT in patients undergoing definitive RT for non-small-cell lung cancer (NSCLC). Data from 63 patients treated on institutional trials were analyzed. Prognostic models of grade 3 or greater (G3 +) RICT based on pre-treatment c-miRNA levels ('c-miRNA'), mean heart dose (MHD) and pre-existing cardiac disease (PCD) ('clinical'), and a combination of these ('c-miRNA + clinical') were developed. Elastic net Cox regression and full cross validation were used for variable selection, model building, and model evaluation. Concordance statistic (c-index) and integrated Brier score (IBS) were used to evaluate model performance. MHD, PCD, and serum levels of 14 c-miRNA species were identified as jointly prognostic for G3 + RICT. The 'c-miRNA and 'clinical' models yielded similar cross-validated c-indices (0.70 and 0.72, respectively) and IBSs (0.26 and 0.28, respectively). However, prognostication was not improved by combining c-miRNA and clinical factors (c-index 0.70, IBS 0.28). The 'c-miRNA' and 'clinical' models were able to significantly stratify patients into high- and low-risk groups of developing G3 + RICT. Chi-square testing demonstrated a marginally significantly higher prevalence of PCD in patients with high- compared to low-risk c-miRNA profile (p = 0.09), suggesting an association between some c-miRNAs and PCD. We identified a pre-treatment c-miRNA signature prognostic for G3 + RICT. With further development, pre- and mid-treatment c-miRNA profiling could contribute to patient-specific dose selection and treatment adaptation.

Syncope and an Intra-Hisian Atrioventricular Block After Radiation Therapy: Electrophysiologic Observations and Review of Literature

We present a case of a patient with recurrent syncope of sudden onset. She had a positive passive head-up tilt test for a mixed type of neurocardiogenic syncope. Additionally, she developed a narrow complex tachycardia on telemetry monitoring. Electrophysiology study revealed an intra-Hisian delay which upon provocation with programmed electrical stimulation, developed into a complete intra-Hisian atrioventricular block. Based on past medical history of radiation therapy for adenocarcinoma of the breast, the etiology of heart block was attributed to the remote effect of radiation-induced cardiac toxicity. Positive head-up tilt test for neurocardiogenic syncope and supraventricular tachycardia were incidental findings that could have confounding influence on management of such patients. J Med Cases. 2019;10(4):116-119 doi: https://doi.org/10.14740/jmc3233

18F]FDG cardiac PET imaging in a canine model of radiation-induced cardiovascular disease associated with breast cancer radiotherapy.

Radiotherapy for the treatment of left-sided breast cancer increases the long-term risk of cardiovascular disease. The purpose of the present study was to noninvasively image the progression of radiation-induced cardiac inflammation in a large animal model using a hybrid PET and MRI system. Five canines were imaged using [18F]fluorodeoxyglucose PET to assess changes in myocardial inflammation. All animals were imaged at baseline, 1 wk, and 1, 3, 6, and 12 mo after focused cardiac external beam irradiation with image guidance. Radiation was delivered in a single fraction. The linear quadratic model was used to convert a typical multifractionated heart dose to a corrected single-fraction biologically equivalent dose. Immunohistochemistry was performed on excised left ventricular tissue samples from all five irradiated canines and one nonirradiated control canine to confirm the presence of inflammation. The mean doses delivered to the entire heart, left ventricle, left anterior descending artery, and left circumflex artery were 1.7 ± 0.2, 2.7 ± 0.2, 5.5 ± 0.9, and 1.1 ± 0.4 Gy, respectively. FDG standard uptake values remained persistently elevated compared with baseline (1.1 ± 0.03 vs. 2.6 ± 0.19, P < 0.05). The presence of myocardial inflammation was confirmed histologically and correlated with myocardial dose. This study suggests a global inflammatory response that is persistent up to 12 mo postirradiation. Inflammation PET imaging should be considered in future clinical studies to monitor the early changes in cardiac function that may play a role in the ultimate development of radiation-induced cardiac toxicity. NEW & NOTEWORTHY Using advanced cardiac PET imaging, we have shown the spatial and quantitative relationship between radiation dose deposition and temporal changes in inflammation. We have shown that the progression of radiation-induced cardiac inflammation is immediate and does not subside for up to 1 yr after radiation. Results are presented in a large animal model that closely resembles the size and vessel architecture of humans. The proposed imaging protocol can be easily replicated for clinical use.

Evaluation of radiation-induced cardiac toxicity in breast cancer patients treated with Trastuzumab-based chemotherapy.

Patients with Her2-positive breast cancer treated with trastuzumab have higher rates of cardiotoxicity (CT). Left-breast radiation might increase the risk for CT from cardiac exposure to radiation. The goal of our study is to evaluate the contribution of radiotherapy (RT) in the development of CT in breast cancer patients receiving trastuzumab. Two hundred and two patients were treated with RT and trastuzumab from 2000 to 2014. The RT plans for left-side disease were recalled from archives. The heart, each chamber, and left anterior descending artery (LAD) were independently contoured. New dose-volume histograms (DVH) were generated. Their serial left-ventricular ejection fractions (LVEF) were studied. CT for left and right side were compared using Fisher's exact test. The DVH data were correlated with the predefined cardiac events using actuarial Cox regression analysis. Compared to the right sided, the left-side cases showed statistically significant development of arrhythmia (14.2%) versus (< 1%) (p < 0.001). Cardiac ischemia was found in 10 patients in left and one patient in right side (p = 0.011). The equivalent uniform dose (EUD) to the left ventricle (LV), right ventricle (RV), and LAD was significantly associated with decrease in LVEF by > 10% (p = 0.037, p = 0.023 and p = 0.049, respectively). Among patients treated for left-sided lesions, there were no significant differences in EF decline. However, there was a higher rate of ischemia and arrhythmia compared to those with right-sided disease. The EUD index of LV, RV, and LAD could be considered as a parameter to describe the risk of radiation-induced CT.

Consomic Rat Models Identify Genetic Factors that Modulate Radiation-Induced Cardiac Toxicity and Inflammation

Consomic Rat Models Identify Genetic Factors that Modulate Radiation-Induced Cardiac Toxicity and Inflammation

Circulating microRNAs as Biomarkers of Radiation-Induced Cardiac Toxicity in Non-Small Cell Lung Cancer

Circulating microRNAs as Biomarkers of Radiation-Induced Cardiac Toxicity in Non-Small Cell Lung Cancer

(P06) Identifying Genetic Factors Influencing Radiation-Induced Cardiac Toxicity Using Novel Genetic Rat Models

(P06) Identifying Genetic Factors Influencing Radiation-Induced Cardiac Toxicity Using Novel Genetic Rat Models

SP-0001: Radiation-induced cardiac toxicity: what have we learnt?

SP-0001: Radiation-induced cardiac toxicity: what have we learnt?

Abstract P2-11-18: The use of consomic animal models to identify genetic factors that modulate radiation-induced cardiac toxicity

Abstract Purpose/Objectives: Radiation therapy is used by more than 50% of breast cancer patients, but radiation doses can be limited by normal tissue side effects. For example, breast cancer radiation therapy can improve breast cancer-specific survival, but increase cardiac deaths in those with left-sided cancers. Identifying genetic factors that can enhance tumor radiation sensitivity while decreasing normal tissue toxicities has the potential to improve the therapeutic ratio of radiation therapy – leading to more cures and less long-term toxicities. The use of animal models with differing genetic backgrounds to assess radiation toxicity, followed by genetic mapping of radiosensitivity phenotypes, has the potential to identify new targets that can predict cardiac toxicity from radiation therapy. This project examines how genetic host factors alter normal tissue toxicity risks from breast cancer radiation. Materials/Methods: Inbred female SS rats and SS.BN3 consomic rats, that are genetically identical to SS rats except that chromosome 3 is inherited from the BN strain, have previously been shown to exhibit different vascular dynamics and breast tumor growth. For this study, adult female SS and SS.BN3 rats received image-guided whole heart radiation to a dose of 21 Gy (3 fields, AP and 2 laterals). Cardiac troponin was serially measured at 2, 6, and 12 weeks, and echocardiograms with strain analysis were performed at baseline and 3 months. The Student's t-test was used to compare values. Results: The SS female rats exhibited enhanced cardiac toxicity compared to SS.BN3 rats, with cardiac troponin levels elevated at 12 weeks (0.32 ng/ml vs.0.08 ng/ml for SS vs. SS.BN3, p=0.01), and moderate to severe pericardial effusions seen in 6 of 9 SS rats vs. 2 of 7 SS.BN3 rats. At 3 months post-radiation, echocardiograms revealed increased left ventricular posterior wall thickness at end diastole (LVPWd) in SS vs. SS.BN3 rats (0.25 vs. 0.20 cm, p=0.002) and increased left ventricular mass (LVM) in SS vs. SS.BN3 rats (1.54 vs. 1.28 g, p&amp;lt;0.001). Taken together, the SS female rats are more sensitive to cardiac irradiation than SS.BN3. Conclusions: These results demonstrate that genetic variant on rat chromosome 3 alter the radiosensitivity to single fraction cardiac radiation therapy. Gene expression analysis and genetic mapping will be performed to identify the causative target(s). These models will also be expanded to test whether similar results are seen with fractionated cardiac radiation therapy. This project has the potential to enhance the effectiveness and toxicity profile of radiation therapy in breast cancer. Citation Format: Bergom C, Schlaak R, Frei A, Fish BL, Harmann L, Gasperetti T, Schottstaedt AM, Flister MJ, Medhora M, Strande JL. The use of consomic animal models to identify genetic factors that modulate radiation-induced cardiac toxicity [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-11-18.

PD-1 Modulates Radiation-Induced Cardiac Toxicity through Cytotoxic T Lymphocytes.

Combined immune checkpoint blockade has led to rare autoimmune complications, such as fatal myocarditis. Recent approvals of several anti-programmed death 1 (anti-PD-1) drugs for lung cancer treatment prompted ongoing clinical trials that directly combine PD-1 inhibitors with thoracic radiotherapy for locally advanced lung cancer. Overlapping toxicities from either modality have the potential to increase the risk for radiation-induced cardiotoxicity (RICT), which is well documented among patients with Hodgkin's disease and breast cancer. To investigate cardiotoxicity without the compounding pulmonary toxicity from thoracic radiotherapy, we developed a technique to deliver cardiac irradiation (CIR) in a mouse model concurrently with PD-1 blockade to determine the presence of cardiac toxicity by using physiological testing and mortality as end points along with histological analysis. We observed an acute mortality of 30% within 2 weeks after CIR plus anti-PD-1 antibody compared with 0% from CIR plus immunoglobulin G (p= 0.023). Physiological testing demonstrated a reduced left ventricular ejection fraction (p < 0.01) by echocardiogram. Tissue analyses revealed increased immune cell infiltrates within cardiac tissue. Depletion of CD8-positive lymphocytes with anti-CD8 antibody reversed the acute mortality, suggesting that the toxicity is CD8-positive cell-mediated. To validate these findings using a clinically relevant fractionated radiotherapy regimen, we repeated the study by delivering five daily fractions of 6 Gy. Similar mortality, cardiac dysfunction, and histological changes were observed in mice receiving fractionated radiotherapy with concurrent anti-PD-1 therapy. This study provides strong preclinical evidence that radiation-induced cardiotoxicity is modulated by the PD-1 axis and that PD-1 blockade should be administered with careful radiotherapy planning with an effort of reducing cardiac dose.

Evaluation of Radiation-Induced Cardiac Toxicity in Breast Cancer Patients Treated with Trastuzumab-Based Chemotherapy

Evaluation of Radiation-Induced Cardiac Toxicity in Breast Cancer Patients Treated with Trastuzumab-Based Chemotherapy

MiR-215 as a Biomarker of Radiation-Induced Cardiac Toxicity

To evaluate the potential of serum micro-RNAs (miRNAs) as early biomarkers of cardiac toxicity in patients with breast cancer. Twenty women with breast cancer located in the left breast were included in this study. Ten had undergone mastectomy, to whom we added 10 age-matched women after breast conserving surgery (BCS). All patients after mastectomy underwent chest wall and axillary irradiation without internal mammary nodes. Total dose of radiation was 50.0Gy delivered in 2.0Gy daily fractions with 3D techniques with a 10-16Gy boost in the BCS group. All patients underwent chemotherapy before RT. Quantitative-PCR (qPCR) panels (Exiqon, Denmark) were used to evaluate the expression of 752 human miRNAs. Results were correlated with dose-volume histogram data and correlated with cytokine concentrations known to be associated with radiation-induced toxicity and cardiac injury: Interleukin-6 (IL-6), lipopolysaccharide-binding protein (LBP) or cardiac troponin T (cTnT). Results: Mean age of the group was 5.75+/-8.08 years. Patients after mastectomy showed significantly higher DVH parameters: V10, Mean heart dose, mean LAD dose and mean LV dose. Thirteen miRNAs showed significant correlation with V10 (table 1). Twelve miRNAs correlated with mean radiation dose delivered to the left anterior descending artery (Table 1). Among those miRNAs four microRNAs significantly correlated with both volumetric parameters: miR-30c, miR-194, miR-215 and miR-106b. Among these, miR-215 was positively correlated with both IL-6 (R=0.81; p=0.004), LBP (R=0.68; p=0.03) and cTnT (R=0.50; p=0.05) while miR-194 correlated with IL-6 (R=0.58; p=0.03) and marginally with LBP (R=0.47; p=0.08).Abstract 2013; Table 1Significant correlations of normalized miRNA expression in the serum of patients with breast cancer who completed radiotherapy for breast cancer. Four microRNAs showed consistent, significant correlations with two critical DVH parameters – V10 and mean LAD doseDVH V10 (correlation coefficient; p value)Mean LAD dose (correlation coefficient; p value)miR-30c-0.4833; 0.031miR-28-0.6799; 0.007miR-30c-0.7706; <0.001miR-30b-0.5824; 0.009miR-1940.6227; 0.010miR-210.5706; 0.009miR-1940.5305; 0.034miR-374a-0.7552; 0.012miR-2150.6275; 0.029miR-1220.5629; 0.010miR-2150.6134; 0.034miR-484-0.5529; 0.017miR-106b-0.5428; 0.030miR-106a-0.5525; 0.012miR-106b-0.5400; 0.031miR-15b-0.5377; 0.021miR-221-0.5439; 0.016let-7g-0.6129; 0.004miR-18a-0.5292; 0.029miR-142-0.4583; 0.042miR-378a0.5136; 0.021miR-1920.4850; 0.048miR-930.6757; 0.032miR-30d0.4483; 0.047miR-29c0.5301; 0.029 Open table in a new tab Serum expression of miR-215 after radiotherapy is associated with cardiac radiotoxicity and could be potentially used as an early biomarker of radiation cardiomyopathy.

The use of concurrent hormonotherapy and radiotherapy does not deteriorate radiation-induced cardiac toxicity.

Postmenopausal patients with breast cancer have two options for adjuvant endocrine therapy, tamoxifen and aromatase inhibitors (AIs) as well as radiotherapy (RT) and chemotherapy. However, there is limited data regarding the optimal sequencing of RT and tamoxifen/AIs. Thus, we aimed to evaluate the effects of tamoxifen and AIs on radiation-induced cardiotoxicity. Eighty ovariectomized rats were divided into eight groups (G). G1 was defined as a control group; G2, G3, G4, and G5 were RT, tamoxifen, anastrozle, and letrozole groups, respectively; G6, G7, and G8 were RT plus tamoxifen, anastrozle, and letrozole groups, respectively. Drugs were started 1 week before RT and continued until the animals were killed 16 weeks after RT. The heart tissues were then dissected and examined with light microscopy to determine endocardial thickness and cardiac fibrosis. The endocardial thickness scores of both RT alone and the tamoxifen groups as well as the cardiac fibrosis score of RT alone were higher than that the control group ( p < 0.05 for all). There was no difference in the endocardial thickness and cardiac fibrosis scores of the RT-only group and the RT plus hormonotherapy groups ( p > 0.05 for all). Concurrent administration of RT and hormonal therapy with either tamoxifen or AIs did not further amplify radiation-induced cardiac toxicity. This issue warrants further study.