Heart dose linked with cardiac events and overall survival in lung cancer radiotherapy: A meta-analysis.

BACKGROUND: The aim of this study was to investigate the link between heart dose and overall survival, the link between heart dose and cardiac events and whether radiation-induced heart diseases were associated with overall survival in lung cancer radiotherapy. METHODS: We performed a literature search by using Pubmed, Embase, China National Knowledge Infrastructure (CNKI) databases. Pairs of reviewers independently screened literature according to the inclusion criteria, extracted data, assessed methodological quality, and publication bias. The primary end points included overall survival and cardiac events. I was calculated in a heterogeneity assessment. Publication bias was evaluated by using Begg funnel plot and Egger test. RESULTS: Ten studies including 1 randomized controlled trial, 3 post hoc analysis of prospective trials, and 6 cohort studies were identified. The meta-analysis showed that heart volume receiving ≥5 Gy (HV5) (hazard ratio [HR] = 1.01; 95% confidence interval [CI]: 1.00-1.01), heart volume receiving ≥30 Gy (HV30) (HR = 1.01; 95% CI: 1.00-1.02), heart volume receiving ≥50 Gy (HV50) (HR = 1.05; 95%CI: 1.00-1.10), and mean heart dose (MHD) (HR = 1.01; 95%CI:1.00-1.02) all were associated with worse overall survival. In addition, the MHD (HR = 1.03; 95% CI: 1.02-1.05), HV5 (HR = 1.02; 95% CI: 1.01-1.03), and HV30 (HR = 1.02; 95% CI: 1.01-1.03) were significantly associated with all grade cardiac events. Meanwhile, compared with those who did not receive radiotherapy, the radiotherapy group experienced a significantly increased risk for cardiac-specific mortality (HR = 1.297; 95% CI: 1.213-1.387). However, the results did not show that cardiac events were associated with overall survival in lung cancer radiotherapy (HR = 1.472; 95% CI: 0.988-2.193). CONCLUSION: Exposure of the heart to radiation increased the risk of cardiac events during radiotherapy for lung cancer. Meanwhile, heart dose including HV5 and HV30 were predictors of overall survival in lung cancer radiotherapy. It is necessary to constrain the heart dose when perform thoracic radiation therapy to decrease the incidence of cardiac events and improve the overall survival.

The role of irradiated heart and left ventricular volumes in heart failure occurrence after childhood cancer.

BACKGROUND: Paediatric cancer survivors have a high risk of developing cardiac diseases, and the most frequent cardiac disease is heart failure (HF). The radiation dose-volume effects in the heart and cardiac substructures have not been explored in childhood cancer survivors (CCS). Therefore, the role of irradiated heart volume in the occurrence of HF among this population remains unclear. The aims of this study were to determine the doses and irradiated volumes of the heart and left ventricle (LV) related to the risk of HF in CCS and to investigate the impact of anthracycline exposure on this risk. METHODS AND RESULTS: A case-control study nested in the French Childhood Cancer Survivors Study cohort. The mean heart and left ventricular doses and volumes indicators were estimated by reconstruction of individual treatments. A total of 239 HF cases and 1042 matched controls were included. The median age of HF diagnosis was 25.1 years. The median volume of the heart that received ≥ 30 Gy was 61.1% for cases and 16.9% for controls. In patients who did not receive anthracycline, the risk of HF was increased 3.6-fold when less than 10% of the LV received ≥ 30 Gy when compared to patients who were not exposed to any cardiac radiation and anthracycline. CONCLUSIONS: Small irradiated volumes of the heart or LV were significantly associated with HF risk. To the author's knowledge, this is the first study to report a dose-response relationship based on dose-volume indicators in CCS, which can be translated efficiently into current clinical practice.

Changes in cardiac volume determined with repeated enhanced 4DCT during chemoradiotherapy for esophageal cancer.

BACKGROUND: Concurrent chemoradiotherapy is considered curative intent treatment for patients with non-operative esophageal cancer. Radiation-induced heart damage receives much attention. We performed repeated four-dimensional computed tomography (4DCT) to detect changes in cardiac volume during radiotherapy for esophageal cancer patients, and explored potential factors responsible for those changes. METHODS: Forty-six patients with esophageal cancer underwent enhanced 4DCT and three-dimensional (3D) CT scans before radiotherapy and every 10 fractions during treatment. The heart was contoured on 3DCT images, 4DCT end expiratory (EE) images and 4DCT maximum intensity projection (MIP) images by the same radiation oncologist. Heart volumes and other relative parameters were compared by the SPSS software package, version 19.0. RESULTS: Compared with its initial value, heart volume was smaller at the 10th fraction (reduction = 3.27%, 4.45% and 4.52% on 3DCT, EE and MIP images, respectively, p < 0.05) and the 20th fraction (reduction = 6.05%, 5.64% and 4.51% on 3DCT, EE and MIP images, respectively, p < 0.05), but not at the 30th fraction. Systolic and diastolic blood pressures were reduced (by 16.95 ± 16.69 mmHg and 7.14 ± 11.64 mmHg, respectively, both p < 0.05) and the heart rate was elevated by 5.27 ± 6.25 beats/min (p < 0.05) after radiotherapy. None of the potential explanatory variables correlated with heart volume changes. CONCLUSIONS: Cardiac volume reduced significantly from an early treatment stage and maintained the reduction until the middle stage. The heart volume changes observed on 3DCT and 4DCT were consistent during radiotherapy. The changes in heart volume, blood pressure and heart rate may be valuable indicators of cardiac impairment and target dose changes.

Heart volume reduction during radiotherapy involving the thoracic region in children: An unexplained phenomenon.

BACKGROUND AND PURPOSE: Radiotherapy involving the thoracic region is associated with cardiotoxicity in long-term childhood cancer survivors. We quantified heart volume changes during radiotherapy in children (<18 years) and investigated correlations with patient and treatment related characteristics. MATERIAL AND METHODS: Between 2010 and 2016, 34 children received radiotherapy involving the thoracic region. We delineated heart contours and measured heart volumes on 114 CBCTs. Relative volume changes were quantified with respect to the volume on the first CBCT (i.e., 100%). Cardiac radiation dose parameters expressed as 2 Gy/fraction equivalent doses were calculated from DVHs. Chemotherapy was categorized as treatment with anthracyclines, alkylating agents, vinca-alkaloids, and other. RESULTS: The overall median heart volume reduction from the first to the last CBCT was 5.5% (interquartile range1.6-9.7%; p < 0.001). Heart volumes decreased significantly between the baseline measurement and the first week (Bonferroni's adjusted p = 0.002); volume changes were not significant during the following weeks. Univariate analysis showed a significant correlation between heart volume reduction and alkylating agents; however, no multivariate analyses could be done to further confirm this. CONCLUSIONS: We found a significant heart volume reduction in children during radiotherapy. Elucidation of underlying mechanisms, clinical relevance, and possible long-term consequences of early heart volume reduction require a prospective follow-up study.

Reduction of heart volume during neoadjuvant chemoradiation in patients with resectable esophageal cancer.

BACKGROUND AND PURPOSE: Neoadjuvant chemoradiation (nCRT) followed by surgery is considered curative intent treatment for patients with resectable esophageal cancer. The aim was to establish hemodynamic aspects of changes in heart volume and to explore whether changes in heart volume resulted in clinically relevant changes in the dose distribution of radiotherapy. METHODS: A prospective study was conducted in patients who were treated with nCRT consisting of carboplatin and paclitaxel concomitant with radiotherapy (41.4 Gy/1.8 Gy per fraction). Physical parameters, cardiac volume on CT and Cone beam CT, cardiac blood markers and cardiac ultrasound were obtained. RESULTS: In 23 patients a significant decrease of 55.3 ml in heart volume was detected (95% CI 36.7-73.8 ml, p<0.001). There was a decrease in both systolic (mean decrease 18 mmHg, 95% CI 11-26 mmHg, p<0.001) and diastolic blood pressure (mean decrease 8 mmHg, 95% CI 2-14 mmHg, p=0.008) and an increase in heart rate with 6 beats/min (95% CI 1-11 beats/min, p=0.021). Except for Troponin T, no change in other cardiac markers and echocardiography parameters were observed. The change in heart volume did not result in a clinically relevant change in radiation dose distribution. CONCLUSION: Heart volume was significantly reduced, but was not accompanied by overt cardiac dysfunction. All observed changes in hemodynamic parameters are consistent with volume depletion. Adaptation of the treatment plan during the course of radiotherapy is not advocated.

Reduction in cardiac volume during chemoradiotherapy for patients with esophageal cancer.

We investigated the change in cardiac volume over the course of chemoradiotherapy in 26 patients treated for esophageal cancer, using cone beam CT imaging. The cardiac volume reduced significantly, with a median reduction of 8%. A significant relationship with planned cardiac dose was not found.

Delineation of the cardiac substructures based on PET-CT and contrast-enhanced CT in patients with left breast cancer treated with postoperative radiotherapy.

The aim of this study is to evaluate the volume differences between contrast-enhanced CT-based left ventricle (LV) and PET-CT-based LV and assess the impact of dose on the substructure volume differences in patients with left breast cancer treated with adjuvant radiotherapy. From October 2008 to February 2009, 14 patients with post-operatively confirmed left breast cancer were enrolled in the current study. The patients were scanned using contrast-enhanced CT for simulation, and (18)F-FDG PET-CT was employed to display the structure of the left ventricle of each before radiotherapy (RT). The LV was delineated based on both contrast-enhanced CT and PET-CT. And other substructures, such as the left anterior descending coronary artery (LAD), were contoured in each patient, with the six-field simple intensity modulated radiotherapy (sIMRT) technique created for all. The mean volumes of the left ventricle based on contrast-enhanced CT (LV-CT) and PET-CT (LV-PET) were found to be 107.296 cm(3) and 112.931 cm(3), respectively (p = 0.06). The volume of LV receiving ≥ 50% prescription dose was significantly correlated with the volume of the heart receiving the same dosage (γ = 0.869). There was less correlation between the volume of LAD and that of the heart under the same condition (γ = 0.22). As a conclusion, the left ventricle can be delineated effectively based on the image of PET-CT, the contrast-enhanced CT based LV can serve as an appropriate alternative. Moreover, the volume of LV receiving high dose in RT closely correlated with the volume of the heart using sIMRT technique, which may pave the way for further exploring radiation-induced cardiac injuries in patients with left breast cancer.

Fases de reconstrucción y exactitud de la tomografía computarizada para cuantificar la función y masa ventricular izquierda / Accuracy of different reconstruction intervals to quantify left ventricular function and mass in cardiac computed tomography examinations

Objetivo. Comparar los parámetros de función y masa ventricular izquierda (VI) obtenidos con reconstrucciones realizadas en intervalos del 5 y 10% del ciclo cardiaco en pacientes con trasplante cardiaco y determinar su exactitud respecto a la resonancia magnética (RM). Material y métodos. Se incluyeron 23 trasplantados cardiacos consecutivos (21 varones; edad media 60±11,7 años) a los que se realizó un estudio cardiaco mediante tomografía computarizada (TC) de doble fuente (TCDF) y RM. Se compararon los parámetros de función y masa VI obtenidos de las imágenes de TCDF reconstruidas en intervalos del 5% (0-95%) y 10% (0-90%) del ciclo cardiaco respecto a los estimados mediante RM. Los parámetros se calcularon con un software de segmentación semiautomático en TCDF y trazando los contornos manualmente en RM. En todos los individuos se estimaron la fracción de eyección (FE), los volúmenes telediastólico (VTD), telesistólico (VTS), latido (VL) y la masa miocárdica. Resultados. La cuantificación de los parámetros de función VI mediante TCDF no mostró diferencias estadísticamente significativas según el número de fases reconstruidas (p>0,05). Respecto a la RM se observó una ligera sobreestimación de VTD, VTS y masa VI al utilizar tanto intervalos del 5% (diferencia media: 11,5±25,1ml; 6,8±10,9ml, y 28,3±21,6g, respectivamente) como 10% (diferencia media: 15,3±26,3ml; 7,4±11,5ml; 29,3±18,7g, respectivamente), con diferencias no significativas para la FE y el VL. Conclusión. En pacientes con trasplante cardiaco la TCDF es una técnica que permite cuantificar la función y la masa VI prácticamente con la misma exactitud que la RM, incluso utilizando intervalos de reconstrucción del 10% (AU)

Purpose. To compare the accuracy of cardiac dual-source CT (DSCT) reconstructions obtained at 5% and 10% of the cardiac cycle and MRI for quantifying global left ventricular (LV) function and mass in heart transplant recipients. Material and methods. We prospectively included 23 heart transplant recipients (21 male, mean age 60±11.7 years) who underwent cardiac DSCT and MRI examinations. We compared LV parameters on cardiac DSCT reconstructions obtained at 5% (0%-95%) and 10% (0%-90%) intervals of the cardiac cycle and on double-oblique short-axis MR images. We determined ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and myocardial mass using commercially available semiautomated segmentation analysis software for DSCT datasets and conventional manual contour tracing for MR studies. Results. Using different reconstruction intervals to quantify LV parameters at DSCT resulted in non-significant differences (P>.05). Compared to MRI, DSCT slightly overestimated LV-EDV, ESV, and mass when both 5% (11.5±25.1ml, 6.8±10.9ml, and 28.3±21.6g, respectively) and 10% (mean difference 15.3±26.3ml, 7.4±11.5ml, and 29.3±18.7g, respectively) reconstruction intervals were used. DSCT and MRI estimates of EF and SV were not significantly different. Conclusion. In heart transplant recipients, DSCT allows reliable quantification of LV function and mass compared with MRI, even using 10% interval reconstructions (AU)

Electrocardiographic changes after radiation therapy for carcinoma of the breast. Incidence and functional significance.

Cardiovascular complications from irradiation for breast carcinoma were assessed by history, physical examination, ECG recording, exercise test and heart volume determination before and two and six months after treatment in 197 unselected patients. A deterioration in general condition during therapy was reported by about 50 per cent of the patients, with shortness of breath and palpitation of the heart as the most frequent complaints and with a gradual improvement after therapy. Clinically, one case of pericarditis was diagnosed. ECG T-wave abnormalities appeared in 35 per cent of the patients after treatment, essentially confined to patients with left-sided pre- or postoperative treatment, where the mean radiation dose to the anterior quarter of the heart usually exceeded 20 Gy. Physical working capacity two and six months after therapy did not seem to be influenced by irradiation alone, and no correlation existed between change in physical working capacity and appearance of ECG T-wave abnormalities. The heart volume increased by more than 200 ml in 2 patients but otherwise the changes in heart volume were small. A high incidence of ECG T-wave abnormalities following left-sided irradiation for breast carcinoma was noted, but in the short term these ECG changes were functionally insignificant.

Effects on the cardiovascular system of irradiation for malignant lymphoma.

In 55 patients irradiated for malignant lymphoma the complaints were recorded as well as ECG, blood pressure, exercise test and heart volume before, during and one and 6 months following treatment. ECG abnormalities and fall in blood pressure occurred during treatment. Reduced physical working capacity was found one month after treatment. After 6 months all parameters had returned to pretreatment levels. Attention should be paid to the considerable reduction in blood pressure that does occur in some cases during treatment.