The purpose of this study is to evaluate acute radiation effect on right ventricular function by myocardial exposure to irradiation.

Transcription

1 Acute cardiac impairment of high-dose radiation exposure: changes of right and left ventricular function by cardiac magnetic resonance after radiotherapy for esophageal cancer Poster No.: C-0402 Congress: ECR 2015 Type: Authors: Keywords: DOI: Scientific Exhibit M. Yonezawa, M. Nagao, S. Kawanami, T. Kamitani, Y. Yamasaki, T. higo, K. Nakamura, H. Yabuuchi, H. Honda; Fukuoka/JP Acute, Radiation therapy / Oncology, Radiation effects, Complications, MR, Radioprotection / Radiation dose, Oncology, Cardiac /ecr2015/C-0402 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 13

2 Aims and objectives Introduction: Myocardial radiation exposure causes various chronic heart impairment: systolic or diastolic dysfunction of left ventricle, conduction disturbance, myocarditis, pericarditis, cardiac effusion and tamponade. These adverse event are caused by inflammation and progressive fibrosis of cardiac tissue including myocardium[1] [2] [3]. Symptomatic heart disease has been well known in survivors of mediastinal radiation for Hodgkin's disease [4]. On the other hand, in acute phase, cardiac functional impairment caused by irradiation is also known [5] [6]. But these reports were all about left ventricular impairment, and no acute radiation impairment on right ventricle has been reported thus far. For many years, emphasis in cardiology was placed on left ventricular (LV) physiology, overshadowing the study of the RV. Cardiac output is mainly depends on LV function and a lot of knowledge about LV function has been accumulated. However, impaired right ventricular function has a negative effect on patients prognosis[7], and the importance of RV function is widely recognized recently [8]. The purpose of this study is to evaluate acute radiation effect on right ventricular function by myocardial exposure to irradiation. Methods and materials Patients and treatment This prospective study was approved by the institutional review board, and written informed consent was obtained from all patients. The 41 patients who were scheduled to receive CCRT for esophageal cancer in our department between January 2011 and July 2014 were consecutively enrolled in this study. Those who had a history of cardiovascular disease (2: history of myocardial infarction, 2: history of percutaneous coronary intervention) and 4 patients who received radiotherapy alone because of renal dysfunction were excluded. Thus a total of 33 patients (26 male and 7 female; years of age; median age 64 years) were included in this study. The locations of the disease were as follows: 7 cervical, 5 upper thoracic, 13 mid-thoracic, and 8 lower thoracic. The stages of the disease according to International Union Against Cancer 1997 criteria were as follows: 6 Stage I, 9 Stage II, 12 Stage III, and 6 Stage IV. The histologic diagnoses were all squamous cell carcinomas. Patient characteristics are summarized in Table 1. Radiotherapy was performed at a daily dose of Gy, five times per week using a Varian 21EX linear accelerator (Varian Medical Systems, Palo Alto, CA). Page 2 of 13

3 Radiotherapy was delivered through anteroposterior portals using 4-, 6-, or 10-MV photon beams with a T-shaped or I-shaped field including primary lesions and regional nodes to Gy, and the boost was delivered through parallel opposed oblique portals avoiding the spinal cord. Twenty-four patients were treated by CCRT with a low-dose protocol (cisplatin 5 mg/m 2 bolus infusion and 5-fluorouracil 300 mg/m2 24-h continuous infusion during radiotherapy), and the remaining 11 patients were treated with a standarddose protocol (cisplatin 70 mg/m 2 bolus infusion on Day 1, and 5-fluorouracil 700 mg/m 2 24-h continuous infusion on Days 1-4; two cycles are given during radiotherapy). Cardiac MRI examinations were performed two times: before and after a radiation exposure of Gy. The treatment schema is shown in Fig. 1. After a radiation exposure of Gy, 24 patients were treated by surgery and 9 patients were treated following radiation dose: total dose of Gy. Patient classification according to RV dose The patients were divided into two groups according to their mean total RV dose 2Gy: a low RV-dose and a high RV-dose group. The contour of RV was defined and the mean RV dose was calculated with an Eclipse planning system (Varian Medical Systems). This procedure was performed by a radiation oncologist (K.M.) with 10 years' experience, who was blinded to the data of MR imaging. Representative dose distributions are shown in Fig. 2. MR imaging Magnetic resonance examination was performed with a 1.5-T system (Gyroscan Intera Achieva; Philips Medical Systems, Best, The Netherlands), and a cardiac coil with five channels was used. The RV function was evaluated using cine MR imaging with 20 heart phases, a 350-mm field of view, 10-mm slice thickness, 0-mm slice gap, 192 x 184 matrix, 3.2-ms repetition time, 1.6-ms echo time, 55 flip angle, and balanced turbo field-echo sequence. The cine MR imaging was obtained before and after a radiation exposure of Gy for all 33 patients. The duration between the first MR examination before CCRT and the start of CCRT was 0-11 days, and the median was 1 day. The duration between the second MR examination and the completion of Gy was 0-4 days, and the median was 1 days. The exact radiation doses to the primary lesion at the MR examination performed at approximately 40 Gy and after CCRT were distributed from 36.2 to 43.2 Gy (median, 41.4 Gy), respectively. Data acquisition and analysis Patient characteristics were compared as follows: age and body mass index were compared between low and high RV-dose groups using a t test, and other categoric data were compared using a Chi-square test. Probability (p) values of <0.05 were considered Page 3 of 13

4 statistically significant. The RV function analysis was performed with View Forum (Philips Medical Systems) and by M.Y. and K.N. in consensus (M.Y. has 11 years of experience in cardiac imaging, and K.N. has 20 years of experience). Both were blinded to the CCRT method used for each patient. Several parameters related to RV function (end-diastolic volume index [RV-EDVI], end-systolic volume index [RV-ESVI], stroke volume index [RV- SVI], ejection fraction [RV-EF] were measured and compared between before CCRT and after Gy using a Wilcoxon matched pairs single rank test. The parameter ratios of RV-EF, RV-EDVI, RVESVI, RV-SVI and body weight at approximately 40 Gy (i.e., the RV-EF, RV-EDVI, RV-ESVI, RVSVI, and body weight at approximately 40 Gy divided by those before CCRT) were compared between the low and high LV-dose groups using a paired t-test. A p value <0.05 was considered statistically significant. Data were expressed as the mean ± SE unless otherwise specified. To minimize the effects of height and body weight, RV-EDVI, RV-ESVI and RVSVI (divided by body surface area) were used. Images for this section: Fig. 1: Dose distributions Page 4 of 13

5 Results Patient classification according to RV dose The low RV-dose group included 12 patients and consisted of cervical and upper thoracic cancers. The mean RV dose was <0.5 Gy (mean, 0.34 Gy) at MR examination at approximately 40 Gy. The high RV-dose group included 21 patients and consisted of mid- and lower thoracic cancers. The mean RV dose was distributed from 9.6 to 42.3 Gy (mean, 33.4 Gy; median, 34.2 Gy) at MR examination at approximately 40 Gy and the mean LV dose was distributed from 3.1 to 32.8 Gy (mean, 17.9 Gy; median, 18.4 Gy). There were no significant differences with respect to age, gender, cardiac risk factors, or chemotherapy method between patients receiving low and high LV doses, but the primary lesion location and disease stage differed significantly between the two dose groups. The classification of patient characteristics according to LV dose is summarized in Table 1(Figure2). Comparison of parameters related to RV function between before and after radiation therapy. In the high RV-dose group, the RV-EF, RV-SVI and RV-EDVI decreased significantly (p < 0.05) after radiation therapy approximately 40 Gy (51.4% ± 4.7%, 30.2 ± 8.5 ml/ m 2, 58.1 ± 13.4ml/m 2 ) compared with before CCRT (56.2% ± 6.4%, 37.5 ± 8.6 ml/m 2, 66.5 ± 11.9ml/m 2 ), respectively (Table1). RV-ESVI showed significant change. As for LV function, LV-EF, LV-SVI and LV-EDVI decreased significantly (p < 0.05) after radiation therapy (Table1). In the low RV-dose group, any parameters of RV and LV showed significant change. The data are summarized in Table 2 and 3(Figure3 and 4). Comparison of parameter ratios related to RV and LV function between the high and low LV-dose groups Significant differences (p < 0.05) in the parameter ratios between the high and low LVdose groups were observed only in the values calculated for RV-EF ratio, RV-SVI ratio, RV-EDV ratio, LV-SV ratio, and LV-EDV ratio. No other parameters showed significance either at approximately 40 Gy. The results are summarized in Table 4(Figure5). Page 5 of 13

6 Images for this section: Fig. 2: Table 1: patient caracteristics Page 6 of 13

7 Fig. 3: Table 2: Change of RV and LV function in high dose group. Page 7 of 13

8 Fig. 4: Table 3: Change of RV and LV function in low dose group Page 8 of 13

9 Fig. 5: Ratio of RV and LV function indices in high and low dose group. Page 9 of 13

10 Fig. 6: A case of high RV dose. Page 10 of 13

11 Conclusion The results of this study showed decline of RV-EF in high dose group, which indicate that RV systolic function was impaired from an early treatment stage in patients who received radiation exposure to myocardium. As shown in this study, acute impairment of LV systolic function by radiation exposure was reported[5], and the results of RV were similar to those of LV. In this study, cardiac function of all cases were preserved, and no cardiac accident was observed. But it is necessary to be careful in case with cardiac dysfunction. In this study, both RV-EDVI and LV-EDVI were decreased in high dose group. EDVI was a parameter of ventricular diastolic function[9], accordingly radiation exposure might affect impairment of ventricular diastolic dysfunction. The functions of the left and right ventricles are linked each other. The LV function and RV function effect via the shared interventricular septum each other, and do the diastolic function, too [10]. This is called ventricular interaction. Normal LV exerts a favorable systolic interaction on the RV, and impaired LV exerts an unfavorable interaction. In this study, both RV and LV received radiation exposure(table 1), and acute radiation injury of RV and LV may affect each other. To our knowledge, this is the first report to detect acute cardiac dysfunction, that is a reduction in RV-EF, RV-EDVI, RV-SVI, using cine MR imaging in patients who received CCRT for esophageal cancer. As for LV-EF, a significant reduction has also been reported in patients [11, 12]. In conclusion, Radiation exposure for myocardium impairs both RV and LV function from an early treatment stage. Personal information References 1. Totterman, K.J., E. Pesonen, and P. Siltanen, Radiation-related chronic heart disease. Chest, (6): p Burns, R.J., et al., Detection of radiation cardiomyopathy by gated radionuclide angiography. The American journal of medicine, (2): p Page 11 of 13

12 3. Constine, L.S., et al., Cardiac function, perfusion, and morbidity in irradiated longterm survivors of Hodgkin's disease. International journal of radiation oncology, biology, physics, (4): p Carver, J.R., et al., American Society of Clinical Oncology clinical evidence review on the ongoing care of adult cancer survivors: cardiac and pulmonary late effects. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, (25): p Hatakenaka, M., et al., Acute cardiac impairment associated with concurrent chemoradiotherapy for esophageal cancer: magnetic resonance evaluation. International journal of radiation oncology, biology, physics, (1): p. e Erven, K., et al., Acute radiation effects on cardiac function detected by strain rate imaging in breast cancer patients. International journal of radiation oncology, biology, physics, (5): p Haddad, F., et al., Right ventricular function in cardiovascular disease, part II: pathophysiology, clinical importance, and management of right ventricular failure. Circulation, (13): p Haddad, F., et al., Right ventricular function in cardiovascular disease, part I: Anatomy, physiology, aging, and functional assessment of the right ventricle. Circulation, (11): p Desai, C.S., et al., Prevalence, prospective risk markers, and prognosis associated with the presence of left ventricular diastolic dysfunction in young adults: the coronary artery risk development in young adults study. American journal of epidemiology, (1): p Schwarz, K., et al., Right ventricular function in left ventricular disease: pathophysiology and implications. Heart, lung & circulation, (7): p Mukherjee, S., et al., The significance of cardiac doses received during chemoradiation of oesophageal and gastro-oesophageal junctional cancers. Clinical oncology, (3): p Tripp, P., et al., Cardiac function after chemoradiation for esophageal cancer: comparison of heart dose-volume histogram parameters to multiple gated acquisition Page 12 of 13

13 scan changes. Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus / I.S.D.E, (6): p Page 13 of 13