5 Year Longitudinal Analysis of Myocardial Perfusion SPECT Scans. Prospective Comparison of Long-Term Cardiac Function of Patients Participating in a Phase III Randomized Study of Breast Conserving Surgery and Radiotherapy

Abstract

Several studies have investigated myocardial perfusion after breast irradiation as a predictor of radiation-induced toxicity. Post Radiation Therapy (RT) perfusion defects have been strongly correlated with cardiac volume radiation field. These perfusion defects appear to be associated with chest pain, abnormalities in wall motion, and declining ejection fraction. A randomized clinical trial was carried out at our institution between 2008 - 2012 to evaluate the benefit of inverse planned IMRT over forward planned 3D-CRT for skin toxicity. This is a companion study to assess long term cardiac function by longitudinally comparing multiple markers of cardiac function using myocardial perfusion scintigraphy performed with single-photon emission computed tomography (SPECT) Eligible patients included T1-2, N0-1, invasive carcinoma of the breast or ductal carcinoma in situ post breast conserving surgery. 99mTc-Sestamibi SPECT scans were obtained at baseline, and 6, 12, 24, and 60 months post RT. Parameters analyzed included perfusion defects, wall thickening (WT), wall motion abnormalities (WM) and dyssynchronous contractions (DS). Analyses were done using spearman R correlation analysis, Mann-Whitney U test and Dunnett's multiple comparisons test. There were no significant differences seen in baseline characteristics (age, pathology, hormone status, technique, use of adjuvant chemo, or cardiac risk factors) between left-sided (n = 102) and right-sided (n = 79) RT patients. As expected, those receiving RT to left side had significantly greater mean cardiac dose (4.3 vs. 0.9Gy; p<0.001) and Dmax (45.4 vs. 6.3Gy; p<0.001). Radiation to the left breast did not significantly alter end diastolic volume, end systolic volume or ejection fraction at any timepoint. There was a significant increase in total perfusion defects seen post RT compared to baseline in left sided patients (4.1% vs. 2.8% p = 0.042) which was not seen in right sided patients. The perfusion defect returned to baseline by 1-year post RT, and remains normal at 2- and 5-years post RT. The global scoring of myocardial perfusion as measured by summed rest score (SRS) also showed a significant increase by 1.35 pts (4.1 vs. 2.8; p = 0.006) post RT for left sided patients. These changes were significantly correlated with max cardiac dose (p = 0.03). No localized perfusion defect, DS, WT, WM changes were seen. No adverse cardiac outcomes were reported. Patients receiving left breast RT did not show differ in standard measures of cardiac function such as ESV, EDV, and EF at any timepoint. There were mild perfusion defects seen post-RT, evidenced by worsened global non-gated SRS and total perfusion defect post RT in left sided patients. Worsened non-gated SRS was correlated with mean cardiac dose. Perfusion deficits normalized by 1-year post RT, and remained unchanged out to 5 years, suggesting a potential for cardiac remodeling post-RT.