Corey Speers1, Venkatesh L Murthy2, Eleanor M Walker3, Carri K Glide-Hurst4, Robin Marsh5, Ming Tang6, Emily L Morris6, Matthew J Schipper7, Richard L Weinberg2, Hunter C Gits8, James Hayman1, Mary Feng9, James Balter5, Jean Moran5, Reshma Jagsi1, Lori J Pierce10. 1. Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan; Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan. 2. Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan; Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan. 3. Department of Radiation Oncology, Henry Ford Cancer Institute, Detroit, Michigan. 4. Department of Human Oncology, School of Medicine and Public Heath, University of Wisconsin-Madison, Madison, Wisconsin. 5. Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan. 6. Department of Biostatistics, University of Michigan, Ann Arbor, Michigan. 7. Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan; Department of Biostatistics, University of Michigan, Ann Arbor, Michigan. 8. Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota. 9. Department of Radiation Oncology, University of California San Francisco, San Francisco, California. 10. Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan; Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan. Electronic address: ljpierce@umich.edu.
Abstract
PURPOSE: Radiation therapy (RT) can increase the risk of cardiac events in patients with breast cancer (BC), but biomarkers predicting risk for developing RT-induced cardiac disease are currently lacking. We report results from a prospective clinical trial evaluating early magnetic resonance imaging (MRI) and serum biomarker changes as predictors of cardiac injury and risk of subsequent cardiac events after RT for left-sided disease. METHODS: Women with node-negative and node-positive (N-/+) left-sided BC were enrolled on 2 institutional review board (IRB)-approved protocols at 2 institutions. MRI was conducted pretreatment (within 1 week of starting radiation), at the end of treatment (last day of treatment ±1 week), and 3 months after the last day of treatment (±2 weeks) to quantify left and right ventricular volumes and function, myocardial fibrosis, and edema. Perfusion changes during regadenoson stress perfusion were also assessed on a subset of patients (n = 28). Serum was collected at the same time points. Whole heart and cardiac substructures were contoured using CT and MRI. Models were constructed using baseline cardiac and clinical risk factors. Associations between MRI-measured changes and dose were evaluated. RESULTS: Among 51 women enrolled, mean heart dose ranged from 0.80 to 4.7 Gy and mean left ventricular (LV) dose from 1.1 to 8.2 Gy, with mean heart dose 2.0 Gy. T1 time, a marker of fibrosis, and right ventricular (RV) ejection fraction (EF) significantly changed with treatment; these were not dose dependent. T2 (marker of edema) and LV EF did not significantly change. No risk factors were associated with baseline global perfusion. Prior receipt of doxorubicin was marginally associated with decreased myocardial perfusion after RT (P = .059), and mean MHD was not associated with perfusion changes. A significant correlation between baseline IL-6 and mean heart dose (MHD) at the end of RT (ρ 0.44, P = .007) and a strong trend between troponin I and MHD at 3 months post-treatment (ρ 0.33, P = .07) were observed. No other significant correlations were identified. CONCLUSIONS: In this prospective study of women with left-sided breast cancer treated with contemporary treatment planning, cardiac radiation doses were very low relative to historical doses reported by Darby et al. Although we observed significant changes in T1 and RV EF shortly after RT, these changes were not correlated with whole heart or substructure doses. Serum biomarker analysis of cardiac injury demonstrates an interesting trend between markers and MHD that warrants further investigation. Published by Elsevier Inc.
PURPOSE: Radiation therapy (RT) can increase the risk of cardiac events in patients with breast cancer (BC), but biomarkers predicting risk for developing RT-induced cardiac disease are currently lacking. We report results from a prospective clinical trial evaluating early magnetic resonance imaging (MRI) and serum biomarker changes as predictors of cardiac injury and risk of subsequent cardiac events after RT for left-sided disease. METHODS: Women with node-negative and node-positive (N-/+) left-sided BC were enrolled on 2 institutional review board (IRB)-approved protocols at 2 institutions. MRI was conducted pretreatment (within 1 week of starting radiation), at the end of treatment (last day of treatment ±1 week), and 3 months after the last day of treatment (±2 weeks) to quantify left and right ventricular volumes and function, myocardial fibrosis, and edema. Perfusion changes during regadenoson stress perfusion were also assessed on a subset of patients (n = 28). Serum was collected at the same time points. Whole heart and cardiac substructures were contoured using CT and MRI. Models were constructed using baseline cardiac and clinical risk factors. Associations between MRI-measured changes and dose were evaluated. RESULTS: Among 51 women enrolled, mean heart dose ranged from 0.80 to 4.7 Gy and mean left ventricular (LV) dose from 1.1 to 8.2 Gy, with mean heart dose 2.0 Gy. T1 time, a marker of fibrosis, and right ventricular (RV) ejection fraction (EF) significantly changed with treatment; these were not dose dependent. T2 (marker of edema) and LV EF did not significantly change. No risk factors were associated with baseline global perfusion. Prior receipt of doxorubicin was marginally associated with decreased myocardial perfusion after RT (P = .059), and mean MHD was not associated with perfusion changes. A significant correlation between baseline IL-6 and mean heart dose (MHD) at the end of RT (ρ 0.44, P = .007) and a strong trend between troponin I and MHD at 3 months post-treatment (ρ 0.33, P = .07) were observed. No other significant correlations were identified. CONCLUSIONS: In this prospective study of women with left-sided breast cancer treated with contemporary treatment planning, cardiac radiation doses were very low relative to historical doses reported by Darby et al. Although we observed significant changes in T1 and RV EF shortly after RT, these changes were not correlated with whole heart or substructure doses. Serum biomarker analysis of cardiac injury demonstrates an interesting trend between markers and MHD that warrants further investigation. Published by Elsevier Inc.
Authors: Shahed N Badiyan; Lindsay L Puckett; Gregory Vlacich; Walter Schiffer; Lauren N Pedersen; Joshua D Mitchell; Carmen Bergom Journal: Curr Treat Options Oncol Date: 2022-09-10