Abstract 4749: A phase II study using cardiac MRI to assess cardiac injury in breast cancer patients receiving three-dimensional conformal regional nodal radiotherapy (3DCRT) with heart dose constraints
Authors: Bergom Carmen , Rubenstein Jason , Welsh Aimee , Prior Philip , Eastwood Daniel , Zhang Mei-Jie , Wilson J. Frank , White Julia , Bradley Julie 
Published: July 2017

Abstract
Purpose/Objectives: Regional nodal radiotherapy (RNR) can improve survival for node positive breast cancer (NPBC) patients, yet this benefit is offset by potential late cardiac toxicity. Most cardiac toxicity reports from RNR have been in eras where no specific dose or volume heart constraint was used. Cardiac MRI (CMR) is ideal to assess ventricular function and volumes. We report a phase II trial designed to assess cardiac injury by CMR in NPBC patients who received chemotherapy (CT) and RNR planned with 3DCRT using heart constraints.
Materials/Methods: 244 NPBC patients treated with 3DCRT RNR following surgery planned with heart constraints between 2000-2008 were screened. Eligibility included prior anthracycline CT, no cardiac disease pre-NPBC, and no recurrent disease. Patients with active atrial fibrillation were excluded. The cardiac dose constraint utilized was V25&lt;10% of the heart. Mean heart dose was not constrained. Eligible women were invited via letter to enroll in the IRB-approved trial. CMR parameters to be evaluated included indicators of left ventricular (LV) function: ejection fraction (EF), LV mass (LVMI), and LV dimensions, as well as late gadolinium enhancement (LGE) and total heart extracellular volume fraction (ECV) as measures of cardiac injury and/or early cardiac fibrosis. Planned analysis included correlation of CMR parameters with cardiac dose-volume constraints using Spearman and Pearson correlations.
Results: The first 15 L-sided and 5 R-sided patients consented underwent CMR. Median age at diagnosis was 50 (32-77); median age at CMR was 60 (40-83). Median time after 3DCRT was 8.3 yr (5.7-14.4). The median L-sided mean heart dose was 4.8 Gy (1.1-11.2) and V25 was 5.7% (0-12%). No patient had clinical cardiac disease at time of CMR. Median LVEF was 63%. No LGE and no abnormal total heart ECV values (&gt;25%) were obtained. Values mildly outside normal limits were seen for LVMI or LV dimensions in 4/15 (27%) L-sided and 2/5 (40%) right-sided patients. No correlations were seen between heart mean and max doses, V5, V10, V25, and V45 and the CMR variables of LVEF, LV mass, and LV dimensions. Two patients had valvular abnormalities found on CMR (L-sided with aortic regurgitation and R-sided with mitral regurgitation).
Conclusions: CMR findings were largely within normal limits at a median follow of 8.3 years in this cohort of NPBC patients who received prior cardiotoxic chemotherapy and RNR planned with heart constraints. A subset of patients had subclinical mildly abnormal LV measurements, but these did not correlate with heart dose or laterality, and the significance remains unknown. In this cohort, no significant cardiac injury from RNR as measured with CMR was seen. Conversely, CMR may not be a sensitive tool for subclinical partial heart injury from RNR. Larger corroborating studies are warranted.
Citation Format: Carmen Bergom, Jason Rubenstein, Aimee Welsh, Philip Prior, Daniel Eastwood, Mei-Jie Zhang, J. Frank Wilson, Julia White, Julie Bradley. A phase II study using cardiac MRI to assess cardiac injury in breast cancer patients receiving three-dimensional conformal regional nodal radiotherapy (3DCRT) with heart dose constraints [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4749. doi:10.1158/1538-7445.AM2017-4749