1059 - Detection of Early Cardiotoxicity after Anthracyclines and Mediastinal Radiotherapy Using Cardiac PET/MRI

G. Ntentas^1,2, M. S. Nazir^3,4, E. Reyes⁵, K. Owczarczyk⁶, R. Crawley³, D. Smith⁶, S. Ahmad⁷, A. Qureshi⁶, J. L. Brady⁷, I. Reading⁸, M. Marber⁹, S. Barrington¹⁰, and G. Mikhaeel⁶; ¹Department of Medical Physics and Clinical Engineering, Guy´s and St Thomas´ Hospital, London, United Kingdom, ²Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom, ³Kings College London, School of Biomedical Engineering & Imaging Sciences, London, United Kingdom, ⁴Cardio-oncology unit, Royal Brompton Hospital, London, United Kingdom, ⁵St Bartholomew’s Hospital, Department of Cardiology, London, United Kingdom, ⁶Guys and St Thomas NHS Foundation Trust, Department of Clinical Oncology, London, United Kingdom, ⁷Guys and St Thomas NHS Foundation Trust, London, United Kingdom, ⁸University Hospital Southampton, Faculty of Medicine, Southampton, United Kingdom, ⁹Kings College London, Department of Cardiology, London, United Kingdom, ¹⁰Kings College London and Guys and St Thomas PET Centre, School of Biomedical Engineering and Imaging Sciences, Kings College London, Kings Health Partners, London, United Kingdom

Purpose/Objective(s): Anthracyclines (AC) or mediastinal radiotherapy (RT) are associated with cardiotoxicity. However, limited imaging studies examine early changes (<1yr) or their relative contribution to cardiotoxicity. We sought to address this by simultaneous cardiac ¹⁸F-FDG PET/MRI. Materials/

Methods: In a prospective study, patients (pts) with mediastinal lymphoma had cardiac ¹⁸F-FDG PET/MRI at 4 timepoints: Baseline, 2 weeks post AC, 2 weeks post RT, 6 months (m) post RT. Esophageal & lung cancer pts had concurrent platinum-based chemoradiotherapy and had 3 scans: Baseline, post RT, 6m post RT. MRI assessed biventricular ejection fractions (EF%) and volumes (V), myocardial T1, T2 maps and late gadolinium enhancement (LGE). ¹⁸F-FDG PET was used to assess cardiac inflammation and to obtain segmental standardized mean and max uptake values (SUV) in the myocardium. Paired t-tests or Wilcoxon signed-rank were used to assess significance. Patient advocates contributed to the design and evaluation of the study.

Results: 24 pts were recruited between Nov 21 – Jun 23, (8 lymphoma, 11 esophageal, 5 lung) mean age 57y (23-80). The mean AC dose for lymphoma pts was 244 mg/m² and mean heart dose (MHD) was 2.3 Gy, 15.3 Gy for esophageal and 11.0 Gy for lung. We observed significant reductions in both ventricular EF% and V in the post RT scans. On average the left ventricle (LV) recovered by 6m, however, the right ventricle (RV) EF% and stroke V remained reduced, Table 1. Notably, the RVEF% remained reduced by >10% for 8 pts, 6 of whom were esophageal with MHD >15 Gy, in these pts there was also abnormal focal ¹⁸F-FDG uptake in the basal myocardial segments in the 6m post RT scans which was not present on earlier scans. When analyzing only the lymphoma pts, all the above parameters decreased after AC but not after RT and all recovered by 6m apart from RVEF% which remained reduced (-6% ± 6 p=0.08). LGE, T1 and T2 did not change significantly from baseline.

Conclusion: To our knowledge, this is the first study to report that RV myocardial function is significantly reduced following AC and RT, it persisted at 6m post RT and was >10% in 38% of pts. Most of these patients received MHD >15Gy and had abnormal myocardial ¹⁸F-FDG PET uptake in the basal region which received the highest RT doses suggesting an inflammatory component to the process of cardiotoxicity. A reduction in RVEF% and focal myocardial ¹⁸F-FDG PET uptake may be useful biomarkers of early cardiotoxicity and initiation of cardio-oncology follow up.

	Baseline	? Post AC (Lymphoma only)	? Post RT	? 6 m post RT
	Mean [95% CI]
LVEF %	58 [53, 62]	-7 [-12, -2] p=0.01	-4 [-7, -1] p=0.02	-2 [-6, 1] p=0.24
RVEF %	59 [54, 64]	-8 [-16, 0] p=0.05	-7 [-11, -3] p<0.001	-8 [-11, -4] p<0.0001
LV EDV ml	73 [66, 81]	-2 [-6,3] p=0.4	-6 [-10, -3] p=0.003	-4 [-9, 2] p=0.20
RV EDV ml	73 [64, 81]	-2 [-7,3] p=0.4	-8 [-14, -2] p=0.01	-3 [-9, 4] p=0.40
LV SV ml	42 [37, 47]	-6 [-11, -1] p=0.02	-6 [-10, -3] p=0.001	-3 [-7, 1] p=0.09
RV SV ml	42 [38, 46]	-7 [-15, 1] p=0.07	-9 [-13, -5] p<0.0001	-6 [-11, -2] p<0.001
EDV: End Diastolic Volume, SV Stroke Volume