2081 - Prospective Evaluation of Early Cardiotoxicity in Patients Undergoing Photon or Proton Radiation Therapy for Locally-Advanced Distal Esophageal Cancer
Presenter(s)
N. Gupta1, N. Waller2, T. Kearney1, J. Paredes2, T. Kanholm2, B. E. Lewis3, B. Srichai4, A. K. Cheema5, and K. R. Unger1; 1Department of Radiation Medicine, MedStar Georgetown University Hospital, Washington, DC, 2Nelson Scientific labs LLC, Potomac, MD, 3Hackensack University Medical Center, Hackensack, NJ, 4Department of Cardiology, Medstar Georgetown University Hospital, Washington, DC, DC, 5Departments of Oncology, Biochemistry, Molecular and Cellular Biology, and Radiation Medicine, Georgetown University, Georgetown University Medical Center, Washington, DC, DC
Purpose/Objective(s): Chemoradiation with or without esophagectomy is a standard treatment for locally advanced esophageal cancer (EC). Radiation therapy (RT) for EC has been associated with an increased risk of cardiac death in long term survivors, however early onset cardiac toxicities are not well characterized. This prospective study aims to assess early treatment related structural and functional heart toxicity using cardiac MRI (CMR) in EC patients treated with photon or proton RT.
Materials/Methods: Twenty-one patients undergoing chemoradiation for locally-advanced distal EC were enrolled (17 male, 4 female; mean age 66.8 ± 11.4 years; 9 IMRT, 12 proton). CMR with first-pass perfusion imaging at rest and following the administration of regadenoson, and late gadolinium enhancement imaging was performed at baseline and 3-5 months postRT. Metrics included LV/RV ejection fraction (EF), stroke volume (SV), cardiac output (CO), end diastolic/systolic volume (EDV/ESV), myocardial mass (MM), and respective indexes (SVI, CI, EDVI/ESVI, MMI).
Patients were stratified into subgroups by the presence of cardiac fibrosis or perfusion abnormalities: Stable (no pre or postRT findings), Incident (no preRT findings and new postRT findings), Persistent (findings at both timepoints). Baseline differences were assessed using one-way ANOVA; within-group pre-post changes by paired t-tests; between-group differences by ANOVA/ANCOVA; and longitudinal effects by linear mixed-effects models adjusted for RT modality, age, and sex.Results: Eight (42%) patients developed new or worsening cardiac abnormalities (4 proton and 4 photon); 7, 3, and 9 patients were in the stable, incident, persistent subgroups, respectively; 2 patients withdrew. No significant baseline differences were noted across subgroups. Persistent patients showed LV functional decline (LV SV: ? -8.89 mL; p = 0.042; LV CO: ? -0.69 L/min; p = 0.030) and Incident patients showed increased LVESV (? +12 mL; p = 0.0091) and LVESVI (? +7 mL/m2; p = 0.045). PostRT MMI differed significantly by structural trajectory (F(2,12) = 6.93, p = 0.011; Stable: 53.0 g/m²; Incident: 61.3 g/m²; Persistent: 53.2 g/m²). In a fully adjusted linear mixed-effects model, the Incident group showed greater pre-post increases in LVEDVI (ß = 17.33; p = 0.017), LVESVI (ß = 7.17; p = 0.045), and LVESV (ß = 14.17; p = 0.049) compared to Stable patients. Age was independently associated with LVESVI (ß = -0.49; p = 0.043) and LVESV (ß = -0.98; p = 0.047), while RT modality was associated with LVESV (ß = 21.01; p = 0.042). No significant effect of sex was identified. New structural damage involved the basal to mid-inferior and inferoseptal walls.
Conclusion: Early cardiac toxicity was common following photon and proton RT for EC. LVESV, LVEDVI, and MMI were significantly elevated after RT in patients with new-onset cardiac abnormalities, while pre-existing cardiac abnormalities was associated with LV functional decline.