Dosimetric predictors of asymptomatic heart valvular dysfunction following mediastinal irradiation for Hodgkin's lymphoma

Purpose: To identify dose-heart-volume constraints that correlate with the risk of developing asymptomatic valvular defects (VD) in Hodgkin's lymphoma (HL) patients treated with three-dimensional radiotherapy (RT). Patients and methods: Fifty-six patients undergoing cytotoxic chemotherapy (CHT) and involved-field radiation treatment for HL were retrospectively analyzed. Electro-echocardiography was performed before CHT, after CHT, and after RT. For the entire heart, for right and left ventricle (RV, LV), right and left atrium (RA, LA) percentage of volume exceeding 5-30 Gy in increment of 5 Gy (V x), and dosimetric parameters were calculated using 1.6 Gy fraction as reference. To evaluate clinical and dosimetric factors possibly associated with VD, univariate and multivariate logistic regression analyses were performed. Results: At a median follow up of 70.5 months, 32.1% of patients developed VD (regurgitation and/or stenosis): 25.0% developed mitral, 5.4% developed aortic, and 14.3% tricuspid VD. In particular the percentage of LA exceeding 25 Gy (LA-V 25) and the percentage of LV exceeding 30 Gy (LV-V 30) correlated with mitral and aortic VD with an odds ratio (OR) of 5.7 (LA-V 25 > 63.0% vs. LA-V 25 ≤ 63.0%) and OR of 4.4 (LV-V 30 > 25% vs. LV-V 30 ≤ 25%), respectively. RV-V 30 correlated with tricuspid VD (OR = 7.2, RV-V 30 > 65% vs. RV-V 30 ≤ 65%). Conclusion: LA-V 25, LV- and RV-V 30 prove to be predictors of asymptomatic alteration of valve functionality.