Echocardiographic Functional Outcomes Following Regional Nodal Irradiation for Breast Cancer Using Volumetric Modulated Arc Therapy

Abstract

Regional nodal irradiation (RNI) for breast cancer yields improvements in disease outcomes, yet comprehensive target coverage often increases cardiac radiation therapy (RT) dose. Volumetric modulated arc therapy (VMAT) may mitigate high-dose cardiac exposure, although it often increases the volume of low-dose exposure. The cardiac implications of this dosimetric configuration (in contrast to historic 3D conformal techniques) remain uncertain. Eligible patients receiving adjuvant RNI using VMAT for locoregional breast cancer were prospectively enrolled in an IRB-approved study. Echocardiograms were performed prior to RT, at the conclusion of RT, and 6 months following RT. Echocardiographic parameters were measured by a single reader and measures were compared pre- and post-RT via the signed-rank test. Changes in echocardiographic parameters over time were compared to mean and max heart doses via the Spearman correlation test. Among 19 evaluable patients (median age 38 years), 89% (n = 17) received doxorubicin and 37% (n = 7) received trastuzumab/pertuzumab combination therapy. All patients received VMAT-based whole-breast/chest wall and RNI. The average mean heart dose was 456 cGy (range, 187-697 cGy) and the average max heart dose was 3001 cGy (1560-4793 cGy). Among salient echocardiographic parameters, no significant decrement in cardiac function was observed when comparing pre-RT to 6 months post-RT: mean left ventricular ejection fraction (LVEF) was 61.8% (SD 4.4%) pre-RT and 62.7% (SD 3.8%) 6 months post-RT (P = .493); mean global longitudinal strain (GLS) was -19.3% (SD 2.2%) pre-RT and -19.6% (SD 1.8%) 6 months post-RT (P = .627). No individual patient exhibited reduced LVEF or sustained decrement in GLS. No correlations were observed for changes in LVEF or GLS when compared to mean or maximum heart doses (P > .1 for all). VMAT for left-sided RNI yielded no significant early decrement in echocardiographic parameters of cardiac function, including LVEF and GLS, within this limited cohort. No patient exhibited significant LVEF changes, and none exhibited sustained decrements in GLS. VMAT may be a reasonable approach to cardiac avoidance in patients requiring RNI, including those receiving anthracyclines and HER2-directed therapy. Larger cohorts with longer follow-ups will be needed to validate these findings.