Our understanding of the relationship between cardiac morbidity and mean heart dose among survivors of mediastinal lymphoma (mHL) dates back to the use of standard large-field 2D techniques. Over time, RT treatment in mHL has evolved with smaller, more personalized radiation fields and more conformal techniques, like 3D conformal RT (3D), intensity-modulated RT (IMRT), and proton therapy (PT). We investigated the relationship between mean heart dose and cardiac substructures across treatment fields and delivery techniques. We retrospectively developed IFRT (n=37) plans among selected patients with mHL treated with involved-site radiation therapy (ISRT) between 2008 and 2017. Doses to the cardiac substructures were exported to a dosimetric database of ISRT plans for mHL, including 3D (n=25), IMRT (n=28), and PT (n=36). The structures included the heart, left anterior descending artery (LAD), mitral valve (MV), tricuspid valve (TV), aortic valve (AV), left and right ventricles (LV, RV), and left and right atriam (LA, RAPlans were scaled to a prescription dose of 30 Gy and the mean heart dose was evaluated for correlation (R2) and slope (beta) of the relationship with mean dose to the cardiac substructures. The table reports the correlation coefficient (R2) and slope for the relationships between mean heart dose and mean cardiac substructure dose, demonstrating less correlation with increasingly conformal delivery. A strong correlation (R2≥70%) was seen for IFRT with RV, LV, and LAD; for 3D with RV and LV; and for IMRT with RV and LV. No strong correlation was observed for PT. When evaluating the slope (beta) for a relationship between mean heart dose and mean LAD dose, the slope was steepest for IFRT (1.86) and PT (1.69) compared to IMRT (1.36) and 3D (1.14), suggesting that a lower mean heart dose can be associated in some instances with a higher mean LAD dose with IFRT and PT compared to IMRT or 3D RT. For the LV, the slope was steepest for IFRT (2.07) followed by 3D (1.25), IMRT (1.17), and then PT (0.98). The relationship between mean heart dose and mean substructure dose changes with increasingly conformal techniques. Calculating mean heart dose as a surrogate for cardiac risk is no longer sufficient. Contouring the cardiac substructures, especially the LAD and LV, is important in understanding the late cardiac risks in the modern era of RT.Abstract 176; TableIFRT3DCRTIMRTPROTONSStructureRhoBETARhoBETARhoBETARhoBETAName(R2)(Slope)(R2)(Slope)(R2)(Slope)(R2)(Slope)Aortic Valve6%0.077%0.1035%0.7143%1.47Left Atrium48%0.2965%0.5453%0.8444%1.41Right Atrium11%0.1034%0.9236%0.8726%0.85Left Ant. Desc. art76%1.8662%1.1460%1.3652%1.69Mitral Valve50%0.7252%0.6138%0.8237%1.34Tricuspid Valve5%0.0850%1.2243%0.9616%0.51Left Ventricle95%2.0772%1.2574%1.1761%0.98Right Ventricle80%0.9085%1.1381%1.0937%0.79 Open table in a new tab