Mean heart dose (MHD) correlates with late cardiac toxicity among survivors of lymphoma receiving involved-field radiation therapy (IFRT). We investigated MHD and cardiac substructure dose across older and newer radiation fields and techniques to understand the value of evaluating MHD alone. Methods and Materials: After institutional review board approval, we developed a database of dosimetry plans for 40 patients with mediastinal lymphoma, which included IFRT (anterior-posterior and posterior-anterior), involved-site radiation therapy (ISRT) þ 3dimensional conformal radiation therapy (3DCRT), ISRT þ intensity modulated radiation therapy, and ISRT þ proton therapy plans for each patient. Each plan was evaluated for dose to the heart and cardiac substructures, including the right and left ventricles (RV, LV) and atria (RA, LA); tricuspid, mitral (MV), and aortic valves; and left anterior descending coronary artery (LAD). Correlation between MHD and cardiac substructure dose was assessed with linear regression. A correlation was considered very strong, strong, moderate, or weak if the r was !0.8, 0.6-0.79, 0.4-0.59, or <0.4, respectively. Results: A very strong correlation was observed between MHD and the mean cardiac substructure dose for each plan as follows: IFRTdLV, RV, LA, MV and LAD; ISRT þ 3DCRTdLV, RV, MV, TV, and LA; ISRT þ intensity modulated radiation therapydLV and RV; ISRT þ proton therapydnone. The following strong correlations were observed: IFRTdRA; ISRT þ 3DCRTdLAD, RA, AV; ISRT þ IMRTdLA, RA, LAD, AV, TV, and MV; ISRT þ proton therapydLV only. Conclusions: In the management of mediastinal lymphoma, more conformal treatment techniques can lead to more heterogeneous dose distributions across the heart, which translate into weaker relationships between mean heart dose and mean cardiac substructure doses. Consequently, models for assessing the risk of cardiac toxicity after radiation therapy that rely on MHD can be misleading when using modern treatment fields and techniques. Contouring the cardiac substructures and evaluating their dose is important when using contemporary RT.

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BackgroundHeparin-induced antibodies (HIA) are responsible for causing heparin-induced thrombocytopenia and thrombosis. Research has shown that the temporality of heparin-induced antibodies does not follow the classic immunologic response. The immunobiology of HIA generation remains unclear with varying in vitro and in vivo data. Outpatients undergoing hemodialysis (HD) are exposed to heparin chronically. The HIA immune response can therefore be investigated in vivo in this population.MethodsWe examined the time between the start of HD using unfractionated heparin and HIA levels in 212 outpatients during a 6-year period. Antibodies were detected on enzyme-linked immunosorbent assay. HIA levels were analyzed to determine significance of the trend over time. HIA subgroups were also analyzed for correlation with subsequent thrombotic events and platelet count during follow up.ResultsOverall, the HIA response in HD was found to peak early with waning antibody response despite continued exposure to heparin. The peak prevalence of a strong immune response (optical density > 1.000) was early and short lived, while weaker immune response (optical density 0.400–1.000) persisted for the first 6 months then declined. The mean follow-up time per patient was 2.3 ± 1.4 years. Despite circulating HIA, including high titers, no patients developed HIT in this sample. There was no association between HIA and thrombocytopenia. There was increased incidence of thrombosis in patients with strong HIA compared to other groups, but this did not achieve statistical significance.ConclusionsThe data suggest a significant temporal pattern of HIA in outpatients undergoing HD using unfractionated heparin. Positive HIA was not found to be significantly associated with thrombocytopenia or thrombosis risk in these patients. However, while not achieving statistical significance, subsequent thrombotic events occurred most frequently in the strong positive HIA group (optical density > 1.000). Further research into HIA and risk of thrombosis in this population is needed.