Predicting radiotherapy dose to the heart and the risk of radiation-related cardiac toxicity for Hodgkin lymphoma patients, using pre-chemotherapy PET-CT scans
Consolidative radiotherapy (RT) used to treat early-stage Hodgkin lymphoma (HL) reduces the chance of recurrence , but may cause late toxicity including cardiovascular disease (CVD) . The risk of CVD can be estimated from the radiation dose received by the heart from RT, but currently this is only known once a RT plan has been produced.
The aim of this study was to develop a model to predict the dose the heart would receive, and thereby the risk of CVD, from RT using information available at the time of HL diagnosis.
The cohort was 169 patients treated with RT who had pre-chemotherapy PET-CT scans (pcPET-CT); 83% had stage 2 disease, and 91% had primary rather than relapsed HL. For each patient, the distribution of HL on the pcPET-CT was documented, and the mean heart dose (MHD) extracted from the RT plan. A multivariable linear regression model was built to predict MHD. Predicted MHDs were used in combination with a dose-response relationship for the risk of ischaemic heart disease (IHD) , and background IHD rates, to estimate absolute excess risk (AER) of IHD from RT.
The model that best predicted MHD included the extent to which HL overlapped the heart, presence of hilar disease, width of mediastinal disease, RT delivery technique and breathing mode. The mean prediction error was 2.9 Gray (Gy) (range 0.2 to 12.1). Individual patient AER of IHD calculated using the predicted MHD were closely correlated with the AER calculated using the RT plan MHD (Figure 1). AERs calculated using the MHD from each method were not statistically significantly different (paired t-test p=0.88; mean within-patient difference 0.9%).
Patient-specific risks from consolidative RT can be estimated using pcPET-CT. Work is ongoing to refine this model using a larger dataset, and develop models to predict other organ doses and associated risks. If validated, such estimates could inform shared decision-making about the use of RT to treat an individual with HL.
 Shaikh MP et al. Consolidation radiotherapy following positron emission tomography complete response in early-stage Hodgkin lymphoma: a meta-analysis. Leuk Lymphoma 2020;0:1
 Gustavsson A et al. A systematic overview of radiation therapy effects in Hodgkin’s lymphoma. Acta Oncol (Madr) 2003;42:589
 van Nimwegen FA et al. Radiation dose-response relationship for risk of coronary heart disease in survivors of Hodgkin lymphoma. J Clin Oncol 2016;34:235