Informing radiotherapy decisions in stage I/IIa Hodgkin lymphoma: Modelling life expectancy using radiation dosimetry

In recent randomized trials, omitting consolidative radiotherapy in early-stage Hodgkin lymphoma (ESHL) increased relapses. However, decades of follow-up are required to observe whether lower initial disease control is compensated by reduced risk of late effects. Extrapolation beyond trial follow-up is therefore necessary to inform current treatment decisions. To this end, we developed a microsimulation model to estimate lifetime quality-adjusted life years (QALYs) after combined modality treatment (CMT) or chemotherapy-alone for stage I/IIa ESHL. For CMT, the model included risks of breast and lung cancer, coronary heart disease and ischemic stroke. Comparative outcomes were assessed for a clinically relevant range of example patients differing by age, sex, smoking status, and representative organ-at-risk (OAR) radiation doses informed by the RAPID trial. Analysis was performed with and without a 3∙5% discount rate on future health. Smoking status had a large effect on optimal treatment choice. CMT was superior for nearly all never smoker example patients irrespective of age, sex, and OAR doses. At a maximum, CMT produced a 1.095 (95% CI: 1.054 to 1.137) gain in undiscounted QALYs for a 20y male never-smoker with unilateral neck disease. In contrast, current smokers could substantially gain from chemotherapy-alone. Again at a maximum, a 20y male patient with bilateral neck and whole mediastinum involvement gained 3.500 (95% CI: 3.400 to -3.600) undiscounted QALYs with chemotherapy-alone. Overall, CMT was more favorable the younger the patient, when future health discounting was included, and in never-smokers