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

Abstract

In recent randomized trials, omitting consolidative radiotherapy (RT) 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 organs 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 regardless of age, sex, and OAR doses. At a maximum, CMT produced a 1.095 (95% CI: 1.054-1.137) gain in undiscounted QALYs for a 20-year-old male never smoker with unilateral neck disease. In contrast, current smokers could substantially gain from chemotherapy-alone treatment. Again at a maximum, a 20-year-old male current smoker with bilateral neck and whole mediastinum involvement gained 3.500 (95% CI: 3.400 to 3.600) undiscounted QALYs with chemotherapy-alone treatment. Overall, CMT was more favorable the younger the patient, when future health discounting was included, and in never smokers.

Reappraisal of the role of radiation therapy in lymphoma treatment

“…Hence, avoiding RT, even at great costs, seems to have gained wide popularity. However, if this comes at a cost from more intensive systemic treatments or a higher risk of relapse, then trying to avoid radiotherapy may backfire 20–24 . Serious long‐term side effects are also caused by systemic treatments, for example, second malignancies and cardiac toxicities.…”

“…However, if this comes at a cost from more intensive systemic treatments or a higher risk of relapse, then trying to avoid radiotherapy may backfire. [20][21][22][23][24] Serious long-term side effects are also caused by systemic treatments, for example, second malignancies and cardiac toxicities. What we need are tools to find the optimal combination of systemic treatments and modern RT, taking lymphoma subtype, anatomic location and extent of disease, patient age, sex, comorbidities, and preferences into account.…”