Pediatric Hodgkin lymphoma: trade-offs between short- and long-term mortality risks

As pediatric Hodgkin lymphoma (HL) survival rates approach > 95%, treatment decisions are increasingly based on minimizing late effects. Using a model-based approach, we explored whether the addition of radiotherapy contributes to improved overall long-term survival. We developed a state-transition model to simulate the lifetime HL clinical course, and we compared 2 treatment strategies: chemotherapy alone (CT) and chemoradiotherapy (CRT). Data on HL relapse, late recurrence, and excess second cancer and cardiac late-effects mortality were estimated from the published literature and databases. Outcomes included conditional life expectancy, cause-specific mortality, and proportion alive at age 50. For a hypothetical cohort of HL patients (diagnosis age 15), conditional life expectancy was 57.2 years with CT compared with 56.4 years with CRT. Estimated lifetime HL mortality risk was 3.6% with CT versus 2.2% with CRT. In contrast, combined risk of excess late-effects mortality was lower for CT (1.8% vs 7.4% with CRT). Among those alive at age 50, only 9.2% of those initially treated with CT were at risk for radiation-related late effects (100% for CRT). Initial treatment with CT may be associated with longer average per-person life expectancy. These results support the need for careful consideration of the risk-benefit profile of radiation as frontline therapy in pediatric patients.