Purpose: As survival rates for pediatric Hodgkin’s disease (HD) approximate 90-100%, treatment decisions are increasingly based upon minimizing late-effects risk and late mortality. While more intensive HD treatment may lead to lower relapse rates, patients face higher risks of late-effects mortality, including second cancers. Yet less intensive treatment may compromise initial disease control. Using a model-based approach, we provide insight on trade-offs between short- and long-term mortality risks on overall survival.
Methods: We developed a state-transition model to simulate the lifetime clinical course of patients diagnosed with HD during childhood. We compared two general treatment strategies, chemotherapy alone and chemotherapy combined with radiation therapy (chemoradiotherapy). Relapses for both strategies were treated with salvage therapy. Data on (1) probability of relapse from original cancer, (2) late-recurrence mortality, (3) excess mortality from second cancer and cardiac late-effects, and (4) background mortality were estimated from published literature and databases. Outcomes included cause-specific mortality, cumulative mortality probability, conditional life expectancy, and proportion alive at age 50.
Results: For a cohort of HD patients diagnosed at age 15, conditional life expectancy was 57.2 years with chemotherapy alone compared to 56.4 years with chemoradiotherapy. The estimated lifetime HD mortality risk associated with chemotherapy alone was 3.6% versus 2.2% with chemoradiotherapy. In contrast, there was a lower risk of second cancers with chemotherapy alone (0.9%) compared with chemoradiotherapy (2.4%). Similarly, there was a lower risk of cardiac deaths with chemotherapy alone (0.9%) compared with chemoradiotherapy (5.0%). Among individuals alive at age 50, only 9.2% of those treated with chemotherapy alone were at risk for radiation-related late-effects (compared to 100% for chemoradiotherapy). Sensitivity analysis found that chemotherapy alone was the preferred strategy unless its probability of relapse was 40% higher or the excess risk associated with radiation-related cardiac events for chemoradiotherapy was 60% lower. Probabilistic sensitivity analysis estimated that the probability that chemotherapy alone was associated with higher LE was 0.69, and for a shorter 25-year time horizon, 0.47.
Conclusions: Chemotherapy alone may lead to more favorable survival when both short- and long-term outcomes are considered, although outcomes for shorter time horizons are less certain. Omitting radiation as frontline therapy, as has become increasingly common in adults, should also be considered for pediatric HD patients.
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