Using nonrandomized studies to inform complex clinical decisions: the thorny issue of cranial radiation therapy for T-cell acute lymphoblastic leukemia.

ABSTRACT

BACKGROUND: There are no randomized controlled trials to inform the decision of which cranial radiation therapy (CRT) strategy to apply to pediatric patients with T-cell acute lymphoblastic leukemia (ALL). PROCEDURE We performed a decision analysis using a Markov model in which we compared the life expectancy and quality-adjusted life expectancy when administering one of three CRT strategies to a cohort of patients with T-cell ALL (1) omission of CRT for all patients; (2) CRT only for those with evidence of leukemic involvement in the central nervous system at diagnosis (therapeutic strategy); or (3) CRT for all (prophylactic strategy). RESULTS: When considering plausible event-free survival rates and late mortality after cure for groups of pediatric patients with T-cell ALL, the strategies of omitting CRT, administering therapeutic CRT, and administering prophylactic CRT result in similar short-term (7-year) survival. When considering the increased contribution of deaths from late effects, the strategy of prophylactic CRT is associated with lower life expectancy when compared to the other two strategies. The Monte Carlo probabilistic sensitivity analysis demonstrated that the strategy of prophylactic CRT was the preferred strategy only 5% of the time. CONCLUSIONS: Similar short-term survival may be expected when comparing the strategies of total omission of CRT, therapeutic CRT, and prophylactic CRT for patients with T-cell ALL. Long-term survival is likely inferior for the strategy of prophylactic CRT. The synthesis of nonrandomized trials and the application of decision analysis can help inform complex decision making in pediatric oncology.