Pediatric hodgkin lymphoma: maximizing efficacy and minimizing toxicity

Historically, both adult and childhood Hodgkin lymphoma (HL) were treated with full-dose (35-45 Gy) extended-field radiation therapy (RT). Although this treatment was the first to produce reliable disease control, the resulting late toxicity led pediatric oncologists to pioneer the use of combined chemotherapy and low-dose (15-25 Gy) involved-field RT for all stages of HL. Currently, standard treatment of childhood HL is risk adapted; those with favorable risk disease typically receive 2 to 4 cycles of multi-agent chemotherapy with low-dose IFRT, whereas those with higher-risk disease receive more intensive chemotherapy before IFRT. This approach produces long-term survival rates >90% while limiting exposure to anthracyclines, alkylators, and radiation to normal tissues. In contrast to adult HL, IFRT remains an important component of the treatment of advanced-stage HL in pediatric patients. Current clinical trials for children with HL aim to further segregate patients into risk strata such that those who are highly curable can receive less toxic therapy, whereas high-risk patients can receive augmented therapy. Response-adapted therapy, in which overall treatment intensity is modified according to the initial response to chemotherapy, is emerging as a potential means of further reducing therapy for some while maintaining high cure rates. The challenge is to refine therapy in a rare disease in which long-time intervals are necessary to observe an adequate number of events (treatment failure or late effects) to answer judicious questions.