Adolescents with Hodgkin Lymphoma Treated on Adult and Pediatric Protocols Have Distinct Therapeutic Outcome.

Hodgkin Lymphoma (HL) is a B cell malignancy, highly curable in the modern era (1989–2004). It is the most common cancer in the 15–19 age range. In the United States, adolescents with de novo HL may be treated on either pediatric or adult protocols. To identify outcomes of adolescents with HL, we conducted a comprehensive literature review and statistical analysis of all treatment trials (N > 50 pts) published in the past 15 years. Trials were selected for their relevance to treatment and disease outcome in adolescents with the following search criteria: Hodgkins disease, therapy, treatment, adolescents (13–18 years), and adults (19–44 years). The search retrieved 120 randomized control trials and 57 Phase II trials. 117 trials were eliminated due to inappropriate histology, non-clinical endpoints, topic reviews or otherwise not meeting established criteria. 79 studies were eligible for analysis. 15 pediatric treatment protocols (13 multi-center, 7 randomized) met established criteria. 7 identified the number of adolescents on trial (N=958/2675; 36%). Only 3 of these studies evaluated adolescent outcome; one trial demonstrated an inferior event-free survival for the adolescent subgroup vs. all children (72.0% vs. 89.0%; p-value 0.006, Chi Square Test). 57 adult treatment studies (39 multi-center, 44 randomized) were reviewed. 7 identified the number of adolescents on trial (N=422/2522; 17%). Only one provided information on adolescent outcome, which experienced a superior overall survival compared with the entire population (86.0% vs. 73.1%; p-value 0.030, Chi Square Test). None of the trials with both pediatric and adult subjects (7 multi-center, 4 randomized) provided information on the adolescent subgroup. In comparing pediatric and adult trials, we found remarkable differences in therapeutic approaches (all pediatric studies included XRT as a treatment component compared to 58% of adult studies) and in trial design (77% of adult studies were randomized compared to 47% of pediatric studies; p-value 0.0234, Fishers Exact Test). The adolescent population with HL is significantly understudied despite reasonable clinical trial participation and relatively high prevalence. In fact, only 4 published trials provided outcome information on adolescents with HL; in 2, outcome was statistically different from the rest of the study population, suggesting this subgroup may benefit from a specialized treatment approach. It is critical for future treatment trials to analyze results of the adolescent population to determine whether unique biological features, therapeutic practices, or host factors contribute to prognosis and outcome.