Integration of Pediatric Hodgkin Lymphoma Treatment and Late Effects Guidelines: Seeing the Forest Beyond the Trees

The successful integration of clinical trials into pediatric oncology has led to steady improvement in the 5-year survival rate for children diagnosed with Hodgkin lymphoma (HL). It is estimated that >95% of children newly diagnosed with HL will become long-term survivors. Despite these successes, survival can come at a cost. Historically, long-term survivors of HL have a high risk of late-occurring adverse health effects and increased risk of nonrelapse mortality compared with the general population. The recognition of late-occurring events paired with the decades of life remaining for children cured of HL have made paramount the need to develop effective treatments that minimize the risk of late toxicity. Toward this goal, multiple, dose-intense, risk- and response-based regimens that use lower cumulative doses of chemotherapy and radiation have been developed. Appropriate frontline treatment selection requires a level of familiarity with the efficacy, acute toxicity, convenience, and late effects of treatments that may be impractical for providers who infrequently treat children with HL. There is an increasing need for guideline developers to begin to merge considerations from both frontline treatment and survivorship guidelines into practical documents that integrate potential long-term health risks. Herein, we take the first steps toward doing so by aligning cumulative treatment exposures, anticipated risks of late toxicity, and suggested surveillance recommendations for NCCN-endorsed Pediatric HL Guidelines. Future studies that integrate simulation modeling will strengthen this integrated approach and allow for opportunities to incorporate regimen-specific risks, health-related quality of life, and cost-effectiveness into decision tools to optimize HL therapy.