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

Abstract

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.

Advances in Hodgkin Lymphoma: Including the Patient’s Voice

“…Following patients over the last several decades allowed us to recognize the long-term health effects of curative therapeutic approaches, and subsequently long-term follow-up is essential to avoid trading one toxicity for another. Harmonization efforts for supportive care and long-term follow-up recommendations are underway and will be beneficial to provide therapy-specific and risk-adapted monitoring for toxicities and effects of therapy (2,6,70,(72)(73)(74). Ehrhardt makes a compelling argument to assess and consider the risk of late toxicities, converting this risk assessment into actionable data for the choice of upfront therapy (6).…”

“…Harmonization efforts for supportive care and long-term follow-up recommendations are underway and will be beneficial to provide therapy-specific and risk-adapted monitoring for toxicities and effects of therapy (2,6,70,(72)(73)(74). Ehrhardt makes a compelling argument to assess and consider the risk of late toxicities, converting this risk assessment into actionable data for the choice of upfront therapy (6).…”

“…After the advent of successful treatment with radiotherapy (RT) and then subsequently chemotherapy, death rates from HL have declined since 1975, with an additional impressive decrease of 4% per year from 2008 to 2017. Recent data highlight excellent overall survival (OS) of 87% at 5 years across the age span and 95% for pediatric patients (1,6). The failure rate of first-line therapies has similarly declined with 90% event free survival (EFS) in early stage disease and 80-85% EFS in advanced staged disease (7).…”

“…With such high survival rates, focus over the last three decades has shifted to reducing both the acute and long-term effects of treatment while maintaining long-term EFS and OS. This focus is important as treatment of relapsed/refractory disease requires additional exposure to toxicity through salvage regimens, RT, and potentially high dose therapy with autologous hematopoietic cell transplant (HDT/AHCT) (6).…”

Construction of a Non-Mutually Exclusive Decision Tree for Medication Recommendation of Chronic Heart Failure

“…The core challenge in the construction of the decision tree relies on the integration of clinical rules ( Ehrhardt et al, 2021 ). For some diseases, such as type 2 diabetes and hypertension, the whole population should be partitioned systematically according to the clinical guidelines.…”