An estimated 1100 children and adolescents younger than 20 years are diagnosed with Hodgkin lymphoma (HL) annually in the United States.1 Because of improvements in conventional therapy over recent decades, the rate of 5-year disease-free survival in HL is now 80% to 85%, with significantly better HL-specific survival among children compared with older patient groups.1
However, high rates of treatment-related morbidity have been observed in long-term survivors of HL, including cardiovascular, pulmonary, thyroid, cerebrovascular, and gonadal complications.1 An elevated risk of developing second malignant neoplasms has also been linked with curative HL therapy.2
“These late treatment sequelae negatively [affect] survivors’ health status and predispose them to premature death,” wrote Sharon M Castellino, MD, MSc, of the department of pediatrics at Emory School of Medicine in Atlanta, Georgia, and colleagues in a report published in the British Journal of Haematology.1 “Contributors to the lifelong burden of morbidity in young patients with HL include: acute toxicity and impaired health-related quality of life during and following treatment; latent effects of initial or relapse therapies; and financial hardship during therapy, which follows into the survivorship period for decades.”
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The researchers described factors that contribute to this “survivorship gap” in children and adolescents with HL, which they framed in terms of primary and secondary prevention strategies to minimize late effects. They noted that refining primary treatment approaches is the first key to narrowing the survivorship gap in HL. For example, targeted strategies specific to pediatric patients may allow for reductions in alkylating agent and anthracycline doses while preserving antilymphoma efficacy, and response-adapted approaches based on interim imaging have been shown to reduce radiation volumes. “In fact, recent pediatric trials indicate the feasibility of response-adapted omission of radiation,” the researchers wrote.1
Decreases in the doses and field extent of radiation have reduced normal tissue volume exposure and thus the risk of mortality associated with second malignant neoplasms and cardiovascular disease.1,3 “The possibility of further reducing normal tissue exposure with positron emission tomography-based response adaptation in combination with conformal fields, deep inspiration breath hold, and proton therapy is being evaluated in pediatric trials [ClinicalTrials.gov Identifiers: NCT02166463, NCT03907488, NCT02684708],” the researchers pointed out.1
They identified several priorities for further refinement of primary treatment strategies for pediatric patients with HL, including harmonization of risk classification and response criteria to facilitate comparison across groups. Several international groups are currently pursuing this effort in the Staging Evaluation and Response Criteria Harmonization initiative.4