In an analysis from the Childhood Cancer Survivor Study reported in the Journal of Clinical Oncology, Kevin C. Oeffinger, MD, and colleagues found that adoption of risk-adapted therapy in the 1990s was associated with reduced risk of serious chronic health conditions in pediatric Hodgkin lymphoma survivors vs patients treated in earlier decades.
Study Details
The study included data on 2,996 5-year Hodgkin lymphoma survivors in the Childhood Cancer Survivor Study who had been diagnosed from 1970 to 1999. The cumulative incidence of severe to fatal chronic conditions (grades 3–5) was assessed using self-report conditions, medically confirmed subsequent malignant neoplasms, and cause of death based on the National Death Index.
This study demonstrates that risk-adapted therapy for pediatric Hodgkin lymphoma has resulted in a significant reduction in serious long-term outcomes.— Kevin C. Oeffinger, MD, and colleagues
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Key Findings
Over the 3 decades of study, alterations in treatment included elimination or reduction of dose and volume of radiation and increased use of intermediate-dose alkylators and intermediate-dose anthracyclines.
Survivors had a mean age of 35.8 years (range = 12–58 years) at last follow-up.
In the entire cohort, the cumulative incidence of any grade 3 to 5 condition by age 35 was 31.4% (95% confidence interval [CI] = 29.2%–33.5%). Female patients were twice as likely to have a grade 3 to 5 condition vs males (41.3% vs 23.1%; hazard ratio [HR] = 2.1, 95% CI = 1.8–2.4).
Among survivors who underwent salvage therapy or hematopoietic cell transplantation for recurrence, the risk of a grade 3 to 5 condition was 4.7-fold higher vs survivors treated with a hybrid chemotherapeutic regimen alone. Risk in the former group was similar to that among survivors receiving high-dose extended-field radiotherapy (HR = 1.2, 95% CI = 0.9–1.5, for comparison).
From the 1970s to the 1990s, the decade-specific risk of a grade 3 to 5 condition was reduced by 20% (HR = 0.8, 95% CI = 0.7–0.9, P = .002 for trend); a prominent reduction in risk was observed for subsequent malignant neoplasms, with the cumulative incidence at age 35 decreasing from 10.9% in the 1970s to 5.7% in the 1990s.
In analysis comparing risk among survivors (n = 229) receiving a contemporary regimen prototype for low-intermediate risk disease (defined as doxorubicin < 250 mg/m2, cyclophosphamide 2,000–3,900 mg/m2, any vincristine, and any prednisone, with or without involved field radiation ≤ 26 Gy) vs those treated with chest radiotherapy at ≥ 35 Gy with or without chemotherapy (n = 1,215), the contemporary regimen was associated with a 40% reduction in risk of a grade 3 to 5 condition (cumulative incidence at age 30 = 14.5% vs 25.1%; HR = 0.6, 95% CI = 0.4–0.8).
The investigators concluded, “This study demonstrates that risk-adapted therapy for pediatric Hodgkin lymphoma has resulted in a significant reduction in serious long-term outcomes.”
Dr. Oeffinger, of Duke University/Duke Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by grants from the National Cancer Institute and the Meg Berté Owen Foundation. For full disclosures of the study authors, visit ascopubs.org.
