Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: A report from the children's oncology group study AHOD0031

Purpose The Children's Oncology Group study AHOD0031, a randomized phase III study, was designed to evaluate the role of early chemotherapy response in tailoring subsequent therapy in pediatric ntermediate-risk Hodgkin lymphoma. To avoid treatment-associated risks that compromise long-term health and to maintain high cure rates, dose-intensive chemotherapy with limited cumulative doses was used.

Patients and Methods Patients received two cycles of doxorubicin, bleomycin, vincristine, etoposide, cyclophosphamide, and prednisone (ABVE-PC) followed by response evaluation. Rapid early responders (RERs) received two additional ABVE-PC cycles, followed by complete response (CR) evaluation. RERs with CR were randomly assigned to involved-field radiotherapy (IFRT) or no additional therapy; RERs with less than CR were nonrandomly assigned to IFRT. Slow early responders (SERs) were randomly assigned to receive two additional ABVE-PC cycles with or without two cycles of dexamethasone, etoposide, cisplatin, and cytarabine (DECA). All SERs were assigned to receive IFRT.

Results Among 1,712 eligible patients, 4-year event-free survival (EFS) was 85.0%: 86.9% for RERs and 77.4% for SERs (P <.001). Four-year overall survival was 97.8%: 98.5% for RERs and 95.3% for SERs (P <.001). Four-year EFS was 87.9% versus 84.3% (P =.11) for RERs with CR who were randomly assigned to IFRT versus no IFRT, and 86.7% versus 87.3% (P =.87) for RERs with positron emission tomography (PET)-negative results at response assessment Four-year EFS was 79.3% versus 75.2% (P =.11) for SERs who were randomly assigned to DECA versus no DECA, and 70.7% versus 54.6% (P =.05) for SERs with PET-positive results at response assessment.

Conclusion This trial demonstrated that early response assessment supported therapeutic titration (omitting radiotherapy in RERs with CR; augmenting chemotherapy in SERs with PET-positive disease) Strategies directed toward improved response assessment and risk stratification may enhance tailoring of treatment to patient characteristics and response.