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

Debra L. Friedman, Lu Chen, Suzanne Wolden, Allen Buxton, Kathleen McCarten, Thomas J. FitzGerald, Sandra Kessel, Pedro A. De Alarcon, Allen R. Chen, Nathan Kobrinsky, Peter Ehrlich, Robert E. Hutchison, Louis S. Constine, Cindy L. Schwartz

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)3651-3658
Number of pages8
JournalJournal of Clinical Oncology
Volume32
Issue number32
DOIs
StatePublished - Nov 10 2014

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Friedman, D. L., Chen, L., Wolden, S., Buxton, A., McCarten, K., FitzGerald, T. J., Kessel, S., De Alarcon, P. A., Chen, A. R., Kobrinsky, N., Ehrlich, P., Hutchison, R. E., Constine, L. S., & Schwartz, C. L. (2014). 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. Journal of Clinical Oncology, 32(32), 3651-3658. https://doi.org/10.1200/JCO.2013.52.5410