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.

J Clin Oncol

Debra L. Friedman, Vanderbilt University School of Medicine and Vanderbilt-Ingram Cancer Center, Nashville, TN; Lu Chen and Allen Buxton, Children's Oncology Group, Monrovia, CA; Suzanne Wolden, Memorial Sloan Kettering Cancer Center, New York; Robert E. Hutchison, State University of New York Upstate Medical University, Syracuse; Louis S. Constine, University of Rochester, Rochester, NY; Kathleen McCarten, Thomas J. FitzGerald, and Sandra Kessel, Quality Assurance Review Center, Providence, RI; Pedro A. De Alarcon, University of Illinois College of Medicine, Peoria, IL; Allen R. Chen, Johns Hopkins University, Baltimore, MD; Nathan Kobrinsky, Sanford Medical Center and Roger Maris Cancer Center, Fargo, ND; Peter Ehrlich, C.S. Mott Children's Hospital and University of Michigan, Ann Arbor, MI; and Cindy L. Schwartz, MD Anderson Cancer Center, Houston, TX.

Published: November 2014

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 intermediate-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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044PMC
http://dx.doi.org/10.1200/JCO.2013.52.5410DOI Listing

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