title: 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.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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. debra.l.friedman@vanderbilt.edu.
authors.forename: Debra L
authors.initials: DL
authors.lastname: Friedman
authors.affiliation: 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.
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Wolden
authors.affiliation: 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.
authors.forename: Allen
authors.initials: A
authors.lastname: Buxton
authors.affiliation: 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.
authors.forename: Kathleen
authors.initials: K
authors.lastname: McCarten
authors.affiliation: 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.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: FitzGerald
authors.affiliation: 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.
authors.forename: Sandra
authors.initials: S
authors.lastname: Kessel
authors.affiliation: 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.
authors.forename: Pedro A
authors.initials: PA
authors.lastname: De Alarcon
authors.affiliation: 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.
authors.forename: Allen R
authors.initials: AR
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Nathan
authors.initials: N
authors.lastname: Kobrinsky
authors.affiliation: 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.
authors.forename: Peter
authors.initials: P
authors.lastname: Ehrlich
authors.affiliation: 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.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Hutchison
authors.affiliation: 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.
authors.forename: Louis S
authors.initials: LS
authors.lastname: Constine
authors.affiliation: 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.
authors.forename: Cindy L
authors.initials: CL
authors.lastname: Schwartz
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D012074:Remission Induction; D012307:Risk Factors; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects; D055815:Young Adult
chemical_list: D003561:Cytarabine; D001761:Bleomycin; D014750:Vincristine; D005047:Etoposide; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide; D002945:Cisplatin; D011241:Prednisone