title: Patterns of relapse from a phase 3 Study of response-based therapy for intermediate-risk Hodgkin lymphoma (AHOD0031): a report from the Children's Oncology Group.
abstract: OBJECTIVE
  The study was designed to determine whether response-based therapy improves outcomes in intermediate-risk Hodgkin lymphoma. We examined patterns of first relapse in the study.
  
  
  METHODS
  From September 2002 to July 2010, 1712 patients <22 years old with stage I-IIA with bulk, I-IIAE, I-IIB, and IIIA-IVA with or without doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide were enrolled. Patients were categorized as rapid (RER) or slow early responders (SER) after 2 cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide (ABVE-PC). The SER patients were randomized to 2 additional ABVE-PC cycles or augmented chemotherapy with 21 Gy involved field radiation therapy (IFRT). RER patients were stipulated to undergo 2 additional ABVE-PC cycles and were then randomized to 21 Gy IFRT or no further treatment if complete response (CR) was achieved. RER without CR patients were non-randomly assigned to 21 Gy IFRT. Relapses were characterized without respect to site (initial, new, or both; and initial bulk or initial nonbulk), and involved field radiation therapy field (in-field, out-of-field, or both). Patients were grouped by treatment assignment (SER; RER/no CR; RER/CR/IFRT; and RER/CR/no IFRT). Summary statistics were reported.
  
  
  RESULTS
  At 4-year median follow-up, 244 patients had experienced relapse, 198 of whom were fully evaluable for review. Those who progressed during treatment (n=30) or lacked relapse imaging (n=16) were excluded. The median time to relapse was 12.8 months. Of the 198 evaluable patients, 30% were RER/no CR, 26% were SER, 26% were RER/CR/no IFRT, 16% were RER/CR/IFRT, and 2% remained uncategorized. The 74% and 75% relapses involved initially bulky and nonbulky sites, respectively. First relapses rarely occurred at exclusively new or out-of-field sites. By contrast, relapses usually occurred at nodal sites of initial bulky and nonbulky disease.
  
  
  CONCLUSIONS
  Although response-based therapy has helped define treatment for selected RER patients, it has not improved outcome for SER patients or facilitated refinement of IFRT volumes or doses.
authors.affiliation: Mount Sinai Medical Center, New York, New York.
authors.forename: Kavita V
authors.initials: KV
authors.lastname: Dharmarajan
authors.affiliation: Vanderbilt University, Nashville, Tennessee.
authors.forename: Debra L
authors.initials: DL
authors.lastname: Friedman
authors.affiliation: MD Anderson Cancer Center, Houston, Texas.
authors.forename: Cindy L
authors.initials: CL
authors.lastname: Schwartz
authors.affiliation: Children's Oncology Group, Arcadia, California.
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.affiliation: Quality Assurance Review Center, Lincoln, Rhode Island.
authors.forename: T J
authors.initials: TJ
authors.lastname: FitzGerald
authors.affiliation: Rhode Island Hospital/Warren Alpert Medical School at Brown University, Providence, Rhode Island.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: McCarten
authors.affiliation: Quality Assurance Review Center, Lincoln, Rhode Island.
authors.forename: Sandy K
authors.initials: SK
authors.lastname: Kessel
authors.affiliation: Quality Assurance Review Center, Lincoln, Rhode Island.
authors.forename: Matt
authors.initials: M
authors.lastname: Iandoli
authors.affiliation: University of Rochester Medical Center, Rochester, New York.
authors.forename: Louis S
authors.initials: LS
authors.lastname: Constine
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, New York. Electronic address: woldens@mskcc.org.
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Wolden
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage; D002648:Child; D003131:Combined Modality Therapy / Q000379:methods; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D005500:Follow-Up Studies; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D011241:Prednisone / Q000008:administration & dosage; D012008:Recurrence; D012306:Risk; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D001761:Bleomycin; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone