title: An individual patient-data comparison of combined modality therapy and ABVD alone for patients with limited-stage Hodgkin lymphoma.
abstract: BACKGROUND
  Treatment options for patients with nonbulky stage IA-IIA Hodgkin lymphoma include combined modality therapy (CMT) using doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) plus involved-field radiation therapy (IFRT), and chemotherapy with ABVD alone. There are no mature randomized data comparing ABVD with CMT using modern radiation techniques.
  
  
  METHODS
  Using German Hodgkin Study Group HD10/HD11 and NCIC Clinical Trials Group HD.6 databases, we identified 588 patients who met mutually inclusive eligibility criteria from the preferred arms of HD10 or 11 (n = 406) and HD.6 (n = 182). We evaluated time to progression (TTP), progression-free (PFS) and overall survival, including in three predefined exploratory subset analyses.
  
  
  RESULTS
  With median follow-up of 91 (HD10/11) and 134 (HD.6) months, respective 8-year outcomes were for TTP, 93% versus 87% [hazard ratio (HR) 0.44, 95% confidence interval (CI) 0.24-0.78]; for PFS, 89% versus 86% (HR 0.71, 95% CI 0.42-1.18) and for overall survival, 95% versus 95% (HR 1.09, 95% CI 0.49-2.40). In the exploratory subset analysis including HD10 eligible patients who achieved complete response (CR) or unconfirmed complete response (CRu) after two cycles of ABVD, 8-year PFS was 87% (HD10) versus 95% (HD.6) (HR 2.8; 95% CI 0.64-12.5) and overall survival 96% versus 100%. In contrast, among those without CR/CRu after two cycles of ABVD, 8-year PFS was 88% versus 74% (HR 0.35; 95% CI 0.16-0.79) and overall survival 95% versus 91%, respectively (HR 0.42; 95% CI 0.12-1.44).
  
  
  CONCLUSIONS
  In patients with nonbulky stage IA-IIA Hodgkin lymphoma, CMT provides better disease control than ABVD alone, especially among those not achieving complete response after two cycles of ABVD. Within the follow-up duration evaluated, overall survivals were similar. Longer follow-up is required to understand the implications of radiation and chemotherapy-related late effects.
  
  
  RESULTS
  The trials included in this analysis were registered at ClinicalTrials.gov: HD10 - NCT00265018, HD11 - NCT00264953, HD.6 - NCT00002561.
authors.affiliation: NCIC Clinical Trials Group and Queen's University, Kingston, Ontario, Canada.
authors.forename: A E
authors.initials: AE
authors.lastname: Hay
authors.forename: B
authors.initials: B
authors.lastname: Klimm
authors.forename: B E
authors.initials: BE
authors.lastname: Chen
authors.forename: H
authors.initials: H
authors.lastname: Goergen
authors.forename: L E
authors.initials: LE
authors.lastname: Shepherd
authors.forename: M
authors.initials: M
authors.lastname: Fuchs
authors.forename: M K
authors.initials: MK
authors.lastname: Gospodarowicz
authors.forename: P
authors.initials: P
authors.lastname: Borchmann
authors.forename: J M
authors.initials: JM
authors.lastname: Connors
authors.forename: J
authors.initials: J
authors.lastname: Markova
authors.forename: M
authors.initials: M
authors.lastname: Crump
authors.forename: A
authors.initials: A
authors.lastname: Lohri
authors.forename: J N
authors.initials: JN
authors.lastname: Winter
authors.forename: B
authors.initials: B
authors.lastname: Dörken
authors.forename: R G
authors.initials: RG
authors.lastname: Pearcey
authors.forename: V
authors.initials: V
authors.lastname: Diehl
authors.forename: S J
authors.initials: SJ
authors.lastname: Horning
authors.forename: H T
authors.initials: HT
authors.lastname: Eich
authors.forename: A
authors.initials: A
authors.lastname: Engert
authors.forename: R M
authors.initials: RM
authors.lastname: Meyer
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001761:Bleomycin / Q000627:therapeutic use; D059248:Chemoradiotherapy; D003606:Dacarbazine / Q000627:therapeutic use; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000627:therapeutic use; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D016896:Treatment Outcome; D014747:Vinblastine / Q000627:therapeutic use
chemical_list: D001761:Bleomycin; D014747:Vinblastine; D003606:Dacarbazine; D004317:Doxorubicin
keywords: Hodgkin lymphoma; chemotherapy; clinical trial; combined modality therapy; progression-free survival; radiation therapy