title: Second malignancy risk associated with treatment of Hodgkin's lymphoma: meta-analysis of the randomised trials.
abstract: BACKGROUND
  Despite several investigations, second malignancy risks (SMR) following radiotherapy alone (RT), chemotherapy alone (CT) and combined chemoradiotherapy (CRT) for Hodgkin's lymphoma (HL) remain controversial.
  
  
  METHODS
  We sought individual patient data from randomised trials comparing RT versus CRT, CT versus CRT, RT versus CT or involved-field (IF) versus extended-field (EF) RT for untreated HL. Overall SMR (including effects of salvage treatment) were compared using Peto's method.
  
  
  RESULTS
  Data for between 53% and 69% of patients were obtained for the four comparisons. (i) RT versus CRT (15 trials, 3343 patients): SMR were lower with CRT than with RT as initial treatment (odds ratio (OR) = 0.78, 95% confidence interval (CI) = 0.62-0.98 and P = 0.03). (ii) CT versus CRT (16 trials, 2861 patients): SMR were marginally higher with CRT than with CT as initial treatment (OR = 1.38, CI 1.00-1.89 and P = 0.05). (iii) IF-RT versus EF-RT (19 trials, 3221 patients): no significant difference in SMR (P = 0.28) although more breast cancers occurred with EF-RT (P = 0.04 and OR = 3.25).
  
  
  CONCLUSIONS
  Administration of CT in addition to RT as initial therapy for HL decreases overall SMR by reducing relapse and need for salvage therapy. Administration of RT additional to CT marginally increases overall SMR in advanced stages. Breast cancer risk (but not SMR in general) was substantially higher after EF-RT. Caution is needed in applying these findings to current therapies.
authors.affiliation: German Hodgkin Study Group, University of Cologne, Germany. jeremy.franklin@uk-koeln.de
authors.forename: J
authors.initials: J
authors.lastname: Franklin
authors.forename: A
authors.initials: A
authors.lastname: Pluetschow
authors.forename: M
authors.initials: M
authors.lastname: Paus
authors.forename: L
authors.initials: L
authors.lastname: Specht
authors.forename: A-P
authors.initials: AP
authors.lastname: Anselmo
authors.forename: A
authors.initials: A
authors.lastname: Aviles
authors.forename: G
authors.initials: G
authors.lastname: Biti
authors.forename: T
authors.initials: T
authors.lastname: Bogatyreva
authors.forename: G
authors.initials: G
authors.lastname: Bonadonna
authors.forename: C
authors.initials: C
authors.lastname: Brillant
authors.forename: E
authors.initials: E
authors.lastname: Cavalieri
authors.forename: V
authors.initials: V
authors.lastname: Diehl
authors.forename: H
authors.initials: H
authors.lastname: Eghbali
authors.forename: C
authors.initials: C
authors.lastname: Fermé
authors.forename: M
authors.initials: M
authors.lastname: Henry-Amar
authors.forename: R
authors.initials: R
authors.lastname: Hoppe
authors.forename: S
authors.initials: S
authors.lastname: Howard
authors.forename: R
authors.initials: R
authors.lastname: Meyer
authors.forename: D
authors.initials: D
authors.lastname: Niedzwiecki
authors.forename: S
authors.initials: S
authors.lastname: Pavlovsky
authors.forename: J
authors.initials: J
authors.lastname: Radford
authors.forename: J
authors.initials: J
authors.lastname: Raemaekers
authors.forename: D
authors.initials: D
authors.lastname: Ryder
authors.forename: P
authors.initials: P
authors.lastname: Schiller
authors.forename: S
authors.initials: S
authors.lastname: Shakhtarina
authors.forename: P
authors.initials: P
authors.lastname: Valagussa
authors.forename: J
authors.initials: J
authors.lastname: Wilimas
authors.forename: J
authors.initials: J
authors.lastname: Yahalom
mesh_terms: D003131:Combined Modality Therapy; D006689:Hodgkin Disease / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D016609:Neoplasms, Second Primary / Q000453:epidemiology*; D016032:Randomized Controlled Trials as Topic