title: Omitting radiotherapy in early positron emission tomography-negative stage I/II Hodgkin lymphoma is associated with an increased risk of early relapse: Clinical results of the preplanned interim analysis of the randomized EORTC/LYSA/FIL H10 trial.
abstract: OBJECTIVE
  Combined-modality treatment is standard treatment for patients with clinical stage I/II Hodgkin lymphoma (HL). We hypothesized that an early positron emission tomography (PET) scan could be used to adapt treatment. Therefore, we started the randomized EORTC/LYSA/FIL Intergroup H10 trial evaluating whether involved-node radiotherapy (IN-RT) could be omitted without compromising progression-free survival in patients attaining a negative early PET scan after two cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) as compared with standard combined-modality treatment.
  
  
  METHODS
  Patients age 15 to 70 years with untreated clinical stage I/II HL were eligible. Here we report the clinical outcome of the preplanned interim futility analysis scheduled to occur after documentation of 34 events in the early PET-negative group. Because testing for futility in this noninferiority trial corresponds to testing the hypothesis of no difference, a one-sided superiority test was conducted.
  
  
  RESULTS
  The analysis included 1,137 patients. In the favorable subgroup, 85.8% had a negative early PET scan (standard arm, one event v experimental arm, nine events). In the unfavorable subgroup, 74.8% had a negative early PET scan (standard arm, seven events v experimental arm, 16 events). The independent data monitoring committee concluded it was unlikely that we would show noninferiority in the final results for the experimental arm and advised stopping random assignment for early PET-negative patients.
  
  
  CONCLUSIONS
  On the basis of this analysis, combined-modality treatment resulted in fewer early progressions in clinical stage I/II HL, although early outcome was excellent in both arms. The final analysis will reveal whether this finding is maintained over time.
authors.affiliation: John M.M. Raemaekers and Richard van der Maazen, Radboud University Medical Center, Nijmegen; Pieternella J. Lugtenburg, Erasmus University Medical Center, Rotterdam; Gustaaf van Imhoff, University Medical Centre Groningen, Groningen, the Netherlands; Marc P.E. André and Thierry van der Borght, Centre Hospitalier Universitaire (CHU) L'Université Catholique de Louvain Mont Godinne, Yvoir; Yolande Lievens, Ghent University Hospital, Ghent; Tiana Raveloarivahy and Catherine Fortpied, European Organisation for Research and Treatment of Cancer, Brussels, Belgium; Massimo Federico and Monica Bellei, University of Modena and Reggio Emilia, Modena; Ercole Brusamolino, Istituto Clinico Humanitas, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan; Manuel Gotti, Fondazione IRCCS Policlinico San Matteo, Pavia; Allessandro Re, Spedali Civili Hospital, Brescia; Elisabetta Abruzzese, San Eugenio Hospital, Tor Vergata University, Rome; Annibale Versari, Arcispedale Santa Maria Nuova, IRCCS di Reggio Emilia, Reggio Emilia, Italy; Theodore Girinsky and Christophe Fermé, Institut Gustave Roussy, Villejuif; Reman Oumedaly, CHU Caen; Stephane Bardet, Centre Francois Baclesse, Caen; Pauline Brice, Hôpital Saint-Louis, Paris; Reda Bouabdallah, Institut Paoli Calmette, Marseille; Catherine J. Sebban, Centre Léon Bérard, Lyon; Aspasia Stamatoullas, Centre Henri Becquerel, Rouen; Frank Morschhauser, CHU de Lille, Lille; Pierre Olivier, CHU Nancy, Nancy; Rene-Olivier Casasnovas, CHU de Dijon, Dijon; Michel Meignan, Hôpital Henri Mondor, Creteil, France; and Martin Hutchings, Rigshospitalet, Kopenhagen, Denmark.
authors.forename: John M M
authors.initials: JM
authors.lastname: Raemaekers
authors.forename: Marc P E
authors.initials: MP
authors.lastname: André
authors.forename: Massimo
authors.initials: M
authors.lastname: Federico
authors.forename: Theodore
authors.initials: T
authors.lastname: Girinsky
authors.forename: Reman
authors.initials: R
authors.lastname: Oumedaly
authors.forename: Ercole
authors.initials: E
authors.lastname: Brusamolino
authors.forename: Pauline
authors.initials: P
authors.lastname: Brice
authors.forename: Christophe
authors.initials: C
authors.lastname: Fermé
authors.forename: Richard
authors.initials: R
authors.lastname: van der Maazen
authors.forename: Manuel
authors.initials: M
authors.lastname: Gotti
authors.forename: Reda
authors.initials: R
authors.lastname: Bouabdallah
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Sebban
authors.forename: Yolande
authors.initials: Y
authors.lastname: Lievens
authors.forename: Allessandro
authors.initials: A
authors.lastname: Re
authors.forename: Aspasia
authors.initials: A
authors.lastname: Stamatoullas
authors.forename: Frank
authors.initials: F
authors.lastname: Morschhauser
authors.forename: Pieternella J
authors.initials: PJ
authors.lastname: Lugtenburg
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Abruzzese
authors.forename: Pierre
authors.initials: P
authors.lastname: Olivier
authors.forename: Rene-Olivier
authors.initials: RO
authors.lastname: Casasnovas
authors.forename: Gustaaf
authors.initials: G
authors.lastname: van Imhoff
authors.forename: Tiana
authors.initials: T
authors.lastname: Raveloarivahy
authors.forename: Monica
authors.initials: M
authors.lastname: Bellei
authors.forename: Thierry
authors.initials: T
authors.lastname: van der Borght
authors.forename: Stephane
authors.initials: S
authors.lastname: Bardet
authors.forename: Annibale
authors.initials: A
authors.lastname: Versari
authors.forename: Martin
authors.initials: M
authors.lastname: Hutchings
authors.forename: Michel
authors.initials: M
authors.lastname: Meignan
authors.forename: Catherine
authors.initials: C
authors.lastname: Fortpied
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage; D059248:Chemoradiotherapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D003606:Dacarbazine / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006689:Hodgkin Disease / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D009367:Neoplasm Staging; D049268:Positron-Emission Tomography / Q000379:methods; D011241:Prednisone / Q000008:administration & dosage; D011344:Procarbazine / Q000008:administration & dosage; D011446:Prospective Studies; D014747:Vinblastine / Q000008:administration & dosage; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D001761:Bleomycin; D011344:Procarbazine; D014750:Vincristine; D014747:Vinblastine; D005047:Etoposide; D003606:Dacarbazine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone