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

J Clin Oncol. 2014 Apr 20;32(12):1188-94. doi: 10.1200/JCO.2013.51.9298. Epub 2014 Mar 17.

Abstract

Purpose: 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.

Patients and 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.

Conclusion: 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.

Trial registration: ClinicalTrials.gov NCT00433433.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bleomycin / administration & dosage
  • Chemoradiotherapy
  • Cyclophosphamide / administration & dosage
  • Dacarbazine / administration & dosage
  • Disease-Free Survival
  • Doxorubicin / administration & dosage
  • Etoposide / administration & dosage
  • Female
  • Hodgkin Disease / diagnostic imaging
  • Hodgkin Disease / drug therapy*
  • Hodgkin Disease / pathology
  • Hodgkin Disease / radiotherapy*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Positron-Emission Tomography / methods
  • Prednisone / administration & dosage
  • Procarbazine / administration & dosage
  • Prospective Studies
  • Vinblastine / administration & dosage
  • Vincristine / administration & dosage
  • Young Adult

Substances

  • Bleomycin
  • Procarbazine
  • Vincristine
  • Vinblastine
  • Etoposide
  • Dacarbazine
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone

Supplementary concepts

  • ABVD protocol
  • BEACOPP protocol

Associated data

  • ClinicalTrials.gov/NCT00433433