Adapted treatment guided by interim PET-CT scan in advanced Hodgkin's lymphoma

P. Johnson, M. Federico, P. A. Kirkwood, A. Fosså, Leanne Berkahn, A. Carella, F. D'Amore, Gunilla Enblad, A. Franceschetto, Michael J. Fulham, S. Luminari, MarkG O'Doherty, Pip Patrick, J. T. Roberts, Gamal Sidra, R. L. Stevens, P. Smith, Judith Trotman, Zaid Viney, J. RadfordSally F. Barrington

Research output: Contribution to journalArticle

Abstract

BACKGROUND: We tested interim positron-emission tomography-computed tomography (PET-CT) as a measure of early response to chemotherapy in order to guide treatment for patients with advanced Hodgkin's lymphoma. METHODS: Patients with newly diagnosed advanced classic Hodgkin's lymphoma underwent a baseline PETCT scan, received two cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy, and then underwent an interim PET-CT scan. Images were centrally reviewed with the use of a 5-point scale for PET findings. Patients with negative PET findings after two cycles were randomly assigned to continue ABVD (ABVD group) or omit bleomycin (AVD group) in cycles 3 through 6. Those with positive PET findings after two cycles received BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone). Radiotherapy was not recommended for patients with negative findings on interim scans. The primary outcome was the difference in the 3-year progression-free survival rate between randomized groups, a noninferiority comparison to exclude a difference of 5 or more percentage points. RESULTS: A total of 1214 patients were registered; 937 of the 1119 patients (83.7%) who underwent an interim PET-CT scan according to protocol had negative findings. With a median follow-up of 41 months, the 3-year progression-free survival rate and overall survival rate in the ABVD group were 85.7% (95% confidence interval [CI], 82.1 to 88.6) and 97.2% (95% CI, 95.1 to 98.4), respectively; the corresponding rates in the AVD group were 84.4% (95% CI, 80.7 to 87.5) and 97.6% (95% CI, 95.6 to 98.7). The absolute difference in the 3-year progression-free survival rate (ABVD minus AVD) was 1.6 percentage points (95% CI, -3.2 to 5.3). Respiratory adverse events were more severe in the ABVD group than in the AVD group. BEACOPP was given to the 172 patients with positive findings on the interim scan, and 74.4% had negative findings on a third PET-CT scan; the 3-year progression-free survival rate was 67.5% and the overall survival rate 87.8%. A total of 62 patients died during the trial (24 from Hodgkin's lymphoma), for a 3-year progression-free survival rate of 82.6% and an overall survival rate of 95.8%. CONCLUSIONS: Although the results fall just short of the specified noninferiority margin, the omission of bleomycin from the ABVD regimen after negative findings on interim PET resulted in a lower incidence of pulmonary toxic effects than with continued ABVD but not significantly lower efficacy. © Copyright 2016 Massachusetts Medical Society. All rights reserved.
Original languageEnglish
Pages (from-to)2419-2429
Number of pages11
JournalNew England Journal of Medicine
Volume374
Issue number25
DOIs
Publication statusPublished - 2016

Keywords

  • bleomycin
  • brentuximab vedotin
  • cyclophosphamide
  • dacarbazine
  • doxorubicin
  • etoposide
  • fluorodeoxyglucose f 18
  • prednisone
  • procarbazine
  • vinblastine
  • vincristine
  • antineoplastic agent
  • adult
  • advanced cancer
  • age distribution
  • Article
  • cancer combination chemotherapy
  • cancer mortality
  • cancer prognosis
  • cancer radiotherapy
  • cancer staging
  • cancer survival
  • cardiovascular disease
  • computer assisted emission tomography
  • controlled study
  • drug efficacy
  • dyspnea
  • fatigue
  • febrile neutropenia
  • female
  • fever
  • follow up
  • Hodgkin disease
  • human
  • image analysis
  • interim positron emission tomography computed tomography
  • lung disease
  • major clinical study
  • male
  • middle aged
  • multicenter study
  • multiple cycle treatment
  • neurologic disease
  • neutropenia
  • outcome assessment
  • overall survival
  • pneumonia
  • priority journal
  • progression free survival
  • randomized controlled trial
  • survival rate
  • survival time
  • thrombocytopenia
  • thromboembolism
  • treatment planning
  • treatment response
  • young adult
  • adolescent
  • clinical trial
  • computer assisted tomography
  • disease free survival
  • mortality
  • positron emission tomography
  • prospective study
  • radiography
  • scintiscanning
  • treatment outcome
  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols
  • Bleomycin
  • Dacarbazine
  • Disease-Free Survival
  • Doxorubicin
  • Female
  • Hodgkin Disease
  • Humans
  • Male
  • Middle Aged
  • Positron-Emission Tomography
  • Prospective Studies
  • Survival Rate
  • Tomography, X-Ray Computed
  • Treatment Outcome
  • Vinblastine
  • Young Adult

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    Johnson, P., Federico, M., Kirkwood, P. A., Fosså, A., Berkahn, L., Carella, A., D'Amore, F., Enblad, G., Franceschetto, A., Fulham, M. J., Luminari, S., O'Doherty, M., Patrick, P., Roberts, J. T., Sidra, G., Stevens, R. L., Smith, P., Trotman, J., Viney, Z., ... Barrington, S. F. (2016). Adapted treatment guided by interim PET-CT scan in advanced Hodgkin's lymphoma. New England Journal of Medicine, 374(25), 2419-2429. https://doi.org/10.1056/NEJMoa1510093