Results of a trial of PET-directed therapy for early-stage Hodgkin's lymphoma.

BACKGROUND It is unclear whether patients with early-stage Hodgkin's lymphoma and negative findings on positron-emission tomography (PET) after three cycles of chemotherapy with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) require radiotherapy. METHODS Patients with newly diagnosed stage IA or stage IIA Hodgkin's lymphoma received three cycles of ABVD and then underwent PET scanning. Patients with negative PET findings were randomly assigned to receive involved-field radiotherapy or no further treatment; patients with positive PET findings received a fourth cycle of ABVD and radiotherapy. This trial assessing the noninferiority of no further treatment was designed to exclude a difference in the 3-year progression-free survival rate of 7 or more percentage points from the assumed 95% progression-free survival rate in the radiotherapy group. RESULTS A total of 602 patients (53.3% male; median age, 34 years) were recruited, and 571 patients underwent PET scanning. The PET findings were negative in 426 of these patients (74.6%), 420 of whom were randomly assigned to a study group (209 to the radiotherapy group and 211 to no further therapy). At a median of 60 months of follow-up, there had been 8 instances of disease progression in the radiotherapy group, and 8 patients had died (3 with disease progression, 1 of whom died from Hodgkin's lymphoma); there had been 20 instances of disease progression in the group with no further therapy, and 4 patients had died (2 with disease progression and none from Hodgkin's lymphoma). In the radiotherapy group, 5 of the deaths occurred in patients who received no radiotherapy. The 3-year progression-free survival rate was 94.6% (95% confidence interval [CI], 91.5 to 97.7) in the radiotherapy group and 90.8% (95% CI, 86.9 to 94.8) in the group that received no further therapy, with an absolute risk difference of -3.8 percentage points (95% CI, -8.8 to 1.3). CONCLUSIONS The results of this study did not show the noninferiority of the strategy of no further treatment after chemotherapy with regard to progression-free survival. Nevertheless, patients in this study with early-stage Hodgkin's lymphoma and negative PET findings after three cycles of ABVD had a very good prognosis either with or without consolidation radiotherapy. (Funded by Leukaemia and Lymphoma Research and others; RAPID ClinicalTrials.gov number, NCT00943423.).

[1]  J. Raemaekers,et al.  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. , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  J. Radford Treatment for early-stage hodgkin lymphoma: has radiotherapy had its day? , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  R. Greil,et al.  Dose-intensification in early unfavorable Hodgkin's lymphoma: final analysis of the German Hodgkin Study Group HD14 trial. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  Bingshu E. Chen,et al.  ABVD alone versus radiation-based therapy in limited-stage Hodgkin's lymphoma. , 2012, The New England journal of medicine.

[5]  J. Raemaekers,et al.  Premature ovarian failure and fertility in long-term survivors of Hodgkin's lymphoma: a European Organisation for Research and Treatment of Cancer Lymphoma Group and Groupe d'Etude des Lymphomes de l'Adulte Cohort Study. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[6]  P. Marsden,et al.  Establishment of a UK-wide network to facilitate the acquisition of quality assured FDG-PET data for clinical trials in lymphoma. , 2011, Annals of oncology : official journal of the European Society for Medical Oncology.

[7]  A. LaCasce,et al.  Clinically significant cardiac disease in patients with Hodgkin lymphoma treated with mediastinal irradiation. , 2011, Blood.

[8]  R. Greil,et al.  Intensified chemotherapy and dose-reduced involved-field radiotherapy in patients with early unfavorable Hodgkin's lymphoma: final analysis of the German Hodgkin Study Group HD11 trial. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  R. Greil,et al.  Reduced treatment intensity in patients with early-stage Hodgkin's lymphoma. , 2010, The New England journal of medicine.

[10]  J. Radford,et al.  Concordance between four European centres of PET reporting criteria designed for use in multicentre trials in Hodgkin lymphoma , 2010, European Journal of Nuclear Medicine and Molecular Imaging.

[11]  A. Pettitt,et al.  Randomized comparison of the stanford V regimen and ABVD in the treatment of advanced Hodgkin's Lymphoma: United Kingdom National Cancer Research Institute Lymphoma Group Study ISRCTN 64141244. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  V. Diehl,et al.  Escalated-dose BEACOPP in the treatment of patients with advanced-stage Hodgkin's lymphoma: 10 years of follow-up of the GHSG HD9 study. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[13]  H. Amthauer,et al.  Positron emission tomography has a high negative predictive value for progression or early relapse for patients with residual disease after first-line chemotherapy in advanced-stage Hodgkin lymphoma. , 2008, Blood.

[14]  J. Raemaekers,et al.  Chemotherapy plus involved-field radiation in early-stage Hodgkin's disease. , 2007, The New England journal of medicine.

[15]  A. Horwich,et al.  Myocardial infarction mortality risk after treatment for Hodgkin disease: a collaborative British cohort study. , 2007, Journal of the National Cancer Institute.

[16]  J. Raemaekers,et al.  Combined-modality therapy for clinical stage I or II Hodgkin's lymphoma: long-term results of the European Organisation for Research and Treatment of Cancer H7 randomized controlled trials. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  Martin Hutchings,et al.  FDG-PET after two cycles of chemotherapy predicts treatment failure and progression-free survival in Hodgkin lymphoma. , 2006, Blood.

[18]  J. Connors,et al.  Randomized comparison of ABVD chemotherapy with a strategy that includes radiation therapy in patients with limited-stage Hodgkin's lymphoma: National Cancer Institute of Canada Clinical Trials Group and the Eastern Cooperative Oncology Group. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[19]  N. Mikhaeel,et al.  Prognostic value of interim FDG-PET after two or three cycles of chemotherapy in Hodgkin lymphoma. , 2005, Annals of oncology : official journal of the European Society for Medical Oncology.

[20]  A. Purushotham,et al.  Breast cancer in women after treatment for Hodgkin's disease. , 2003, The Lancet. Oncology.

[21]  J. Leonard,et al.  PET predicts prognosis after 1 cycle of chemotherapy in aggressive lymphoma and Hodgkin's disease. , 2002, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[22]  John D Boice,et al.  Lung cancer following chemotherapy and radiotherapy for Hodgkin's disease. , 2002, Journal of the National Cancer Institute.

[23]  A. Zauber,et al.  Incidence of second cancers in patients treated for Hodgkin's disease. , 1995, Journal of the National Cancer Institute.

[24]  K. Propert,et al.  Chemotherapy of advanced Hodgkin's disease with MOPP, ABVD, or MOPP alternating with ABVD. , 1992, The New England journal of medicine.

[25]  S. Hancock,et al.  Thyroid diseases after treatment of Hodgkin's disease. , 1991, The New England journal of medicine.

[26]  M Tubiana,et al.  Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin's disease: Cotswolds meeting. , 1989, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[27]  D. Deakin,et al.  A randomised study of adjuvant chemotherapy after mantle radiotherapy in supradiaphragmatic Hodgkin's disease PS IA-IIB: a report from the Manchester lymphoma group. , 1984, British Journal of Cancer.

[28]  D. Crowther,et al.  The effects of Hodgkin's disease and combination chemotherapy on gonadal function in the adult male , 1982, Cancer.

[29]  G. Bonadonna,et al.  Combination chemotherapy of Hodgkin's disease with adriamycin, bleomycin, vinblastine, and imidazole carboxamide versus MOPP , 1975, Cancer.

[30]  T. Mcelwain Combination chemotherapy of Hodgkin's disease. , 1971, British journal of haematology.

[31]  C. J. Karzmark,et al.  Physical and dosimetric aspects of the radiotherapy of malignant lymphomas. I. The mantle technique. , 1970, Radiology.

[32]  C. J. Karzmark,et al.  Physical and dosimetric aspects of the radiotherapy of malignant lymphomas. II. The inverted-Y technique. , 1970, Radiology.

[33]  John McGrath,et al.  Hodgkin’s Disease , 1933, JAMA.