Secondary malignant neoplasms, progression-free survival and overall survival in patients treated for Hodgkin lymphoma: a systematic review and meta-analysis of randomized clinical trials
Dennis A. Eichenauer,
Ingrid Becker,
Ina Monsef,
Nicholas Chadwick,
Vitaliana de Sanctis,
Massimo Federico,
Catherine Fortpied,
Alessandro M. Gianni,
Michel Henry-Amar,
Peter Hoskin,
Peter Johnson,
Stefano Luminari,
Monica Bellei,
Alessandro Pulsoni,
Matthew R. Sydes,
Pinuccia Valagussa,
Simonetta Viviani,
Andreas Engert,
Jeremy Franklin
Affiliations
Dennis A. Eichenauer
First Department of Internal Medicine and German Hodgkin Study Group (GHSG), University Hospital Cologne, Germany
Ingrid Becker
Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne, Germany
Ina Monsef
Cochrane Haematological Malignancies Group, First Department of Internal Medicine, University Hospital Cologne, Germany
Nicholas Chadwick
University College London (UCL) Cancer Trials Centre, UK
Vitaliana de Sanctis
Department of Radiotherapy, University “La Sapienza”, Rome, Italy
Massimo Federico
University of Modena and Reggio Emilia, Modena, Italy
Catherine Fortpied
European Organisation of Research and Treatment of Cancer (EORTC), Brussels, Belgium
Alessandro M. Gianni
Istituto Nazionale dei Tumori, Milan, Italy
Michel Henry-Amar
Centre de Traitement des Données du Cancéropôle Nord-Ouest, Centre François Baclesse, Caen, France
Peter Hoskin
Mount Vernon Cancer Centre, Northwood, UK
Peter Johnson
Cancer Research UK Centre, University of Southampton, UK
Stefano Luminari
University of Modena and Reggio Emilia, Modena, Italy;Hematology, Arcispedale S. Maria Nuova IRCCS, Reggio Emilia, Italy
Monica Bellei
University of Modena and Reggio Emilia, Modena, Italy
Alessandro Pulsoni
Cellular Biotechnology and Hematology Department, University “La Sapienza”, Rome, Italy
Matthew R. Sydes
Medical Research Council (MRC), Clinical Trials Unit at University College London (UCL), UK
Pinuccia Valagussa
Istituto Nazionale dei Tumori, Milan, Italy
Simonetta Viviani
Istituto Nazionale dei Tumori, Milan, Italy
Andreas Engert
First Department of Internal Medicine and German Hodgkin Study Group (GHSG), University Hospital Cologne, Germany
Jeremy Franklin
Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne, Germany
Treatment intensification to maximize disease control and reduced intensity approaches to minimize the risk of late sequelae have been evaluated in newly diagnosed Hodgkin lymphoma. The influence of these interventions on the risk of secondary malignant neoplasms, progression-free survival and overall survival is reported in the meta-analysis herein, based on individual patient data from 9498 patients treated within 16 randomized controlled trials for newly diagnosed Hodgkin lymphoma between 1984 and 2007. Secondary malignant neoplasms were meta-analyzed using Peto’s method as time-to-event outcomes. For progression-free and overall survival, hazard ratios derived from each trial using Cox regression were combined by inverse-variance weighting. Five study questions (combined-modality treatment vs. chemotherapy alone; more extended vs. involved-field radiotherapy; radiation at higher doses vs. radiation at 20 Gy; more vs. fewer cycles of the same chemotherapy protocol; standard-dose chemotherapy vs. intensified chemotherapy) were investigated. After a median follow-up of 7.4 years, dose-intensified chemotherapy resulted in better progression-free survival rates (P=0.007) as compared with standard-dose chemotherapy, but was associated with an increased risk of therapy-related acute myeloid leukemia/myelodysplastic syndromes (P=0.0028). No progression-free or overall survival differences were observed between combined-modality treatment and chemotherapy alone, but more secondary malignant neoplasms were seen after combined-modality treatment (P=0.010). For the remaining three study questions, outcomes and secondary malignancy rates did not differ significantly between treatment strategies. The results of this meta-analysis help to weigh up efficacy and secondary malignancy risk for the choice of first-line treatment for Hodgkin lymphoma patients. However, final conclusions regarding secondary solid tumors require longer follow-up.
