BACKGROUND: Children and adolescents with early-stage classical Hodgkin lymphoma have a 5-year event-free survival of 90% or more with vincristine, etoposide, prednisone, and doxorubicin (OEPA) plus radiotherapy, but late complications of treatment affect survival and quality of life. We investigated whether radiotherapy can be omitted in patients with adequate morphological and metabolic responses to OEPA. METHODS: The EuroNet-PHL-C1 trial was designed as a titration study and recruited patients at 186 hospital sites across 16 European countries. Children and adolescents with newly diagnosed stage IA, IB, and IIA classical Hodgkin lymphoma younger than 18 years of age were assigned to treatment group 1 to be treated with two cycles of OEPA (vincristine 1·5 mg/m2 intravenously, capped at 2 mg, on days 1, 8, and 15; etoposide 125 mg/m2 intravenously, on days 1-5; prednisone 60 mg/m2 orally on days 1-15; and doxorubicin 40 mg/m2 intravenously on days 1 and 15). If no adequate response (a partial morphological remission or greater and PET negativity) had been achieved after two cycles of OEPA, involved-field radiotherapy was administered at a total dose of 19·8 Gy (usually in 11 fractions of 1·8 Gy per day). The primary endpoint was event-free survival. The primary objective was maintaining a 5-year event-free survival rate of 90% in patients with an adequate response to OEPA without radiotherapy. We performed intention-to-treat and per-protocol analyses. The trial was registered at ClinicalTrials.gov (NCT00433459) and with EUDRACT, (2006-000995-33) and is completed. FINDINGS: Between Jan 31, 2007, and Jan 30, 2013, 2131 patients were registered and 2102 patients were enrolled onto EuroNet-PHL-C1. Of these 2102 patients, 738 with early-stage disease were allocated to treatment group 1. Median follow-up was 63·3 months (IQR 60·1-69·8). We report on 714 patients assigned to and treated on treatment group 1; the intention-to-treat population comprised 713 patients with 323 (45%) male and 390 (55%) female patients. In 440 of 713 patients in the intention-to-treat group who had an adequate response and did not receive radiotherapy, 5-year event-free survival was 86·5% (95% CI 83·3-89·8), which was less than the 90% target rate. In 273 patients with an inadequate response who received radiotherapy, 5-year event-free survival was 88·6% (95% CI 84·8-92·5), for which the 95% CI included the 90% target rate. The most common grade 3-4 adverse events were neutropenia (in 597 [88%] of 680 patients) and leukopenia (437 [61%] of 712). There were no treatment-related deaths. INTERPRETATION: On the basis of all the evidence, radiotherapy could be omitted in patients with early-stage classical Hodgkin lymphoma and an adequate response to OEPA, but patients with risk factors might need more intensive treatment. FUNDING: Deutsche Krebshilfe, Elternverein für Krebs-und leukämiekranke Kinder, Gießen, Kinderkrebsstiftung Mainz of the Journal Oldtimer Markt, Tour der Hoffnung, Menschen für Kinder, Mitteldeutsche Kinderkrebsforschung, Programme Hospitalier de Recherche Clinique, and Cancer Research UK.

Children and Young People's Cancer Service University College Hospital London London UK

Clinical Department of Paediatric Haematology Oncology and Stem Cell Transplantation University Medical Centre Ljubljana and University Children's Hospital Ljubljana Slovenia

Department of Cellular Pathology University College Hospital London London UK

Department of Nuclear Medicine Tenon Hospital APHP and Sorbonne Université Paris France

Department of Nuclear Medicine University of Leipzig Leipzig Germany

Department of Paediatric Haematology and Oncology Medical University of Vienna Vienna Austria

Department of Paediatric Haematology and Oncology National Institute of Children's Disease and Comenius University Bratislava Slovakia

Department of Paediatric Haematology and Oncology Royal Hospital for Children and Young People University of Edinburgh Edinburgh UK

Department of Paediatric Haematology and Oncology University Hospital Motol Prague Czech Republic

Department of Paediatric Haematology Oncology Sorbonne Université and Assistance Publique des Hopitaux de Paris Hôpital a Trousseau Paris France

Department of Paediatric Oncology and Haematology Institute of Paediatrics Jagiellonian University Medical College Krakow Poland

Department of Paediatric Oncology at Astrid Lindgrens Children's Hospital Karolinska University Hospital Stockholm Sweden

Department of Paediatric Oncology Justus Liebig University Giessen Giessen Germany

Department of Paediatrics and Adolescent Medicine The Juliane Marie Centre University Hospital Rigshospitalet Copenhagen Denmark

Department of Paediatrics University of Schleswig Holstein Kiel Germany

Department of Pathology Armand Trousseau Hospital Paris France

Department of Radiology University Hospital Halle Halle Germany

Hospital Universitario Virgen Macarena Universidad de Sevilla Seville Spain

Institute for Medical Informatics Statistics and Epidemiology University of Leipzig Leipzig Germany

Institute of Pathology Justus Liebig University Giessen Giessen Germany

Medical Faculty and Department of Radiation Oncology Martin Luther University Halle Wittenberg Halle Germany

Oslo Universitetssykehus Radiumhospitalet Oslo Norway

Our Lady's Hospital for Children's Health Dublin Ireland

Paediatric Haematology and Oncology Department of Oncology University Hospitals Leuven KU Leuven Leuven Belgium

Pediatric Hematology Oncology Unit Division of Pediatrics Department Woman Mother Child University Hospital of Lausanne and University of Lausanne Lausanne Switzerland

Princess Máxima Centre for Paediatric Oncology Utrecht and Erasmus Sophia Children's Hospital Rotterdam Netherlands

Service d'Hématologie Pédiatrique Hôpital Robert Debré Paris France

St Anna Children's Hospital Medical University of Vienna Vienna Austria

Strahlentherapie Allgemeines Krankenhaus Wien Medizinische Universitätsklinik Wien Vienna Austria

Lancet Oncol. 2023 Mar;24(3):196-197. doi: 10.1016/S1470-2045(23)00058-X. PubMed

Lancet Oncol. 2023 Jun;24(6):e230. doi: 10.1016/S1470-2045(23)00211-5. PubMed

Lancet Oncol. 2023 Jun;24(6):e231. doi: 10.1016/S1470-2045(23)00235-8. PubMed

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Zobrazit více v PubMed

ClinicalTrials.gov
NCT00433459

EudraCT
2006–000995-33