Maximum tumor diameter is associated with relapse risk in limited-stage Hodgkin lymphoma: an international study

Abstract: Tumor bulk is an established prognostic factor in Hodgkin lymphoma (HL), but most patients with limited-stage (LS) HL do not have “bulk” by standard definitions. In the RAPID trial, maximum tumor diameter (MTD) was associated with relapse risk in LS-HL patients achieving positron emission...

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Main Authors: Elizabeth H. Phillips, Nicholas Counsell, Tim Illidge, Marc Andre, Igor Aurer, Valeria Fiaccadori, Catherine Fortpied, Anouk Neven, Massimo Federico, Sally F. Barrington, John Raemaekers, John Radford
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:Blood Advances
Online Access:http://www.sciencedirect.com/science/article/pii/S2473952925000072
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author Elizabeth H. Phillips
Nicholas Counsell
Tim Illidge
Marc Andre
Igor Aurer
Valeria Fiaccadori
Catherine Fortpied
Anouk Neven
Massimo Federico
Sally F. Barrington
John Raemaekers
John Radford
author_facet Elizabeth H. Phillips
Nicholas Counsell
Tim Illidge
Marc Andre
Igor Aurer
Valeria Fiaccadori
Catherine Fortpied
Anouk Neven
Massimo Federico
Sally F. Barrington
John Raemaekers
John Radford
author_sort Elizabeth H. Phillips
collection DOAJ
description Abstract: Tumor bulk is an established prognostic factor in Hodgkin lymphoma (HL), but most patients with limited-stage (LS) HL do not have “bulk” by standard definitions. In the RAPID trial, maximum tumor diameter (MTD) was associated with relapse risk in LS-HL patients achieving positron emission tomography negativity (PET-) after doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). We aimed to externally validate these findings in the H10 trial. Stage I/IIA HL patients, without mediastinal bulk, who achieved PET- with ABVD were included. Patients received 3 ABVD plus radiotherapy (n = 208) or 3 ABVD alone (n = 211) in RAPID, and 3 to 4 ABVD plus radiotherapy (n = 556) or 4 to 6 ABVD alone (n = 303) in H10. MTD was strongly associated with event-free survival (relapse or HL-related death) in H10 (hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.07-1.38; P = .003), a similar effect to that seen in RAPID (HR, 1.19; 95% CI, 1.02-1.39; P = .02), giving an estimated 21% risk increase per centimeter MTD (HRpooled, 1.21; 95% CI, 1.09-1.33; P < .001). Effect sizes were similar for patients treated with ABVD alone and ABVD plus radiotherapy, with no differential effect (pinteraction = 0.97). Treatment modality and MTD were independent risk factors; patients with higher MTD receiving chemotherapy alone had the greatest relapse risk. This international validation study confirms MTD is strongly associated with relapse risk in patients with LS-HL achieving PET- and informs decision-making around risk-adapted application of radiotherapy. The trials were registered at www.clinicaltrials.gov as #NCT00943423 and #NCT00433433.
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spelling doaj-art-6b0f00b5fc0448a0bd1da5bcdbacf8d12025-08-20T02:13:40ZengElsevierBlood Advances2473-95292025-05-01992266227410.1182/bloodadvances.2024015140Maximum tumor diameter is associated with relapse risk in limited-stage Hodgkin lymphoma: an international studyElizabeth H. Phillips0Nicholas Counsell1Tim Illidge2Marc Andre3Igor Aurer4Valeria Fiaccadori5Catherine Fortpied6Anouk Neven7Massimo Federico8Sally F. Barrington9John Raemaekers10John Radford11Division of Cancer Sciences, University of Manchester and Manchester Academic Health Science Centre, Manchester, United Kingdom; Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom; Correspondence: Elizabeth H. Phillips, Division of Cancer Sciences, University of Manchester and Manchester Cancer Research Center, The Christie Hospital, Unit 26, Wilmslow Rd, Manchester M20 4BX, United Kingdom;Cancer Research UK and University College London Cancer Trials Centre, Cancer Institute, University College London, London, United KingdomDivision of Cancer Sciences, University of Manchester and Manchester Academic Health Science Centre, Manchester, United Kingdom; Department of Clinical Oncology, The Christie NHS Foundation Trust, Manchester, United KingdomDepartment of Haematology, Centre Hospitalier Universitaire, Université Catholique de Louvain Namur, Yvoir, BelgiumDivision of Hematology, Department of Internal Medicine, University Hospital Centre Zagreb, and Medical School, University of Zagreb, Zagreb, CroatiaDepartment of Statistics, European Organisation for the Research and Treatment of Cancer, Brussels, Belgium; Department of Hematology, University College London Hospital, London, United KingdomDepartment of Statistics, European Organisation for the Research and Treatment of Cancer, Brussels, BelgiumDepartment of Statistics, European Organisation for the Research and Treatment of Cancer, Brussels, Belgium; Competence Center for Methodology and Statistics, Luxembourg Institute of Health, Strassen, LuxembourgCHIMOMO Department, University of Modena and Reggio Emilia, Modena, ItalyKing's College London and Guy's and St Thomas' PET Centre, School of Biomedical Engineering and Imaging Sciences, King's College London, King's Health Partners, London, United KingdomRadboud University Medical Center, Nijmegen, The NetherlandsDivision of Cancer Sciences, University of Manchester and Manchester Academic Health Science Centre, Manchester, United Kingdom; Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United KingdomAbstract: Tumor bulk is an established prognostic factor in Hodgkin lymphoma (HL), but most patients with limited-stage (LS) HL do not have “bulk” by standard definitions. In the RAPID trial, maximum tumor diameter (MTD) was associated with relapse risk in LS-HL patients achieving positron emission tomography negativity (PET-) after doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). We aimed to externally validate these findings in the H10 trial. Stage I/IIA HL patients, without mediastinal bulk, who achieved PET- with ABVD were included. Patients received 3 ABVD plus radiotherapy (n = 208) or 3 ABVD alone (n = 211) in RAPID, and 3 to 4 ABVD plus radiotherapy (n = 556) or 4 to 6 ABVD alone (n = 303) in H10. MTD was strongly associated with event-free survival (relapse or HL-related death) in H10 (hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.07-1.38; P = .003), a similar effect to that seen in RAPID (HR, 1.19; 95% CI, 1.02-1.39; P = .02), giving an estimated 21% risk increase per centimeter MTD (HRpooled, 1.21; 95% CI, 1.09-1.33; P < .001). Effect sizes were similar for patients treated with ABVD alone and ABVD plus radiotherapy, with no differential effect (pinteraction = 0.97). Treatment modality and MTD were independent risk factors; patients with higher MTD receiving chemotherapy alone had the greatest relapse risk. This international validation study confirms MTD is strongly associated with relapse risk in patients with LS-HL achieving PET- and informs decision-making around risk-adapted application of radiotherapy. The trials were registered at www.clinicaltrials.gov as #NCT00943423 and #NCT00433433.http://www.sciencedirect.com/science/article/pii/S2473952925000072
spellingShingle Elizabeth H. Phillips
Nicholas Counsell
Tim Illidge
Marc Andre
Igor Aurer
Valeria Fiaccadori
Catherine Fortpied
Anouk Neven
Massimo Federico
Sally F. Barrington
John Raemaekers
John Radford
Maximum tumor diameter is associated with relapse risk in limited-stage Hodgkin lymphoma: an international study
Blood Advances
title Maximum tumor diameter is associated with relapse risk in limited-stage Hodgkin lymphoma: an international study
title_full Maximum tumor diameter is associated with relapse risk in limited-stage Hodgkin lymphoma: an international study
title_fullStr Maximum tumor diameter is associated with relapse risk in limited-stage Hodgkin lymphoma: an international study
title_full_unstemmed Maximum tumor diameter is associated with relapse risk in limited-stage Hodgkin lymphoma: an international study
title_short Maximum tumor diameter is associated with relapse risk in limited-stage Hodgkin lymphoma: an international study
title_sort maximum tumor diameter is associated with relapse risk in limited stage hodgkin lymphoma an international study
url http://www.sciencedirect.com/science/article/pii/S2473952925000072
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