Follow-up of the GHSG HD16 trial of PET-guided treatment in early-stage favorable Hodgkin lymphoma.

Journal

Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895

Informations de publication

Date de publication:
16 Oct 2023
Historique:
received: 02 08 2023
accepted: 05 10 2023
revised: 25 09 2023
medline: 17 10 2023
pubmed: 17 10 2023
entrez: 16 10 2023
Statut: aheadofprint

Résumé

The primary analysis of the GHSG HD16 trial indicated a significant loss of tumor control with PET-guided omission of radiotherapy (RT) in patients with early-stage favorable Hodgkin lymphoma (HL). This analysis reports long-term outcomes. Overall, 1150 patients aged 18-75 years with newly diagnosed early-stage favorable HL were randomized between standard combined-modality treatment (CMT) (2x ABVD followed by PET/CT [PET-2] and 20 Gy involved-field RT) and PET-2-guided treatment omitting RT in case of PET-2 negativity (Deauville score [DS] < 3). The study aimed at excluding inferiority of PET-2-guided treatment and assessing the prognostic impact of PET-2 in patients receiving CMT. At a median follow-up of 64 months, PET-2-negative patients had a 5-year progression-free survival (PFS) of 94.2% after CMT (n = 328) and 86.7% after ABVD alone (n = 300; HR = 2.05 [1.20-3.51]; p = 0.0072). 5-year OS was 98.3% and 98.8%, respectively (p = 0.14); 4/12 documented deaths were caused by second primary malignancies and only one by HL. Among patients assigned to CMT, 5-year PFS was better in PET-2-negative (n = 353; 94.0%) than in PET-2-positive patients (n = 340; 90.3%; p = 0.012). The difference was more pronounced when using DS4 as cut-off (DS 1-3: n = 571; 94.0% vs. DS ≥ 4: n = 122; 83.6%; p < 0.0001). Taken together, CMT should be considered standard treatment for early-stage favorable HL irrespective of the PET-2-result.

Identifiants

DOI: 10.1038/s41375-023-02064-y PMID: 37845285
pubmed: 37845285
doi: 10.1038/s41375-023-02064-y
pii: 10.1038/s41375-023-02064-y
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2023. The Author(s).

Références

Yahalom J. Don’t throw out the baby with the bathwater: on optimizing cure and reducing toxicity in Hodgkin’s lymphoma. J Clin Oncol. 2006;24:544–8.
doi: 10.1200/JCO.2005.04.4396 pubmed: 16446326
Girinsky T, van der Maazen R, Specht L, Aleman B, Poortmans P, Lievens Y, et al. Involved-node radiotherapy (INRT) in patients with early Hodgkin lymphoma: concepts and guidelines. Radiother Oncol. 2006;79:270–7.
doi: 10.1016/j.radonc.2006.05.015 pubmed: 16797755
Koontz BF, Kirkpatrick JP, Clough RW, Prosnitz R, Gockerman J, Moore J, et al. Combined-modality therapy versus radiotherapy alone for treatment of early-stage Hodgkin’s disease: cure balanced against complications. J Clin Oncol. 2006;24:605–11.
doi: 10.1200/JCO.2005.02.9850 pubmed: 16446333
Behringer K, Goergen H, Hitz F, Zijlstra J, Greil R, Markova J, et al. Omission of dacarbazine or bleomycin, or both, from the ABVD regimen in treatment of early-stage favorable Hodgkin’s lymphoma (GHSG HD13): an open-label, randomized, non-inferiority trial. Lancet. 2015;385:1418–27.
doi: 10.1016/S0140-6736(14)61469-0 pubmed: 25539730
Sasse S, Brockelmann PJ, Goergen H, Pluetschow A, Mueller H, Kreissl S, et al. Long-term follow-up of contemporary treatment in early-stage Hodgkin lymphoma: updated analyses of the German Hodgkin Study Group HD7, HD8, HD10, and HD11 trials. J Clin Oncol. 2017;35:1999–2007.
doi: 10.1200/JCO.2016.70.9410 pubmed: 28418763
Brockelmann PJ, Sasse S, Engert A. Balancing risk and benefit in early-stage classical Hodgkin lymphoma. Blood 2018;131:1666–78.
doi: 10.1182/blood-2017-10-772665 pubmed: 29500174
Connors JM. State-of-the-art therapeutics: Hodgkin’s lymphoma. J Clin Oncol. 2005;23:6400–8.
doi: 10.1200/JCO.2005.05.016 pubmed: 16155026
Meyer RM, Gospodarowicz MK, Connors JM, Pearcey R, Bezjak A, Wells W, 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. J Clin Oncol. 2005;23:4634–42.
doi: 10.1200/JCO.2005.09.085 pubmed: 15837968
Canellos GP. Chemotherapy alone for early Hodgkin’s lymphoma: an emerging option. J Clin Oncol. 2005;23:4574–6.
doi: 10.1200/JCO.2005.01.911 pubmed: 15837972
Engert A, Plutschow A, Eich HT, Lohri A, Doerken B, Borchmann P, et al. Reduced treatment intensity in patients with early-stage Hodgkin’s lymphoma. N. Engl J Med. 2010;363:640–52.
doi: 10.1056/NEJMoa1000067 pubmed: 20818855
Radford J, Illidge T, Counsell N, Hancock B, Pettengell R, Johnson P, et al. Results of a trial of PET-directed therapy for early-stage Hodgkin’s lymphoma. N. Engl J Med. 2015;372:1598–607.
doi: 10.1056/NEJMoa1408648 pubmed: 25901426
Raemaekers JM, Andre MP, Federico M, Girinsky T, Oumedaly R, Brusamolino E, 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. J Clin Oncol. 2014;32:1188–94.
doi: 10.1200/JCO.2013.51.9298 pubmed: 24637998
Fuchs M, Goergen H, Kobe C, Kuhnert G, Lohri A, Greil R, et al. Positron emission tomography-guided treatment in early-stage favorable Hodgkin lymphoma: final results of the international, randomized phase III HD16 trial by the German Hodgkin Study Group. J Clin Oncol. 2019;37:2835–45.
doi: 10.1200/JCO.19.00964 pubmed: 31498753
Meignan M, Gallamini A, Haioun C. Report on the first international workshop on interim-PET-Scan in lymphoma. Leuk Lymphoma. 2009;50:1257–60. https://doi.org/10.1080/10428190903040048 .
doi: 10.1080/10428190903040048 pubmed: 19544140
Oertel M, Hering D, Nacke N, Kittel C, Kroeger K, Kriz J, et al. Radiation therapy in the German Hodgkin Study Group HD 16 and HD 17 trials: quality assurance and dosimetric analysis for Hodgkin lymphoma in the modern era. Adv Radiat Oncol. 2023;8:101169.
doi: 10.1016/j.adro.2022.101169 pubmed: 36896214
van Heek L, Stuka C, Kaul H, Mueller H, Mettler J, Hitz F, et al. Predictive value of baseline metabolic tumor volume in early-stage favorable Hodgkin lymphoma—data from the prospective, multicenter phase III HD16 trial. BMC Cancer. 2022;22:672.
doi: 10.1186/s12885-022-09758-z pubmed: 35717166 pmcid: 9206242
Maco M, Kupcova K, Herman V, Ondeckova I, Kozak T, Mocikova H, et al. Circulating tumor DNA in Hodgkin lymphoma. Ann Hematol. 2022;101:2393–403.
doi: 10.1007/s00277-022-04949-x pubmed: 36074181 pmcid: 9546971
Andre MPE, Girinsky T, Federico M, Reman O, Fortpied C, Gotti M, et al. Early positron emission tomography response-adapted treatment in stage I and II Hodgkin lymphoma: final results of the randomized EORTC/LYSA/FIL H10 trial. J Clin Oncol. 2017;35:1786–94.
doi: 10.1200/JCO.2016.68.6394 pubmed: 28291393
Aurer I, Neven A, Fiaccadori V, Counsell N, Phillips E, Clifton-Hadley L, et al. Relapses in interim pet negative limited stage Hodgkin lymphoma patients receiving ABVD with or without radiotherapy–analysis of EORTC/FIL/LYSA H10 and UK NCRI rapid trials. Hematol Oncol. 2021;39:abstr. 71.
Olszewski AJ, Shrestha R, Castillo JJ. Treatment selection and outcomes in early-stage classical Hodgkin lymphoma: analysis of the National Cancer Data Base. J Clin Oncol. 2015;33:625–33.
doi: 10.1200/JCO.2014.58.7543 pubmed: 25584010
Schmitz N, Glass B, Dreger P, Haferlach T, Horst HA, Ollech-Chwoyka J, et al. High-dose chemotherapy and hematopoietic stem cell rescue in patients with relapsed Hodgkin’s disease. Ann Hematol. 1993;66:251–6.
doi: 10.1007/BF01738475 pubmed: 8099502
Josting A, Muller H, Borchmann P, Baars J, Metzner B, Doehner H, et al. Dose intensity of chemotherapy in patients with relapsed Hodgkin’s lymphoma. J Clin Oncol. 2010;28:5074–80.
doi: 10.1200/JCO.2010.30.5771 pubmed: 20975066
Brockelmann PJ, Goergen H, Kohnhorst C, von Tresckow B, Moccia A, Markova J, et al. Late relapse of classical Hodgkin lymphoma: an analysis of the German Hodgkin Study Group HD7 to HD12 trials. J Clin Oncol. 2017;35:1444–50.
doi: 10.1200/JCO.2016.71.3289 pubmed: 28240973
Kreissl S, Goergen H, Muller H, Meissner J, Mehnert A, Buerkle C, et al. Survivors’ perspectives on risks and benefits of Hodgkin lymphoma treatment: results of a survey by the German Hodgkin Study Group. Leuk Lymphoma. 2018;3:1–10.
Eichenauer DA, Buhnen I, Baues C, Kobe C, Kaul H, Greil R, et al. Interim PET-guided treatment for early-stage NLPHL: a subgroup analysis of the randomized GHSG HD16 and HD17 studies. Blood. 2023;142:553–60.
Baues C, Goergen H, Fuchs M, Rosenbrock J, Celik E, Eich HT, et al. Involved-field radiation therapy prevents recurrences in the early stages of Hodgkin lymphoma in PET-negative patients after ABVD chemotherapy: relapse analysis of GHSG phase 3 HD16 trial. Int J Radiat Oncol Biol Phys. 2021;111:900–6.
doi: 10.1016/j.ijrobp.2021.07.1697 pubmed: 34389407

Auteurs

Michael Fuchs (M)

German Hodgkin Study Group (GHSG), Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Cologne, Germany.

Anne Sophie Jacob (AS)

German Hodgkin Study Group (GHSG), Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Cologne, Germany.

Helen Kaul (H)

German Hodgkin Study Group (GHSG), Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Cologne, Germany.

Carsten Kobe (C)

Department of Nuclear Medicine, University of Cologne, Cologne, Germany.
ORCID: 0000-0002-2909-0826

Georg Kuhnert (G)

Nuclear Medicine Siegen I Kreuztal, Siegen, Germany.

Thomas Pabst (T)

Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland.
ORCID: 0000-0002-6055-5257

Richard Greil (R)

IIIrd Medical Department, Paracelcus Medical University and Salzburg Cancer Research Institute, Salzburg, Austria.
Salzburg Cancer Research Institute and AGMT (Arbeitsgemeinschaft Medikamentöse Tumortherapie), Salzburg, Austria.

Paul J Bröckelmann (PJ)

German Hodgkin Study Group (GHSG), Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Cologne, Germany.
ORCID: 0000-0001-9662-9900

Max S Topp (MS)

Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany.

Marianne Just (M)

Dres. med. Just/Düwel/Riesenberg/Steinke/Schäfer, Studiengesellschaft, Bielefeld, Germany.

Bernd Hertenstein (B)

Department of Internal Medicine I, Klinikum Bremen Mitte, Bremen, Germany.

Martin Soekler (M)

Onkology, Spital Thun, Switzerland, formerly University of Tübingen, Tübingen, Germany.

Martin Vogelhuber (M)

Medizinische Klinik III, Universitätsklinik Regensburg, Regensburg, Germany.

Josée M Zijlstra (JM)

Department of Hematology, Amsterdam UMC, Vrije Universiteit, Amsterdam, Netherlands.

Ulrich Bernd Keller (UB)

Department of Internal Medicine III, Klinikum "Rechts der Isar", Munich, Germany.
ORCID: 0000-0002-8485-1958

Stefan W Krause (SW)

Department of Internal Medicine 5, Haematology/Oncology, Uniklinikum Erlangen, Erlangen, Germany.
ORCID: 0000-0002-5259-4651

Ulrich Dührsen (U)

Department of Haematology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.

Julia Meissner (J)

University of Heidelberg, Heidelberg, Germany.
ORCID: 0000-0003-1908-2096

Andreas Viardot (A)

Department of Internal Medicine III, University Hospital Ulm, Ulm, Germany.

Hans-Theodor Eich (HT)

Department of Radiotherapy, University Hospital of Muenster, Muenster, Germany.

Christian Baues (C)

Department of Radiotherapy, University of Cologne, Cologne, Germany.

Volker Diehl (V)

German Hodgkin Study Group (GHSG), Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Cologne, Germany.

Andreas Rosenwald (A)

Institute of Pathology, Julius Maximilian University of Würzburg and Comprehensive Cancer Center Mainfranken, Würzburg, Germany.

Ina Buehnen (I)

German Hodgkin Study Group (GHSG), Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Cologne, Germany.

Bastian von Tresckow (B)

German Hodgkin Study Group (GHSG), Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Cologne, Germany.
Department of Haematology and Stem Cell Transplantation, West German Cancer Center and German Cancer Consortium (DKTK partner site Essen), University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
ORCID: 0000-0003-1410-4487

Markus Dietlein (M)

Department of Nuclear Medicine, University of Cologne, Cologne, Germany.

Peter Borchmann (P)

German Hodgkin Study Group (GHSG), Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Cologne, Germany.

Andreas Engert (A)

German Hodgkin Study Group (GHSG), Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Cologne, Germany.

Dennis A Eichenauer (DA)

German Hodgkin Study Group (GHSG), Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Cologne, Germany. dennis.eichenauer@uk-koeln.de.
ORCID: 0000-0002-1927-3514

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