Impact of individualized treatment on recovery from fatigue and return to work in survivors of advanced-stage Hodgkin's lymphoma: results from the randomized international GHSG HD18 trial

J Ferdinandus; H Müller; C Damaschin; A S Jacob; J Meissner; F Krasniqi; U Mey; D Schöndube; J Thiemer; S Mathas; J Zijlstra; R Greil; M Feuring-Buske; J Markova; J U Rüffer; C Kobe; H-T Eich; C Baues; M Fuchs; P Borchmann; K Behringer

doi:10.1016/j.annonc.2023.11.014

Impact of individualized treatment on recovery from fatigue and return to work in survivors of advanced-stage Hodgkin's lymphoma: results from the randomized international GHSG HD18 trial

Ann Oncol. 2024 Mar;35(3):276-284. doi: 10.1016/j.annonc.2023.11.014. Epub 2023 Dec 5.

Authors

J Ferdinandus¹, H Müller², C Damaschin², A S Jacob², J Meissner³, F Krasniqi⁴, U Mey⁵, D Schöndube⁶, J Thiemer⁷, S Mathas⁸, J Zijlstra⁹, R Greil¹⁰, M Feuring-Buske¹¹, J Markova¹², J U Rüffer¹³, C Kobe¹⁴, H-T Eich¹⁵, C Baues¹⁶, M Fuchs², P Borchmann², K Behringer²

Affiliations

¹ Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Medical Faculty and University Hospital Cologne, Cologne; German Hodgkin Study Group (GHSG), Cologne. Electronic address: justin.ferdinandus@uk-koeln.de.
² Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Medical Faculty and University Hospital Cologne, Cologne; German Hodgkin Study Group (GHSG), Cologne.
³ Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
⁴ Medical Oncology, University Hospital of Basel, Basel; Swiss Group for Clinical Cancer Research, Bern.
⁵ Swiss Group for Clinical Cancer Research, Bern; Oncology and Hematology, Kantonsspital Graubuenden, Chur, Switzerland.
⁶ Department of Oncology and Hematology, Helios Klinikum Bad Saarow, Bad Saarow.
⁷ Department of Hematology and Oncology, Klinikum der Philipps-Universität Marburg, Marburg.
⁸ Charité-Universitätsmedizin Berlin, Hematology, Oncology and Tumor Immunology, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin; Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), Group Biology of Malignant Lymphomas, Berlin; Experimental and Clinical Research Center (ECRC), a cooperation between the MDC and the Charité, Berlin, Germany.
⁹ Department of Hematology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.
¹⁰ Illrd Medical Department, Paracelsus Medical University, Salzburg; Salzburg Cancer Research Institute and AGMT, Salzburg, Austria.
¹¹ Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany.
¹² Department of Internal Medicine-Hematology, University Hospital Kralovske Vinohrady, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
¹³ German Fatigue Society, Cologne.
¹⁴ German Hodgkin Study Group (GHSG), Cologne; Department of Nuclear Medicine, University Hospital of Cologne, Cologne.
¹⁵ German Hodgkin Study Group (GHSG), Cologne; Department of Radiotherapy, University Hospital of Muenster, Muenster.
¹⁶ German Hodgkin Study Group (GHSG), Cologne; Department of Radiooncology, Marienhospital Herne, Ruhr University Bochum, Bochum, Germany.

PMID: 38061428
DOI: 10.1016/j.annonc.2023.11.014

Abstract

Background: Persisting cancer-related fatigue impairs health-related quality of life (HRQoL) and social reintegration in patients with Hodgkin's lymphoma (HL). The GHSG HD18 trial established treatment de-escalation for advanced-stage HL guided by positron emission tomography after two cycles (PET-2) as new standard. Here, we investigate the impact of treatment de-escalation on long-term HRQoL, time to recovery from fatigue (TTR-F), and time to return to work (TTR-W).

Patients and methods: Patients received European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) and life situation questionnaires at baseline, interim, end of treatment, and yearly follow-up. TTR-F was defined as time from the end of chemotherapy until the first fatigue score <30. TTR-W was analyzed in previously working or studying patients and measured from the end of treatment until the first documented work or education. We compared duration of treatment on TTR-F and TTR-W using Cox proportional hazards regression adjusted for confounding variables.

Results: HRQoL questionnaires at baseline were available in 1632 (83.9%) of all randomized patients. Overall, higher baseline fatigue and age were significantly associated with longer TTR-F and TTR-W and male sex with shorter TTR-W. Treatment reduction from eight to four chemotherapy cycles led to a significantly shorter TTR-F [hazard ratio (HR) 1.41, P = 0.008] and descriptively shorter TTR-W (HR 1.24, P = 0.084) in PET-2-negative patients. Reduction from six to four cycles led to non-significant but plausible intermediate accelerations. The addition of rituximab caused significantly slower TTR-F (HR 0.70, P = 0.0163) and TTR-W (HR 0.64, P = 0.0017) in PET-2-positive patients. HRQoL at baseline and age were the main determinants of 2-year HRQoL.

Conclusions: Individualized first-line treatment in patients with advanced-stage HL considerably shortens TTR-F and TTR-W in PET-2-negative patients. Our results support the use of response-adapted shortened treatment duration for patients with HL.

Keywords: Hodgkin’s lymphoma; fatigue; quality of life; recovery; return to work; survivorship.

MeSH terms

Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Fatigue / etiology
Hodgkin Disease* / pathology
Humans
Male
Quality of Life
Return to Work
Survivors