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.

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 a cooperation between the MDC and the Charité Berlin Germany

Department 1 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 Cologne

Department of Hematology Amsterdam UMC Vrije Universiteit Amsterdam Cancer Center Amsterdam Amsterdam The Netherlands

Department of Hematology and Oncology Klinikum der Philipps Universität Marburg Marburg

Department of Internal Medicine 3 University Hospital of Ulm Ulm Germany

Department of Internal Medicine 5 University of Heidelberg Heidelberg Germany

Department of Internal Medicine Hematology University Hospital Kralovske Vinohrady 3rd Faculty of Medicine Charles University Prague Czech Republic

Department of Oncology and Hematology Helios Klinikum Bad Saarow Bad Saarow

German Fatigue Society Cologne

German Hodgkin Study Group Cologne; Department of Nuclear Medicine University Hospital of Cologne Cologne

German Hodgkin Study Group Cologne; Department of Radiooncology Marienhospital Herne Ruhr University Bochum Bochum Germany

German Hodgkin Study Group Cologne; Department of Radiotherapy University Hospital of Muenster Muenster

Illrd Medical Department Paracelsus Medical University Salzburg; Salzburg Cancer Research Institute and AGMT Salzburg Austria

Medical Oncology University Hospital of Basel Basel; Swiss Group for Clinical Cancer Research Bern

Swiss Group for Clinical Cancer Research Bern; Oncology and Hematology Kantonsspital Graubuenden Chur Switzerland

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