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

BACKGROUND: Persisting cancer-related fatigue impairs health related quality of life (HRQoL) and social re-integration in patients with Hodgkin lymphoma (HL). The GHSG HD18 trial established PET-2 guided treatment de-escalation for advanced-stage HL 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 EORTC QLQ-C30 and life situation questionnaires at baseline, interim, end-of-treatment, and yearly follow-up. TTR-F was defined as time from end of chemotherapy until the first fatigue score < 30. TTR-W was analyzed in previously working or studying patients and measured from end of treatment until 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 (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. 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 2y 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.