Health-related quality of life in patients with advanced soft tissue sarcoma receiving first-line palliative chemotherapy (HOLISTIC): longitudinal results from a prospective, observational cohort study.

Background: Previous research suggests that health-related quality of life (HRQoL) in patients with advanced soft tissue sarcoma (STS) is often severely impacted, but data on longitudinal changes during chemotherapy are lacking. We aimed to address this knowledge gap. Methods: This prospective, observational cohort study (HOLISTIC) assessed HRQoL in patients with advanced STS during first-line palliative chemotherapy, focusing on Global Health Scores (GHS) change after 4 cycles (T4). Eligible patients were recruited from five centres in the Netherlands (n = 63) and two centres in the United Kingdom (UK, n = 72). Clinical and sociodemographic data were collected, and HRQoL was measured using the EORTC QLQ-C30 at baseline (T0) and before each cycle. The primary outcome of this study was the change in GHS on the EORTC QLQ-C30 between baseline and after 4 cycles of first-line palliative chemotherapy. Changes in GHS were tested using paired sample t-tests and linear mixed-effects models (LME). For patients who did not complete 4 cycles, the last score post baseline (i.e. T3, T2) was used (i.e. T4/final). This study is registered with ClinicalTrials.gov, NCT03621332. Findings: Between March 2018 and March 2020, 137 patients from the UK (n = 72) and the Netherlands (n = 65) were enrolled. Two patients never started chemotherapy and were excluded. Of the remaining 135 patients, 60 (44%) had at least 4 cycles of chemotherapy and 91 (68%) completed the questionnaire at T0 together with at least the questionnaire at T2, T3 and/or T4. Mean GHS significantly deteriorated from 68.2 (T0) to 60.7 (T4/final) with a mean difference between T0 and T4/final of -11.3 points (95% CI 7.6-15.0, p < 0.001). GHS worsened both in patients with partial response/stable disease (-12.3 points, 95% CI 7.9-16.8, p < 0.001) and in patients with progressive disease (-10.9 points, 95% CI 2.3-19.6, p = 0.015). Baseline GHS were lower (i.e. worse) for patients with ECOG PS 1-2 (77.1 vs 84.7 [ECOG PS 0], p = 0.023), patients from the UK (77.4 vs 84.7 [NL], p = 0.008) and patients with anaemia (78.6 vs 84.7 [no anaemia], p = 0.040). The decline in GHS over time was more pronounced in patients with ECOG PS 0 (-4.7 points per cycle) compared to those with ECOG PS 1 or 2 (-1.4 points per cycle, (p = 0.014). Interpretation: First-line palliative chemotherapy in advanced STS is associated with a significant decrease in GHS, irrespective of tumour response. These results emphasise the importance of integrating patient-reported outcomes (PROs) in clinical trials and routine care, and may enable informed decision making by patients with advanced STS starting palliative chemotherapy. Future research should explore implementing PROs in practice, using them to guide treatment, and how chemotherapy vs disease progression affects QoL. Funding: Eli Lilly and Company.