The health-related quality of life of sarcoma patients treated with neoadjuvant versus adjuvant radiotherapy – Results of a multi-center observational study

•In a nationwide study, real-world data on the quality of life of patients with soft tissue sarcoma were collected and evaluated by adjusting for tumor-specific factors according to whether radiotherapy took place pre- or postoperatively.•Most subdomains and overall quality of life did not differ between neoadjuvant and adjuvant radiotherapy. Pain and role functioning were better in patients with adjuvant radiotherapy whereas sleep was worse compared to patients with neoadjuvant radiotherapy.•Both groups had poorer quality of life compared to the general population in all domains investigated.•In preoperatively irradiated patients, the quality of life was better after 2 years.•These findings are essentially concordant with the only randomised trial of radiotherapy timing and thus provide real-world data relevant to patients. The sequence of radiotherapy and resection in patients with soft tissue sarcomas is usually discussed on an individual basis. Better understanding of potential differences of health-related quality of life (QoL) between patients undergoing adjuvant (ART) versus neoadjuvant radiotherapy (NART) is therefore helpful for clinical decision making. Adult sarcoma patients from 39 hospitals completed the European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30). Differences in global QoL, physical functioning, role functioning, fatigue, pain, and insomnia between ART versus NART were investigated with multivariate regression, adjusting for age, gender, chemotherapy, grading, stage, tumor location, recurrence/distant metastasis, sarcoma type, time since last treatment, and treatment status using validated thresholds. A total of 1110 patients participated. Of them, 340 had received radiotherapy (NART: n = 95, 28%; ART: n = 245, 72%). Global QoL was 59.3 on average after NART and 60.5 after ART (Badj = 1.0, p = 0.74). Physical functioning was 65.9 compared to 70.5 (Badj = 4.2; p = 0.16), role function 48.8 vs. 56.7 (Badj = 7.0, p = 0.08), fatigue 47.5 vs. 45.4 (Badj = -1.2; p = 0.71), pain 40.2 vs. 34.1 (Badj = -6.8; p = 0.08), and insomnia 33.7 vs. 41.6 (Badj = 5.5, p = 0.16). Among patients with NART, clinically relevant QoL impairments were less frequent 2 years after treatment compared to