Development and validation of a customised PRO-CTCAE scale for adult-type diffuse gliomas (VERONICA): a multicentre,...

Patient-reported outcomes (PROs) are essential for assessing symptomatic adverse events (AEs) from a patient perspective, which significantly impact the quality of life and clinical outcomes in patients with glioma. However, no validated patient-reported outcome measures (PROMs) exist to quantify symptomatic AEs in adult-type diffuse gliomas.

The study was conducted in two parts. First, we developed a customised Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) scale for adult-type diffuse gliomas using the Simplified Chinese PRO-CTCAE® item library, informed by initial item screening, patient pilot testing, and a two-round Delphi survey. Delphi experts were recruited through the National Glioma Multidisciplinary Team (MDT) Alliance (NGMA) and invited by email in June 2022 (1st round) and August 2022 (2nd round). We subsequently conducted a multicentre, prospective, observational cohort study (VERONICA) at 13 glioma treatment centres in China between September 2022 and March 2025. Eligible participants were adults aged 18 years or older with a diagnosis of adult-type diffuse glioma, who were able to understand and complete the questionnaires; patients with severe cognitive impairment, severe language dysfunction, or other conditions precluding questionnaire completion were excluded. The primary outcome was the psychometric performance of the customised PRO-CTCAE scale, including test-retest reliability, convergent validity, known-groups validity, and responsiveness, evaluated longitudinally across repeated study visits. VERONICA is registered with ClinicalTrials.gov, NCT05486923.

For the Delphi survey, all seven invited experts from six centres participated in 1st round (response rate 100·0%), with moderate agreement in symptom rankings (Kendall's W = 0·415; p < 0·001). In 2nd round, 16 of 20 invited experts from 14 centres participated (response rate 80·0%), with consistent agreement in expert ratings (Kendall's W = 0·351; p < 0·001). The final version of the customised PRO-CTCAE scale comprised 53 items covering 31 symptoms, together with one open-ended free-text item. For VERONICA, 450 participants were enrolled across 13 glioma treatment centres. Mean age was 49·1 years (SD 12·8), and the mean Karnofsky Performance Status (KPS) at baseline (Visit 2) was 72·2 (SD 17·1). 424 provided data eligible for at least one prespecified psychometric analysis. Test-retest reliability was acceptable (intraclass correlation coefficient [ICC] ≥0·70 for 47 of 53 items). Convergent validity was supported by correlations in the expected direction with matched European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) domains, with predominantly moderate-to-strong associations (25 items with r ≥ 0·50). Known-groups validity was supported by discrimination between KPS <70 and ≥70 (Cohen's d ≥ 0·20 for 49 of 53 items; p < 0·05 for 43 of 49 items). In Global Impression of Change (GIC)-anchored responsiveness analyses, 37 items showed standardised response means (SRMs) ≥0·20 among participants reporting worsened overall status.

The customised PRO-CTCAE scale showed robust psychometric performance for adult-type diffuse gliomas. Remote, longitudinal administration supports low-burden quantification of patient-reported symptomatic AEs in clinical trials and routine neuro-oncology practice. Future work should assess implementation in routine care and clinical trials, and extend translation, cultural adaptation, and validation across different languages.

Beijing Medical Award Foundation; Shanghai Municipal Health Commission; Department of Science and Technology of Ningxia Hui Autonomous Region; Huashan Hospital, Fudan University (Clinical Research Project).