NOTQ-10 ADOPTION OF NEUROCOGNITIVE AND QUALITY OF LIFE ASSESSMENTS IN CNS METASTASES CLINICAL TRIALS: A CLINICALTRIALS.GOV REGISTRY ANALYSIS

Abstract

In 2013 and 2018, respectively, RANO neurocognitive (NC) and RANO-PRO guidelines standardized recommendations for NC and quality of life (QOL) assessments in brain metastases; however, the extent to which these guidelines have influenced trial design remains unknown. We conducted a cross-sectional analysis of interventional trials registered on ClinicalTrials.gov (January 2010–March 2026) specifically targeting CNS metastases, using four search terms (brain, CNS, cerebral, and intracranial metastases). Trials were coded for NC and QOL assessment inclusion, instrument selection, and concordance with RANO (HVLT-R + TMT + COWAT) and RANO-PRO (MDASI-BT, EORTC QLQ-C30, EORTC QLQ-BN20, FACT-Br, or EQ-5D) recommendations. Of 336 trials screened, 251 were included. NC assessments were incorporated in 18.3% and QOL in 28.7% of trials, with neither increasing significantly after guideline publication (NC: 23.1% pre- vs. 17.5% post-2013, p = 0.404; QOL: 34.0% pre- vs. 25.5% post-2018, p = 0.146). NC as a primary outcome significantly decreased post-2013 (15.4% vs. 4.2%, p = 0.017). RANO NC concordance was 28.3% overall, while RANO-PRO concordance was 77.8%. On multivariable analysis, intervention type was the strongest predictor of both NC and QOL inclusion (p < 0.001 for both), with radiation trials demonstrating the highest rates (NC: 51.2%; QOL: 55.8%) compared to systemic therapy alone trials (NC: 4.5%; QOL: 17.9%). Phase 1 trials were significantly less likely to include QOL assessments (OR = 0.318, 95% CI 0.138–0.732, p = 0.007), and time period (pre- vs post-guideline) was not significant after controlling for other factors. NC inclusion also varied by funding source: NIH (42.9%) and Cooperative Group (31.3%) trials having the highest rates compared to Industry (12.2%) and Academic (17.4%). Despite guidelines, NC and QOL assessment incorporation in CNS metastases trials has not increased and remains concentrated in radiation trials, while systemic therapy trials—which represent the growing majority of CNS-directed research—rarely incorporate these patient-centered endpoints. These findings highlight a critical gap between recommendations and practice.