Natural History Study of Adults with Primary Central Nervous System Tumors: Initial Results for First 1,000 Participants

Abstract Background Primary central nervous system tumors (PCNST) are rare, understudied tumors for which knowledge of their clinical course, biology, physical, and psychological impact is limited. The National Cancer Institute’s Neuro-Oncology Branch Natural History Study was developed to better understand the long-term disease course and outcomes experienced by these patients. Methods Past medical histories, tumor tissue (if available), and patient-reported outcomes assessing symptom burden, general health status, anxiety, depression, and perceived cognitive deficits were collected at study enrollment. Sociodemographic, clinical, molecular, and patient-reported outcome data were analyzed descriptively. Results Among the first 1,000 participants, 796 had primary brain tumors (PBT) and 92 had primary spine tumors (PST); 88 were excluded. The cohort was predominantly male (56%), White (81%), and non-Hispanic (89%). Based on advanced molecular testing at enrollment, 190 (21%) patients had a change in diagnosis or subclassification since their initial diagnosis. Meningioma cases reported family brain tumor history more frequently than others. Most PBTs were diagnosed within 6-months of symptoms, while most PSTs were diagnosed ≥1 year after. Patients with PBT and PST reported an average of 10 symptoms, with 4 and 5 symptoms rated as moderate/severe, respectively. Nearly half of PBT participants reported anxiety or depression (46%) and difficulty with usual activities (48%). PST participants reported higher functional impairment and worse general health status. Conclusion These findings underscore the substantial burden of PCNSTs and highlight the value of longitudinal, tumor-agnostic data in generating real-world insights into the disease trajectories of these rare and heterogeneous tumors to inform clinical research.