1033 - A Prospective Neurocognitive and Functional MRI Study Comparing Patients with Glioma and Well-Circumscribed Brain Tumors after Cranial Irradiation

08:20am - 08:25am ET

Room 254

Presenter(s)

Zhihua Liu, PhD - Washington University School of Medicine in St Louis, St. Louis, MO

Z. Liu¹, C. Luo², T. Mitchell³, V. E. Lander⁴, T. Cronkite¹, J. S. Shimony⁵, R. Fucetola⁶, A. Snyder^5,7, T. Zhu⁸, and J. Huang^1,9; ¹Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, ²Department of Surgery, Division of Public Health Sciences, Washington University School of Medicine, St. Louis, MO, ³WashU Medicine, Department of Radiation Oncology, St. Louis, MO, ⁴WashU Medicine, Department of Radiation Oncology, Saint Louis, MO, ⁵Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, ⁶Department of Neurology, Washington University School of Medicine, St. Louis, MO, ⁷Department of Radiology, Division of Medical Oncology, Washington University School of Medicine, St. Louis, MO, ⁸University of North Carolina at Chapel Hill, Chapel Hill, NC, ⁹Siteman Cancer Center, Barnes Jewish Hospital, St. Louis, MO

Purpose/Objective(s): Neurocognitive function (NCF) decline in patients with glioma following radiation therapy (RT) may be confounded by tumor infiltration and chemotherapy effects. This prospective study evaluated patterns of NCF decline and associated brain network-level disturbances in patients with well-circumscribed brain tumors (WCBT) compared with glioma following RT.

Materials/Methods: In this prospective observational study, patients with glioma or WCBT underwent NCF testing, patient reported outcome (PRO) assessment, and resting-state functional MRI (rs-fMRI) at baseline and 6 months after partial-brain fractionated external-beam RT. Glioma patients received concurrent/adjuvant chemotherapy, while WCBT patients did not. NCF was assessed using five tests from the NIH Toolbox Fluid Cognition Battery, combined into an age-normalized composite score (NCF_comp). PRO was assessed using the M.D. Anderson Symptom Inventory Brain Tumor Module (MDASI-BT). rs-fMRI data were processed using seed-based functional connectivity (FC) analysis and evaluated with connectivity regression modeling. NCF change was quantified as percent change from baseline (?NCF) or 6-month decline defined by the reliable change index.

Results: From 9/2020 to 10/2024, 50 glioma and 22 WCBT patients were enrolled; 36 and 18 completed both pre- and post-RT NCF testing, respectively. The glioma cohort consisted of 22 IDH-mutant gliomas and 14 IDH-wildtype glioblastomas. WCBT cohort consisted of 14 meningiomas, 2 solitary fibrous tumors, 1 craniopharyngioma and 1 neurocytoma. 3 WCBT patients had sub-optimal rs-MRI data and were excluded from FC analysis. Compared to the glioma cohort, WCBT patients were older, more frequently female, had smaller tumors and had less brain volumes irradiated. Baseline NCF_comp was higher but not statistically different in WCBT vs glioma (median 98.5 vs 88.0, p=0.08). Post-RT NCF change did not differ significantly between WCBT and glioma cohorts (median ?NCF_comp of -4.6% vs +1.4%, p=0.42; 6-month NCF_comp decline of 50% vs 36%, p=0.39). Symptom scores on MDASI-BT were not significantly different between the two cohorts at baseline or 6 months (all p=NS). However, rs-fMRI of WCBT and glioma cohorts showed distinct patterns of network-level FC alterations associated with NCF_comp decline, suggesting divergent mechanisms of network disruption.

Conclusion: Despite the absence of infiltrative tumor, chemotherapy exposure, and lower irradiated brain volumes, patients with WCBT exhibited post-RT NCF decline comparable to those with glioma. These findings suggest that cranial irradiation and downstream patient-specific biological response may be dominant drivers of NCF decline following RT. rs-fMRI shows promise as an imaging biomarker of post-RT cognitive injury and provides complementary information to conventional NCF testing.