2597 - Association of ALPS-Index and Glymphatic Flow with Neurocognitive Changes in Patients Receiving Brain Irradiation: Secondary Analysis of a Prospective Study

A. Saraf¹, J. Ford², M. W. Parsons³, I. S. Wang², N. Horick⁴, B. Y. Yeap⁵, J. Dietrich², and H. A. Shih⁶; ¹Brigham and Women’s Hospital/Dana Farber Cancer Institute, Boston, MA, ²Massachusetts General Hospital, Boston, MA, ³Pappas Center for Neuro-Oncology and Department of Psychiatry, Massachusetts General Hospital, Boston, MA, ⁴Biostatistics Center, Massachusetts General Hospital, Boston, MA, ⁵Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, ⁶Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA

Purpose/Objective(s): Neurocognitive decline is common after brain radiotherapy (RT); however, the mechanisms of injury are not well understood. Changes in brain glymphatic flow have been associated with cognitive decline in other neurologic conditions. Diffusion Tensor Image Analysis along the Perivascular Space (DTI-ALPS) is a novel surrogate biomarker for glymphatic function. We sought to correlate the ALPS-index with cognition in patients receiving brain RT and to evaluate changes in ALPS-indices before and after whole and partial brain irradiation. Materials/

Methods: A single institution, prospective, single-arm study was conducted in patients receiving brain RT to evaluate correlates of neurocognitive outcomes. All patients received fractionated brain RT between 2015-2019. Patients completed formal standardized neurocognitive testing, quality of life surveys, and multiparametric brain imaging at baseline, 8 weeks, 6 months, 12 months, and 24 months after RT. Associations between baseline characteristics, ALPS-index, and neurocognitive outcomes (defined here as the Trails B test) were performed by Mann-Whitney test.
Results: A total of 15 patients were enrolled, 7 of whom had diffusion imaging suitable for DTI-ALPS at 1 month and 6 months and are included in this study. All 7 completed neurocognitive assessments at baseline, 4/7 completed testing at 6 months and 3/7 at 12 and 24 months. Five patients received RT for brain metastasis (2 whole brain RT [WBRT], range dose 30-35Gy/10-14fx, and 3 partial brain RT [PBRT], range RT dose 39-39Gy/13-13fx), while 2 patients received RT for medulloblastoma (range WBRT dose 23.4-23.4Gy(RBE) and posterior fossa boost to total 54-54Gy(RBE)). Of those who received WBRT and underwent an 8-week follow-up MRI (n=4), the ALPS-index had a mean decrease of 6.8% (range 0 – 18.5%), whereas those who received PBRT (n=3) had increased ALPS-index of 2.8% (p=0.057). ALPS-index in patients with a stable Trails B over time (n=2) had a mean increase in ALPS-index of 0.1% at 12 months, whereas the subject with a markedly decreased Trails B had a decrease of 4.9% in the ALPS-index. Three subjects completed the 24-month study. The two subjects who received WBRT had decreasing ALPS-indices, one with a nadir at 8 weeks and the other with a nadir at 6 months. Both WBRT patients had recovered and surpassed their baseline ALPS-index at 2 years. The patient who had received PBRT demonstrated increasing ALPS-indices, peaking at 12 months and returning to baseline at 24 months. Change in ALPS index was not statistically associated with age >65yo, number of brain lesions, RT dose, or receipt of chemotherapy.
Conclusion: WBRT is associated with decrease in ALPS index at 6 months and decline in cognition. Partial brain RT was associated with increasing ALPS-indices, which may represent a homeostatic response in those with more preserved glymphatic function. Future studies should investigate the role of glymphatic drainage in the brain with mechanism of neurocognitive decline after brain RT.