Abstract

Abstract BACKGROUND The cause for neurocognitive function (NCF) impairments in patients with lower grade glioma (LGG) is typically multifactorial. The aim of this study was to explore the relationship between NCF and the radiological appearance of the brain before start of radiotherapy (RT) in LGG patients. MATERIAL AND METHODS Around start of RT we evaluated NCF of LGG patients treated with proton therapy. The assessment included 10 neuropsychological tests with 20 measures that could be categorized over 6 cognitive domains. Raw test scores were converted to Z scores based on normative data. Mild cognitive impairment (MCI) was defined as a Z score of less than -2 on a single measure, or Z score of less than -1.5 on multiple measures. An impaired cognitive domain was defined as a mean composite Z score of less than -1.5. The radiological appearance of the brain outside the tumor region was assessed on a pre-RT planning MRI using the Fazekas score and Global Cortical Atrophy (GCA) score. For statistical analysis we used Chi Square tests and Mann-Whitney U tests. RESULTS Between 2018 and March 2022, 126 LGG patients started RT treatment, 119 patients (94%) had NCF assessment pre-RT and were available for analysis. Median age was 41 years, 51% of patients was male, reported comorbidities included hypertension in 7%, diabetes mellitus in 3% and cardiovascular 13% of patients. The World Health Organization (WHO) performance scores and the Neurologic Assessment in Neuro-Oncology (NANO) scores were 0 - 1, in 98%, and 92% of patients. The Fazekas score was 0 in 75%, 1 in 18% and 2 in 6% and 3 in 2% of patients. The GCA score was 0 in 59%, 1 in 38%, 2 in 3% of patients. In 77 (65%) patients the performance on the NCF assessment indicated the presence of MCI. Patients with MCI had a significant radiologically worse appearance of the brain (Fazekas score 1 or higher 31.2% versus 14.3%, p = 0.043; and GCA score 1 or higher 49.4% versus 26.2%, p = 0.014). Domain impairments were present in executive functions and attention (26%); verbal memory (23%); verbal functions (20%); non-verbal memory (20%); processing speed (18%); and working memory (14%). Fazekas score 1 or higher was significantly associated with lower composite Z scores of verbal functions (median (IQR) -0.84 (1.12) versus -0.40 (0.94), p=0.014); verbal memory (median (IQR) -0.66 (1.26) versus -0.20 (1.35), p=0.045) and non-verbal memory (median (IQR) -0.45 (2.10) versus -0.20 (1.36), p=0.037). There were no significant associations found between the GCA score and domain composite scores. CONCLUSION This cohort of LGG patients had a good clinical and neurological baseline function pre-RT. We found significant relationships between NCF and both white matter damage and atrophy of the brain. The Fazekas and GCA score are objective and easily obtained radiological measures, that could be a relevant parameter to record in LGG patients.

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