ESTRO 2024 - Abstract Book

S897

Clinical - CNS

ESTRO 2024

Material/Methods:

This study reports the interim results of a phase II, multicenter, prospective, single-blinded, randomized controlled trial. Patients with mild AD who meet the inclusion criteria (age between 60 and 85 years, diagnosed with AD based on the new diagnostic criteria for AD outlined by the National Institute on Aging and Alzheimer’s Association, stable maintenance of general AD drug treatment for more than 3 months, amyloid accumulation in the brain confirmed by amyloid positron emission tomography (PET) and mild AD (score range of 13 to 24 on the Korean Mini-Mental State Examination [K-MMSE] or 0.5 or 1 on the Clinical Dementia Rating scale [CDR])) were randomly assigned to three groups: experimental I (24 cGy/6 fractions), experimental II (300 cGy/6 fractions), or the sham RT group (0 cGy/6 fractions). The experimental groups received radiation therapy twice per week for 3 weeks. Genetic testing (apolipoprotein E genotyping) was performed for all patients. The effectiveness of LDRT was assessed through amyloid PET, brain magnetic resonance imaging (MRI) and neurocognitive function tests at baseline, 6 and 12 months post-LDRT. The primary endpoint is the change in cognitive function test scores estimated by the Alzheimer’s Disease Assessment Scale -Korea (ADAS-K) compared to baseline after 6 months of LDRT. The secondary endpoints include the changes in the standardized uptake value ratio (SUVR) of amyloid PET scans and the score change of K-MMSE-2, CDR, CGA-NPI and K-iADL after 6, 12 months from baseline. This study is registered at ClinicalTrials.gov NCT05635968, and this study is supported by a grant of Korea Hydro & Nuclear Power company R&D fund Grant No. A21IP11. Out of the 28 patients who underwent randomization (one patient was excluded due to treatment-unrelated orthostatic hypotension), 15 patients (5 patients assigned to each 3 groups) who completed neurocognitive function tests, amyloid PET and brain MRI 6 months post LDRT were analyzed. In the control group, all 5 patients experienced a decline in cognitive function test scores across all cognitive assessments, while the experimental group showed mixed results. Four patients (2 patients in each of experimental group I and II) demonstrated improvement in their ADAS-K scores. The baseline ADAS-K, CDR, K-MMSE scores were not statistically different between the groups. However, at 6 months, ADAS-K, CDR and K-MMSE (p=0.055, 0.027, and 0.049, respectively) scores were different among the three groups through the Kruskal wallis test. There was a statistically significant difference between the control group and the experimental group I in ADAS-K (median 42 vs 30, p=0.047) and K MMSE (median 19 vs 23, p=0.049) scores through the Wilcoxon rank-sum test. The treatment was well-tolerated in all treatment groups, with no grade I or higher adverse events reported. Results:

Conclusion:

Whole-brain LDRT for AD patients was tolerable and demonstrated a reduction in the deterioration of cognitive function and clinical symptoms when compared with control group in this interim analysis.

Keywords: Alzheimer's disease, low dose radiation therapy

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