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Impact of Apolipoprotein E Genotype on Neurocognitive Function in Patients With Brain Metastases: An Analysis of NRG Oncology's RTOG 0614.
- Source :
-
International Journal of Radiation Oncology, Biology, Physics . Jul2024, Vol. 119 Issue 3, p846-857. 12p. - Publication Year :
- 2024
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Abstract
- Whole-brain radiation therapy (WBRT) is a common treatment for brain metastases and is frequently associated with decline in neurocognitive functioning (NCF). The e4 allele of the apolipoprotein E (APOE) gene is associated with increased risk of Alzheimer disease and NCF decline associated with a variety of neurologic diseases and insults. APOE carrier status has not been evaluated as a risk factor for onset time or extent of NCF impairment in patients with brain metastases treated with WBRT. NRG/Radiation Therapy Oncology Group 0614 treated adult patients with brain metastases with 37.5 Gy of WBRT (+/– memantine), performed longitudinal NCF testing, and included an optional blood draw for APOE analysis. NCF test results were compared at baseline and over time with mixed-effects models. A cause-specific Cox model for time to NCF failure was performed to assess the effects of treatment arm and APOE carrier status. APOE results were available for 45% of patients (n = 227/508). NCF did not differ by APOE e4 carrier status at baseline. Mixed-effects modeling showed that APOE e4 carriers had worse memory after WBRT compared with APOE e4 noncarriers (Hopkins Verbal Learning Test–Revised total recall [least square mean difference, 0.63; P =.0074], delayed recognition [least square mean difference, 0.75; P =.023]). However, APOE e4 carrier status was not associated with time to NCF failure (hazard ratio, 0.86; 95% CI, 0.60-1.23; P =.40). Memantine delayed the time to NCF failure, regardless of carrier status (hazard ratio, 0.72; 95% CI, 0.52-1.01; P =.054). APOE e4 carriers with brain metastases exhibited greater decline in learning and memory, executive function, and the Clinical Trial Battery Composite score after treatment with WBRT (+/– memantine), without acceleration of onset of difference in time to NCF failure. [ABSTRACT FROM AUTHOR]
- Subjects :
- *APOLIPOPROTEIN E
*APOLIPOPROTEIN E4
*VERBAL learning
*EXECUTIVE function
*GENOTYPES
Subjects
Details
- Language :
- English
- ISSN :
- 03603016
- Volume :
- 119
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- International Journal of Radiation Oncology, Biology, Physics
- Publication Type :
- Academic Journal
- Accession number :
- 177750152
- Full Text :
- https://doi.org/10.1016/j.ijrobp.2023.12.004