TY - JOUR
T1 - Impact of Apolipoprotein E Genotype on Neurocognitive Function in Patients With Brain Metastases
T2 - An Analysis of NRG Oncology's RTOG 0614
AU - Wefel, Jeffrey S.
AU - Deshmukh, Snehal
AU - Brown, Paul
AU - Grosshans, David R.
AU - Sulman, Erik P.
AU - Cerhan, Jane H.
AU - Mehta, Minesh P.
AU - Khuntia, Deepak
AU - Shi, Wenyin
AU - Mishra, Mark V.
AU - Suh, John H.
AU - Laack, Nadia N.
AU - Chen, Yuhchyau
AU - Curtis, Amarinthia (Amy)
AU - Laba, Joanna M.
AU - Elsayed, Ahmed
AU - Thakrar, Anu
AU - Pugh, Stephanie L.
AU - Bruner, Deborah W.
N1 - Publisher Copyright:
© 2023 Elsevier Inc.
PY - 2024
Y1 - 2024
N2 - Purpose: 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. Methods and Materials: 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. Results: 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). Conclusions: 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.
AB - Purpose: 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. Methods and Materials: 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. Results: 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). Conclusions: 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.
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U2 - 10.1016/j.ijrobp.2023.12.004
DO - 10.1016/j.ijrobp.2023.12.004
M3 - Article
C2 - 38101486
AN - SCOPUS:85184042041
SN - 0360-3016
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
ER -