Impact of apolipoprotein E (APOE) genotype on neurocognitive function (NCF) in patients with brain metastasis (BM): An analysis of NRG Oncology’s RTOG 0614.
Bibliographic record
Abstract
2065 Background: Whole brain radiotherapy (WBRT) is a common treatment for BM and is associated with decline in NCF. The APOE e4 allele is associated with increased risk of Alzheimer’s disease, and NCF decline after chemotherapy for non-CNS cancer, treatment for primary brain tumor, and in irradiated mouse models. APOE carrier status has not been evaluated as a risk factor for impaired NCF in patients with BM before and after WBRT. Methods: RTOG 0614 treated adult patients with BM with 37.5 Gy of WBRT (+/- memantine), performed NCF testing (HVLT-R, TMT, COWA) at baseline, 8, 16, 24, and 52 weeks, and included an optional blood draw for APOE analysis. APOE alleles were evaluated by real-time PCR based SNP analysis using TaqMan genotyping. NCF test results were compared at baseline and over time with mixed effects models adjusted for baseline score, treatment arm, time, and interaction between time and APOE carrier status. A cause-specific Cox model for time to NCF failure was performed to assess the effects of treatment arm (memantine versus placebo) and APOE carrier status (e4 versus no e4). Results: APOE results were available for 45% (n = 227/508) of patients. No pretreatment differences were detected between patients with APOE available versus not available. APOE e4 carrier status was evenly distributed between treatment arms (e4 positive = 29.5%). NCF test results did not differ by APOE e4 carrier status at baseline, but e4 carriers were less often white and had started WBRT at study entry more often. Mixed effects modeling showed that patients without an APOE e4 allele had better memory after WBRT compared to patients with an APOE e4 allele (HVLT-R Total Recall [estimate = 2.44, p = 0.026], Delayed Recognition [estimate = 1.15, p = 0.024]). For time to NCF failure, treatment arm was significant (HR = 0.715, 95% CI: 0.513-0.998, p = 0.0487) in favor of memantine; however, APOE e4 status was not (HR = 0.865, 95% CI: 0.606-1.233, p = 0.422). Conclusions: Patients with an APOE e4 allele exhibited worse memory function after treatment with WBRT (+/- memantine), but no difference in time to NCF failure. APOE carrier status was not associated with NCF in patients with BM prior to WBRT. Clinical trial information: NCT00566852.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".