5 The Impact of Sex and Associations With Treatment Exposures on Neurocognitive Impairment in Pediatric Cancer Survivors: A report from the Childhood Cancer Survivor Study
Bibliographic record
Abstract
Objective: Sexual dimorphism in human brain structure and behavior is influenced by exposure to sex hormones during critical developmental periods. In children, cancer and cancer treatments may alter hormone activity and brain development, impacting neurocognitive functions. Participants and Methods: Five-year survivors of childhood cancer (N=15,560) diagnosed at <21 years from 1970 to 1999, and 3,206 siblings from the Childhood Cancer Survivor Study completed the Neurocognitive Questionnaire (NCQ), a measure of self-reported task efficiency (TE), emotion regulation (ER), Organization, and working memory (WM). We compared rates of cognitive impairment (i.e., NCQ scores >90th percentile) in survivors and same-sex siblings, and sex differences in risk factors for cognitive impairment (i.e., treatment exposures, chronic health conditions (CHCs), cancer diagnosis, age at diagnosis) using modified Poisson regressions. Results: Survivors were more likely to report cognitive impairment than same-sex siblings (Males: TE OR=2.3, p<.001; ER OR=1.7, p=.008; Organization OR=1.5, p=.04; WM OR=2.3, p<.001. Females: TE OR=2.6, p<.001; ER OR=1.9, p<.001; Organization OR=1.5, p=.02; WM OR=2.6, p<.001). Within survivors, females were more likely than males to report impairment in TE (OR=1.2, p=.001), ER (OR=1.5, p<.001), and WM (OR=1.2, p<.001). There were no sex differences in symptom severity in siblings (all ps>.05). Risk factors for cognitive impairment in survivors included cranial radiation dose (TE <20Gy OR=1.5, p=.008, ≥20Gy OR=2.5, p<.001; ER OR=1.5, p<.001; Organization <20 Gy OR=1.4, p<.001; < WM 20 Gy OR=1.8, p<.001, ≥20Gy OR=2.7, p<.001), presence of moderate to severe CHCs (TE 1 CHC OR=1.9, p<.001, >1 CHC OR=3.6, p<.001; ER 1 CHC OR=1.7, p<.001, >1 CHC OR=2.2, p<.001; Organization 1 CHC OR=1.5, p=.001, >1 CHC OR=2.5, p<.001; WM 1 CHC OR=1.8, p<.001, >1 CHC OR=4.1, p<.001). There were sex differences in cognitive impairment risk factors in survivors. In females, cranial radiation dose (<20 Gy TE OR=1.6, p=.02; ≥20Gy TE OR=1.4, p=.01), leukemia diagnosis (TE OR=1.4, p=.02), or diagnosis age between 3-5 years (WM OR=1.4, p=.02) conferred higher risk for cognitive impairment compared to males with the same history. Females diagnosed with Hodgkin’s lymphoma (Organization OR=0.61, p=.05) or non-Hodgkin’s lymphoma (Organization OR=0.55, p=.03) were at lower risk for cognitive impairment compared to males. Conclusions: We found sex-specific differences in rates of, and risk factors for, neurocognitive impairment, suggesting a sex vulnerability. Future studies examining interactions between sex hormones and treatment exposures during brain development will enable tailoring treatments follow-up interventions to ensure that quality of life is maximized.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".