PATH-79. High-grade astrocytoma with piloid features (HGAP) comprehensive update: histological grading, molecular markers and clinical outcomes
Bibliographic record
Abstract
Abstract BACKGROUND HGAP was first described in 2018. However, prognostic factors of clinical outcome are not well-understood secondary to recent recognition and paucity of data for this diagnostic entity. Here, we utilize a large HGAP cohort (n=252) to survey the genomic landscape and explore prognostic correlates. METHODS NIH DNA methylation profiling was performed to identify HGAP cases and combined with publicly available datasets. Evaluable molecular markers, patient demographics, tumor location, imaging reports, treatment history (e.g. temozolomide, targeted therapy, surgery, and radiation) and survival data were assessed. Kaplan-Meier analysis was performed. RESULTS The cohort included cases that matched to HGAP on the NIH/Bethesda methylation classifier at ≥0.9 confidence score. More males (60%) than females (40%) were in the cohort. Twenty-one percent of patients were known to have neurofibromatosis type 1. Posterior fossa location was predominant (57%, n=131). Common genomic findings included alterations in NF1 (58%), ATRX (50%), FGFR1 (15%), TP53 (9%) and PIK3CA (8%). CDKN2A/B homozygous deletion was identified in 80% of cases. MGMT promoter methylation was found in 55% of cases. Median progression free survival (mPFS) was 24 months (mo), and median overall survival (mOS) was 108 mo. Central histological review revealed 67% of cases were high-grade. High-grade histopathology (brisk mitotic activity) was not associated with survival. Immunohistochemical ATRX loss was associated with shorter mPFS (18.0 mo vs 35.5 mo, p=0.04) and mOS (93.7 mo vs not reached, p=0.04). The presence of ATRX genetic alterations was associated with shorter mOS (30 mo vs not reached, p=0.008). CDKN2A/B homozygous deletion and MGMT status were not correlative with patient outcome. CONCLUSION HGAP is a glial neoplasm that shows frequent tumor recurrence. The majority of HGAP cases are high-grade. Our analysis of correlates with patient outcome suggests immunohistochemical ATRX loss and molecular ATRX alteration may be important poor prognostic markers.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.002 |
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 source (direct Gemma or distilled Codex), 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".