65. INVASIVE HISTOPATHOLOGY DRIVES POOR OUTCOMES IN SURGICALLY RESECTED BRAIN METASTASES
Bibliographic record
Abstract
Abstract BACKGROUND Brain metastasis (BrM) patients treated with surgery and radiotherapy frequently experience local recurrence (LR), leptomeningeal metastasis (LM), and poor overall survival (OS). We sought to correlate the presence of invasive or circumscribed histopathological growth pattern, observed in the BrM lesion and surrounding brain, with these outcomes, and to study molecular mediators of parenchymal invasion. METHODS We assessed the HGP of H&E-stained slides from 164 surgically resected BrM from 147 patients. HGP was correlated with incidence of LR, LM and OS. Single-cell RNA sequencing (scRNAseq) was performed on three invasive HGP patients, sampling the metastasis center (MC) and surrounding brain (SB) outside of the contrast-enhancing region. Orthotopic patient-derived xenograft models (OPDX) were established from N=30 brain metastasis via intracranial propagation. RESULTS 56/164 BrM specimens (34%) showed a circumscribed growth pattern between the tumor and adjacent brain (cHGP) while 108/164 (66%) showed significant invasion of tumor lobules or single cells into the brain parenchyma (iHGP). iHGP was associated with LR, LM and shortened OS in BrM patients. OPDX models of BrM retain features of patient BrM, including HGP. scRNAseq identified abundant cancer cells in SB that overexpressed a number of genes involved in cell survival, invasion and metastasis compared to matched cancer cells in MC. Validation of these targets with immunohistochemistry in patient and OPDX tissues revealed cold-inducible RNA binding protein (CIRBP) overexpression in iHGP patient and OPDX BrM. Modulation of CIRBP expression in OPDX and cell line models of iHGP BrM delayed BrM progression and extended OS. CONCLUSION iHGP is a poor prognostic indicator in patients with surgically resected BrM, establishing HGP as an important prognostic factor that should be considered by clinicians treating BrM patients. We identify CIRBP as a functional mediator of this process.
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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 | 0.000 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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".