LGG-18. MOLECULAR ALTERATIONS PREDICT RESPONSE TO CHEMOTHERAPY AND OUTCOME OF PEDIATRIC LOW-GRADE GLIOMA
Bibliographic record
Abstract
BACKGROUND: Pediatric low-grade glioma (pLGG) is the most common childhood brain tumor. Recently, alterations of the RAS/MAPK pathway have been identified as the major driver of PLGG however little is known about prognostic implications. DESIGN/METHODS: We undertook a large population based study of all pLGG diagnosed from 1985–2015. Detection of known pLGG-related fusions was evaluated by NanoString and point mutations BRAF-V600E and H3.3K27M were evaluated using QX200™Droplet Digital™PCR. Results were correlated with outcome and response to chemotherapy. RESULTS: BRAF was found to be altered (KIAA1549-BRAF or BRAF-V600E) in 57% of patients in our pLGG cohort with full clinical and molecular data (n=480). Other alterations accounted for 6% of cases (FGFR1-TACC1(n=9), MYBL1(n=5), H3.3K27M(n=10)). The remaining 37% pLGG cases did not harbor any of evaluated alterations. Additional 134 patients with neurofibromatosis-1(NF1) were included in survival analysis. Kaplan-Meier analysis revealed 10-year PFS 72.3% for NF1, 68.3% for all KIAA1549-BRAF, and 28.4% for BRAF-V600E(p<0.0001). Among other alterations, H3.3K27M delineated a poor prognostic group with behavior similar to high-grade glioma. All patients with FGFR1-TACC1 and MYBL1 were alive at the time of analysis despite several observed progressions. Furthermore, we evaluated whether differences in survival could be correlated with response to conventional therapy in 92 patients. Change in tumor size at 6 months of chemotherapy differed depending on alteration. 45% of patients with BRAF-KIAA1549 responded to first line chemotherapy, and only 7.5% progressed. Similarly, 35% of NF1 patients responded and none progressed. In contrast, only 15% BRAF-V600E responded and more than half of tumors exhibited growth after six months of chemotherapy. CONCLUSIONS: In contrast to BRAF-V600E, KIAA1549-BRAF defines a group of pLGG patients with excellent prognosis and response to chemotherapy similar to NF1. Biopsy should be mandated in order to predict outcome, response to chemotherapy and evaluate targets for novel therapies.
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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) | 0.001 | 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 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".