ATCT-09IDH1 R132H MUTATIONS IN NRG ONCOLOGY/RTOG 9802: PHASE III STUDY OF RADIATION THERAPY (RT) ALONE VS RT PLUS PROCARBAZINE, CCNU, AND VINCRISTINE (PCV) IN PATIENTS WITH LOW GRADE GLIOMA (LGG)
Bibliographic record
Abstract
BACKGROUND: RT/PCV produces longer progression-free (PFS) and overall survival (OS) in LGG patients versus RT alone. Molecular markers have not been reported previously. METHODS: 251 eligible LGG patients were randomized to receive RT or RT/PCV. Immunohistochemistry, performed with the monoclonal antibody against IDH1 R132H, was scored positive when tumor cells showed cytoplasmic staining. Wilcoxon tests were performed to assess PFS and OS for IDH1-R132H positive vs negative patients, and, for IDH1-R132H mutated patients, for differences by treatment arm. RESULTS: Tissue suitable for IDH-R132H immunohistochemistry was interpretable for 113 (57/126 [45%] and 56/125 [45%]) patients in the RT vs RT/PCV arms, respectively. IDH1-R132H mutations were detected in 35/57 (61.4%) and 36/56 (64.3%) in the RT and RT/PCV arms, respectively, and in 77.6%, 53.8% and 48.0% of patients with oligodendroglioma, oligoastrocytoma, and astrocytoma, respectively. For patients without vs with IDH1-R132H mutations: median PFS was 1.5 vs 7.6 years (p < 0.001); and OS was 5.1 vs 13.1 years, respectively (p = 0.002). For patients with IDH1-R132H mutations: median, 5-year, and 10-year PFS were 4.7 years, 43%, and 21% in the RT arm, vs not reached (NR) (7.6+ years), 75%, and 64% with RT /PCV, respectively (p = 0.003). For patients with IDH1-R132H mutations: median, 5-year, and 10-year OS were 10.1 years, 69%, and 53% with RT, and NR (11.3+ years), 83%, and 75% with RT + PCV (p = 0.04). Tissue sufficient for determination of other genetic alterations was available in only 25% of patients, so reliable assessment is not feasible. CONCLUSIONS: IDH1-R132H mutations are associated with prolonged PFS and OS, regardless of treatment. In patients with IDH1-R132H mutations, RT + PCV is associated with longer PFS and OS compared with RT alone. SUPPORT: This project was supported by grants U10CA21661, U10CA180868, U10CA180822 and U10CA37422 from the National Cancer Institute (NCI).
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.001 |
| 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".