Non-canonical IDH-Mutant Astrocytomas: Prevalence, Natural History, and Survival Analysis
Bibliographic record
Abstract
Introduction:Mutations of the IDH gene have been proposed to exhibit a significant role in the tumorigenesis, progression, and prognosis of gliomas.The most common mutation is a missense mutation that affects amino acid residue 132 and is associated with longer survival in patients with glioma than in patients with glioma without IDH1 mutations.Other non-R132H mutations known as non-canonical IDH mutations are less common (7-20%). Objectives:We aimed to provide a detailed and comprehensive analysis of the non-canonical IDHmutant astrocytomas in this single-center cohort, looking at the prevalence, natural history, and prognosis of this tumor in a real-world setting. Hypothesis:We hypothesize that the results of this clinical review would help in identifying the natural history of the non-canonical IDH mutated astrocytomas and help in decision-making in treating patients harboring the mutations. Methods:We identified 115 patients (1993-2022) with IDH1/2 mutated astrocytomas and analyzed the molecular markers, patient characteristics, histology, treatment, recurrence and/or progression, PFS, and OS. Results:Eighteen patients (15.6%) were harboring the non-canonical IDH mutations (R132C 44%, R132S 33%, R132G 17%, and R172M 6%).Patients with non-canonical IDH-mutant astrocytomas were younger with a median age at diagnosis of 35-year (p=0.009).Right hemispheric involvement was more common in the non-canonical group (61%), with frontal lobe predominance (50%).In both groups, there was a higher prevalence of WHO grade 2/3 astrocytomas than grade four astrocytomas.Interestingly, 17% of the non-canonical were of grade 4 upon initial diagnosis.Recurrence and/or progression were seen in 55% of the noncanonical cohort.Longer PFS was observed in non-canonical astrocytomas with lower WHO grade (p=0.01), and in patients treated with GTR compared to STR (p= 0.035).Higher WHO grade of the non-canonical associated with shorter OS (p= 0.01).Similarly, a higher WHO grade of recurrence was associated with poor OS post-recurrence (p< 0.01).R132H-mutant astrocytomas showed longer OS when compared to the non-canonical IDH-mutant astrocytomas.However, the overall survival did not differ significantly between the two cohorts (p= 0.59). Conclusion:This is one of the largest retrospectives, real-life datasets describing the prevalence and the natural history of the non-canonical IDH-mutant astrocytomas which was not reported before.Due to the nature of the study and the small sample size, our analysis failed to show a strong correlation between the non-canonical IDH-mutant astrocytomas and the R132H mutation and the OS.Additional studies should be conducted with larger sample sizes and should also assess the type and dose of chemotherapy/radiotherapy used in non-canonical IDH-mutant astrocytoma.ATRX: α-thalassemia/mental retardation syndrome X-linked Bx: Biopsy
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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 | 0.001 | 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".