Related Experiment Video
Updated: Jul 24, 2025
Primary Orthotopic Glioma Xenografts Recapitulate Infiltrative Growth and Isocitrate Dehydrogenase I Mutation
Published on: January 14, 2014
IDH-mutant grade 4 astrocytoma: a comparison integrating the clinical, pathological, and survival features between
Yanwei Liu1,2, Dezhi Gao3,2, Huiyuan Chen4
1Departments of1Radiation Oncology and.
Objective:
IDH-mutant grade 4 astrocytomas (AIDHmut/G4) are divided into primary de novo (pAIDHmut/G4) and secondary with a history of prior lower-grade gliomas (LGGs; sAIDHmut/G4). The mutational spectrum and DNA methylation patterns are homogeneous within de novo pAIDHmut/G4 and evolved sAIDHmut/G4, but the two groups have different diagnoses, management, and outcomes. This study sought to systematically compare the clinical, pathological, and survival characteristics between them.
Methods:
Of the 871 grade 4 astrocytomas with data for IDH mutation, 698 (80.1%) were primary and 173 (19.9%) were secondary. Of the 698 primary tumors, 103 (14.8%) were pAIDHmut/G4, and of the 173 secondary tumors, 108 (62.4%) were sAIDHmut/G4. Clinical, pathological, and survival features were compared between pAIDHmut/G4 and sAIDHmut/G4. Multivariate analyses were performed to identify prognostic factors.
Results:
Patients with sAIDHmut/G4 had significantly shorter median overall survival (OS; 11.8 vs 34.2 months, hazard ratio [HR] 2.69, 95% confidence interval [CI] 1.367-5.306, p = 0.004) and progression-free survival (PFS; 8.5 vs 24.3 months, HR 2.83, 95% CI 1.532-5.235, p = 0.001) than patients with pAIDHmut/G4. In patients with sAIDHmut/G4, resection status and chemotherapy were independent prognostic factors for OS and PFS; in patients with pAIDHmut/G4, LGG component, resection status, and O6-methylguanine DNA methyltransferase promoter methylation were independent prognostic factors. The therapeutic strategies of LGGs did not influence survival of patients with sAIDHmut/G4, but patients who had not received radiotherapy or chemotherapy when they were diagnosed with LGGs were found to benefit from radiotherapy or chemotherapy when they progressed to sAIDHmut/G4.
Conclusions:
The different clinical characteristics, survival, and risk factors between sAIDHmut/G4 and pAIDHmut/G4 provide a reference to guide treatment decisions in AIDHmut/G4.
Insights
Secondary IDH-mutant grade 4 astrocytomas (sAIDHmut/G4) have significantly shorter survival than primary de novo tumors (pAIDHmut/G4). Treatment decisions for AIDHmut/G4 should consider these distinct clinical and prognostic factors.
Area of Science:
- Neuro-oncology
- Molecular Pathology
- Clinical Neurology
Background:
- IDH-mutant grade 4 astrocytomas (AIDHmut/G4) are classified as primary de novo (pAIDHmut/G4) or secondary (sAIDHmut/G4) based on prior lower-grade gliomas (LGGs).
- While molecular profiles are similar, distinct clinical, diagnostic, and prognostic characteristics are suspected between these subtypes.
- This study systematically compares pAIDHmut/G4 and sAIDHmut/G4.
Purpose of the Study:
- To systematically compare the clinical, pathological, and survival characteristics of primary de novo IDH-mutant grade 4 astrocytomas (pAIDHmut/G4) and secondary IDH-mutant grade 4 astrocytomas (sAIDHmut/G4).
- To identify independent prognostic factors for overall survival (OS) and progression-free survival (PFS) in both pAIDHmut/G4 and sAIDHmut/G4 patient cohorts.
- To provide a clinical reference for guiding treatment decisions in AIDHmut/G4.
Main Methods:
- Retrospective analysis of 871 grade 4 astrocytomas with IDH mutation data.
- Categorization into primary (n=103) and secondary (n=108) IDH-mutant grade 4 astrocytomas.
- Comparison of clinical, pathological, and survival features, with multivariate analyses for prognostic factors.
Main Results:
- Secondary AIDHmut/G4 (sAIDHmut/G4) exhibited significantly shorter median OS (11.8 vs 34.2 months) and PFS (8.5 vs 24.3 months) compared to primary AIDHmut/G4 (pAIDHmut/G4).
- In sAIDHmut/G4, resection status and chemotherapy were independent prognostic factors for OS and PFS.
- In pAIDHmut/G4, LGG component, resection status, and O6-methylguanine DNA methyltransferase promoter methylation were independent prognostic factors.
Conclusions:
- Significant differences in clinical characteristics, survival, and risk factors exist between sAIDHmut/G4 and pAIDHmut/G4.
- These findings offer a valuable reference for optimizing treatment strategies in IDH-mutant grade 4 astrocytomas.
- Previous LGG treatment did not impact sAIDHmut/G4 survival, but radiotherapy/chemotherapy benefited patients progressing to sAIDHmut/G4.
