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Published on: May 9, 2025
IDH-Mutant Low-grade Glioma: Advances in Molecular Diagnosis, Management, and Future Directions
Antonio Dono1,2, Leomar Y Ballester1,2,3, Ditte Primdahl4
1Vivian L. Smith Department of Neurosurgery, The University of Texas Health Science Center, 6431 Fannin Street, MSB 3.000, Houston, TX, 77030, USA.
Purpose Of Review:
IDH-mutant low-grade gliomas (LGG) have emerged as a distinct clinical and molecular entity with unique treatment considerations. Here, we review updates in IDH-mutant LGG diagnosis and classification, imaging biomarkers, therapies, and neurocognitive and patient-reported outcomes.
Recent Findings:
CDKN2A/B homozygous deletion in IDH-mutant astrocytoma is associated with shorter survival, similar to WHO grade 4. The T2-FLAIR mismatch, a highly specific but insensitive sign, is diagnostic of IDH-mutant astrocytoma. Maximal safe resection is currently indicated in all LGG cases. Radiotherapy with subsequent PCV (procarbazine, lomustine, vincristine) provides longer overall survival compared to radiotherapy alone. Temozolomide in place of PCV is reasonable, but high-level evidence is still lacking. LGG adjuvant treatment has important quality of life and neurocognitive side effects that should be considered. Although incurable, IDH-mutant LGG have a favorable survival compared to IDH-WT glioma. Recent advances in molecular-based classification, imaging, and targeted therapies will hopefully improve survival and quality of life.
Insights
Updates in IDH-mutant low-grade gliomas (LGG) reveal key diagnostic and therapeutic advances. While incurable, these gliomas show improved survival with new molecular classifications and targeted therapies.
Area of Science:
- Neuro-oncology
- Molecular Pathology
- Radiology
Background:
- IDH-mutant low-grade gliomas (LGG) represent a distinct clinical and molecular subtype.
- Understanding their unique characteristics is crucial for effective management.
Purpose of the Study:
- To review recent advancements in the diagnosis, classification, and treatment of IDH-mutant LGG.
- To discuss imaging biomarkers, therapeutic strategies, and outcomes.
Main Methods:
- Review of current literature on IDH-mutant LGG.
- Analysis of diagnostic criteria, molecular markers, and treatment protocols.
- Evaluation of neurocognitive and patient-reported outcomes.
Main Results:
- CDKN2A/B homozygous deletion correlates with poorer survival in IDH-mutant astrocytoma.
- T2-FLAIR mismatch is a specific diagnostic sign for IDH-mutant astrocytoma.
- Maximal safe resection is recommended for all LGG.
- Radiotherapy with PCV (procarbazine, lomustine, vincristine) improves survival over radiotherapy alone; temozolomide is an alternative.
- Adjuvant treatments have significant quality of life and neurocognitive side effects.
Conclusions:
- IDH-mutant LGG have a better prognosis than IDH-wildtype glioma.
- Advances in molecular classification, imaging, and targeted therapies offer hope for improved survival and quality of life.
