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A Protocol for Explant Cultures of IDH1-mutant Diffuse Low-grade Gliomas
Published on: May 9, 2025
[Treatment of Lower-Grade Glioma:Emergence of IDH Inhibitors and Changes in Therapeutic Decision-Making]
1Department of Neurosurgery, Kyoto University Graduate School of Medicine.
Abstract:
Lower-grade gliomas comprise a biologically heterogeneous group of adult diffuse gliomas, primarily defined by their molecular alterations. In current practice, management should integrate maximal safe resection, individualized use of radiotherapy, and rational systemic therapy based on the tumor subtype, growth pattern, and anticipated long-term functional outcomes. Surgery remains the cornerstone of treatment because the extent of resection influences tumor control, seizure burden, functional outcomes, and timing of adjuvant therapy. Although radiotherapy is effective, its timing, dose, and field design should be optimized to preserve neurocognitive function and quality of life in patients with prolonged life expectancy. Combined chemoradiotherapy remains essential for select high-risk tumors, whereas temozolomide alone cannot be considered a universal substitute for radiotherapy-based strategies. The emergence of IDH inhibitors, particularly vorasidenib, has expanded therapeutic options for select patients with residual or recurrent non-enhancing grade 2 IDH-mutant gliomas following surgery by prolonging progression-free survival and delaying the need for subsequent intervention, without apparent deterioration in health-related quality of life or neurocognition. This review summarizes current evidence and proposes a practical framework for integrating surgery, radiotherapy, conventional chemotherapy, and IDH inhibition into routine clinical decision-making.
Insights
This review highlights integrating surgery, radiotherapy, and chemotherapy for adult diffuse gliomas. New IDH inhibitors like vorasidenib offer improved outcomes for specific glioma subtypes.
Area of Science:
- Neuro-oncology
- Molecular Oncology
- Clinical Neurology
Background:
- Lower-grade gliomas are diverse adult diffuse gliomas defined by molecular changes.
- Current management combines surgery, radiotherapy, and systemic therapy based on tumor characteristics and prognosis.
Purpose of the Study:
- To review current evidence on managing lower-grade gliomas.
- To propose a framework for integrating multimodal treatment strategies, including novel therapies.
Main Methods:
- Literature review of current evidence on surgical resection, radiotherapy, chemotherapy, and IDH inhibitors.
- Analysis of treatment impacts on tumor control, functional outcomes, and quality of life.
Main Results:
- Maximal safe resection is crucial for tumor control and functional outcomes.
- Optimized radiotherapy and chemotherapy are vital, with combined chemoradiotherapy for high-risk tumors.
- IDH inhibitors, such as vorasidenib, show promise in prolonging progression-free survival for specific IDH-mutant gliomas.
Conclusions:
- A multidisciplinary approach integrating surgery, radiotherapy, chemotherapy, and IDH inhibition is essential for personalized lower-grade glioma management.
- Optimizing treatment timing and modality is key to balancing efficacy with neurocognitive preservation and quality of life.

