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Anaplastic Glioma: Treatment Approaches in the Era of Molecular Diagnostics
Michael W Ruff1,2, Joon Uhm3,4
1Division of Neuro-Oncology Mayo Clinic, Rochester, MN, USA. ruff.michael@mayo.edu.
Opinion Statement:
The treatment paradigm for anaplastic glioma has shifted, owing to new diagnostic criteria and new phase III clinical trial evidence. In 2016, the WHO classification of brain tumors including diffuse gliomas was redefined to include molecular criteria, often supplanting the morphological appearance of the tumor cells. This was necessary as prognosis is more closely associated with molecular diagnosis than with morphology and grade. Recently, the benefit of adjuvant chemotherapy in addition to radiotherapy has been demonstrated in both anaplastic oligodendroglioma and anaplastic astrocytoma, as well as lower grade gliomas with the most marked benefit evident in IDH-mutated (astrocytoma) and 1p/19q co-deleted (oligodendroglial) tumors. The defining principle of recent breakthroughs has been the benefit of combinatorial therapy (chemo-radiation) as opposed to treatment in series or treatment of either modality after a period of observation upon evidence of progression.
Insights
The treatment for anaplastic glioma now incorporates molecular diagnostics and combined chemo-radiation therapy. This approach offers improved prognosis, particularly for IDH-mutated and 1p/19q co-deleted gliomas.
Area of Science:
- Neuro-oncology
- Molecular Pathology
- Clinical Trials
Background:
- The 2016 WHO classification redefined brain tumor diagnosis using molecular criteria over morphology.
- Prognosis in gliomas is now more strongly linked to molecular markers than traditional grading.
- Recent phase III trials provide new evidence for adjuvant therapies.
Purpose of the Study:
- To review the evolving treatment landscape for anaplastic glioma.
- To highlight the impact of molecular subtyping on therapeutic strategies.
- To emphasize the benefits of combinatorial chemo-radiation therapy.
Main Methods:
- Analysis of recent phase III clinical trial data.
- Review of updated World Health Organization (WHO) classification guidelines for brain tumors.
- Evaluation of molecular markers (IDH mutation, 1p/19q co-deletion) in glioma treatment.
Main Results:
- Adjuvant chemotherapy combined with radiotherapy demonstrates significant benefit in anaplastic gliomas.
- The most pronounced benefits are observed in IDH-mutated astrocytomas and 1p/19q co-deleted oligodendrogliomas.
- Combinatorial chemo-radiation is superior to sequential or observed treatment approaches.
Conclusions:
- The standard of care for anaplastic glioma has shifted towards molecularly informed, combinatorial therapy.
- Molecular diagnostics are crucial for predicting treatment response and patient outcomes.
- Chemo-radiation represents a paradigm shift, improving outcomes for specific glioma subtypes.
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