What are the characteristics of a high-grade Isocitrate Dehydrogenase (IDH) wild-type astrocytoma located in the thalamus?

From the Guidelines

High grade IDH wild-type astrocytoma of the thalamus should be treated with maximal safe surgical resection when possible, followed by concurrent radiation therapy and temozolomide chemotherapy, as this approach has been shown to improve outcomes in patients with similar tumor types 1. The recommended radiation dose is typically 60 Gy in 1.8-2 Gy fractions, with daily temozolomide at 75 mg/m² for 6 weeks, then adjuvant temozolomide (150-200 mg/m² for 5 days every 28 days) for 6-12 cycles. For thalamic tumors, complete resection is often challenging due to the deep location and proximity to critical structures, so stereotactic biopsy may be performed instead to confirm diagnosis. Some key points to consider in the treatment of high grade IDH wild-type astrocytoma of the thalamus include:

• Molecular testing is essential, as IDH wild-type status indicates a more aggressive tumor behavior similar to glioblastoma 1
• Treatment planning should involve a multidisciplinary tumor board including neurosurgery, radiation oncology, and neuro-oncology
• Patients typically require anticonvulsant medication (such as levetiracetam 500-1000 mg twice daily) if seizures occur, and dexamethasone (4-16 mg daily in divided doses) to control cerebral edema, though steroid use should be minimized when possible
• Regular MRI monitoring every 2-3 months during treatment and follow-up is necessary to assess response The prognosis for high-grade IDH wild-type astrocytomas is generally poor, with median survival typically ranging from 12-18 months, though individual outcomes vary based on age, performance status, extent of resection, and response to therapy. It's worth noting that the evidence for the treatment of high grade IDH wild-type astrocytoma of the thalamus is largely based on extrapolation from other tumor types, such as glioblastoma, and that further research is needed to determine the optimal treatment approach for this specific tumor type 1.

From the Research

High Grade IDH Wild Type Astrocytoma of Thalamus

• High-grade astrocytomas are aggressive and incurable primary brain tumors, with radiation therapy and concurrent and adjuvant temozolomide chemotherapy being the standard-of-care treatment for newly diagnosed glioblastoma 2
• Anaplastic Astrocytoma (AA) is a malignant, diffusely infiltrating, primary brain tumor, with IDH wild-type form having a worse prognosis than IDH mutated tumor 3
• IDH1 mutant malignant astrocytomas are more amenable to surgical resection and have a survival benefit associated with maximal surgical resection, whereas IDH1 wild-type tumors do not show a significant survival benefit with further resection of nonenhancing disease 4
• IDH wild-type (wt) grade 2/3 astrocytomas are a heterogenous group of tumors with disparate clinical and molecular profiles, and the use of a panel of molecular markers can help reclassify IDH-wt grade 2/3 diffuse astrocytic gliomas (DAGs) and identify a subset with an aggressive clinical course similar to IDH-wt glioblastomas (GBMs) 5
• Most IDH wild type astrocytomas can be allocated to other tumor entities on a molecular basis, such as the molecular equivalent of conventional glioblastoma (GBM) or GBM-H3F3A mutated (GBM-H3), and the diagnosis of IDHwt diffuse astrocytoma or anaplastic astrocytoma should be used with caution 6

Treatment Options

• Radiation therapy with concurrent and adjuvant temozolomide chemotherapy is the standard-of-care treatment for newly diagnosed glioblastoma 2
• Maximal safe resection followed by radiotherapy and chemotherapy with temozolomide is the standard of care for anaplastic astrocytoma 3
• Investigational treatments, including numerous molecularly targeted agents and immunotherapeutic approaches, are currently being evaluated for high-grade astrocytomas 2
• The treatment of IDH wild-type astrocytomas remains challenging, and some trials are ongoing to evaluate new potential drugs, alone or in combination with chemotherapy 3

Prognosis

• IDH wild-type astrocytomas have a worse prognosis than IDH mutated tumors 3
• The survival benefit associated with surgical resection differs based on IDH1 genotype in malignant astrocytic gliomas, with IDH1 mutant gliomas having a better prognosis than IDH1 wild-type tumors 4
• IDH wild-type grade 2/3 astrocytomas have a heterogeneous clinical and molecular profile, and the use of a panel of molecular markers can help identify a subset with an aggressive clinical course similar to IDH-wt glioblastomas (GBMs) 5