What are the treatment recommendations for patients with gliomas, including glioblastoma?

From the Guidelines

Treatment for gliomas, particularly glioblastoma, typically involves a multimodal approach, starting with maximal safe surgical resection, followed by concurrent chemoradiation therapy with temozolomide and radiation, and then adjuvant temozolomide, as recommended by the most recent guidelines 1.

Key Considerations

• The standard of care begins with maximal safe surgical resection to remove as much tumor as possible while preserving neurological function.
• Concurrent chemoradiation therapy with temozolomide (75 mg/m² daily) and radiation (60 Gy in 30 fractions) for 6 weeks is a crucial component of treatment.
• Adjuvant temozolomide (150-200 mg/m² for 5 days every 28 days) for 6-12 cycles is also recommended.
• For patients over 65 years, hypofractionated radiation with temozolomide may be used, as supported by studies such as NOA-08 1.
• Tumor treating fields (TTFields) therapy can be added after chemoradiation to improve survival, although its use is limited by cost and burden concerns 1.

Molecular Markers and Treatment

• IDH mutation and 1p/19q codeletion status are important molecular markers that guide treatment decisions.
• IDH-mutant tumors are more likely to respond to chemotherapy, and treatment may be less aggressive, with observation after surgery or radiation with or without chemotherapy.
• MGMT promoter methylation status is also important, particularly in elderly patients or those with poor performance status, as it can guide the use of temozolomide or radiation therapy 1.

Supportive Care

• Supportive care is essential and includes dexamethasone for cerebral edema, antiepileptic drugs for seizures, and venous thromboembolism prophylaxis.
• Geriatric assessment is recommended for patients over 65 years to better predict medical vulnerabilities and estimate toxicity to chemotherapy 1.

Conclusion is not allowed, so the answer will continue with more details and considerations.

Some of the key recommendations from the guidelines include:

• Glioma classification should follow the most recent WHO Classification of Tumors of the Central Nervous System, complemented by cIMPACT-NOW updates 1.
• Immunohistochemistry for mutant IDH1 R132H protein and nuclear expression of ATRX should be performed routinely in the diagnostic assessment of diffuse gliomas 1.
• MGMT promoter methylation status should be determined in glioblastoma, notably in elderly or frail patients, to aid in decision-making for the use of temozolomide 1.

From the FDA Drug Label

Temozolomide capsules are indicated for the treatment of adult patients with newly diagnosed glioblastoma multiforme concomitantly with radiotherapy and then as maintenance treatment. Temozolomide capsules are indicated for the treatment of adult patients with refractory anaplastic astrocytoma, i.e., patients who have experienced disease progression on a drug regimen containing nitrosourea and procarbazine.

The treatment recommendations for patients with gliomas, including glioblastoma, are as follows:

• Newly Diagnosed Glioblastoma Multiforme: Temozolomide capsules are administered at 75 mg/m² daily for 42 days concomitant with focal radiotherapy, followed by maintenance temozolomide capsules for 6 cycles.
• Refractory Anaplastic Astrocytoma: Temozolomide capsules are administered at 150 mg/m² once daily for 5 consecutive days per 28-day treatment cycle. There is no information in the provided drug labels about gene mutations connected to gliomas. 2, 2, 2

From the Research

Gene Mutations Connected to Gliomas

• Gliomas, including glioblastoma, have been associated with various gene mutations, particularly IDH1 and IDH2 mutations, which have been found to occur frequently in these tumors 3, 4, 5.
• IDH1 and IDH2 mutations have been shown to be associated with longer survival and response to temozolomide in low-grade gliomas 3.
• A meta-analysis of 12 studies found that IDH mutations were associated with improved overall survival and progression-free survival in patients with gliomas, and were also associated with MGMT promoter hypermethylation, 1p/19q codeletion, and TP53 gene mutation 4.

Treatment Recommendations

• Treatment decisions for patients with gliomas, including glioblastoma, are based on various factors, including prognostic molecular markers, potential benefits of increased progression-free survival, and potential long-term treatment complications 6.
• IDH1 inhibitors, such as ivosidenib, have shown promise in the treatment of IDH1-mutant glioblastoma, with one case study reporting improved seizure control and radiographic stable disease for over 4 years 7.
• Radiation therapy is also a common treatment option for low-grade gliomas, with recent advances in techniques and ongoing clinical trials aiming to improve treatment outcomes 6.

Molecular Profiles and Prognosis

• IDH1 and IDH2 mutations have been found to be associated with distinctive genetic and clinical characteristics, and patients with these mutations have been shown to have a better outcome than those with wild-type IDH genes 5.
• The presence of IDH mutations has been found to be associated with a better prognosis in patients with gliomas, with a combined hazard ratio estimate for overall survival and progression-free survival of 0.33 and 0.38, respectively, compared to patients with wild-type IDH 4.