What is the standard treatment approach for patients with glioma IDH (Isocitrate Dehydrogenase) wild type?

From the Guidelines

The standard treatment approach for patients with glioma IDH wild type typically involves maximal safe surgical resection followed by concurrent chemoradiation with temozolomide (75 mg/m² daily during radiation) and then adjuvant temozolomide (150-200 mg/m² for 5 days every 28 days for 6-12 cycles), as recommended by the most recent guidelines 1. This approach is particularly important for glioblastoma, the most aggressive form of IDH wild-type glioma.

• Radiation therapy usually consists of 60 Gy delivered in 30 fractions, as used in the EORTC 26981-22981 trial 1.
• For elderly patients or those with poor performance status, hypofractionated radiation with or without temozolomide may be considered, with options including 40.05 Gy in 15 fractions over 3 weeks 1 or 40 Gy in 15 fractions over 3 weeks 1.
• Tumor treating fields (TTFields) may be added after chemoradiation to improve survival.
• MGMT promoter methylation status should be tested as it predicts benefit from temozolomide, with temozolomide being more effective in patients with MGMT promoter-methylated tumors 1.
• IDH wild-type gliomas generally have a poorer prognosis than IDH-mutant gliomas because they are more aggressive and less responsive to treatment, making aggressive multimodal therapy essential.
• Regular MRI monitoring is necessary to assess treatment response and detect recurrence early, as these tumors often progress rapidly. Key considerations in treatment planning include the patient's age, performance status, and tumor characteristics, with the goal of maximizing survival and quality of life while minimizing treatment-related toxicity.

From the FDA Drug Label

The addition of concomitant and maintenance temozolomide to radiotherapy in the treatment of patients with newly diagnosed GBM showed a statistically significant improvement in overall survival compared to radiotherapy alone Five hundred and seventy-three patients were randomized to receive either temozolomide (TMZ)+Radiotherapy (RT) (n=287) or RT alone (n=286).

The standard treatment approach for patients with glioma IDH wild type is concomitant temozolomide and radiotherapy, followed by maintenance temozolomide.

• Temozolomide dose: 75 mg/m2 once daily during radiotherapy, followed by 150 or 200 mg/m2 on Days 1 to 5 of every 28-day cycle.
• Radiotherapy: focal radiation therapy delivered as 60 Gy/30 fractions.
• This approach has shown a statistically significant improvement in overall survival compared to radiotherapy alone 2.

From the Research

Glioma IDH Wild Type Treatment Approach

• The standard treatment approach for patients with glioma IDH (Isocitrate Dehydrogenase) wild type is not explicitly defined in the provided studies, but some insights can be gathered from the available evidence.
• For glioblastoma, which is a type of glioma, the first-line management includes maximum safe surgical resection followed by involved-field radiotherapy plus concomitant and six cycles of maintenance temozolomide chemotherapy 3.
• In the case of recurrent glioblastoma, lomustine alone has been increasingly used as a control arm in clinical trials, assigning this drug a standard-of-care position in this setting 3.
• The effectiveness of temozolomide and lomustine in glioblastoma cell lines can be increased by the use of Tumor Treating Fields (TTFields) 4.
• For IDH-wild-type lower-grade gliomas, maximizing the extent of resection (EOR) is associated with longer survival, and a threshold of at least 97.0% EOR or a maximum residue of 3.0 cm3 is necessary to impact overall survival positively 5.

Treatment Options

• Lomustine-temozolomide combination therapy has shown promise in improving survival compared to standard temozolomide therapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter 6.
• Temozolomide versus procarbazine, lomustine, and vincristine in recurrent high-grade glioma has been compared in a randomized trial, which found no clear survival benefit when comparing PCV with TMZ 7.
• The use of TTFields concomitant with TMZ or CCNU has shown additive or synergistic effects in MGMT-expressing or non-expressing cells, respectively 4.

Key Considerations

• The treatment approach for glioma IDH wild type should be individualized based on the specific characteristics of the patient and the tumor.
• Further research is needed to determine the optimal treatment strategy for glioma IDH wild type.
• The available evidence suggests that maximizing EOR and using combination therapies such as lomustine-temozolomide may improve survival outcomes in patients with glioma IDH wild type 3, 5, 6.