Glioblastoma (GBM) is the most aggressive and common malignant brain tumor in adults. This cancer presents a significant challenge due to its rapid growth and invasive nature. Despite therapeutic advancements, it often recurs even after extensive treatment.
Understanding IDH Wild-Type Glioblastoma
The term “IDH wild-type” refers to glioblastomas that do not possess a specific genetic mutation in the Isocitrate Dehydrogenase 1 (IDH1) or Isocitrate Dehydrogenase 2 (IDH2) genes. This absence of mutation distinguishes these tumors from IDH-mutant gliomas, which have different biological behaviors and prognoses. The World Health Organization (WHO) Classification of Tumors of the Central Nervous System, updated in 2021, now defines glioblastoma as an IDH wild-type tumor.
IDH wild-type glioblastoma represents the majority, approximately 90%, of all glioblastoma cases. These tumors are more aggressive and have a less favorable outlook compared to their IDH-mutant counterparts. They exhibit fast-growing and infiltrative patterns, often spreading into surrounding brain tissue, which makes complete surgical removal difficult. Molecular features associated with IDH wild-type glioblastoma include mutations in the TERT promoter, amplification of the EGFR gene, or a combined gain of chromosome 7 and loss of chromosome 10.
How IDH Wild-Type Glioblastoma is Diagnosed
The diagnostic process for IDH wild-type glioblastoma begins with imaging studies, most commonly a Magnetic Resonance Imaging (MRI) scan of the brain. MRI provides detailed images that can reveal the presence and extent of a brain tumor, often showing characteristic ring-enhancing lesions. However, imaging alone cannot definitively diagnose the specific type of tumor.
Following imaging, a biopsy or surgical resection of the tumor is performed. Tissue samples are then examined by a neuropathologist. Molecular testing of this tissue determines the IDH status. The “wild-type” designation confirms the absence of these mutations, solidifying the diagnosis of IDH wild-type glioblastoma in conjunction with other histological and molecular features, as per the 2021 WHO classification.
Treatment Options for IDH Wild-Type Glioblastoma
Treatment for IDH wild-type glioblastoma involves a multimodal approach, aiming to remove as much of the tumor as safely possible and then target remaining cancer cells. The initial step is often maximal safe surgical resection. Greater tumor removal, specifically 98% or more, has been associated with a longer healthy period.
Following surgery, standard treatment includes radiation therapy combined with chemotherapy. Temozolomide, an oral chemotherapy drug, is frequently administered concurrently with radiation therapy and then as an adjuvant treatment. This combined approach, often referred to as the Stupp protocol, has been shown to improve survival rates.
Tumor Treating Fields (TTFields) therapy is another treatment option. This non-invasive therapy involves placing transducer arrays on the scalp to deliver low-intensity alternating electric fields that disrupt cancer cell division. TTFields therapy has received FDA approval for both newly diagnosed and recurrent glioblastoma and is often used in combination with temozolomide. Treatment plans are individualized, taking into account factors like the patient’s overall health and the tumor’s specific characteristics.
Outlook and Prognosis
The outlook for patients with IDH wild-type glioblastoma remains challenging. Despite comprehensive treatment, recurrence is common, often within two centimeters of the original resection site. The median overall survival for IDH wild-type glioblastoma is around 12.6 to 15 months, with a five-year survival rate less than 10%.
Several factors can influence an individual’s prognosis. These include the patient’s age at diagnosis, with younger patients having a better outlook, and the extent of tumor resection achieved during surgery. The methylation status of the MGMT promoter gene is also a significant biomarker, with methylated tumors showing a better response to temozolomide and a more favorable prognosis.