Astrocytoma, IDH-mutant, is a specific type of brain tumour known as a glioma. It originates from the astrocytes, which are supportive glial cells found in the brain. This tumour is typically diagnosed in young to middle-aged adults.
A key characteristic of astrocytoma, IDH-mutant, is its diffuse nature, meaning it does not have clear boundaries and tends to infiltrate the surrounding brain tissue.
According to the World Health Organization (WHO) 2021 classification of brain tumours, this tumour is defined by a specific genetic change, or mutation, in one of two genes: IDH1 or IDH2.
Astrocytoma, IDH-mutant, is categorised into three grades, which indicate how the tumour is likely to behave:
Generally a slow-growing tumour.
A faster-growing tumour that is more likely to spread within the brain.
The most aggressive grade, often displaying signs such as dead tissue (necrosis).
The symptoms of an astrocytoma, IDH-mutant, can vary significantly depending on where the tumour is located in the brain. Common signs may include:
Diagnosing an astrocytoma involves a series of steps to accurately identify the tumour type, grade, and molecular characteristics.
The process usually begins with a Magnetic Resonance Imaging (MRI) scan. This provides detailed images of the brain, allowing doctors to identify any abnormal areas. Specialised MRI techniques may be used to assess the tumour's behaviour and potential aggressiveness.
If a tumour is suspected, the patient is referred to a multidisciplinary team (MDT) of specialists. This team typically includes neurosurgeons, neurologists, oncologists, radiologists, and specialist nurses who collaborate on a treatment plan.
To confirm the diagnosis, a small sample of the tumour tissue is taken, often during a surgical procedure (which may be combined with tumour removal). This sample is then examined under a microscope.
The tumour sample undergoes testing for specific genetic changes, most importantly the IDH1 and IDH2 gene mutations. The presence of these mutations confirms the diagnosis as astrocytoma, IDH-mutant. This genetic information is crucial for determining the tumour's likely behaviour and guiding treatment decisions.
In some cases, additional scans or tests may be required to gather more information for surgical or treatment planning.
Doctors use genetic testing to help confirm the diagnosis, predict the tumour's behaviour, and select the most effective treatment. Key tests performed on the tumour sample include:
Testing for mutations in the IDH1 or IDH2 genes, which defines the tumour as an IDH-mutant astrocytoma. If the mutation is absent, the tumour may instead be classified as a glioblastoma.
Testing for this specific genetic signature, which is characteristic of a different type of tumour called oligodendroglioma. Confirming that this codeletion is not present helps to affirm the diagnosis of astrocytoma.
A mutation in the ATRX gene is common in astrocytomas and helps support the diagnosis and distinguish it from other gliomas.
For higher-grade tumours, testing for the deletion of both copies of the CDKN2A/B gene is essential. This homozygous deletion signifies more aggressive tumour behaviour and leads to a classification of Grade 4, regardless of its appearance under the microscope.
This change can switch off a gene that typically repairs damaged DNA. When this occurs, certain chemotherapy drugs, like temozolomide, can be more effective because the tumour cells are less able to fix the damage caused by the treatment. This change is generally associated with a better response to treatment and outcome.
Treatment for astrocytoma is highly individualised and depends primarily on the tumour's grade, its location, and the presence of specific genetic mutations. The primary treatments include surgery, radiotherapy, and chemotherapy.
The main goal is to remove as much of the tumour as safely possible while protecting vital brain functions. Surgery also provides the necessary tissue for diagnostic and molecular analysis. Complete removal is not always possible if the tumour is in a high-risk area.
For some lower-grade tumours, an initial approach may be active monitoring, where regular MRI scans are used to track tumour growth before intervention is required.
Typically offered after surgery to target and destroy any remaining cancer cells, reducing the chance of recurrence. It may also be used as the main treatment if surgery is not feasible, or as a palliative option to help relieve symptoms.
Uses drugs to kill or halt the growth of cancer cells, often in combination with radiotherapy or as a follow-up (adjuvant) treatment.
Provide patients with access to innovative, emerging therapies and enhanced monitoring, contributing to better outcomes for future patients.
This is a vital part of management to control symptoms such as seizures, pain, fatigue, and neurological issues. This may include:
After initial treatment, regular follow-up appointments and MRI scans are scheduled to monitor for any signs of tumour recurrence or progression and to adjust the treatment plan as necessary.
For tumours that return after initial treatment, additional cycles of chemotherapy—typically with Temozolomide, PCV, or single-agent Lomustine (CCNU)—may be offered. Further surgery or radiotherapy may also be considered by the clinical team.
The likely prognosis for an astrocytoma tumour varies based on the tumour grade and its molecular features. IDH-mutant astrocytomas generally have a more favourable outlook compared to IDH-wildtype gliomas (such as glioblastoma). The presence of the CDKN2A/B deletion in Grade 4 astrocytomas, however, is associated with a poorer outcome. Long-term survival is achievable, particularly for lower-grade tumours with favourable molecular profiles.
The exact cause of astrocytoma is currently unknown. The majority of cases occur sporadically without an identifiable genetic or environmental risk factor. Research is ongoing to better understand the underlying mechanisms that lead to the development of this tumour.