Brain tumours and cancers

Gliomas

Gliomas are a type of tumor that arises from glial cells in the central nervous system (CNS), which includes the brain and spinal cord. Glial cells provide support and protection to neurons, and there are different types of glial cells, such as astrocytes, oligodendrocytes, and ependymal cells. Gliomas can originate from any of these cell types and can be classified based on the specific cell they arise from, as well as other characteristics. The grading of gliomas is based on the World Health Organization (WHO) classification system, ranging from grade I (least aggressive) to grade IV (most aggressive). Glioblastoma multiforme (GBM) is the most malignant and aggressive type. Treatment for gliomas often involves a combination of surgery, radiation therapy, and chemotherapy, and the approach depends on factors such as the tumor type, grade, and location.

Very often, other than cellular and microscopic appearance, pathologists and doctors need to perform further testing to sub-classify gliomas. 

The first step is to ascertain IDH status. IDH (Isocitrate Dehydrogenase) mutation refers to a genetic alteration in the IDH genes, specifically IDH1 (Isocitrate Dehydrogenase 1) and IDH2 (Isocitrate Dehydrogenase 2). Prognosis is more favorable for mutants. 

The 1p/19q co-deletion is a specific genetic alteration commonly observed in oligodendrogliomas, a type of glioma. The presence of 1p/19q co-deletion is considered a favorable prognostic marker. 

For patients who do not have IDH or 1p19q co-deletion, they have a more aggressive form of glioma known as GBM (glioblastoma multiforme). Doctors can check for MGMT methylation result. Patients with MGMT-methylated glioblastomas tend to have a better prognosis and longer overall survival compared to those with unmethylated MGMT.  Patients with MGMT-methylated glioblastomas tend to have a better prognosis and longer overall survival compared to those with unmethylated MGMT as the tumours are more sensitive to temozolamide, an oral chemotherapy agent taken for GBM. 

Sometimes, your doctors may recommend next generation sequencing. This approach allows for a more personalized and potentially more effective treatment strategy, as opposed to a one-size-fits-all approach.  One commercial test done commonly in Singapore is a local kit developed jointly by several stakeholders (Lucence United) 

Gliomas are a spectrum, and while GBM still remains an aggressive disease with limited treatment options, in the future, scientists hope that with precision medicine and molecular profiling, doctors can identify specific genetic mutations and molecular signatures associated with GBM. This information is crucial for developing targeted therapies tailored to the individual characteristics of each patient’s tumor.

Other emerging technologies include tumour-treating fields, nanotechnology, nano-particle drug conjugates and FLASH proton therapy. 

 

Proton beam therapy

Proton Beam Therapy is particularly useful for treating gliomas—a type of brain tumor—due to its ability to deliver highly precise radiation to the tumor while minimizing damage to surrounding healthy brain tissue. This precision is especially important in gliomas, which often occur in sensitive areas of the brain, making traditional radiation methods challenging due to the risk of damaging critical functions such as speech, movement, and vision. Proton therapy can be used when:

1. Tumors are located near vital structures, such as the brainstem or optic nerves, where conventional radiation might cause severe side effects.
2. The tumor is deep-seated in the brain, where protons can deliver focused radiation without passing through large areas of healthy tissue.
3. After surgery, to target any remaining cancer cells while sparing healthy brain tissue to prevent cognitive and neurological side effects.

In cases of high-grade gliomas or recurrent tumors, proton therapy can improve treatment outcomes by enhancing tumor control and reducing complications.

However, in grade IV gliomas, the prognosis is often short, and hence the long-term advantage of proton beam therapy may not manifest.

Proton beam therapy is most useful in gliomas such as low grade or IDH-mutant gliomas where long-term survival is expected. 

 

Other brain tumours

Other than gliomas, several types of brain tumors can benefit from Proton Beam Therapy due to its precision and ability to minimize radiation exposure to healthy tissues. These include:

1. Meningiomas: Tumors that arise from the membranes surrounding the brain and spinal cord. Proton therapy can be effective, especially when the tumor is near critical areas like the optic nerves or brainstem.

2. Pituitary Tumors: Tumors affecting the pituitary gland, which is located at the base of the brain. Proton therapy is particularly useful when the tumor is close to the optic nerves or other vital structures, as it can precisely target the tumor while minimizing damage to surrounding tissues.

3. Craniopharyngiomas: Benign but locally invasive tumors that occur near the pituitary gland and optic pathways. Proton therapy is ideal for treating these tumors, as it delivers targeted radiation to the tumor while sparing critical brain structures.

4. Chordomas: Though primarily a bone tumor, chordomas often involve the skull base and can affect critical brain structures. Proton therapy is effective in treating these tumors due to its precision and ability to spare healthy brain tissue.

5. Medulloblastomas: Common in pediatric patients, these tumors are located in the cerebellum and may require radiation to the entire craniospinal axis. Proton therapy can deliver precise radiation to the tumor while minimizing side effects to the developing brain and spine.

6. Germ Cell Tumors: Tumors that originate from reproductive cells, often found in the pineal or suprasellar regions. Proton therapy can provide targeted radiation to these tumors, reducing potential damage to the surrounding brain and endocrine systems.