The brain is protected by the skull and the spinal cord is protected by the vertebral column. The brain and spinal cord are covered by 2 membranes known as meninges that further protect the CNS from outside shocks. The space between the 2 meninges and hollow space within the brain (the ventricles) and spinal cord are filled with a liquid known as cerebrospinal fluid.
Various parts of brain
The largest hemispherical part made-up of 2 halves, responsible for voluntary muscle movements, thought, emotion, memory, thinking, reasoning, and interpretation of sensory signals from the sensory organs;
Present below the cerebrum in the posterior fossa and help in maintaining balance and coordination in body movements; and
Connects the brain to the spinal cord and have various centers for controlling vital functions like breathing, heartbeat, swallowing, gastric reflux, and others.
There are 12 cranial nerves that connect different body parts with the brain via brain stem and without the involvement of the spinal cord. The spinal cord consists of long nerve fibers that control the function of bowel, bladder, and muscles in the limbs.
Types of primary CNS tumors
This type of tumors arises from the glial cells, the neuron supporting cells, are known as gliomas. There are 3 types of glial cells and consequently 3 types of tumors arising from them as described below:
As the name indicate astrocytomas arise from the astrocytes, the supporting cells for neurons. The astrocytes form a scar tissue in response to an injury to the brain tissue and help in repairing the damage. Astrocytomas account for about 20% of all CNS cancers/tumors and can quickly spread throughout the CNS. They frequently involve nearby brain tissue and rarely spread outside of the CNS. Pilocytic astrocytoma, subependymal giant cell astrocytomas (SEGAs), diffuse astrocytomas, pleomorphic xanthoastrocytomas (PXAs), and Optic gliomas are some less aggressive forms of astrocytomas. Anaplastic astrocytoma and glioblastoma are aggressive forms of astrocytoma.
Oligodendrogliomas arises from the oligodendrocytes, the supporting cells that synthesize a fatty substance known as myelin. The myelin covers and insulates the axon of various neurons and help in faster signal transmission. The aggressive form is known as anaplastic oligodendroglioma. Oligodendrogliomas account for about 2% of all CNS cancers/tumors.
Ependymoma arises from the ependymal cells, the cells that line the ventricles and secrete CSF. Ependymomas generally spread via CSF route and may sometimes lead to hydrocephalus, a condition characterized by the ventricle’s enlargement due to blockage in the path of CSF. The aggressive form is known as anaplastic ependymoma. They account for about 2% of all CNS cancers/tumors.
Meningioma arises from the meninges, the membranes that cover the brain and consist of the CSF within the space between them (the subarachnoid space). Meningiomas account for about 30% of all CNS cancers/tumors and are the most common brain tumors in adults. Although, the benign form is mostly observed, meningiomas may occur as aggressive form (anaplastic or malignant) that tend to grow and spread quickly.
Embryonal Tumors (Medulloblastoma)
Embryonal brain tumor arises from the neuroectodermal cells. Medulloblastoma is the most common type of embryonal tumor that arises in the cerebellum. These tumors generally involve nearby brain tissue and can spread very quickly via CSF route. They were referred to as primitive neuroectodermal tumors (PNETs) in the past. They are generally observed in children and very rare in adults. They account for about 2% of all CNS cancers/tumors.
Mixed Glial and Neuronal Tumors
This type of brain tumors involve both glial cells and neurons. They are generally benign. Examples of such tumors include dysembryoplastic neuroepithelial tumors (DNETs) and ganglioglioma. Gangliogliomas are more common in children than adults.
Germ Cell Tumor
As the name indicate, these tumors arise from the germ cells in the brain. The presence of germ cells in the brain is abnormal and these cells are normally present in the egg cells in women and sperm cells in men. However, in some individuals, these cells may be present at certain abnormal locations within the brain (most common region of germ cells’ location in the brain include pineal gland or above the pituitary gland) and give rise to germ cell tumors. Germinoma, choriocarcinoma, embryonal carcinoma, teratoma, and yolk sac tumor are examples of germ cells tumors. These tumors are generally seen in children and are rare in adults. They can sometimes be diagnosed with the help of tumor markers present in the CSF.
Schwannomas or neurilemmomas are the type of CNS tumors that arise from the Schwann cells surrounding the cranial or spinal nerves. They account for about 8% of all CNS cancers/tumors. They are generally benign but can cause symptoms related to the nerve affected. For example, if they affect cranial nerve responsible for hearing, they can cause loss of hearing.
Craniopharyngioma is believed to arise from the epithelial cells at the junction of the infundibular stalk and the pituitary gland (residual cells of the Rathke pouch). The tumor is generally slow-growing and is mostly associated with a proteinaceous fluid-filled cyst. Both tumor and cyst can press on the nearby structures causing symptoms. The pituitary gland and the optic nerve are mostly involved, and thus, these tumors are frequently associated with hormonal imbalance and vision problems. These are more common in children than adults.
This type of cancers arises from the bones at the base of the skull or at the lower end of the spine. They are usually slow-growing but can grow in nearby soft tissues. They have a high recurrence rate.
Primary CNS Lymphoma
The NHLs that starts in the CNS are called primary CNS NHLs. The primary CNS NHLs generally originate from the B-cells and are generally aggressive. These cancers frequently invade nearby brain tissue and usually present as a multifocal disease. These are mostly observed in immunocompromised individuals, such as those with an organ transplantation or patients with AIDS. They account for about 3% of all CNS cancers/tumors.
Almost all pituitary tumors are glandular and known as pituitary adenomas. These tumors mostly start in the anterior lobe of the pituitary gland and are mostly benign. These tumors can cause a problem of hormonal imbalance (hyper- or hyposecretion of anterior pituitary hormones) or can press on other structures, such as optic chiasm. They account for about 10% to 15% of all CNS cancers/tumors. Pituitary adenomas are further classified as functional and non-functional tumors based on their ability to secrete hormones.
These tumors mostly arise in the cerebellum and may occur in some other locations like the brain stem, spinal cord, or cerebrum. Most cases of hemangioblastomas are associated with von Hippel-Lindau disease, a hereditary syndrome caused by a germline mutation in the VHL gene. The tumors are highly vascular and are usually associated with a fast-growing cyst which is responsible for early symptoms. These tumors mostly affect individuals aged between 30 to 40 years.
Choroid Plexus Tumor
These tumors mainly include choroid plexus papilloma (benign form) and choroid plexus carcinoma (malignant/cancerous form). The choroid plexus carcinomas are mostly associated with Li-Fraumeni syndrome, a hereditary syndrome caused by a germline mutation in the TP53 gene. These are rare forms of CNS cancers/tumors and mostly affect children below the age of 12 years. These tumors mostly occur in lateral ventricles and may lead to blockage of CSF flow, and thus, hydrocephalus. They generally involve nearby brain tissue and can spread via CSF route.
The treatment approach for various types of brain tumors mainly depend on the type and location of the tumor. Hence diagnosis of the exact location and know the types of brain tumor is the key before starting the treatment. There are some other rare brain tumors not included in above list due to a low occurrence.
Symptoms and Signs
- Headache that gets worse over time
- Problem in balance and coordination
- Problem with vision, speech, swallowing, or hearing
- Weakness in arms/legs
- Drowsiness, Confusion, mood or behavioral change
- Problem with bowel or bladder
Symptoms usually depend upon the region of the brain involved by the tumor as different parts of brain control different body functions.
Risk Factors for Brain Tumor
Following are the risk factors for various types of bone tumor.
Exposure to Radiation
Exposure to radiation is only well-established risk factor for the development of CNS tumor. Individuals with a history of exposure to radiation, for example, for the treatment of other cancers remain at high risk of developing CNS tumors. They generally develop 10 to 15 years after radiation treatment.
Following are some examples:
- Mutation in Neurofibromatosis type 1 (NF1) gene is associated with higher risk of schwannomas, meningiomas, and certain types of gliomas.
- Mutation in Neurofibromatosis type 2 (NF2) gene is associated with increased risk of vestibular schwannomas (acoustic neuromas), meningiomas, and spinal cord ependymomas.
- Von Hippel-Lindau disease increases the risk of developing hemangioblastomas and other non-CNS tumors.
- Li-Fraumeni syndrome increases the risk of developing gliomas and certain other non-CNS tumors.
- Tuberous sclerosis is linked with the development of subependymal giant cell astrocytomas (SEGAs) and some other CNS and non-CNS tumors.
Exposure to certain chemicals
Chronic exposure to certain chemicals like petroleum products, polycyclic aromatic hydrocarbons, vinyl chloride, aspartame, insecticides, and herbicides have been reported to elevate the risk of developing certain types of CNS tumors.
Risk of developing certain types of CNS tumors is higher in individuals who have a history of infection with certain viruses, like Epstein-Barr virus (EBV) or human cytomegalovirus (hCMV).
Weakened immune system
Individuals with a weak immune system that may be due to HIV infection, auto-immune disease, or immunosuppressants in patients who have undergone an organ transplant are considered at higher risk of developing primary CNS lymphomas.
Exposure to strong electromagnetic fields and excessive cell-phone use has also been reported to increase the risk of brain tumors in some studies; however, the association was not proved in other studies.
Age: Most CNS cancers/tumors types are common among old-age individuals with an exception of a few types that are more common among children.
Gender: Meningiomas and schwannomas are more common in women, while primary CNS lymphomas, gliomas, and medulloblastomas are more common in men.
Ethnicity: Meningiomas are most commonly reported in African Americans while gliomas and medulloblastomas are more common in Caucasians.
Brain Tumor Staging and Grading Investigations
Imaging tests are the mainstay of diagnosis for CNS tumors. These tests help in scanning the CNS and can accurately diagnose the location, size, and shape of the tumor. These tests play important role in defining the extent of disease. They are employed after treatment to evaluate the treatment efficacy and to detect any signs of disease progression/recurrence.
Magnetic resonance imaging (MRI) scan
This technique provides detailed images of internal body structures using radio waves, strong magnetic field, and gadolinium-based contrast material (which is used via intravenous injection to improve the clarity of the MRI images).
This is the most widely used technique for the diagnosis of CNS cancers/tumors because it can provide very detailed images of the brain and spinal cord tissue. Some more advanced MRI techniques are frequently used for the diagnosis of CNS cancers/tumors, which provide important information about the disease. Following are such techniques.
Magnetic resonance angiography (MRA) provides detailed images of the CNS vasculature and is very helpful in planning surgery.
Magnetic resonance spectroscopy (MRS) provides information about the composition in a particular area and can differentiate between the healthy and diseased tissue. It can further signal the type of defect in the suspected area.
Functional MRI (fMRI) highlights the slight change in blood flow in a particular part of the brain activated in real time. Thus, this technique is very helpful in mapping tumor-adjacent areas of the brain that are responsible for specific function, such as speech, though, movement, etc. This can be used for preserving important function by an appropriate planning of the indicated treatment (surgery or radiation).
Computed tomography (CT) scan
In this technique, detailed cross-sectional images of body organs are generated using x-rays with contrast agents. This technique can provide images of the CNS tumor. However, it is not primarily employed for the diagnosis of CNS tumors and is reserved for patients who cannot undergo MRI examination, such as those with an implanted pacemaker, metal fragment, paramagnetic surgical clips, extreme obesity, or those who have fear for closed spaces.
This technique can sometimes be used to highlight the CNS vasculature by CT angiography. Also, this technique can be used for determining the extent of disease and for planning the treatment in case radiation therapy is indicated for the treatment.
Biopsy samples contain a small number of cells or a tiny piece of tissue collected from the affected area with the help of a biopsy instrument. These samples are generally collected simultaneously with the main surgical procedure or sometimes before the main surgical procedure planned for the treatment of CNS tumor.
The collected biopsy sample is then tested in a laboratory and can help in establishing the diagnosis of CNS tumor based on the presence of characteristic cells.
In lumbar puncture, a sample of cerebrospinal fluid (CSF, a biological fluid that surrounds the brain and spinal cord) is collected with the help of a needle inserted up to the subarachnoid space around the spinal cord through the lower part (lumbar region) of the spine.
The collected sample is then analyzed in a laboratory for the presence of cancer cells (or tumor markers). This is generally employed for the CNS tumors that may spread via CSF or for primary CNS lymphomas. The detection of certain tumor markers in the CSF can establish the diagnosis of germ cell tumors. This technique can also be used to deliver a treatment into the CSF, if required.
Prognostic factors for Brain Tumors
Besides the grades of CNS cancers/tumors, many factors have been identified which can predict the outlook of the CNS cancer/tumor. These factors are generally taken into account before starting the treatment of the disease. The prognostic factors for CNS cancers/tumors include-
- the type of cancer/tumor,
- extent of spread,
- patient’s age,
- patient’s performance status, etc
Brain Cancer Grading
Once the diagnosis of brain cancer is determined through various investigations, World Health Organization (WHO) grading system is the most widely used to describe the severity of CNS tumor based on the appearance of cancer cells under a microscope.
The cancer cells look like normal cells. These are typically slow-growing tumors that do not invade nearby brain tissue.
The cancer cells look like normal cells. These are slow-growing tumors that can involve nearby brain tissue and can transform to aggressive forms over time.
The cancer cells do not look like normal cells. These are fast-growing tumors that can involve nearby brain tissue and require intensive treatment.
The cancer cells do not look like normal cells. These are very aggressive and fast-growing tumors that can involve nearby brain tissue and require most intense treatment.
Treatment of various types of Brain Tumors
The treatment approach for various types of brain tumors mainly depend on the type and location of the tumor. Hence diagnosis of the exact location and the type of brain tumor is the key before starting the treatment, along with grade/stage of brain tumor, etc.
In the case of low-grade astrocytomas (e.g. pilocytic astrocytoma, and SEGA), maximal tumor excision without compromising any neurological function is considered the preferred treatment approach. Post-operative radiation therapy should be considered in high-risk individuals and those with incomplete resection. For SEGA that can not be removed completely, targeted therapy may be employed to shrink the tumor.
In the case of high-grade astrocytomas (e.g. Anaplastic astrocytoma and glioblastoma), maximal tumor excision without compromising on important neurological function is considered as the first-line treatment. Radiotherapy with or without chemotherapy is generally indicated after surgery.
In the case of oligodendrogliomas, maximal tumor excision without compromising any neurological function is considered the preferred treatment approach. Post-operative radiotherapy and/or chemotherapy may be considered in the case of high-grade disease or incomplete resection.
In the case of ependymomas, maximal tumor excision without compromising any neurological function is considered the preferred treatment approach. Post-operative radiotherapy should be considered in the case of high-grade disease, incomplete resection, or presence of cancer cells in the CSF a few weeks after surgery.
Treatment for meningioma may be done as below. In the case of low-grade asymptomatic meningioma (tumor size <3 cm), observation without any treatment is considered as the preferred approach, especially in elderly patients.
In case of symptomatic meningioma, maximal tumor excision without compromising any neurological function is considered the preferred treatment approach. Post-operative radiotherapy may be considered in the case of high-grade disease, incomplete resection, or high-risk individuals. Radiotherapy can be employed as the first-line treatment for patients who are not good candidates for surgery.
In the case of embryonal tumors, maximal tumor excision without compromising any neurological function is considered the preferred treatment approach. Post-operative radiotherapy and chemotherapy may be employed in the case of high-risk individuals (large cell or anaplastic medulloblastoma, supratentorial PNET, disease dissemination, unresectable or residual tumors).
Mixed Glial and Neuronal Tumors
Maximal tumor excision without compromising any neurological function is considered the preferred treatment approach for these tumors. In the case of a negative resection margin, patients may be observed without any additional therapy. Post-operative radiotherapy should be considered in the case of high-grade disease or incomplete resection.
Germ Cell Tumor
Most germ cell tumors are not amenable to surgical resection due to their invading/spreading nature and non-accessible location. Thus, most germ cell tumors are treated with radiotherapy as the first line treatment. Post-radiation chemotherapy may be employed in the case of large tumors or remaining tumor cells.
In the case of schwannomas, maximal tumor excision without compromising any neurological function is considered the preferred treatment approach. Postoperative radiotherapy (radiosurgery) should be considered in the case of incomplete resection or where complete resection is not possible.
In the case of craniopharyngiomas, maximal tumor excision without compromising any neurological function is considered the preferred treatment approach. In the case of complete resection, no other treatment is required. However, complete tumor resection is not possible in most cases due to the proximity of the tumor to important structures, like the pituitary gland, hypothalamus, optic nerves, and blood vessels. Thus, postoperative radiotherapy (radiosurgery) is generally employed to kill any remaining tumor cells.
Chordoma and Chondrosarcoma
In the case of chordomas and chondrosarcomas, maximal tumor excision without compromising any neurological function is considered the preferred treatment approach. In the case of complete resection, no other treatment is required. However, complete tumor resection is not possible in most cases due to the inaccessible tumor location, infiltrative nature of the tumor, and the proximity of the tumor to important structures, like the chiasm or the brainstem. Thus, postoperative radiotherapy (radiosurgery) is generally employed (especially in the case of chondrosarcoma) to kill any remaining tumor cells.
Primary CNS Lymphoma
In the case of primary CNS NHLs, intravenous chemotherapy is considered the first-line treatment. Intrathecal chemotherapy may also be employed in case of the presence of cancer cells in the CSF. Concurrent administration of corticosteroid is usually employed to relieve disease symptoms. Radiotherapy is also a part of chemotherapy regimens, but may be avoided in elderly patients in view of side effects.
In the case of the functional prolactin-secreting adenoma, drugs that inhibit prolactin secretion (e.g. cabergoline or bromocriptine) are used as the preferred treatment. In the case of the functional growth hormone (GH)-secreting adenoma, surgical resection of the tumor is the preferred treatment option. Somatostatin analogs (e.g. Octreotide, lanreotide, and pasireotide) are given before surgery to shrink the tumor size. Radiotherapy may be employed if the tumor was not completely removed by surgery.
For functional corticotropin (ACTH)-secreting adenomas, surgical resection of the tumor is the preferred treatment option. Radiotherapy may be employed if the tumor was not completely removed by surgery.
For thyrotropin (TSH)- secreting adenoma, surgical resection of the tumor is the preferred treatment option. Drugs (e.g. Octreotide, lanreotide, cabergoline, or bromocriptine) are given if the surgery did not reduce the hormonal level. Radiotherapy may be employed if the tumor was not completely removed by surgery.
For gonadotropin (FSH/LH)- secreting adenoma, surgical resection of the tumor is the preferred treatment option. Radiotherapy may be employed if the tumor was not completely removed by surgery.
For non-functional pituitary adenomas, observation without any treatment is considered as the preferred approach for small (<1 cm in size, and not causing any symptom) tumors. For large tumors pressing on nearby structures, surgical resection of the tumor is the preferred treatment option. Radiotherapy may be employed to kill any residual tumor cells.
In the case of hemangioblastomas, maximal tumor excision without compromising any neurological function is considered the preferred treatment approach. Post-operative radiotherapy may be considered in the case of high-grade disease, or incomplete resection. Radiotherapy can be employed as the first-line treatment for patients who are not the good candidates for surgery.
Choroid Plexus Tumor
In the case of choroid plexus papillomas (benign form), maximal tumor excision without compromising any neurological function is considered the preferred treatment approach. Post-operative radiotherapy should be considered in the case of incomplete resection or where complete resection is not possible.
In the case of choroid plexus carcinoma, maximal tumor excision without compromising any neurological function is considered the preferred treatment approach. Post-operative radiotherapy should be considered in the case of high-grade disease, incomplete resection, or high-risk individuals. Radiotherapy can be employed as the first-line treatment for patients who are not the good candidates for surgery. Instead of radiotherapy, chemotherapy may be employed after surgery in infants and young children.
Surgery for Brain Tumor
Surgery is the treatment of choice for most low-grade and some intermediate-grade brain cancers/tumors that have not spread to distant parts and can be completely removed by a surgical procedure. Apart from the main objective of removing the maximum possible tumor tissue without compromising any neurological function, surgery can also be employed for other purposes, such as for the collection of the biopsy sample from the affected area and to relieve symptoms of a high-grade disease.
Craniotomy is the most common surgical procedure employed for the treatment of intracranial tumors. Special instruments are used to cut open a piece of the skull over the tumor and tumor tissue is removed with the help of surgical instruments. Surgical treatment of brain cancer is generally complex and requires intensive planning with imaging studies.
For the treatment of brain tumor, an external beam radiation therapy (EBRT) technique is generally employed. Three-dimensional conformal radiation therapy (3D-CRT), Intensity modulated radiation therapy (IMRT), Conformal proton beam radiation therapy, and Stereotactic radiosurgery (SRS)/stereotactic radiotherapy (SRT) are some advanced techniques commonly used for the brain cancer treatment.
Chemotherapy means treatment with anti-cancer drugs that kill or decrease the growth of rapidly-growing cancer cells. Chemotherapeutic drugs have to cross the blood-brain barrier (BBB) before showing their effect on the brain tumor cells. Most conventional drugs cannot cross the BBB, and thus, are not useful for the treatment of brain tumor.
Chemotherapy may be employed in combination with radiation therapy or surgery for the management of CNS tumors, especially in the case of aggressive cancer types. Depending upon the type of cancer, single drug or certain combination regimen involving multiple drugs can be used for the treatment of CNS tumors.
Some chemotherapy drugs effective in brain tumor are-
Targeted drugs for brain tumors work by targeting a specific gene or protein characteristic of the cancer cells. For example, Bevacizumab is the targeted drug used for the treatment of brain tumors expressing vascular endothelial growth factor (VEGF) receptors, and Everolimus targets mTOR protein that helps cancer cells to grow. These drugs are employed for the treatment of recurrent or advanced-stage disease when other treatment options cannot be used or are not effective.
Best Brain (CNS) Cancer Specialist in Delhi
Dr Sunny Garg is a renowned Medical Oncologist in New Delhi with an experience of around 10 years of treating brain cancer patients. He has treated brain tumor patients with Chemotherapy and Targeted Therapy. He is currently practicing at Manipal Hospital, Dwarka.
Diagnostic modalities available at our hospital include Stereotactic Brain Biopsy, Open Biopsy, Genetic and Molecular Testing, MRI Brain, etc. Other treatment facilities for Brain Cancer available are Surgical Resection, Craniotomy, Radiation Therapy, etc.
Call +91 9686813020 for appointment.