BRAIN CANCER

What is brain cancer?

Brain cancer is a disease of the brain in which cancer cells (malignant) arise in the brain tissue. Cancer cells grow to form a mass of cancer tissue (tumor) that interferes with brain functions such as muscle control, sensation, memory, and other normal body functions. Tumors composed of cancer cells are called malignant tumors, and those composed of noncancerous cells are called benign tumors. Cancer cells that develop from brain tissue are called primary brain tumors while tumors that spread from other body sites to the brain are termed metastatic brain tumors. Statistics suggest that brain cancer occurs infrequently and is likely to develop in about 22,000 new people per year in 2009, with about 13,000 deaths as estimated by the National Cancer Institute (NCI).

Not all brain tumors are alike, even if they arise from the same type of brain tissue. Tumors are assigned a grade depending on how the cells in the tumor appear microscopically. The grade also provides insight as to the cell's growth rate. NCI lists the following grades:

• Grade I: The tissue is benign. The cells look nearly like normal brain cells, and they grow slowly.

• Grade II: The tissue is malignant. The cells look less like normal cells than do the cells in a grade I tumor.

• Grade III: The malignant tissue has cells that look very different from normal cells. The abnormal cells are actively growing (anaplastic).

• Grade IV: The malignant tissue has cells that look most abnormal and tend to grow quickly.

The most common primary brain tumors are usually named for the brain tissue type from which they originally developed. These are gliomas, meningiomas, pituitary adenomas, vestibular schwannomas, and primitive neuroectodermal tumors (medulloblastomas). Gliomas have several subtypes which include astrocytomas, oligodendrogliomas, ependymomas, and choroid plexus papillomas. When the grades are coupled with the tumor name, it gives doctors a better understanding about the severity of the brain cancer. For example, a grade III (anaplastic) glioma is an aggressive tumor, while an acoustic neuroma is a grade I benign tumor. However, even benign tumors can cause serious problems if they grow big enough to cause increased intracranial pressure or obstruct vascular structures or cerebrospinal fluid flow.

What is metastatic brain cancer?

Cancer cells that develop in a body organ such as the lung (primary cancer tissue type) can spread via the bloodstream or lymphatic system to other body organs such as the brain. Tumors formed by such cancer cells that spread (metastasize) to other organs are called metastatic tumors. Metastatic brain cancer is a mass of cells (tumor) that originated in another body organ and has spread into the brain tissue. Metastatic tumors in the brain are more common than primary brain tumors. They are usually named after the tissue or organ where the cancer first developed (for example, metastatic lung or breast cancer tumors in the brain, which are the most common types found).

What causes brain cancer?

Primary brain tumors arise from many types of brain tissue (for example, glial cells, astrocytes, and other brain cell types). Metastatic brain cancer is caused by the spread of cancer cells from a body organ to the brain. However, the causes for the change from normal cells to cancer cells in both metastatic and primary brain tumors are not fully understood. Data gathered by research scientists show that people with certain risk factors are more likely to develop brain cancer. Individuals with risk factors such as having a job in an oil refinery, as a chemist, embalmer, or rubber-industry worker show higher rates of brain cancer. Some families have several members with brain cancer, but heredity as a cause for brain tumors has not been proven. Other risk factors such as smoking, radiation exposure, and viral infection (HIV) have been suggested but not proven to cause brain cancer. There is no good evidence that brain cancer is contagious, caused by head trauma, or caused by cell phone use. Although many lay press and Web articles claim that aspartame (artificial sweetener) causes brain cancer, as of 2009, the FDA maintains that it does not cause brain cancer and base their findings on over 100 toxicological and clinical studies regarding the sweetener's safety.

Signs and symptoms

Symptoms of brain tumors may depend on two factors: tumor size (volume) and tumor location. The time point of symptom onset in the course of disease correlates in many cases with the nature of the tumor ("benign", i.e. slow-growing/late symptom onset, or malignant, fast growing/early symptom onset) is a frequent reason for seeking medical attention in brain tumor cases.

Large tumors or tumors with extensive perifocal swelling edema inevitably lead to elevated intracranial pressure (intracranial hypertension), which translates clinically into headaches, vomiting (sometimes without nausea), altered state of consciousness (somnolence, coma), dilatation of the pupil on the side of the lesion (anisocoria), papilledema (prominent optic disc at the funduscopic examination). However, even small tumors obstructing the passage of cerebrospinal fluid (CSF) may cause early signs of increased intracranial pressure. Increased intracranial pressure may result in herniation (i.e. displacement) of certain parts of the brain, such as the cerebellar tonsils or the temporal uncus, resulting in lethal brainstem compression. In young children, elevated intracranial pressure may cause an increase in the diameter of the skull and bulging of the fontanelles.

Depending on the tumor location and the damage it may have caused to surrounding brain structures, either through compression or infiltration, any type of focal neurologic symptoms may occur, such as cognitive and behavioral impairment, personality changes, hemiparesis, hypesthesia, aphasia, ataxia, visual field impairment, facial paralysis, double vision, tremor etc. These symptoms are not specific for brain tumors—they may be caused by a large variety of neurologic conditions (e.g. stroke, traumatic brain injury). What counts, however, is the location of the lesion and the functional systems (e.g. motor, sensory, visual, etc.) it affects.

A bilateral temporal visual field defect (bitemporal hemianopia—due to compression of the optic chiasm), often associated with endocrine disfunction—either hypopituitarism or hyperproduction of pituitary hormones and hyperprolactinemia is suggestive of a pituitary tumor.

Treatment and prognosis

Many meningiomas, with the exception of some tumors located at the skull base, can be successfully removed surgically. In more difficult cases, stereotactic radiosurgery, such as Gamma knife, Cyberknife or Novalis Tx radiosurgery, remains a viable option.

Most pituitary adenomas can be removed surgically, often using a minimally invasive approach through the nasal cavity and skull base (trans-nasal, trans-sphenoidal approach). Large pituitary adenomas require a craniotomy (opening of the skull) for their removal. Radiotherapy, including stereotactic approaches, is reserved for the inoperable cases.

Although there is no generally accepted therapeutic management for primary brain tumors, a surgical attempt at tumor removal or at least cytoreduction (that is, removal of as much tumor as possible, in order to reduce the number of tumor cells available for proliferation) is considered in most cases. However, due to the infiltrative nature of these lesions, tumor recurrence, even following an apparently complete surgical removal, is not uncommon. Several current research studies aim to improve the surgical removal of brain tumors by labeling tumor cells with a chemical (5-aminolevulinic acid) that causes them to fluoresce. Postoperative radiotherapy and chemotherapy are integral parts of the therapeutic standard for malignant tumors. Radiotherapy may also be administered in cases of "low-grade" gliomas, when a significant tumor burden reduction could not be achieved surgically.

Survival rates in primary brain tumors depend on the type of tumor, age, functional status of the patient, the extent of surgical tumor removal, to mention just a few factors.

UCLA Neuro-Oncology publishes real-time survival data for patients with this diagnosis. They are the only institution in the United States that shows how brain tumor patients are performing on current therapies. They also show a listing of chemotherapy agents used to treat high grade glioma tumors.

Patients with benign gliomas may survive for many years, while survival in most cases of glioblastoma multiforme is limited to a few months after diagnosis if treatment is ignored.

The main treatment option for single metastatic tumors is surgical removal, followed by radiotherapy and/or chemotherapy. Multiple metastatic tumors are generally treated with radiotherapy and chemotherapy. Stereotactic radiosurgery (SRS), such as Gamma Knife, Cyberknife or Novalis Tx, radiosurgery, remains a viable option. However, the prognosis in such cases is determined by the primary tumor, and it is generally poor.

Radiotherapy is the most common treatment for secondary cancer brain tumors. The amount of radiotherapy depends on the size of the area of the brain affected by cancer. Conventional external beam whole brain radiotherapy treatment (WBRT) or 'whole brain irradiation' may be suggested if there is a risk that other secondary tumors will develop in the future. Stereotactic radiotherapy is usually recommended in cases of under three small secondary brain tumors.

In 2008 a study published by the University of Texas M. D. Anderson Cancer Center indicated that cancer patients who receive stereotactic radiosurgery (SRS) and whole brain radiation therapy (WBRT) for the treatment of metastatic brain tumors have more than twice the risk of developing learning and memory problems than those treated with SRS alone.

A shunt operation is used not as a cure but to relieve the symptoms. The hydrocephalus caused by the blocking drainage of the cerebrospinal fluid can be removed with this operation.

Research to treatment with the vesicular stomatitis virus

In 2000, researchers at the University of Ottawa, led by John Bell PhD., have discovered that the vesicular stomatitis virus, or VSV, can infect and kill cancer cells, without affecting healthy cells if coadministered with interferon.

The initial discovery of the virus' oncolytic properties were limited to only a few types of cancer. Several independent studies have indentified many more types susceptible to the virus, including glioblastoma multiforme cancer cells, which account for the majority of brain tumors.

In 2008, researchers artificially engineered strains of VSV that were less cytotoxic to normal cells. This advance allows administration of the virus without coadministration with interferon. Consequently administration of the virus can be given intravenously or through the olfactory nerve. In the research, a human brain tumor was implanted into mice brains. The VSV was injected via their tails and within 3 days all tumor cells were either dead or dying.

Research on virus treatment like this has been conducted for some years, but no other viruses have been shown to be as efficient or specific as the VSV mutant strains. Future research will focus on the risks of this treatment, before it can be applied to humans.

Brain tumors in infants and children

A brain-stem glioma in four year old. MRI sagittal, without contrast

In the US, about 2000 children and adolescents younger than 20 years of age are diagnosed with malignant brain tumors each year. Higher incidence rates were reported in 1975–83 than in 1985–94. There is some debate as to the reasons; one theory is that the trend is the result of improved diagnosis and reporting, since the jump occurred at the same time that MRIs became available widely, and there was no coincident jump in mortality. The CNS cancer survival rate in children is approximately 60%. The rate varies with the type of cancer and the age of onset: younger patients have higher mortality.

In children under 2, about 70% of brain tumors are medulloblastoma, ependymoma, and low-grade glioma. Less commonly, and seen usually in infants, are teratoma and atypical teratoid rhabdoid tumor.[16] Germ cell tumors, including teratoma, make up just 3% of pediatric primary brain tumors, but the worldwide incidence varies significantly.