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Primary

Primary brain tumors are those that arise within the brain itself, unlike metastatic tumors that travel to the brain from a distant site. The most common types of primary brain tumors in adults are gliomas, glioblastomas, and lymphomas.

Gliomas

Gliomas are a family of tumors comprising primarily of astrocytomas and oligodendrogliomas, the most aggressive primary brain tumor being the glioblastoma (GBM). These tumors are the most common primary brain tumors in adults.

Symptoms & Diagnosis

The typical symptoms of brain tumors are headaches, nausea, confusion or seizures, which may be caused by increased intracranial (within the head) pressure. An MRI scan is usually used to diagnose gliomas, such as glioblastoma. However, newer technologies such as Magnetic Resonance Spectroscopy (MRS), which looks at the chemical make-up of a tumor, can be helpful in diagnosis before a patient undergoes biopsy.

Determining Treatment Options

The first step is a biopsy or larger surgical removal of the tumor. Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center surgeons use the latest advances in neurosurgical navigational techniques as well as intra-operative MRI, to ensure precise removal during biopsy or resection. The tissue obtained during the biopsy or resection is helpful in determining the type of cell and how aggressive the brain tumor is. Neuropathologists grade tumors based on the World Health Organization (WHO) system. The higher the number, the more aggressive the tumor.

The information obtained from the biopsy will influence how the tumor is treated. Molecular testing, which provides information about the genetic makeup of a tumor, is playing an increasing role in treatment decisions and the development of new targeted therapies.

Treatment Options

One of the latest treatment options for brain tumors is convection-enhanced delivery (CED). Convection enhanced delivery allows potent drugs that would otherwise be too toxic to the body, or those that are not capable of passing through the blood-brain barrier, to be slowly and continuously infused into certain brain tumors.

Cleveland Clinic's Rose Ella Burkhardt Brain Tumor Center has ongoing pharmaceutical and NCI-sponsored trials using continuous infusions of immunotoxins (IL1 -PE38) for recurrent high-grade gliomas like glioblastoma. Ongoing neurosurgical trials through the American College of Surgeons Oncology Group also are available. Computer-assisted stereotactic navigational techniques, pioneered at Cleveland Clinic and used during CED, have resulted in improved patient outcomes.

The Center offers conventional radiotherapy as well as stereotactic radiosurgery utilizing the Gamma Knife. In January 2010, specialists at Cleveland Clinic's Gamma Knife Center treated their 3000th case with this non-surgical, outpatient procedure. Our Gamma Knife Center has also upgraded to the Gamma Knife Perfexion, the most technologically advanced model available. The new model offers enhanced planning using all image modalities, including PET CT and MRI, as well as reduced treatment time. In addition, Rose Ella Burkhardt Brain Tumor Center specialists also utilize the Novalis radiosurgery equipment. This provides treatment via intensity modulated radiotherapy (IMRT), which shapes the radiation beam and modifies its intensity to deliver highly focused radiation to the target area.

Radiation can also be delivered locally using Gliasite brachytherapy in which liquid radiation is placed into a balloon that has been implanted in the surgical cavity of a resected tumor. Clinical trials are currently being completed through multicenter pharmaceutical studies and through the New Approaches to Brain Tumor Therapy consortium. The Center has participated in several radiation sensitizer studies and remains active in the Radiation Therapy Oncology Group.

Glioblastoma

The most commonly diagnosed primary malignant brain tumor of adults is the glioblastoma multiforme (GBM).

What is a Glioblastoma?

The glioblastoma multiforme is graded by the World Health Organization as a grade IV astrocyotoma (the highest grading designation). This classification also includes the grade IV variants: giant cell glioblastoma and gliosarcoma.

The characteristic features of a glioblastoma multiforme is that is grows fast and invades into adjacent tissue. Under the microscope one can find astrocytic cells, mitotic figures (dividing cells), new blood vessel growth (angiogenesis) and dead cells called necrosis. A Glioblastoma multiforme can occur at any age but is typically seen in people between 45 and 70 years old. These brain tumors are found most commonly in the subcortical white matter of the frontal lobes, and the tumor cells can cross from one side of the brain to the other (usually in a structure called the corpus callosum). Rarely does the tumor affect sites outside of the brain. Active research is under way to help identify the cause of these tumors. Less than five percent of all primary brain tumors such as the glioblastoma multiforme have any known hereditary factors.

Symptoms & Diagnosis

The most common signs and symptoms of glioblastoma multiforme are seizures, progressive headaches, or progressive loss of brain function (such as speech, strength, memory, etc.). Computerized Axial Tomography (CT) scans and Magnetic Resonance Imaging (MRI) scans with and without contrast typically show an enhancing abnormality that "lights-up" after contrast is given. Edema or swelling is also commonly seen on these studies. Magnetic Resonance Spectroscopy (MRS), Magnetic Resonance Cerebral Blood Volume (MRCBV) or Positron Emission Tomography (PET) may give insights into the metabolism of the area of abnormality.

Treatment Options

For a glioblastoma multiforme, patients may undergo a surgical procedure called a craniotomy for diagnostic and or debulking (removing as much tumor as possible) purposes. Since these tumors infiltrate into the brain to variable distances, not all the malignant cells can be removed; thus, additional treatment is most commonly recommended. A pathologist who will identify the tumor type examines tissue taken at the time of surgery.

Glioblastoma multiforme represents a heterogeneous cell population, which means that certain cells may be more resistant to treatment than others. This is what makes a glioblastoma multiforme difficult to treat. The most common treatment performed worldwide after surgery is radiation therapy, so patients need to be seen by a radiation oncologist. Radiation typically takes place five days a week over a six-week period. The radiation first is given to a specified area of the brain to help reach the tumor cells that are further away. A radiation "boost" then is given closer to the area of the glioblastoma bulk, where more tumor cells are located.

Chemotherapy has been used for many years to treat these brain tumors and has been given before, during or after radiation therapy. Historically BCNU, CCNU and Procarbazine have been used. More recently Temodar has been used and shown to improve prognosis when given early in the disease. Chemotherapy also can be placed locally at the time of surgery using a Gliadel wafer, which is impregnated with BCNU and placed around the surgical cavity during tumor resection.

New Treatments

At Cleveland Clinic, we have access to alternative radiation delivery methods including stereotactic radiotherapy (Gamma Knife), Intensity Modulated Radiotherapy (IMRT ) and Novalis. Radiation can also be given using implanted seeds (I131) or by placing liquid radiation into a balloon (GliaSite), which is placed into the surgical cavity after tumor removal. Drugs called Radiation Sensitizers given at the time of radiation also are used in a clinical research setting as part of a clinical trial.

Many clinical trials are under way around the country investigating novel drugs for the treatment of these brain tumors. Cleveland Clinic is a member of various consortiums investigating some of these new drugs. We offer clinical trials through ABTC, (American Brain Tumor Consortium), RTOG (Radiation Therapy Oncology Group), SWOG (Southwest Oncology Group), and NABTT (New Approaches to Brain Tumor Therapy - a National Cancer Center Consortium). We also run a number of industry-sponsored clinical trials to study new and novel drugs such as immunotoxins delivered by convection enhanced delivery - a process where the drug is slowly, continuously pumped through the brain over several days. The Tarceva Trial, for example, is measuring the effect of an epidermal growth factor receptor (EGFR) antagonist, because EGFR has been shown to be overexpressed in some GBMs.

A recurrent glioblastoma multiforme can be treated in a fashion similar to upfront GBMs. Certain clinical trials are used in the upfront setting and other trials are under way for the treatment of recurrent tumors. Active clinical trials also are ongoing around the country using gene therapy, monoclonal antibodies and various biological modifiers.

Lymphomas

Lymphomas, also referred to as central nervous system lymphoma or primary central nervous system lymphoma (PCNSL), is a form of Non-Hodgkin's Lymphoma.

What are Lymphomas?

The most common cause of lymphomas is an overproduction of a certain type of white blood cell, called B-lymphocytes. Lymphomas may occur in individuals with healthy immune systems or in patients whose immune system is compromised, such as those who have AIDS or those who have undergone an organ transplant.

Although the incidence of lymphomas is increasing nationwide, these tumors still only account for one to two percent of primary brain tumors. The most commonly affected sites are the cerebral hemispheres but cells can be found in the cerebral spinal fluid (CSF), eyes (ocular), spinal cord, or other organ systems. In patients who do not have an impaired immune system, primary central nervous system tumors have a peak incidence in patients in their 60s and 70s.

Symptoms & Diagnosis

The most common symptom is trouble with thinking, learning or making judgments, called cognitive changes. However, headaches and problems walking, slurred speech or tremor also may occur. When the eyes are affected, it signals more aggressive lymphoma. It may be months or years before the central nervous system is affected.

Diagnosis is made by a biopsy of the affected site after an abnormality has been noted on a MRI of the brain, or through an examination of cells obtained from the cerebral spinal fluid or the vitreous fluid of the eye.

Treatment Options

Historically, whole brain radiation has been the primary treatment since lymphoma involves the entire brain. Whole-brain radiation is an effective treatment with approximately 50% of patients showing a complete response. However, when whole brain radiation is not combined with other treatments, patients often relapse. Patients who survive long-term following whole brain radiation often encounter significant cognitive problems related to treatment.

Today, chemotherapy is routinely used alone, or in conjunction with radiation to improve long-term outcomes. The most common chemotherapy drug is methotrexate, which may be administered through intra-venous delivery, intra-arterial delivery or intra-ocular delivery. Chemotherapy also may be given directly into the cerebral spinal fluid through a reservoir (Ommya).

All chemotherapy delivered into the body must cross the blood-brain barrier to obtain entrance into the cerebral spinal fluid, which limits the use of many chemotherapy drugs. Although intra-venous methotrexate with whole brain radiation has been shown to almost double survival, long-term radiation side effects persist.

New Treatments

The Rose Ella Burkhardt Brain Tumor Center is investigating several new treatments currently being used for brain tumor symptoms in clinical trials. Learn more about current clinical trials.

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