Successfully treating brain tumors is very difficult because of the brain's natural defense, the blood-brain barrier. For the past 22 years, the BBB Program at OHSU has been extensively researching the effective delivery of chemotherapy drugs for treating malignant brain tumors.
In the early 1980s, Edward A. Neuwelt, M.D., an OHSU neurosurgeon, pioneered a unique method of outwitting the brain's protective blood-brain barrier. By temporarily opening this barrier, chemotherapy and tumor specific antibodies can pass into the brain and reach the tumor. Dr. Neuwelt continues to devote his efforts to researching and refining this treatment for patients with brain tumors.
Physicians often recommend one or more treatment options based on the patient's tumor type, tumor location, prior treatment and general health. These options include surgery, radiation, standard chemotherapy, intra-arterial chemotherapy, and blood-brain barrier disruption (BBBD) with intra-arterial chemotherapy.
A craniotomy is the most common surgical approach to remove brain tumors. The amount of tumor removed depends on the tumor type, its location in relation to surrounding brain structures, and the extent to which it has spread in the brain.
Yet even if surgery removes most of the tumor, some microscopic, rapidly dividing tumor cells still remain. Surgery is not considered a cure for most brain tumors, except for certain non-malignant tumors such as meningioma and acoustic neuroma. Therefore, the patient will need additional treatments after surgery. Surgery is usually not used if the patient has more than one brain tumor except to make a diagnosis by obtaining a biopsy.
The goal of radiation therapy is to destroy cancer cells by injuring their ability to divide. Depending on their tumor type, patients may receive radiation as their sole treatment. Radiation and/or radio surgery may also be used before or after chemotherapy, but our data, as well as others, show that chemotherapy is more effective prior to radiation. Our preclinical studies also show that radiation has fewer side effects when chemotherapy is done first (Remsen 1995).
Chemotherapy affects tumor cells by stopping their rapid growth or division. Chemotherapy is given by pill or injection into a vein, an artery or the cerebral spinal fluid. Because some drugs work better together, patients often receive more than one chemotherapy agent.
Blood-Brain Barrier Disruption (BBBD) treatment
The brain's protective barrier is composed of tightly knit endothelial cells, which line the walls of the blood vessels in the brain. These tightly knit cells create a barrier that blocks the entry of various substances, including many therapeutic agents.
By temporarily shrinking these cells with a concentrated sugar solution, we can open this barrier, allowing chemotherapy drugs to pass into the brain and reach the tumor. Compared with standard chemotherapy, Blood-Brain Barrier Disruption treatment increases the delivery of the chemotherapy drugs to the tumor and its surrounding area by tenfold to a hundredfold (Neuwelt 1998).
Osmotic opening of the blood-brain barrier
Osmotic opening of the blood-brain barrier. When endothelial cells that line capillary walls are exposed to a concentrated sugar solution, the cells shrink, thus opening the tight junctions between them.
Adapted from: SI Rapoport, Blood-Brain Barrier in Physiology and Medicine. Raven Press, 1976.
All candidates for the Blood-Brain Barrier Disruption (BBBD) Program may speak with a nurse to discuss treatment and to determine if the patient candidate is eligible to participate in the BBBD program.
If the candidate believes he or she meets the basic requirements for treatment, he or she next visits the OHSU Neuro-Oncology clinic to meet Dr. Neuwelt and the team clinicians. At the clinic visit a complete history and physical examination is done, brain scans are reviewed and further discussion regarding treatment as well as risks and benefits occurs.
Patients who are undergoing BBBD treatment usually stay at OHSU Hospital for four days. On the first day, the patient goes to the pre-admission testing clinic where the BBB nurse practitioner performs a complete history and physical examination, orders all necessary laboratory tests, schedules an anesthesia evaluation, and requests a CT or MRI of the head.
The patient is then admitted to the oncology ward of the hospital. That evening the patient receives intravenous fluids and anti-seizure medication. On the second and third days, patients undergo BBBD treatment with chemotherapy.
BBBD is an angiographic procedure (a process in which we make X-ray pictures of blood vessels) performed in an operating room or in a radiology suite. While patients are asleep under general anesthesia, we insert a very narrow catheter (tube) into the femoral artery, just below the hip, and advance it into one of the neck arteries at the base of the brain.
We then infuse a concentrated sugar solution (mannitol) through the catheter to temporarily open the tight junctions of the blood-brain barrier. Immediately after the mannitol, we give our patients chemotherapy intra-arterially through the same catheter. Patients also receive chemotherapy intravenously during the treatment.
During the BBBD procedure, patients are closely monitored by the BBB physician and an anesthesiologist. After the treatment, in the recovery room and on the oncology ward, nurses continue to monitor and care for patients very carefully. Most patients can return home on the fourth morning.
Generally, patients in the BBB Program are treated every four weeks for one year. After completing the year of monthly treatments, our patients return to Dr. Neuwelt's clinic and undergo regularly scheduled brain MRI or CT scans of the head.
After patients have completed their treatment program, our nurse practitioners continue to communicate often with them through phone conversations and the nurses maintain close contact with patients' primary care physician.
Blood-Brain Barrier Disruption treatment may be effective in reducing the size of a brain tumor. However, we cannot guarantee that it will be effective in treating every patient. Through research and the opportunity to work with many patients, we are striving to significantly alter the outcome of this disease. We learn from each patient, and the information we acquire in treating each one is used on behalf of other patients.