BBBD
Therapy
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.
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). |
Delivery
of chemotherapy in the angiography suite.
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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.)
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Pretreatment
Evaluation
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.
Treatment
Process
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.
Disclaimer
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. |