Brian D. Kavanagh, MD: This tumor board conference will focus
on the case of a 54-year-old woman with a 2-month history of
headaches and seizures, who was diagnosed as having a primary brain
tumor. The key features of the diagnostic work-up and management
strategy will be presented, and relevant topics of ongoing basic
research will be discussed. First, Dr. Manning will present the case history.
Matthew A. Manning, MD: The patient is a 54-year-old woman who
pre-sented in December 1996 with a rightsided headache and
generalized seizure. A magnetic resonance imaging (MRI) scan of the
brain at that time was normal. In January 1997, the woman experienced
another severe headache and a second seizure. Repeat radiographic
imaging again was interpreted as normal, and anticonvulsants were
started. Her headaches continued to worsen, and an MRI performed in
February 1997 revealed a right frontal enhancing brain mass that
appeared to be a primary brain tumor.
The patients medical history is remarkable only for asthma and
mild emphysema. The family history included a grandmother with
gastric cancer. The patient had been taking estrogen replacement
therapy since menopause 3 years earlier, and she was allergic to peroxide.
The patient is married and has three healthy children. She works full
time in the family business. She smoked one to two packs of
cigarettes daily for 30 years, but she quit smoking 3 years
previously. She does not drink alcoholic beverages or use illegal drugs.
A review of systems revealed no complaints other than the previously
noted neurologic symptoms. Karnofsky performance status was 90.
Physical examination, including a detailed neurologic examination,
was entirely normal for a woman of her age in generally good health.
Laboratory studies, including a complete blood count and serum
chemistries, were normal, and a chest radiograph demonstrated no
infiltrates or mass lesions.
On March 11, 1997, the patient underwent a right frontal craniotomy
with gross total resection of what was identified histopathologically
as a glioblastoma multiforme. There were no postoperative
complications or neurologic deficits.
The patient was then enrolled on the Massey Cancer Center 96-12
protocol, through which she received 50 Gy of wide-field,
conventionally fractionated external-beam radiotherapy, followed by
24 Gy administered via four weekly concomitant stereotactic boost
treatments, for a total of 74 Gy to the tumor bed. The patient has
also received three of four planned cycles of carmustine (BCNU
[BiCNU]) therapy, administered intravenously at a dose of 80
mg/m²/d for 3 days every 8 weeks.
Dr. Kavanagh: Dr. Pizzuti, this patient underwent several
radiographic imaging studies shortly before the lesion was
recognized. Please comment on whether, in retrospect, there were any
irregularities on the initial radiographic studies that might have
suggested the diagnosis earlier. Also, are there any other processes
that could cause such a dramatic change on an MRI within such a short period?
Thomas Pizzuti, MD: Although the MRI obtained in December 1996
did contain a small periventricular area of abnormality, possibly
related to prior ischemia, there was no evidence of a lesion in the
area later seen to be involved by the mass (Figure
1a). The study obtained in January 1997 was similarly unremarkable.
It is obviously quite disturbing that such a large, enhancing mass in
the right frontal lobe region was seen just 2 months later (Figure
1b). This lesions rapid progression and pattern of central
necrosis are highly suggestive of a high-grade primary brain tumor,
but the differential diagnosis would also include a metastatic lesion
from another malignancy and an infectious process forming an abscess.
A follow-up MRI study also is available for comparison. The right
frontal region is notable for the expected postoperative changes, but
there is no evidence of recurrent tumor (Figure
Lisa A. Kachnic, MD: Dr. Broaddus, what do you consider to be
the standard of care for managing patients with glioblastoma
multiforme? What are the effects of recent advances in neurosurgical technology?
William C. Broaddus,MD, PhD: In general, the primary
radiographic contrast-enhancing tumor and any associated necrotic
tissue should be resected as completely as possibly without causing
significant postoperative neurologic deficits, and adjuvant therapy
should be given to all patients. Numerous reports have indicated
that, the greater the extent of tumor resection, the better is
patient survival. Also, the surgeon should minimize the amount of
normal surrounding brain tissue that is removed in the process. In
this particular case, the tumor was actually in a favorable site for
an attempt at extensive resection, since it was peripherally located
away from deeper critical structures.
Stereotactic Localization Technology
Recent advances in neurosurgical technology have not really changed
the basic principles of management of glioblastoma multiforme. The
goals of management remain the same, and adjuvant therapy is still
recommended in all cases. However, the recently developed technology
for intraoperative stereotactic localization is particluarly helpful
in allowing a surgeon to be much more aggressive in marginal cases in
which a tumor may approach critical structures without yet invading them.
The primary determinant of a tumors resectability remains its
location within the brain, and obviously there is no way to change
that. However, with stereotactic localization technology, the
tumors relationship to surrounding structures can be seen much
more clearly than before.
The system essentially translates the three-dimensional tumor imaging
data from the preoperative MRI and gives the surgeon real-time
feedback during surgery about the location of the scalpel within the
head relative to the tumor. For cases in which the tumor closely
approximates critical structures, such as the optic apparatus or
brainstem, the surgeon can be more confident about scalpel position
and, thus, can resect more of the tumor adjacent to these structures.
Even in a case such as this one, where the tumor is in a relatively
favorable location, stereotactic localization still provides an
important technical advantage. In this particular case, because such
accurate knowledge of tumor location was available, I could approach
the tumor directly through a more limited incision and craniotomy.
Consequently, I could minimize the amount of surrounding normal brain
tissue resected during the procedure.
Correlation Between MRI and Surgical Findings
Dr. Kachnic: How well does the MRI appearance actually
correlate with findings during surgery? Can the surgeon really detect
a difference in texture between areas of the brain near the tumor
that look edematous and areas that look normal?
Dr. Broaddus: It is amazing how closely the surgical findings
correlate with the MRI findings when the stereotactic system is being
used. In a typical patient with glioblastome multiforme, the major
abnormality on the scan is the enhancing lesion, which is surrounded
by brain that appears edematous. Currently, I use an incremental
surgical technique whereby I remove a layer of tumor and then assess
my location, especially if I am approaching an area where there would
be significant adverse effects on neurologic function from injury to
the normal brain. After Ive gone past the relatively firmer
areas of tumor, I typically break through into white matter that has
a very watery appearance and that, in fact, often is even visibly
I should acknowledge that some surgeons do not feel comfortable
relying on stereotactic technology to guide them into deeper
resections because they recognize that once a surgical procedure is
underway, the brain anatomy is different from what was seen on the
preoperative MRI because tissue is being moved and removed. However,
I generally find that the system gives me very good information to
help me remain aware of the three-dimensional anatomy.