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(Drug information on 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 1c).
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 weeping fluid.
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.