Browse Category: Neuro oncology

The pathogenesis of most primary brain tumors

For the most part we still don’t truly understand the pathogenesis of most primary brain tumors, or the epidemiology as far as predisposing risk. There are certainly several genetic disorders for which there seems to be a predilection for primary brain tumors. They include neurofibromatosis, tuberous sclerosis, Turcot syndrome. But these account for well less than 1% of all the cases of primary brain tumors. We still are somewhat in the dark, relative to the etiology of this disease.

Astrocytomas are the most common primary brain tumor in adults and represents the most significant problem in adults. When we speak of astrocytomas, we divide them into low and high-grade tumors. The high-grade tumors include tumors known as anaplastic astrocytomas, which include glioblastoma multiforme. When we talk about the grading system for astrocytomas, it is in fact somewhat complicated. There are a number of different grading systems. The oldest and original one was the Kernohan system, which was a four-tier system. With grades I and II of four being classified as low-grade astrocytomas or grades III and IV being high grade astrocytomas. A grade III of four is an anaplastic astrocytoma, while grade IV of four is a glioblastoma multiforme. The problem with the Kernohan system is that, although the system did pretty well as far as prognosticating between low- and high-grade tumors, it was not very good at separating out prognostic variables between grades I and II, versus grades III and IV. And because of this discrepancy, back in the 1980s, many people went to a simpler system, a three-tier system, originally designed by ECOG. In this system grade I of three is considered a low grade astrocytoma, grade III of three is considered a glioblastoma and grade II of three is considered an anaplastic astrocytoma. If you look at survival curves in this three-tier system, you do indeed see very nice separations of the curves. The problem is that the vast majority of the patients fall into a category of grade II of three, astrocytoma.

Although low grade astrocytomas have a long natural history, these are not benign diseases. Given that these patients are young, generally speaking, this again cannot be in any way classified as a benign tumor. In fact, these are infiltrative, slowly but progressively growing tumors. Radiographically, they appear on CT scan as low- attenuating, poorly defined, non-contrast enhancing masses. While on MRI scan one generally sees increased P2 signal and they are non gadolinium enhancing. Unfortunately there is very little randomized data to suggest optimum management for these patients. The reason for this is twofold: It’s been very difficult to conduct clinical trials secondary to both the relatively long natural history of this disease and the relative rarity. So most of our recommendations relative to low-grade gliomas are based on biases and anecdotal and/or retrospective data. Currently in most large brain tumor centers, is if a low-grade glioma can be safely resected, then all attempts are made to do so. On the other hand, as one gets to a higher-grade tumor, grade II astrocytoma, it appears as though the benefits of more full resections are less pronounced. In fact the role for surgery for lower-grade tumors.

Neuro oncology

Neuro-oncology encompasses both primary brain tumors as well as secondary tumors. In other words, tumors from systemic cancers that involve the central nervous system. It’s really much too large an area to cover in one hour, so what I thought I would do is spend the majority of time talking to you about primary brain tumors, because I think most medical oncologists are least familiar with these tumors. Yet, increasingly so, medical oncologists are going to be seeing these tumors.

When one actually looks at SIR data from the NCI one can see a bi-modal distribution in the incidence of primary brain tumors. It can peak for the first few years of life, which then falls off and then begins to rise in late adolescence, peaking around the age of 60. In fact, these tumors represent very significant problems. They are the second leading cause of cancer mortality in patients under the age of 34, and the fourth leading cause of death in patients between the ages of 34 and 54. And in fact, primary brain tumors – now that leukemia has been cured in 70-80% of children – has really become the primary oncologic problem in the pediatric population. Plus, primary brain tumors do in fact present a significant cancer problem in the United States.

Depending on the classification, there are as many as 15-30 different primary brain tumors. Meningiomas are very common but they are generally restricted to surgical management and radiation and only occasionally – for rare syndromes where we see malignant meningiomas – do medical oncologists see these patients.

When we talk about brain tumors almost regardless of the type of histology, we can group the syndromes, as far as how patients present, into the following signs and symptoms. The common presenting symptom is one of headaches. Seizures are seen in approximately half the patients, as are mental status changes and some kind of motor deficits. With the more readily available access to CAT scans and MRI scans, we are picking up patients earlier in the course of their disease, and that the number of patients who are actually presenting with significant increased intracranial pressure has significantly decreased.