Online Health Chat with Dr. Michael Vogelbaum

October 15, 2010

Introduction

Cleveland_Clinic_Host: Approximately 20,000 people in the U.S. are diagnosed with a primary brain tumor each year. Primary brain tumors are those that arise within the brain itself, unlike metastatic tumors that travel to the brain from cancer that has formed in another part of the body. These types of brain tumors occur in people of all ages, but they are statistically more frequent in children and older adults. The most common types of primary brain tumors in adults are gliomas, glioblastomas, and lymphomas.

Michael Vogelbaum, MD, PhD, is the Associate Director of the Brain Tumor and Neuro-Oncology Center, Director of the Center for Translational Therapeutics and has been a member of the professional staff in the Cleveland Clinic’s Department of Neurological Surgery since 1999.

Specializing in the diagnosis and treatment of benign and malignant tumors of the brain and spinal cord, Dr. Vogelbaum interests also include stereotactic (image-guided) surgery, Gamma Knife therapy and the molecular biology of brain tumors. He has joint appointments with the Cleveland Clinic Gamma Knife Center and the Lerner Research Institute’s Department of Cancer Biology.

He received his undergraduate degree from Johns Hopkins University, Baltimore, MD, his medical degree from University of Virginia School of Medicine, Charlottesville, VA, his doctorate degree from the University of Virginia, Charlottesville, VA, and completed his residency training at Barnes-Jewish Hospital, St. Louis, MO.

To make an appointment with Dr. Vogelbaum or any of the other specialists in our Brain Tumor and Neuro-Oncology Center at Cleveland Clinic, please call 216.636.5860 or toll-free at 866.588.2264. You can also visit us online at www.clevelandclinic.org/braintumor.

Cleveland_Clinic_Host: Welcome to our Online Health Chat with Dr. Michael Vogelbaum. We are happy to have him here today for our chat on Understanding Risk Factors, Symptoms and Treatment Options for Primary Brain Tumors. Let’s begin with the questions.

Overview of Brain Tumors

starkwood: What percentage of brain tumors turn out to be cancerous?

Speaker_-_Dr__Michael_Vogelbaum: Overall, about 1/3 of brain tumors are "malignant". However, the term malignant, when applied to brain tumors, can have a different meaning than with other types of cancers. Some brain tumors are referred to as "low grade". One should not consider these to be "benign" as, over time, they tend to progress to becoming "high grade" or, more clearly malignant. Truly benign brain tumors, for example, most meningiomas, are more common than the malignant varieties (for example, gliomas).

bim: Are cancerous brain tumors treated the same as noncancerous brain tumors?

Speaker_-_Dr__Michael_Vogelbaum: Cancerous (i.e. malignant) brain tumors are treated very differently from noncancerous (truly benign) brain tumors. Furthermore, there are various types of cancerous and noncancerous brain tumors and each different type may be treated differently. In the most general terms, truly benign brain tumors may be considered curable by surgery alone (but not all of them).

Malignant tumors, on the other hand, are rarely cured by surgery alone, although there are some "low-grade" types of these tumors for which surgery can have a long-lasting benefit and other therapies are not needed for many years. Radiation therapy and chemotherapy are much more commonly used for cancerous tumors. However, we may also use these treatments for benign tumors that are refractory to surgery, or that have grown into areas where they would be dangerous to remove.

glendy: When you say that someone has a low-grade glioma or other tumor, what exactly does that mean?

Speaker_-_Dr__Michael_Vogelbaum: This is a very important question as sometimes even doctors get the distinctions wrong! The grade of glioma is assessed by the pathologist who looks at a surgical specimen obtained by a limited biopsy or a more extensive tumor removal.

There are very specific factors that go into making the grade: how cellular is the tumor, how abnormal are the tumor cells, what percentage of the tumor cells are dividing, are there areas where the tumor has grown so quickly that it became starved for nutrients and portions of it died ("necrosis"), and is the tumor creating new vessels for itself ("vascular proliferation").

Low grade tumors (referred to also as "WHO grade II") have fewer of these abnormalities than do high grade tumors. WHO grade IV is the highest grade, and these tumors are also referred to as GBM. While these seem like distinct entities (low grade, anaplastic (WHO grade III) and GBM), the truth is that they are a continuum of the same disease. Left alone, and sometimes even after treatment, over time low grade tumors become high grade tumors.

So, the concept that a "low grade" glioma is "benign" is a fallacy. For many years, though, this is what doctors have told their patients (we do like to be optimistic, when possible). But the reality is that, while their overall course is better than those that are found to be high grade at the time of diagnosis, they should not be considered benign, and even when stable over years, should continue to be monitored closely.

Diagnosis

chopchop: How can you have worsening of symptoms with an Astrocytoma that hasn’t changed in more than a year (according to MRI and brain scan)?

Speaker_-_Dr__Michael_Vogelbaum: A very interesting question, because we definitely see this! MRI has revolutionized our ability to detect, monitor and plan treatments (including surgery) for brain tumors. It provides a more detailed view of the brain's structure than any prior imaging modality, and has other ways to provide us with information about blood supply, function, chemistry and so on. Before that, we had CT scans (which revolutionized neurosurgery in the 1970's), and before that detection and localization of brain lesions relied upon detailed and thorough neurological exams and other very indirect imaging techniques. In other words, the surgeon often did not really know what he/she would encounter when starting the operation.

But as good as MRI is, it has its limits. It does not show us what is happening at the microscopic level with respect to anatomy or even function.

We already know that we cannot detect the full extent of spread of a glioma, even with the most sensitive imaging techniques. So microscopic infiltration can be occurring without any obvious change on MRI.

Also, the treatments can have microscopic side effects that cannot be imaged.

In the past few years there has been increasing interest in the use of very detailed neuropsychological assessments (the circle is closed, we are back to using the neurological exam again) to try to detect tumor progression before it is obvious on MRI. Some studies seem to suggest that this may be the case.

Signs & Symptoms

jumpup: My father was recently diagnosed with a brain tumor that has since been designated cancerous. Prior to his diagnosis, my father exhibited no symptoms. Following his diagnosis, his health deteriorated quickly. Is this common to have sudden onset of symptoms or could this be primarily psychological?

Speaker_-_Dr__Michael_Vogelbaum: The story that you tell is very common. There are many factors that determine what types of symptoms (what the patient notices) or signs (what the physician sees) that are produced by a brain tumor. For example, the tumor's location is a very important factor.

The brain is divided into functional areas. Some areas have clearly defined functions (for example, control of movement, speech, language, visual processing and so on), whereas others do not have clearly defined functions but are important for higher level aspects of personality, concentration, intelligence and so on. Furthermore, one side often is more important for some functions (for example, speech, memory and language) than the other. A growing lesion will produce symptoms that relate to its location. Lesions growing in an area with a clearly defined function are likely to produce symptoms very early in the course of growth, whereas those growing in a "silent" area may become very large before producing symptoms.

A second factor is the rate of growth. A slowly growing tumor (i.e. over years) may become very large, even in or near a functional area, before it is detected, whereas a rapidly growing one will likely produce symptoms early in its course. The brain can accommodate slow growth, but eventually, it reaches its limit of accommodation and then symptoms may come on and progress very rapidly, like you have described.

Treatment

carly: What is the first suggested treatment for a newly diagnosed glioblastoma?

Speaker_-_Dr__Michael_Vogelbaum: I am not sure how the diagnosis of glioblastoma (GBM) was made here (whether by biopsy alone, or more extensive tumor removal), so I'll include comments about surgery with my discussion of the "standard" treatment for GBM.

First of all, one needs to obtain tissue confirmation of diagnosis after an MRI or CT suggests that a patient has a GBM. This can come in the form of a limited biopsy (usually called a stereotactic biopsy), or a more extensive removal of the bulky part of the tumor. I'll discuss how that decision is made when answering another question about surgery. Unfortunately, surgery is essentially never curative for GBM, because the tumor cells are infiltrative. This means that there can be microscopically infiltrating diseased cells, many inches away from the bulky tumor. In some patients this may extend into the other side of the brain.

Removal of all of this infiltrative disease would be associated with permanent and devastating loss of neurological function. So that is where medical therapies come into play. The so-called standard approach, in 2010, is fractionated radiotherapy combined with oral daily chemotherapy (temozolomide) followed by chemotherapy (temozolomide), usually given 5 days per month for 6 to 12 months (barring tumor progression during therapy). For many patients, this approach can provide tumor control (i.e. lack of further growth) or even improvement of the MRI for many months, and for some, more than 1 to 2 years. Unfortunately, we do not have a cure for GBM and so we try to offer novel and innovative treatments for patients willing and able to enter into a clinical trial (many of these potential treatments are not yet approved by the FDA).

jelbell: What is the difference between gamma knife surgery and linac stereotactic radiosurgery and fractionated stereotactic radiosurgery? Which do you recommend for gbm?

Speaker_-_Dr__Michael_Vogelbaum: For Gamma Knife vs. LINAC, this is similar to the questions: Coke vs. Pepsi, or McDonald's vs. Burger King. Gamma Knife and LINAC based radiosurgery are different technologies that are designed to produce the same result, and most evidence suggests that they are no different in terms of outcomes. The important differences may affect behind the scenes activities.  Fractionated stereotactic radiosurgery is different from single fraction radiosurgery in terms of the risk benefit ratio for certain lesions adjacent to normal structures that cannot tolerate high radiation doses (for example, the optic nerves).

Which do I recommend for GBM? In general, none of these. The evidence to date suggests that radiosurgery is not very effective for GBM and it is associated with a high risk of radiation injury. Radiosurgery, is a very focused treatment; GBM is a diffuse disease. In my mind, use of radiosurgery for GBM largely should be limited to a clinical trial setting for most patients, and I am currently running a clinical trial of radiosurgery for this purpose.

Inoperable Brain Tumor

tintin: What exactly makes a tumor inoperable?

Speaker_-_Dr__Michael_Vogelbaum: As I promised earlier, I will now discuss how we decide when to operate on a patient with a brain tumor (as opposed to just doing a limited biopsy). I'm going to address this question for patients with gliomas (tumors within the brain). The answer for tumors outside of the brain (for example, meningiomas, is slightly different).

First, let me address the issue of why we recommend surgery for a tumor when we know that the procedure is unlikely to be curative.  Often, patients present to us with mass effect related symptoms.  The skull is rigid and large enough to contain the normal sized adult brain and not much more.  A growing tumor within the skull over time produces elevated pressure which can lead to restriction of blood flow…a potentially dangerous situation.  So tumor mass removal can help to relieve this pressure and mass-effect related symptoms; a benefit in itself.  Also, there is evidence that removal of nearly all of the obvious tumor mass is associated with a longer survival.  So even if it is not curative, surgery can provide meaningful benefits to appropriately selected patients.

How do we define “appropriately selected patients”?  That is an important question because we have evidence as well that new, permanent neurological deficits after surgery are associated with a worsened outcome.  So we try our best to identify those patients who are at greatest risk for acquiring new deficits postoperatively, so that we can more effectively balance what we assess to be the risk/benefit ratio for those patients.  There are many factors that influence the risk of surgery and the definition of what is and what is not operable.  For example, tumors may arise in locations of the brain where safe surgical access is very limited (e.g. the brainstem).  Or they may be very diffusely infiltrated into superficial and deep areas of the brain and hence only a limited removal can be performed safely.  Tumors also may arise in or adjacent to areas that have clearly defined functions (such as movement, speech, language, memory, vision).  We have a number of tools we use to pre-operatively and intra-operatively identify and reduce the risks of surgery in those cases, but none of these tools are perfect indicators of outcome.  And there are a variety of medical factors which may affect the patient’s suitability to undergo anesthesia and surgery, in general.  Ultimately, a surgeon’s judgment and experience are used to make the decision about whether a surgery is possible or not, and what may seem inoperable to some surgeons may be routine for others.

Closing

Cleveland_Clinic_Host: I'm sorry to say that our time with Dr. Michael Vogelbaum is now over. Thank you again Dr. Vogelbaum for taking the time to answer our questions about Understanding Risk Factors, Symptoms and Treatment Options for Primary Brain Tumors.

Speaker_-_Dr__Michael_Vogelbaum: Thanks for chatting with me today. These were some really great questions! I hope I have the opportunity to do this again sometime.

More Information

• To make an appointment with Dr. Vogelbaum or any of the other specialists in our Brain Tumor and Neuro-Oncology Center at Cleveland Clinic, please call 216.636.5860 or toll-free at 866.588.2264. You can also visit us online at www.clevelandclinic.org/braintumor.
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