What causes a cell or cells in the brain to go awry and develop into a tumor? If only we knew, scientists might be able to create better treatments. Or, better yet, doctors might be able to prevent brain tumors from growing in the first place.

Researchers at the UC Brain Tumor Center are hoping that the Ohio Brain Tumor Research Study will help provide some answers to the fundamental question of why brain tumors develop. Christopher McPherson, MD, Director of the Division of Surgical Neuro-Oncology in the Department of Neurosurgery and principal investigator in UC’s portion of the Ohio Brain Tumor Research Study, offered insights into the nature of the study and what researchers hope to accomplish.

Q: Which research institutions are involved in this study?
A: The Ohio Brain Tumor Research Study is a joint venture of the four brain tumor centers in Ohio:
 

• the Brain Tumor and Neuro-Oncology Center at Case Western Reserve University and the Case Comprehensive Cancer Center
• the Cleveland Clinic Foundation
• Ohio State University
• and the Brain Tumor Center at the University of Cincinnati Neuroscience Institute.

Q: What is the research study’s objective?
A:  The study is looking at risk factors for brain tumors. We want to know what causes them. Although a few things are known to cause brain tumors – radiation, for example, and rare genetic syndromes – we haven’t been able to pinpoint other risk factors. When I see patients, usually the first thing they ask is, “How did I get this?”

We also are hoping to sharpen our ability to diagnose the more than 125 different brain tumor subtypes. Brain tumors, in addition to being different from each other, are not always uniform. For example, the cells in one area of a tumor can have greater malignancy than cells in another part of the tumor. If we can diagnose a brain tumor by its genetic signature rather than by its history or how it appears under a microscope, we may be able to improve treatments and step up prevention.

Q: How are researchers gathering their data?
A: This research study is open to people who have been newly diagnosed with a primary malignant or benign brain tumor – a tumor that has originated in the brain. Once a patient has enrolled in the study, we will collect biological samples and information about how the patient lives and any environmental exposures he or she may have had. We will also review their medical history.

Study participants initially go through a 30- to 45-minute telephone interview. During that phone call, they are asked questions related to many different risk factors, such as where they live, their family history, their diet and lifestyle, and environmental exposures. That information is then directly paired with the individual’s genetics, which have been derived from tissue and blood samples. We’re trying to find genetic markers that could be central to identifying risk for a brain tumor or treating it. Study participants also are asked to participate in follow-up phone calls.

Q: What kind of biological samples are acquired?
A:  During an office visit, a saliva sample is taken from the patient’s cheek with a swab, and a blood sample is drawn. During a biopsy or surgery to remove the tumor, a sample of the tumor is also collected.

Q: What will become of the tissue sample?
A: The tissue samples will be stored in a tissue bank that will serve as a resource for all of the Ohio centers. The tissue will be saved so that it can be used in future research projects and as new questions about brain tumors arise.

Q: This research study sounds unique. Are there others like it in other states?
A: There are other epidemiology consortiums nationwide, but I am not aware of any other states that have anything like this.
 

CINCINNATI--A minimally invasive endoscopic procedure holds promise for safely removing large brain tumors from an area at the bottom of the skull, near the sinus cavities, clinical researchers at the Brain Tumor Center at the University of Cincinnati Neuroscience Institute (UCNI) have found.

The findings, published in the April 2010 issue of the Journal of Neurosurgery and published online in October 2009, have important implications for patients with large pituitary tumors (pituitary macroadenomas).

“This is the first time that a quantitative advantage has been shown for the use of endoscopy in cranial surgery,” says Philip Theodosopoulos, MD, Principal Investigator of the Study, Director of Skull Base Surgery at UC, and a neurosurgeon with the Mayfield Clinic.

“This signals the dawn of a new era in minimally invasive cranial surgery. We have moved from the realm of assessing whether it is feasible to studying its clinical effectiveness. In this way, it is slowly starting to change from a novelty to standard treatment, setting the bar for the quality of surgical outcomes higher than ever before.”

Although tumors of the pituitary gland, located near the base of the skull, are benign, pituitary macroadenomas can wreak havoc, causing acromegaly (an overproduction of growth hormone), Cushing disease (an overproduction of the hormone cortisol), and hyperthyroidism, as well as visual problems, headaches, and dizziness.

When removing pituitary macroadenomas (tumors that are larger than 10 millimeters), surgeons have employed three distinct routes to the tumor:

1. Through the skull, in a procedure called a craniotomy;
2. Through an incision under the upper lip and then through the septum, which must be split apart
3. Through the nostrils -- a transnasal approach -- without an incision

The endoscopic transsphenoidal approach, Dr. Theodosopoulos says, follows natural anatomical corridors and causes less disruption of nasal tissues. This approach, as the new study reveals, also holds benefits related to complete tumor removal, which is important for the patient’s quality of life.

Removing an entire pituitary macroadenoma can be difficult because the tumor’s growth pattern can cause it to extend through the sinus corridor, which is out of the surgeon’s view.

Surgeons can ensure that the entire tumor has been removed if their hospital operating room is equipped with a technology known as intraoperative MRI, or ioMRI. The surgery-prolonging technology enables surgeons to take MRI scans while the patient is still under anesthesia and on the operating table. The UC Neuroscience Institute at University Hospital has had ioMRI since 1999, but the expensive technology is not available at most hospitals.

An endoscopic approach, by contrast, allows the surgeon to check for remaining tumor with “intrasellar endoscopy.” Using a tiny, sophisticated camera on an angled endoscope, the surgeon can peer around bends and into crevasses to identify any remaining tumor. “The endoscopic approach holds the potential for less invasive treatment for all patients and more complete tumor resections for individuals treated in hospitals without access to intraoperative MRI,” Dr. Theodosopoulos says.

During the retrospective study at University Hospital, the team analyzed surgical outcomes of 27 consecutive patients between 2005 and 2007 who had undergone endoscopic removal of pituitary macroadenomas. The search for unexpected residual tumor was conducted two ways in all patients: first with the tiny endoscopic camera (intrasellar endoscopy) and then with intraoperative MRI.

Following the initial endoscopic tumor removal, intrasellar endoscopy revealed that 23 of the 27 patients (85 percent) had no unexpected residual tumor. Surgeons were able to safely perform additional surgery on three of the four patients who had unacceptable residual tumor.

Following the endoscopic procedures, all patients were checked with intraoperative MRI, which revealed that tumor removal was successful in 26 patients (96 percent).

The study results show that maximum tumor removal can be successfully achieved with endoscopy and without intraoperative MRI, Dr. Theodosopoulos says. He adds, however, that the findings could be strengthened by a larger study.

Additional study participants included John M. Tew, MD (Mayfield Clinic, UC Department of Neurosurgery, and UCNI), Lee Zimmer, MD, PhD (UC Department of Otolaryngology and UCNI), James Leach, MD (Cincinnati Children’s Hospital Medical Center and UCNI), Bharat Guthikonda, MD (UC Department of Neurosurgery), and Amanda Denny, MD (UC Department of Endocrinology). Also participating was Sebastien Froelich, MD (Department of Neurosurgery, University of Strasbourg, France).

The UCNI group is one of the world’s busiest centers for minimally invasive removal of pituitary tumors. It has pioneered two innovative endoscopic surgical corridors, has performed more than 300 endoscopic cases, and has published results in more than 10 peer-reviewed journals.

CINCINNATI–Anya Sanchez, MD, MBA, has been named Administrative Director of the University of Cincinnati Neuroscience Institute (UCNI) at University Hospital. Dr. Sanchez is responsible for the management and oversight of day-to-day operations for the tertiary/quaternary program’s seven centers of excellence.

Kimbaird Avant, MS, has been hired to manage the UC Brain Tumor Center, one of the seven centers of excellence. Mr. Avant is responsible for brain tumor operational efficiencies and center development.

Prior to joining UCNI, Dr. Sanchez was the Director of the Physicians in Leadership Program for Sg2, LLC, an international healthcare intelligence firm based in Chicago. She also served as Senior Consultant at Sg2 in a dual role as Project Manager and Clinical Lead on the firm's strategic consulting team, providing clinical oversight and managing project team efficiency, project profitability, client relationships, and business development opportunities. Before joining Sg2, Dr. Sanchez served as the Director of Operations at Becker & Associates, a healthcare regulatory consulting firm in Washington, DC.

Though her primary focus throughout her career has been in the area of neuroscience, she also has experience developing strategic plans and implementing tactics for multiple service lines and across entire hospitals and regional health systems.

Of her new role at UCNI, Sanchez said, “It’s a privilege to be part of such a great organization. The Institute’s dedication to patient care, research and education is truly inspiring, and it is exciting to see how UCNI is changing lives every day.”

Dr. Sanchez earned her bachelor of arts in biology and psychology, with a minor in neuroscience, from Miami University, in Oxford, Ohio.  She received her doctor of medicine from the University of Toledo and her master of business administration from Georgetown University. 

A native of Cincinnati, Dr. Sanchez recently returned to her hometown of Lebanon, Ohio, where she resides with her husband and their three children.

Mr. Avant has worked for more than 19 years in health care project management and information technology. He spent most of his career at Cincinnati Children’s Hospital Medical Center, working in the neurosurgery operating room, the Department of Information Systems and, most recently, as an Application Specialist in the Division of Behavioral Medicine and Clinical Psychology. Mr. Avant served on the Board of Directors for Children’s Medical Center Federal Credit Union for more than five years.

Mr. Avant earned an associate of science degree in computer network administration from Cincinnati State Technical and Community College, a bachelor of science in management from Indiana Wesleyan University and a master’s of science in executive leadership and organizational change from Northern Kentucky University. 

Mr. Avant and his wife are the parents of two daughters.
 

CINCINNATI–Christopher McPherson, MD, a neurosurgeon with the Mayfield Clinic and the Brain Tumor Center at the University of Cincinnati Neuroscience Institute, has been elected to the Executive Committee of the Section on Tumors of the American Association of Neurological Surgeons (AANS) and Congress of Neurological Surgeons (CNS).

Dr. McPherson, who will also serve on the Research Committee, is Assistant Professor of Neurosurgery and Director of the Division of Surgical Neuro-Oncology at UC.

The Section on Tumors performs a wide range of activities relating to education, research, and the coordination of neuro-oncology programs for the AANS and CNS. The Section includes more than 1,600 neurosurgeons, neuro-oncologists, and other health-care professionals who specialize in the care of patients with brain tumors.

Ronald Warnick, MD, Chairman of the Mayfield Clinic and Director of the UC Brain Tumor Center, served as Chairman of the Section on Tumors from 2005 to 2007.

CINCINNATI -- Ronald Warnick, M.D., Chairman of the Mayfield Clinic, Director of the Brain Tumor Center at the University of Cincinnati Neuroscience Institute, and Co-Director and a developer of the Precision Radiotherapy Center in West Chester, Ohio, is one of America’s leading experts in the treatment of brain tumors. He is a past Chairman of the American Association of Neurological Surgeons/Congress of Neurological Surgeons Section on Tumors and is currently a co-investigator in nine clinical trials underway at the Brain Tumor Center.

During a recent interview, Dr. Warnick discussed advances in brain tumor therapy that are likely to an impact on treatments in the years ahead.

Q: Where will the next major advances in brain tumor therapy come from?

A: The next advances in brain tumor therapy are going to come from the laboratory, where scientists are studying the molecular aspects of brain tumors. Some of these laboratory experiments will lead to potential therapies, and we will then test them in clinical trials. We will then take the results of those clinical trials back to the laboratory and refine those treatments. This cycle of transferring findings from the laboratory to the clinic and back to the laboratory is what I call the discovery-to-recovery phase and the recovery-to-discovery phase. We need physicians and scientists to work together to translate laboratory findings into the next major advances in brain tumor therapy.

Q: What is brain tumor profiling, and what is the current status of this technique?

A: An important aspect of brain tumor treatment and management of patients relates to something that we call brain tumor profiling. I liken this concept to an FBI agent who profiles a criminal. The FBI agent studies crimes the criminal has committed, correlates those crimes with a personality type, and then tries to anticipate the individual’s future criminal behavior. We’re doing the same thing when we take a sample of tumor and we look at it under the microscope and look at certain features and then try to predict how that tumor will act in a particular patient.

In the past we had only one way of doing this: We acquired the tissue through a biopsy or operation, stained it, and then looked at it under a microscope. We would make a diagnosis and then tell the patient his or her average prognosis. But now we can be much more sophisticated. We can take that tissue and conduct a molecular analysis of it. I like to think of this as a gene fingerprint. Just as you have specific fingerprints on your fingers, each tumor also has a specific gene fingerprint. From this we can not only obtain the diagnosis of the tumor, but we can also begin to start categorizing the prognosis of patients and their tumors.

For example, during the last six months a diagnostic test called Decision Dx-GBM has become available. We can take a sample of the tumor and send it to a central laboratory. Pathologists look at nine separate genes and, based on those results, they can determine which of five prognosis groups the patient falls into. This is helpful in itself; but even more helpful is the ability of that gene fingerprint to tell us which treatment would work best for each individual patient.

In the past, we were forced to take a cookie-cutter approach. If the tumor was diagnosed as a glioblastoma, we used a standard treatment, which is radiation combined with chemotherapy. What brain tumor profiling offers is not only a sophisticated prediction of outcome, but also a selection of appropriate therapy for a patient with that tumor. A gene fingerprint of a patient’s tumor might reveal that a particular marker, such as EGFR, is positive in that patient, for example. This means, then, that we need to use a treatment that is anti-EGFR. If the patient has this marker, we want to attack that particular marker in order to kill the tumor cell. Some patients might be EGFR-positive, some might be VEGF-positive, and some might be positive for both. So their treatments will be different. This is also what is meant by the term “personalized medicine.” It means that we are personalizing, or tailoring, the treatment approach to a particular patient and his or her tumor. It is no longer a cookie-cutter approach; it is more like getting a custom-tailored suit.

While the test that allows us to determine the initial gene fingerprint has been available for about six months, the ability to tailor treatment based on that gene fingerprint is in progress, in patients and in clinical trials. It is not accepted as standard treatment yet.

Q: What is immunotherapy and its potential to fight brain tumors?

A: It is helpful to understand that every one of us is reliant on our immune cells to detect and kill cancer cells that may spontaneously form in our bodies. And the immune system generally does a good job of that. However, in patients who have glioblastoma, the number of those cancer-fighting immune cells is decreased by 75 percent. These patients only have 25 percent of the normal number of immune cells. We are not sure whether the glioblastoma causes this situation or whether these patients have an impaired immune system that has led to the glioblastoma. The latter is a strong possibility.

The reduced number of immune cells is not the only problem for patients with glioblastoma. A second problem is that the remaining cancer-fighting immune cells are impaired. They try to recognize and kill the tumor, but for some reason they are unable to get the job done. So we have to boost the numbers of cancer-fighting immune cells as well as their activity, their strength.

We do that by using a vaccine to re-educate these immune cells to be stronger cancer-fighting cells. And, luckily, there is a type of white blood cell in the body called the dendritic cell. This immune cell, which resembles an octopus, likes to digest tumor cells, and in so doing it pushes fragments of the tumor out onto its branches, or arms. When the arms of this dendritic cell – or teacher cell -- come in contact with inactive immune cells – or student cells – the student cells become activated and can home in on the tumor and kill it. When we re-educate these cells to become active, they then divide and produce children and grandchildren, which all have the same characteristics, because they have been educated and taught to fight and recognize the tumor. It is as if you had trained a pack of guard dogs.

A Phase II study of a dendritic cell-based vaccine (the DC Vax trial) involves taking dendritic cells from a patient newly diagnosed with glioblastoma and sending them to a central laboratory, where they are then incubated with tissue from the patient’s own brain tumor. During the incubation, or fermenting, process, the dendritic cells chomp up and digest the tumor and become primed to be “teachers.” The dendritic cells are then sent back to the patient’s hospital, where they are injected under the patient’s skin. The cells educate the body’s immune cells, which move from that site under the skin to the brain and attack the tumor.

The UC Brain Tumor Center was one of the early centers involved in this therapeutic clinical trial, whose patients also underwent surgery and received radiation therapy and chemotherapy. The trial is currently closed to enrollment, but we have acquired some promising information from the results of the first 20 patients. The therapy seems to be well tolerated; and of the 20 patients who received this therapy, 19 have lived longer than the average for this tumor. As such, DC Vax has a real potential to become a standard therapy for glioblastoma.

Q: What can you tell us about the DCX-110 vaccine?

A: Immunotherapy refers to the harnessing of the body’s immune system to fight the tumor. One way to accomplish this is through a vaccine. We all know that vaccines are used to prevent infection, hepatitis, influenza, polio. Vaccines are made by taking the virus and weakening it so that it cannot cause infection. Then that weakened virus is injected into a patient or person, where it causes an immune response and prevents the person from getting the true infection if it is ever encountered. Medical scientists have long dreamed of developing a vaccine for brain tumors. The ideal solution would be a vaccine that would prevent you from ever getting a brain tumor. A second-best option would be a vaccine that could rev up a patient’s immune system so that he or she that could fight the tumor. This is the kind of vaccine that is currently being studied and developed.

During our research we have discovered that glioblastoma cells have little switches on their surface. When these switches are turned on they send a signal to the cell’s command center, and the cell is stimulated to grow and divide. We know that in about 40 percent of glioblastomas the switch is stuck in a permanent “on” position. So the goal of a new brain tumor vaccine is to turn off these switches and thus kill the cell. This treatment is called CDX-110, although the trial is often called the Celldex trial after the name of the drug manufacturer (Celldex Therapeutics). A Phase II trial involving this vaccine is underway here in Cincinnati and at 30 other centers.

The trial represents one of our first applications of tumor profiling, or gene fingerprinting. We take a sample of brain tumor tissue from all patients who are newly diagnosed with glioblastoma and test for the presence of the “on switch.” The 40 percent of patients whose genes test positively for the “on switch” should, theoretically, respond positively to a vaccine that seeks to turn the switches off. These patients (who also undergo radiation and chemotherapy) receive regular injections of the on-switch vaccine under the skin. The vaccine actually causes an immune reaction, and you can see a rash forming. Those cells are then basically activated, revved up to attack the “on switch” of glioblastoma. The cells migrate to the brain and turn off the glioblastoma cell and prevent it from dividing. Results of this study will become known sometime in 2010.

Q: What is an angiogenesis inhibitor, and how might it help in the fight against brain tumors?

A: Brain tumor angiogenesis is another “near-future” strategy – one that is in clinical trials and, if successful, is five years away from becoming standard therapy. Brain tumor angiogenesis is a complicated terminology, but it comes down to something very basic: glioblastomas are tumors that tend to have a very significant blood supply from the brain. For example, if you look at an angiogram of a patient with a glioblastoma, you will see a huge number of new blood vessels that have formed. These vessels are important to the tumor because they feed it oxygen, glucose, and other nutrients. The glioblastoma is a smart tumor that has figured out a way to trick the brain’s blood vessels into giving it more of what it needs. The tumor’s cells do this by sending out a signal that stimulates the blood vessels to form new blood vessels. These new blood vessels feed the tumor, bring it more nutrients, allow it to grow and divide, and cause more problems. This cycle continues unless we can stop those false signals.

We have a recently approved therapy, called Avastin, which can do just this. It is an intravenous medication that blocks at least one of tumor’s signals. This leads to a decrease in the number of blood vessels that form and the amount of blood that is feeding the tumor. Eventually, the tumor shrinks. Avastin was approved by the FDA because of very promising results in patients who had exhausted other therapies. After being given the drug, these patients saw their tumors shrink dramatically.

The UC Brain Tumor Center and 34 others are currently studying a similar angiogenesis inhibitor called Recentin, an oral medication that is manufactured by AstraZeneca. The study is comparing the results of three groups of patients: 1) those who take Recentin alone; 2) those who take Recentin in combination with an oral chemotherapy agent (CCNU); 3) and those who take only CCNU. The centers expect to collectively enroll 300 patients, and the trial will close in the summer of 2010. The advantage of Recentin over Avastin is that it is oral. Eventually, down the road, the standard treatment for glioblastoma could consist of oral Temodar (our most common chemotherapy agent) and oral Recentin.

Q: What is the latest news about neural stem cells?

A: First, I’d like to clarify that the stem cells we’re talking about with glioblastoma are not embryonic stem cells. These are stem cells that we all have in our bodies. These particular stem cells are found deep in the brain, around the fluid space called the ventricle, and are responsible for producing various types of brain cells, or neural cells. Stem cells are normal and good, but occasionally they get knocked akilter. That happens when a neural stem cell undergoes a mutation or permanent change. It could be from some external stimulus, like radiation. But whatever the cause, this neural stem cell becomes a cancer stem cell, and we know, from previous studies, that glioblastoma starts and grows from cancer stem cells.

I liken cancer stem cells to the queen bee of the hive. They live forever, they produce the worker bees or the worker tumor cells, and they’re very difficult to kill. Normally, our treatments are very effective at killing the worker bees. But for a variety of reasons, about 1 percent of tumor cells are very resistant to radiation and chemotherapy and do not die. These remaining cells are the cancer stem cells, the queen bee. We have found that they will be suppressed for about 24 hours after chemotherapy, but they very quickly revive themselves and begin growing and dividing again. This is our major problem. Over time, this 1 percent of remaining cells will produce more worker bees, and, before you know it, the tumor has returned.

So, what we need to do is study why cancer stem cells are resistant to radiation and chemotherapy. That is being done in the laboratory right now. Scientists in the laboratory are asking how can we change this cancer stem cell, how can we modify it, so that it will become sensitive to radiation or chemotherapy. Therapies involving the sensitization or modification of cancer stem cells could go into clinical trials in five years and could become standard treatments in 10 years.

There are other ways we might attack cancer stem cells, however. We know that stem cells have certain markers on their surface. Some of these markers are specific to cancer stem cells, and CD 133 is one of them. If we have a specific immunotherapy, like an antibody, or a vaccine that could recognize CD 133, this could be used to selectively eliminate cancer stem cells, like a surgical strike in a war. The other possibility that is being studied involves injecting a modified herpes virus that would infect only cancer stem cells. The herpes virus would divide and grow and finally kill the cell.

Q: Does nanotechnology hold promise for brain tumor therapy?

A: Nanotechnology is a technology that focuses on the development of machines that range in size from 10 to 100 nanometers. One nanometer is 1 million times smaller than the head of a pin. These machines cannot be seen with a naked eye or even a regular microscope. You need a scanning electronic microscope to see them. These nanomachines are not constructed from metal or plastic but from the body’s building blocks, whether DNA, RNA, or protein. They can navigate through tissues and they can sense objects. They can smell tumor cells, for example, and they can be designed to perform certain tasks. There are some whose job is to form a channel through the membrane of a cell to allow chemotherapy agents to flow through.

Some nanomachines truly exist, and some exist only in scientists’ minds. So how would we use nanomachines to treat brain tumors? Well, one possibility is to deliver nanomachines made of iron oxides into brain cells. Because MR imaging is based on magnetic fields, and since iron is magnetic, then we might be able to visualize individual tumor cells that contain the magnetic particles. Right now we can only see large tumor masses. If we could image every tumor cell that exists in the brain, we might be able to treat them more effectively.

Another possibility is that nanomachines could deliver a drug that sensitizes the tumor cell to radiation or chemotherapy. They could also help drugs pass through the blood brain barrier. Or the nanomachine could enter the cell and disrupt the command center machinery of the cell. Some of these uses are in the minds of scientists and some are in experiments right now. But they certainly are not in clinical trials. Those that exist are only being tested in animal models.

Q: In summary, how optimistic are you about the future of brain tumor therapy?

A: I believe that in 10 or 15 years the field will be quite different. I believe that when we do imaging of a patient with a brain tumor, we will use a much more powerful form of MRI than we currently use. It will not only show structural images of where the tumor is and what it is pressing against, but the MRI itself – even without a biopsy -- will tell us the gene fingerprint of the tumor. And from this fingerprint, we will be able to know the type of tumor and its grade.

With knowledge of a patient’s gene fingerprint, we will be able to provide optimal treatment that is tailored to that individual patient. If there are seven common fingerprints in glioblastoma, for example, we may well end up with a particular therapy for each type. This treatment could come in the form of immunotherapy or a vaccine, or it could involve nanotechnology. It will probably be delivered intravenously. And whether it is involves immunotherapy or nanotechnology, it will be very specific for the tumor and will deliver some kind of anti-cancer agent only to the tumor cells.
 

CINCINNATI–Stereotactic radiosurgery for metastatic brain tumors can be accomplished safely and effectively without immobilizing a patient’s head with an invasive head frame, researchers at the Brain Tumor Center at the University of Cincinnati Neuroscience Institute have found. Their findings are published in two manuscripts in the July issue of the International Journal of Radiation Oncology, Biology, and Physics.

Stereotactic radiosurgery, often referred to as “surgery without the knife,” involves the destruction of cancerous tissue with precisely targeted beams of radiation. Since the advent of radiosurgery, and up until now at most radiosurgery centers, the standard of care has required the fixation of a rigid, invasive stereotactic head frame to the skull in order to immobilize the patient and provide a frame of reference for targeting the radiosurgery.

The head frame is attached to the skull with surgically implanted pins and can be associated with patient discomfort, anxiety and increased recovery time. 

The UC Brain Tumor Center team found that treatment accuracy and success in eliminating brain metastases for patients fitted with a fabricated, noninvasive mask were comparable to those experienced by patients whose treatment involved an invasive head frame. The researchers also determined that the mask system was adequate for patient mobilization.

John Breneman, M.D., Professor of Radiation Oncology, was principal investigator of the team’s paper that detailed clinical outcomes; Michael Lamba, Ph.D., a UC physicist, was principal investigator of a paper that evaluated technical aspects of image-guided positioning of the fabricated mask. Co-investigators were Ronald Warnick, M.D., Director of the Brain Tumor Center and a neurosurgeon with the Mayfield Clinic; Ryan Steinmetz, M.D., a radiation oncologist with Oncology Partners Network; and Aaron Smith, D.O., a neurosurgeon from Columbus, Ohio.

Their studies involved patients who were treated at the Precision Radiotherapy Center of West Chester, Ohio. Precision Radiotherapy is a partnership of the Mayfield Clinic and UC Physicians.

The Precision Radiotherapy team began developing “frameless” radiosurgery in mid-2005 and initially used the technology for only those patients who had tumors in areas of the brain not associated with critical functions such as language and reasoning. Over the following two years the success of this approach allowed expansion of the indications for “frameless” radiosurgery to a point where the team now treats all of its radiosurgery patients with this method.

The frameless method involves fabricating a clamshell mask that precisely fits the patient and is equipped with infrared fiducial reflectors to help monitor the patient during treatment. In preparation for treatment, CT scans and contrast-enhanced MRI scans are taken of the patient with the mask in place. Immediately prior to treatment, with the patient again wearing the mask, additional x-rays are acquired. With the patient aligned on the treatment couch, radiation is delivered in arcs that rotate around the target.

In preclinical studies, using a phantom instead of a real patient, Dr. Lamba and the radiosurgery team confirmed that frameless targeting was as accurate as radiosurgery with the invasive, fixated frame. In the subsequent study of 49 patients treated with frameless radiosurgery for one or more brain metastases between August 2005 and October 2006, local control of the patients’ lesions and patient survival at one year compared favorably to studies of patients treated with frame-based techniques.

With the frameless method, local control of brain metastases was 80 percent at 12 months and 78 percent at both 18 months and 24 months. Patient survival was 44 percent at one year, 29 percent at 18 months and 16 percent at 24 months. These figures were equivalent to other patient series using frame-based techniques as well as the researchers’ own previously reported outcomes.

Dr. Breneman and Dr. Warnick point to several benefits of the frameless technique. “In the most obvious benefit, it has eliminated the discomfort and anxiety caused by the head ring,” Dr. Warnick said. “Patients who have undergone stereotactic radiosurgery both with a head ring and without clearly preferred the latter method.”

“The frameless technique also facilitates the implementation of fractionated radiosurgery, which our team is currently studying,” Dr. Breneman said. “Preliminary indications suggest that this technique – the delivery of lower doses of radiation over a period of days -- can significantly reduce treatment complications in selected patients.”

Dr. Warnick added that the frameless technique has opened up radiosurgery “from a small select group to a greater universe of patients.” Where previously many patients were excluded, now virtually every patient with a brain metastasis can be treated painlessly with stereotactic radiosurgery. “For example, we can now treat patients with large numbers of metastases by enabling these patients to be treated in multiple sessions without the necessity of re-attaching a head ring,” Dr. Warnick said. “We have treated as many as 14 metastases in a single patient on three successive days.”

The Brain Tumor Center’s radiation oncology team used Novalis® technology, manufactured by BrainLAB AG, to perform their research. The Novalis® system is equipped with an image-guided technology and real-time infrared fiducial tracking. The research team received approximately $10,000 in the form of a nonrestricted educational grant from BrainLAB to support the development of their study of frameless radiosurgery. Warnick has received occasional honoraria from BrainLAB in the past as a member of its speaker’s bureau.

* * * *

The Precision Radiotherapy Center offers stereotactic radiosurgery for treatment of tumors both inside and outside the head. Candidates for treatment include patients with benign and malignant tumors of the brain, head, neck, spine, lung, liver, and prostate.

The UC Brain Tumor Center treats hundreds of patients from the Greater Cincinnati region and beyond each year. The multidisciplinary center, which includes specialists in neurosurgery, radiology, radiation oncology, otolaryngology, internal medicine and physical medicine and rehabilitation, is committed to evidence-based medicine, compassionate care, research, and the utilization of emerging therapies and technologies.

The UC Neuroscience Institute, a regional center of excellence, is dedicated to patient care, research, education, and the development of new treatments for stroke, brain and spinal tumors, epilepsy, traumatic brain and spinal injury, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, disorders of the senses (swallowing, voice, hearing, pain, taste, and smell), and psychiatric conditions (bipolar disorder, schizophrenia, and depression).

The Mayfield Clinic is recognized as one of the nation's leading physician organizations for clinical care, education, and research of the spine and brain. Supported by 20 neurosurgeons, three neurointensivists, an interventional radiologist, and a pain specialist, the Clinic treats 20,000 patients from 35 states and 13 countries in a typical year. Mayfield's physicians have pioneered surgical procedures and instrumentation that have revolutionized the medical art of neurosurgery for brain tumors and neurovascular diseases and disorders.

CINCINNATI–After a review of 284 cases, specialists at the Brain Tumor Center at the University of Cincinnati Neuroscience Institute have concluded that performing a stereotactic needle biopsy in an area of the brain associated with language or other important functions carries no greater risk than a similar biopsy in a less critical area of the brain.

The retrospective study, led by Christopher McPherson, MD, Director of the Division of Surgical Neuro-Oncology at UC and a Mayfield Clinic neurosurgeon, was published online on May 1 in the Journal of Neurosurgery. View the abstract ►

The UC study compared the complication rates of stereotactic biopsies in functional, or “eloquent,” areas of the brain that were associated with language, vision, and mobility to areas that were not associated with critical functions. Eloquent areas included the brainstem, basal ganglia, corpus callosum, motor cortex, thalamus, and visual cortex. Complications were defined as the worsening of existing neurological deficits, seizures, brain hemorrhaging, and death.

“Needle biopsies in eloquent areas have generally been acknowledged to be safe, because the needle causes only a small amount of disruption to the brain,” Dr. McPherson explained. “But until now, researchers had not actually documented that biopsies in eloquent areas were as safe as those in non-eloquent areas.”

To make that comparison, Dr. McPherson’s team studied records of 284 stereotactic needle biopsies performed by 19 Mayfield Clinic neurosurgeons between January 2000 and December 2006. In the 160 biopsies that involved eloquent areas of the brain, complications occurred in nine cases (5.6 percent of the total). In the 124 biopsies that involved non-eloquent areas, complications occurred in 10 cases (8.1 percent). The difference was not statistically significant.

Overall, 19 of the 284 patients, or 6.7 percent, suffered complications. Thirteen of those patients recovered completely or somewhat from their complications, while six (2.1 percent of the total number of patients biopsied) experienced permanent neurological decline.

“Diagnosing and treating brain tumors always carries risk,” Dr. McPherson said. “Within that context, the results of this large sampling of biopsies are encouraging overall and reinforce our belief that stereotactic biopsy is a valuable diagnostic tool. Stereotactic biopsy is a safe way for us to remove a tissue sample for the diagnosis of a brain tumor, even when the tumor is in a challenging and dangerous part of the brain.”

Additional co-authors of the study are Ronald Warnick, MD, Director of the UC Brain Tumor Center and Chairman of the Mayfield Clinic; James Leach, MD, Associate Professor of Neuroradiology at UC, Cincinnati Children’s Hospital Medical Center, and the UC Neuroscience Institute; and Ellen Air, MD, PhD, a resident in the UC Department of Neurosurgery.

The UC Brain Tumor Center treats hundreds of patients from the Greater Cincinnati region and beyond each year. The multidisciplinary center, which includes specialists in neurosurgery, radiology, radiation oncology, otolaryngology, internal medicine and physical medicine and rehabilitation, is committed to evidence-based medicine, compassionate care, research, and the utilization of emerging therapies and technologies.

The UC Neuroscience Institute, a regional center of excellence, is dedicated to patient care, research, education, and the development of new treatments for stroke, brain and spinal tumors, epilepsy, traumatic brain and spinal injury, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, disorders of the senses (swallowing, voice, hearing, pain, taste and smell), and psychiatric conditions (bipolar disorder, schizophrenia, and depression).

The Mayfield Clinic is recognized as one of the nation's leading physician organizations for clinical care, education, and research of the spine and brain. Supported by 20 neurosurgeons, three neurointensivists, an interventional radiologist, and a pain specialist, the Clinic treats 20,000 patients from 35 states and 13 countries in a typical year. Mayfield's physicians have pioneered surgical procedures and instrumentation that have revolutionized the medical art of neurosurgery for brain tumors and neurovascular diseases and disorders.

A fund for socks and other essentials for patients with brain tumors

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December 23 will always have special meaning for Mary Siereveld. On that date in 2005 the Kentucky woman underwent brain surgery at University Hospital in Cincinnati. John M. Tew, M.D., a neurosurgeon with the Mayfield Clinic and the Brain Tumor Center at the University of Cincinnati Neuroscience Institute, removed a 1½-inch by 2-inch tumor that was pressing on Mary’s brainstem. Mary spent Christmas in the hospital, recovering. She also spent many hours thinking about Christmas and the values that were most important to her. 

In past years Mary had been immersed in the decorative trappings of Christmas. “My thoughts of Christmas had always been Martha Stewart-like: every corner decorated with red and green, lighted candles in every window, a garland around the front door, cookies baked, all the presents wrapped under the tree, and a from-scratch Betty Crocker fruitcake,” Mary recalls.

But during her stay on the neuroscience floor at University Hospital, her most treasured moments had nothing to do with garlands or wrapping. They included, rather, a kindly visit from two strangers, her first shower after surgery, fresh hospital socks each day, and a lengthy conversation with Dr. Tew on Christmas Day.

“Martha Stewart never came calling that year,” Mary says. “God had other plans for me. Now that I look back, it was the best Christmas ever for me. Angels disguised as doctors, nurses, and hospital staff were so attentive to my needs.”

Every year since then, on December 23, Mary returns to University Hospital with a heartfelt letter and simple gift for patients who are staying on the neuroscience floor. The gift is a pair of fuzzy socks. “A fresh, clean pair of hospital-issue socks was something that I looked forward to each day,” she remembers. “They were warm. They were versatile. I wore them all day and all night. With the help of a physical therapist, I walked up and down the halls a few times a day in them. It was a small thing, but I grew to love them each day when I received them. They symbolized consistency, and they were tangible things that were literally taking me down the road to recovery.”

In 2009 Mary and the University Hospital Foundation established Mary’s Socks Fund. The fund provides socks for patients with brain tumors during the holidays and also helps to fill basic, unmet needs for patients who experience significant hardship during their illness and hospitalization. To make a donation to Mary’s Socks Fund through the University Hospital Foundation, please visit the following link:

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CINCINNATI–-Neurosurgeons at the Brain Tumor Center at the University of Cincinnati Neuroscience Institute are taking part in what they call a “renaissance of the laser in neurosurgery.”

The renaissance has been sparked by a new microsurgical “laser scalpel” that enables neurosurgeons to bend a CO2 laser beam in their quest to eradicate complicated tumors that are embedded in remote or sensitive areas of the brain and spine. The new tool, which consists of a flexible, CO2 laser-compatible fiber coupled to a pen-like surgical instrument, allows neurosurgeons to operate near critical structures, such as the spinal cord and brainstem, while minimizing thermal injury to healthy tissue.

“This new microsurgical tool has led to the rebirth and renaissance of the CO2 laser,” said John M. Tew, MD, Clinical Director of the UC Neuroscience Institute and a Mayfield Clinic neurosurgeon. “There’s a lot of excitement among those of us who treat patients with tumors that are difficult to reach.”

The laser, called BeamPath™ NEURO, is manufactured by OmniGuide, Inc., of Cambridge, Mass.

“Aside from being a dramatic technological advance, this new laser redefines the limits of what can be performed safely along many difficult to reach corners of the brain,” said Philip Theodosopoulos, MD, Director of Skull Base Surgery at the UC Neuroscience Institute’s Brain Tumor Center and a Mayfield Clinic neurosurgeon.

Tew and Theodosopoulos have used the laser successfully in 10 cases since September. The neurosurgeons have used, or will use, the laser in the treatment of brain tumors (including pituitary tumors and acoustic neuromas), spinal cysts and tumors, and arteriovenous malformations.

The laser is especially valuable in the treatment of tumors that have calcified or are entangled in areas of the central nervous system that are critical for speech, reasoning and movement.

Lasers were first used in neurosurgery 30 years ago. Pioneered by Tew and others in the late 1970s and 1980s, they enabled surgeons to carefully vaporize cancerous tissue, one thin layer at a time. In 1984 Tew became the first surgeon in the United States to receive FDA approval to use the YAG (yttrium-aluminum-garnet) laser to vaporize previously inoperable brain tumors.

But because of the long wavelength of CO2 laser energy, the early lasers were unwieldy. Mounted on a microscope, they used a rigid arm and could be directed only at tumors within the surgeon’s direct line of sight. This “point-and-shoot” process, which lacked flexibility, fell out of favor, especially as technological advances enabled physicians to target tumors in other ways.

Tew noted in a 1986 journal article that the inability to maneuver the CO2 beam “is a practical handicap that will probably be solved by the development of more efficient fiber bundles.”

That prediction came to fruition with the development of the BeamPath™ NEURO laser. BeamPath™ NEURO allows the laser beam to bend through a flexible fiber lined with layers of microscopic mirrors. The “perfect mirror,” which reflects lights of all wavelengths, was conceived of and developed by researchers at MIT and was initially intended for military applications. The technology was licensed to OmniGuide in 2003.

The laser provides significant benefits to patients by reducing the time required for surgery.

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The UC Neuroscience Institute, a regional center of excellence at UC and University Hospital, is dedicated to patient care, research, education, and the development of new treatments for stroke, brain and spinal tumors, epilepsy, traumatic brain and spinal injury, Alzheimer’s disease, Parkinson’s disease, disorders of the nerves and muscles, disorders of the senses (swallowing, voice, hearing, pain, taste and smell), and psychiatric conditions (bipolar disorder, schizophrenia and depression).

The Mayfield Clinic is recognized as one of the nation's leading physician organizations for clinical care, education, and research of the spine and brain. Supported by 20 neurosurgeons, three neurointensivists, an interventional radiologist, and a pain specialist, the Clinic treats 20,000 patients from 35 states and 13 countries in a typical year. Mayfield's physicians have pioneered surgical procedures and instrumentation that have revolutionized the medical art of neurosurgery for brain tumors and neurovascular diseases and disorders.