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Brain Tumor Program

 
City of Hope researchers are conducting clinical trials of innovative therapies to find more effective treatments for patients with brain tumors.
 
New Clinical Study for Recurrent Glioblastoma Being Conducted at City of Hope

Neural Stem Cells have a natural ability to home to tumor cells throughout the brain. They can be genetically-modified to produce chemotherapy at sites of tumor. Neural stem cells are being investigated as a possible treatment for brain tumors.
 
IRB# 13401: A Phase I Study of Cytosine Deaminase-Expressing Neural Stem Cells with Oral 5-Fluorocytosine and Leucovorin for Treatment of Recurrent High-Grade Gliomas is currently enrolling patients over the age of 18 with recurrent grade III or IV gliomas.
 
During removal or biopsy of tumor, research participants will receive local injections of genetically-modified neural stem cells (NSCs).  These NSCs express the activating enzyme cytosine deaminase (CD), which converts the prodrug 5-fluorocytosine (5-FC) into the chemotherapy agent 5-fluorouracil (5-FU). Research participants will then take 5-FC orally for seven days. As the 5-FC crosses into the brain, the CD-expressing NSCs (which have migrated to residual cancer sites) are expected to convert the 5-FC into 5-FU.  The 5-FU and its toxic metabolites will diffuse out of the NSC to preferentially kill rapidly dividing tumor cells. It is hoped that this strategy will have a large “bystander effect,” meaning that one NSC can kill off many surrounding tumor cells while minimizing toxicity to healthy tissues. Some study patients will also take leucovorin with 5-FC. Leucovorin is an oral medication that can help 5-FU work better against cancer cells.  A Rickham catheter, placed in the brain at the time of surgery, will be used to administer additional doses of NSCs every 2 weeks, followed each time by 7 day courses of oral 5-FC (and possibly leucovorin).
 
Partial Eligibility Requirements:
 
  • Patient has had a prior, histologically-confirmed diagnosis of a grade III or grade IV glioma (including glioblastoma, anaplastic astrocytoma, gliosarcoma, anaplastic oligodendroglioma or anaplastic oligoastrocytoma.
  • Patient is eligible for a debulking craniotomy or biopsy independent of intended treatment with genetically-modified NSCs and 5-FC.
  • Patient's high-grade glioma has recurred or progressed after chemoradiation.
 
If you are interested in learning more about this clinical trial or in referring a patient for enrollment, please contact Alexandra Ching, N.P., at 626-471-9393 or via email at neurosurgery@coh.org.  For a summary of this study including the full eligibility criteria, visit City of Hope’s clinical trials website at http://clinicaltrials.coh.org and enter “13401” in the keyword search.
 

Our Approach - Brain Tumors

As a patient at City of Hope, you have a highly experienced and dedicated team to treat your brain tumor. Whether you have a benign pituitary tumor or an aggressive glioblastoma, we offer a comprehensive, individualized approach to treating brain tumors.
 
Our Brain Tumor Team, including surgeons, medical oncologists and radiation oncologists, creates treatment plans tailored to each patient. Where possible, our surgeons use minimally invasive surgical techniques that minimize injury to the brain and surrounding structure. And our radiation oncologists use state-of-the-art radiation therapy techniques, including Helical TomoTherapy and stereotactic radiosurgery (SRS), which deliver highly localized doses of radiation to primary tumors and metastases while sparing as much normal tissue as possible. 
 
City of Hope researchers are conducting clinical trials of innovative therapies to find more effective treatments for patients with brain tumors. We believe the future of neurosurgery and brain tumor treatment involves the merger of science and technology, and we are developing advanced, creative methods that aim to give the upper hand to patients battling malignant brain tumors.
 
These highly complex approaches include gene therapy and immunotherapy – methods that seek to circumvent barriers that hinder effective treatment. We are particularly excited about studies that harness the neural stem cell’s ability to travel to the tumor and bring chemotherapy to the brain, and the use of genetically modified T cells as an immunotherapy strategy to help your immune system fight off the cancer.
 
In addition, our researchers are developing methods of measuring drug levels in the brain to determine which promising chemotherapy agent should be used in brain tumor patients. We are also developing minimally invasive techniques that allow localized removal of brain tumors and delivery of treatments. 
 
Through our research, our ultimate goal is not to simply improve survival rates, but to eradicate the lethal threat of glioblastoma altogether.
 
 

 
 
 

Brain Tumor Clinical Trials

City of Hope currently has many clinical trials in progress, a number of which address malignant brain tumors. Clinical trials offer patients new and promising experimental treatments not available elsewhere. In fact, nearly one in two patients at City of Hope is part of a clinical trial. These trials evaluate the safety and efficacy of prospective therapies. Participants in clinical trials receive excellent care and are closely monitored. We encourage all brain tumor patients to participate in clinical trials since that will enable us to find better treatments for brain tumors.
 
 
For more information about the studies listed below including eligibility criteria, please call: 626-471-9393. For a summary of these studies including eligibility criteria, visit the City of Hope clinical trials website.
 
Newly Diagnosed
 
11216 
A Phase III clinical trial using a vaccine targeting EGF
An International, Randomized, Double-Blind, Controlled Study of Rindopepinut/GM-CSF with Adjuvant Temozolomide in Patients with Newly Diagnosed, Surgically Resected, EGFRvIII-positive Glioblastoma (The "ACT IV" Study)

Rindopepinut is a vaccine targeted against EGFRvIII gene, which is active in approximately 30% of glioblastoma patients. It is designed to target tumor cells that remain after surgery and chemoradiation.

Patients who are interested in enrolling in this clinical trial need to meet specific eligibility requirements, which include:
 
  • Brain Tumor must test positive for EGFRvIII
  • Participants will be randomized to receive either  vaccine or placebo
 
 
 
11180  
A Phase III Clinical Trial Evaluating DCVax®-Brain, Autologous Dendritic Cells Pulsed with Tumor Lysate Antigen for the Treatment of Glioblastoma
 
13126  
A prospective, Multi-Center Trial of Novo TFF-100A together with Temozolomide Compared to Temozolomide Alone in Patients with Newly Diagnosed Gioblastoma
 
 
Recurrent Disease
 
13401
A Phase I Study of Cytosine Deaminase-Expressing Neural Stem Cells with Oral 5-Fluorocytosine and Leucovorin for Treatment of Recurrent High-Grade Gliomas is currently enrolling patients over the age of 18 with recurrent grade III or IV gliomas.
 
Neural Stem Cells have a natural ability to home to tumor cells throughout the brain. They can be genetically-modified to produce chemotherapy at sites of tumor. Neural stem cells are being investigated as a possible treatment for brain tumors.
 
During removal or biopsy of tumor, research participants will receive local injections of genetically-modified neural stem cells (NSCs).  These NSCs express the activating enzyme cytosine deaminase (CD), which converts the prodrug 5-fluorocytosine (5-FC) into the chemotherapy agent 5-fluorouracil (5-FU). Research participants will then take 5-FC orally for seven days. As the 5-FC crosses into the brain, the CD-expressing NSCs (which have migrated to residual cancer sites) are expected to convert the 5-FC into 5-FU.  The 5-FU and its toxic metabolites will diffuse out of the NSC to preferentially kill rapidly dividing tumor cells. It is hoped that this strategy will have a large “bystander effect,” meaning that one NSC can kill off many surrounding tumor cells while minimizing toxicity to healthy tissues. Some study patients will also take leucovorin with 5-FC. Leucovorin is an oral medication that can help 5-FU work better against cancer cells.  A Rickham catheter, placed in the brain at the time of surgery, will be used to administer additional doses of NSCs every 2 weeks, followed each time by 7 day courses of oral 5-FC (and possibly leucovorin).
 
Partial Eligibility Requirements:
 
  • Patient has had a prior, histologically-confirmed diagnosis of a grade III or grade IV glioma (including glioblastoma, anaplastic astrocytoma, gliosarcoma, anaplastic oligodendroglioma or anaplastic oligoastrocytoma.
  • Patient is eligible for a debulking craniotomy or biopsy independent of intended treatment with genetically-modified NSCs and 5-FC.
  • Patient's high-grade glioma has recurred or progressed after chemoradiation.
 
If you are interested in learning more about this clinical trial or in referring a patient for enrollment, please contact Alexandra Ching, N.P., at 626-471-9393 or via email at neurosurgery@coh.org.  For a summary of this study including the full eligibility criteria, visit City of Hope’s clinical trials website at http://clinicaltrials.coh.org and enter “13401” in the keyword search.
 
13116
A Phase I Gene Therapy Trial of the Safety and Tolerability of Toca 511 in patients Recurrent High Grade Glioma
 
LEARN MORE ABOUT THE TOCA 511 & TOCA FC STUDIES
TOCA 511 & TOCA FC mechanism
This is a very exciting new experimental gene therapy treatment for high grade brain tumors. The basic concept is that a virus (Toca 511) is injected into the tumor. This virus was designed to infect only the brain tumor cells and leave the normal cells alone. When it infects a cell, it adds a gene to the cell which encodes for an enzyme that can convert an antibiotic drug (Toca FC) into a toxic chemotherapy (5-FU), selectively in the tumor. This drug (Toca FC) is given orally every few weeks, and it kills the tumor cells that have enough copies of this enzyme to convert Toca FC to 5-FU. The tumor cells that are infected but don't have enough of the enzyme act as a reservoir - they start the process over again - spreading the infection for a few more weeks, and these cycles are repeated over and over again until the entire tumor is potentially gone.
 
If you were diagnosed with Recurrent High Grade Glioma (HGG) (glioblastoma multiforme, anaplastic astrocytoma, anaplastic oligodendroglioma and anaplastic oligoastrocytoma) that have increased in size following treatment with surgery, radiation therapy and temozolomide. The Toca 511 and Toca FC studies might be the studies for you.
 
Who can participate in the Toca 511 & Toca FC studies? You may qualify for a Toca 511 & Toca FC study if you:
 
  • Are at least 18 years old (upper limit of 80 years in one of the studies)
  • Have recurrent HGG
     
Your doctor will be able to review with you these and other eligibility criteria. For more information about the Toca 511 & Toca FC studies, please contact Jana Portnow M.D. or Behnam Badie M.D. at  626-471-9393 or visit www.tocagen.com.
 
 

Brain Tumor Research

 
At City of Hope, our team of researchers and physicians is dedicated to developing more effective treatments without the burden of toxic side effects. This mission is being carried out with the greatest urgency. It is here where we are conducting translational research — bringing together the most promising science, technologies, clinical studies and patient care in a research continuum that accelerates the development of more effective treatments in our fight against brain tumors and spine tumors. Methods range from mechanical devices to immune-and-gene-based therapies.
 
IMMUNOTHERAPY

Unlike drugs that act by chemically killing cancer cells or halting their growth, immunotherapy uses the body’s own immune system to trigger its ability to seek out and kill cancer. City of Hope scientists are working on several immunotherapy approaches designed to exploit the body’s natural defenses against the disease:

Nanotubes: Small and Lethal Envelopes Used to Kill Cancer

Nanotubes are microscopic technology shaped into tiny tubes about 1/10,000th the width of a human hair.  Behnam Badie, M.D., is working closely with Jacob Berlin, Ph.D., to use nanotubes to deliver a drug called CpG, which activates immune cells called macrophages to recognize and attack tumor cells. Because nanotubes can carry the drug directly to macrophages around the tumor, patients can receive stronger dosages, tolerate their therapy better and recover more quickly.
Principal investigators: Behnam Badie, M.D. ; Jacob Berline, Ph.D. and Leying (Larry) Zhang, Ph.D.
 
Nanoparticles: Guiding Cancer Treatment to the Tumor with Magnets

Behnam Badie, M.D., is collaborating with scientists at Caltech to design a dynamically programmable, low-intensity magnetic field to route and traffic macrophages that have been treated with CpG to tumor sites. In this method, patients would receive CpG-loaded nanoparticles engineered with an iron oxide, so that the macrophages become magnetic.  The magnetic field is generated by a grid, which allows for control over the spatial and temporal profile. Dr. Badie believes that directing CpG-treated macrophages to the areas where they are needed will make this treatment approach even more effective and durable.
Principal investigator: Behnam Badie, M.D.
 
Macrophages and Microglia: Harnessing the Immune System's Clean-up Crew

Macrophages are immune cells that act as scavengers feeding upon dead cells, foreign substances, and other debris in the body. Microglia are macrophages specific to the central nervous system. Microglia are normally inactive but become activated in response to inflammation, infection and trauma. Once activated, they proliferate and migrate to the site of injury. Behnam Badie, M.D., is researching ways to improve outcomes in post-surgical brain tumor patients by re-engineering the microglia to deliver therapeutic agents to the tumor site, killing residual tumor cells. He also aims to extend the life of T cells using microglia and test their efficacy against cancer. This study will likely garner results within a year, setting the stage for Phase I clinical trials.
Principal investigators: Behnam Badie, M.D. , and Leying (Larry) Zhang, Ph.D.
 
T cells: Maximizing a Patient's Immune System

The Cellular Immunotherapy program, led by Stephen J. Forman, M.D., F.A.C.P. , chair, Hematology & Hematopoietic Cell Transplantation, continues to develop innovative treatments that reduce the need for harsh radiation and chemotherapy. One of the most exciting programs underway at City of Hope, the cellular immunotherapy program is developing technology to take T cells from a cancer patient and reprogram them through genetic engineering to target and eradicate the patient’s cancer.
 
Using pioneering technology, we have been able to isolate immune cells from a patient’s blood sample and then engineer those cells to express an artificial receptor that will seek out and attack cancer cells. In the lab, our researchers then grow billions of identical, reprogrammed T cells. In the clinic, the T cells are re-infused into the patient, where they go to work eliminating the cancer. Under Forman’s leadership, City of Hope has conducted the first-ever FDA-authorized clinical trials using reprogrammed T cell therapy for lymphoma, neuroblastoma and glioma.
 
In the glioma study currently underway, patients are infused with engineered T cells that respond to an antigen called CD8. An antigen is any foreign substance to which the body reacts by dispatching antibodies such as T cells. These reprogrammed T cells act as homing devices to take the body’s T cells to the cancer. Although only glioma patients were initially targeted for treatment, researchers have plans to expand this therapy to another brain tumor, medulloblastoma, in pediatric patients.
Principal investigator: Stephen J. Forman, M.D., F.A.C.P.
 
Generation 2 T cells: Universal T cells

One prong of research seeks to formulate a T cell that is protected from rejection by the patient’s own immune system, thus becoming a potential “universal T cell” for patients everywhere. Specifically, Generation 2 T cells are programmed to be accepted without triggering a rejection reaction. By developing such a T cell, our researchers thus create a means to mass produce T cells from one patient on behalf of thousands more. The first glioma patient treated with Generation 2 T cells was in 2007 — the first in the world to be treated with this novel therapy.
Principal investigator: Stephen J. Forman, M.D., F.A.C.P.
 
Generation 3 T-cells: Stacking the Deck Against Cancer

While City of Hope researchers develop the autoimmune-resistant T cell, they plan to adapt it to create Generation 3 T cells. The goal is to develop technology that enables researchers to equip Generation 2 T cells with additional cancer-fighting therapeutic material to strengthen their impact against cancer. John Rossi, Ph.D., chairman and professor of Molecular Biology at City of Hope, and Forman are using interfering ribonucleic acid (RNAi) inside T cells to make them even more effective cancer combatants. A drug using RNAi is set for clinical trials.
Principal investigators: Stephen J. Forman, M.D., F.A.C.P. , and John Rossi, Ph.D.
 
 
STEM CELL THERAPY
 
Neural Stem Cells: One-Way Tickets to Tumors

Neural stem cells selectively travel to tumor cells. Karen Aboody, M.D., has begun groundbreaking research in discovering and exploiting this finding, allowing her to use neural stem cells to selectively deliver therapeutic agents to target tumor cells in the brain. The neural stem cells are genetically modified to produce therapeutic gene products, which effectively infiltrate and kill brain tumor cells.
Principal investigator: Karen Aboody, M.D.
 
Finding Better Treatments for Brain Tumors

Cancers that originate in the brain, termed primary brain tumors, are among the most difficult to treat. The effectiveness of chemotherapy is often hindered by the presence of the blood brain barrier, which prevents most drugs from getting into the brain. Traditional chemotherapy tends to kill both cancer cells and normal cells, often resulting in undesired side effects.
City of Hope researchers are studying ways to target only the brain tumor while limiting damage to normal brain tissue using neural stem cells (NSCs) to deliver anti-cancer treatment directly to tumor cells. NSCs hold the promise of improved treatment for brain cancers because they have a natural ability to seek out and distribute themselves within a tumor, as well as track to other sites of tumor in the brain. Because they can find tumor cells, NSCs may offer a new way to bring more chemotherapy directly to brain tumors. After modifying the NSCs by transferring a therapeutic gene into them, NSCs can serve as vehicles to deliver anti-cancer treatment directly to the primary tumor, as well as potentially to target malignant cells that have spread away from the original tumor site.
Principal investigator: Jana Portnow, M.D.
 
Caption: Neural Stem Cells (NSCs) have a natural tendency to migrate to tumor cells. The orally given inactive drug (prodrug) crosses the blood brain barrier and is converted into a chemotherapeutic agent within the NSC. The agent is then released from the NSC to selectively destroy dividing tumor cells. This strategy has a large ‘bystander effect’ thereby resulting in destroying many surrounding tumor cells with just one NSC.
 
 
GENE THERAPY
 
Creating an Innovative Approach to Therapy

Macrophages are plentiful around tumor sites; however, they aid tumor growth instead of mounting an immune attack.  Behnam Badie, M.D., has found that these tumor-associated macrophages express high levels of an enzyme that inhibits the attack of T cells, the next line of immune response, and he has devised a pioneering concept to use tumor-associated macrophages to deliver genetic material to tumors.
 
The first step is a bone marrow transplant to remove the patient’s existing immune system and replace it with white blood cells that give rise to new modified macrophages. These macrophages are engineered with an inactive gene, which needs a promoter to become active. The modified macrophage will still respond to the tumor’s manipulation by traveling to the tumor site and secreting proteins that stimulate tumor growth. These proteins are the “promoters” that activate the genetic material.
 
At the same time, the patient is administered a prodrug, which is inactive. The activated gene makes material that converts the prodrug into active chemotherapy — which kills tumor cells. Meanwhile, that same active genetic material induces suicide in macrophages, so that they can no longer be employed for tumor growth. And because these modified macrophages are born from the new white blood cells, if the tumor reappears, the new macrophages will halt new tumor growth.
Principal Investigator: Behnam Badie, M.D.
 
 
Gene Therapy for Metastatic Brain Tumors

Despite advances in surgical techniques and the use of radiotherapy and chemotherapy, metastatic brain tumor still remains a disease of high mortality; therefore alternative treatments warrant further investigation. Gene therapy is one such alternative treatment, and is based upon understanding the disease at a molecular level.
 
Gene therapy is an experimental treatment that involves introducing genetic material (DNA or RNA) into a person’s cells to fight disease. The purpose of cancer gene therapy is to eliminate tumor cells while sparing non-tumor cells from the cytotoxic (cell-killing) effects of the cancer treatment. In general, a gene cannot be directly inserted into a person’s cell. It must be delivered to the cell using a carrier, or “vector.” The vectors most commonly used in gene therapy are viruses.
 
Researchers are exploring adeno-associate virus (AAV) as a gene therapy vector because of a number of positive attributes:
  • AAV appears to be non-pathogenic (the virus doesn’t cause disease).
  • It can easily infect most cells.
  • It stably integrates into the host cell DNA at a specific site without causing harmful mutations.
  • It causes very little immune response.
 
Given the above, we propose inserting a suicide gene, which is only expressed in metastatic brain tumors but not in normal cells, into the AAV virus vector. The virus, bearing the suicide gene, then infects cells; however, only metastatic brain tumor cells are affected by the cancer-killing suicide gene protein. This extraordinary approach should provide the selectivity necessary to treat this challenging disease.
Principal investigators: Michael Y. Chen, M.D., Ph.D. , and Rahul Jandial, M.D., Ph.D.
 
 
Convection-enhanced Delivery

Michael Y. Chen, M.D., is studying a gene therapy approach that makes use of the basic biological difference between normal brain tissue and cancer tissue. Tyrosinase promoter is a cellular switch that is highly functional in cancer tissue while inactive in normal brain tissue. The saporin protein is a compound that acts on the “switch” activity, such as the tyrosinase promoter, and converts itself into a therapeutic agent. Dr. Chen’s research team intends to use the tyrosinase promoter as a switch to control the expression of the therapeutic agent saporin that will limit destruction to only cancer cells. The saporin gene will be introduced into a viral gene therapy vector and implanted into the tumor via Convection-enhanced Delivery (CED). CED is the process of continued injection under increased pressure of a fluid containing a therapeutic agent.
Principal investigator: Michael Y. Chen, M.D., Ph.D.
 
 
MINIMALLY INVASIVE APPROACHES
 
Designing Leading-Edge Technology for Delivering Targeted Treatment

Behnam Badie, M.D., has designed a minimally invasive technique to debulk and treat brain tumors without open surgery – making treatment more effective while reducing trauma, the amount of drug used and time involved. The technique involves Badie inserting into the tumor a narrow cylinder, through which a small instrument reaches in and debulks it. The result is a reservoir in the center of the tumor into which a small tube is inserted and left just under the scalp to inject large amounts of targeted therapy.
Principal investigator: Behnam Badie, M.D.
 
 
CHEMOTHERAPY

Uncovering New Targets for Treatment

Macrophages are a first line of immune defense. They detect foreign debris, like bacteria and viruses, and present the proteins from these invaders to T cells, another type of immune cell that then mounts a coordinated attack. Brain tumor cells evade this response and more – they manipulate macrophages to work for them by supplying the tumor with oxygen and nutrients. Macrophages found around tumor cells also secrete proteins that encourage tumor cell growth.
 
Behnam Badie, M.D., and his team are researching new therapies to fight or reverse this manipulated response. They have found a protein secreted by tumor cells called S100B, which they believe plays a feature role in cancer’s ability to attract and subvert macrophages, and they are now working with City of Hope’s High Throughput Screening Core to identify lead compounds that inhibit S100B.
Principal investigator: Behnam Badie, M.D.

Microdialysis Catheter

Delivering substances to the brain has long been a barrier to effective treatment of brain tumors. New targeted therapies that can cross the blood-brain barrier offer promising treatment options. However, difficulties in determining whether these agents can attain therapeutic levels within the brain hinder their screening and evaluation.
 
To determine how chemotherapy drugs perform within the brain, City of Hope researchers are implanting eligible brain tumor patients who volunteer for the study with a microdialysis catheter, which is a temporary small tube that has a semi-permeable membrane at the tip. Through this tube, they can sample the fluid in the brain to measure concentrations of chemotherapy. The results will help reveal how drugs work to fight cancer cells in real time, leading to more effective treatments in the future.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 

Brain Tumor Team

Brain Tumor Information

About Brain Tumors
 
The brain can be affected by many different kinds of growths, which are called tumors. Malignant (cancerous) tumors can arise within the brain itself, or they may begin in another part of the body and spread to the brain (metastasize).

Primary tumors are those that originate in the brain tissue. Secondary tumors begin as cancers in another part of the body, such as the lung, which then metastasize to the brain.

Not all growths are cancerous. Some are not malignant (that is, they are benign tumors). But because the brain is enclosed within the rigid skull, any abnormal tissue growth can cause problems. In recent years, advances in surgery, radiation and chemotherapy have improved outcomes for people with brain tumors.

Advanced diagnostic and surgical techniques, better radiation therapy technologies and other novel treatments are all being used at City of Hope to stop the growth and spread of brain tumors. And in partnership with our patients, we are continually exploring even more effective treatments through clinical trials and research, including more effective chemotherapies, gene therapies and immunotherapies.

Common Forms of Brain Cancer
 
  •     Glioma
  •     Glioma - Astrocytoma
  •     Glioma - Ependymoma
  •     Glioma - Glioblastoma
  •     Medulloblastoma
  •     Meningioma
  •     Metastatic Brain Tumors
  •     Pituitary Tumor (Adenoma)
  •     Schwannoma
 
Risk Factors

Certain factors may increase your risk of developing brain tumors:
 
  •     Male gender - In general, brain tumors are more common in males than females. However, meningiomas are more common in females.
  •     Being Caucasian
  •     Family history - People with family members who have gliomas may be more likely to develop this disease.
  •     Radiation or chemical exposure at work


Brain Tumor Symptoms

A doctor should be seen if the following symptoms appear:
 
  •     Frequent headaches
  •     Vomiting
  •     Loss of appetite
  •     Changes in mood and personality
  •     Changes in ability to think and learn
  •     Seizures
 
 
Diagnosing Brain Tumors
 
Several tests may be used to diagnose brain tumors, including:
 
  • Physical exam and history
  • Neurologic exam 
    The doctor checks for alertness, muscle strength, coordination, reflexes and response to pain. The doctor also examines the eyes to look for swelling caused by a tumor pressing on the nerve that connects the eye and brain.
  • CT or CAT (Computerized Axial Tomography) scan
    This procedure uses a computer connected to an X-ray machine to obtain detailed pictures of areas inside the body. A dye may be used to help visualize organs or tissues more clearly.
  • MRI (magnetic resonance imaging)
    MRI creates a series of detailed pictures of areas inside the body, using the combination of a powerful magnet, radio waves and computer imaging.
  • Biopsy
    Tissue samples are examined under the microscope to determine what types of cells are present.
 
 
 

Brain Tumor Treatment Approaches

The City of Hope Brain Tumor Clinic offers patients the latest, most advanced treatment modalities. Our physicians specialize in the management of a variety of brain tumors, and through close collaboration, provide individualized patient care.
 
Neurosurgery is commonly used to treat patients with brain tumors. Our neurosurgeons have particular interest and expertise in the treatment of nervous system tumors including gliomas, metastatic tumors, meningiomas, pituitary, vestibular schwannomas (acoustic neuromas), skull base, peripheral nerve, spine, and spinal cord tumors. Our modern operating rooms are equipped with latest computerized stereotactic guidance systems and intra-operative imaging and monitoring modalities. Our group has special interest in the use of minimally invasive techniques, functional brain mapping, and stereotactic radiation therapy.
 
We believe that optimum care for patients with malignant brain tumor is only possible through a multidisciplinary approach with active involvement of neurosurgeons, neuro-oncologists, radiation oncologists, support staff and social services.
 
 

 
When applicable, our specialists utilize minimally invasive surgery (MIS) with advanced technologies such as laparoscopy. This surgery features small incisions and potentially:
 
Less blood loss, pain and visible incisions;
 
Shorter hospital stay and recovery time;
 
Fewer complications and quicker return to normal activities.
 
 
One of the following surgical procedures may be used:
 
 
 
 
  • Intraoperative cortical mapping
This technology gives the surgeon a computerized map of key brain regions, including speech, motor and sensory centers. By avoiding these critical areas, the risk of neurological damage is minimized while allowing as much of the tumor to be removed as possible.
  • Image-guided surgical navigation
In certain cases, City of Hope surgeons use this technology to guide the removal of tumors that are difficult to visualize or are located in “high-risk” areas of the brain. Using preoperative magnetic resonance images (MRIs), this highly accurate system allows for more complete removal of the tumor.
  • Endoscopic surgery
Certain brain surgery procedures may be performed through an endoscope - a thin, lighted tube that requires a small opening and accommodates tiny surgical tools. Smaller openings minimize postoperative discomfort and risk of infection. City of Hope researchers are working to develop a miniaturized surgical system that will allow brain surgeries to be even less invasive, with an even lower risk of complications.
 
 
Radiation therapy uses high-energy X-rays or other types of radiation to kill cancer cells. Our Radiation Oncology was the first in the western United States to offer the  Helical TomoTherapy Hi-Art System , one of the first radiation therapy systems of its kind to integrate radiation therapy and tumor imaging capabilities comparable to a diagnostic computed tomography (CT) scan.
 
The Helical TomoTherapy Hi-Art system integrates two types of technology – spiral CT scanning and intensity modulated radiation therapy, or IMRT , that produces hundreds of pencil beams of radiation (each varying in intensity) that rotate spirally around a tumor. The high dose region of radiation can be shaped or sculpted to fit the exact shape of each patient’s tumor, resulting in more effective and potentially curative doses to the cancer. This, in turn, reduces damage to normal tissues and offers fewer complications.
 
TomoTherapy is particularly useful in treating children with certain brain tumors. Because it operates with absolute precision, normal brain tissue is protected, reducing the risk of long-term cognitive problems.
 
 
Chemotherapy
Chemotherapy - the use of anticancer medicines - is another strategy used to combat cancers of the brain. Drugs may be given alone, or in combination with surgery and radiation therapy.
 
Generally, brain tumors are more difficult to treat with drugs than other cancers. This is because most drugs cannot cross the blood-brain barrier, a natural wall that prevents toxic chemicals from reaching brain cells. However, new drugs are being developed that can either cross the barrier or be delivered directly to the brain. An example of this is gene therapy.
 
At City of Hope our clinical and research teams are exploring new ways to treat brain tumors using gene therapy which is based upon understanding the disease at a molecular level. Gene therapy is an experimental treatment that involves introducing genetic material (DNA or RNA) into a person’s cells to fight disease. The purpose of cancer gene therapy is to eliminate tumor cells while sparing non-tumor cells from the cytotoxic (cell-killing) effects of the cancer treatment.
 
Learn more about City of Hope’s gene therapy research or active brain tumor clinical trials .

Brain Tumor Resources

All of our patients have access to City of Hope's Sheri & Les Biller Patient and Family Resource Center , which offers a wide array of support and educational services. Patients and loved ones may work with a coordinated group of social workers, psychiatrists, psychologists, patient navigators, pain management specialists and spiritual care providers at the center, as well as participate in programs such as music therapy, meditation and many others.
 
Additional Resources
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Hear Dr. Behnam Badie's interview on KPCC-Southern California Public Radio: Nanotechnology May Offer New Hope For Cancer Patients .
 

Support this program

It takes the help of a lot of caring people to make hope a reality for our patients. City of Hope was founded by individuals' philanthropic efforts 100 years ago. Their efforts − and those of our supporters today − have built the foundation for the care we provide and the research we conduct. It enables us to strive for new breakthroughs and better therapies − helping more people enjoy longer, better lives.

For more information on supporting this specific program, please contact us below.

Kimberly Wah
Director
Phone: 213-241-7275
Email: kwah@coh.org

 
 

Brain Tumors

Brain Tumor Program

 
City of Hope researchers are conducting clinical trials of innovative therapies to find more effective treatments for patients with brain tumors.
 
New Clinical Study for Recurrent Glioblastoma Being Conducted at City of Hope

Neural Stem Cells have a natural ability to home to tumor cells throughout the brain. They can be genetically-modified to produce chemotherapy at sites of tumor. Neural stem cells are being investigated as a possible treatment for brain tumors.
 
IRB# 13401: A Phase I Study of Cytosine Deaminase-Expressing Neural Stem Cells with Oral 5-Fluorocytosine and Leucovorin for Treatment of Recurrent High-Grade Gliomas is currently enrolling patients over the age of 18 with recurrent grade III or IV gliomas.
 
During removal or biopsy of tumor, research participants will receive local injections of genetically-modified neural stem cells (NSCs).  These NSCs express the activating enzyme cytosine deaminase (CD), which converts the prodrug 5-fluorocytosine (5-FC) into the chemotherapy agent 5-fluorouracil (5-FU). Research participants will then take 5-FC orally for seven days. As the 5-FC crosses into the brain, the CD-expressing NSCs (which have migrated to residual cancer sites) are expected to convert the 5-FC into 5-FU.  The 5-FU and its toxic metabolites will diffuse out of the NSC to preferentially kill rapidly dividing tumor cells. It is hoped that this strategy will have a large “bystander effect,” meaning that one NSC can kill off many surrounding tumor cells while minimizing toxicity to healthy tissues. Some study patients will also take leucovorin with 5-FC. Leucovorin is an oral medication that can help 5-FU work better against cancer cells.  A Rickham catheter, placed in the brain at the time of surgery, will be used to administer additional doses of NSCs every 2 weeks, followed each time by 7 day courses of oral 5-FC (and possibly leucovorin).
 
Partial Eligibility Requirements:
 
  • Patient has had a prior, histologically-confirmed diagnosis of a grade III or grade IV glioma (including glioblastoma, anaplastic astrocytoma, gliosarcoma, anaplastic oligodendroglioma or anaplastic oligoastrocytoma.
  • Patient is eligible for a debulking craniotomy or biopsy independent of intended treatment with genetically-modified NSCs and 5-FC.
  • Patient's high-grade glioma has recurred or progressed after chemoradiation.
 
If you are interested in learning more about this clinical trial or in referring a patient for enrollment, please contact Alexandra Ching, N.P., at 626-471-9393 or via email at neurosurgery@coh.org.  For a summary of this study including the full eligibility criteria, visit City of Hope’s clinical trials website at http://clinicaltrials.coh.org and enter “13401” in the keyword search.
 

Our Approach

Our Approach - Brain Tumors

As a patient at City of Hope, you have a highly experienced and dedicated team to treat your brain tumor. Whether you have a benign pituitary tumor or an aggressive glioblastoma, we offer a comprehensive, individualized approach to treating brain tumors.
 
Our Brain Tumor Team, including surgeons, medical oncologists and radiation oncologists, creates treatment plans tailored to each patient. Where possible, our surgeons use minimally invasive surgical techniques that minimize injury to the brain and surrounding structure. And our radiation oncologists use state-of-the-art radiation therapy techniques, including Helical TomoTherapy and stereotactic radiosurgery (SRS), which deliver highly localized doses of radiation to primary tumors and metastases while sparing as much normal tissue as possible. 
 
City of Hope researchers are conducting clinical trials of innovative therapies to find more effective treatments for patients with brain tumors. We believe the future of neurosurgery and brain tumor treatment involves the merger of science and technology, and we are developing advanced, creative methods that aim to give the upper hand to patients battling malignant brain tumors.
 
These highly complex approaches include gene therapy and immunotherapy – methods that seek to circumvent barriers that hinder effective treatment. We are particularly excited about studies that harness the neural stem cell’s ability to travel to the tumor and bring chemotherapy to the brain, and the use of genetically modified T cells as an immunotherapy strategy to help your immune system fight off the cancer.
 
In addition, our researchers are developing methods of measuring drug levels in the brain to determine which promising chemotherapy agent should be used in brain tumor patients. We are also developing minimally invasive techniques that allow localized removal of brain tumors and delivery of treatments. 
 
Through our research, our ultimate goal is not to simply improve survival rates, but to eradicate the lethal threat of glioblastoma altogether.
 
 

 
 
 

Clinical Trials

Brain Tumor Clinical Trials

City of Hope currently has many clinical trials in progress, a number of which address malignant brain tumors. Clinical trials offer patients new and promising experimental treatments not available elsewhere. In fact, nearly one in two patients at City of Hope is part of a clinical trial. These trials evaluate the safety and efficacy of prospective therapies. Participants in clinical trials receive excellent care and are closely monitored. We encourage all brain tumor patients to participate in clinical trials since that will enable us to find better treatments for brain tumors.
 
 
For more information about the studies listed below including eligibility criteria, please call: 626-471-9393. For a summary of these studies including eligibility criteria, visit the City of Hope clinical trials website.
 
Newly Diagnosed
 
11216 
A Phase III clinical trial using a vaccine targeting EGF
An International, Randomized, Double-Blind, Controlled Study of Rindopepinut/GM-CSF with Adjuvant Temozolomide in Patients with Newly Diagnosed, Surgically Resected, EGFRvIII-positive Glioblastoma (The "ACT IV" Study)

Rindopepinut is a vaccine targeted against EGFRvIII gene, which is active in approximately 30% of glioblastoma patients. It is designed to target tumor cells that remain after surgery and chemoradiation.

Patients who are interested in enrolling in this clinical trial need to meet specific eligibility requirements, which include:
 
  • Brain Tumor must test positive for EGFRvIII
  • Participants will be randomized to receive either  vaccine or placebo
 
 
 
11180  
A Phase III Clinical Trial Evaluating DCVax®-Brain, Autologous Dendritic Cells Pulsed with Tumor Lysate Antigen for the Treatment of Glioblastoma
 
13126  
A prospective, Multi-Center Trial of Novo TFF-100A together with Temozolomide Compared to Temozolomide Alone in Patients with Newly Diagnosed Gioblastoma
 
 
Recurrent Disease
 
13401
A Phase I Study of Cytosine Deaminase-Expressing Neural Stem Cells with Oral 5-Fluorocytosine and Leucovorin for Treatment of Recurrent High-Grade Gliomas is currently enrolling patients over the age of 18 with recurrent grade III or IV gliomas.
 
Neural Stem Cells have a natural ability to home to tumor cells throughout the brain. They can be genetically-modified to produce chemotherapy at sites of tumor. Neural stem cells are being investigated as a possible treatment for brain tumors.
 
During removal or biopsy of tumor, research participants will receive local injections of genetically-modified neural stem cells (NSCs).  These NSCs express the activating enzyme cytosine deaminase (CD), which converts the prodrug 5-fluorocytosine (5-FC) into the chemotherapy agent 5-fluorouracil (5-FU). Research participants will then take 5-FC orally for seven days. As the 5-FC crosses into the brain, the CD-expressing NSCs (which have migrated to residual cancer sites) are expected to convert the 5-FC into 5-FU.  The 5-FU and its toxic metabolites will diffuse out of the NSC to preferentially kill rapidly dividing tumor cells. It is hoped that this strategy will have a large “bystander effect,” meaning that one NSC can kill off many surrounding tumor cells while minimizing toxicity to healthy tissues. Some study patients will also take leucovorin with 5-FC. Leucovorin is an oral medication that can help 5-FU work better against cancer cells.  A Rickham catheter, placed in the brain at the time of surgery, will be used to administer additional doses of NSCs every 2 weeks, followed each time by 7 day courses of oral 5-FC (and possibly leucovorin).
 
Partial Eligibility Requirements:
 
  • Patient has had a prior, histologically-confirmed diagnosis of a grade III or grade IV glioma (including glioblastoma, anaplastic astrocytoma, gliosarcoma, anaplastic oligodendroglioma or anaplastic oligoastrocytoma.
  • Patient is eligible for a debulking craniotomy or biopsy independent of intended treatment with genetically-modified NSCs and 5-FC.
  • Patient's high-grade glioma has recurred or progressed after chemoradiation.
 
If you are interested in learning more about this clinical trial or in referring a patient for enrollment, please contact Alexandra Ching, N.P., at 626-471-9393 or via email at neurosurgery@coh.org.  For a summary of this study including the full eligibility criteria, visit City of Hope’s clinical trials website at http://clinicaltrials.coh.org and enter “13401” in the keyword search.
 
13116
A Phase I Gene Therapy Trial of the Safety and Tolerability of Toca 511 in patients Recurrent High Grade Glioma
 
LEARN MORE ABOUT THE TOCA 511 & TOCA FC STUDIES
TOCA 511 & TOCA FC mechanism
This is a very exciting new experimental gene therapy treatment for high grade brain tumors. The basic concept is that a virus (Toca 511) is injected into the tumor. This virus was designed to infect only the brain tumor cells and leave the normal cells alone. When it infects a cell, it adds a gene to the cell which encodes for an enzyme that can convert an antibiotic drug (Toca FC) into a toxic chemotherapy (5-FU), selectively in the tumor. This drug (Toca FC) is given orally every few weeks, and it kills the tumor cells that have enough copies of this enzyme to convert Toca FC to 5-FU. The tumor cells that are infected but don't have enough of the enzyme act as a reservoir - they start the process over again - spreading the infection for a few more weeks, and these cycles are repeated over and over again until the entire tumor is potentially gone.
 
If you were diagnosed with Recurrent High Grade Glioma (HGG) (glioblastoma multiforme, anaplastic astrocytoma, anaplastic oligodendroglioma and anaplastic oligoastrocytoma) that have increased in size following treatment with surgery, radiation therapy and temozolomide. The Toca 511 and Toca FC studies might be the studies for you.
 
Who can participate in the Toca 511 & Toca FC studies? You may qualify for a Toca 511 & Toca FC study if you:
 
  • Are at least 18 years old (upper limit of 80 years in one of the studies)
  • Have recurrent HGG
     
Your doctor will be able to review with you these and other eligibility criteria. For more information about the Toca 511 & Toca FC studies, please contact Jana Portnow M.D. or Behnam Badie M.D. at  626-471-9393 or visit www.tocagen.com.
 
 

Research

Brain Tumor Research

 
At City of Hope, our team of researchers and physicians is dedicated to developing more effective treatments without the burden of toxic side effects. This mission is being carried out with the greatest urgency. It is here where we are conducting translational research — bringing together the most promising science, technologies, clinical studies and patient care in a research continuum that accelerates the development of more effective treatments in our fight against brain tumors and spine tumors. Methods range from mechanical devices to immune-and-gene-based therapies.
 
IMMUNOTHERAPY

Unlike drugs that act by chemically killing cancer cells or halting their growth, immunotherapy uses the body’s own immune system to trigger its ability to seek out and kill cancer. City of Hope scientists are working on several immunotherapy approaches designed to exploit the body’s natural defenses against the disease:

Nanotubes: Small and Lethal Envelopes Used to Kill Cancer

Nanotubes are microscopic technology shaped into tiny tubes about 1/10,000th the width of a human hair.  Behnam Badie, M.D., is working closely with Jacob Berlin, Ph.D., to use nanotubes to deliver a drug called CpG, which activates immune cells called macrophages to recognize and attack tumor cells. Because nanotubes can carry the drug directly to macrophages around the tumor, patients can receive stronger dosages, tolerate their therapy better and recover more quickly.
Principal investigators: Behnam Badie, M.D. ; Jacob Berline, Ph.D. and Leying (Larry) Zhang, Ph.D.
 
Nanoparticles: Guiding Cancer Treatment to the Tumor with Magnets

Behnam Badie, M.D., is collaborating with scientists at Caltech to design a dynamically programmable, low-intensity magnetic field to route and traffic macrophages that have been treated with CpG to tumor sites. In this method, patients would receive CpG-loaded nanoparticles engineered with an iron oxide, so that the macrophages become magnetic.  The magnetic field is generated by a grid, which allows for control over the spatial and temporal profile. Dr. Badie believes that directing CpG-treated macrophages to the areas where they are needed will make this treatment approach even more effective and durable.
Principal investigator: Behnam Badie, M.D.
 
Macrophages and Microglia: Harnessing the Immune System's Clean-up Crew

Macrophages are immune cells that act as scavengers feeding upon dead cells, foreign substances, and other debris in the body. Microglia are macrophages specific to the central nervous system. Microglia are normally inactive but become activated in response to inflammation, infection and trauma. Once activated, they proliferate and migrate to the site of injury. Behnam Badie, M.D., is researching ways to improve outcomes in post-surgical brain tumor patients by re-engineering the microglia to deliver therapeutic agents to the tumor site, killing residual tumor cells. He also aims to extend the life of T cells using microglia and test their efficacy against cancer. This study will likely garner results within a year, setting the stage for Phase I clinical trials.
Principal investigators: Behnam Badie, M.D. , and Leying (Larry) Zhang, Ph.D.
 
T cells: Maximizing a Patient's Immune System

The Cellular Immunotherapy program, led by Stephen J. Forman, M.D., F.A.C.P. , chair, Hematology & Hematopoietic Cell Transplantation, continues to develop innovative treatments that reduce the need for harsh radiation and chemotherapy. One of the most exciting programs underway at City of Hope, the cellular immunotherapy program is developing technology to take T cells from a cancer patient and reprogram them through genetic engineering to target and eradicate the patient’s cancer.
 
Using pioneering technology, we have been able to isolate immune cells from a patient’s blood sample and then engineer those cells to express an artificial receptor that will seek out and attack cancer cells. In the lab, our researchers then grow billions of identical, reprogrammed T cells. In the clinic, the T cells are re-infused into the patient, where they go to work eliminating the cancer. Under Forman’s leadership, City of Hope has conducted the first-ever FDA-authorized clinical trials using reprogrammed T cell therapy for lymphoma, neuroblastoma and glioma.
 
In the glioma study currently underway, patients are infused with engineered T cells that respond to an antigen called CD8. An antigen is any foreign substance to which the body reacts by dispatching antibodies such as T cells. These reprogrammed T cells act as homing devices to take the body’s T cells to the cancer. Although only glioma patients were initially targeted for treatment, researchers have plans to expand this therapy to another brain tumor, medulloblastoma, in pediatric patients.
Principal investigator: Stephen J. Forman, M.D., F.A.C.P.
 
Generation 2 T cells: Universal T cells

One prong of research seeks to formulate a T cell that is protected from rejection by the patient’s own immune system, thus becoming a potential “universal T cell” for patients everywhere. Specifically, Generation 2 T cells are programmed to be accepted without triggering a rejection reaction. By developing such a T cell, our researchers thus create a means to mass produce T cells from one patient on behalf of thousands more. The first glioma patient treated with Generation 2 T cells was in 2007 — the first in the world to be treated with this novel therapy.
Principal investigator: Stephen J. Forman, M.D., F.A.C.P.
 
Generation 3 T-cells: Stacking the Deck Against Cancer

While City of Hope researchers develop the autoimmune-resistant T cell, they plan to adapt it to create Generation 3 T cells. The goal is to develop technology that enables researchers to equip Generation 2 T cells with additional cancer-fighting therapeutic material to strengthen their impact against cancer. John Rossi, Ph.D., chairman and professor of Molecular Biology at City of Hope, and Forman are using interfering ribonucleic acid (RNAi) inside T cells to make them even more effective cancer combatants. A drug using RNAi is set for clinical trials.
Principal investigators: Stephen J. Forman, M.D., F.A.C.P. , and John Rossi, Ph.D.
 
 
STEM CELL THERAPY
 
Neural Stem Cells: One-Way Tickets to Tumors

Neural stem cells selectively travel to tumor cells. Karen Aboody, M.D., has begun groundbreaking research in discovering and exploiting this finding, allowing her to use neural stem cells to selectively deliver therapeutic agents to target tumor cells in the brain. The neural stem cells are genetically modified to produce therapeutic gene products, which effectively infiltrate and kill brain tumor cells.
Principal investigator: Karen Aboody, M.D.
 
Finding Better Treatments for Brain Tumors

Cancers that originate in the brain, termed primary brain tumors, are among the most difficult to treat. The effectiveness of chemotherapy is often hindered by the presence of the blood brain barrier, which prevents most drugs from getting into the brain. Traditional chemotherapy tends to kill both cancer cells and normal cells, often resulting in undesired side effects.
City of Hope researchers are studying ways to target only the brain tumor while limiting damage to normal brain tissue using neural stem cells (NSCs) to deliver anti-cancer treatment directly to tumor cells. NSCs hold the promise of improved treatment for brain cancers because they have a natural ability to seek out and distribute themselves within a tumor, as well as track to other sites of tumor in the brain. Because they can find tumor cells, NSCs may offer a new way to bring more chemotherapy directly to brain tumors. After modifying the NSCs by transferring a therapeutic gene into them, NSCs can serve as vehicles to deliver anti-cancer treatment directly to the primary tumor, as well as potentially to target malignant cells that have spread away from the original tumor site.
Principal investigator: Jana Portnow, M.D.
 
Caption: Neural Stem Cells (NSCs) have a natural tendency to migrate to tumor cells. The orally given inactive drug (prodrug) crosses the blood brain barrier and is converted into a chemotherapeutic agent within the NSC. The agent is then released from the NSC to selectively destroy dividing tumor cells. This strategy has a large ‘bystander effect’ thereby resulting in destroying many surrounding tumor cells with just one NSC.
 
 
GENE THERAPY
 
Creating an Innovative Approach to Therapy

Macrophages are plentiful around tumor sites; however, they aid tumor growth instead of mounting an immune attack.  Behnam Badie, M.D., has found that these tumor-associated macrophages express high levels of an enzyme that inhibits the attack of T cells, the next line of immune response, and he has devised a pioneering concept to use tumor-associated macrophages to deliver genetic material to tumors.
 
The first step is a bone marrow transplant to remove the patient’s existing immune system and replace it with white blood cells that give rise to new modified macrophages. These macrophages are engineered with an inactive gene, which needs a promoter to become active. The modified macrophage will still respond to the tumor’s manipulation by traveling to the tumor site and secreting proteins that stimulate tumor growth. These proteins are the “promoters” that activate the genetic material.
 
At the same time, the patient is administered a prodrug, which is inactive. The activated gene makes material that converts the prodrug into active chemotherapy — which kills tumor cells. Meanwhile, that same active genetic material induces suicide in macrophages, so that they can no longer be employed for tumor growth. And because these modified macrophages are born from the new white blood cells, if the tumor reappears, the new macrophages will halt new tumor growth.
Principal Investigator: Behnam Badie, M.D.
 
 
Gene Therapy for Metastatic Brain Tumors

Despite advances in surgical techniques and the use of radiotherapy and chemotherapy, metastatic brain tumor still remains a disease of high mortality; therefore alternative treatments warrant further investigation. Gene therapy is one such alternative treatment, and is based upon understanding the disease at a molecular level.
 
Gene therapy is an experimental treatment that involves introducing genetic material (DNA or RNA) into a person’s cells to fight disease. The purpose of cancer gene therapy is to eliminate tumor cells while sparing non-tumor cells from the cytotoxic (cell-killing) effects of the cancer treatment. In general, a gene cannot be directly inserted into a person’s cell. It must be delivered to the cell using a carrier, or “vector.” The vectors most commonly used in gene therapy are viruses.
 
Researchers are exploring adeno-associate virus (AAV) as a gene therapy vector because of a number of positive attributes:
  • AAV appears to be non-pathogenic (the virus doesn’t cause disease).
  • It can easily infect most cells.
  • It stably integrates into the host cell DNA at a specific site without causing harmful mutations.
  • It causes very little immune response.
 
Given the above, we propose inserting a suicide gene, which is only expressed in metastatic brain tumors but not in normal cells, into the AAV virus vector. The virus, bearing the suicide gene, then infects cells; however, only metastatic brain tumor cells are affected by the cancer-killing suicide gene protein. This extraordinary approach should provide the selectivity necessary to treat this challenging disease.
Principal investigators: Michael Y. Chen, M.D., Ph.D. , and Rahul Jandial, M.D., Ph.D.
 
 
Convection-enhanced Delivery

Michael Y. Chen, M.D., is studying a gene therapy approach that makes use of the basic biological difference between normal brain tissue and cancer tissue. Tyrosinase promoter is a cellular switch that is highly functional in cancer tissue while inactive in normal brain tissue. The saporin protein is a compound that acts on the “switch” activity, such as the tyrosinase promoter, and converts itself into a therapeutic agent. Dr. Chen’s research team intends to use the tyrosinase promoter as a switch to control the expression of the therapeutic agent saporin that will limit destruction to only cancer cells. The saporin gene will be introduced into a viral gene therapy vector and implanted into the tumor via Convection-enhanced Delivery (CED). CED is the process of continued injection under increased pressure of a fluid containing a therapeutic agent.
Principal investigator: Michael Y. Chen, M.D., Ph.D.
 
 
MINIMALLY INVASIVE APPROACHES
 
Designing Leading-Edge Technology for Delivering Targeted Treatment

Behnam Badie, M.D., has designed a minimally invasive technique to debulk and treat brain tumors without open surgery – making treatment more effective while reducing trauma, the amount of drug used and time involved. The technique involves Badie inserting into the tumor a narrow cylinder, through which a small instrument reaches in and debulks it. The result is a reservoir in the center of the tumor into which a small tube is inserted and left just under the scalp to inject large amounts of targeted therapy.
Principal investigator: Behnam Badie, M.D.
 
 
CHEMOTHERAPY

Uncovering New Targets for Treatment

Macrophages are a first line of immune defense. They detect foreign debris, like bacteria and viruses, and present the proteins from these invaders to T cells, another type of immune cell that then mounts a coordinated attack. Brain tumor cells evade this response and more – they manipulate macrophages to work for them by supplying the tumor with oxygen and nutrients. Macrophages found around tumor cells also secrete proteins that encourage tumor cell growth.
 
Behnam Badie, M.D., and his team are researching new therapies to fight or reverse this manipulated response. They have found a protein secreted by tumor cells called S100B, which they believe plays a feature role in cancer’s ability to attract and subvert macrophages, and they are now working with City of Hope’s High Throughput Screening Core to identify lead compounds that inhibit S100B.
Principal investigator: Behnam Badie, M.D.

Microdialysis Catheter

Delivering substances to the brain has long been a barrier to effective treatment of brain tumors. New targeted therapies that can cross the blood-brain barrier offer promising treatment options. However, difficulties in determining whether these agents can attain therapeutic levels within the brain hinder their screening and evaluation.
 
To determine how chemotherapy drugs perform within the brain, City of Hope researchers are implanting eligible brain tumor patients who volunteer for the study with a microdialysis catheter, which is a temporary small tube that has a semi-permeable membrane at the tip. Through this tube, they can sample the fluid in the brain to measure concentrations of chemotherapy. The results will help reveal how drugs work to fight cancer cells in real time, leading to more effective treatments in the future.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 

Brain Tumor Team

Brain Tumor Team

Brain Tumor Information

Brain Tumor Information

About Brain Tumors
 
The brain can be affected by many different kinds of growths, which are called tumors. Malignant (cancerous) tumors can arise within the brain itself, or they may begin in another part of the body and spread to the brain (metastasize).

Primary tumors are those that originate in the brain tissue. Secondary tumors begin as cancers in another part of the body, such as the lung, which then metastasize to the brain.

Not all growths are cancerous. Some are not malignant (that is, they are benign tumors). But because the brain is enclosed within the rigid skull, any abnormal tissue growth can cause problems. In recent years, advances in surgery, radiation and chemotherapy have improved outcomes for people with brain tumors.

Advanced diagnostic and surgical techniques, better radiation therapy technologies and other novel treatments are all being used at City of Hope to stop the growth and spread of brain tumors. And in partnership with our patients, we are continually exploring even more effective treatments through clinical trials and research, including more effective chemotherapies, gene therapies and immunotherapies.

Common Forms of Brain Cancer
 
  •     Glioma
  •     Glioma - Astrocytoma
  •     Glioma - Ependymoma
  •     Glioma - Glioblastoma
  •     Medulloblastoma
  •     Meningioma
  •     Metastatic Brain Tumors
  •     Pituitary Tumor (Adenoma)
  •     Schwannoma
 
Risk Factors

Certain factors may increase your risk of developing brain tumors:
 
  •     Male gender - In general, brain tumors are more common in males than females. However, meningiomas are more common in females.
  •     Being Caucasian
  •     Family history - People with family members who have gliomas may be more likely to develop this disease.
  •     Radiation or chemical exposure at work


Brain Tumor Symptoms

A doctor should be seen if the following symptoms appear:
 
  •     Frequent headaches
  •     Vomiting
  •     Loss of appetite
  •     Changes in mood and personality
  •     Changes in ability to think and learn
  •     Seizures
 
 
Diagnosing Brain Tumors
 
Several tests may be used to diagnose brain tumors, including:
 
  • Physical exam and history
  • Neurologic exam 
    The doctor checks for alertness, muscle strength, coordination, reflexes and response to pain. The doctor also examines the eyes to look for swelling caused by a tumor pressing on the nerve that connects the eye and brain.
  • CT or CAT (Computerized Axial Tomography) scan
    This procedure uses a computer connected to an X-ray machine to obtain detailed pictures of areas inside the body. A dye may be used to help visualize organs or tissues more clearly.
  • MRI (magnetic resonance imaging)
    MRI creates a series of detailed pictures of areas inside the body, using the combination of a powerful magnet, radio waves and computer imaging.
  • Biopsy
    Tissue samples are examined under the microscope to determine what types of cells are present.
 
 
 

Treatments

Brain Tumor Treatment Approaches

The City of Hope Brain Tumor Clinic offers patients the latest, most advanced treatment modalities. Our physicians specialize in the management of a variety of brain tumors, and through close collaboration, provide individualized patient care.
 
Neurosurgery is commonly used to treat patients with brain tumors. Our neurosurgeons have particular interest and expertise in the treatment of nervous system tumors including gliomas, metastatic tumors, meningiomas, pituitary, vestibular schwannomas (acoustic neuromas), skull base, peripheral nerve, spine, and spinal cord tumors. Our modern operating rooms are equipped with latest computerized stereotactic guidance systems and intra-operative imaging and monitoring modalities. Our group has special interest in the use of minimally invasive techniques, functional brain mapping, and stereotactic radiation therapy.
 
We believe that optimum care for patients with malignant brain tumor is only possible through a multidisciplinary approach with active involvement of neurosurgeons, neuro-oncologists, radiation oncologists, support staff and social services.
 
 

 
When applicable, our specialists utilize minimally invasive surgery (MIS) with advanced technologies such as laparoscopy. This surgery features small incisions and potentially:
 
Less blood loss, pain and visible incisions;
 
Shorter hospital stay and recovery time;
 
Fewer complications and quicker return to normal activities.
 
 
One of the following surgical procedures may be used:
 
 
 
 
  • Intraoperative cortical mapping
This technology gives the surgeon a computerized map of key brain regions, including speech, motor and sensory centers. By avoiding these critical areas, the risk of neurological damage is minimized while allowing as much of the tumor to be removed as possible.
  • Image-guided surgical navigation
In certain cases, City of Hope surgeons use this technology to guide the removal of tumors that are difficult to visualize or are located in “high-risk” areas of the brain. Using preoperative magnetic resonance images (MRIs), this highly accurate system allows for more complete removal of the tumor.
  • Endoscopic surgery
Certain brain surgery procedures may be performed through an endoscope - a thin, lighted tube that requires a small opening and accommodates tiny surgical tools. Smaller openings minimize postoperative discomfort and risk of infection. City of Hope researchers are working to develop a miniaturized surgical system that will allow brain surgeries to be even less invasive, with an even lower risk of complications.
 
 
Radiation therapy uses high-energy X-rays or other types of radiation to kill cancer cells. Our Radiation Oncology was the first in the western United States to offer the  Helical TomoTherapy Hi-Art System , one of the first radiation therapy systems of its kind to integrate radiation therapy and tumor imaging capabilities comparable to a diagnostic computed tomography (CT) scan.
 
The Helical TomoTherapy Hi-Art system integrates two types of technology – spiral CT scanning and intensity modulated radiation therapy, or IMRT , that produces hundreds of pencil beams of radiation (each varying in intensity) that rotate spirally around a tumor. The high dose region of radiation can be shaped or sculpted to fit the exact shape of each patient’s tumor, resulting in more effective and potentially curative doses to the cancer. This, in turn, reduces damage to normal tissues and offers fewer complications.
 
TomoTherapy is particularly useful in treating children with certain brain tumors. Because it operates with absolute precision, normal brain tissue is protected, reducing the risk of long-term cognitive problems.
 
 
Chemotherapy
Chemotherapy - the use of anticancer medicines - is another strategy used to combat cancers of the brain. Drugs may be given alone, or in combination with surgery and radiation therapy.
 
Generally, brain tumors are more difficult to treat with drugs than other cancers. This is because most drugs cannot cross the blood-brain barrier, a natural wall that prevents toxic chemicals from reaching brain cells. However, new drugs are being developed that can either cross the barrier or be delivered directly to the brain. An example of this is gene therapy.
 
At City of Hope our clinical and research teams are exploring new ways to treat brain tumors using gene therapy which is based upon understanding the disease at a molecular level. Gene therapy is an experimental treatment that involves introducing genetic material (DNA or RNA) into a person’s cells to fight disease. The purpose of cancer gene therapy is to eliminate tumor cells while sparing non-tumor cells from the cytotoxic (cell-killing) effects of the cancer treatment.
 
Learn more about City of Hope’s gene therapy research or active brain tumor clinical trials .

Resources

Brain Tumor Resources

All of our patients have access to City of Hope's Sheri & Les Biller Patient and Family Resource Center , which offers a wide array of support and educational services. Patients and loved ones may work with a coordinated group of social workers, psychiatrists, psychologists, patient navigators, pain management specialists and spiritual care providers at the center, as well as participate in programs such as music therapy, meditation and many others.
 
Additional Resources
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Hear Dr. Behnam Badie's interview on KPCC-Southern California Public Radio: Nanotechnology May Offer New Hope For Cancer Patients .
 

Support This Program

Support this program

It takes the help of a lot of caring people to make hope a reality for our patients. City of Hope was founded by individuals' philanthropic efforts 100 years ago. Their efforts − and those of our supporters today − have built the foundation for the care we provide and the research we conduct. It enables us to strive for new breakthroughs and better therapies − helping more people enjoy longer, better lives.

For more information on supporting this specific program, please contact us below.

Kimberly Wah
Director
Phone: 213-241-7275
Email: kwah@coh.org

 
 
Quick Links
Refer a Patient
Physicians can choose a number of options to refer a patient:

  • Call 800-826-HOPE (4673) to speak with a patient referral specialist.
  • Fax the patient face sheet to 626-301-8432
  • Complete an online callback request form
 
Featured Videos
Brain Tumor Medical Minute
Division of Neurosurgery
City of Hope has some of the most advanced tools for the surgical removal of brain and spine tumors. Learn how these tools have enabled surgery of the highest precision while minimizing adverse outcomes.
 
City of Hope’s Division of Neurosurgery focuses on surgical treatment of both benign and malignant brain, spine and pituitary tumors. Our physicians are nationally-recognized experts in neurosurgery and neuro-oncology, and employ today’s leading edge therapies.

For questions or additional information, please call 626-471-7100.


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  • The body’s immune system is usually adept at attacking outside invaders such as bacteria and viruses. But because cancer originates from the body’s own cells, the immune system can fail to see it as foreign. As a result, the body’s most powerful ally can remain largely idle against cancer as the disease progres...
  • On Jan. 1, 2015, five City of Hope patients who have journeyed through cancer will welcome the new year with their loved ones atop City of Hope’s Tournament of Roses Parade float. The theme of the float is “Made Possible by HOPE.” The theme of the parade is “Inspiring Stories.” Her...
  • Are you thinking about switching from traditional cigarettes to e-cigarettes for the Great American Smokeout? Are you thinking that might be a better option than the traditional quit-smoking route? Think again. For lung expert Brian Tiep, M.D., the dislike and distrust he feels for e-cigs comes down to this: Th...
  • Hematologist Robert Chen, M.D., is boosting scientific discovery at City of Hope and, by extension, across the nation. Just ask the National Cancer Institute. The institution recently awarded Chen the much-sought-after Clinical Investigator Team Leadership Award for boosting scientific discovery at City of Hope...
  • Great strides have been made in treating cancer – including lung cancer – but by the time people show symptoms of the disease, the cancer has usually advanced. That’s because, at early stages, lung cancer has no symptoms. Only recently has lung cancer screening become an option. (Read more about the risks...
  • Identifying cures for currently incurable diseases and providing patients with safe, fast and potentially lifesaving treatments is the focus of City of Hope’s new Alpha Clinic for Cell Therapy and Innovation (ACT-I). The clinic is funded by an $8 million, five-year grant from the California Institute for Regene...
  • Cancer is a couple’s disease. It affects not just the person diagnosed, but his or her partner as well. It also affects the ability of both people to communicate effectively. The Couples Coping with Cancer Together program at City of Hope teaches couples how to communicate and solve problems as a unit. He...
  • Chemotherapy drugs work by either killing cancer cells or by stopping them from multiplying, that is, dividing. Some of the more powerful drugs used to treat cancer do their job by interfering with the cancer cells’ DNA and RNA growth, preventing them from copying themselves and dividing. Such drugs, however, l...
  • During October, everything seems to turn pink – clothing, the NFL logo, tape dispensers, boxing gloves, blenders, soup cans, you name it – in order to raise awareness for what many believe is the most dangerous cancer that affects women: breast cancer. But, in addition to thinking pink, women should...
  • In February 2003, when she was only 16 months old, Maya Gallardo was diagnosed with acute myelogenous leukemia (AML) and, to make matters much worse, pneumonia. The pneumonia complicated what was already destined to be grueling treatment regimen. To assess the extent of her illness, Maya had to endure a spinal ...
  • Former smokers age 55 to 74 who rely on Medicare for health care services have just received a long-hoped-for announcement. Under a proposed decision from the Centers for Medicare and Medicaid Services, they’ll now have access to lung cancer screening with a low-dose CT scan. The proposed decision, announ...
  • City of Hope has a longstanding commitment to combating diabetes, a leading national and global health threat. Already, it’s scored some successes, from research that led to the development of synthetic human insulin – still used by millions of patients – to potentially lifesaving islet cell transplants. Diabet...
  • Dee Hunt never smoked. Neither did her five sisters and brothers. They didn’t have exposure to radon or asbestos, either. That didn’t prevent every one of them from being diagnosed with lung cancer. Their parents were smokers, but they’d all left home more than 30 years before any of them were diagn...
  • They may not talk about it, but women with cancers in the pelvic region, such as cervical cancer, bladder cancer and uterine cancer, often have problems controlling their urine, bowel or flatus. Although they may feel isolated, they’re far from alone. Many other women have such problems, too. In fact, nea...
  • Cancer that spreads to the liver poses a significant threat to patients, and a great challenge to surgeons. The organ’s anatomical complexity and its maze of blood vessels make removal of tumors difficult, even for specialized liver cancer surgeons. Following chemotherapy, the livers of cancer patients are not ...