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Clinical Neuro-Oncology Program
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Home > Patient Care > Clinical Neuro-Oncology Program
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The Clinical Neuro-Oncology Program sees approximately 2400 patients each year, of whom approximately 500 are new patients with primary malignant brain tumors, including both newly diagnosed and recurrent malignant tumors in adults and children, and all grades of disease. The most common tumor type seen is glioblastoma multiforme. On average, each year, about 50 patients newly diagnosed with glioblastoma multiforme, 20 patients newly diagnosed with low-grade tumors, and 100 patients with recurrent malignant glioma are enrolled into clinical research protocol studies. Altogether, approximately 200 patients each year are enrolled in research protocols in the Neuro-Oncology Program.
 
Strategies for maintaining local control of tumors after surgery include radiation oncologic approaches, such as brachytherapy, medical oncologic methods like convection-enhanced delivery of therapeutic agents to the brain and immunotoxin therapy, advanced imaging techniques for determining blood flow and perfusion, and advanced systems for functional and metabolic imaging. The Brain Tumor Research Center's (BTRC) focus on translational research makes the most recent and promising investigational regimens available to patients who participate in clinical trials.
 
Clinical Neuro-Oncology
Pediatric Clinical Neuro-Oncology
Radiation Oncology
 
Clinical Neuro-Oncology
 
The Clinical Neuro-Oncology Program seeks to improve survival in adults and children with malignant brain tumors through research treatment protocols that use novel agents and strategies based on basic and translational research, both within the Program and the UCSF Comprehensive Cancer Center and from other sources, such as the National Cancer Institute, as well as from interactions with other academic research centers and industry. The Clinical Neuro-Oncology Program at UCSF is one of the largest in the country, and in calendar year 2000 enrolled 223 patients into research studies, including studies of quality of life, fatigue, and the use of complementary medicine. The Program is currently funded by four major NIH grants that support this effort. These include a Program Project Grant, a Specialized Program of Research Excellence grant, and two cooperative grants that fund consortia of institutions that conduct clinical research in adults and children — the North American Brain Tumor Consortium (NABTC) and the Pediatric Brain Tumor Consortium (PBTC).
 
The Program Project Grant that in part supports the clinical aspect of the Neuro-Oncology Program includes studies involving gene therapy and convection-based infusion of agents into the brain tumor and brain adjacent to tumor. Examples of surgically-based research protocols include the use of two novel phase-1 studies of IL-13/pseudomonas exotoxin and TGF-α/pseudomonas exotoxin given by convection-enhanced delivery systems, and a phase-1 gene therapy study using adenovirus/interferon-β for local delivery. Radiation-based studies, including a phase-1 trial of interstitial brachytherapy and a phase-2 trial of radiation plus daily temozolomide and cis-retinoic acid for newly diagnosed glioblastoma multiforme, are also emphasized. A recently closed phase-2 study of radiation plus temozolomide and thalidomide completed accrual of 60 patients in 13 months, suggesting that the mechanism is in place to quickly enroll patients into phase-2 trials for newly diagnosed disease using radiation therapy and/or novel agents, projects undertaken under the Specialized Programs of Research Excellence (SPORE) Grant from the National Institutes of Health (NIH).
 
The NABTC, which has its operations office at UCSF, is headed by Michael Prados MD, Director of the Clinical Neuro-Oncology Program and clinical principal co-investigator on the UCSF SPORE Grant. The NABTC has enrolled more than 600 patients into phase-1 and phase-2 studies over the past 4 years and is a national resource for the conduct of investigator-initiated clinical research. The NABTC treats primarily patients with recurrent tumors by using phase-1 and early pilot phase-2 trials that are pharmacologically based with molecular correlates. Examples include the use of antiangiogenic agents, small-molecule tyrosine kinase inhibitors, and inhibitors of signal transduction. All of the NABTC trials, with few exceptions, permit new agents to be given to patients before surgical resection for specific analysis of tissue distribution and molecular "target" impact in situ.
 
With funding provided by the NIH Program Project Grant, the NABTC, the PTBC, and the UCSF SPORE Grant, an infrastructure has been developed that allows convection-based delivery of experimental agents directly into brain parenchyma, gene therapy studies, novel phase-1 and phase-2 trials that use targeted molecular-based agents, together with the necessary pharmacokinetic studies required by these early trials. The Clinical Neuro-Oncology Program is committed to continue conducting phase-1 trials that evolve out of basic science discoveries in translational efforts to develop more effective therapies while providing the maximum possible quality of life permitted by the patient's condition.
 
Pediatric Clinical Neuro-Oncology
 
After surgery, chemotherapy and radiation therapy are important adjuvant treatments for many childhood brain tumors. As radiation therapy can affect developing brain, chemotherapy is often used to delay or avert its use in very young children. UCSF's Pediatric Brain Tumor Center provides the most advanced neuro-oncology therapies available, together with neuropsychological consultation and close ties to organizations sponsoring support groups and resources for patients. A team of pediatric oncologists, pediatric nurse practitioners, social workers, child life specialists and a school liaison specialist coordinate care and education for patients and their families. UCSF is a member of the National Cancer Institute's Pediatric Brain Tumor Consortium (PBTC) for clinical trials of new therapies. Assisted by pediatric oncologist Dr. Anuradha Banerjee, Dr. Michael Prados is principal investigator of this Consortium site at UCSF.
 
Together with Dr. Prados, Director of the Clinical Neuro-Oncology Program, pediatric neuro-oncologist Dr. Banerjee and their residents and postdoctoral fellows see more than 50 new patients each year, most of whom enter into a clinical research protocol involving experimental forms of radiation therapy and/or chemotherapy. Clinical research protocols include phase 3 trials seeking to improve cure rates and reduce radiation toxicity in cases of medulloblastoma and germinoma by utilizing intensive chemotherapy with reduced and doses of radiation, conformal radiation delivery, or high-dose chemotherapy regimens with autologous stem-cell rescue for very young patients to avert or delay radiation therapy at a vulnerable age, and novel phase 1 and 2 trials investigating the use of innovative, molecularly targeted therapies and combination chemoradiation therapy protocols for patients with very high-risk disease. Finally, the UCSF Pediatric Neuro-oncology program is pioneering protocol development using a novel drug-delivery approach called convection-enhanced delivery, in which an experimental, targeted antitumor agent is directly infused in the tumor cavity to try to prevent recurrent disease in patients at high risk of relapse.
 
Our goal is to cure whenever possible, but always to care. Because many pediatric brain tumors carry an extremely poor prognosis, the UCSF Clinical Neuro-Oncology Program for Children also participates actively in the newly established Pediatric Palliative Care program at UCSF Children's Hospital. Ongoing research to understand how best to improve the quality of life and end-of-life management for patients in whom treatment has failed helps us to understand how to best maximize all aspects of care for patients suffering from these devastating diseases. Funding for most of the clinical activities of the program comes from grants from the NIH, and many trials are sponsored by the National Cancer Institute. Other funding sources include private foundations, pharmaceutical companies, and private donations.
 
Radiation Oncology
 
In 1895, William Roentgen discovered that photographic film placed in a light-tight container near a gas discharge tube became blackened. He attributed this to 'a new kind of ray', subsequently called xrays. Within a few years, gas-discharge tubes were in medical use in Europe and in the US. Today, fully half of all cancer patients, and many with benign tumors, receive xray treatment. Most contemporary treatments are carried out with linear accelerators, called linacs, which produce highly collimated, intense, high energy xray beams, capable of penetrating deep within tissue to kill tumor cells. Other types of radiation beams are available, such as proton, heavy ion, and electron beams, and all have been used over the past three decades by Brain Tumor Research Center (BTRC) investigators to treat brain tumor patients. Over the past three decades, approximately 5000 brain tumor patients have been treated by UCSF Radiation Oncology faculty. Forty one clinical BTRC trials that have involved radiation therapy for brain tumors have been carried out, and 701 brain tumor patients have been treated with radiation according to BTRC protocols since 1990.
 
The past three decades have seen remarkable technical advances in radiation therapy of brain tumors. Thirty years ago the location and extent of brain tumors were often poorly appreciated because three-dimensional imaging was then unavailable, and the majority of patients were treated with generous, opposed-lateral radiation beams, often with low-energy xrays with poor penetration. As a result, patients received substantial dose to large volumes of normal tissue. Today's brain tumor treatments are planned with computerized three-dimensional planning software that integrates magnetic resonance imaging and/or magnetic resonance spectroscopy and/or computed tomography and/or positron emission tomography information into the planning process. In addition, advances in the physics and engineering of radiation dose delivery allow radiation dose to be conformed in three dimensions to the three-dimensional tumor configuration. These advances together minimize the volume of normal brain tissue receiving full dose and guarantee full dose delivery to the tumor.
 
BTRC clinicians and scientists have published hundreds of papers that have shaped modern radiation therapy for brain tumors and have provided new understanding of the cellular, biochemical, and biomolecular effects of radiation and the interaction of radiation with adjuvant therapies.
 
Brachytherapy
 
Brachytherapy is a treatment method in which sealed radioactive sources are placed in or near tumors. It is used to give high local doses of radiation to tumor cells while minimizing the dose to surrounding normal tissue. This is a particularly appealing treatment method for brain tumors, which are nearly always closely associated with critical normal tissue. The depth of penetration of the emitted radiation, the type of radiation emitted, and the time course over which the radiation is delivered to achieve a particular dose are determined by the characteristics of the isotope selected.
 
In the past 25 years, more than 800 patients have received brachytherapy for a brain tumor at UCSF. The majority of patients treated had a malignant glial tumor, for which brachytherapy was either part of a patient's initial management or as part of a patient's management for recurrence. However, a wide variety of other tumors have been treated, including meningioma and metastases. Patients are selected for brachytherapy at a weekly multidisciplinary tumor board.
 
Clinical brachytherapy for brain tumors was pioneered at UCSF and has been supported by scientific research within the BTRC. As a result of the many clinical reports and book chapters on brachytherapy for brain tumors that have been published by BTRC clinicians and scientists, the technique has grown in popularity throughout the world and is now available at hundreds of hospitals. Although several different isotopes have been used, most patients have been treated with radioactive iodine (125I). This isotope emits xrays of low energy, which is important to avoid damaging surrounding normal tissue within the brain and to avoid overexposing hospital personnel, and can be obtained in a wide variety of activities, which is important for customizing dose distributions for the individual patient.
 
For many years, small plastic catheters were placed at precise locations within gross tumor, following which radioactive 125I seeds were temporarily 'afterloaded' into the catheters, with seeds separated in the catheters by small spacers. Patients remained hospitalized while the radiation was absorbed by the tumor cells, typically for about five days. Thereafter, the seeds and catheters were removed and the patient was discharged to go home and resume normal activity. In some cases, during hospitalization, heat treatment, called hyperthermia, was used in conjunction with the radioactive sources, since heat and radiation together kill tumor cells effectively. More recently, UCSF has pioneered permanent, rather than temporary, brachytherapy. With permanent brachytherapy, a neurosurgeon resects all gross tumor, after which 125I seeds are permanently fixed to the wall of the resection cavity with surgical adhesive. This automatically results in a highly conformal radiation dose to the cavity rim, the region where tumor recurrences are otherwise most likely. Early results indicate far fewer side effects than with temporary brachytherapy.
 
More information about UCSF Cancer Center clinical trials for adults and children
 
 
Associated Faculty
Director of the Division of Neuro-Oncology
Susan M. Chang MD
 
Director of Clinical Services
Nicholas Butowski MD
 
Director of Translational Research
Michael D. Prados MD
 
Clinical Director, Radiation Oncology
Patricia Sneed MD
 
Faculty Practitioners
Anuradha Banerjee MD, MPH
Mitchel S. Berger MD
Sandeep Kunwar MD
Michael W. McDermott MD
Andrew T. Parsa MD, PhD
Clinical Neuro-Oncology Program
Department of Neurological Surgery
University of California, San Francisco
400 Parnassus Avenue [A-808, UCSF Box 0372]
San Francisco, California 94143-0372
tel 415-353-7500; fax 415-353-2167


 
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