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Neuro-Oncology : Staff

Kathy Warren, M.D. Section Head

A photo of Kathy Warren, M.D.,Section Head
Kathy Warren, M.D. Section Head

Biography:
Dr. Warren received her B.S. in Medical Technology in 1982, and her M.D. from Tufts University School of Medicine in 1990. She completed a residency in pediatrics at Children's National Medical Center, followed by a fellowship in Pediatric Oncology at the National Cancer Institute. She is board certified in Pediatric Hematology/Oncology. Dr. Warren is a Tenure Track Clinician in the Pediatric Oncology Branch, and Head of the Pediatric Neuro-Oncology Section. Her research interests include performance of clinical trials, particularly in children with tumors of the central nervous system, non-invasive evaluation/imaging of the brain, and neurotoxicity resulting from tumors and their treatment.

Research:
View Dr. Warren's Current Clinical Trials

Patients may also be eligible for enrollment on investigational studies performed in the POB under the Pharmacology & Experimental Therapeutics Section.

Project I: Clinical development of new agents and novel therapeutic approaches for pediatric patients with CNS tumors.
There are approximately 3000 new cases of pediatric CNS tumors diagnosed in the United States each year, compared to an estimated 21,000 adults.  Pediatric brain tumors represent a heterogeneous group of diseases, and a significant proportion of tumors are considered benign or low-grade. The 5-year survival for these children is currently over 70%, reflecting the large percentage of low-grade gliomas.  However, for those children with malignant tumors including diffuse intrinsic brainstem gliomas and high-grade gliomas, and those with recurrent ependymomas and medulloblastomas, the 5-year survival is dismal, approaching <10%.  Despite neurosurgical and radiotherapeutic advances, no significant improvement in survival has been made for patients suffering from these tumors in several decades.
The armamentarium for the treatment of pediatric CNS tumors includes surgery, radiation and chemotherapy.  Although surgery may be curative for focal, benign tumors, adjuvant therapy is necessary for invasive, malignant lesions.  Radiation therapy is toxic to the developing brain and avoided or deferred if possible, in very young children.  Although chemotherapy plays an important role, improvement in the survival of pediatric patients with malignant gliomas and recurrent malignant tumors, has been modest, at best, and for some tumors, such as diffuse intrinsic pontine gliomas, no chemotherapy has ever demonstrated an ability to improve patient outcome.
Given the higher number of adults diagnosed with brain tumors each year and the hesitancy to test new agents in the pediatric population prior to their initial development in adults, few agents are available for clinical development in children, and those that are available lag behind development in adults.  In addition to the sometimes disparate tolerability and pharmacokinetics between adult and pediatric patients, pediatric CNS tumors differ from adult CNS tumors in histology, biology, pathophysiology, and location, and therefore efficacy data available for adults may not apply to pediatric patients.   Rational drug development based on relevant pharmacokinetics (PK), such as CNS penetration, is infrequently performed, and early studies instead frequently aim to identify a maximum tolerated dose rather than a targeted effective dose.  The major goals of the pediatric neuro-oncology section are rational, PK-based, drug development in the pediatric population, and investigation of novel therapeutic approaches, such as convection-enhanced delivery.

Research Aims
1. Clinical development of new anticancer agents for the treatment of childhood CNS tumors through the use of preclinical testing, pharmacokinetic modeling, performance of early clinical trials, and collaboration within national pediatric consortia.  Our research focuses on overcoming obstacles to treatment rather than empiric testing of agents.  Previous and ongoing projects have included strategies to: overcome drug resistance, optimize exposure , and swiftly develop agents in children after initial adult studies.
2. Development of novel approaches to the treatment of these tumors through alternate delivery strategies, including convection-enhanced delivery, intra-arterial administration, and intrathecal administration.

Project II: Assessment of tumor biology to identify novel targets and biomarkers.
Assessing tumor characteristics noninvasively is particularly important in pediatric neuro-oncology given the technical and ethical limitations of repeat tissue sampling in these children.  In addition, no tissue is routinely obtained, even at diagnosis, for DIPG or optic pathway gliomas, as these tumors are diagnosed radiographically by MRI in the setting of a typical clinical presentation. Endpoints for assessing drug activity in clinical trials involving CNS tumors have included changes in the measurements of tumor size as measured by magnetic resonance imaging relative to a pretreatment or best response scan.  Tumor reduction may be indicative of efficacy of a cytotoxic agent, but the application and clinical development of molecularly targeted agents, antiangiogenic therapeutics and metronomic therapies have presented new challenges in terms of defining efficacy, as immediate cytotoxicity may not be evident and effects on tumor cells are more difficult to establish.  Defining and incorporating innovative endpoints in clinical trials designed to determine the biologic and therapeutic activity of new agents is a major focus of my research.  In addition, the lack of tissue samples, particularly for patients with DIPG, has limited intellectual and clinical advancement.

Research Aims

  1. Development of objective, sensitive, specific imaging techniques that can noninvasively characterize tumor tissue and reliably differentiate tumor and treatment effects.
Increase availability and better utilization of tumor tissue to investigate the biology of gliomas.
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This Page Last Reviewed on February 26, 2013

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