INTRAAXIAL TUMORS

Co-Chairs: Faith Davis, Ph.D., and Lisa DeAngelis, M.D.

Participants: Michael Berens Mitchel Berger Rebecca Betensky Pim Brouwers Peter Burger J. Gregory Cairncross Webster Cavenee R. Edward Coleman Ronald A. DePinho Howard A. Fine Candece Gladson Joseph C. Gloriosa

Peter Ho Fred Hochberg Susan Hockfield Eric C. Holland William G. Kaelin Jr. Kathleen Lamborn John Mazziotta Minesh Mehta Ravi Menon Christina A. Meyers Maiken Needergaard Donna Neuberg

Edward A. Neuwelt Lawrence Pizzi Jasti S. Rao Greg Riggins Elizabeth Stevenson Michael Walker Albert Wong Roy S. Wu W. K. Alfred Yung

STATEMENT OF THE PROBLEM

Intraaxial tumors comprise a complex mixture of low- and high-grade lesions occurring in both children and adults. This report restricts its discussion to adult tumors other than malignant gliomas, specifically low-grade gliomas, lymphomas, and germ cell tumors.

Low-grade gliomas can be divided into two general categories: infiltrating and localized. Infiltrating tumors include, but are not limited to, fibrillary astrocytomas, oligodendrogliomas, and ependymomas. Non-infiltrating tumors include pleomorphic xanthoastrocytomas, pilocytic astrocytomas, and dysembryoplastic neuroepithelial tumors. Despite their rarity, primary central nervous system (CNS) lymphomas and germ cell tumors are also important because some patients are cured of their tumors. However, not all patients are cured, and some of those who are suffer long-term neurotoxicity.

CHALLENGES

Although numerous in the aggregate, each tumor type is uncommon. Patient numbers are small, and no single institution acquires adequate numbers to answer important questions.

Tissue for study is limited. Often only a needle biopsy is available, and sometimes, as in infiltrating low-grade gliomas, no tissue is available. This creates particular challenges for molecular studies. Imaging techniques may provide an alternative approach for the investigators to non-invasively "examine" the entire tumor. Development of biological and molecular imaging technologies is essential for further understanding of these less common intraaxial neoplasms.

RESEARCH AND SCIENTIFIC PRIORITIES

Low-Grade Gliomas

Priority 1: Better understand the natural history of low-grade gliomas with an emphasis on mechanisms of progression, infiltration or lack of it in non-invasive diagnosis. Imaging strategies should be developed to:

• Identify the extent of infiltrating tumor

• Predict progression

• Identify heterogeneity prior to surgery or biopsy

Priority 2: Develop techniques to molecularly characterize tumors on small biopsy samples.

• Particular emphasis should be placed on the molecular signature of tumors that infiltrate and progress to higher grade.

• Conduct population-based studies to allow assessment of etiology and new treatment strategies, including their toxicity and patients' quality of life.

Primary CNS Lymphoma and Germ Cell Tumors

Priority 3: Understand the natural history of primary CNS lymphomas.

• Epidemiologic studies are needed to identify environmental factors other than immune suppression that appear to be leading to an increased incidence of lymphomas.

• Molecular characterization of CNS lymphomas is required to determine how they differ from systemic lymphoma, identify the cell of origin, and predict prognosis. Molecular characterization of germinomas is needed for prognostic prediction.

Priority 4: Develop more effective therapies.

• Conduct long-term studies on dose intensity for the treatment of lymphomas and determination of optimum volume for radiation therapy for germinomas.

• Determine the relationship between molecular characterization of the tumor and response to therapy is required.

• Long-term studies of neurotoxicity require development of quantitative quality of life and neurocognitive instruments, development of treatment strategies to improve cognition, and further study on how the tumor itself may affect brain function.

RESOURCES NEEDED

• Funding for the establishment of cell lines of each of these tumor types is necessary to learn more about the biology of these tumors.

• A central repository for tissue banking for genetic analysis of tumors should be established to draw samples from all over the country.

• A central registry or database should be established to accumulate clinical information on diagnosis, response to treatment, neurotoxicity, and long-term follow-up of patients with these tumors. Support should be provided for long-term longitudinal studies.