Advisory Committee Members participating in the teleconference:
Richard D. Klausner, M.D., Director, National Cancer Institute (Chair)
Martin D. Abeloff, M.D., Johns Hopkins Oncology Center (Board of Scientific Counselors)
Michael Katz, M.B.A., International Myeloma Foundation (Director's Consumer Liaison Group)
Phillip A. Sharp, Ph.D., Massachusetts Institute of Technology (National Cancer Advisory Board)
Bruce Stillman, Ph.D., Cold Spring Harbor Laboratory (Board of Scientific Counselors)

Ex Officio Members present:
Marvin Kalt, Ph.D., National Cancer Institute
Alan S. Rabson, M.D., Deputy Director, National Cancer Institute)

Executive Secretary:
Susan J. Waldrop, National Cancer Institute

Other participants:
Norma Davis, National Cancer Institute
P. Fernandes, Bennett, Turner, & Coleman, North American Brain Tumor Coalition
Joel Finkelstein, Oncology.com
Thomas Jacobs, Ph.D., National Institute of Neurological Disorders and Stroke, Executive Director, Brain Tumor Progress Review Group
Richard Kaplan, M.D., National Cancer Institute, Executive Director, Brain Tumor Progress Review Group
David N. Louis, M.D., Massachusetts General Hospital, Co-Chair, Brain Tumor Progress Review Group
Chitra Mohla, National Cancer Institute
Kate Nagy, National Cancer Institute
Cherie Nichols, M.B.A., National Cancer Institute
Jerome B. Posner, M.D., Memorial Sloan-Kettering Cancer Center, Co-Chair, Brain Tumor Progress Review Group
Susan L. Weiner, Ph.D., North American Brain Tumor Coalition, Brain Tumor Progress Review Group
Annabelle Uy, National Cancer Institute

The purpose of the teleconference was to present to the Advisory Committee to the Director (ACD) for discussion and acceptance the draft report of the Brain Tumor Progress Review Group. The ACD must formally accept the report to enable NCI to develop an implementation plan based on the report's recommendations.

Ms. Waldrop noted that the meeting was open to the public and that the meeting summary would be posted on NCI's public Web site. She further noted that at its last meeting the ACD had accepted the report of the Colorectal Cancer Progress Review Group and that a plan is now being developed for implementing that group's recommendations. Ms. Waldrop stated for the record that ACD members had been determined to have no conflicts of interest with respect to the matters under discussion at this meeting.

Dr. Klausner thanked the co-chairs and executive directors of the Brain Tumor Progress Review Group and the staff of the NCI Office of Science Planning and Assessment for their hard work in producing the PRG report.

Dr. Posner said that this PRG report was unique in several respects. Firstly, it is the first such report to be produced as a result of a cooperative venture between two Institutes to address a problem that interests both. Dr. Posner thanked Dr. Klausner and Dr. Gerald Fischbach, Director of the National Institute of Neurological Disorders and Stroke (NINDS) , for making this cooperative venture possible; the executive directors of the PRG, Dr. Richard Kaplan of NCI and Dr. Thomas Jacobs of NINDS, for their role in forging collaboration between the two Institutes; and the NCI staff for their organizational skills, which facilitated production of the draft PRG report in just nine months from the group's first meeting. Dr. Posner noted that both the membership of the Brain Tumor PRG and participation in the PRG roundtable meeting was highly interdisciplinary, bringing together fundamental neuroscientists and cancer biologists as well as clinicians in oncology and neuroscience.

Tumors of the central nervous system (CNS) present challenges not found in other types of cancer, said Dr. Posner. These tumors attack the essence of the "self"; surgical removal of the entire organ or the tumor with a generous surround of normal tissue is not an option; and most brain tumors are relatively insensitive to other cancer treatment, including radiation and chemotherapy. The biology of the brain is also unique in many respects. For example, the blood-brain barrier often protects tumors from systemically administered agents; brain tumors are less susceptible than tumors in other organs to attack by the immune system; and the invasiveness of many brain tumors makes complete surgical removal impossible.

Another unique aspect was the wide variety of tumors that the PRG had to consider; the World Health Organization lists 126 different types of CNS tumors, including tumors of the brain itself, tumors of the covering membranes, tumors involving glands and intracranial structures, and tumors that metastasize to the brain from other organs. Unlike most other cancers, brain tumors affect both adults and children; brain tumors are the second most common cancer in children after leukemia. Brain tumors in children present unique challenges and opportunities.

The PRG report has two main sections: scientific priorities, which are hypothesis-driven, and resource priorities, which are hypothesis-generating. Dr. Louis said that although many of the report's recommendations overlap with those of previous PRGs, a number of recommendations are specific to the brain tumor field. He summarized those recommendations as follows:

Scientific Priorities

• Biology. Additional basic research is critically needed on the regulation and dysregulation of the blood-brain barrier; the definition of the cells of origin for most brain tumors; and the process of invasion of brain tumor cells into adjacent brain tissue.
• Clinical priorities. The development of new therapeutic agents is critically important, as is the need to develop better early markers of outcome that address quality of life and biological endpoints of therapeutic response.

Resource Priorities

• Tissue and data banks. The development of banks of brain tumor tissue linked to clinical information that facilitates study of this tissue is a major challenge. Furthermore, the relative rarity of many types of brain tumors and the small size of many biopsies present particular impediments to tissue sharing.
• Models. Better animal models are critically needed to advance both brain tumor biology and therapy. Currently funded mouse models do not address the full range of brain tumors and fall short on important clinical issues such as overcoming the blood-brain barrier and dealing with therapeutic delivery issues.
• Improved communications. A major realization that emerged at the PRG roundtable meeting was that many important problems fall at the juncture of cancer biology and neurobiology and that more interaction is essential both between individual scientists in these fields and between NCI and NINDS.

• Resolving the problem of investigator access to brain tissues involves, firstly, improving knowledge of and access to existing tissue banks and, secondly, making better use of available fixed tissues. NCI initiatives are now under way both to make better use of archival specimens and to encourage the development of scaling technologies for genetic, genomic, proteomic and other approaches to limiting tissues. In addition, the Adult Brain Tumor Treatment Consortium is formulating a plan to acquire fresh tissues and make them available as a resource.
• The overarching scientific priorities identified in the PRG report encompass both adult and pediatric tumors, although the report recognizes that pediatric brain tumors differ significantly from adult tumors in terms of lineage, sites of origin, clinical presentation, and other features. The impact on the developing brain of treating brain tumors in children is an area of special concern. Long-term follow-up, especially relating to quality of life issues, is particularly important in children. Efforts are under way in various quarters to overcome lingering resistance to making new therapies available to the pediatric population as soon as they become available to adults.

The ACD unanimously accepted the report of the Brain Tumor PRG for transmittal to NCI for consideration and development of an implementation plan. Dr. Klausner said NCI and NINDS staff will begin immediately to identify mechanisms for implementing the PRG's recommendations. A follow-up meeting will be held with the PRG to further discuss both the recommendations and the proposed implementation strategy. This will be the first time that the implementation of a PRG report will involve two institutes working collaboratively.

It was noted that once accepted by the ACD the PRG report becomes a public document; the report will be available on NCI's Web site (with a link from the home page) as of noon today.

The teleconference was adjourned at 10:10 a.m.