The teleconference of the Advisory Committee to the Director, National Cancer Institute, was convened on April 24, 2000, at 11:30 a.m. EST at the National Institutes of Health, Building 31, Conference Room 11A10.

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)
Frederick R. Appelbaum, M.D., Fred Hutchinson Cancer Research Center (Board of Scientific Advisors)
Waun Ki Hong, M.D., University of Texas M.D. Anderson Cancer Center (Board of Scientific Advisors)
Michael Katz, M.B.A., International Myeloma Foundation (Director's Consumer Liaison Group)
Amy S. Langer, M.B.A., National Alliance of Breast Cancer Organizations (Consumer Representative)
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 Carroll-Davis, National Cancer Institute
Barbara A. Conley, M.D., National Cancer Institute (Executive Director, Colorectal Cancer Progress Review Group)
Dave Curieton, Cancerpage.com
Raymond Dubois, M.D., Ph.D., Vanderbilt University Medical Center (Co-Chair, Colorectal Cancer Progress Review Group)
Joel Finkelstein, Oncology.com
Kirsten Goldberg, The Cancer Letter
Lynette Grouse, National Cancer Institute
Terri Hallquist, National Cancer Institute
Lauren Heter, The Blue Sheet
Tom Hogan, The Blue Sheet
Bernard Levin, M.D. University of Texas M.D. Anderson Cancer Center (Co-Chair, Colorectal Cancer Progress Review Group)
Chitra Mohla, National Cancer Institute
Kate Nagy, National Cancer Institute
Cherie Nichols, M.B.A., National Cancer Institute
Susan Rossi, Ph.D., National Cancer Institute
Dvorit Samid, Roche Laboratories
Alain Thibault, Roche Laboratories
Annabelle Uy, National Cancer Institute

The purpose of the teleconference was to report to the Advisory Committee to the Director (ACD) the recommendations of the Colorectal Cancer Progress Review Group.

Ms. Waldrop said that minutes of previous ACD meetings had been approved by mail ballot and were available on the NCI Web site. She stated for the record that there were no conflicts of interest with respect to the items being discussed.

Dr. Klausner briefly reported the following new developments at NCI since the last ACD meeting:

• Carl Barrett has joined NCI as Director, Division of Basic Sciences.
• NCI has signed a Memorandum of Understanding with the Centers for Disease Control and Prevention to enhance planning and implementation of national cancer surveillance activities.
• NCI has also signed an agreement with the Department of Defense and the Veterans Administration to expand the existing NCI/DoD/VA clinical trials program.
• Institute Directors will vote later this week on a plan for implementing the recommendations of the NIH Bioinformation Science and Technology Initiative.
• NCI has completed its strategic plan for dealing with health disparities. The NCI plan will now be incorporated into the trans-NIH strategic plan for dealing with health disparities.
• DoD is adopting the Common Scientific Outline (CSO) that was developed as a byproduct of the NCI Progress Review Group process. The CSO is also being shared with other funding agencies both in the United States and overseas. It will be further refined and should help to facilitate the coordination of funding activities by many different agencies.

Dr. Klausner thanked the co-chairs of the Colorectal Cancer Progress Review Group for their efforts in overseeing the production of the group's report. He noted that the ACD must formally accept the report to enable NCI to develop an implementation plan based on the report's recommendations.

Drs. Dubois and Levin thanked the NCI staff for their support during the development of the PRG report. They and Dr. Klausner particularly acknowledged the contribution of Dr. Barbara Conley, Executive Director of the PRG.

Drs. Dubois and Levin highlighted the following key points from the PRG report:

Biology

• More studies are needed of normal gut development.
• Pathways of disease progression need to be better defined.
• The establishment of centers of excellence might hasten progress in these areas.

Genetics and Etiology

• More support is needed for population-based epidemiologic studies, including studies to link genetic polymorphisms with diet, lifestyle, and other variables in special populations.
• There is a need to validate early and intermediate biomarkers.
• All genes that predispose to colorectal cancer should be identified as soon as possible, with specific emphasis on modifier genes.
• Given current knowledge of colorectal cancer genetics, it should be possible to link specific tumor genetic subtypes by histologic type and other factors that could be used to improve drug development, intervention selection, and prognosis assessment

Early Detection and Diagnosis

• It is important to identify early markers of neoplastic development so that at-risk individuals can be identified as early in the disease process as possible.
• Research is needed to better understand barriers to the use of current screening technologies and develop strategies for increasing the proportion of the population that is screened for colorectal cancer.
• The development of a test or biomarker for adenomas (making colonoscopy unnecessary) would be of enormous significance.

The co-chairs also drew attention to the following cross-cutting themes that emerged from the PRG's discussions:

• Repositories of large data sets (such as biological samples) need to be linked to informatics centers, thus increasing the utility of such resources by making them more accessible to investigators who are trying to answer diagnostic, prognostic, and therapeutic questions.
• Better cross-disciplinary communication among, for example, basic scientists, medical oncologists, and gastroenterologists-as well as enhanced partnerships between government, academia, and industry-should be encouraged in order to foster innovative approaches to the discovery and development of more effective modalities for preventing, diagnosing, and treating colorectal cancer.
• More research is needed to develop more effective treatment options for advanced colorectal cancer.
• Greater efforts are needed to achieve a consensus on the ethics of genetic research, the risks and benefits, and the standards for regulation of such research.
• The peer review process needs to be strengthened to provide the expertise necessary for review of multidisciplinary research proposals such as those related to translational and prevention research.

The following points were made in response to questions from ACD members:

• The PRG report was written in full awareness of the epidemiologic study recently published in the New England Journal of Medicine, which showed that dietary fiber failed to protect against the recurrence of colorectal adenomas which are precursors of colorectal cancer. Notwithstanding this study's results, many questions remain unanswered concerning the effect of the environment, including diet and lifestyle, on the development of colorectal cancer. For example, good epidemiologic data suggest that a high intake of red meat increases colorectal cancer risk and that folate supplementation may reduce risk. There is a need to progress from dietary association studies to clinical trials of dietary interventions. It was agreed that statements and recommendations concerning diet need to clarify that "diet" is not synonymous with "fiber."
• The potential of COX-2 inhibitors as chemopreventive agents in colorectal cancer is referred to in both the Biology and Prevention sections of the PRG report. It was also noted that NCI has recently launched a multicenter clinical trial of sporadic adenomas.
• In the establishment of a bioinformatics network for colorectal cancer research it would be important to address the reluctance of some investigators to share data and resources. A model for overcoming this barrier exists in the Early Detection Research Network, in which investigators who receive NCI funding to participate in the network make a commitment to share their data and resources.
• The research priorities identified in the PRG report will be refined and sharpened during the implementation process. One of the challenges in producing a report such as this one is that all participants have different priorities and all need to be satisfied that the issues they consider most important have been adequately addressed.
• Given the current rate of about 56,000 deaths annually from colorectal cancer and the estimate that as many as 30,000 lives could be saved annually through proper implementation of current screening recommendations, it would not be inaccurate to state that better screening has the potential to reduce colorectal cancer mortality by 50%. Chemoprevention also has the potential to reduce colorectal cancer mortality by 50%. It was noted that all of the research priorities identified by the Behavioral and Health Services Research working group relate to developing the knowledge base necessary to devise strategies for improving screening utilization. Dr. Klausner noted that a national effort is now underway to bring together the expertise of NCI, CDC, and other organizations such as the American Cancer Society to create national screening programs for colorectal cancer. Dr. Levin mentioned that a national guide to screening resources is now available.
• The Cancer Control and Survivorship working group's recommendation to assess the effectiveness of colorectal cancer treatments in elderly and special populations could be strengthened by expansion to include assessment of screening and prevention strategies in these populations.

The co-chairs noted that it had been very helpful to have Dr. Harold Moses, a co-chair of the Breast Cancer PRG, address the colorectal group about the concrete outcomes that had resulted from that PRG process. Dr. Moses' comments had helped to overcome some initial skepticism about whether this process would yield positive results.

The ACD unanimously accepted the report of the Colorectal Cancer PRG for transmittal to NCI for consideration and development of an implementation plan. Dr. Klausner said NCI staff will analyze the extent to which the PRG's recommendations can be implemented by means of existing NCI programs and resources and which recommendations would require the creation of new programs or resources. A follow-up meeting will be held with the PRG to further discuss both the recommendations and NCI's proposed implementation strategy. An important component of the implementation strategy will be engaging professional societies, advocacy organizations, etc., in making researchers aware of the existence of funding opportunities specifically related to colorectal cancer research. Dr. Klausner added that NCI is currently trying to develop mechanisms and processes for monitoring both the short-term and long-term outcomes of the PRG process.

The teleconference was adjourned at 12:25 p.m.