The teleconference of the Advisory Committee to the Director, National Cancer Institute, was convened on August 29, 2001, at 9:30 a.m. EST at the National Institutes of Health, Building 31, Conference Room 11A03.

Advisory Committee Members participating in the teleconference:
Richard D. Klausner, M.D., Director, National Cancer Institute (Chair)
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)
Craig Thompson, M.D., University of Pennsylvania Cancer Center (Board of Scientific Counselors)
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:
James Corrigan, Ph.D. National Cancer Institute
Norma Davis, National Cancer Institute
Thomas Glynn, Ph.D., American Cancer Society
Richard Kaplan, M.D., National Cancer Institute
Kate Nagy, National Cancer Institute
Cherie Nichols, M.B.A., National Cancer Institute
John C. Ruckdeschel, M.D., H. Lee Moffitt Cancer Center and Research
Institute, University of South Florida (Co-Chair, Lung Cancer Progress Review Group)
Scott Saxman, M.D., National Cancer Institute (Executive Director, Lung Cancer Progress Review Group)
Margaret R. Spitz, M.D., MPH, University of Texas M.D. Anderson Cancer Center (Co-Chair, Lung Cancer Progress Review Group)

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 Lung Cancer Progress Review Group (PRG). The ACD must formally accept the report to enable NCI to develop an implementation plan based on the report's recommendations.

Dr. Richard Klausner, Chair, ACD, welcomed everyone in attendance. He noted that Dr. Stillman was participating in his last teleconference as an ad hoc member and welcomed Dr. Thompson, the new chair of the BSC.

On behalf of the Lung Cancer PRG, Dr. Ruckdeschel thanked the NCI staff who provided support for the report's preparation. Although it is widely known that lung cancer kills more people than any other cancer, research on this disease has been hampered by therapeutic nihilism and social attitudes that tend to blame lung cancer patients for their illness, he said. A further problem is a shortage of general thoracic surgeons and pulmonologists trained in the treatment of lung cancer.

Dr. Ruckdeschel noted that the PRG made a number of recommendations that can be addressed through the continuation or enhancement of ongoing NCI initiatives in the following areas: bioinformatics, animal models, molecular profiling of tumors, special populations and population disparities, tissue and data repositories, drug development and clinical trials infrastructures, and centers of excellence in communication.

The PRG identified the following top-priority recommendations that address overarching issues:

• Cross-disciplinary lung cancer consortia. Foster the creation of scientifically integrated, multi-disciplinary research consortia organized around the problem of lung cancer rather than around specific research disciplines. Such a step would create a critical mass of scientific experts working together to conduct the large-scale research studies and clinical trials that are needed.
• Tobacco control. Develop and expand new approaches to the biology and treatment of nicotine addiction and mount studies to explore the differential toxicity of various tobacco and nicotine products, including so-called "safe" or low-tar cigarettes. Continue to systematically evaluate population-based tobacco control efforts. Expand the use of existing guidelines and develop new approaches to smoking cessation and relapse prevention. Adopt and implement these guidelines in lung cancer prevention, screening, and treatment trials. Because tobacco control issues transcend the problem of lung cancer, the PRG recommended that NCI convene a Tobacco PRG.
• Early detection. Facilitate and hasten the evaluation of spiral computed tomography (CT) scanning to detect lung cancer at an early stage, reverse the current stage distribution at presentation, and reduce mortality from lung cancer.
• Outcomes. Design, implement, and study "best practices" in lung cancer management. Currently, the extent to which best practices and existing guidelines are employed in the community is unknown. Expansion of the CanCORS program would allow a common data set on which to validate new measures of quality care and evaluate novel programs of service delivery.
• Training programs. Facilitate and encourage training programs that emphasize multi-disciplinary science and clinical care. Early and mid-career programs for training in lung cancer care and research need to be expanded and innovative designs encouraged.

Dr. Spitz summarized the PRG's principal recommendations in the areas of biology, etiology, and chemoprevention as follows:

Biology. New biological insights are critical to outline the molecular and cellular pathways of lung carcinogenesis. The PRG recommended that the contribution of injury, inflammation, and infection to lung carcinogenesis be explored by means of a concerted multidisciplinary approach.

Etiology. There are currently no validated risk-assessment models for lung cancer that incorporate biomarkers of susceptibility. Etiologic factors need to be explored in special populations, including former smokers, women, minorities, and nonsmokers. Focused studies are needed to correlate high and low-penetrance susceptibility genes in an integrated context.

Chemoprevention. No effective chemopreventive agents, appropriate target populations, or validated surrogate endpoints have yet been identified. There is a need to conduct smaller, targeted, mechanistic studies and develop selective agents that target specific pathways, thereby limiting toxicity, as well as to consider combination regimens and novel delivery approaches and to capitalize on new diagnostic imaging approaches.

In the ensuing discussion, Dr. Ruckdeschel said that the organization and activity of the recommended Lung Cancer Consortia would closely resemble the former NCI-sponsored Lung Cancer Study Group, which was active from 1977 to 1988. It would extend the focus of the lung cancer SPORES to clinical, behavioral, and population-based research.

Dr. Klausner noted that the NCI Board of Scientific Advisers (BSA) has engaged in intense discussions over the past two years in an effort to design a series of studies assessing the value of spiral CT scanning. A proposal for a large randomized trial resulted in a tie vote of the BSA. Currently a working group of BSA members is working with NCI to devise a way to move forward. This process has highlighted the difficulties involved in considering the evaluation of spiral CT scanning, he said.

Dr. Ruckdeschel noted that a randomized trial of spiral CT scanning would be very costly because of the need to enroll between 20,000 and 80,000 patients. Despite the difficulties, however, progress has been made toward the design and funding of an international randomized trial.

A discussion took place about the value of tissue repositories that are not linked to specific research questions. Dr. Klausner noted that considerable uncertainty exists over how to establish useful tissue resources. He added that new funding mechanisms have recently been created to support discovery of molecular targets.

It was noted that advocacy by lung cancer patients has been weak because mortality from the disease is 85% and because of widespread reluctance to devote resources to a disease that is perceived as self-inflicted. Such attitudes may be beginning to change, however, now that more than 50% of lung cancers occur in former smokers.

In regard to the recommendation for a Tobacco PRG, Dr. Klausner noted that tobacco has been identified as an Extraordinary Opportunity in the NCI Bypass Budget and has also been the subject of a report by the NCI Tobacco Research Implementation Group, which is to be reconvened. He added that the PRG process was intended to be disease-specific and that NCI has other planning and implementation processes for addressing issues that transcend a specific disease. Dr. Klausner further noted that he will be reporting to the next meeting of the BSA on discussions that NCI has initiated with the National Institute on Drug Abuse concerning the development of a joint research consortium focused on developing new treatments for nicotine addiction.

ACD members unanimously accepted the report of the Lung Cancer PRG for transmittal to NCI for consideration and development of an implementation plan. Dr. Hong, who was a member of the Lung Cancer PRG, abstained from the vote. 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 PRG co-chairs and executive director and the ACD members for their work. A follow-up meeting will be held with the PRG to further discuss both the recommendations and the proposed implementation strategy.

The teleconference was adjourned at 10:50 a.m. EST.