Advisory Committee Members participating in the teleconference:
Andrew von Eschenbach, M.D., Director, National Cancer Institute (Chair)
Frederick R. Appelbaum, M.D., Fred Hutchinson Cancer Research Center (Board of Scientific Advisors)
Michael B. Kastan, M.D., Ph.D., St. Jude Children's Research Hospital (Board of Scientific Advisors)
LaSalle D. Leffall, M.D., Howard University School of Medicine (President's Cancer Panel)
Barbara LeStage, Chair, Director's Consumer Liaison Committee, National Cancer Institute
Craig Thompson, M.D., University of Pennsylvania Cancer Center (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:
Lisa Stevens, Ph.D., National Cancer Institute

PRG Leadership
Timothy J. Eberlein, M.D., Co-Chair, Stomach and Esophageal Cancers PRG
Ernest T. Hawk, M.D., M.P.H., Executive Director, Stomach and Esophageal Cancers PRG
Brian Reid, M.D., Ph.D., Co-Chair, Stomach and Esophageal Cancers PRG

NCI Staff
Norma Davis, National Cancer Institute
Deborah Duran, Ph.D., National Cancer Institute
Cherie Nichols, M.B.A., National Cancer Institute

Other participants:
Paul B. Phelps, Palladian Partners (recorder)

The purpose of the teleconference was to present to the Advisory Committee to the Director (ACD), for its discussion and acceptance, the draft report of the Stomach and Esophageal Cancers Progress Review Group (PRG). ACD must formally accept the report to enable NCI to develop an implementation plan based on the report's recommendations. Dr. Andrew von Eschenbach welcomed those in attendance.

Dr. Eberlein noted that stomach and esophageal cancers are relatively rare in the United States, with only 35,000 new cases per year, but worldwide incidence is 1.3 million cases per year and they are the second leading cause of cancer death in the world. In addition, U.S. incidence is rising, and these diseases have a disproportionate impact on minority populations, especially African American males. As a result, they offer a natural opportunity for research and outreach tailored to minority patients and physicians.

Both morbidity and mortality are complicated by a long premalignant phase during which the patient experiences few weight loss and nutritional deficits. This pattern has a negative effect on quality of life and cost of care, as well as effectiveness. Only 22 percent of stomach cancer patients, and 14 percent of those with esophageal cancers, experience five-year disease-free survival. This, in turn, points to an opportunity to intervene earlier with the help of new screening and diagnostic technologies.

At the same time, stomach and esophageal cancers present a unique opportunity to gain access to the tumors at all stages of disease, and to collect, store, and study tissue samples for basic research. A host of environmental interactions are suspected, providing an additional opportunity to use genomic and molecular approaches. Known and suspected risk factors include obesity, Helicobacter pylori, gastrointestinal reflux disease (GIRD), and others. PRG organizers believed that pharmacogenetics would play an important role in discovery; that protein expression and molecular profiling would be important tools in identifying and understanding each type of tumor; and that better animal models would be needed in conjunction with population studies. Overall, these cancers present an outstanding opportunity for multidisciplinary research and translation of basic discoveries into clinical treatments.

A planning meeting was held in January 2002, followed by a two-day roundtable in May 2002. Attendance was multidisciplinary and included patient advocates as well as researchers, clinicians, industry representatives, and health care administrators. Ten different working groups addressed the state of the science, gaps in current knowledge, and opportunities for research with regard to three disease sites (gastric adenocarcinoma, esophageal adenocarcinoma, and esophageal squamous cell carcinoma), and four populations of patients: at-risk, premalignant, localized malignant, and late malignant. In each of these areas, the PRG's deliberations addressed ten guiding scientific principles (Prevention, Biology, Genetics, Predictive & Prognostic Markers, Tumor Models, Imaging Technologies, Etiology, Outcomes, Surveillance/Data, and Therapeutics). The PRG developed 21 preliminary recommendations that, through combination and streamlining, were reduced to the 10 recommendations that are included in the draft report:

1. Population Studies: Establish collaborations for conducting multi-institutional, interdisciplinary, population-based, endoscopic studies to identify populations at greatest risk for gastric cancer, esophageal adenocarcinoma and esophageal squamous cancer, and to determine the prevalence and natural history of premalignant lesions.
   

2. Prevention: Develop prevention strategies based on the mechanisms of host-environment interactions that lead to metaplasia and neoplasia of the stomach and esophagus.
   

3. Patient and Provider Education: Educate patients and their families, health care professionals and the public regarding risk factors, risk reduction and treatment options and outcomes for gastroesophageal cancers and their precursor states.
   

4. Therapy: Develop and test novel therapeutics and optimize existing treatments for gastroesophageal cancers and their precursors based on identification and understanding of the molecular pathways involved in oncogenesis, tumor response, and resistance.
   

5. Therapeutic Targets: Define host and molecular/biologic tumor characteristics to customize treatment and best predict recurrence and survival.
   

6. Markers and Molecular Profiling: Profile the molecular, cellular and epidemiological features of gastroesophageal tumors and their precursor lesions in order to identify diagnostic, prognostic, predictive, preventive, and therapeutic targets.
   

7. Outcomes: Develop and refine disease-specific, patient-oriented methods to assess quality of life, quality of care and cost-effectiveness of treatment in patients with gastroesophageal cancers and their precursors though all stages of disease and treatment, and include these instruments in clinical trials and observational studies.
   

8. Host-Environmental Interactions: Identify, develop, and validate genetic, biochemical and biological markers that will help to uncover host-environmental interactions in esophageal and gastric carcinogenesis.
   

9. Technologies for Screening and Surveillance: Develop noninvasive and minimally invasive technologies for screening and surveillance of premalignant and malignant gastroesophageal lesions.
   

10. Preclinical Models: Establish models to understand the biology of gastroesophageal cancers and their precursor lesions, and create preventive, diagnostic and treatment strategies.
    

Dr. Reid explained that the PRG believes that these recommendations would be best implemented through SENTRNet, which he described as a "tissue-based translational research network" that would meet the challenges and exploit the opportunities presented by these diseases. Among the challenges: a paucity of patients, poorly understood risk factors and etiology, enormous cause of morbidity and mortality, and a shortage of both clinical practitioners and mechanistic researchers. Among the opportunities: integrating research on a range of diseases, utilizing available diagnostics, identifying measures for prevention and early detection, and providing a model for collaborative research on other cancers.

Dr. Reid added that SENTRNet would have multi-agency, multi-institutional, and multidisciplinary collaborations with shared leadership and management and a focus on interactive, translational research with clinical applications. Key elements include six "core centers" (two for translational research and one each for administration, informatics and pathology) plus a virtual tissue repository and approximately 12 to 14 clinical research centers. This mechanism will differ from current structures in that it will employ a business approach to management, guided by a strategy of mutual dependence and managed progressive growth. It will also follow a knowledge management and technology advances strategy that will facilitate effective collaborations on standardized protocols. Top research priorities will be (1) population-based cohort studies, (2) prevention trials, (3) patient and physician education, (4) collaborative clinical trials with standardized protocols, and (5) development of molecular markers and targets and animal models. He believes that this model could be developed in one year and would provide an infrastructure for other cancers with low incidence and high morbidity and mortality. SENTRNet would provide the necessary infrastructure for carrying out the identified research, capturing new research opportunities, and having a significant impact on these diseases.

ACD members had several questions about how the PRG recommendations will be merged with the proposed SENTRNet, and how this collaborative mechanism would set policies and make decisions, taking into consideration the PRG recommendations. Dr. Reid directed them to pages 22-30 of the draft report, which describes a steering committee representing the member institutions and participating disciplines. Individual investigators would receive appropriate training and incentives for sharing. The research priorities of SENTRNet are the same as the PRG recommendations.

Dr. Appelbaum suggested that budget constraints may affect NCI's resources and priorities in coming years and asked how these recommendations might be integrated with existing mechanisms, such as Cooperative Centers and SPOREs. Dr. Reid said that there were many obvious opportunities for collaboration with these partners; however, the current structures cannot address these stomach/esophageal cancer issues without substantial changes. Due to the paucity of patients at any one site, there must be a collaborative network of clinical research centers governed by one protocol. SENTRNet could be fully implemented across five years with a funding windfall. The centralized structures and at least three clinical research centers could be implemented in the first two years. The remaining clinical research centers and translational labs could be added as more funding becomes available. In addition, several potential funding partners were identified, such as NIDDK, NIAID and private industry.

Ms. LeStage was glad to see that the report gave high priority to quality-of-life issues, which are sometimes ignored in favor of marginal increases in survival, and she encouraged NCI to emphasize these issues in responding to the PRG's recommendations. Other Advisory Committee members noted that many new imaging technologies could be useful for noninvasive screening and diagnosis of esophageal and gastric cancers. Dr. Reid agreed that these issues warrant greater attention, and added that patient advocates and gastroenterologists had been enthusiastic participants in the PRG and major drivers in developing its recommendations. The PRG also included epidemiologists and population specialists, but not the Harvard Center for Cancer Prevention. Dr. Eberlein agreed to contact this center as soon as the SENTRNet proposal is more clearly developed. He agreed that it was important to develop a critical mass of clinical sites, adding that the 10 or 15 centers that currently see almost all of the cases in the United States would be the initial targets in the development of SENTRNet.

Dr. von Eschenbach again raised the concern of limited funds. He suggested that a proposal to create SENTRNet might be more favorably received, and more easily implemented, if its programs were more closely integrated with those of existing NCI-sponsored mechanisms and initiatives, such as the SPORES.

ACD members voted unanimously to accept the draft report of the PRG. The report itself will be posted to the NCI website, and an internal NCI working group will now develop a response to the report, mapping the PRG recommendations against existing resources and programs and, where needed, identifying opportunities for new initiatives through which they can be implemented. Dr. von Eschenbach thanked the PRG members and staff for their efforts on this project.

The teleconference adjourned at 2:30 p.m.