The teleconference of the Advisory Committee to the Director, National Cancer Institute, was convened on November 20, 2001, at 11:00 a.m. EST at the National Institutes of Health, Building 31, Conference Room 11A03.

Advisory Committee members participating in the teleconference:
Alan S. Rabson, M.D., Acting Director, National Cancer Institute (Chair)
Frederick R. Appelbaum, M.D., Fred Hutchison 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, Massachusetts Institute of Technology (National Cancer Advisory Board)
Barbara LeStage (Director's Consumer Liaison Group)

Ex Officio members participating:
Marvin Kalt, Ph.D., National Cancer Institute

Executive Secretary:
Chitra Mohla, National Cancer Institute

Other participants:
Norma Davis, National Cancer Institute
Deborah Duran, Ph.D., National Cancer Institute
David Goldstein, National Cancer Institute
William J. Hoskins, M.D., Memorial Sloan Kettering Cancer Center (Co-Chair, Gynecologic Cancers Progress Review Group)
Anna Levy, National Cancer Institute
Cherie Nichols, M.B.A., National Cancer Institute
Edward C. Trimble, National Cancer Institute (Executive Director, Gynecologic Cancers Progress Review Group)
Nicole Urban, Sc.D., Fred Hutchinson Cancer Research Center (Co-Chair, Gynecologic Cancers Progress Review Group)
Sandy Williams, 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 Gynecologic Cancers ProgressReview Group (GYN PRG). The ACD must formally accept the report to enable NCI to develop an implementation plan based on the report's recommendations.

NCI Acting Director Dr. Alan Rabson, in the Chair, welcomed everyone in attendance. Ms. Mohla 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.

PRESENTATION: FINAL DRAFT REPORT OF THE GYNECOLOGIC CANCERS PROGRESS REVIEW GROUP

Dr. Urban briefly described the process the GYN PRG had used to ensure that appropriate attention was paid to the research needs of the three tumor types (cervical, ovarian, and endometrial) it was charged with addressing. Drs. Urban and Hoskins summarized the 10 ranked research priorities that the GYN PRG report identified. The GYN PRG considers implementation of these priorities to be essential if significant progress is to be achieved in the next 5 years toward the cure of gynecologic cancers.

1. Essential Research Priority

• Develop and make available to the cancer research community a Virtual Shared Specimen Resource (VSSR) to support gynecological cancer research.

• Rationale: Research progress is impeded by a dearth of high-quality, fresh-frozen, annotated specimens available to the gynecologic research community. In part because technologies are developing so rapidly, cutting-edge research requires specimens that are obtained at critical points in the disease process, processed and stored in evolving ways, and associated with high-quality clinical and follow-up data.
• The VSSR will facilitate molecular profiling to identify the molecular signatures of gynecologic cancers as well as the discovery of markers of gynecologic cancer risk, premalignant and malignant disease, and new approaches to preventing and treating progressive disease.
• Features of the VSSR would include specific scientific goals, a coordinating center, and an advisory committee to ensure efficiency, equity, quality, and inventory control in specimen collection, management, and distribution. The VSSR would be "virtual" in the sense that information describing the specimens would be managed centrally, although the specimens themselves would reside in various institutions.
• Recommended actions:
  (1) NCI should provide the resources needed to facilitate development of a VSSR for gynecologic cancer research.
  (2) An advisory committee composed of leaders in gynecologic cancer research should monitor and oversee the progress of the resource and the research it supports.
  (3) Multiple institutions should collaborate in the development and use of the VSSR.

2. High-Impact Priorities

• Identify precursor lesions, markers of risk and early detection, molecular disease classifications, prognostic indicators, and new targets for prevention and treatment.

• Rationale: Although early detection and prevention offer the best hope for reducing mortality from gynecologic cancers and improving quality of life for cancer survivors, no effective screening strategies exist for ovarian or endometrial cancer; precursor lesions for ovarian cancer and Type II endometrial cancer are unknown; and only limited means exist for identifying women at high risk for these diseases.
• To advance knowledge in all these areas-screening, risk, treatment, and prognosis-molecular markers associated with cervical, endometrial, and ovarian cancers must be identified. Markers for early detection and risk will help diagnose cancer in its earliest stages; molecular targets for treatment can lead to more individualized and less toxic therapies; and markers for response to therapy and prognosis will help tailor therapies according to the molecular profile of each woman's cancer.
• Recommended actions: An efficient, equitable means of ensuring the availability of appropriate human specimens is essential to make progress in comparative genomics or proteomics or in molecular profiling of the gynecologic cancers. Specimens must be accompanied by associated clinical information.

• Develop effective human papillomavirus (HPV) vaccines to prevent biotransmission and development of neoplasia.

• Rationale: Cervical cancer remains one of the leading causes of cancer deaths among women throughout the world. Research has made clear the primary role of HPV in the development of cervical neoplasia. The development and implementation of effective HPV prophylactic and therapeutic vaccine strategies has the potential to nearly eradicate cervical cancer. In addition, development of effective prophylactic and therapeutic vaccines could dramatically reduce the cost of screening for cervical cancer. Although HPV vaccine research has been under way for some time, no effective prophylactic and therapeutic vaccine has yet been identified and a number of key issues remain to be addressed.
• Recommended actions: Research toward an HPV vaccine would be enhanced by encouraging studies to improve basic understanding of mucosal immunity in the cervix, understanding the initiation of effective mucosal immunity, and researching who develops chronic HPV infection and in whom it can be eradicated.

• Conduct research to (1) understand and improve quality of life, and (2) reduce or eliminate disparities related to care among patients with gynecologic cancers.

• Rationale: Much is unknown about how to ensure that all women with gynecologic cancers experience optimal health-related quality of life. Disparities in the care of some patients may lead to vastly different outcomes. Significant research support is needed to understand and develop interventions that will improve quality of life for all women; and to understand and overcome the underlying factors that result in disparities in care.
• Recommended actions: (1) Conduct large observational cohort studies of patients with newly and previously diagnosed gynecologic cancers to investigate the impact of targeted interventions on patient-centered outcomes, identify the influence of modifiable risk factors on gynecologic cancers, and discover options to eliminate disparities in the delivery of high-quality cancer care.
  (2) Conduct intensive research to develop and evaluate interventions to maintain and enhance health-related quality of life in women with gynecologic cancers.

3. Scientific Opportunities

In addition to the above essential and high-impact priorities, the GYN PRG identified six Scientific Opportunities that it recommends should also be an important part of NCI's research plan for gynecologic cancer.

• Characterize the hormonal, immunologic, and epithelial/stromal interactions that result in the development of gynecologic cancers.
• Develop imaging techniques to evaluate tumor biology, molecular signatures, and therapeutic response.
• Develop relevant preclinical models for gynecologic cancers.
• Find ways to overcome resistance to chemotherapy and radiotherapy.
• Develop individualized and optimized radiation therapy techniques in conjunction with other treatment modalities.
• Encourage increased participation in clinical trials in gynecologic cancer.

DISCUSSION

The following points emerged in response to questions from ACD members:

• A question was raised concerning the knowledge of the ongoing HPV vaccine trials that are relatively small and uncoordinated. Challenges in the design of vaccine trials include issues such as selecting the correct patient population and choosing the correct surrogate markers. NCI is currently supporting a trial of a promising vaccine in Costa Rica, a country with a high incidence of cervical cancer. Vaccine researchers who participated in the GYN PRG roundtable meeting felt that a better understanding of mucosal immunity is a prerequisite for the development of effective vaccines. The co-chairs acknowledge their knowledge of the current state of the science, shared the highlights from prior discussions about the topic and agreed to consider adding a statement to the PRG report to address the need to address issues with communities in third-world countries where most trials of cervical cancer vaccines are taking place.
• A question was raised inquiring about the opportunities for imaging research range from initial patient evaluation to evaluation of patients undergoing therapy. Preliminary data are becoming available on PET scanning in gynecologic cancers. The leadership explained that the Roundtable participants addressed this topic understood the importance of using existing modalities but also believe that developing molecular techniques have the potential to greatly expand the use of these modalities in gynecologic cancers. This information is included in the breakout recommendations found in the appendix of the report and is included as a scientific opportunity. However, the issue was not deemed as one of the top priorities that the PRG selected to advance the field.
• Advocacy involvement was considered critical to the advancement of the research priorities. a) It was also noted that collaborations could be developed with advocacy groups to increase accrual for the proposed large observational studies of quality of care and survivorship issues.
  b) Incentives will be needed to persuade investigators to make their tissues available to a central resource such as the proposed VSSR. The provision of clinical data associated with tissues, while essential to ensure that tissues are useful for research purposes, raises confidentiality issues that must be addressed; the involvement of advocacy organizations will be essential in this process.
• There was total agreement of the importance of both points. Although advocates were included in several sections of the report, a statement to include an advocacy representative in the advisory committee of the proposed VSSR will be added to the report.
• A discussion took place about the appropriateness of incorporating measurable goals and objectives into the GYN PRG report developed by PRG members. It was suggested that the most appropriate point at which to introduce metrics might be at the implementation stage. It was agreed that it the entire PRG will have a role in the development of appropriate metrics.

On a voice vote, ACD members accepted the report of the Gynecologic Cancers PRG for transmittal to NCI for consideration and development of an implementation plan. Dr. Rabson thanked the PRG co-chairs and executive director for their work on the report. The co-chairs thanked NCI staff for their support during the report's preparation.

The teleconference was adjourned at 12:00 noon EST..