EVOLVING PARADIGMS IN RESEARCH AND CARE
Committee on the State of the Science in Ovarian Cancer Research
Board on Health Care Services
Institute of Medicine
THE NATIONAL ACADEMIES PRESS
THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001
This activity was supported by Contract No. 200-2011-38807 with the Centers for Disease Control and Prevention. Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for the project.
International Standard Book Number-13: 978-0-309-38046-1
International Standard Book Number-10: 0-309-38046-4
Library of Congress Control Number: 2016933599
Digital Object Identifier: 10.17226/21841
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Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2016. Ovarian cancers: Evolving paradigms in research and care. Washington, DC: The National Academies Press. doi: 10.17226/21841.
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COMMITTEE ON THE STATE OF THE SCIENCE
IN OVARIAN CANCER RESEARCH
JEROME F. STRAUSS III (Chair), Dean, School of Medicine and Professor of Obstetrics and Gynecology; Executive Vice President for Medical Affairs, Virginia Commonwealth University School of Medicine
RONALD D. ALVAREZ, Professor and Ellen Gregg Shook Culverhouse Chair, Division of Gynecologic Oncology, University of Alabama at Birmingham
DEBORAH J. BOWEN, Professor, University of Washington
KATHLEEN R. CHO, Peter A. Ward Professor and Vice Chair for Academic Affairs, Department of Pathology, University of Michigan Medical School
HEIDI DONOVAN, Professor and Vice Chair for Research, Department of Health and Community Systems; Director, Office of Community Partnerships, University of Pittsburgh School of Nursing
DEBRA DUQUETTE, State Genomics Coordinator, Board-Certified Genetic Counselor, Michigan Department of Health and Human Services
ROBERT A. HIATT, Professor and Chair, Epidemiology and Biostatistics; Associate Director for Population Sciences, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco
BETH Y. KARLAN, Director, Women’s Cancer Program, Division of Gynecologic Oncology, Cedars-Sinai Medical Center; Professor, Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles
DOUGLAS A. LEVINE, Attending Surgeon, Memorial Sloan Kettering Cancer Center
TERRY MAGNUSON, Sarah Graham Kenan Professor and Chair, Department of Genetics; Vice Dean for Research, University of North Carolina at Chapel Hill School of Medicine
LISA MEIER McSHANE, Mathematical Statistician, Chief, Biostatistics Branch, Biometric Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health
KUNLE ODUNSI, Cancer Center Deputy Director, M. Steven Piver Professor and Chair, Department of Gynecological Oncology; Executive Director, Center for Immunotherapy; Program Leader, Tumor Immunology and Immunotherapy, Roswell Park Cancer Institute
MARY JACKSON SCROGGINS, Founding Partner, Pinkie Hugs, LLC; Co-Founder, In My Sister’s Care
ANIL K. SOOD, Professor and Vice Chair, Departments of Gynecologic Oncology & Reproductive Medicine and Cancer Biology, and Co-Director, Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center
SHELLEY S. TWOROGER, Associate Professor of Medicine and Epidemiology, Harvard Medical School/Harvard T.H. Chan School of Public Health/Brigham and Women’s Hospital
TRACY A. LUSTIG, Study Director
MARK D. STEWART, Research Associate
NOA L. NIR, Senior Program Assistant
SHARYL J. NASS, Director, Board on Health Care Services; Director, National Cancer Policy Forum
1 January 2015 through April 2015.
2 April 2015 through August 2015.
This report has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the institution in making its published report as sound as possible and to ensure that the report meets institutional standards for objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We wish to thank the following individuals for their review of this report:
MICHAEL A. BOOKMAN, Arizona Oncology
ROBERT E. BRISTOW, University of California, Irvine
SETSUKO K. CHAMBERS, University of Arizona
MARTHA (MEG) GAINES, University of Wisconsin–Madison
SUSAN GALBRAITH, AstraZeneca
PATRICIA A. GANZ, University of California, Los Angeles
JOE GRAY, Oregon Health & Science University
TAMARA A. HENRY, The George Washington University
GEOFFREY KIM, U.S. Food and Drug Administration
ANN KOLKER, Ovarian Cancer National Alliance (retired)
GUILLERMINA LOZANO, The University of Texas MD Anderson Cancer Center
DAVID J. MOONEY, Harvard University
DARWIN J. PROCKOP, Texas A&M University Health Science Center
JOELLEN M. SCHILDKRAUT, University of Virginia School of Medicine
REBECCA SUTPHEN, University of South Florida Morsani College of Medicine; InformedDNA
NICOLE URBAN, Fred Hutchinson Cancer Research Center
Although the reviewers listed above have provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations nor did they see the final draft of the report before its release. The review of this report was overseen by OLUFUNMILAYO F. OLOPADE, The University of Chicago, and ELI Y. ADASHI, The Warren Alpert Medical School, Brown University. They were responsible for making certain that an independent examination of this report was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content of this report rests entirely with the authoring committee and the institution.
This congressionally mandated report, sponsored by the Centers for Disease Control and Prevention, assesses the state of research on ovarian cancers from multiple perspectives, and by multiple disciplines. The report has its origins in the Gynecologic Cancer Education and Awareness Act, more commonly known as Johanna’s Law, signed into law by President George W. Bush on January 12, 2007. It was named for Johanna Silver Gordon, a school teacher who died of ovarian cancer.
The findings of the committee are based on its internal expertise and input from external experts representing multiple domains of cancer research and cancer care (e.g., ovarian cancer researchers; clinicians who counsel and treat women with risk of ovarian cancer or with an ovarian cancer diagnosis; funding agencies, both governmental and private; advocacy groups; and of course women who have the disease and their families). The scientific evidence supporting the conclusions and recommendations is presented in a series of chapters that are sequenced to follow the cancer care continuum. The chapters emphasize key new information and highlight unmet needs that are unique to cancers of the ovary and their disease trajectories.
An overarching conclusion is that ovarian cancer is not one disease. There are a number of different tumor types with characteristic histologic features, distinctive molecular signatures, and disease trajectories. Moreover, these tumors are heterogeneous, and they can arise from different tissues of the female reproductive tract. Although the report touches on a number of the different ovarian cancer types, its main focus is on the most common and most lethal type, high-grade serous carcinoma.
This report is particularly timely because of the emergence of new concepts regarding the nature and origin of ovarian cancers. These new concepts have profound implications for the taxonomy of ovarian cancers; the interpretation of older literature that failed to make distinctions among ovarian cancer types; the identification of risk factors for specific ovarian cancer types; opportunities for improved early detection, prevention, and targeted molecular treatments; and the design of clinical trials. For example, the discovery that many high-grade serous ovarian carcinomas arise from a small population of cells in the distal end of the fallopian tubes, rather than the ovary per se, at once reveals the challenges of improving existing early detection and screening methods and focuses attention on potential new approaches to sampling the site of origin to identify precancerous lesions in women at risk for ovarian cancer. Additionally, these new concepts expose deficiencies in our knowledge, such as the need to identify factors that allow cells exfoliated from the tubes or other tissues of the reproductive tract to engraft and proliferate in the ovaries, as well as other common sites of metastasis. Importantly, these concepts inform potential prevention strategies for high-risk individuals, such as salpingectomy.
The 5-year survival of women with the most common and fatal type of ovarian cancer, high-grade serous carcinoma, has increased over the past four decades as a result of advances in specialty care and the development of effective first-line chemotherapy (i.e., platinum compounds in combination with drugs of the taxane family). However, there are concerning racial disparities and a number of unresolved issues regarding the optimal treatment of newly diagnosed women, which if addressed could lead to further reductions in morbidity and mortality. Moreover, important discoveries that directly influence clinical recommendations or care have not been widely adopted. For example, the recognition that a significant number of high-grade serous carcinomas arise in women harboring germline mutations in the BRCA1 or BRCA2 genes allows for genetic testing in families, risk prediction, and prevention interventions. Despite this important discovery of a major ovarian cancer risk factor, genetic testing and counseling for families at risk has not been universally adopted. The reasons underlying the lack of uptake remain to be determined.
The committee noted that the research agenda for ovarian cancers needs to be all encompassing given the disease trajectories. Although the most common and fatal ovarian cancers often respond initially to surgical cytoreduction and chemotherapy, they usually recur as a result of the development of resistance to existing chemotherapy drugs. The committee identified a need for social and behavioral research to improve the quality of life of survivors, research on palliative and end-of-life care, in addition to research on new primary therapies and methods to prevent the development of chemoresistance.
While pointing out these unmet research needs, the committee recognized that ovarian cancer clinical researchers face unique challenges because the disease is relatively rare among gynecologic malignancies. This relative rarity focused attention on the need to develop new clinical trial designs that are information rich in terms of molecular characterization and metadata so that clinically useful conclusions can be drawn quickly from smaller study enrollments.
In its evaluation of the state of research and promising opportunities emerging from the new understanding of the pathobiology of cancers of the ovary, the committee concluded that there is a need for research on and development of more effective dissemination strategies, that can inform diverse audiences, so that advances in the understanding of risk factors for all populations, new approaches for screening and early detection, information on optimal treatment regimens and new therapeutics, and ways to improve quality of life and end-of-life care are known by women, their health care providers, and those responsible for carrying out and sponsoring basic, translational, clinical, and comparative effectiveness research.
Jerome F. Strauss III, Chair
Committee on the State of the Science in Ovarian Cancer Research
The Committee on the State of the Science in Ovarian Cancer Research benefited from the contributions of many individuals. The committee takes this opportunity to recognize those who so generously gave their time and expertise to inform its deliberations.
This report was sponsored by the Centers for Disease Control and Prevention. We wish to thank Greta Massetti, Lisa Richardson, David Serwitz, Cheryll Thomas, and Tailee Tucker.
The committee benefited from presentations made by a number of experts outside the committee. The following individuals shared their experiences and perspectives during public meetings of the committee:
Calaneet Balas, Ovarian Cancer National Alliance
Christine Berg, Johns Hopkins Medicine
Ronny Drapkin, University of Pennsylvania
Karen Emmons, Kaiser Permanente
Simon Gayther, University of Southern California
Tony Ho, AstraZeneca
Melinda Irwin, Yale University
Guillermina Lozano, The University of Texas MD Anderson Cancer Research Center
Susan Lutgendorf, University of Iowa
Martin McIntosh, Fred Hutchinson Cancer Research Center
Alexander Nikitin, Cornell University
Nicolas Wentzensen, National Cancer Institute
Lari Wenzel, University of California, Irvine
The committee commissioned a paper to provide background information for its deliberations and to synthesize the evidence on particular issues. We thank the following individuals for their contributions to this paper:
Carolyn Lefkowits, University of Colorado
Rachel Ruskin, University of Oklahoma Health Sciences Center
We extend special thanks to the following individuals who were additional sources of information, generously giving their time and knowledge to further the committee’s efforts:
Mary Eiken, Society of Gynecologic Oncology
Rachel Gandell, American Congress of Obstetricians and Gynecologists
Shannon Hawkins, Indiana University
Elise Kohn, National Cancer Institute
Laura Koontz, Ovarian Cancer National Alliance
Percy Ivy, National Cancer Institute
Debbie Miller, Ovarian Cancer Trial Awareness Network & Empowerment
Patricia Modrow, U.S. Department of Defense Ovarian Cancer Research Program
Britton Trabert, National Cancer Institute
Finally, many within the National Academies of Sciences, Engineering, and Medicine were helpful to the study staff. The staff would like to thank Erin Balogh, Daniel Bearss, Patrick Burke, Chelsea Frakes, Greta Gorman, Jim Jensen, Nicole Joy, Linda Kilroy, Leslie Kwan, Katye Magee, Fariha Mahmud, Sandra McDermin, Janice Mehler, Rebecca Morgan, Bettina Ritter, and Jennifer Walsh. We also thank Heather Phillips and Robert Pool, copyeditors.