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Suggested Citation:"Front Matter." 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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Ovarian Cancers

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

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THE NATIONAL ACADEMIES PRESS

Washington, DC

www.nap.edu

Suggested Citation:"Front Matter." 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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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

Additional copies of this report are available for sale from the National Academies Press, 500 Fifth Street, NW, Keck 360, Washington, DC 20001; (800) 624-6242 or (202) 334-3313; http://www.nap.edu.

Copyright 2016 by the National Academy of Sciences. All rights reserved.

Printed in the United States of America

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.

Suggested Citation:"Front Matter." 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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The National Academy of Sciences was established in 1863 by an Act of Congress, signed by President Lincoln, as a private, nongovernmental institution to advise the nation on issues related to science and technology. Members are elected by their peers for outstanding contributions to research. Dr. Ralph J. Cicerone is president.

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The three Academies work together as the National Academies of Sciences, Engineering, and Medicine to provide independent, objective analysis and advice to the nation and conduct other activities to solve complex problems and inform public policy decisions. The Academies also encourage education and research, recognize outstanding contributions to knowledge, and increase public understanding in matters of science, engineering, and medicine.

Learn more about the National Academies of Sciences, Engineering, and Medicine at www.national-academies.org.

Suggested Citation:"Front Matter." 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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Suggested Citation:"Front Matter." 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.
×

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

Suggested Citation:"Front Matter." 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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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

Study Staff

TRACY A. LUSTIG, Study Director

MARK D. STEWART, Research Associate

SAPANA R. VORA, Christine Mirzayan Science and Technology Policy Graduate Fellow1; Research Associate2

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.

Suggested Citation:"Front Matter." 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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Reviewers

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

Page viii Cite
Suggested Citation:"Front Matter." 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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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.

Suggested Citation:"Front Matter." 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.
×

Preface

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.

Suggested Citation:"Front Matter." 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.
×

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.

Suggested Citation:"Front Matter." 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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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

Suggested Citation:"Front Matter." 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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Suggested Citation:"Front Matter." 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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Acknowledgments

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

Suggested Citation:"Front Matter." 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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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.

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Suggested Citation:"Front Matter." 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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Suggested Citation:"Front Matter." 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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Suggested Citation:"Front Matter." 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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Suggested Citation:"Front Matter." 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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Suggested Citation:"Front Matter." 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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In an era of promising advances in cancer research, there are considerable and even alarming gaps in the fundamental knowledge and understanding of ovarian cancer. Researchers now know that ovarian cancer is not a single disease--several distinct subtypes exist with different origins, risk factors, genetic mutations, biological behaviors, and prognoses. However, persistent questions have impeded progress toward improving the prevention, early detection, treatment, and management of ovarian cancers. Failure to significantly improve morbidity and mortality during the past several decades is likely due to several factors, including the lack of research being performed by specific disease subtype, lack of definitive knowledge of the cell of origin and disease progression, and incomplete understanding of genetic and non-genetic risk factors.

Ovarian Cancers examines the state of the science in ovarian cancer research, identifies key gaps in the evidence base and the challenges to addressing those gaps, considers opportunities for advancing ovarian cancer research, and examines avenues for translation and dissemination of new findings and communication of new information to patients and others. This study makes recommendations for public- and private-sector efforts that could facilitate progress in reducing the incidence of morbidity and mortality from ovarian cancers.

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