IMPROVING
CANCER
DIAGNOSIS
AND CARE

Clinical Application of Computational Methods
in Precision Oncology

PROCEEDINGS OF A WORKSHOP

Emily Zevon, Margie Patlak, and Sharyl J. Nass, Rapporteurs

National Cancer Policy Forum

Board on Health Care Services

Health and Medicine Division

THE NATIONAL ACADEMIES PRESS
Washington, DC
www.nap.edu

THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001

This activity was supported by Contract No. 200-2011-38807 (Task Order No. 75D30118F00071) and Contract No. HHSN263201800029I (Task Order No. HHSN26300008) with the Centers for Disease Control and Prevention and the National Cancer Institute/National Institutes of Health, respectively, and by the American Association for Cancer Research, American Cancer Society, American College of Radiology, American Society of Clinical Oncology, Association of American Cancer Institutes, Association of Community Cancer Centers, Bristol-Myers Squibb, Cancer Support Community, CEO Roundtable on Cancer, Flatiron Health, Helsinn Therapeutics (U.S.), Inc., LIVESTRONG Foundation, Merck, National Comprehensive Cancer Network, Novartis Oncology, Oncology Nursing Society, and Pfizer Inc. 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: 978-0-309-49081-8
International Standard Book Number-10: 0-309-49081-2
Digital Object Identifier: https://doi.org/10.17226/25404

Additional copies of this publication are available 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 2019 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. 2019. Improving cancer diagnosis and care: Clinical application of computational methods in precision oncology: Proceedings of a workshop. Washington, DC: The National Academies Press. doi: https://doi.org/10.17226/25404.

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WORKSHOP PLANNING COMMITTEE¹

CHRISTOPHER R. COGLE (Chair), Professor of Medicine, Pierre Chagnon Professor of Stem Cell Biology and Bone Marrow Transplant, University of Florida; Scholar in Clinical Research, Leukemia & Lymphoma Society

AMY P. ABERNETHY, Chief Medical Officer, Chief Scientific Officer, and Senior Vice President, Oncology, Flatiron Health²

CONSTANTINE GATSONIS, Henry Ledyard Goddard University Professor, Founding Chair, Department of Biostatistics, Founding Director, Center for Statistical Sciences, Brown University School of Public Health

LORI HOFFMAN HŌGG, Veterans Health Administration National Program Manager, Prevention Policy, National Center for Health Promotion and Disease Prevention; National Oncology Clinical Advisor, Office of Nursing Services, Department of Veterans Affairs

HEDVIG HRICAK, Chair, Department of Radiology, Memorial Sloan Kettering Cancer Center

SAMIR N. KHLEIF, Director, Jeannie and Tony Loop Immuno-Oncology Lab; Biomedical Scholar and Professor of Oncology, Georgetown Lombardi Comprehensive Cancer Center, Georgetown University Medical Center

MIA LEVY, Director, Rush University Cancer Center; Associate Professor of Medicine, Division of Hematology and Oncology; and System Vice President, Cancer Services, Rush University System for Health

DAVID MAGNUS, Thomas A. Raffin Professor of Medicine and Biomedical Ethics, Professor of Pediatrics and Medicine, and Director, Center for Biomedical Ethics, Stanford University

MARTIN J. MURPHY, Chief Executive Officer, CEO Roundtable on Cancer

BAKUL PATEL, Associate Director, Digital Health, Center for Devices and Radiological Health, Food and Drug Administration

___________________

¹ The National Academies of Sciences, Engineering, and Medicine’s planning committees are solely responsible for organizing the workshop, identifying topics, and choosing speakers. The responsibility for the published Proceedings of a Workshop rests with the workshop rapporteurs and the institution.

² In February 2019, Dr. Abernethy became Principal Deputy Commissioner of Food and Drugs at the Food and Drug Administration.

ROBERT A. WINN, Associate Vice Chancellor, Community-Based Practice; Professor of Medicine, Division of Pulmonary and Critical Care Medicine, University of Illinois at Chicago; Director, University of Illinois Cancer Center

Project Staff

ERIN BALOGH, Senior Program Officer

RUTH COOPER, Senior Program Assistant (from October 2018)

NATALIE LUBIN, Senior Program Assistant (until October 2018)

CYNDI TRANG, Research Assistant (until September 2018)

EMILY ZEVON, Associate Program Officer (from October 2018)

SHARYL J. NASS, Forum Director and Director, Board on Health Care Services

NATIONAL CANCER POLICY FORUM¹

EDWARD J. BENZ, JR. (Chair), President and Chief Executive Officer Emeritus, Dana-Farber Cancer Institute; Richard and Susan Smith Distinguished Professor of Medicine, Genetics and Pediatrics, Harvard Medical School

LUCILE L. ADAMS-CAMPBELL, Professor of Oncology, Associate Director for Minority Health and Health Disparities Research, and Senior Associate Dean, Community Outreach and Engagement, Georgetown Lombardi Comprehensive Cancer Center

GARNET L. ANDERSON, Senior Vice President and Director, Public Health Sciences Division, Fred Hutchinson Cancer Research Center; Affiliate Professor, Department of Biostatistics, University of Washington

KENNETH ANDERSON, Kraft Family Professor of Medicine, American Cancer Society Clinical Research Director, Jerome Lipper Multiple Myeloma Center, Harvard Medical School, Dana-Farber Cancer Institute

WILLIAM L. BAILEY, Vice President, Medical & Scientific Affairs Research & Development, Helsinn Therapeutics (U.S.), Inc.

KAREN BASEN-ENGQUIST, Annie Laurie Howard Research Distinguished Professor, Professor of Behavioral Science, and Director, Center for Energy Balance in Cancer Prevention and Survivorship, The University of Texas MD Anderson Cancer Center

CHRIS BOSHOFF, Chief Development Officer, Oncology, Global Product Development, Pfizer Inc.

CATHY J. BRADLEY, Associate Dean for Research, Colorado School of Public Health, Professor and Deputy Director, University of Colorado Cancer Center

OTIS W. BRAWLEY, Bloomberg Distinguished Professor, Department of Epidemiology, Bloomberg School of Public Health, Department of Oncology, School of Medicine, Johns Hopkins University

ROBERT W. CARLSON, Chief Executive Officer, National Comprehensive Cancer Network

___________________

¹ The National Academies of Sciences, Engineering, and Medicine’s forums and roundtables do not issue, review, or approve individual documents. The responsibility for the published Proceedings of a Workshop rests with the workshop rapporteurs and the institution.

NANCY E. DAVIDSON, President and Executive Director, Seattle Cancer Care Alliance; Senior Vice President, Director, and Full Member, Clinical Research Division, Fred Hutchinson Cancer Research Center; Head, Department of Medicine, Division of Medical Oncology, University of Washington

GEORGE D. DEMETRI, Professor of Medicine and Director, Ludwig Center, Harvard Medical School; Senior Vice President for Experimental Therapeutics, Dana-Farber Cancer Institute; Associate Director for Clinical Sciences, Dana-Farber/Harvard Cancer Center

JAMES H. DOROSHOW, Deputy Director for Clinical and Translational Research, National Cancer Institute

NICOLE F. DOWLING, Associate Director for Science, Division of Cancer Prevention and Control, Centers for Disease Control and Prevention

SCOT W. EBBINGHAUS, Vice President and Therapeutic Area Head, Oncology Clinical Research, Merck Research Laboratories

KOJO S. J. ELENITOBA-JOHNSON, Professor, Perelman School of Medicine; Director, Center for Personalized Diagnostics and Division of Precision and Computational Diagnostics, University of Pennsylvania

AWNY FARAJALLAH, Vice President, Head, US Medical Oncology, Bristol-Myers Squibb

STANTON L. GERSON, Director, Case Comprehensive Cancer Center; Professor of Hematological Oncology, Case Western Reserve University; Director, University Hospitals Seidman Cancer Center

LORI HOFFMAN HŌGG, Veterans Health Administration National Program Manager, Prevention Policy, National Center for Health Promotion and Disease Prevention; National Oncology Clinical Advisor, Office of Nursing Services, Department of Veterans Affairs

LINDA HOUSE, President, Cancer Support Community

HEDVIG HRICAK, Chair, Department of Radiology, Memorial Sloan Kettering Cancer Center

ROY A. JENSEN, President, Association of American Cancer Institutes; Director, The University of Kansas Cancer Center; William R. Jewell, M.D. Distinguished Masonic Professor, Kansas Masonic Cancer Research Institute

LISA KENNEDY SHELDON, Chief Clinical Officer, Oncology Nursing Society

SAMIR N. KHLEIF, Director, Jeannie and Tony Loop Immuno-Oncology Lab; Biomedical Scholar and Professor of Oncology, Georgetown Lombardi Comprehensive Cancer Center, Georgetown University Medical Center

RONALD M. KLINE, Medical Officer, Patient Care Models Group, Center for Medicare & Medicaid Innovation, Centers for Medicare & Medicaid Services

MICHELLE M. LE BEAU, Arthur and Marian Edelstein Professor of Medicine and Director, The University of Chicago Medicine Comprehensive Cancer Center

MIA LEVY, Director, Rush University Cancer Center; Associate Professor of Medicine, Division of Hematology and Oncology; and System Vice President, Cancer Services, Rush University System for Health

J. LEONARD LICHTENFELD, Interim Chief Medical Officer, American Cancer Society

NEAL J. MEROPOL, Vice President, Research Oncology, Flatiron Health

MARTIN J. MURPHY, Chief Executive Officer, CEO Roundtable on Cancer

RANDALL A. OYER, Medical Director, Oncology, Ann B. Barshinger Cancer Institute, Penn Medicine Lancaster General Health

RICHARD PAZDUR, Director, Oncology Center of Excellence; Acting Director, Office of Hematology and Oncology Products, Food and Drug Administration

RICHARD L. SCHILSKY, Senior Vice President and Chief Medical Officer, American Society of Clinical Oncology

DEBORAH SCHRAG, Chief, Division of Population Sciences, Professor of Medicine, Department of Medical Oncology, Harvard Medical School, Dana-Farber Cancer Institute

LAWRENCE N. SHULMAN, Professor of Medicine, Deputy Director for Clinical Services, and Director, Center for Global Cancer Medicine, Abramson Cancer Center, University of Pennsylvania

DAN THEODORESCU, Director, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center

VERENA VOELTER, Head, United States Oncology Clinical Development & Medical Affairs, Novartis Pharmaceuticals Corporation

GEORGE J. WEINER, C.E. Block Chair of Cancer Research, Professor of Internal Medicine, and Director, Holden Comprehensive Cancer Center, The University of Iowa

ROBERT A. WINN, Associate Vice Chancellor, Community-Based Practice; Professor of Medicine, Division of Pulmonary and Critical Care Medicine, University of Illinois at Chicago; Director, University of Illinois Cancer Center

National Cancer Policy Forum Staff

ERIN BALOGH, Senior Program Officer

RUTH COOPER, Senior Program Assistant

ANNALEE GONZALES, Administrative Assistant

NATALIE LUBIN, Research Assistant

MICAH WINOGRAD, Financial Officer

EMILY ZEVON, Associate Program Officer

SHARYL J. NASS, Forum Director and Director, Board on Health Care Services

Reviewers

This Proceedings of a Workshop was 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 National Academies of Sciences, Engineering, and Medicine in making each published proceedings as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and responsiveness to the charge. The review comments and draft manuscript remain confidential to protect the integrity of the process.

We thank the following individuals for their review of this proceedings:

Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the content of the proceedings nor did they see the final draft before its release. The review of this proceedings was overseen by DANIEL R. MASYS, University of Washington School of Medicine. He was responsible for making certain that an independent examination of this proceedings was carried out in accordance with standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the rapporteurs and the National Academies.

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Acknowledgments

Support from the many annual sponsors of the National Academies of Sciences, Engineering, and Medicine’s National Cancer Policy Forum is crucial to the work of the forum. Federal sponsors include the Centers for Disease Control and Prevention and the National Cancer Institute/National Institutes of Health. Non-federal sponsors include the American Association for Cancer Research, American Cancer Society, American College of Radiology, American Society of Clinical Oncology, Association of American Cancer Institutes, Association of Community Cancer Centers, Bristol-Myers Squibb, Cancer Support Community, CEO Roundtable on Cancer, Flatiron Health, Helsinn Therapeutics (U.S.), Inc., LIVESTRONG Foundation, Merck, National Comprehensive Cancer Network, Novartis Oncology, Oncology Nursing Society, and Pfizer Inc.

The forum wishes to express its gratitude to the expert speakers whose presentations helped further the dialogue and advance progress in the use of high-dimensional omics data, computational methods, and clinic infrastructures enabling precision oncology care. The forum also wishes to thank the members of the planning committee for their work in developing an excellent workshop agenda.

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Contents

ACRONYMS AND ABBREVIATIONS

PROCEEDINGS OF A WORKSHOP

WORKSHOP OVERVIEW

NEW PARADIGM IN CANCER DIAGNOSIS AND CARE

Computational Technologies

Machine Learning

Machine Learning Applications in Radiology

Health Apps

TRANSLATION CHALLENGES

Data Quality and Completeness

Risk of Bias

Validation of Computational Precision Oncology

Test Development and Analytical Validation Steps

Statistical Validation

Clinical Validation

Face Validity

Gaps in Reproducibility

Regulatory Oversight

Digital Data Standards

Devices

Software as a Medical Device

Quantitative Imaging Devices

Laboratory Developed Tests

Patient Privacy

General Data Protection Regulation

California Consumer Privacy Act of 2018

Communicating Results and Risks to Patients

Challenges for Payers

RESEARCH NEEDED

EXAMPLES OF CARE DELIVERY MODELS FOR COMPUTATIONAL PRECISION MEDICINE

Moffitt Cancer Center Precision Oncology Program

Intermountain Healthcare Precision Oncology Program

Department of Veterans Affairs’ National Precision Oncology Program

University of California

Vanderbilt–Ingram Cancer Center’s My Cancer Genome

LESSONS LEARNED FROM IMPLEMENTING COMPUTATIONAL PRECISION ONCOLOGY CARE

Financial Support

Patient-Centered and Clinician-Friendly Design

Informed Consent

Improve Clinician Understanding of Omics and Analytics

Standards

Data Sharing

Large-Scale Public Databases

Incentives for Sharing Data

Enabling Patient Sharing of Data

Data Protection

Multidisciplinary Teamwork

WRAP-UP

REFERENCES

APPENDIX A: STATEMENT OF TASK

APPENDIX B: WORKSHOP AGENDA

Boxes, Figures, and Tables

BOXES

1 Suggestions from Individual Workshop Participants to Improve the Translation of Computational Precision Oncology into Clinical Practice

2 Overview of the First Workshop on Improving Cancer Diagnosis and Care

3 Requirements for a Rigorous Validation of a Predictor

4 Project GENIE

5 Health 0.0 at the Massachusetts Institute of Technology

FIGURES

1 The process of making a fit-for-purpose real-world dataset

2 Risk-based approach to assessing importance of independent review

3 Precision oncology workflow at Intermountain Healthcare

4 Department of Veterans Affairs’ National Precision Oncology Program data flow

5 Infrastructure of the Center for Data-Driven Insights and Innovation

TABLES

1 Device Class and Premarket Requirements

2 Individual Rights Under the General Data Protection Regulation and the HIPAA Privacy Rule

3 Results Disclosure Communication Approaches

Acronyms and Abbreviations