iCaRe 2

1. iCaRe2 Integrated Cancer Data Repository for Cancer Research icare2.unmc.edu Oleg Shats oshats@unmc.edu Fred & Pamela Buffett Cancer Center University of Nebraska Medical Center May 9, 2019

2. Outline What is iCaRe2? Timeline Software architecture User interfaces Data being collected Organizational model Data feeds How to obtain data for research Utilization Demos

3. Acknowledgements The iCare2 is supported predominantly by UNMC Fred and Pamela Buffett Cancer Center with some support from the UNMC College of Medicine. At various phases, iCaRe2 registries were also supported by National Institutes of Health (NIH), NE DHSS LB506 program, UNMC Clinical Research Center, NU Foundation, and the Leona M. and Harry B. Helmsley Foundation.

4. icare2.unmc.edu irequest.unmc.edu

5. What is iCaRe2? A multi-institutional resource that collects and manages standardized, multi-dimensional, longitudinal data and biospecimens on adult cancer patients, high-risk individuals, and normal controls. The goals are: to advance comprehensive studies of risk factors of cancer development and progression to enable the design of novel strategies for prevention, screening, early detection, and personalized treatment of cancer.

6. What is iCaRe2? A HIPAA-compliant socio-technical system that addresses various aspects of interactions between: people (patients, clinical personnel, technicians, researchers, and administrators from multiple centers) technology (methods, tools, and databases) environment (governance procedures, laws and regulations, intellectual property issues, data and process flow, etc.)

7. Key Characteristics Open to any cancer center/hospital to participate Confederation principle as an organizational model Enrolls adult cancer patients (newly diagnosed and survivors), high-risk individuals and controls Patient portal withextensive patient questionnaire Collect blood and provide access to tissue samples Metadata-driven software architecture Automated workflows and pipelines for data integration

8. Timeline Pre-iCaRe2 registries iCaRe2 Healthy controls Pancreatic Breast Thyroid

9. iCaRe2 Registries  (investigator-initiated projects) • Pancreatic Cancer (PI: Dr. Quan Ly) • Breast Cancer (PIs: Drs. Ken Cowan, Jessica Maxwell) • Thyroid Tumor & Cancer (PI: Dr. Whitney Goldner) • Healthy Controls Registry / GPHID (PI: Dr. Ken Cowan) • Genitourinary Cancers (PI: Dr. Shawna Boyle) • Thoracic Oncology (PIs: Drs. David Berkheim, Apar Ganti) • Head and Neck Cancers (PI: Dr. Zafar Sayed) • Gastrointestinal & Abdominal Cavity Cancers (PIs: Drs. Jason Foster, Jean Grem) • Central Nervous System Tumors (PI: Dr. Nicole Shonka) • Leukemia and Myeloid Neoplasm (PI: Dr. Vijaya Bhatt) • Melanoma (PI: Dr. Alissa Marr) • Sarcoma (PI: Dr. Sean McGarry) • Gynecologic Cancers (PI: Dr. Kerry Rodabaugh) • Plasma Cell Dyscrasias Collaborative Registry (PI: Dr. Sarah Holstein) • Neuroendocrine Tumors (PIs: Drs. Abbey Fingeret, Kelsey Klute) • Unknown Primary cancers (PI: Dr. Apar Ganti)

10. Flashback: Working Groups for the Pancreatic Cancer Collaborative Registry (PCCR) IRB (Dr. Prentice) Ernest Prentice, Ph.D., U of Nebraska Med Center Henry Lynch, M.D., Creighton University Wendy Rubinstein, Ph.D., Northwestern University Pathology/Specimen (Drs. Hruban and Whitcomb) Ralph H. Hruban, M.D., Johns Hopkins University   Malcolm Bilimoria, M.D., Northwestern University Karen Kaul, M.D., Northwestern University Ernest Prentice, Ph.D., U of Nebraska Medical Center David Whitcomb, M.D., Ph.D., University of Pittsburgh Imaging (Dr. Brentnall) Mimi Canto, M.D., Johns Hopkins Hospital Teri Brentnall, M.D., University of Washington Babak (Bob) Etemad, M.D., U of Pittsburgh Med Center Joe Anderson, M.D., U of Nebraska Medical Center Maurits Wiersema, M.D., Mayo Clinic   PI: Randall Brand, M.D., U of Nebraska Medical Center Epi/Instrument (Drs. Lowenfels and Petersen) Henry Lynch, M.D., Creighton University Ralph H. Hruban, M.D., Johns Hopkins University Gloria Peterson, Ph.D., Mayo Clinic Rachael Stolzenberg-Solomon, M.P.H., Ph.D., NCI Albert B. Lowenfels, M.D., New York Medical College Richard H. Bell, Jr., M.D. , Northwestern University Wendy Rubinstein, Ph.D., Northwestern University Malcolm Bilimoria, M.D., Northwestern University Mark Talamonti, M.D., Northwestern University Simon Sherman, Ph.D., U of Nebraska Med Center Oleg Shats, M.S., U of Nebraska Medical Center David C Whitcomb M.D., Ph.D., U of Pittsburgh Chicago, October 31, 2001

11. Metadata Builder • NCI’s cancer Data Standards Registry and Repository (caDSR) Terminologies SNOMED-CT ICD-O-3 NAACCR Patient Questionnaire Data elements, Permissible values, Units of measure iCaRe2 Registries iCaRe2 Biobank OpenSpecimen Core Data Elements Cancer Registry External Data Sources Hospital Cancer Registry … Frozen & Paraffin Tissue Banks … Mapping rules Extended Data Elements Metadata Repository Cancer Registry Internal Staging DB Cancer-specificData Elements Metadata-driven Automated Registry Builder Mapping Pipelines Metadata-driven Extract-Transform-Load (ETL) procedures Clinical Data Elements Cancer Registry Validation rules, Dependency rules, Customization rules Look-n-feel attributes Form hierarchy, etc. ETL procedures Administrative Data Elements Users Integrated Data Repository Patient Master Index De-identification procedures De-id PHI Data Reporting & Mining Module Authorized Users Honest Broker process Visualization Dashboard Tableau Server iConsent: Electronic consenting iCaRe2: Infrastructure and Dataflow • Internal • Components • User • Interfaces iRequest: requests for data Researchers from participating centers iCaRe2 personnel Participants

12. http://cancerinformatics.unmc.edu/dashboards/icare2/ iCaRe2 Dashboard

13. Metadata Builder (Oracle APEX)

14. Registry’s GUI

17. Integration Dashboard (BC)

18. Sequencing Data

19. Bioinformatics Data

20. icaRe2 Biobank: OpenSpecimen

21. Data Mining Source code of OpenSpecimen, Krishagni Solutions is partially utilized (BSD-3 Style license)

23. Workflow for Feedback

24. Electronic Consenting

25. Electronic Data Requests

26. Electronic Data Requests

27. Types of Collected Data

28. Patient Questionnaires Common Core Questionnaire (CCQ) • Standardized forms for demographic, family and medical history, tobacco and alcohol usage, etc. Extended/optional questionnaire • Library of standardized forms for physical activity, dietary habits, vitamins, quality of life, etc. Cancer-specific forms • reason for seeking care, medications, symptoms, etc. Follow-up questionnaires CCQ is mapped to the NCI’s Cancer Data Standards Registry and Repository (caDSR)

29. NCI's caDSR

30. Organizational Model Confederation Principle: • Allows centers, irrespective of their size or location, to participate in data collection and collaborative studies • Provides each participating institution with an equal representation in the steering committee • Ensures that a center retains all rights to its own data • Collected data can be used by others only upon approval from data owners • We act as an “honest broker”

31. Operation • All participating centers obtain an IRB approval from their institutions and accept the Bylaws • Subjects sign informed consent to participate (online or paper) • Subjects complete detailed baseline questionnaire (online or paper) • Follow-up questionnaires are optional • Subjects donate blood and allow access to tissue leftover after completion of routine diagnostic or clinical procedures • Clinical personnel enters medical data (manual abstraction from EHR) • Data is transferred from the hospital Ca registry (if available) • Work is underway to link pathology and molecular studies data from NE-CARES • The goal is to feed structured clinical data from EHR

32. Data feed: Hospital Ca Registry • All Ca patients treated at Nebraska Medicine • There is six months delay • Bi-weekly feed in NAACCR format • Mapped to iCaRe2 cases by MRN • Data elements: • Demographic (DOB, gender, race, ethnicity, occupation, marital status, address) • Diagnostics (date, age, comorbidities, primary site, laterality, histologic type, grade, TNM staging) • Treatment (surgeries, therapies with dates, agents) • Cancer-specific factors • Recurrence (locoregional, distant mets, sites of mets, date) • Outcome (date of last update, vital status, date of death, cause of death)

33. Data feed: NE-CARES • Under development • All records mapped to iCaRe2 cases by MRN • Data elements: • Tissue availability in tissue banks • Structured pathology data from synoptic reports • Molecular observations (sequence variants)

34. iCaRe2 OpenSpecimen iCaRe2 biobank Tissues Manual review by Pathologist NE-CARES coPath FreezerWorks Clinical samples Frozen tissue bank Paraffin tissue bank

35. How can the data be obtained?irequest.unmc.edu • Research using identifiable data and/or biospecimens from iCaRe2 (may also have access to the medical record) • iCaRe2 approval • Expedited IRB • SRC approval • Research using de-identified data (will not have access to the medical record) • iCaRe2 approval only • Does not require IRB approval

36. Workflow for Data Requests

37. Projects utilizing iCaRe2 data • Circulating Tumor Cells in Pancreatic Ca (PC) –Grem • Pathobiology of PC: Identification & Evaluation of Biomarkers & Therapeutic Targets – Batra • PC Rapid Autopsy Program – Hollingsworth • Biomarker validation for Pancreatic Neoplasms – Batra • Identification of synergistic interactions between modifiable risk factors in PC development – Farazi • Assessment of dietary microRNAs as confounders in cancer biomarker studies – Cui • Cancer Dx and phenotype in relation to Vit D status – Hanson • Signaling Molecule Alterations in Colon Cancer – Black • Mechanisms of TGF-B mediated suppression of metastasis in colon cancer – Jenny Wang • Mucins in colorectalcancer – Batra • HIPEC in abdominal cancers – Foster • Serum MUC5AC levels in lung cancer – Ganti • Stage IIIa NSC lung cancer WES – Trujillo • ProstateCancer microRNA – LaGrange • A prognosis marker for prostate cancer – Pi-Wan Cheng Breast cancer (BC) whole genome sequencing – Cowan/Guda/Agendia and IBM Watson BC Inflammatory Biomarker – Cowan /Biodesix XPF-ERCC1 - predictable marker for chemotherapy BC – Bessho BC Tumor Margins detection using electrical and optical properties – West Behavioral and Genetic Factors Associated with Sleep Quality in BC – Berger Dietary intake and BC development – Hanson Familial BC – SanMing Wang Formation of estrogen-DNA adducts as a biomarker of breast cancer risk – Rogan Prevalence of Colorectal Adenomas in Breast Cancer Survivors – Tandra Papillary Thyroid Cancer (TC) WES – Goldner Modifiable Risk Factors in TC – R. Smith Metabolomic Eval. of benign and malignant Thyroid nodules – Goldner

38. Results are published in: • Am J Gastroenterol. • BMC Cancer • Breast J. • Cancer Inform. • Int J Endocrinol. • International Journal of Cancer • J of Oncology Navigation & Survivorship • Laryngoscope • Otolaryngol Head Neck Surg. • Supportive Care in Cancer • PLoS One

39. Participating centers iCaRe2 is currently utilized at 58 institutions (83 distinct sites) from 23 U.S. states and one center in Italy.

40. Numbers at a glance 59 Centers 83 Distinct Sites • 27,160 Cases • 16,513 UNMC Patient Cases; 4,154 with Blood 30 patients a month consented at UNMC in average

41. Next objectives increase enrollment broaden coverage improve data validation rules expand data feeds from clinical data sources continue harmonizing data elements with standard terminologies boost utilization

42. iCaRe2 key personnel Kenneth Cowan, MD, PhD Executive Director Whitney Goldner, MD Lead PI Ben Swanson, MD, PhD Lead Pathologist Michelle Desler, MS Lead Research Coordinator Oleg Shats, MS IT / Informatics Director Jianmin (JJ) Feng, MS Database Developer & Administrator Taelyr Weekly, MPH, RN-BC Clinical Research Coordinator Pei Xian Chen, MD Research Technologist Amy Wells, MS Research Technologist ALL Centers’ PIs and Coordinators

43. Questions? Technical: Oleg Shats - oshats@unmc.edu Operational: Michelle Desler - mdesler@unmc.edu Organizational: Dr. Whitney Goldner – wgoldner@unmc.edu

44. iCaRe2 Resources Main website: icare2.unmc.edu Requests for Data: irequest.unmc.edu ‘iCaRe2 at a glance’ Dashboard (Intranet access only): cancerinformatics.unmc.edu/dashboards/icare2 OpenSpecimen: openspecimen.unmc.edu 16 Registries: bccr.unmc.edu, tccr.unmc.edu, etc. Remote consent (prototype - pending IRB approval): www.unmc.edu/cancercenter/registry/enroll