1. 1 An Update on the Informatics Supported Annotation and Integration of Datasets for the Gynecologic Disease Program (GDP) Waqas Amin MD 1, Sambit K. Mohanty MD 1&7, Anil V. Parwani MD PhD 1&3, Sharon B. Winters MS 1, Nancy B. Whelan BS 1, Althea M. Schneider BS 1, John T. Milnes BS 1, Charma D. Chaussard BS 4, Gail Harger MS 2, Katherine Farrow BS 2, Debra Bass MS 2, Tim D. Fennell MS 1, Hai Hu PhD 6, Thomas C. Krivak MD 4, Rajiv Dhir MD 3, Robert P. Edwards MD 4, Larry Maxwell MD 5 Michael J. Becich MD PhD 1&3, 1 Department of Biomedical Informatics and 2 Department of Epidemiology, University of Pittsburgh, PA. USA. 3Department of Pathology and 4 Department of Obstetrics Gynecology, Magee-Women Hospital, University of Pittsburgh Medical Center, PA USA. 5 Walter Reed Army Medical Center, Washington, DC. USA. 6 Windber Research Institute Windber, PA, USA. 7 Winthrop University Hospital, New York, USA

2. 2 Introduction:  The Gynecologic Disease Program (GDP), a.k.a Gynecologic Cancer Center, is funded by the Department of Defense (DOD).  Primary objective is to develop state-of-the-art capabilities in clinical and basic science research aimed at improving screening, early detection, prevention, and treatment of gynecologic disease.  Collaborators: Walter Reed Army Medical Center, University of Pittsburgh Cancer Institute, Windber Research Institute and Georgetown Medical Center.  At UPitt this program constitutes three cores:  Luminex  Proteomics  Tissue Banking Informatics

3. 3 Objectives:  To create a well-characterized and standard-based biospecimen repository for Ovarian and Endometrial malignancies.  To facilitate the collection and transfer of well annotated datasets to the central data warehouse (Windber Research Institute).  To create an internal storage system of transferred data using the Clinical Trial Management Application (CTMA).

4. 4 Common Data Elements  Through the combined efforts of experts from various fields, Common Data Elements (demographic, epidemiologic, clinical, pathologic specimen and block annotation, genotype, follow up and outcome) were developed for gynecological conditions.  Common Data Elements (CDEs) allow consistency and interoperability in biospecimen collection and better understanding of research and experimental data.  Major standards used to build CDEs:  College of American Pathology (CAP) checklists  Elements from coPath-synoptics  North American Association of Cancer Registry (NAACR) core elements

5. 5 OVARIAN TUMORS OTHERS (HYPERPLASIAS) GDP # (for patient) Date of Surgery Surgical Procedure Macroscopic Attributes - Anatomic Location - Size Microscopic Attributes - Histologic Type - Grade (Silverberg grade etc.) - Perifocal reaction - Nodal status - Pathologic Stage PATHOLOGY DATA (coPATH and Synoptics – CAP Checklist) EXTRAOVARIAN ABDOMINAL TUMORS ENDOMETRIAL TUMORS

6. 6 OVARIAN TUMORS OTHERS (HYPERPLASIAS) GDP # (for patient) Date of Surgery Surgical Procedure Clinical Staging (AJCC Staging) Therapy related variables Recurrence / Metastasis attributes Vital status Biochemical data - Tumor markers - Hormone receptors CANCER REGISTRY DATA ELEMENTS (NAACCR STANDRARD) EXTRAOVARIAN ABDOMINAL TUMORS ENDOMETRIAL TUMORS

7. 7 Core Data Sources: Cancer Registry System Clinical Trial Management Application Central Data Center (WRI) Pathological Evaluation (coPATH and synoptic) Questionnaire Data De-identified Data Export

8. 8  Pre-operative Case/Control Matching  Postoperative Questionnaire  HOPE Ovarian  Endometrial Questionnaire Data:

9. 9 Pathology Data ( coPATH & Synoptics) Synoptic worksheet are implemented for use in data acquisition. This provides a structured way of entering the diagnostic / prognostic information for particular pathology specimen and ultimately serves as medium for capturing and storing data for translational research. The data is stored as discrete data elements which appear as an accession summary within the final pathology report. The synoptic data is manually or electronically imported into the CTMA for linking pathological details on banked tissues.

10. 10 UPMC Cancer Registry  The UPMC Registry Information Services (RIS) is designed for the collection, management and analysis of demographic, grading, staging, treatment and progression data on cancer patients  Primary sources for documentation are both the “paper” and “electronic” medical records from which data is abstracted into the Cancer Registry database by Certified Cancer Registrars.  The entire UPMC RIS is built on the North American Association of Central Cancer Registries (NAACCR) data standard architecture.

11. 11 Treatment Follow Up Recurrence Data imported from Cancer Registry Tool. Data entry done at source application (IMPAC) by cancer registrars. CANCER REGISTRY DATA ELEMENTS (NAACCR STANDRARD)

12. 12 Technology:  Clinical Trial Management Application is a web-based Java application for managing various aspects of clinical trails, research protocols and outcome initiatives.  Provides an integrated set of components for managing administrative and regulatory tracking (e.g., IRB-related issues).  Facilitates study protocol schema, treatment calendar and financial management issues for capturing study specific patient information.  Used for internal storage of data in GDP study.

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14. 14 Result:  At UPMC (Magee Women’s Hospital) total number of consented patients is 109. Endometrial cancer (45), ovarian cancer (13), withdrew from the project (33), benign conditions (12), and the rest are pending for surgical procedures.  Patient privacy protection is of utmost importance and is enforced in accordance with Health Insurance Portability and Accountability Act (HIPAA) and only de-identified is transferred to WRI  Well-structured study protocol is implemented for the acquisition of high quality and well characterized annotated biospecimens and transfer of data to central data warehouse (WRI).

15. 15 Overall Workflow for GDP

16. 16 Overall Workflow for GDP RNC assigns a GDP Number to the patient, or case, fills out the Paper-based and Web-based (Clinical Trials Management Application [CTMA]) Pre-operative Case/Control Matching Questionnaire, and collects blood sample. Patient consented by Research Nurse Coordinator (RNC) and enrolled in GDP study.

17. 17 Overall Workflow for GDP CASE COMPLETE FROM GDP STUDY MALIGNANT BENIGN Post-operative blood sample collected. Patient undergoes operation and surgical specimen is accessioned for pathological examination (generating coPATH Data). Biospecimen are stored in Magee women Hospital Tissue bank tissue bank and data is Stored in TBINV

18. 18 RNC completes Paper-based and Web-based (CTMA) Post-operative questionnaire (HOPE for Ovarian / Endometrial post-operative questionnaire) and collects blood sample. Data Manager, Department of Epidemiology, University of Pittsburgh Department of Biomedical Informatics (DBMI) and Cancer Registry Team RNC MAKES A COPY OF ENTIRE QUESTIONNAIRE DATA & SENDS THE ORIGINAL AND THE COPY TO THE FOLLOWING: ORIGINALCOPY Workflow for GDP Scansoft Processing Hope Survey

19. 19 Transfer Electronic version of Questionnaire Data (Excel layout) to Windber Research Institute (WRI) and send one copy to DBMI. Workflow for GDP Scansoft CSV Output Files Data Transfer

20. 20 DBMI post-doctoral fellows enter pathology data into CTMA (internal use) which is pulled into Excel layout for WRI. Medical Registry data directly pulled for transfer to WRI (Excel layout). Tissue bank inventory data is pulled out in Excel format and transfer to WRI Workflow for GDP CTMA Annotation

21. 21 Workflow for GDP Transfer Pathology and Registry Data to WRI Excel File Generation

22. 22 Conclusion:  The Gynecologic Disease Program acts as a central repository for clinically annotated gynecological tumor tissues for the research community.  This tissue banking initiative provides an infrastructure of joint multi-institutional bioinformatics network that facilitates the sharing of clinically annotated data and high quality biospecimens to support important research activities.  With information gained from these research activities, we will continue to improve screening, early detection, prevention, and treatment of gynecologic disease.

23. 23 Acknowledgments Collaborators: –Walter Reed Army Medical Center –University of Pittsburgh Cancer Institute –Windber Research Institute –Georgetown Medical Center Leadership Dr. Ronald HerbermanDr. Michael Becich Dr. Robert EdwardsDr. Larry Maxwell Dr. Rajiv DhirDr. Michael Feldman Dr. Anil Parwani

24. 24 THANK YOU