1. October 9 th, 2015 University of Pennsylvania TIES Cancer Research Network Y3 Face to Face Meeting U24 CA 180921 Session 1 Project Status Updates

2. 2 University of Pennsylvania Abramson Cancer Center TCRN Update Michael Feldman, MD, PhD

3. Penn Team Michael Feldman, Assoc Prof Path & Lab Med – Site PI Joellen Weaver – Director SOM Biobank – Regulatory and Admin Nate Digiorgio – Sys Admin and DBA Kevin Lux – Interface Tara McSherry – End user training and support, QA Fred Valdivieso – Tissue bank manager – honest broker

4. Database Latest code set running 5.3.1 Records coded ~750K – Active coding pipeline via daily data load from Medview (home grown web portal for lab results) – Catching all Surg path cases from 3 hospitals downtown hospitals at Penn Medicine (65K/yr) – PAH was not online in 2014

5. Penn TIES Website Penn site is up and running User enrollment and authorization Rules of the road Documents AUA, MTA’s… Link to instructional videos Information related to TIES and our instance

6. QA Review of QA results identified – Automated search identified 300 records – Manual scrub of records Missed name (Full name, Lname, Fname) most common Reports were manually scrubbed and returned into data set

7. Roll Out Started rolling out – Surgical pathologists (5 to date) – Remaining pathologists this year (25) – Presentation to Cancer leadership very positive Deployed to Cancer center IT lead Start deploying to translational investigators SOM Biobank as honest broker Presentation to Pathology leadership – Departmental division directors – Anatomic Pathology Directors – Pathology staff

8. Value TIES study in prep to research Breast cancer researcher – Looking for invasive breast cancer by year since 2010 – Studying metabolism in cancer wanted to make sure we had enough cases at Penn to address questions using retrospective case control study design

9. Value Radiology Retrospective cohort study Find all cases of in situ lobular breast cancer diagnosed on core biopsies who did not have DCIS or invasive carcinoma – What did follow-up resection show? – Correlate with radiology finding – Question is what group of LCIS needs further surgical treatment when only LCIS is diagnosed on a core biopsy

10. Structured + NLP How can we link structured data with TIES? – Pathology Biobank – LIMS is labvantage, same at RPCI – Oncology – tumor registry Metriq similar to Pitt and RPCI

11. Virtual slides at Penn Behind firewall – Aperio image server – Aperio inmage scanner – Moving to Philips platform Work with Pitt to develop tools to integrate vSlides into TCRN TIES deployment

12. How can TIES be expanded (more corpuses) Radiology – Oncology Diagnosis Response Criteria (RECIST) – Lesion changes, Lymph node size, bone lesion, PET… Heterogeneity – structural (CT and MRI) and genomic (PET) Integrated process research – precision medicine

13. TIES at ‘Georgia Regents University’ – F2F Roni Bollag, MD, PhD Nita Maihle, PhD Jennifer Irons Carrick, BS Sameera Qureshi, BS Rahil Khan, BS

14. Who is GRU? MCG (1833–2011) GHSU (2011–2013) 2013: Georgia Regents University = GHSU + ASU one of only four public comprehensive research institutions in the state of Georgia

15. Now AU

16. Founded in 1828 – 13 th -oldest medical school – 8 th -largest medical school Nine Colleges 9000 students (across campuses 240 medical students/year) Supporting GR Health System – 478-bed Georgia Regents Medical Center – 154-bed Children's Hospital of Georgia

17. GRU Cancer Center The GRU Cancer Center has three expressions, one laboratory-based, one clinic-based and one education-based. Each of the GRU Cancer Center facilities are designed with a purpose. Using a modern, scientific approach known as evidence- based design along with the expert advice of cancer patient advisors, our treatment facilities bring in nature and sunlight and puts patients in charge in as many ways possible. Our research facilities celebrate innovation, combining form with function to offer our scientists an environment for collaboration and discovery.

18. GRUCC Areas of Research Focus Cancer Immunology, Inflammation and Tolerance Cancer Prevention & Control Molecular Oncology & Biomarkers Tumor Signaling & Angiogenesis

19. Our Team Repository Side: Jinni Carrick – Biorepository Registrar Sameera Qureshi – Biorepository Lab Associate Rahil Khan – Biorepository Lab Assistant Denise Harper – Biorepository Admin. Assistant Roni Bollag –Biorepository Director Samir Khleif – Cancer Center Director Nita Maihle – Cancer Center Liaison for TIES

20. Our Team (con’t) IT Side: Mia Jolly – Business Analyst/Project Coordinator Pankhil Patel – DBA Mike Hyrman – Encore consultant for data download Colleen Cain – Director Enterprise Application Systems Charles Busbee – Manager Database & Application Administration Michael Casdorph – Associate VP Academic & Research Technology

21. The GRU Biorepository:  Provide MCG researchers access to high quality, annotated specimens, to support basic and clinical cancer research  Shared resource for the Cancer Center, important for its NCI designation process (P30 grant) BRAG-Onc:  Serves as coordinating hub and central repository for the statewide repository network

22. BRAG-Onc Mission The goal of the Biorepository Alliance of Georgia-Oncology Program (BRAG-Onc) is to establish a state-wide process for the banking of tumor tissue and blood samples from a population that reflects the diversity of the cancer patient population of the state to support basic and clinical research.

23. GRU Biorepository Inventory Sample Inventory* for the GRU/BRAG-Onc Biorepository: Collection SiteTotal Donors ConsentedTotal Specimens ALL (Acute Lymphocytic Leukemia) 28215 AML (Acute Myelogenous Leukemia) 2072736 ANAL (Anal) 1379 BLAD (Bladder) 3183841 BONE (Sarcomas of Bone) 435 BRST (Breast) 8928062 CERV (Cervical) 29142 CLL (Chronic Lymphocyctic Leukemia) 841049 CML (Chronic Myelogenous Leukemia) 64833 CNS (Central Nervous System: Brain and Peripheral NS) 3473106 COLN (Colorectal) 3753990 CTCL (Cutaneous T-Cell Lymphoma) 331 EDMT (Endometrial) 33195 ENDO (Endocrine: Parathyroid, Adrenal, Thyroid) 5455844 ESPH (Esophageal) 21265 GALL (Gallbladder) 15126 GAST (Gastric) 89843 GDM (Gross Metastatic Disease) 00 GYO (Gynocologic: omentum, other) 2741669 HEME (Hematopoietic disorders, MGUS, MDS, other) 2902039 HEPT (Hepatic, Biliary Tree) 1872416 HNO (Head and Neck: Other and unknown) 6025619 INC (Incomplete, open) 00 INTS (Small Intestine) 31208 LEUK (Leukemias) 51696 LNO (Lymph Node, node biopsies) 149 1021 LRNX (Head and Neck: Larynx and Hypopharynx) 96897 Collection SiteTotal Donors ConsentedTotal Specimens LUNG (Lung) 3583851 LYMPH (Lymphomas: Hodgkin, Non-Hodgkin) 2661907 MCL (Mantle Cell Lymphoma) 862 MELA (Melanoma) 56534 MESO (Mesothelioma) 00 MM (Multiple Myeloma) 3133313 NASL (Head and Neck: Nasal Cavity, Sinuses, Nasopharynx, Oral Cavity, Oropharynx) 1531486 OPTH (Ophthalmic Sites) 316 OTH (Other (Spleen)) 771133 OVAR (Ovarian, Fallopian, or Peritoneal) 2101174 PANC (Pancreatic) 1461392 PEDT (Pediatric Tumors) 224 PROS (Prostate) 4214651 RENL (Renal and Ureter) 4775857 SALV (Head and Neck - Salivary Glands, Paraglangliomas) 128987 SARC (Soft Tissue Sarcoma) 44473 SKIN (Skin - Non Melanomas) 1601092 TBD (To be determined) 33215 TEST (Testicular) 25251 THOR (Thoracic, other) 46451 THYM (Thymus) 17195 UNK (Unknown, unknown orgin) 129801 URTH (Urethral, Penile) 17157 UTER (Uterine) 241 1195 VUL (Vulva, Vagina) 26121 All 810377295

24. TCRN Challenges EHR = Cerner Millenium / Pathnet (switched from Copath in 2005) Biorepository Database: TissueMetrix – Possibly soon to convert to OnCore/ LabVantage / LabMatrix… Mostly non-functional for translational research applications

25. GRU Pathology 12 - 14,000 surgical specimens/year Since 2000 (target for retrospective data capture) – 255,000 reports MCG surgical emphases: endocrine oncology, urologic oncology, gynecological oncology

26. GRU Biorepository Team added to caTIES Added to TIES-TCRN study Our Progress

27. Compliance at GRU obtained IRB sanction of TIES consortium aggregate data to be designated as non- human subjects research IRB renewal for TIES project

28. IRB Approval

29. IT support at GRU engaged the services of Mike Hyrman at Encore Health Resource, LLC to develop code to export retrospective surgical pathology reports from Cerner Pathnet into firewall-protected honest brokerage archive

30. Governance at GRU Creation of GRU TIES project approval committee to evaluate external and internal TIES project submissions, in conformance with TCRN governance mandate. – Natasha Savage – Nita Maihle – Roni Bollag

31. Safe Harbor at GRU DeID software package licensed (Y2) from DeIData systems implemented to generate over 140,000 reports with scrubbed identifiers Phase I and II complete for DeID QA audit. Phase III nearly complete

32. Total Reports to-date 148,430 reports Report Types Autopsy Surgical Bone marrow Cytology (likely superfluous)

33. Phase II – bin by year

34. Phase II – bin by age

35. Phase II – bin by gender (?)

36. Pilot Project Approval

37. Summary GRU node is up and running… Compliance is current from institutional perspective Gaps in data upload – needs to be tweaked QA is in progress (I and II complete) Logistics in pilot project implementation: – So far, so good…

38. Looking Forward to the Future!

39. TCRN F2F Meeting 2015

40. Roswell Park Cancer Institute Independent, free standing cancer institute since 1898 NCI designated comprehensive cancer center since 1974 Buffalo, New York 27 acre main campus and three affiliated sites 133 hospital beds 3,282 employees, including 308 faculty members, 606 nurses, and over 100 senior scientists 20 scientific shared resources including biospecimens and data banks

41. Roswell Park Cancer Institute 5,284 hospital admissions, 205,000 outpatient visits, 31,000 patients under active care/year Cancer Registry Cases In 2014: 3,425 ( analytic class 00-22) 486 (non-analytic class 32—1 st course elsewhere, subsequent treatment at RPCI) 1,670 (non-analytic class 30-43, including consults, e.g., path) Population catchment area: 8 county regions of Western New York, 1.5 M (86%) of RPCI patients 48 states 13 foreign countries

42. RPCI TIES Current Statistics Data from 1995 to 2013 Cancer Patients: 72,376 Cancer Pathology Cases: 156,555 2014-2015 to be loaded Beyond 2015, live HL7 feed every six months Number of registered users: 14

43. IT Tasks Completed since last F2F Executed RPCI HIPAA Checker scripts to check for Patient Names, MRNs, and Accession Numbers missed by De-ID and the TIES auto- scrubber (by design) RPCI TIES Web Site is completed and opened to the public (https://www.roswellpark.edu/ties)https://www.roswellpark.edu/ties Set up automated live feeds of pathology reports to a dedicated folder on the TIES private server for 2015 onward Completed Phase 1, 2, and 3 QA of reports loading, De-I, and querying accuracy

44. IT Tasks Completed since last F2F Executed RPCI HIPAA Checker scripts to check for Patient Names, MRNs, and Accession Numbers missed by De-ID and the TIES auto- scrubber (by design) RPCI TIES Web Site is completed and opened to the public (https://www.roswellpark.edu/ties)https://www.roswellpark.edu/ties Set up automated live feeds of pathology reports to a dedicated folder on the TIES private server for 2015 onward Completed Phase 1, 2, and 3 QA of reports loading, De-ID, and querying accuracy

45. Next IT Tasks TIES – LIMS Interface Search for corresponding tissue samples available in LIMS. To accomplish this we need a way to get the Case Set data from TIES central hub. Create an API Write the case set information into the RPCI-TIES database besides the TIES Hub Load 2014 and 2015 pathology reports

46. Query Quality Assurance Process 1.Used seven test queries to analyze accuracy 2.Designed and executed an initial query 3.Manually checked each report to assess accuracy 4.Based on results, we refined the query 1.For some queries, multiple sub-queries were executed and the results combined 2.As one example, to look for patients with invasive ductal carcinoma of the breast, we searched for “invasive ductal carcinoma of the breast” AND “invasive ductal carcinoma, breast” 5.In addition, to compare results, we conducted a corresponding query against the Cancer Registry database

47. Query Quality Assurance Results Terms present in the text, but not as the current diagnosis, was the most common error. The pathologist would mention the search terms in the “Diagnosis” section but in a different context, e.g., “Patient has a history of Hodgkin’s lymphoma”

48. One Actual Example of Using TIES in Combination with Cancer Registry for Patient Cohort Selection Identify patients who have had a surgery at RPCI for Serous Adenocarcinoma of the Ovary AND a recurrence 1.First, we searched for patients who had the same diagnosis multiple times (recurrence) 2.Designed two queries: “Serous Ovarian Adenocarcinoma” and “Serous Adenocarcinoma, Ovary” 3.Created one case set of all results and exported to excel (almost 1,000 total reports) 4.Identified patients that had multiple reports and manually reviewed the reports (71 reports, 35 patients) 5.Used CR data for the clinical selection criteria 6.Used final list to search for tissue

49. De-ID QA Preliminary Results All pathology reports for CY 1997 and 2002 were loaded into TIES and run through the TIES De-ID software. Using the TIES built-in randomization function, a subset of reports where chosen for each year of reporting and manually reviewed for under or over scrubbing of PHI data. Preliminary results using De-ID only without added scripts:

50. De-ID QA Final Results Run RPCI HIPAA Checker for all loaded reports to identify PHI missed by De-ID software Of the 156,555 reports, 7,549 were flagged as missed PHI and quarantined for manual review and scrubbing 3,920 (52%) found to have actual missed PHI Types of PHI missed by De-ID software Patient Names Patient MRNs Pathology report numbers

51. De-ID QA Final Results After all scripts were run and manual checks were completed, 7,549 (4.82%) reports were manually checked and scrubbed during the De-ID validation 3,920 (51.9%) reports contained PHI that was not scrubbed by the TIES De-ID Software Overall, assuming the accuracy RPCI HIPAA checker, our findings indicate that the De- ID and TIES Auto-Scrubber missed PHI in 2.5% of the total RPCI reports.

52. De-ID QA Final Results RPCI Checker MRN 1.Designed a script to search for the different formats of a MRN present in path reports 2.Manually reviewed reports with missed MRNs 3.Run TIES autoscrubber to reduce the number of MRNs to be checked manually 4.Reran the script 5.Flagged reports were quarantined and then manually reviewed

53. RPCI Researchers Qs at TIES Introductory Presentation What other clinical data is accessible? What type of reports are searchable? Would you have molecular results? Could you also search radiology reports? (Clinical staging) Can you search other centers data without IRB approval? Could RPCI investigators search radiology reports loaded in other TIES nodes?

54. RPCI-TIES/TCRN Team and Roles Dr. Carmelo Gaudioso, RPCI CoI., member of executive TCRN Committee Monica Lopez Murphy, TIES Regulatory Administrator and member of the TCRN P & P subcommittee Kelly Duncan, TIES Regulatory Administrator, user educator Mayur Sakthivel, TIES IT Administrator, responsible for RPCI TIES IT development

55. Progress Toward Implementation TIES is live as 09/09/2015 14 active user accounts Dissemination program Presentations and TIES Demo DSRGs Scientific Programs Fellows Significant investigator interest Website, fliers, Mission Magazine article Scheduled user training sessions

56. Q&A Thanks! Questions-Comments?