Breast Cancer TAUG Overview and Implementation

Transcription

1 Breast Cancer TAUG Overview and Implementation Anita Umesh, Ph.D. Senior Scientist, Enterprise Informatics Illumina, Inc. Bay Area CDISC User Group 9 December Illumina, Inc. All rights reserved. Illumina, IlluminaDx, BaseSpace, BeadArray, BeadXpress, cbot, CSPro, DASL, DesignStudio, Eco, GAIIx, Genetic Energy, Genome Analyzer, GenomeStudio, GoldenGate, HiScan, HiSeq, Infinium, iselect, MiSeq, Nextera, NuPCR, SeqMonitor, Solexa, TruSeq, TruSight, VeraCode, the pumpkin orange color, and the Genetic Energy streaming bases design are trademarks or registered trademarks of Illumina, Inc. All other brands and names contained herein are the property of their respective owners.

2 Agenda Important Considerations in Oncology Breast Cancer: Overview Breast Cancer TAUG: Objective(s) Breast Cancer TAUG: Focus of the User Guide Breast Cancer TAUG: What s Different? Breast Cancer TAUG: Topics Breast Cancer TAUG: Known Issues Illumina s Use Case: Introduction Illumina s Use Case: Example of Challenges Wish-list for SDTM Examples 2

3 Important Considerations in Oncology Broad categories Solid tumors Hematologic malignancies Diagnosis Staging (AJCC TNM) Clinical Pathological Grading Histology Molecular markers Anatomic location versus relative location Treatment Intent: Curative, Palliative Setting: Neoadjuvant, Adjuvant, Metastatic Endpoints Treatment efficacy: CR, PR, SD, etc. Overall survival, Disease-free survival, Progression-free survival 3

4 Breast Cancer: Overview Solid tumor arising in the breast epithelial cells Usually originates in ducts or lobes Axillary nodes % of newly diagnosed cancers, 15% of cancer deaths in women (US) Five-year survival: 89.4% ( , SEER) 4

5 Breast Cancer TAUG: Objective(s) Provide guidance on Systematically collecting relevant data Tabulation of collected data with minimum loss of information Facilitation of downstream analysis How is this achieved in the TAUG? Concept maps Represents key concepts identified for BrCa Example CRFs Data collection Example SDTM tables Modeling of collected data Example analysis datasets Downstream analysis 5

6 Breast Cancer TAUG: Focus of the User Guide Describe common data in for breast cancer studies Enable understanding for data managers, statisticians, programmers to apply standards Define biomedical concepts Enable use of consistent terminology for aggregation, comparison of data across studies and drug programs Intent Setting 6

7 Breast Cancer TAUG: What s Different? Representation of Non-Standard Variables (NSVs) Adopted the practices proposed in SDTMIG v3.3 Batch 2 SDTM-based examples containing use of a variable outside the standard set of variables are not represented with Supplemental Qualifier records but with NSVs appended to the end of the parent domain Followed by sample value-level metadata for the NSVs For clarity, NSVs are shown with black in the header row, separated from the standard variables by a small space. 7

8 Breast Cancer TAUG: What s Different? (cont d) Introduction of NSVs with controlled terminology Treatment Intent: TRTINT Curative, Palliative Treatment Setting: TRTSTT Neoadjuvant, Adjuvant, Metastatic 8

9 Breast Cancer TAUG Topics Diagnosis Staging Pathology Prior Treatments Risk Factors Treatments Tumor Identification, Assessment, and Disease Response Disease Recurrence Known Issues 9

10 Breast Cancer TAUG Topics: Section 3.1 Diagnosis 10

11 Breast Cancer TAUG Topics: Section 3.2 Disease staging (AJCC: T, N, M) Clinical (ctnm) Pathologic (ptnm) 11

12 Breast Cancer TAUG Topics: Section 3.3 Pathology Concept Map 12

13 Breast Cancer TAUG Topics: Section 3.3 (cont d) Pathology Explanation of some key concepts Molecular measurements ER, PR, Her2, Ki-67 labeling index Cancer measurements Tumor size, Cellularity, Number of Lymph Nodes Positive, Residual Cancer Burden, etc. Primary Tumor Grade Assessments Invasive Carcinoma Grade, DCIS Grade, LCIS Grade Prespecified Findings Calcification, Extranodal Extension, Lypho-vascular Invasion, etc. Genetic/Molecular Analysis BRCA1 Mutation, BRCA2 Mutation, Gene Expression Profile Histologic/Morphologic/Molecular Types DCIS, LCIS, Invasive Carcinoma, Basal-like Breast Cancer (BLBC), HER2-Enriched, Invasive Ductal Carcinoma, NOS, Luminal A, Luminal B, etc 13

14 Breast Cancer TAUG Topics: Section 3.3 (cont d) Pathology Example: ER by IHC Overall status for ER and details used for determination Detail: Percentage of cells staining positive, proportion score (PS) Detail: Stain intensity positivity score (IS) Detail: Total score (TS). NSV: Number of points in the scale for multi-point scale Controlled terminology for MITSTDTL is in development 14

15 Breast Cancer TAUG Topics: Section 3.4 Prior Treatments CRF and Example Table Relevance: Recurrent, metastatic studies; New diagnoses for prior other cancers 15

16 Breast Cancer TAUG Topics: Section 3.5 Risk Factors Descriptions Major Comorbid Conditions Family History BRCA1, BRCA2 mutations, etc. 16

17 Breast Cancer TAUG Topics: Section 4.1 Treatments 17

18 Breast Cancer TAUG Topics: Section 4.2 Tumor Identification, Assessment, and Disease Response -- CRF 18

19 Breast Cancer TAUG Topics: Section 4.3 Disease Recurrence Concept Map 19

20 Breast Cancer TAUG Topics: Section 4.3 Disease Recurrence -- Example 20

21 Breast Cancer TAUG: Known Issues AJCC TNM and overall staging Pathology/histology Treatment regimens that span across domains Medication + Radiation + Surgery Use RELREC for now Line of therapy Method of scoring Allred score versus H-score versus Remmele scoring 21

22 Illumina s Use Case: Introduction Illumina develops, manufactures and markets integrated systems for the analysis of genetic variation and biological function Sequencers (highest market share) Goal: To use SDTM as a model to harmonize across datasets coming from disparate sources Oncology, Autoimmune disorders, Cardiovascular disease, Metabolic disease, Infectious disease Major use case is to tie together: Biospecimen information Pathology information Biomarker test results Clinical records 22

23 Illumina s Use Case: Example of challenges Biospecimen collection information to be captured using PGx-IG ER, PR positivity to be captured in MI (per TAUG) Her2 positivity to be captured in MI (if IHC) Her2 positivity to be captured using PGx-IG (if ISH) Other molecular assay results to be captured using PGx-IG Tumor identification, result information to be collected in TU/TR Are these not all tests done in a lab? Are they not all part of Tumor Identification, Tumor Results? Where to logically put the data? Where to put simple data such as tumor biopsy = Primary tumor, Metastatic tumor, Recurrent tumor? Difficulty in capturing NO information Was tumor identified = NO 23

24 Wish List for SDTM Examples Histology Irrespective of location aids analyses of squamous cell carcinoma of lung and breast together Location analysis exists currently so why not for histology? Staging Integrated use-case example that encompasses clinical data with specimen data with downstream molecular assay data Baseline tumor As part of TU? MH? BE/BS? Primary or metastatic? Collecting NO information Was tumor identified, YES/NO Circumvents data-loss 24

25 2014 Illumina, Inc. All rights reserved. Illumina, IlluminaDx, BaseSpace, BeadArray, BeadXpress, cbot, CSPro, DASL, DesignStudio, Eco, GAIIx, Genetic Energy, Genome Analyzer, GenomeStudio, GoldenGate, HiScan, HiSeq, Infinium, iselect, MiSeq, Nextera, NuPCR, SeqMonitor, Solexa, TruSeq, TruSight, VeraCode, the pumpkin orange color, and the Genetic Energy streaming bases design are trademarks or registered trademarks of Illumina, Inc. All other brands and names contained herein are the property of their respective owners. End