The Role of Banked Human Tissue in Cancer Research

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The Role of Banked Human Tissue in Cancer Research

• Stephen J. Qualman M.D.
• Childrens Hospital, Columbus, Ohio

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Childrens Oncology Group

• Unification of 4 North American based
  pediatric clinical trials groups
• Childrens Cancer Group
• Pediatric Oncology Group
• National Wilms Tumor Study Group
• Intergroup Rhabdomyosarcoma Study Group

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COG Member Institutions, 2002
CCOPs/MBCCOPs
.
Members in Hawaii, Alaska, Australia, New
Zealand,Switzerland, Netherlands not displayed
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Number of COG Institutions Submitting Specimens
242
236
225
219
210
186
143
43
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Specimen Flow at the BPC
Investigators
Leukemia Biology Specimens
B I O P A T H O L O G Y
Procurement Lab
Wilms Biology Specimens
C E N T E R
Histology Lab
COG Solid Tumor Tissue Bank Biology Specimens
Submitting Institutions
COG Pathology Center Pathology Specimens
Reference Lab
STS Pathology/Biology Specimens
Repository
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Number of COG Specimens Provided to Investigators
22067
21637
20857
14428
9320
7445
1402
698
609
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Specimen Container
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Two-day Temperature Curve of E-11C Dual Shipper
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Specimen Bar Coding
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Specimen Transport

• Procuring institutions ship specimens within
  24-hours of collection using the BPCs courier
  account number and dual-chamber kits in
  compliance with International Air Transport
  Association (IATC) Section 1.5.0.2 and Federal
  Regulations Section 172.7

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Conforms with International Air Transport
Association (IATA) Section 1.5.0.2 CFR sec 172.7
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Specimen Transport

• A 1-800 number is available to institutions
  submitting specimens and investigators using
  tissue to facilitate communication.

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The Biopathology Centers

• The BPC provides banking and informatics services
  to
• pediatric Cooperative Human Tissue Network
  (pCHTN)
• Childrens Oncology Group (COG)
• Gynecologic Oncology Group (GOG)
• Childhood Cancer Survivor Study (CCSS)

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The Biopathology Centers

• In the last decade, the BPC has served nearly
  85,000 tumor or related tissue specimens linked
  to patient clinical outcome to over 300 different
  investigators.

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The mission of the College, the principal
organization of board certified pathologists, is
to represent the interests of the patients, the
public and the pathologists by fostering
excellence in the practice of pathology and
laboratory medicine worldwide.
Time line for pediatric tumor protocol
development defining uniform pathology diagnosis
and procurement standards
7/1/01 Conception
11/2/01 - Wilms Tumor
2/8/02 - Rhabdomyosarcoma
7/12/02 - Neuroblastoma
11/8/02 - Ewing Sarcoma
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Data Management

• The majority of documents maintained by the BPC
  fall into three categories
• Registration documents
• Operative reports
• Pathology reports
• Copies of the associated pathology reports are
  sent along to researchers with submitted
  specimens, but are stripped of patient
  identifiers.

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Informatics

• Informatics can facilitate
• Patient registration
• Specimen tracking
• Tissue cataloging
• Quality assurance
• Specimen availability
• Tracking informed consent
• Institutional compliance
• Generation of tissue bank reports

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Informatics

• An ideal informatics system ensures data is
• Available over a long period of time
• Maintained in a standardized format
• Able to be disseminated to others as needed
• Collected from collaborative sources and combined

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Intergroup Specimen Banking Committee

• The Cooperative Group Chairs, along with the
  National Cancer Institute, recognized the need
  for common data elements across data systems. As
  a result, the Intergroup Specimen Banking
  Committee was formed in 1999

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Intergroup Specimen Banking Committee

• identify existing standard, policies and
  procedures, particularly those in common usage,
  which would address the needs of intergroup
  banking, rather than invent new ones. The goal
  was to deliver a set of recommendations that
  would require the least amount of work, change
  and expense to implement, while providing
  sufficient guidance to the research community to
  facilitate useful banking efforts in support of
  correlative science, to avoid unnecessary
  conflict and to ensure a sufficient standard of
  quality
• Report of the Intergroup Specimen Banking
  Committee, 1999

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Intergroup Specimen Banking Committee

• Minimum data requirements for banking
• All samples and sub-samples must have a unique
  identifier
• The system must adhere to standard coding
  mechanism
• The system must be able to maintain an
  up-to-date inventory by unique identifier
• The database containing information on sample
  locations (inventory) may reside solely at the
  bank
• Report of the Intergroup Specimen Banking
  Committee, 1999

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Intergroup Specimen Banking Committee

• The system must be able to
• Flag (reserve) specimens for a particular study
• Track the type of informed consent
• Track specimens and allow for withdrawal of
  consent
• Report and provide query results across groups
• Provide quality control/checks on imported data
• Report of the Intergroup Specimen Banking
  Committee, 1999

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Informed Consent

• By utilizing a three-item checkbox on an informed
  consent form, the patient may designate whether
  their tissue or case data may be used for
• Cancer research
• General medical research
• Future patient contact for needed clinical
  follow-up

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Data Linkage

• Data records which can be directly or indirectly
  associated with a persons name or other
  identifying information are referred to as linked
  data.
• The BPC informatics system uses specialized codes
  to maintain patient confidentiality. The BPC
  system must connect to the Cooperative Group
  Statistical Data Centers system via a virtual
  private network to link the clinical data to the
  specimen data.

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Virtual Private Networks

• Streamline patient enrollment
• Streamline specimen registration process
• Synchronize information between physically
  different sites
• Create virtual tissue banks from inventory of
  different sites

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Virtual Private Networks

• Primary requirements for implementation of a
  secure VPN
• Authentication
• Strong data encryption
• Transaction privacy
• Encryption key unique to each session
• Scalability
• Audit information
• Immediate intrusion/attack detection

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Metrics of Performance

• A bank should be assessed by both deposits and
  withdrawals
• A banking operation is defined by who is served
  and what is published.

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• The BPCs role is not just to serve the
  established investigator. Bank should have the
  flexibility to support new or entrepreneurial
  young investigators with exciting new scientific
  ideas.

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Metrics of Performance

• Assessments determined by
• Feedback questionnaire process
• Updated investigator biosketches
• Project summaries
• Current and submitted grant proposals
• Publications from banked materials

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Performance Findings

• Nearly 80 of investigators using BPC tissue
  receive NIH support (either intramural or
  extramural)
• Over 300 publications have resulted from
  research using BPC tissues in the past 10 years
• 20 of papers appeared in journals considered to
  have a major impact

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Number of Publications Produced Using Tissues
from the GOG Tissue Bank
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Prediction of Central Nervous System Embryonal
Tumour Outcome Based on Gene Expression
Pomeroy SL, et al. Nature 45 436-442, 2002
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Patients with Metastatic Alveolar Rhabdomyosarcoma
1.0
0.9
PAX7-FKHR
0.8
0.7
0.6
Proportion of patients
0.5
0.4
0.3
0.2
PAX3-FKHR
0.1
Log Rank Test p0.0015
0.0
0
1
2
3
4
5
6
7
8
9
10
Overall survival (years)
Sorensen PHB, et al. J Clin Oncol 2002 (in press)
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Uses of Banked Tissue
MoAb, CGH FISH 8
Growth factors/ hormone receptors 8
36DNA Studies
24 Protein/enzyme
24RNA Studies
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Questionnaire Results
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Top 10 Difficulties
10. CHTN doesnt collect or ship pathogens
9. Laws prohibiting research using fetal tissue
8. Requests for entire organs
7. Requests for normal tissues (eg brain tissue)
6. Timing of tissue procurement
5. Tissue rarity
4. Tissue consent
3. If, and/or but requests
2. Tissue culture
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1 Difficulty
Limitation on amount of tissue available
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Specific Challenges

• The ultimate role of the pathologist as a tumor
  banker in this setting is that of a tissue
  refiner and data miner.

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