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NCI CO-OPERATIVE CANCER GROUPS

Richard Jordan DDS PhD Director RTOG Biospecimen Resource

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The “war” on cancer

•  National Cancer Institute (NCI) – Clinical trials evaluation program (CTEP)

•  Cooperative groups (11) – Clinical trials: Data groups, Tissue Banks, etc.

•  RTOG: Focus on radiation Rx for cancer

•  Group Banking Committee (GBC) – Coordinate tissue resources of Cooperative Groups

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Value of Cooperative Groups •  Study of large diverse patient populations •  Well-controlled therapeutic intervention(s) •  Long term & detailed clinical follow-up &

outcome •  Biospecimens for translational biomarker

validation •  Well annotated & linked to clinical data /

outcome •  Single centralized repository •  Standardized processing and storage

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Clinical Trials Co-operative Groups

•  American College of Radiology Imaging Network (ACRIN) •  American College of Surgeons Oncology Group (ACOSOG) •  Cancer and Leukemia Group B (CALGB) •  Children's Oncology Group (COG) •  Eastern Cooperative Oncology Group (ECOG) •  Gynecologic Oncology Group (GOG) •  National Surgical Adjuvant Breast and Bowel Project (NSABP) •  North Central Cancer Treatment Group (NCCTG) •  Radiation Therapy Oncology Group (RTOG) •  Southwest Oncology Group (SWOG) •  **National Cancer Institute of Canada, Clinical Trials Group

(NCIC)

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ALLIANCE ECOG NRG ONCOLOGY

SWOG COG

CALGB ACOSOG

NCCTG

ECOG

ACRIN

NSABP RTOG

GOG SWOG COG

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Co-operative Group Banks

1. ALLIANCE: 5 Banks - ACOSOG (St. Louis, MO) - NCCTG (Rochester, MN) - CALGB Lung (Boston); Solid +CALGB Leukemia (Columbus)

2. ECOG-ACRIN: 4 Banks 3. COG: 1 Bank (Columbus) 4. SWOG: 1 Bank (Columbus) 5. NRG Oncology: 3 Banks

- GOG: 1 Bank (Columbus) - NSABP: 1 Bank (Pittsburgh) - RTOG: 1 Bank (San Francisco)

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Radiation Therapy Oncology Group (RTOG)

•  Formed in 1968; Headquarters in Philadelphia; “central command”

•  ~ 300 Member Institutions •  Launch clinical trials •  Core scientific support groups •  Interactions: HQ / Biospecimen

Resource/ TRP

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RTOG  Clinical  Trials  (Protocols)  

•  ~460  total  trials;  90,000  pa1ents  •  ~  36  ac1vely  enrolling  •  Study  PI,  Pathologist,  Med.  Oncologist,  Surgeon,  Sta1s1cian  

•  Local  PI,  enrolling  MD,  support  staff  

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RTOG Achievements SITE ACHIEVEMENT Brain Oligodendroglioma improved survival in del 1p and 19q Brain Temozolomide after radiotherapy (MGMT methylation)

Metastases to brain

Whole brain radiotherapy followed by stereotactic radiosurgery improved survival 33% vs. whole brain treatment alone

Head & neck Addition of cetuximab improves survival

Head & neck Concurrent radiation and chemotherapy following surgery significantly reduces recurrent disease

Lung Adjuvant chemotherapy significantly improves PFS vs. neoadjuvant chemotherapy

Pancreas Gemcitabine improves survival after surgery

Prostate Radiotherapy + hormone suppression improves survival

10 WWW.RTOG.ORG  

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RTOG TRP Review Process Application - for specimens from trials that have met their primary endpoints Preliminary Review Team = PIs, study chairs, disease committee chairs, TRP liaisons & Chair, administration and ad hoc group of external scientists

CTEP Review – 100 subjects rule MTA – Material Transfer Agreement between RTOG and investigator’s institution  

RTOG BSR Ships Specimens

REQUEST MADE BY INVESTIGATOR (LOI)

Application for

RTOG Biospecimens

Sent for Tissue Availability Acknowledgement

RTOG Steering Committee Review

Sent for Statistical Feasibility Acknowledgement

Disease Group Review (Preliminary Review)

CTEP Review

Approval letter to investigator

MTA process

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•  Coordinate use of kits, sample shipment & receipt, QA, banking, and distribution of biospecimens

•  Work with site committees to optimize standard protocols for biospecimen processing during trial design

•  Prepare samples for Translational Research Projects, including pathology review and construction of tissue microarrays (TMA’s) as requested

•  Provide materials for central review by Pathology Committee

•  Participate in national initiatives for harmonization of procedures (Group Banking Committee)

RTOG Biospecimen Resource Activities

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Major accomplishments

•  Comprehensive Biobanking (FFPE, frozen tissue, blood, serum, plasma, CSF, urine)

•  SOPs for ALL ongoing processes •  Scientific Evaluations (TRP & Trial Protocols) •  Comprehensive QA process •  Digital pathology – Aperio for on-line central

pathology review •  Core Research for GU PO1 and Brain SPORE

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RTOG Inventory

Total: 24681 cases, 55606 specimens, 269418 aliquots 151 total trials with specimens

204 cases with frozen tumor specimens 4107 cases w buffy coat/whole blood, 3642 plasma, 3802 serum

•  Brain 4267 cases (10302 specimens) 40 trials

•  GU 11780 cases (25810 specimens) 35 trials

•  GI 3264 cases (6790 specimens) 20 trials

•  Gyn 314 cases (696 specimens) 9 trials

•  Head/Neck 4404 cases (10503 specimens) 21 trials

•  Lung 762 cases (2651 specimens) 15 trials

•  Sarcoma 271 cases (631 specimens) 8 trials

•  TMAs 32 TMAs (3242 cases) 33 trials

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RTOG Biospecimen Resource Control Mini-TMA- 0525 Brain

0525-MiniTMA: Brain 20 Cases- 3 replicate Tumor plugs per case and 5 Cases with Normal: 3 replicate Normal plugs from Adjacent Normal Tissue

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RTOG Tissue Micro Arrays •  33 TMAs in Inventory:

– 634 cases with 3580 cores •  8 Brain TMAs from 13 studies •  6 GI TMAs from 4 studies •  3 GU TMAs from 5 studies •  3 GYN TMAs from 3 studies •  10 H&N TMAs from 7 studies •  2 Sarcoma TMAs from 1 study •  1 Control mixed TMA from 4 sites.

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Central Pathology Review Goal:

–  Streamline the process of Pathology Central Review

–  Avoid shipping slides and paperwork –  Make it easier for the central review pathologists

Solution:

•  Scan Slides using the Aperio Slide Scanner for digital web review.

•  Provide a secure link for review and recording of data

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Tissue Inventory Informatics

•  Maintain inventory of biospecimens available for translational projects

•  Legacy database in Freezerworks •  Evaluated caTissue and Oncor suite BSM •  Inventory is uploaded quarterly to RTOG web

site •  Inventory summaries are also made available to

NCI Group Banking Committee •  Harmonizing using STARS program