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Translational Research Program (TRP) Chair: Adam P. Dicker, MD, PhD Brain Arnab Chakravarti, MD Breast Wendy Woodward, MD, PhD Steven Chimura, MD, PhD Gastrointestinal Chandan Guha, MD Sunil Krishnan, MD Genitourinary Allan Pollack, MD, PhD Head & Neck Christine H. Chung, MD Gynecology Joanne Weidhaas, MD, PhD Molecular Signatures Christine H. Chung, MD Normal Tissue Effects Deborah Citrin, MD Barry Rosenstein, PhD Ulrich Rodeck, MD, PhD Bioinformatics Joseph O. Deasy, PhD Soren Bentzen, PhD Publications Arnab Chakravarti, MD Sarcoma William Kraybill, MD David Kirsh, MD, PhD Dina Lev, MD, PhD Tissue Bank Fred Waldman, MD, PhD Trans-Canada Robert G. Bristow, MD, PhD Matthew B. Parliament, MD Lung Quynh Le, MD, PhD Protons Jason Efstathiou, DSc, MD EORTC Eric Deutch, MD

Translational Research Program (TRP) Chair: Adam P. Dicker, MD, PhD Brain Arnab Chakravarti, MD Breast Wendy Woodward, MD, PhD Steven Chimura, MD, PhD

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Translational Research Program (TRP)

Chair: Adam P. Dicker, MD, PhD

Brain Arnab Chakravarti, MD

Breast Wendy Woodward, MD, PhD Steven Chimura, MD, PhD

Gastrointestinal Chandan Guha, MD Sunil Krishnan, MD

Genitourinary Allan Pollack, MD, PhD

Head & Neck Christine H. Chung, MD

Gynecology Joanne Weidhaas, MD, PhD

Molecular Signatures Christine H. Chung, MD

Normal Tissue Effects Deborah Citrin, MD Barry Rosenstein, PhD Ulrich Rodeck, MD, PhD

Bioinformatics Joseph O. Deasy, PhD Soren Bentzen, PhD

Publications Arnab Chakravarti, MD

Sarcoma William Kraybill, MD David Kirsh, MD, PhD Dina Lev, MD, PhD

Tissue Bank Fred Waldman, MD, PhD

Trans-Canada Robert G. Bristow, MD, PhD Matthew B. Parliament, MD

Lung Quynh Le, MD, PhD

Protons Jason Efstathiou, DSc, MD

EORTC Eric Deutch, MD

Radiation Therapy

Oncology GroupRTOG StrengthsRTOG Strengths

• Unique Mission

• Outstanding Scientific Leadership

• Transformational Research

• Growing Accrual

• Translational Research with Funding

• Pivotal Phase III Trials

• Leader in New Technologies

Radiation Therapy

Oncology GroupStrengthsStrengths• Outstanding Databases

• Growing Membership Base

• Outstanding Staff in HQ and Biostat

• Unique Link with ATC and RPC

• Non-Federal Sources of Funding

• Unique Relationship with ACR

• Core Group of Member Institutions

• Canadian-European-Asian Link

4 4

Goals of the TRPGoals of the TRP

• Leverage the rapid evolution of translational research to support RTOG’s mission– Representation in TRP

• Surgery, Pathology, Medical Oncology, Radiation Oncology, Basic Science, Translational Science, Statistics, Patient Advocacy

– New liaisons and subcommittees• ATIC• Breast• Molecular Signatures • Outcomes/Quality of Life, Normal Tissue• Protons• Bioinformatics • Trans-Canada

5 5

Operational Roles of TRPOperational Roles of TRP

• Recruit scientistsRecruit scientists

• Identify promising Identify promising resources/technologiesresources/technologies

• Group member education and feedbackGroup member education and feedback

• Seed grant funding for novel ideasSeed grant funding for novel ideas

6

Process for Evaluating Seed Grant ProposalsProcess for Evaluating Seed Grant Proposals

Biospecimen Biospecimen ResourceResource

Biospecimen Biospecimen ResourceResource

RTOG RTOG StatisticsStatisticsRTOG RTOG

StatisticsStatisticsDisease Site Disease Site

LiaisonsLiaisonsDisease Site Disease Site

LiaisonsLiaisons

External Advisory External Advisory CommitteeCommittee

Feedback to Feedback to ApplicantApplicant

Feedback to Feedback to ApplicantApplicant

TRP ChairTRP ChairTRP ChairTRP Chair

RTOG HQRTOG HQRTOG HQRTOG HQ

RTOG Steering RTOG Steering Committee Committee

RTOG Steering RTOG Steering Committee Committee

RFA and application, www.RTOG.org

7 7

Scientific Roles of TRPScientific Roles of TRP

• Hypothesis generation and Hypothesis generation and validationvalidation

• Incorporation of TRP endpoints into Incorporation of TRP endpoints into trialstrials

• Trial analysis and factors modelingTrial analysis and factors modeling

8 8

Themes of TRPThemes of TRP

• Identify signatures of resistant local Identify signatures of resistant local diseasedisease

• Identify markers for patterns of Identify markers for patterns of failurefailure

• Identify and improve normal tissue Identify and improve normal tissue risk prediction modelsrisk prediction models

Required Infrastructure

• Tumor and Tissue Bank (LDS, Utah)

• Biostatistical Link with Clinical Data

• Translational Researchers across the globe

• Peer-Reviewed Funding (RO1, R29, GO)

• RT Delivery Databases (St Louis)

• Outcomes Databases (Philadelphia)

Translational ResearchTranslational Research

Radiation TherapyOncology Group RTOG Biospecimen Resource

Fred Waldman, M.D.,Ph.D.Fred Waldman, M.D.,Ph.D.

Jeff Simko, M.D., Ph.D.Jeff Simko, M.D., Ph.D.

Richard Jordan, Ph.D., DDSRichard Jordan, Ph.D., DDS

Ken Aldape, M.D., Ph.D.Ken Aldape, M.D., Ph.D.

Sandy DeVries, M.S.Sandy DeVries, M.S.

Radiation TherapyOncology Group

Inventory as of January, 2010

• Brain 3159 cases/ 35 trials• GU 10586 cases / 32 trials• GI 3032 cases / 18 trials• Gyn 283 cases / 7 trials• Head/Neck 4220 cases / 17 trials• Lung 448 cases / 13 trials• Sarcoma 213 cases / 8 trials• TMAs 27 TMAs

Total 21,977 cases / 132 trials(2264 cases w buffy coat, 2156 plasma, 2438

serum)

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Biomarkers/biological factorsBiomarkers/biological factors

Dosi

metr

ic f

act

ors

Dosi

metr

ic f

act

ors

Outcomes = physics Outcomes = physics andand biology biology

Outco

me

varia

tion

Outco

me

varia

tion

Statistical models of Statistical models of combined factorscombined factors

Joe Deasy, Wash Univ.

13

Global RTOG Strategy

Candidate gene Candidate gene

polymorphisms and polymorphisms and

RT/Chemo toxicityRT/Chemo toxicity

Opportunities for survivorship studies

14

HypothesisHypothesis

•Patients with identical DVHs/field size will have different toxicities that are governed by gene polymorphisms that influence signal amplification from DNA damaging agents.

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Research LinksResearch Links• Links to National Research CommunityLinks to National Research Community

– NCI Steering Committee Involvement

– SPORE/PO1 Collaborations

– SWOG Interactions

– AACR

– ASTRO (RTOG Foundation)

– RFA on RTOG website

• Links to International Research CommunityLinks to International Research Community

– EORTC and NCIC Representation