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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)
1212
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.
1515
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