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 Group RTOG 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 Group Strengths 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 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 TRP Operational Roles of TRP Recruit scientistsRecruit scientists Identify promising resources/technologiesIdentify promising resources/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 Proposals Biospecimen Resource RTOG Statistics Disease Site Liaisons External Advisory Committee Feedback to Applicant TRP Chair RTOG HQ RTOG Steering Committee RFA and application,

7 7 Scientific Roles of TRP Scientific Roles of TRP Hypothesis generation and validationHypothesis generation and validation Incorporation of TRP endpoints into trialsIncorporation of TRP endpoints into trials Trial analysis and factors modelingTrial analysis and factors modeling

8 8 Themes of TRP Identify signatures of resistant local diseaseIdentify signatures of resistant local disease Identify markers for patterns of failureIdentify markers for patterns of failure Identify and improve normal tissue risk prediction modelsIdentify and improve normal tissue risk 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 Research

Radiation Therapy Oncology Group RTOG Biospecimen Resource Fred Waldman, M.D.,Ph.D. Jeff Simko, M.D., Ph.D. Richard Jordan, Ph.D., DDS Ken Aldape, M.D., Ph.D. Sandy DeVries, M.S.

Radiation Therapy Oncology Group Inventory as of January, 2010 Brain3159 cases/ 35 trials GU10586 cases / 32 trials GI3032 cases / 18 trials Gyn283 cases / 7 trials Head/Neck4220 cases / 17 trials Lung448 cases / 13 trials Sarcoma213 cases / 8 trials TMAs27 TMAs Total21,977 cases / 132 trials (2264 cases w buffy coat, 2156 plasma, 2438 serum)

12 Biomarkers/biological factors Dosimetric factors Outcomes = physics and biology Outcome variation Statistical models of combined factors Joe Deasy, Wash Univ.

13 Global RTOG Strategy Candidate gene polymorphisms and RT/Chemo toxicity Opportunities for survivorship studies

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

15 Research 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