Translational Research Program TRP Chair Adam P Dicker

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

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 Radiation Therapy Oncology Group

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 4 4

Operational Roles of TRP • Recruit scientists • Identify promising resources/technologies • Group member education and feedback • Seed grant funding for novel ideas 5 5

Process for Evaluating Seed Grant Proposals RTOG HQ RTOG Statistics Biospecimen Resource TRP Chair External Advisory Committee Disease Site Liaisons RTOG Steering Committee Feedback to Applicant RFA and application, www. RTOG. org 6

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

Themes of TRP • Identify signatures of resistant local disease • Identify markers for patterns of failure • Identify and improve normal tissue risk prediction models 8 8

Required Infrastructure Translational Research • Tumor and Tissue Bank (LDS, Utah) • Biostatistical Link with Clinical Data • Translational Researchers across the globe • Peer-Reviewed Funding (RO 1, R 29, GO) • RT Delivery Databases (St Louis) • Outcomes Databases (Philadelphia)

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 De. Vries, M. S.

Inventory as of January, 2010 Radiation Therapy Oncology Group • • Brain GU GI Gyn Head/Neck Lung Sarcoma TMAs 3159 cases/ 35 trials 10586 cases / 32 trials 3032 cases / 18 trials 283 cases / 7 trials 4220 cases / 17 trials 448 cases / 13 trials 213 cases / 8 trials 27 TMAs Total 21, 977 cases / 132 trials (2264 cases w buffy coat, 2156 plasma, 2438 serum)

Dosimetric factors Outcomes = physics and biology e om tc u O on ti ria va Biomarkers/biological factors Statistical models of combined factors Joe Deasy, Wash Univ. 12 12

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

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. 14

Research Links • Links to National Research Community – NCI Steering Committee Involvement – SPORE/PO 1 Collaborations – SWOG Interactions – AACR – ASTRO (RTOG Foundation) – RFA on RTOG website • Links to International Research Community – EORTC and NCIC Representation 15 15