1. ECOG-ACRIN Imaging Research Associate Education Symposium November 12, 2015

2. Presentation Objectives The Role of Standard of Care Imaging in Research Trials IROC’s Role for NCTN in managing SOC imaging IROC’s organization and services Case examples from the COG Challenges and Opportunities

6. IROC’s Structure American College of Radiology Clinical Research Center in Philadelphia is the Grantee for the IROC Grant Sub-awards to: IROC Rhode Island PI: T.J. FitzGerald IROC Houston PI: D. Followill IROC Ohio PI: M.V. Knopp IROC Philadelphia (RT) PI: J. Galvin IROC Philadelphia (Imaging) PI: M. Rosen IROC St. Louis PI: J. Michalski IROC Executive Committee Co-Directors: D. Followill, Houston (RT) and M.V. Knopp, Ohio (Imaging) IROC Admin: King/O’Meara/Laurie

7. IROC’s Mission Provide integrated radiation oncology and diagnostic imaging quality control programs in support of the NCI’s NCTN Network thereby assuring high quality data for clinical trials designed to improve the clinical outcomes for cancer patients worldwide

8. IROC’s Core Services 1.Site Qualification (FQs, ongoing QA (OSLD, visits), proton approval, resources) 2.Trial Design Support/Assistance (Key contact QA centers, protocol review, templates) 3.Credentialing (Tiered system to minimize institution effort) 4.Data Management (Data collection, pre-review, post-review for analysis) 5.Case Review (Pre-, on-, post-treatment reviews, facilitate review logistics)

9. NCTN GroupRadiation OncologyImaging AllianceRhode IslandOhio COGRhode Island ECOG-ACRINRhode IslandPhiladelphia (DI) NRG OncologyPhiladelphia (RT)Philadelphia (DI) SWOGRhode IslandOhio Key Contact QA Centers IROC Houston is the key contact center for all RT credentialing questions.

10. Case Review Diagnostic Imaging Central Reviews – Confirm eligibility and staging – Confirm response – Confirm progression/relapse – Correlate patterns of failure – Can be performed in real-time to direct patient treatment or retrospective to confirm local patient management and reporting – Can be performed on-site or remotely using secure VPN connections RT Reviews – Interventional reviews (pre-treatment or early on-treatment) to assure that patient’s treatment plan is per protocol requirements. Possible to modify planning to protocol compliance – Post treatment reviews performed to confirm patient’s treatment was delivered per protocol. RT details from this review are transferred for protocol analysis.

11. 1733 enrollments AHOD0031: Chemotherapy With or Without Additional Chemotherapy and/or Radiation Therapy in Treating Children With Newly Diagnosed Hodgkin's Disease

12. AHOD1331: A Randomized Phase III Study of Brentuximab Vedotin (SGN-35, IND #117117) for Newly Diagnosed High-Risk Classical Hodgkin Lymphoma (cHL) in Children and Adolescents

13. 14.4 Central Review of Imaging Studies Central review of images will be performed to confirm institutional reporting. 14.4.1 Real-time central review Real time central review to assess response for all patients will be done after the second cycle of chemotherapy and at the completion of chemotherapy for patients who had PET positive disease at the end of 2 cycles of chemotherapy. Copies of all imaging studies at baseline and after 2 cycles of chemotherapy should be submitted (chest radiograph, CT with contrast, FDG-PET imaging) as detailed below. Institutional imaging reports and the AHOD1331 Staging and Response Worksheet should be submitted with these scans. In instances in which the central imaging review assessment of disease status differs from that of the institution, a web-based conference will be organized by IROC RI (QARC) to expedite resolution of any discrepancies in interpretation of the imaging data. Subjects found to not meet study eligibility staging criteria at the time of central review for early response assessment (after 2 cycles of chemotherapy) will be deemed ineligible. Institutions will be notified and required to remove patient from protocol therapy, and the patient will be considered off study. As a reminder, institutions may seek input from IROC prior to study enrollment if there are questions regarding study eligibility based on imaging measurements regarding LMA or bulk.

14. Packer RJ, Gajjar A, Vezina G, Rorke-Adams L, Burger PC, et al. Phase III Study of Craniospinal Radiation Therapy Followed by Adjuvant Chemotherapy for Newly Diagnosed Average-Risk Medulloblastoma. J Clin Oncol. 2006:4202-4208; DOI:10.1200/JCO.2006.06.4980. A9961: Pediatric Medulloblastoma

15. AHEP0731: Treatment of Children with All Stages of Hepatoblastoma

17. ARST0332: Risk-Based Treatment for Pediatric Non- Rhabdomyosarcoma Soft Tissue Sarcomas (NRSTS) 16.6 Submission of Imaging Studies for Central Review Requirements for All Patients Central review to assess baseline tumor characteristics will be performed on all patients. Studies to be submitted within 5 days of study enrollment include:  Primary site CT or MRI scan obtained at study enrollment prior to tumor resection. If no preresection scan was obtained, this requirement is waived. If multiple imaging studies were obtained prior to protocol enrollment, the imaging study showing the largest tumor diameter and the study performed closest to the time of enrollment should be submitted.  Patients with metastases: All imaging studies that identify metastases at study enrollment 16.6.2 Requirements for Treatment Arm D Patients Central review to assess tumor response by diagnostic imaging will be performed on patients enrolled on Treatment Arm D. Studies to be submitted for these patients include:  Primary site CT or MRI scan obtained at study enrollment (as in Section 16.6.1); baseline scans must be obtained within 3 weeks of study entry and before initiation of therapy.  Primary site CT or MRI scan obtained at Week 13 prior to definitive tumor resection (required)  Patients with metastases: All imaging studies that identified metastases at study enrollment and the same scans obtained at Week 13 (required)  FDG scan obtained at study enrollment and at Week 13 prior to definitive tumor resection (optional) The same imaging modality (CT or MRI) must be used at both

18. ARST0332: Risk-Based Treatment for Pediatric Non- Rhabdomyosarcoma Soft Tissue Sarcomas (NRSTS)

19. Challenges and Opportunities TRIAD – Access to TRIAD is controlled by User roles on the Site’s roster Different Paradigm when the research staff are medical oncology based. New Roster being developed with RT and Imaging facilities identified. Will be able to link participating Imaging and/or RT facilities to patient enrollments rather than have all Imaging personnel on Site’s Group Roster. Who are the Imaging personnel we want to engage? Facility Inventories – what information should we obtain for imaging facilities participating in studies with SOC imaging only.