1. Challenges in Credentialing Institutions and Participants in Advanced Technology Clinical Trials Geoffrey Ibbott, David Followill, Andrea Molineu, Jessica Lowenstein, Paola Alvarez, Joye Roll Supported by NCI grants CA 10953 (RPC) and CA 81647 (ATC)

2. QA for Advanced Technology, Dallas, February 2007 2 Learning Objectives Role of RPC in support of clinical trials Sources of requirements for credentialing Goals of credentialing Procedures for credentialing Results from credentialing procedures Remaining challenges in credentialing

3. QA for Advanced Technology, Dallas, February 2007

4. 4 Brief Background Formed by agreement between AAPM and CRTS Founded in 1968 to monitor institution participation in clinical trials Funded continuously by NCI as structure of cooperative group programs have changed Credentialing added as complexity of trials has increased Now 38 years of experience of monitoring institutions and reporting findings to study groups and community

5. QA for Advanced Technology, Dallas, February 2007 NCI QARC RPC QA PROGRAM RPC QA PROGRAM ITC (High tech Protocols) ITC RTOG/ACR RCET RPC has relationships with all study groups and with Advanced Technology Consortium ACOSOG COG SWOG CALGB ECOG NSABP NCCTG GOG ACRIN RTOG COMS CTSU

6. QA for Advanced Technology, Dallas, February 2007 Activities specific to advanced technology trials Measurements specifically addressing advanced technologies: dynamic wedges, MLC-shaped fields, small fields, etc. Credentialing using benchmarks (compatibility with QARC maintained where relevant) Credentialing using phantoms Independent recalculation of dose distributions with Eclipse planning system and RPC “standard” data

7. QA for Advanced Technology, Dallas, February 2007 7 Digital Data Submission > 300 institutions have demonstrated ability to submit digital data to ITC Data-quality QA by ITC; Contour review Dosimetry QA review by RPC online using RRT RPC compares plan and phantom data, MD conducts clinical review

8. QA for Advanced Technology, Dallas, February 2007 Education Evaluate ability to deliver dose Improve understanding of protocol Reduce deviation rate Purposes of Credentialing

9. QA for Advanced Technology, Dallas, February 2007 General Credentialing Process Feedback to Institution Previous patients treated with technique Facility questionnaire Knowledge assessment questionnaire Benchmark case or phantom Electronic data submission RPC QA & dosimetry review Clinical review by radiation oncologist

10. QA for Advanced Technology, Dallas, February 2007 10 Questionnaires Facility Questionnaire Documents equipment Allows evaluation of QA procedures Knowledge Assessment Tests physician’s knowledge of the protocol

11. QA for Advanced Technology, Dallas, February 2007 11 Brachytherapy Credentialing Paper- or CT-based benchmark RPC uses ATC remote review tool Evaluate single source calculation Prostate or breast HDR or LDR QARC used identical methods for prostate LDR

12. QA for Advanced Technology, Dallas, February 2007 12 3D Conformal Radiation Therapy (3D CRT) Evaluate 3D treatment planning process and ability to provide documentation Conducted by QARC and RPC ~500 institutions credentialed to date Some through NSABP/RTOG partial breast irradiation protocol

13. QA for Advanced Technology, Dallas, February 2007 13 IMRT Benchmark for Credentialing Institution transfers structures to CT data set Prepares and submits IMRT plan Demonstrates ability to plan using IMRT Meet constraints on doses to PTV and OAR Supplies results of QA measurements

14. QA for Advanced Technology, Dallas, February 2007 RPC Phantoms prostate IMRT: 4, incl. prosthesis thorax SBRT: 3 phantoms, 6 under construction liver SBRT: 3, incl. motion H&N IMRT: 25 in service SRS: 2 in service, others sent by RDS

15. QA for Advanced Technology, Dallas, February 2007 15 Phantom Mailings by Year

16. QA for Advanced Technology, Dallas, February 2007 16 IMRT Credentialing 250+ institutions have successfully irradiated an RPC IMRT phantom

17. QA for Advanced Technology, Dallas, February 2007

18. Plan vs. Treatment

19. QA for Advanced Technology, Dallas, February 2007 Phantom Results Comparison between institution’s plan and delivered dose. Criteria for agreement: 7% or 4 mm DTA * 30% of institutions failed H&N phantom on the first attempt PhantomH&NProstateThoraxLiver Irradiations25473306 Pass179*55173 Fail71971 Under analysis or at institution 30661 Year introduced20012004 2005

20. Explanations for Failures Explanation Minimum # of occurrences incorrect output factors in TPS1 incorrect PDD in TPS1 Software error1 inadequacies in beam modeling at leaf ends (Cadman, et al; PMB 2002) 14 not adjusting MU to account for dose differences measured with ion chamber 3 errors in couch indexing with Peacock system 3 2 mm tolerence on MLC leaf position1 setup errors7 target malfunction1

21. QA for Advanced Technology, Dallas, February 2007 21 Credentialing for Lung Protocols RPC evaluates dose to TLDs Criteria: ± 0.05 Evaluate DTA from film data ± 5 mm at all sides of target Analysis neglects variation across target RPC has proposed to include evaluation of dose across target 21

22. 22 RPC Lung Phantom PTV

23. QA for Advanced Technology, Dallas, February 2007 23 Modifications to Phantoms for IGRT Presently rely on surface markers and laser alignment IGRT systems require internal fiducials and/or anatomy for image- based alignment

24. QA for Advanced Technology, Dallas, February 2007 Evaluation of Heterogeneity Corrections with RPC Thorax Phantom Convolution/superposition algorithm showing good agreement with measurements Pencil-beam algorithm showing poor agreement with measurements

25. QA for Advanced Technology, Dallas, February 2007 Results of Credentialing (closed studies) Study Major Deviations Minor Deviations Number of Patients GOG 165 HDR Cervix Credentialed inst 01570 RTOG 95-17 HDR & LDR Breast (all) 04100 RTOG 0019 LDR Prostate (values for dose only) 06 117 reviewed (total 129 eligible)

26. QA for Advanced Technology, Dallas, February 2007 Results of Credentialing (closed studies) Study Major Deviations Minor Deviations Number of Patients GOG 165 HDR Cervix Credentialed inst 01570 Non-credentialed5787275 RTOG 95-17 HDR & LDR Breast (all) 04100 RTOG 0019 LDR Prostate (values for dose only) 06 117 reviewed (total 129 eligible)

27. QA for Advanced Technology, Dallas, February 2007 27 Challenges in Credentialing Need to streamline process Status of institution submission Need additional phantoms To meet demand To evaluate new techniques (protons, IGRT) CT benchmarks to be readable by all TPSs Working to develop: Monte Carlo calculations Improved software to compare plan with film/TLD data Improved dosimetry systems 27

28. QA for Advanced Technology, Dallas, February 2007 28 Credentialing Status Inquiry

29. QA for Advanced Technology, Dallas, February 2007 Status of RPC Preparations for Monitoring Proton Facilities RPC visited PTC-H during construction to learn about facility design and operation Visits to PTC-H and to UF/Jacksonville to measure and verify beam output, depth dose characteristics Irradiated TLD at 3 facilities under more than 30 combinations of energy, field size, depth Evaluated radiochromic film for use in proton beams Presently testing BANG® gel & Presage™ dosimeters Evaluating OSL dosimeters

30. QA for Advanced Technology, Dallas, February 2007 30