International RT Clinical Trial Group Membership & Quality Control BY DR YING XIAO

Transcription

1 International RT Clinical Trial Group Membership & Quality Control BY DR YING XIAO

2 Disclosures The Department of Radiation Oncology at Hospital of University of Pennsylvania has a research agreement with Varian Medical Systems. Dr. Ying Xiao has received speakers honoraria from Varian Medical Systems. Dr. Xiao has funding support from NCI/NIH and from Pennsylvania Department of Health

3 INTENDED USE STATEMENT Varian Medical Systems linear accelerators are intended to provide stereotactic radiosurgery and precision radiotherapy for lesions, tumors, and conditions anywhere in the body where radiation treatment is indicated. SAFETY Radiation treatments may cause side effects that can vary depending on the part of the body being treated. The most frequent ones are typically temporary and may include, but are not limited to, irritation to the respiratory, digestive, urinary or reproductive systems, fatigue, nausea, skin irritation, and hair loss. In some patients, they can be severe. Treatment sessions may vary in complexity and time. Radiation treatment is not appropriate for all cancers. Medical Advice Disclaimer Varian as a medical device manufacturer cannot and does not recommend specific treatment approaches. Individual treatment results may vary. For more information, visit MyVarian.com. FOR HEALTH CARE PROFESSIONALS ONLY

4 rials/january%202016%20meeting%20resources/intro%20sessions/atlanta%202016%20nrg%20mem bership%20mp_corrected.pdf Membership in NRG Oncology Mimi Passarello, MBA

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6 Department of Health and Human Services NIH FDA CDC NCI National Eye Inst. National Human Genome Res. Inst. Div. Cancer Treatment & Diagnosis (DCTD) Div. Of Cancer Prevention (DCP) Cancer Therapy Evaluation Program (CTEP) Pharmaceutical Management Branch (PMB) Clinical Trials Monitoring Branch (CTMB) Clinical Investigations Branch (CIB)

7 NCI National Clinical Trials Network The NCTN structure includes five U.S. Network groups and the Canadian Collaborating Clinical Trials Network. Membership in the individual NCTN groups is based on criteria that are specific to each group. Sites can belong to more than one group, and membership in at least one group allows a site to participate in the trials led by any NCTN group for which their investigators are qualified. Consequently, researchers from NCORP, academic centers, community practices, and international members associated with the Network groups may all enroll patients onto NCTN trials. 7

8 Membership Types / Funding Sources TIER 1 Parent: Main Member (accruing or TIER 2 Children: Affiliates TIER 3 Grandchildren: Sub-Affiliates non-accruing)

9 Membership Types (cont.) TIER 1 Parent: NCORP Grantee (Administrative) TIER 2 Children: NCORP Components NCORP Sub- TIER 3 Grandchildren: Components

10 Lead Academic Participating Site (LAPS) Definition Designated by and funded through a grant from the Division of Cancer Treatment and Diagnosis (DCTD). Provide direct medical care to patients/study participants and have a comprehensive medical training program, as well as preclinical laboratories that perform basic research.

11 Membership Types (cont.) TIER 1 Parent: Lead Academic Participating Sites (LAPS) TIER 2 Children: LAPS LAPS MM Integrated Components LAPS Affiliates LAPS Aligned Affiliates TIER 3 Grandchildren: LAPS Sub-Affiliates LAPS Aligned Sub-Affiliates within grant

12 Sub Affiliate / Sub Component Definition Healthcare practice locations, for example, clinics, physician offices or treatment locations. These locations are used by registered investigators to consent, register / enroll and treat patients. Can be Sub Affiliate of a Tier 1 or Tier 2. Usually owned by institution in tier above them Not convenience sites or clinics with physicians rotating through

13 Membership Requirements TIER 1: Parents (Main Member, NCORP, LAPS) Required to accrue 15 patient cases per year to NRG Maintain satisfactory data quality and audit performance Affiliate accrual will count toward the 15 case requirement Accrual credited to NRG will also count

14 Membership Requirements TIER 1: Parents (Main Member, NCORP, LAPS) (cont.) Parent institutions are able to designate up to 3 PIs - Should represent different medical specialties Per case reimbursement for affiliates will go to the Parent

15 Membership Requirements Affiliate Members Aligned with a Main Member Affiliates permitted to contract with only one Main Member North American affiliates required to accrue 3 cases per year International affiliates required to accrue 7 cases per year

16 Adding Institutions to the NRG Oncology Roster New Main Members / NCORPs / LAPS (TIER 1): Extensive review by Membership Committee LAPS and NCORPs (entire grant package accepted) New Affiliates: Review by membership staff for completeness Signed by Main Member Approved by Deputy Chair of Membership New Sub Affiliates: Review by membership staff for completeness

17 Membership questions: Roster questions:

18 Quality Implementation Guidance NRG & protocols Enforcements IROC core functions

19 Critical Impact of Radiotherapy Protocol Compliance and Quality TROG L. J. Peters et al, Journal of Clinical Oncology, vol. 28, Number 18, June 2010

20 Failure To Adhere To Protocol Associated With Decreased Survival: RTOG 9704 R. Abrams et al, Int. J. Radiation Oncology Biol. Phys., Vol. 82, No. 2, pp , 2012

21 A literature study Ohri, N., Shen, X., Dicker, A. P., Doyle, L. A., Harrison, A. S., & Showalter, T. N. (2014). Radiotherapy Protocol Deviations and Clinical Outcomes, 1 10.

22 Significant HR

23 Goal & Purpose of the Clinical Trial Enterprise The overall goal for the NCTN is to conduct randomized phase 2 and phase 3 clinical treatment trials and primary advanced imaging trials across a broad range of diseases and diverse patient populations as part of the NCI s overall clinical research program for adults and children with cancer. The overall goal for the NCORP is to conduct trials to improve cancer prevention, cancer control, screening, cancer care delivery, and post-treatment management. All NCORP sites enroll patients in NCTN trials. 23

24 Aims of CIRO 1) Promote innovative RT research within the entire NCTN Accelerate the testing of new radiation oncology innovations in NCTN clinical trials in all groups Facilitate the application of innovations across all appropriate protocols 2) Foster intergroup collaboration and protocol harmonization in terms of inclusion and description of RT techniques and delivery devices Reduce timelines for development of new protocols Improve the clarity of NCTN protocols

25 WEBPAGE The CIRO webpage provides several resources for the network such as atlases, protocol templates for RT sections, and applications to facilitate RT data preparation and submission.

26 Opportunities Co-authorship on clinical trials related reports Clinical trial result for physicist PI Secondary analysis of trials data QA effectiveness research Learn structure and implementation of clinical trials Stimulate interest in secondary analysis of clinical trial digital data collaboration with NCTN Group and QA core

27 Example of Concept Questionnaire

28 Radiation Therapy Section Templates Templates for each disease site Example links: Templates for Head and Neck Including H&N Atlas Link Including NRG Protocol Radiation Therapy Template (including Proton and Photon)

29 Example for RO section Template

30 RO section Template cont d

31 Example Structure Name Library

32 Plan evaluation Eclipse Plan Evaluation Scripts Website: Innovation-in-Radiation-Oncology

33 Brain Site Example

34 Brain Site Example-BN001 Plan Evaluation Eclipse Scripts Constraints Template for BN001

35 Brain Site Example-BN001 Plan Evaluation Eclipse Scripts Plan Evaluation Results for BN001

36 MiM Scripts Dose Constraints Head and Neck Examples

37 IROC s five programmatic QA approaches Site Qualification Trial design support Credentialing Data (prereview) Management Case Review Data (postreview) Management

38 Centralized data submissions, review and analyses

39 Credentialing

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41 Direct Peer Review RapidPlan models built using the trial cases provide direct peer review to the score 3 plans

42 Example: HN002c0088 spinal cord variation acceptable Protocol dose constraint: HN002 D0.03cc<=45Gy, DVH estimation produced by model indicating that the plan can be further improved

43 Another Example 0631c0113 OARs failed to meet protocol constraints SpinalCord_Prt Esophagus Spinal Cord Original Plan failed to meet Protocol dose constraint: SpinalCord D0.35cc<=10.25Gy

44 RTOG0617 Plans Before and After Re-optimization with RTOG1308

45 Giaddui, T., Chen, W., Yu, J., Lin, L., Simone, C. B., Yuan, L., Xiao, Y. (2016). Establishing the feasibility of the dosimetric compliance criteria of RTOG 1308:phase III randomized trial comparing overall survival after photon versus protonradiochemotherapy for inoperable stage II-IIIB NSCLC. Radiation Oncology, 11(1),66. Use knowledge-engineering for NRG/RTOG 1308 Dosimetric Feasibility Study RT Parameter per protocol Variation acceptable % of PTV covered by prescription dose 95% 95% of the PTV is covered by 95% of the prescription dose % of ITV (motion-incorporated CTV) 100 % 99% Maximum PTV dose PTV (0.03 cc) 120% RX 125 % RX Minimum PTV dose (0.03 cc) 85 % RX 75 % RX Normal lung (Both lungs minus GTV) V5 60% V20 37 % Mean dose < 20 Gy (RBE) V5 65% V20 40% Mean Dose: 22 Gy (RBE) Esophagus Max dose: 74 Gy (RBE) 1cc of partial circumference Max dose: 74 Gy (RBE) 1.5cc of partial circumference Brachial Plexus V cc V cc V cc V cc V cc V cc V cc V cc Spinal Cord V50 < 0.03 cc V52 < 0.03 cc Heart V30 50% V45 35% 50 % V30 55 % 35% V45 40 %

46 Predictions from KBP Dosimetric Criteria Treatment planning system Knowledge based engineering tool Spinal Cord 40 ± 2 44 ± 2 Maximum Dose (Gy) Esophagus Maximum 68 ± 3 75 ± 2 Dose (Gy) Heart V 30 Gy (%) 16 ± 4 15 ± 3 Heart V 45 Gy (%) 10 ± 3 9 ± 2 Lung V 20Gy (%) 27 ± 2 29 ± 2 Lung mean dose (Gy) 17 ± 1 18 ± 2

47 Comparing photon vs. proton Structure PTV Dosimetric Photon IMRT Proton PSPT Parameter % of cases failed % of cases failed to meet the to meet the criteria criteria % of PTV covered 0 0 by RX PTV minimum PTV maximum 0 4 Spinal Cord Maximum dose 4 0 Total Lung (both V5 4 0 lungs GTV) V Mean dose 12 4 Heart V V Brachial Plexus V V V75 5 0

48 Outcome Driven QA Guidelines Available Treatment Options Radiation vs. Surgery IMRT vs. Proton vs. Brachytherapy Technology advancement linked with producing biological and, especially, molecular genetic information from tumors and the host Acknowledgment of the importance of translational research and, especially, its association with well-described clinical studies. Integrated database Establishment of linkage between a given response and the outcome Other factors, HPV, age Seminars in Radiation Oncology, April 2012

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