1. ACRIN Abdominal Committee ACRIN Gynecologic Committee Fall Meeting 2010

2. ACRIN Gynecologic Committee Perfusion CT (DCE-CT) as an early predictor of response to combined cytotoxic and anti- angiogenic chemotherapy and as a surrogate marker of long-term outcome for patients with advanced stage epithelial ovarian, peritoneal and fallopian tube cancer: A companion study to GOG 262 ACRIN 6695 Chaan Ng

3. ACRIN Gynecologic Committee BACKGROUND: Biomarkers Overall survival Response Biomarkers in oncology -Assessment of tumor response -Predictors of response -Prognostic markers CEA, PSA, Ca125 TNM RECIST

4. ACRIN Gynecologic Committee BACKGROUND: CT Perfusion CT Perfusion –Tissue viability Angiogenesis –Functional evaluation Tumor blood flow, volume, permeability –Combined with routine CT staging

5. ACRIN Gynecologic Committee BACKGROUND: “THE QUESTION” Utility of CT perfusion in oncology Translatability of CT perfusion into clinical environment

6. ACRIN Gynecologic Committee BACKGROUND: THE STUDY ACRIN 6695 GOG 262

7. ACRIN Gynecologic Committee PROTOCOL SCHEMA

8. ACRIN Gynecologic Committee

9. “Conventional” “Dose-dense” Primary Endpoint: -Progression-free survival (PFS) Secondary Endpoints: -Overall Survival (OS) -Response Rate (RR) -Toxicity -Translational Research -Quality of Life

10. ACRIN Gynecologic Committee

12. IMAGING OBJECTIVES: Primary Whether larger changes in tumor perfusion parameters (T 2 - T 0 ) are predictive of better progression-free-survival rate at 6 months (PFS 6m ) –[Early predictor of response?] –[Prior to first routine CT restaging]

13. ACRIN Gynecologic Committee

14. Contrast body CT

15. ACRIN Gynecologic Committee TARGET LESION Precontrast –>1cm short axis –> 10 HU on pre-contrast (50% of lesion) Postcontrast –> 5 HU enhancement (in 50% of lesion)

16. ACRIN Gynecologic Committee CT CONTRAST Oral contrast –Negative or positive contrast IV contrast –>300 mgI 2 /mL –3-4 mL/s –0.8 mL/kg body weight (max. 70 mL volume)

17. ACRIN Gynecologic Committee TARGET LESION: examples

18. ACRIN Gynecologic Committee TARGET LESION: examples

19. ACRIN Gynecologic Committee TARGET LESION > 2cm Round or oval –Not plaques Avoid motion –Retroperitoneum –Pelvis Enhancement –Cyst, ascites, hematoma Postop changes

20. ACRIN Gynecologic Committee ELIGIBILITY Eligible for GOG Adequate renal function No contraindication to IV contrast medium Diabetics on Metformin Consent process –Correlative within Consent Form of participating GOG sites, with “opt-out”

21. ACRIN Gynecologic Committee ANALYSES Central perfusion CT data analysis –Ting Lee –ACRIN HQ Data available for alternative analyses –GE model –Other vendors

22. ACRIN Gynecologic Committee ACCRUAL ACRIN = 70 evaluable –GOG = 625 Attrition –In practice we need 25-30% of GOG accrual

23. ACRIN Gynecologic Committee CHALLENGES Accrual –Sites –GOG –Target lesions Radiation dose

24. ACRIN Gynecologic Committee SITES Looking for collaborating sites

25. ACRIN Gynecologic Committee

26. ACRIN Abdominal Committee ACRIN Gynecologic Committee CONTACT DETAILS Chaan Ng Department of Radiology MD Anderson Cancer Center Houston, TX 77030-4009 Phone: 713-792-6759 Email: cng@mdanderson.org Ting-Yim Lee Imaging Research Labs, Robarts Research Institute London, Ontario, Canada Phone: 519-663-5777 ext. 24131 Email: tlee@imaging.robarts.ca