1. Functional Imaging with PET for Sarcoma Rodney Hicks, MD, FRACP Director, Centre for Molecular Imaging Guy Toner, MD, FRACP Director, Medical Oncology The Peter MacCallum Cancer Centre, Melbourne, Australia

2. Functional Imaging with PET in Sarcoma Potential Applications Benign versus malignant Grading Biopsy guidance Staging Therapeutic monitoring Restaging ( local recurrence)

3. Functional Imaging with PET in Sarcoma Potential Applications Benign versus malignant Grading Biopsy guidance Staging Therapeutic monitoring Restaging ( local recurrence)

4. Folpe AL et al. Clin Cancer Res 2000; 6: 1279-1287 Grade vs SUV (By percentile) n = 89 25%50%75% BEN1.53.86.9 G11.552.654.11 G23.406.0510.25 G34.226.8519.35 PET in Sarcoma Applications – Tumour Grading

5. Right gluteal malignant fibrous histiocytoma Very high SUV Widely disseminated metastases at 12 months PET in Sarcoma Applications – Tumour Grading p7003s0

6. Pelvic spindle cell sarcoma Neoadjuvant Rx then resected at 3 months No recurrence at 12 months p6694s0 PET in Sarcoma Applications – Tumour Grading

7. Functional Imaging with PET in Sarcoma Potential Applications Benign versus malignant Grading Biopsy guidance Staging Therapeutic monitoring Restaging ( local recurrence)

8. Large left thigh mass with MRI features consistent with liposarcoma Biopsy guided to highest metabolic region confirmed high grade tumour Multiple subcutaneous metastases also detected by PET PET in Sarcoma Applications – Biopsy Guidance p6826s0

9. Functional Imaging with PET in Sarcoma Potential Applications Benign versus malignant Grading Biopsy guidance Staging Therapeutic monitoring Restaging ( local recurrence)

10. 1. Franzius C et al Ann Oncol 2001; 12:479-486 2. Lucas JD et al J Bone Joint Surg Br 1998; 80:441-447 3. Franzius C et al Eur J Nucl Med 2000; 27:1305-1311 PET in Sarcoma Applications - Staging CT is superior to stand-alone FDG PET for detecting lung mets (1,2) PET can identify false positive CT masses NPV is proportional to uptake in primary tumor FDG PET has higher sensitivity than CT for soft tissue metastases (2) Whole-body FDG PET may be superior to bone scan for bone metastases (3)

11. Franzius C et al Ann Oncol 2002;13:157-160 Garcia R et al J Nucl Med 1996; 37:1476-1479 el Zeftawy H et al Cancer Biother Radiopharm 2001; 16:37-46 Bredella M et al AJR 2002; 179:1145-1150 Johnson GR et al Clin Nucl Med 2003; 28:815-820 FDG-PET is not disabled by metal susceptibility or metal beam hardening artefacts Multiple studies indicating good accuracy of FDG PET for detecting late local recurrence PET in Sarcoma Applications – Suspected Local Recurrence

12. Functional Imaging with PET in Sarcoma Potential Applications Benign versus malignant Grading Biopsy guidance Staging Therapeutic monitoring Restaging ( local recurrence)

13. Survival by PET response in 88 patients receiving radical radiotherapy Mac Manus et al, J Clin Oncol 2003 FDG PET in Lung Cancer Therapeutic Monitoring

14. Osteosarcoma of the left femur treatment with neoadjuvant chemotherapy Near complete metabolic response PET in Sarcoma Applications – Therapeutic Monitoring p8455s0s1 Baseline Post-Chemo Projection Images PET Fused PET-CT

17. Clinical Trial Proposal PET

18. Clinical Trial Proposal PET

19. Study Design Screen SU11248 50mg po qdBreakSU11248 50mg po qdBreak 0461012Week28 All Patients (30-40 planned):  Response (RECIST)    FDG PET   PK/PD  10 patients per group:  FLT PET   Miso PET   15 O-Water PET  Biopsy

20. Two Types of Response Week 0 Week 32 Week 0 Week 12 1-Shrinkage 2-Central Necrosis

21. Biologic & Anti-Tumor Activity FDG PETFLT PET Week 2 Week 12 Week 0

22. Pre- Treatment Week 24

23. PET For Therapeutic Monitoring Serial FDG Imaging Metastatic malignant melanoma Mixed metabolic response - CMR in right chest wall lesion Had 10 days of drug, 6 day break and on drug at 50% dose Baseline FDG PET Week 2 FDG PET SU-11248-pt-014

24. PET For Therapeutic Monitoring Serial FDG Imaging Metastatic malignant melanoma Rapid clinical and FDG progression on reduced dose due to toxicity Baseline FDG PET Week 4 FDG PET SU-11248-pt-014

25. Functional Imaging with PET in Sarcoma Potential Applications - Conclusions Grading & Benign versus Malignant provides useful complementary information must be considered in context of clinical picture chondroid matrix and sclerosing liposarcoma may produce false negative result further studies required to determine if independently prognostic Biopsy guidance very valuable, particularly PET/CT

26. Functional Imaging with PET in Sarcoma Potential Applications - Conclusions Staging & re-staging useful whole-body screen NPV proportional to uptake in primary tumor helpful in assessing possible local recurrence Therapeutic monitoring potentially of enormous clinical value changes evident rapidly (weeks) further studies required to improve quantification of response potential advantages for alternative tracers e.g. FLT