1. University of Pennsylvania Department of Orthopaedic Surgery Joseph King, Eileen Crawford, Abass Alavi, Arthur Staddon, Lee Hartner, Richard Lackman and Christian Ogilvie PET Scan Markers for Survival in Patients with Soft Tissue Sarcomas

2. University of Pennsylvania Department of Orthopaedic Surgery Background Soft tissue sarcomas (STS) are a heterogeneous group of malignant tumors Prognosis determined by CT, MRI, and biopsy Problems/challenges: –Local extent, metastasis, recurrence –Diagnosis, grading, monitoring treatment response

3. University of Pennsylvania Department of Orthopaedic Surgery Background FDG uptake proportional to growth rate of neoplastic cells PET SUVmax > 6 in sarcomas related to survival and progression 1 PET has shown promise in predicting survival for lung and breast carcinomas 2-4 Poor PET response to chemotherapy in STS (< 40% decline in FDG uptake) associated with increased rate of recurrence and death 5 1) Eary et al 2002 2) Kramer et al. 2006 3) Chen et al. 2004 4) Schwartz et al. 2005 5) Sheutz et al. 2005

4. University of Pennsylvania Department of Orthopaedic Surgery Purpose Determine predictors of survival based on FDG-PET imaging for patients with soft tissue sarcomas –SUVmax –Response to chemotherapy –PET active lung nodules

5. University of Pennsylvania Department of Orthopaedic Surgery Hypothesis Predictors for decreased survival will include: –High maximum standard uptake value (SUV) –FDG-enhancing lung nodules –Poor SUV-based response to chemotherapy

6. University of Pennsylvania Department of Orthopaedic Surgery Materials and Methods Study Design: Retrospective review Study Group: –Treated with chemotherapy +/- resection High or intermediate grade sarcoma Primary tumor > 5 cm, or metastatic disease –PET scans done between 2003-2006 –1 st PET done before all disease resected –Minimum follow-up 6 months –14 patients with pre- and post-chemo PET scans

7. University of Pennsylvania Department of Orthopaedic Surgery Materials and Methods Study Group: –32 patients with STS –14 excluded Bone sarcoma Also had carcinoma No gross disease at time of initial scan Inadequate documented follow up

8. University of Pennsylvania Department of Orthopaedic Surgery Materials and Methods Outcome Measures: 1. Maximum SUV (primary sarcoma or metastasis) 2. Number and location of PET detected metastatic lesions 3. SUV-based response to chemotherapy –Response: ≥ 40% decrease in SUV in over ½ of lesions –Stability: < 40% decrease in SUV in over ½ of lesions –Progression: SUV increase or new lesions

9. University of Pennsylvania Department of Orthopaedic Surgery Patient Characteristics DiagnosisN Leiomyosarcoma10 Synovial sarcoma7 Liposarcoma4 Malignant fibrous histiocytoma4 Sarcoma NOS2 Rhabdomyosarcoma1 Myxofibrosarcoma1 Atrial sarcoma1 Desmoplastic round cell tumor1 Extraosseous Ewing sarcoma1 Mean age = 47 (range 20-74) 13 had mets on presentation 15 developed mets during f/u LocationN Lower extremity11 Pelvis6 Chest5 Abdomen5 Upper extremity4 Back1

10. University of Pennsylvania Department of Orthopaedic Surgery Results Mean follow-up = 49 months (range 7-172 months) 10 alive at last f/u  6 with NED, 4 with metastatic disease 5 patients had local recurrence after resection  mean time to LR was 2.4 years Prognostic factorNMean Survival (months)P-value SUVmax < 62215.10.93 SUVmax ≥ 61014.7 No nodules1921.60.007 1-3 nodules910.7 No nodules1921.60.003 4+ nodules46.2 1-3 nodules910.70.20 4+ nodules46.2 Progression63.90.05 No progression816.8

11. University of Pennsylvania Department of Orthopaedic Surgery p=0.76

12. University of Pennsylvania Department of Orthopaedic Surgery p=0.01

13. University of Pennsylvania Department of Orthopaedic Surgery p=0.001

14. University of Pennsylvania Department of Orthopaedic Surgery Conclusions PET scan markers for decreased survival in patients with high grade STS include: –Presence of FDG-enchancing lung nodules –SUV-based disease progression during chemotherapy SUVmax ≥ 6 was not a predictor for decreased survival

15. University of Pennsylvania Department of Orthopaedic Surgery Discussion Obtaining pre- and post-treatment PET scans to evaluate treatment response of localized or metastatic STS provides useful prognostic information Maximum SUV was not found to have prognostic significance in this study –Lots of metastatic disease: selection bias with under representation of patients with lower histologic grade and better prognosis?

16. University of Pennsylvania Department of Orthopaedic Surgery Future directions Larger prospective studies of response to chemotherapy underway Data on histologic subtypes –Liposarcoma: Brenner et al. 2006 –Rhabdomyosarcoma: Klem et al. 2007 Probes other that glucose –Hypoxia –Apoptosis

17. University of Pennsylvania Department of Orthopaedic Surgery Thank You!