1. CLINICAL CHARACTERISTICS AND OUTCOMES FOR BENIGN AND MALIGNANT SOLITARY FIBROUS TUMOR / HEMANGIOPERICYTOMA (SFT/HPC) – A SINGLE CENTER EXPERIENCE Nicholas DeVito, M.D.; Evita Henderson, M.D.; Gang Han, Ph.D.; Damon Reed, M.D.; Marilyn Bui, M.D., Ph.D.; Robert Lavey, M.D., M.P.H.; Lary Robinson, M.D.; Jonathan S. Zager, M.D.; Ricardo J Gonzalez, M.D.; Vernon K. Sondak, M.D.; G. Douglas Letson, M.D.; Anthony Conley, M.D. Moffitt Cancer Center, University of South Florida, Tampa, FL, USA Connective Tissue Oncology Society November 17 th, 2012 Prague, Czech Republic

2. Introduction and Background Solitary Fibrous Tumor/Hemangiopericytoma (SFT/HPC) is a ubiquitous mesenchymal tumor of fibroblastic type. SFT/HPC typically affects adults from ages 20 to 70 years Vallat-Decouvelaere et al first distinguished malignant from benign variants on the basis of nuclear atypia, hypercellularity, greater than 4 mitosis/10 HPFs, and necrosis However, the correlation between morphology and aggressiveness is poorly defined Surgery is the treatment of choice for local disease, radiation is an option of unclear benefit, and chemotherapy is often a final effort

3. Introduction and Background One recent retrospective study examined the use of temozolomide and bevacizumab to treat SFT/HPC A prospective trial was presented at AACR in 2010 that examined the molecular characteristics and targeted therapeutics for patients with SFT/HPC resistant to conventional chemotherapies. Eleven patients received sunitinib maleate and figitumumab with favorable response

4. Our Purpose This retrospective chart review was conducted to further define the clinical characteristics and outcomes in patients with benign and malignant SFT/HPC We hope that it will further the understanding of this rare disease and become useful as a reference for future clinical trials

5. Methods Patients with pathology defined SFT/HPC who were treated at the Moffitt Cancer Center were first identified through the Total Cancer Care database and then through PowerChart database queries from 1993 to 2011 Two sarcoma pathologists re-reviewed every case in an un-blinded manner Internal Review Board approval under an umbrella protocol for the purpose of retrospective studies Data collected from PowerChart included age of the patient, patient gender and race, vital status, last follow up, age of presentation, primary tumor site, date and site of metastases, chemotherapeutic, surgical and radiotherapeutic interventions

6. Our Patients 82 patients total 47(57%) women 73(89%) Caucasian Median age: 62 years (range, 20 - 89) Thirty-two (39%) pts died as of Nov. 2011 The median follow-up was 55.3 months

7. - Lung/Pleura in 28(34%) - Abdomen/Pelvis in 23(28%) - Extremity in 13(16%) - Head/Neck in 9(11%) Disease Characteristics

8. Benign: 43(52%) Malignant: 39(48%)

9. Benign Malignant

10. Disease Characteristics Benign N (%)Malignant N (% )P-Value Tumor Size < 5 cm15 (35)3 (8) 0.006 5 - 10 cm9 (21)16 (41) > 10 cm15 (35)15 (38.5) Unknown4 (9)5 (13) Mitotic Count < 4/10 HPF40 (93)8 (20.5) < 0.001 4 - 10/10 HPF1 (2)25 (64) >10/10 HPF06 (15) Unknown2 (5)0 CD34 Status Positive33 (77)29 (74) 0.702 Negative5 (12)7 (18) Unknown5 (12)3 (8) Presentation at Dx Metastatic06 (15) 0.057 Localized43 (100)33 (85)

11. Disease Characteristics Compared to benign SFT/HPC, malignant histology was associated with: –larger tumor size –higher mitotic counts –metastatic disease at diagnosis –greater use of chemotherapy and radiation therapy Gender, age, and tumor site were not significantly different between benign and malignant subtypes.

12. Treatments 78 of 82 received surgery Benign N (%)Malignant N (%)P - Value Resection status 0.342 R0 31 (74)19 (53) R1 5 (12)8 (22) R2 2 (5)1 (3) Missing 4 (9.5)8 (22) Chemotherapy 0.003 Yes 5 (12)15 (38) No 38 (88)22 (56) Missing 02 (5) Radiation 0.010 Yes 9 (21)19 (49) No 34 (79)20 (51)

13. Survival Differences Between Benign and Malignant SFT/HPC By univariate analysis, benign vs. malignant variant positively impacted overall survival (P=0.02)

14. Survival Differences in Surgically and Non-Surgically Treated Patients By univariate analysis, complete resection positively impacted overall survival (P<0.0001, HR 0.09)

15. Univariate Survival Analysis VariablesP-value from OS Histologic Status0.02 Tumor Classification0.11 Primary Site0.54 Metastasis at Diagnosis0.09 Chemotherapy Use0.01 Surgery<0.00 Radiation Use0.82 Tumor Size0.36 Mitotic Count0.28

16. Survival Data for Clinical Characteristics Overall Survival (months) Median (months) (95% CI) 1-year % Survival (95% CI) 3-year % Survival (95% CI) 5-year % Survival (95% CI) Hazard Ratio (95% CI) All patients 107.7 (61 - 139.8) 887665N/A Benign SFT/HPC 186.6 (61 - NR) 9286770.42 Malignant SFT/HPC 94.4 (30.6 - 124.9) 846658 Localized Disease at Diagnosis 107.7 (94.4 - 154.9) 8977680.45 Metastatic Disease at Diagnosis 54.6 (3.4 - 139.8) 695126 No Surgery 7.53 (3.43 - 19.8) 250012.48 Surgery 107.7 (94.4 - 154.9) 938069

17. Discussion and Conclusions Malignant SFT/HPC was associated with larger, mitotically active tumors that were more likely to be metastatic at diagnosis compared to benign SFT/HPC Primary site was not associated with tumor behavior Clear survival differences exist between benign and malignant SFT/HPC

18. Discussion and Conclusions Patients treated with chemotherapy had an inferior OS compared to untreated patients, however, this is likely due to the severity of their disease. While surgery is the best treatment option for benign and malignant SFT/HPC, targeted systemic therapies and better understanding of the molecular pathogenesis are needed to improve outcomes for patients with metastatic, malignant SFT/HPC.

19. Acknowledgements Moffitt Cancer Center: –Sarcoma Department –Our Statistician Gang Han –Our Pathologists Dr. Henderson and Dr. Bui –Eric Anderson for facilitating funding for this trip –My Principal Investigator Dr. Anthony Conley University of South Florida, Morsani College of Medicine for supporting my research The Connective Tissue Oncology Society Tufts Medical Center, for arranging my schedule to allow me to present at CTOS