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 SocietyNovember 17th, 2012

Prague, Czech Republic

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

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

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

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

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

Lung/Pleura Abdomen/Pelvis

Extremity Head/Neck0

5

10

15

20

25

30Primary Sites

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

Disease Characteristics

Disease CharacteristicsHistology

BenignMalignant

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

Benign

Malignant

Disease CharacteristicsBenign N (%) Malignant N (% ) P-Value

Tumor Size  < 5 cm 15 (35) 3 (8) 0.006

  5 - 10 cm 9 (21) 16 (41)

  > 10 cm 15 (35) 15 (38.5)

  Unknown 4 (9) 5 (13)

Mitotic Count  < 4/10 HPF 40 (93) 8 (20.5) < 0.001

  4 - 10/10 HPF 1 (2) 25 (64)

  >10/10 HPF 0 6 (15)

  Unknown 2 (5) 0

CD34 Status  Positive 33 (77) 29 (74) 0.702

  Negative 5 (12) 7 (18)

  Unknown 5 (12) 3 (8)Presentation at Dx  Metastatic 0 6 (15)

0.057

  Localized 43 (100) 33 (85)

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.

Treatments78 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 0 2 (5)Radiation     0.010

Yes 9 (21) 19 (49)No 34 (79) 20 (51)

Survival Differences Between Benign and Malignant SFT/HPC

By univariate analysis, benign vs. malignant variant positively impacted overall survival (P=0.02)

Survival Differences in Surgically and Non-Surgically Treated Patients

By univariate analysis, complete resection positively impacted overall survival (P<0.0001, HR 0.09)

Univariate Survival AnalysisVariables P-value from

OSHistologic Status 0.02Tumor Classification 0.11Primary Site 0.54Metastasis at Diagnosis 0.09Chemotherapy Use 0.01Surgery <0.00Radiation Use 0.82Tumor Size 0.36Mitotic Count 0.28

Survival Data for Clinical CharacteristicsOverall 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) 88 76 65 N/A

Benign SFT/HPC 186.6 (61 - NR) 92 86 77 0.42

Malignant SFT/HPC 94.4 (30.6 - 124.9) 84 66 58

Localized Disease at Diagnosis

107.7 (94.4 - 154.9) 89 77 68 0.45

Metastatic Disease at Diagnosis

54.6 (3.4 - 139.8) 69 51 26

No Surgery 7.53 (3.43 - 19.8) 25 0 0 12.48

Surgery 107.7 (94.4 - 154.9) 93 80 69

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

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.

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