Clinical presentation, natural history and therapeutic approach in patients with solitary fibrous tumor (SFT): a retrospective analysis Tim Wessels, Iris Timmermans, Daphne Hompes, Marguerite Stas, Veerle Boecxstaens, Paul de Leyn, Willy Coosemans, Dirk Van Raemdonck, Esther Hauben, Raf Sciot, Paul Clement, Oliver Bechter, Benoit Beuselinck, F. J. Sherida H. Woei-A-Jin, Herlinde Dumez, Patrick Schöffski
Disclosure • No personal conflict of interest, only institutional
Epidemiology of SFT • RARECARE: Estimated incidence of SFT is less than 0.1 per 100.000 person-years ¹ • Frequency of SFT is less than 2% of all Soft Tisue Sarcoma (STS) ² • STS itself account for only 1% of all new diagnosed malignancies ² ¹ Stiller CA, Trama A, Serraino D, Rossi S, Navarro C, Chirlaque MD, et al. Descriptive epidemiology of sarcomas in Europe: report from the RARECARE project. Eur J Cancer. 2013;49(3):684-95. ² Gold JS, Antonescu CR, Hajdu C, Ferrone CR, Hussain M, Lewis JJ, et al. Clinicopathologic correlates of solitary fibrous tumors. Cancer. 2002;94(4):1057-68.
History of SFT - Localized fibrous tumor of the pleura - Localized mesothelioma • 1931: 5 clinical cases of SFT ¹ - Localized benign fibroma • 1942: Hemangiopericytoma (HPC) ² • 2013: Identical genetic alteration: NAB2-STAT6 gene fusion³ ¹ Klemperer P, Coleman BR. Primary neoplasms of the pleura. A report of five cases. Am J Ind Med. 1992;22(1):1-31. ² Stout AP, Murray MR. Hemangiopericytoma: A Vascular Tumor Featuring Zimmermann's Pericytes. Ann Surg. 1942;116(1):26-33. ³S chweizer L, Koelsche C, Sahm F, Piro RM, Capper D, Reuss DE, et al. Meningeal hemangiopericytoma and solitary fibrous tumors carry the NAB2-STAT6 fusion and can be diagnosed by nuclear expression of STAT6 protein. Acta Neuropathol. 2013;125(5):651-8
Clinical presentation and risk assesment of SFT • Unpredictable clinical behaviour • Doege-Potter syndrome (IGF2): 4% ¹ˉ² • Multiple risk stratification models De Perrot et al, Ann Thorac Surg. 2002 Tapias et al. Chest. 2015 Demicco EG, Mod Pathol. 2012 ¹ Fung EC, Crook MA. Doege-Potter syndrome and 'big-IGF2': a rare cause of hypoglycaemia. Ann Clin Biochem. 2011;48(Pt 2):95-6. ² Briselli M, Mark EJ, Dickersin GR. Solitary fibrous tumors of the pleura: eight new cases and review of 360 cases in the literature. Cancer. 1981;47(11):2678-89..
Treatment options of SFT • Treatment – Surgery: R0 – Radiotherapy: – (neo)-adjuvant? – Definite (60Gy) – palliative (39Gy) ¹ – Systemic therapy: Empirical: STS based – anthracycline mPFS: 4m > ifosfamide mPFS: 3m ² – pazopanib ³ ¹ Haas RL, Walraven I, Lecointe-Artzner E, Scholten AN, van Houdt WJ, Griffin AM, et al. Radiation Therapy as Sole Management for Solitary Fibrous Tumors (SFT): A Retrospective Study From the Global SFT Initiative in Collaboration With the Sarcoma Patients EuroNet. Int J Radiat Oncol Biol Phys. 2018;101(5):1226-33. ² Stacchiotti S, Libertini M, Negri T, Palassini E, Gronchi A, Fatigoni S, et al. Response to chemotherapy of solitary fibrous tumour: a retrospective study. Eur J Cancer. 2013;49(10):2376-83 ³ Martin-Broto J, Stacchiotti S, Lopez-Pousa A, Redondo A, Bernabeu D, de Alava E, et al. Pazopanib for treatment of advanced malignant and dedifferentiated solitary fibrous tumour: a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2019;20(1):134-44
Clinical presentation, natural history and therapeutic approach in patients with solitary fibrous tumor: a retrospective analysis
Materials and methods • Review of SFT/HPC pts 01/12/1990 and 30/09/2017 • Sarcoma database LECTOR • Definitions • OS: Interval between first diagnosis of local recurrence/ metastastatic disease and death all causes • PFS: Interval between day of primary surgery until the confirmation of a local or metastatic recurrence • Response rates: Calculated based on investigator assessment at moment of evaluation (Stable Disease (SD), Partial Response (PR), Progressive Disease(PD))
Patient characteristics Patients 94 Age (years) 56 (16-85) Sex Male 52 (55%) Female 42 (45%) Follow up (years) 4.7 (0.1-21.53 ) 2124 STS pts were included in our sarcoma database Prevalence of SFT: 4.4%
Primary site of SFT
Clinical presentation & diagnosis • Symptomatology highly variable • Hypoglycemia: 2 patients (2.1%) (Doege-Potter syndrome ) • No pathognomonic radiological signs • 7.4% SFT was written in a radiological report
Prognosis and recurrence n (%) Patients 94 Synchronous metastasis 6 (6.4) Primary resection 86 (91.5) Local recurrence 23 (26.7) Metachronous metastasis 26 (30.2) No recurrence 37 (43.0)
Overall survival Overall survival Cumulative proportion 100 n= 94 mOS: 56.0m (0.3-258.3) survival (%) 75 50 25 0 0 50 100 150 200 250 300 Time (months)
Local recurrence n= 23 (26.7%) mPFS: 35.5m (1.0-153.8) mOS 45.1m (4.7-118.2)
Metastatic recurrence n= 26 (30.2%) n= 32 mPFS= 36.0m (0.1-157.1) mOS= 19.0m (0.3-149.0)
Treatment: Surgery n (%) Primary surgery 86 R0 39 (45.5) R1 6 (7) Wider resection 2 (33.3) Rx 41 (39.1) R0: microscopic complete resection R1: microscopic residual tumor Rx: unknown resection status
Treatment: Radiotherapy n (%) Primary resection 86 Adjuvant radiotherapy 14 (16.3) local recurrence 1 (7.1) metastatic recurrence 5 (35.7)
Treatment: Systemic therapy n (%) Patients 94 Systemic therapy 28 (29.8) neoadjuvant 2 (2.1) palliative 24 (25.5) neoadjuvant and palliative 2 (2.1)
Treatment: Systemic therapy n=24 mOS: 24.0m (3.2-84.4)
Treatment: Systemic therapy n=26 n=16 mPFS: 4.7m (0.4-23.8) n=10
Treatment: Systemic therapy First response evaluation Second response evaluation Therapy (number of patients) PR SD PD NA PR SD PD NA 1 st line: doxorubicin (n=15) 2/15 4/15 7/15 2/15 2/6 1/6 3/6 x 2 nd line: pazopanib (n=5) 3/5 x 1/5 1/5 1/3 1/3 1/3 x ifosfamide (n=5) x x 4/5 1/5 x x x x dacarbazine (n=2) x 1/2 1/2 x x x 1/1 x 3 rd line: 1/4† pazopanib (n=4) 2/4 1/4 x x 1/3 1/3 1/3* 4 th line: trabectedin (n=3) x 2/3 1/3 x x 2/2 x x Response rates based on investigator opinion at first and second response evaluation: PR: Partial Response, SD: Stable Disease, PD: Progressive Disease, NA: data Not Available, x: No patients with this reponse , †vascular response, no volume response, *therapy stop due to intolerance
Conclusion • Highly variable clinical course • Surgery can be curative, but risk of recurrence is high (local 26.7%, distant 30.2%) • Palliative systemic traetment is associated with a low RR (13.3%) en PFS (4.7m) • Highest RR observed with pazopanib in 2nd and 3rd line • Sample size is too small to draw practice changing conclusions RR: Response rate
Clinical presentation, natural history and therapeutic approach in patients with solitary fibrous tumor: a retrospective analysis Tim Wessels, Iris Timmermans, Daphne Hompes, Marguerite Stas, Veerle Boecxstaens, Paul de Leyn, Willy Coosemans, Dirk Van Raemdonck, Esther Hauben, Raf Sciot, Paul Clement, Oliver Bechter, Benoit Beuselinck, F. J. Sherida H. Woei-A-Jin, Herlinde Dumez, Patrick Schöffski
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