Novel Therapeutic Options for Solitary Fibrous Tumor: Antiangiogenic Therapy and Beyond

Abstract

SFT is an ultrarare mesenchymal ubiquitous tumor, with an incidence rate <1 case/million people/year. The fifth WHO classification published in April 2020 subdivided SFT into three categories: benign (locally aggressive), NOS (rarely metastasizing), and malignant. Recurrence can occur in up to 10–40% of localized SFTs, and several risk stratification models have been proposed to predict the individual risk of metastatic relapse. The Demicco model is the most widely used and is based on age at presentation, tumor size, and mitotic count. Total en bloc resection is the standard treatment of patients with a localized SFT; in case of advanced disease, the clinical efficacy of conventional chemotherapy remains poor. In this review, we discuss new insights into the biology and the treatment of patients with SFT. NAB2–STAT6 oncogenic fusion, which is the pathognomonic hallmark of SFT, is supposedly involved in the overexpression of vascular endothelial growth factor (VEGF). These specific biological features encouraged the successful assessment of antiangiogenic drugs. Overall, antiangiogenic therapies showed a significant activity toward SFT in the advanced/metastatic setting. Nevertheless, these promising results warrant additional investigation to be validated, including randomized phase III trials and biological translational analysis, to understand and predict mechanisms of efficacy and resistance. While the therapeutic potential of immunotherapy remains elusive, the use of antiangiogenics as first-line treatment should be considered.

Magnetic resonance imaging features of a solitary fibrous tumor of the vulva: a case report

“…The promising results obtained so far warrant additional investigations. 37,38 Notably, the treatment of vulvar SFT still carries a risk of intraoperative blood loss and postoperative complications including surgical site infection and anal dysfunction 39 ; however, our patient did not develop these complications.…”

Ex vivo drug testing in an ultra-rare sarcoma reveals therapeutic vulnerability and resistance

“…The NAB2-STAT6 gene fusion was indeed detected from transcriptomic analysis of both hSC06 and hSC31, confirming that both patient-derived lines were indeed SFT. Analysis of intragenic breakpoints within the NAB2 and STAT6 gene loci revealed fusion of NAB2 exon 6 to STAT6 exon 16 in both hSC06 and hSC31, resulting in the expression of the fusion gene NAB2 exon 6- STAT6 exon 16 (6-16) (Fig. 2D).…”

“…ifosfamide) have been advocated as first-line chemotherapy (13), with a retrospective cohort reporting progression free survival of three to five months in line with other STSs (14). Given that SFTs are highly vascularized tumors with high expression rates of angiogenic markers, the efficacy of anti-angiogenic agents have been explored in SFT with retrospective and prospective evidence suggesting efficacy for unresectable disease (15,16). Temozolomide-bevacizumab combination therapy (17,18) as well as sunitinib (19) have produced tumor response and disease control in some patients with advanced SFTs.…”

Spinal Solitary Fibrous Tumors: An Original Multicenter Series and Systematic Review of Presentation, Management, and Prognosis

“…Stereotactic radiosurgery has been used for intracranial SFT, but its use in spinal SFT is sporadic and no conclusion can be drawn. Conventional chemotherapy gives a poor clinical benefit, and anti-angiogenic treatments are the most promising option [ 35 , 36 , 37 ], used in one patient in our series, as a third-line option.…”