Novel therapeutic approaches in the treatment of solitary fibrous tumors: A call for a combination therapy.

Abstract

A solitary fibrous tumor (SFT) is a rare mesenchymal tumor with a high risk of local recurrence and a metastatic potential.1 Because of the rarity of the disease, the data regarding possible nonsurgical treatment options are limited. Until recently, most extensive reports regarding nonsurgical SFT treatment were based on case reports.2 Surgery remains the leading treatment option, and currently, the disease is being surgically managed similarly to soft-tissue sarcomas.3 Sadly, although a combination therapy has been already applied in clinical practice to soft-tissue sarcomas,4 additional therapies such as immunotherapy, have gained only minimal interest in SFTs. In the past few years, however, several new principles concerning the therapy of SFTs have evolved. We read with a great interest the recent study by Haas et al,5 who revealed the major potential of perioperative radiotherapy in the local control of the disease. The authors performed a retrospective analysis across 7 sarcoma centers by collecting data on 549 patients with SFTs who underwent either surgery alone or surgery together with peri/postoperative radiotherapy. To date, this is the largest study regarding the nonsurgical treatment of SFTs. The authors concluded that perioperative radiotherapy should be considered as a treatment option for this rare disease and thus broke the frequently cited claim of the inefficacy of radiotherapy for SFTs. Although the effectivity of standard cytotoxic chemotherapeutic regimens still remains questionable,6 an effort has been made through the past few years to discover different approaches in the treatment of SFTs. Some of these promising approaches, however, have not yet been tested in clinical trials. This is presumably due to the rarity of the disease. Only a small number of targeted therapies have been tested and further occasionally applied in clinical practice.3 The approved targeted therapies selectively target specific molecular pathways that may be involved in angiogenesis or tumorigenesis.3 So far, the most promising targeted therapy for malignant SFTs seems to be bevacizumab, a humanized recombinant antibody against vascular endothelial growth factor (VEGF), together with temozolomide, an alkylating chemotherapeutic. This therapy shows a partial response in 79% of patients.7 Pazopanib has been tested as an anti-VEGF receptor agent in the treatment of SFTs, however, it showed mild antitumor activity only in nondedifferentiated cases.8 On the other hand, sunitinib, a tyrosine kinase inhibitor, showed activity and long-lasting responses in the treatment of SFTs.9 Moreover, the pretreatment status of PDGFRB and/or VEGFR2, evaluated by immunostaining, was not predictive of a response. This suggests that sunitinib may be a promising treatment option for all patients with SFTs.9 Although different immunotherapeutic approaches, such as adoptive cell transfer, checkpoint inhibition, and chimeric antigen receptor T-cell therapy, have already been tested in soft-tissue sarcomas,4 only an anti–PD-L1 checkpoint inhibitor has been used in SFT therapy.10 A single case report by Boothe et al10 illustrates a major effect of anti–PD-L1 therapy in a patient with chemo-refractory and radiation-refractory SFT. The patient had a low PD-L1 expression status (5%) but presented a prompt and nearly complete response to an anti–PD-L1 antibody. The study itself reveals the large potential of checkpoint immunotherapy in SFT treatment. Although SFTs present rare diseases and may have a benign biological nature, local recurrence and metastatic behavior are also highly prevalent. Based on the limited data, we aim to highlight that similarly to soft-tissue sarcomas, radiotherapy, targeted therapy, and immunotherapy should become part of therapeutic algorithms in SFTs. Moreover, clinical testing of other immune checkpoint inhibitors is urgently needed, and only close interdisciplinary cooperation between surgical and nonsurgical institutions can introduce patients with SFTs to novel immunotherapeutic approaches, such as adoptive T-cell transfer and chimeric antigen receptor T-cell immunotherapy. No specific funding was disclosed. The authors made no disclosures.