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Solitary Fibrous Tumor

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A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (30 April 2023) | Viewed by 24974

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Dr. Bahil Ghanim

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1. Karl Landsteiner University of Health Sciences, Dr. Karl-Dorrek-Straße 30, 3500 Krems, Austria
2. Department of General and Thoracic Surgery, University Hospital Krems, Mitterweg 10, 3500 Krems, Austria
Interests: thoracic surgery; solitary fibrous tumor; mesothelioma; lung cancer; orphan disease biomarker
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Special Issue Information

Dear Colleagues,

Solitary fibrous tumor (SFT) is an orphan disease of mesenchymal origin. Based on its anatomic origin, SFT can be divided into thoracic and extrathoracic disease. Furthermore, there is a malignant and benign subtype, but both benign and malignant SFT can currently only be cured by radical surgery. However, even completely resected benign tumors can recur years after surgery, and the clinical behavior remains unpredictable. Chemo- as well as radiotherapy have failed to prolong survival significantly, and data on other treatment modalities, including targeted and immune therapy, are scarce.

Thus, a better biological understanding and further research are urgently required to improve outcome of SFT patients after surgery. The situation for inoperable patients is today even more dramatic since there is no other effective treatment aside from surgery. This Special Issue focuses on clinical and preclinical characterization of this orphan disease to gain more knowledge and define promising treatment modalities for patients suffering from SFT. Studies on novel biomarkers, modern treatment approaches, and those improving the molecular understanding of SFT are invited to contribute to the SFT special issue.

Dr. Bahil Ghanim
Guest Editor

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Keywords

thoracic surgery
surgery
orphan disease
rare disease
targeted therapy
biomarker
molecular biology

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Published Papers (11 papers)

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Editorial

Jump to: Research, Review

2 pages, 141 KiB

Open AccessEditorial

Solitary Fibrous Tumor

by Bahil Ghanim

Cancers 2024, 16(21), 3573; https://doi.org/10.3390/cancers16213573 - 23 Oct 2024

Viewed by 481

Abstract

Solitary fibrous tumor (SFT) is an orphan disease of mesenchymal origin [...] Full article

(This article belongs to the Special Issue Solitary Fibrous Tumor)

Research

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13 pages, 6688 KiB

Open AccessArticle

Demographic and Clinical Characteristics of Malignant Solitary Fibrous Tumors: A SEER Database Analysis

by Mattia Luca Piccinelli, Kyle Law, Reha-Baris Incesu, Stefano Tappero, Cristina Cano Garcia, Francesco Barletta, Simone Morra, Lukas Scheipner, Andrea Baudo, Zhe Tian, Stefano Luzzago, Francesco Alessandro Mistretta, Matteo Ferro, Fred Saad, Shahrokh F. Shariat, Luca Carmignani, Sascha Ahyai, Nicola Longo, Alberto Briganti, Felix K. H. Chun, Carlo Terrone, Derya Tilki, Ottavio de Cobelli, Gennaro Musi and Pierre I. Karakiewicz Show full author list Hide full author list

Cancers 2024, 16(19), 3331; https://doi.org/10.3390/cancers16193331 - 29 Sep 2024

Viewed by 610

Abstract

Background/Objectives: Solitary fibrous tumors (SFTs) represent a rare mesenchymal malignancy that can occur anywhere in the body. Due to the low prevalence of the disease, there is a lack of contemporary data regarding patient demographics and cancer-control outcomes. Methods: Within the SEER database (2000–2019), we identified 1134 patients diagnosed with malignant SFTs. The distributions of patient demographics and tumor characteristics were tabulated. Cumulative incidence plots and competing risks analyses were used to estimate cancer-specific mortality (CSM) after adjustment for other-cause mortality. Results: Of 1134 SFT patients, 87% underwent surgical resection. Most of the tumors were in the chest (28%), central nervous system (22%), head and neck (11%), pelvis (11%), extremities (10%), abdomen (10%) and retroperitoneum (6%), in that order. Stage was distributed as follows: localized (42%) vs. locally advanced (35%) vs. metastatic (13%). In multivariable competing risks models, independent predictors of higher CSM were stage (locally advanced HR: 1.6; metastatic HR: 2.9), non-surgical management (HR: 3.6) and tumor size (9–15.9 cm HR: 1.6; ≥16 cm HR: 1.9). Conclusions: We validated the importance of stage and surgical resection as independent predictors of CSM in malignant SFTs. Moreover, we provide novel observations regarding the independent importance of tumor size, regardless of the site of origin, stage and/or surgical resection status. Full article

(This article belongs to the Special Issue Solitary Fibrous Tumor)

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16 pages, 2396 KiB

Open AccessArticle

Reduction of Tumor Growth with RNA-Targeting Treatment of the NAB2–STAT6 Fusion Transcript in Solitary Fibrous Tumor Models

by Yi Li, John T. Nguyen, Manasvini Ammanamanchi, Zikun Zhou, Elijah F. Harbut, Jose L. Mondaza-Hernandez, Clark A. Meyer, David S. Moura, Javier Martin-Broto, Heather N. Hayenga and Leonidas Bleris

Cancers 2023, 15(12), 3127; https://doi.org/10.3390/cancers15123127 - 9 Jun 2023

Cited by 3 | Viewed by 2312

Abstract

Solitary fibrous tumor (SFT) is a rare soft-tissue sarcoma. This nonhereditary cancer is the result of an environmental intrachromosomal gene fusion between NAB2 and STAT6 on chromosome 12, which fuses the activation domain of STAT6 with the repression domain of NAB2. Currently there is not an approved chemotherapy regimen for SFTs. The best response on available pharmaceuticals is a partial response or stable disease for several months. The purpose of this study is to investigate the potential of RNA-based therapies for the treatment of SFTs. Specifically, in vitro SFT cell models were engineered to harbor the characteristic NAB2–STAT6 fusion using the CRISPR/SpCas9 system. Cell migration as well as multiple cancer-related signaling pathways were increased in the engineered cells as compared to the fusion-absent parent cells. The SFT cell models were then used for evaluating the targeting efficacies of NAB2–STAT6 fusion-specific antisense oligonucleotides (ASOs) and CRISPR/CasRx systems. Our results showed that fusion specific ASO treatments caused a 58% reduction in expression of fusion transcripts and a 22% reduction in cell proliferation after 72 h in vitro. Similarly, the AAV2-mediated CRISPR/CasRx system led to a 59% reduction in fusion transcript expressions in vitro, and a 55% reduction in xenograft growth after 29 days ex vivo. Full article

(This article belongs to the Special Issue Solitary Fibrous Tumor)

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10 pages, 4958 KiB

Open AccessArticle

Value of Cellular Components and Focal Dedifferentiation to Predict the Risk of Metastasis in a Benign-Appearing Extra-Meningeal Solitary Fibrous Tumor: An Original Series from a Tertiary Sarcoma Center

by Mohammad Hassani, Sungmi Jung, Elaheh Ghodsi, Leila Seddigh, Paul Kooner, Ahmed Aoude and Robert Turcotte

Cancers 2023, 15(5), 1441; https://doi.org/10.3390/cancers15051441 - 24 Feb 2023

Cited by 3 | Viewed by 1460

Abstract

Histology has not been accepted as a valid predictor of the biological behavior of extra-meningeal solitary fibrous tumors (SFTs). Based on the lack of a histologic grading system, a risk stratification model is accepted by the WHO to predict the risk of metastasis; however, the model shows some limitations to predict the aggressive behavior of a low-risk/benign-appearing tumor. We conducted a retrospective study based on medical records of 51 primary extra-meningeal SFT patients treated surgically with a median follow-up of 60 months. Tumor size (p = 0.001), mitotic activity (p = 0.003), and cellular variants (p = 0.001) were statistically associated with the development of distant metastases. In cox regression analysis for metastasis outcome, a one-centimeter increment in tumor size enhanced the expected metastasis hazard by 21% during the follow-up time (HR = 1.21, CI 95% (1.08–1.35)), and each increase in the number of mitotic figures escalated the expected hazard of metastasis by 20% (HR = 1.2, CI 95% (1.06–1.34)). Recurrent SFTs presented with higher mitotic activity and increased the likelihood of distant metastasis (p = 0.003, HR = 12.68, CI 95% (2.31–69.5)). All SFTs with focal dedifferentiation developed metastases during follow-up. Our findings also revealed that assembling risk models based on a diagnostic biopsy underestimated the probability of developing metastasis in extra-meningeal SFTs. Full article

(This article belongs to the Special Issue Solitary Fibrous Tumor)

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14 pages, 639 KiB

Open AccessArticle

Risk Stratification for Management of Solitary Fibrous Tumor/Hemangiopericytoma of the Central Nervous System

by Connor J. Kinslow, Ali I. Rae, Prashanth Kumar, Guy M. McKhann, Michael B. Sisti, Jeffrey N. Bruce, James B. Yu, Simon K. Cheng and Tony J. C. Wang

Cancers 2023, 15(3), 876; https://doi.org/10.3390/cancers15030876 - 31 Jan 2023

Cited by 9 | Viewed by 2730

Abstract

Introduction: Solitary fibrous tumor/hemangiopericytoma (SFT/HPC) of the central nervous system (CNS) is a rare meningeal tumor. Given the absence of prospective or randomized data, there are no standard indications for radiotherapy. Recently, the NRG Oncology and EORTC cooperative groups successfully accrued and completed the first prospective trials evaluating risk-adapted adjuvant radiotherapy strategies for meningiomas. Using a similar framework, we sought to develop prognostic risk categories that may predict the survival benefit associated with radiotherapy, using two large national datasets. Methods: We queried the National Cancer Database (NCDB) and the Surveillance, Epidemiology, and End Results (SEER) databases for all newly diagnosed cases of SFT/HPC within the CNS. Risk categories were created, as follows: low risk—grade 1, with any extent of resection (EOR) and grade 2, with gross–total resection; intermediate risk—grade 2, with biopsy/subtotal resection; high risk—grade 3 with any EOR. The Kaplan–Meier method and Cox proportional hazards regressions were used to determine the association of risk categories with overall and cause-specific survival. We then determined the association of radiotherapy with overall survival in the NCDB, stratified by risk group. Results: We identified 866 and 683 patients from the NCDB and SEER databases who were evaluated, respectively. In the NCDB, the 75% survival times for low- (n = 312), intermediate- (n = 239), and high-risk (n = 315) patients were not reached, 86 months (HR 1.60 (95% CI 1.01–2.55)), and 55 months (HR 2.56 (95% CI 1.68–3.89)), respectively. Our risk categories were validated for overall and cause-specific survival in the SEER dataset. Radiotherapy was associated with improved survival in the high- (HR 0.46 (0.29–0.74)) and intermediate-risk groups (HR 0.52 (0.27–0.99)) but not in the low-risk group (HR 1.26 (0.60–2.65)). The association of radiotherapy with overall survival remained significant in the multivariable analysis for the high-risk group (HR 0.55 (0.34–0.89)) but not for the intermediate-risk group (HR 0.74 (0.38–1.47)). Similar results were observed in a time-dependent landmark sensitivity analysis. Conclusion: Risk stratification based on grade and EOR is prognostic of overall and cause-specific survival for SFT/HPCs of the CNS and performs better than any individual clinical factor. These risk categories appear to predict the survival benefit from radiotherapy, which is limited to the high-risk group and, potentially, the intermediate-risk group. These data may serve as the basis for a prospective study evaluating the management of meningeal SFT/HPCs. Full article

(This article belongs to the Special Issue Solitary Fibrous Tumor)

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16 pages, 1483 KiB

Open AccessArticle

Intracranial Solitary Fibrous Tumour Management: A French Multicentre Retrospective Study

by Marine Lottin, Alexandre Escande, Luc Bauchet, Marie Albert-Thananayagam, Maël Barthoulot, Matthieu Peyre, Mathieu Boone, Sonia Zouaoui, Jacques Guyotat, Guillaume Penchet, Johan Pallud, Henry Dufour, Evelyne Emery, Michel Lefranc, Sébastien Freppel, Houman Namaki, Edouard Gueye, Jean-Jacques Lemaire, Bertrand Muckensturm, Robin Srour, Stéphane Derrey, Apolline Monfilliette, Jean-Marc Constans, Claude-Alain Maurage, Bruno Chauffert and Nicolas Penel Show full author list Hide full author list

Cancers 2023, 15(3), 704; https://doi.org/10.3390/cancers15030704 - 24 Jan 2023

Cited by 3 | Viewed by 1895

Abstract

Background: Intracranial solitary fibrous tumour (iSFT) is an exceptional mesenchymal tumour with high recurrence rates. We aimed to analyse the clinical outcomes of newly diagnosed and recurrent iSFTs. Methods: We carried out a French retrospective multicentre (n = 16) study of histologically proven iSFT cases. Univariate and multivariate Cox models were used to estimate the prognosis value of the age, location, size, WHO grade, and surgical extent on overall survival (OS), progression-free survival (PFS), and local recurrence-free survival (LRFS). Results: Eighty-eight patients were included with a median age of 54.5 years. New iSFT cases were treated with gross tumour resection (GTR) (n = 75) or subtotal resection (STR) (n = 9) and postoperative radiotherapy (PORT) (n = 32, 57%). The median follow-up time was 7 years. The median OS, PFS, and LRFS were 13 years, 7 years, and 7 years, respectively. Forty-two patients experienced recurrence. Extracranial metastasis occurred in 16 patients. Median OS and PFS after the first recurrence were 6 years and 15.4 months, respectively. A higher histological grade was a prognosis factor for PFS (p = 0.04) and LRFS (p = 0.03). GTR influenced LRFS (p = 0.03). Conclusion: GTR provided benefits as a first treatment for iSFTs. However, approximately 40% of patients experienced relapse, which remains a challenging state. Full article

(This article belongs to the Special Issue Solitary Fibrous Tumor)

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16 pages, 3515 KiB

Open AccessArticle

Trabectedin Is Active against Two Novel, Patient-Derived Solitary Fibrous Pleural Tumor Cell Lines and Synergizes with Ponatinib

by Bahil Ghanim, Dina Baier, Christine Pirker, Leonhard Müllauer, Katharina Sinn, Gyoergy Lang, Konrad Hoetzenecker and Walter Berger

Cancers 2022, 14(22), 5602; https://doi.org/10.3390/cancers14225602 - 15 Nov 2022

Cited by 7 | Viewed by 2188

Abstract

Solitary fibrous tumor of the pleura (SFT) is a rare disease. Besides surgery combined with radiotherapy in nondisseminated stages, curative options are currently absent. Out of fourteen primo-cell cultures, established from surgical SFT specimens, two showed stable in vitro growth. Both cell models harbored the characteristic NAB2-STAT6 fusion and were further investigated by different preclinical methods assessing cell viability, clone formation, and protein regulation upon single-drug treatment or in response to selected treatment combinations. Both fusion-positive cell models showed—in line with the clinical experience and the literature—a low to moderate response to most of the tested cytotoxic and targeted agents. However, the multi-tyrosine kinase inhibitors ponatinib and dasatinib, as well as the anti-sarcoma compound trabectedin, revealed promising activity against SFT growth. Furthermore, both cell models spontaneously presented strong FGFR downstream signaling targetable by ponatinib. Most interestingly, the combination of either ponatinib or dasatinib with trabectedin showed synergistic effects. In conclusion, this study identified novel trabectedin-based treatment combinations with clinically approved tyrosine kinase inhibitors, using two newly established NAB2-STAT6 fusion-positive cell models. These findings can be the basis for anti-SFT drug repurposing approaches in this rare and therapy-refractory disease. Full article

(This article belongs to the Special Issue Solitary Fibrous Tumor)

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13 pages, 1653 KiB

Open AccessArticle

Clinical, Histological, and Molecular Features of Solitary Fibrous Tumor of Bone: A Single Institution Retrospective Review

by Giuseppe Bianchi, Debora Lana, Marco Gambarotti, Cristina Ferrari, Marta Sbaraglia, Elena Pedrini, Laura Pazzaglia, Luca Sangiorgi, Isabella Bartolotti, Angelo Paolo Dei Tos, Katia Scotlandi and Alberto Righi

Cancers 2021, 13(10), 2470; https://doi.org/10.3390/cancers13102470 - 19 May 2021

Cited by 10 | Viewed by 2232

Abstract

Primary solitary fibrous tumor (SFT) of the bone is extremely rare, with only few cases reported in the literature. We retrieved all cases of primary SFT of the bone treated at our institution and we assessed the morphology and the immunohistochemical and molecular features to investigate the clinical outcome of primary SFT of the bone and any clinical relevance of clinical and histological criteria of aggressiveness currently adopted for the soft tissues counterpart. Morphologically, 15 cases evidenced high cellularity, cytologic atypia, and foci of necrosis and were associated with more than 4 mitotic figures/10 HPF. Immunohistochemical analysis showed an expression of CD34 and of STAT6 immunopositivity in 95% and in 100% of cases, respectively. The presence of NAB2-STAT6 chimeric transcripts was found in 10 out of 12 cases in which RT-PCR analysis was feasible, whereas TERT promoter mutations analysis was feasible in 16 cases and only a C-to-T substitution in a heterozygous state was found in one DNA sample for the C228T genetic variant. P53 variants were assessed in 12 cases: 11 (91.6%) cases showed a variation, while in one case, no alteration was found. Disease-specific survival was 64% at 5 years and 49% at 10 years. Statistical analysis showed no correlation between survival and all the clinicopathological and molecular parameters evaluated. In conclusion, at difference to SFT of soft tissues, aggressive behavior of primary SFT of the bone seems to be independent from mitotic count or any other clinicopathological and molecular features. Full article

(This article belongs to the Special Issue Solitary Fibrous Tumor)

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Review

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17 pages, 326 KiB

Open AccessReview

Surgery for Solitary Fibrous Tumors of the Pleura: A Review of the Available Evidence

by Pietro Bertoglio, Giulia Querzoli, Peter Kestenholz, Marco Scarci, Marilina La Porta, Piergiorgio Solli and Fabrizio Minervini

Cancers 2023, 15(16), 4166; https://doi.org/10.3390/cancers15164166 - 18 Aug 2023

Cited by 5 | Viewed by 1340

Abstract

Solitary fibrous tumors of the pleura (pSFT) are a relatively rare neoplasms that can arise from either visceral or parietal pleura and may have different aggressive biological behaviors. Surgery is well known to be the cornerstone of the treatment for pSFT. We reviewed the existing literature, focusing on the role of surgery in the management and treatment of pSFT. All English-written literature has been reviewed, focusing on those reporting on the perioperative management and postoperative outcomes. Surgery for pSFT is feasible and safe in all experiences reported in the literature, but surgical approaches and techniques may vary according to the tumor dimensions, localization, and surgeons’ skills. Long-term outcomes are good, with a 10-year overall survival rate of more than 70% in most of the reported experiences; on the other hand, recurrence may happen in up to 17% of cases, which occurs mainly in the first two years after surgery, but case reports suggest the need for a longer follow-up to assess the risk of late recurrence. Malignant histology and dimensions are the most recognized risk factors for recurrence. Recurrence might be operated on in select patients. Surgery is the treatment of choice in pSFT, but a radical resection and a careful postoperative follow-up should be carried out. Full article

(This article belongs to the Special Issue Solitary Fibrous Tumor)

11 pages, 1217 KiB

Open AccessReview

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

by Caroline Apra, Amira El Arbi, Anne-Sophie Montero, Fabrice Parker and Steven Knafo

Cancers 2022, 14(12), 2839; https://doi.org/10.3390/cancers14122839 - 8 Jun 2022

Cited by 13 | Viewed by 2079

Abstract

All solitary fibrous tumors (SFT), now histologically diagnosed by a positive nuclear STAT6 immunostaining, represent less than 2% of soft tissue sarcomas, with spinal SFT constituting a maximum of 2% of them, making these tumors extremely rare. We provide an up-to-date overview of their diagnosis, treatment, and prognosis. We included 10 primary STAT6-positive SFT from our retrospective cohort and 31 from a systematic review. Spinal pain was the most common symptom, in 69% of patients, and the only one in 34%, followed by spinal cord compression in 41%, radicular compression, including pain or deficit, in 36%, and urinary dysfunction specifically in 18%. Preoperative diagnosis was never obtained. Gross total resection was achieved in 71%, in the absence of spinal cord invasion or excessive bleeding. Histologically, they were 35% grade I, 25% grade II, and 40% grade III. Recurrence was observed in 43% after a mean 5.8 years (1 to 25). No significant risk factor was identified, but adjuvant radiotherapy improved the recurrence-free survival after subtotal resection. In conclusion, spinal SFT must be treated by neurosurgeons as part of a multidisciplinary team. Owing to their close relationship with the spinal cord, radiotherapy should be considered when gross total resection cannot be achieved, to lower the risk of recurrence. Full article

(This article belongs to the Special Issue Solitary Fibrous Tumor)

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18 pages, 1549 KiB

Open AccessReview

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

by Axel de Bernardi, Armelle Dufresne, Florence Mishellany, Jean-Yves Blay, Isabelle Ray-Coquard and Mehdi Brahmi

Cancers 2022, 14(4), 1064; https://doi.org/10.3390/cancers14041064 - 20 Feb 2022

Cited by 34 | Viewed by 5589

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. Full article

(This article belongs to the Special Issue Solitary Fibrous Tumor)

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