Response to chemotherapy of solitary fibrous tumour: A retrospective study

Stacchiotti, Silvia; Libertini, Michela; Negri, Tiziana; Palassini, Elena; Gronchi, Alessandro; Fatigoni, Sonia; Poletti, Paola; Vincenzi, Bruno; Tos, Angelo Paolo Dei; Mariani, Luigi; Pilotti, Silvana; Casali, Paolo G.

doi:10.1016/j.ejca.2013.03.017

Cited by 80 publications

(55 citation statements)

References 28 publications

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“…Interestingly, patients who progressed under pazopanib had dedifferentiated-SFT, while the responsive case carried a malignant-SFT. This observation suggests that pazopanib might be more active in less aggressive cases, as already observed in SFT patients treated with sunitinib, and by contrast to what was observed with cytotoxic chemotherapy [19]. Worth noting, we obtained a response to sunitinib in a patient progressive to pazopanib consistently with the preclinical evidence of a non-superimposable activity of antiangiogenics in SFT.…”

Section: Discussionsupporting

confidence: 81%

Preclinical and clinical evidence of activity of pazopanib in solitary fibrous tumour

Stacchiotti

Tortoreto

Baldi

et al. 2014

European Journal of Cancer

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Background: To explore the activity of pazopanib in solitary fibrous tumour (SFT). Patients and methods: In a preclinical study, we compared the activity of pazopanib, sorafenib, sunitinib, regorafenib, axitinib and bevacizumab in a dedifferentiated-SFT (DSFT) xenotransplanted into Severe Combined Immunodeficiency (SCID) mice. Antiangiogenics were administered at their reported optimal doses when mean tumour volume (TV) was 80 mm 3 . Drug activity was assessed as TV inhibition percentage (TVI%). From May 2012, six consecutive patients with advanced SFT received pazopanib, on a national name-based programme. In one case sunitinib was administered after pazopanib failure.

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Section: Discussionsupporting

confidence: 81%

Preclinical and clinical evidence of activity of pazopanib in solitary fibrous tumour

Stacchiotti

Tortoreto

Baldi

et al. 2014

European Journal of Cancer

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“…Such changes can be interpreted as being part of tumor cell reprogramming, and may explain the previously described different responses to targeted therapies for malignant and dedifferentiated solitary fibrous tumors. 15,36,37 On the other hand, genomic changes such as del17p/ TP53 mutations and del13q (which seem to be prevalent in dedifferentiated solitary fibrous tumors) can also be occasionally found in tumors whose histology and immunoprofiles are fully consistent with a diagnosis of a malignant solitary fibrous tumor. Two of our malignant TP53 immunopositive cases (nos.…”

Section: Discussionmentioning

confidence: 99%

Solitary fibrous tumors: loss of chimeric protein expression and genomic instability mark dedifferentiation

et al. 2015

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Solitary fibrous tumors, which are characterized by their broad morphological spectrum and unpredictable behavior, are rare mesenchymal neoplasias that are currently divided into three main variants that have the NAB2-STAT6 gene fusion as their unifying molecular lesion: usual, malignant and dedifferentiated solitary fibrous tumors. The aims of this study were to validate molecular and immunohistochemical/biochemical approaches to diagnose the range of solitary fibrous tumors by focusing on the dedifferentiated variant, and to reveal the genetic events associated with dedifferentiation by integrating the findings of array comparative genomic hybridization. We studied 29 usual, malignant and dedifferentiated solitary fibrous tumors from 24 patients (including paired samples from five patients whose tumors progressed to the dedifferentiated form) by means of STAT6 immunohistochemistry and (when frozen material was available) reverse-transcriptase polymerase chain reaction and biochemistry. In addition, the array comparative genomic hybridization findings were used to profile 12 tumors from nine patients. The NAB2/STAT6 fusion was detected in all of the tumors, but immunohistochemistry and western blotting indicated that chimeric protein expression was atypical or absent in 9 out of 11 dedifferentiated tumors. The comparative genomic hybridization results revealed that the usual and malignant solitary fibrous tumors had a simple profile, whereas the genome of the dedifferentiated tumors was complex and unstable, and suggested that 13q and 17p deletions and TP53 mutations may be present in malignant lesions before the full expression of a dedifferentiated phenotype. Solitary fibrous tumor dedifferentiation is associated with the loss of chimeric oncoprotein expression, genomic instability, and cell decommitment and reprogramming. The assessment of dedifferentiated solitary fibrous tumors is based on the presence of the fusion transcripts and, in principle, negative STAT6 immunohistochemistry should not rule out a diagnosis of solitary fibrous tumor. Modern Pathology (2015Pathology ( ) 28, 1074Pathology ( -1083 doi:10.1038/modpathol.2015 published online 29 May 2015 Solitary fibrous tumors are rare mesenchymal tumors (incidence o 1 per million) that were originally described on the pleurae but have subsequently been recognized at virtually all body sites. 1 The current classification includes usual, malignant and the recently described dedifferentiated variants. [1][2][3] The morphobiological features distinguishing the malignant and usual variants are hypercellularity, cell pleomorphism, necrosis and a mitotic index of 44/10 high-power fields. However,

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“…Few responses in patients treated with anthracycline plus dacarbazine þ/À ifosfamide are also reported (5,6). A higher RR can be observed in histologically more aggressive DSFT cases (7).…”

Section: Introductionmentioning

confidence: 86%

Dacarbazine in Solitary Fibrous Tumor: A Case Series Analysis and Preclinical Evidence vis-à-vis Temozolomide and Antiangiogenics

Stacchiotti

Tortoreto

Bozzi

et al. 2013

Clinical Cancer Research

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Purpose: To explore the value of triazines in solitary fibrous tumor (SFT). Experimental Design: We retrospectively reviewed 8 cases of patients with SFT treated with dacarbazine (1,200 mg/m 2 every 3 weeks) as from January 2012. Then, we studied a dedifferentiated-SFT subcutaneously xenotransplanted into severe combined immunodeficient (SCID) mice. Dacarbazine, temozolomide, sunitinib, bevacizumab, and pazopanib were administered at their reported optimal doses for the mouse model when mean tumor volume (TV) was about 80 mm 3 ; each experimental groups included 6 mice. Drug activity was assessed as tumor volume inhibition percentage (TVI%). Dacarbazine was tested according to two different schedules of administration. One hunded twenty days after treatment interruption, mouse tumor samples were analyzed.Results: Among the eight patients treated with dacarbazine, best response evaluation criteria in solid tumors responses (RECIST) were three partial responses, 4 stable disease, 1 progression. Two responsive patients had paraneoplastic hypoglycemia that disappeared after 10 days from starting dacarbazine. In the dedifferentiated-SFT xenograft model, dacarbazine and temozolomide showed the highest antitumor activity (about 95% TVI), confirmed pathologically. Sunitinib and pazopanib were only marginally active (52% and 41% TVI, respectively), whereas bevacizumab caused a 78% TVI. No tumor regrowth was observed up to 100 days from end of treatment with temozolomide and dacarbazine, whereas secondary progression followed sunitinib, pazopanib, and bevacizumab interruption.Conclusions: Dacarbazine as single agent has antitumor activity in SFT. Our preclinical results suggest a cytotoxic effect of temozolomide and dacarbazine, as compared with a cytostatic role for sunitinib, pazopanib, and bevacizumab. A phase II study on dacarbazine in advanced SFT is planned.

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Response to chemotherapy of solitary fibrous tumour: A retrospective study

Cited by 80 publications

References 28 publications

Preclinical and clinical evidence of activity of pazopanib in solitary fibrous tumour

Preclinical and clinical evidence of activity of pazopanib in solitary fibrous tumour

Solitary fibrous tumors: loss of chimeric protein expression and genomic instability mark dedifferentiation

Dacarbazine in Solitary Fibrous Tumor: A Case Series Analysis and Preclinical Evidence vis-à-vis Temozolomide and Antiangiogenics

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