Abstract
Introduction
There is currently no treatment for solitary fibrous tumors/hemangiopericytomas (SFT/H) of the central nervous system recurring after multiple surgeries and radiotherapies. The NAB2-STAT6 gene fusion is the hallmark of these tumors, and upregulates Early Growth Factor, activating several growth pathways.
Methods
We treated two patients presenting pluri-recurrent meningeal SFT/H with Pazopanib, a broad-spectrum tyrosine kinase inhibitor. We analyzed the exome and RNA sequencing data of one of them and, in addition to another meningeal SFT/H, compared it to the transcriptomic profiling of 5 systemic SFT/H.
Results
A dramatic clinical and radiological response was observed in both cases, respectively 84 and 43% decrease after 3 months. As a comparison, Pazopanib has only a stabilizing effect in systemic SFT/H. Indeed, central nervous system SFT/H show overexpression of different tyrosine kinases targeted by Pazopanib.
Conclusions
Two consecutive patients with untreatable central nervous system SFT/H showed a spectacular partial response to Pazopanib, an unprecedented result in SFT/H. This result could be explained by differences in expression profiles and calls for a confirmation in a larger cohort of patients.
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Acknowledgement
We are indebted to Pr P Laurent-Puig for NGS analysis. This work was supported by the grant EXORARE from the Cancéropôle Ile de France/INCa.
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Conception and design: MK, MS. Acquisition of data: KM, MK, MS. Analysis and interpretation of data: CA, AA, KM, MK, MS. Drafting the article: CA. Critically revising the article: AA, MK, MS. Approved the final version of the manuscript: CA, AA, KM, MK, MS. Supervision: MS.
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11060_2018_2870_MOESM1_ESM.xls
Supplementary Table 1 — Results of the differential expression analysis comparing meningeal hemangiopericytoma versus systemic SFT using DESeq2 and adjusting by batch effect. BaseMean represents the base means across samples; log2FoldChange: log2 fold-change (meningeal hemagiopericytoma/systemic SFT); lfcSE: log2 fold-change standard error; stat is the Wald statistic (i.e. log2FoldChange divided by lfcSE) which is compared to a standard Normal distribution to generate a two-tailed p-value column; padj is the p-value adjusted by multiple testing using the Benjamini and Hochberg procedure [17] (XLS 3503 KB)
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Apra, C., Alentorn, A., Mokhtari, K. et al. Pazopanib efficacy in recurrent central nervous system hemangiopericytomas. J Neurooncol 139, 369–372 (2018). https://doi.org/10.1007/s11060-018-2870-0
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DOI: https://doi.org/10.1007/s11060-018-2870-0