Caroline Apra1, Agusti Alentorn1,2, Karima Mokhtari3, Michel Kalamarides1,4, Marc Sanson5,6. 1. Sorbonne Université, UMR S 1127, Inserm U 1127, CNRS UMR 7225, ICM, 75013, Paris, France. 2. Department of Neurology, AP-HP, Groupe Hospitalier Pitié Salpêtrière, 75013, Paris, France. 3. Laboratoire de Neuropathologie R Escourolle, AP-HP, Groupe Hospitalier Pitié Salpêtrière, 75013, Paris, France. 4. Department of Neurosurgery, AP-HP, Groupe Hospitalier Pitié Salpêtrière, 75013, Paris, France. 5. Sorbonne Université, UMR S 1127, Inserm U 1127, CNRS UMR 7225, ICM, 75013, Paris, France. marc.sanson@aphp.fr. 6. Department of Neurology, AP-HP, Groupe Hospitalier Pitié Salpêtrière, 75013, Paris, France. marc.sanson@aphp.fr.
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.
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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