Dramatic radiographic response resulting in cerebrospinal fluid rhinorrhea associated with sunitinib therapy in recurrent atypical meningioma: case report

Abstract

Sunitinib is a multiple tyrosine kinase inhibitor with antiangiogenic, cytostatic, and antimigratory activity for meningiomas. A recent clinical trial of sunitinib for treatment of recurrent Grade II and III meningiomas suggested potential efficacy in this population, but only 2 patients exhibited significant radiographic response with tumor volume reduction. The authors illustrate another such case and discuss a complication related to this dramatic tumor volume reduction in aggressive skull base meningiomas. The authors describe the case of a 39-year-old woman who had undergone repeat surgical interventions and courses of radiotherapy over the previous 11 years for recurrent cranial and spinal meningiomas. Despite 4 operations over the course of 4 years on her right petroclival meningioma with cavernous sinus and jugular fossa extensions, she had progressive neurological deficits and tumor recurrences. The specimen histology progressed from WHO Grade I initially to Grade II at the time of the third recurrence. The lesion was then irradiated 3 times using stereotactic radiosurgery for further recurrences. More recently, the tumor size increased rapidly on imaging, in association with progressive neurological symptoms arising from brainstem compression and vasogenic edema. Institution of sunitinib therapy yielded a dramatic radiographic response, with marked reduction in the tumor volume and reduction of brainstem vasogenic edema within a few weeks of initiation of treatment. The significant radiographic response of tumor in the clival region was also associated with CSF rhinorrhea from a dural breach created by resolution of the invasive skull base meningioma, which necessitated withholding the sunitinib medication. To address the leak, the authors undertook surgical exploration and transsphenoidal packing using an autologous fat graft and a vascularized pedicled nasoseptal flap. The patient has done well during follow-up of 3 months after packing, with no evidence of recurrent CSF leak, and the medication was subsequently restarted. Prior clinical data and the dramatic radiographic response in this patient suggest that sunitinib holds promising therapeutic potential in carefully selected patients with recurrent atypical meningiomas where conventional strategies have been exhausted. There is a potential risk of associated CSF rhinorrhea, especially in more invasive skull base lesions showing dramatic radiographic response.

CSF rhinorrhea following alectinib treatment for anaplastic lymphoma kinase rearranged lung adenocarcinoma - e contrario

“…CSF rhinorrhea has been described following non-surgical treatment (medical management/SBRT) of pituitary tumors and meningiomas. [1,2] To the best of our knowledge, there is a single published case report of CSF rhinorrhea occurring in metastatic lung cancer (EGFR mutated LUAC) after erlotinib treatment. [3] Although the exact mechanism remains unclear, the possibility entertained in our case was something akin to benign intracranial hypertension (subclinical raised ICT), as there was empty sella sign with flattening of posterior globe and perineural enhancement of the optic nerves on imaging, and she had developed CSF rhinorrhea after 12 months of treatment initiation.…”

Receptor Tyrosine Kinases as Candidate Prognostic Biomarkers and Therapeutic Targets in Meningioma

“…Inhibition of platelet-derived growth factor receptor (PDGFR)-mediated signaling by RTK inhibitors sorafenib and regorafenib inhibits the proliferation of IOMM-Lee MGM cells, as well as the growth of experimental IOMM-Lee MGM tumors in vivo in mice inoculated with IOMM-Lee MGM cells into the subarachnoidal space, through PDGFR downregulation and inhibition of expression and phosphorylation of p44/42 ERK [ 25 ]. A few cases of tumor responses to the multiple RTK inhibitor sunitinib have been reported in patients with grade II and III MGMs [ 26 , 27 ]. The subjects in one trial were patients with recurrent or progressive atypical and anaplastic MGM tumors, heavily pretreated and refractory to treatments.…”

Receptor Tyrosine Kinases as Candidate Prognostic Biomarkers in Meningioma

“…Inhibition of PDGF receptor (PDGFR)-mediated signaling by RTK inhibitors sorafenib and regorafenib inhibits the growth of experimental MGM in vitro and in vivo, thought PDGFR downregulation and inhibition of p44/42 ERK [24]. A few cases of tumor responses to the multiple RTK inhibitor sunitinib have been reported in patients with grade II and III MGMs [25,26]. Patients with recurrent MGM tumors refractory to surgery and radiation treated with the oral multi-RTK inhibitor PTK787/ZK 222584 (PTK787) showed that grade II patients had a progression free survival-6 of 64.3 %, a median progression free survival of 6.5 months, and an overall survival of 26.0 months; grade III patients had a progression free survival-6 of 37.5 %, median progression free survival of 3.6 months, and overall survival of 23 months [27].…”