1. Atypical and aggressive meningiomas: Is there a role for radiologists in guiding treatment? #EP-53 Anthony Galinato MD, Feras Mossa-Basha MD, Ishani Dalal MD Department of Radiology, Henry Ford Hospital Detroit, MI

2. Disclosures The authors have no financial interest or other relationship with any commercial organization that may have an interest in the content presented.

3. Purpose Describe difficulties with current treatments for atypical and aggressive meningiomas. Analyze potential use of somatostatin receptor blockers in treating meningiomas in cases of residual or recurrent disease following surgical resection. Demonstrate the radiologist’s role in guiding treatment of atypical and aggressive meningiomas with the use of octreoscans.

4. Background Meningiomas are the most common primary intracranial neoplasm. WHO classification organizes meningiomas into 3 distinct grades based on cell type, mitotic activity, cellularity, necrosis, and brain invasion. – WHO Grade I – benign Most common - 80% of cases – WHO Grade II – atypical 15-20% of cases – WHO Grade III – anaplastic 1-3% of cases

5. Background Axial and coronal T1 weighted post contrast images demonstrate a large enhancing extra-axial lesion in the right paramedian frontoparietal region. There is invasion of the superior sagittal sinus and extension across midline which makes complete surgical resection difficult. Pathology demonstrated atypical meningioma (WHO Grade II).

6. Background Patients with meningiomas can have complicated clinical courses with poor clinical outcomes. The standard treatment of choice for meningiomas historically has been compete surgical resection. Resection of meningiomas are often debilitating with extensive recoveries. Complete resection is often difficult to achieve secondary to difficult locations such as at the skull base, near the sagittal sinus, or in close proximity to cranial nerves.

7. Background Complete resection is achieved in less than 50% of patients. Even in cases where there is complete macroscopic resection, recurrence has been shown to occur in up to 32% of cases after 15 year follow up. Higher recurrence rates are seen in both atypical and anaplastic meningiomas. Hence, physicians have been looking toward alternative medical therapies.

8. Background Post-operative MRI performed 6 months after surgical resection demonstrates residual atypical meningioma along the superior sagittal sinus. Pre-operative 6 months post-operative

9. Background Some meningiomas, may express somatostatin receptors. Somatostatin is a neuropeptide that is normally synthesized by the hypothalamus and helps to regulate GI motility, endocrine functions, and exocrine functions. – Somatostatin is also involved in cancer pathways as it affects angiogenesis and apoptosis. Treatment with somatostatin receptor blockers has the potential for inhibiting meningioma cell growth.

10. Background Nuclear medicine indium-111 pentetreotide scintigraphy (octreoscans) can identify meningiomas that express these somatostatin receptors. Octreoscans utilize a radiolabeled somatostatin analog (pentetreotide) which binds to somatostatin receptors.

11. Background Coronal T1 weighted post contrast imaging (left) demonstrates a residual meningioma following surgery and radiation at the left parietal vertex and along the left temporal lobe. Planar octreoscan image (middle) demonstrates area of increased radiotracer uptake in the regions of residual meningioma, consistent with meningioma with significant expression of somatostatin receptors. SPECT-CT image (right) confirms location of residual meningioma with significant expression of somatostatin receptors in the regions seen on prior MRI.

12. Background Treatment in the form of somatostatin receptor blockers may represent an alternative or adjunctive treatment to the complex and often grueling course of multiple surgical procedures.

13. Materials and Methods A retrospective database search was done to identify patients with a history of meningioma who had octreoscans that were positive for somatostatin receptors within the Henry Ford Health System during the period of January 2005 to November 2014. Relevant medical records and radiologic imaging were reviewed to categorize the patients’ symptomatology, surgical history, pathology results, imaging findings, and treatment plans.

14. Materials and Methods MRI examinations before and after somatostatin receptor blocker treatment were reviewed to assess for progression of disease following initiation of somatostatin receptor blocker treatment.

15. Results A total of seven patients were identified including 4 females and 3 males. In all seven of the cases, the octreoscans were performed after there was MRI evidence of residual or recurrent disease following surgical resection.

16. Results Pathology – 29% of the patients identified had pathology results consistent with meningiomas without atypical features (WHO Grade I). – 57% of the patients had pathology results consistent with meningiomas with atypical features (WHO Grade II). – 14% of the patients had pathology results consistent with anaplastic meningioma (WHO Grade III).

17. Results 14% of the patients had residual or recurrent disease in close proximity to cranial nerves, which limited further surgical resection. In 71% of the cases, medical therapy with a somatostatin receptor blocker was initiated. – One of the patients decided to forgo somatostatin receptor blocker treatment secondary to the patient’s history of diabetes and possible complication of worsening blood sugar levels while on the therapy. – Another patient decided to forgo somatostatin receptor blocker treatment with no clear reason given in the clinical notes.

18. Results In 40% of the patients who underwent therapy with somatostatin receptor blocker therapy, there was no evidence of recurrence or progression of disease after initiation of treatment. The remaining 60% showed progression of disease on MRI following initiation of somatostatin receptor therapy with either increased size of exisiting lesions or the development of new lesions.

19. Results MRI after surgical resection and prior to initiation of Sandostatin therapy (left) demonstrates post-operative changes with no evidence of residual disease. MRI obtained after initiation of Sandostatin therapy (right) demonstrates new enhancing mass in the right subfrontal region consistent with new meningioma and disease progression.

20. Conclusion This study shows that somatostatin receptor blocker therapy can lead to progression-free survival in a certain subset of patients and thus may act as an amenable alternative or adjunct to complicated and possibility debilitating surgical resections in patients with meningiomas expressing somatostatin receptor.

21. Conclusion Radiologists can play a role in guiding treatment of these meningiomas through octreoscans. This can enable the identification of the subset of patients that may benefit from somatostatin receptor blocker therapy, specifically in the population of patients that have undergone multiple surgical resections or in which the meningiomas demonstrate aggressive features which preclude complete surgical resection.

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