Everolimus effectively blocks pulmonary metastases from meningioma
Authors: Federica Bertolini, Annarita Pecchi, Alessandro Stefani, Annalisa Fontana, Giulio Rossi
Journal: Neuro-Oncology (2015)

Brain CT and MRI were performed (February 2011) on a 27-year-old woman with headaches, and a right extra-axial frontoparietal lesion with hemorrhagic component was diagnosed. She developed a spontaneous left pneumothorax prior to the neurosurgical operation. A chest CT scan showed the presence of multiple bilateral cystic pulmonary lesions; a left pleural drain was positioned, and lung biopsies were performed. The histological examination documented lung metastases from meningioma. Immunohistochemistry revealed tumor cells negative for somatostatin-receptor 2 but positive for phospho-mTor and phospho-p70S6. After resolution of the pneumothorax, she underwent neurosurgery (April 2011) with gross total removal of the lesion. The histological examination confirmed the diagnosis of meningioma of the right frontoparietal sagittal sinus (fragments of transitional and papillary meningioma, WHO grade I, 2007, MIB-1 5%). The histology slides of the primary and metastatic sites were reviewed by an expert neuropathologist, and the diagnosis was confirmed. NF2 gene analysis was negative. 68Ga-DOTATOC was negative in the brain and lung. On June 2011, she started hydroxyurea 1000 mg/daily (according to the National Comprehensive Cancer Network guidelines)1 at 75% of the scheduled dose to test toxicity. A brain MRI documented no signs of local relapse, but chest CT scan (July 2011) showed an increase in number and size of the multiple cystic pulmonary lesions; the majority of lung lesions presented as solid nodules with minor cystic component. On July 2011, the dose of hydroxyurea was increased to 1500 mg/daily (20 mg/kg/d, according to NCCN guidelines)1 and continued until July 2012 (progression-free survival: 12 months) when a chest CT documented a progression in the number and size of multiple bilateral cystic lung lesions with a minor solid component; a bilateral pneumothorax was also documented and treated with placement of pleural drainage and pleurodesis (right side). After Ethics Committee approval and written informed consent, our hospital approved the compassionate use of everolimus based on positivity for phospho-mTOR and phospho-p70S6. In August 2012, she started everolimus (AFINITOR) 10 mg per day with a good tolerability profile (mucositis G1, increase in cholesterol serum levels G1, liver toxicity G1). At the present time, she is still experiencing a long-lasting clinical and radiological response with an excellent quality of life. In particular, her chest CT (November 2014) showed stable disease and no relapse of pneumothorax. Brain MRI (January 2015) documented no relapse of the primary meningioma (duration of response: 27 months). Akin to a reduction in number and size of lung metastases (after 4 months of therapy), chest CT showed a switch from nodular to cystic pattern (Fig. 1) and has maintained this pattern with a prevalent cystic component until her last CT. We considered all of these aspects as response to treatment. RECIST criteria for evaluation of response were not applicable in this case due to the peculiarity of radiological presentation (cystic and nodular lesions) and the impossibility of identifying target lesions (for size, number, and characteristics).