Meningiomas are mostly benign tumours originating from the arachnoid cap cells, represent 13-26% of all intracranial tumours. They are more common in older age and in females. Deletion in NF2 gene and exposure to ionizing radiation are established risk factors, while the role of sex hormones is yet not clarified. Five-year survival for typical meningiomas exceeds 80%, but is poorer (5-year survival <60%) in malignant and atypical meningiomas. Papillary and haemangiopericytic morphology, large tumour size, high mitotic index, absence of progesterone receptors, deletions and loss of heterozygosity are poor prognostic factors. Complete surgical excision is the standard treatment. Radiotherapy is currently used in the clinical practice in atypical, malignant or recurrent meningioma at a total dose of 45-60Gy. However, the role of adjuvant irradiation is still controversial and has to be compared in a randomised prospective setting with a policy of watchful waiting. Radiosurgery has gained more and more importance in the management of meningiomas, especially in meningiomas that cannot be completely resected as for many skull base meningiomas. Medical therapy for patients with recurrent, progressive and symptomatic disease after repeated surgery, radiosurgery and radiotherapy is investigational. Hormonal therapy with progesterone antagonists has shown modest results, while chemotherapy with hydroxyurea appears moderately active.

Ependymomas are rare tumours of neuroectodermal origin classified as myxopapillary ependymoma and subependymoma (grade I), ependymoma (grade II) and anaplastic ependymoma (grade III). The more common location is infratentorial (60%). Age <40 years and extent of surgery appear related to better prognosis, while the role of other prognostic factors, such as tumour grade and tumour site are equivocal. This emphasizes the role of surgery as the standard treatment. Postoperative radiotherapy is indicated in high-grade ependymomas, and is recommended in low-grade ependymomas after subtotal or incomplete resection (confirmed by postoperative MR). Deferral of radiotherapy until recurrence may be considered on an individual basis for patients with MR confirmation of a radical resection. Recommended dose to involved fields is 45-54 Gy for low-grade (grade II) and 54-60 Gy for high-grade ependymomas (grade III). There is no proof that postoperative chemotherapy improves the outcome. At recurrence, platinum-, nitrosourea- or temozolomide-based chemotherapy can be administered, although there is no evidence of efficacy.

Temozolomide is effective in some patients with progressive pituitary adenoma or carcinoma. We report a survey study of Italian patients treated with Temozolomide because of aggressive pituitary adenoma or carcinoma resistant to standard therapies. Italian endocrinologists were surveyed and asked to participate into the study. A questionnaire was sent to all those who agreed and had used Temozolomide in at least one patient with pituitary tumor. Database was closed in December 2013. A literature review was also performed. Thirty-one patients were included into the analysis. Mean age at start of Temozolomide treatment was 58.3 ± 1.9 years (± standard error). Six of the 31 (19.4%) Italian patients had a pituitary carcinoma. Twenty-five patients (80.6%) had disease control during Temozolomide treatment, while 6 patients (19.4%) had disease progression. Median follow-up after beginning Temozolomide was 43 months. Thirteen patients had tumor growth after stopping Temozolomide. The 2-year progression-free survival was 47.7% (95% CI 29.5-65.9%), while the 2-year disease control duration was 59.1% (95% CI 39.1-79.1%). Eleven patients died of progressive disease and other two patients of unrelated causes. The 2-year and 4-year overall survival rates were 83.9% (95% CI 70.7-97.1%) and 59.6% (95% CI 40.0-79.2%), respectively. Temozolomide is an additional effective therapeutic option for the treatment of aggressive pituitary tumors. The drug is well tolerated and causes few severe adverse effects. Recurrence of the tumor can occur after an initial positive response and usually portends a grim outcome.

Objective: The prognosis of either pituitary carcinoma or aggressive pituitary adenoma resistant to standard therapies is poor. We assessed the efficacy of treatment with temozolomide, an oral secondgeneration alkylating agent, in a consecutive series of six patients with aggressive pituitary adenomas. Design: This was a 1-year prospective study of temozolomide therapy in six consecutive patients with pituitary carcinoma (one case) or atypical pituitary adenoma (five cases) resistant to standard therapies. There were three males and three females. Age at enrollment ranged between 52 and 64 years. Temozolomide was given orally at a dose of 150-200 mg/m 2 per day for 5 days every 4 weeks for a maximum of 12 cycles. Methods: Response assessment was based on measurable change in tumor size, as assessed on magnetic resonance imaging, and hormone levels. Response was defined as reduction of at least 50% of tumor size and hormone levels. Results: Four patients completed the 12 cycles of temozolomide treatment, as planned. Two patients stopped the drug after 3 and 6 months respectively because of the progression of disease. Two patients responded to temozolomide, while the remaining two patients had stable disease. Immunohistochemistry for O 6 -methylguanine-DNA methyltransferase (MGMT) in tumor sample showed a partial association with treatment response. Conclusions: Temozolomide treatment has a wide range of efficacy in patients with pituitary carcinoma or locally aggressive pituitary adenoma. Positive staining for MGMT seems likely to predict a lower chance of response.

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