This survey confirms that TMZ is established as first-line chemotherapeutic treatment of APT/PC. Clinically functioning tumours, low MGMT and concurrent radiotherapy were associated with a better response. The limited long-term effect of TMZ and the poor efficacy of other drugs highlight the need to identify additional effective therapies.

The WHO categorizes pituitary tumours as typical adenomas, atypical adenomas and pituitary carcinomas, with typical adenomas constituting the major class. However, the WHO classification does not provide an accurate correlation between histopathological findings and clinical behaviour. Tumours lacking typical histological features are classified as atypical, but not all are clinically atypical or exhibit aggressive behaviour. Pituitary carcinomas, by definition, have craniospinal or systemic metastases, although not all display classical cytological features of malignancy. Aggressive pituitary adenomas, defined from a clinical perspective, have earlier and more frequent recurrences and can be resistant to conventional treatments. Specific biomarkers have not yet been identified that can distinguish between clinically aggressive and nonaggressive pituitary adenomas, although the antigen Ki-67 proliferation index might be of value. This Review highlights the need to develop new biomarkers to facilitate the early detection of clinically aggressive pituitary adenomas and discusses emerging markers that hold promise for their identification. Defining aggressiveness is of crucial importance for improving the management of patients by enhancing prognostic predictions and effectiveness of treatment. New drugs, such as temozolomide, have potential use in the management of these patients; anti-VEGF therapy, mTOR and tyrosine kinase inhibitors are also potentially useful in managing selected patients.

The classification of neoplasms of adenohypophysial cells is misleading because of the simplistic distinction between adenoma and carcinoma, based solely on metastatic spread and the poor reproducibility and predictive value of the definition of atypical adenomas based on the detection of mitoses or expression of Ki-67 or p53. In addition, the current classification of neoplasms of the anterior pituitary does not accurately reflect the clinical spectrum of behavior. Invasion and regrowth of proliferative lesions and persistence of hormone hypersecretion cause significant morbidity and mortality. We propose a new terminology, pituitary neuroendocrine tumor (PitNET), which is consistent with that used for other neuroendocrine neoplasms and which recognizes the highly variable impact of these tumors on patients.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the viral strain that has caused the coronavirus disease 2019 (COVID-19) pandemic, has presented healthcare systems around the world with an unprecedented challenge. In locations with significant rates of viral transmission, social distancing measures and enforced 'lockdowns' are the new 'norm' as governments try to prevent healthcare services from being overwhelmed. However, with these measures have come important challenges for the delivery of existing services for other diseases and conditions. The clinical care of patients with pituitary disorders typically involves a multidisciplinary team, working in concert to deliver timely, often complex, disease investigation and management, including pituitary surgery. COVID-19 has brought about major disruption to such services, limiting access to care and opportunities for testing (both laboratory and radiological), and dramatically reducing the ability to safely undertake transsphenoidal surgery. In the absence of clinical trials to guide management of patients with pituitary disease during the COVID-19 pandemic, herein the Professional Education Committee of the Pituitary Society proposes guidance for continued safe management and care of this population.

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Temozolomide, an orally administered alkylating agent, is used to treat malignant gliomas. Recent reports also have documented its efficacy in the treatment of pituitary adenomas and carcinomas. Temozolomide methylates DNA and thereby exhibits an antitumor effect. O 6 -methylguanine-DNA methyltransferase (MGMT), a DNA repair enzyme, removes alkylating adducts induced by temozolomide, counteracting its effects. The authors of this review conducted a Medline database search regarding temozolomide in the treatment of pituitary tumors. Demographic characteristics, tumor types, and therapeutic responses were noted in all patients. Data regarding MGMT immunoexpression, which was documented in some studies, were correlated with information regarding clinical and radiologic responses. To date, there have been 19 reported cases of adenohypophyseal tumors treated with temozolomide, including 13 adenomas and 6 carcinomas. Ten of those 13 adenomas responded favorably, and 2 nonresponsive tumors had highlevel MGMT immunoexpression. All 6 carcinomas responded to therapy, but data regarding MGMT expression were available for only 3 patients, and each had low MGMT expression. In 2 adenomas, morphologic studies were performed both before and after the patients received temozolomide. The responsive tumor had necrosis, hemorrhage, fibrosis, and neuronal differentiation. The nonresponsive tumor had no changes. There have been no reported complications attributable to temozolomide. The current results indicated that temozolomide is efficacious in the treatment of aggressive pituitary adenomas and pituitary carcinomas. Evidence indicated that low-level MGMT immunoexpression is correlated with a favorable response. A significant proportion of pituitary adenomas and carcinomas had low MGMT immunoexpression. Cancer 2011;117:454-62.