Objective: To collect outcome data in a large cohort of patients with aggressive pituitary tumours (APT)/carcinomas (PC) and specifically report effects of temozolomide (TMZ) treatment. Design: Electronic survey to ESE members Dec 2015–Nov 2016. Results: Reports on 166 patients (40 PC, 125 APT, 1 unclassified) were obtained. Median age at diagnosis was 43 (range 4–79) years. 69% of the tumours were clinically functioning, and the most frequent immunohistochemical subtype were corticotroph tumours (45%). Ki-67 index did not distinguish APT from PC, median 7% and 10% respectively. TMZ was first-line chemotherapy in 157 patients. At the end of the treatment (median 9 cycles), radiological evaluation showed complete response (CR) in 6%, partial response (PR) in 31%, stable disease (SD) in 33% and progressive disease in 30%. Response was more frequent in patients receiving concomitant radiotherapy and TMZ. CR was seen only in patients with low MGMT expression. Clinically functioning tumours were more likely to respond than non-functioning tumours, independent of MGMT status. Of patients with CR, PR and SD, 25, 40 and 48% respectively progressed after a median of 12-month follow-up. Other oncological drugs given as primary treatment and to TMZ failures resulted in PR in 20%. Conclusion: 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.

Vitamin D is a pro-hormone characterized by an intricate metabolism and regulation. It is well known for its role in calcium and phosphate metabolism, and in bone health. However, several studies have assessed a huge number of extra-skeletal functions, ranging from cell proliferation in some oncogenic pathways to antioxidant and immunomodulatory functions. Vitamin D exerts its role by binding to VDRs (vitamin D receptors), which are located in many different tissues. Moreover, VDRs are able to bind hundreds of genomic loci, modulating the expression of various primary target genes. Interestingly, plenty of gene polymorphisms regarding VDRs are described, each one carrying a potential influence against gene expression, with relapses in several chronic diseases and metabolic complications. In this review, we provide an overview of the genetic aspects of vitamin D and VDR, emphasizing the gene regulation of vitamin D, and the genetic modulation of VDR target genes. In addition, we briefly summarize the rare genetic disease linked to vitamin D metabolism.