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Treatment of Aggressive Pituitary Adenomas and Carcinomas—An Overview

Published Online: May 14th 2012 US Endocrinology, 2012;8(1):50-2 DOI: http://doi.org/10.17925/USE.2012.08.01.50
Authors: Luis V Syro, Leon D Ortiz, Fabio Rotondo, Humberto Uribe, Luis C Penagos, Eva Horvath, Kalman Kovacs
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Abstract:
Overview

Most pituitary tumors are non-invasive, benign adenomas that remain confined to the sella turcica. Some of them recur, have a rapid growth rate, and invade surrounding tissues. These adenomas, considered aggressive pituitary tumors, are difficult to manage and present problems due to incomplete resection. A pituitary carcinoma is diagnosed when craniospinal and/or systemic metastases are documented. Treatment options for pituitary adenomas are surgery, radiation, and drugs. Recent publications report the efficacy of temozolomide in the treatment of aggressive pituitary adenomas and carcinomas. Indications for, results with, and side effects of temozolomide therapy in aggressive pituitary tumors and pituitary carcinomas are reviewed here. Alternative treatment options for resistant or recurrent pituitary tumors are also discussed.

Keywords

Pituitary adenoma, pituitary carcinoma, O6-methylguanine-DNA methyltransferase (MGMT), temozolomide, everolimus, bevacizumab

Article:

Most pituitary tumors are non-invasive, benign adenomas that remain confined to the sella turcica. Although there is, at present, no accepted definition of aggressive pituitary adenomas, one would suggest that these have a tendency to recur after initial surgery. They have a rapid growth rate and invade surrounding structures such as the sphenoid and cavernous sinus as well as the skull base bone. They are clinically difficult to manage and present major problems due to incomplete resection.1

Most pituitary tumors are non-invasive, benign adenomas that remain confined to the sella turcica. Although there is, at present, no accepted definition of aggressive pituitary adenomas, one would suggest that these have a tendency to recur after initial surgery. They have a rapid growth rate and invade surrounding structures such as the sphenoid and cavernous sinus as well as the skull base bone. They are clinically difficult to manage and present major problems due to incomplete resection.1

Pituitary carcinomas are rare—0.2 % of all pituitary tumors. They present major diagnostic and therapeutic challenges. They may initially appear as benign pituitary adenomas subsequently transforming into an aggressive neoplasm, or they may be aggressive tumors from the beginning.2–4 A pituitary carcinoma is diagnosed when craniospinal and/or systemic metastases are documented.5 Predicting pituitary tumor behavior remains a real challenge. Studies suggest that increased mitotic activity, high Ki-67, nuclear labeling index, and P53 expression might be associated with tumor progression.3,5

Multiple treatment approaches—including surgery, external beam radiotherapy, gamma knife, drugs, and various chemotherapeutic agents—have been used. Until recently, the treatment of pituitary carcinomas was mainly palliative and did not seem to increase overall survival. Progression of disease after a diagnosis of pituitary carcinoma was variable; approximately 75 % of patients with systemic metastasis died of the disease within one year.4 Recent publications report efficacy of temozolomide, an alkylating agent used to treat gliomas, in the management of aggressive pituitary adenomas and carcinomas.6–36 As in gliomas, the outcome of treatment might depend on the expression of O6-methylguanine-DNA methyltransferase (MGMT), a DNA repair enzyme that counteracts the action of temozolomide.6,13,37

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Disclosure

The authors have no conflicts of interest to declare.

Correspondence

Luis V Syro, MD, Department of Neurosurgery, Hospital Pablo Tobón Uribe and Clinica Medellin, Calle 54 # 46-27, Cons 501, Medellin, Colombia. E: lvsyro@une.net.co

Support

The authors are grateful to the Jarislowsky and Lloyd Carr-Harris Foundations for their continuous support.

Received

2012-06-04T00:00:00

References

  1. Buchfelder M, Management of aggressive pituitary adenomas: current treatment strategies, Pituitary, 2009;12(3):256–60.
  2. Kaltsas GA, Nomikos P, Kontogeorgos G, et al., Clinical review: Diagnosis and management of pituitary carcinomas, J Clin Endocrinol Metab, 2005;90(5):3089–99.
  3. Colao A, Ochoa AS, Auriemma RS, et al., Pituitary carcinomas, Front Horm Res, 2010;38:94–108.
  4. Pernicone PJ, Scheithauer BW, Sebo TJ, et al., Pituitary carcinoma: a clinicopathologic study of 15 cases, Cancer, 1997;79(4):804–12.
  5. Heaney AP, Clinical review: Pituitary carcinoma: difficult diagnosis and treatment, J Clin Endocrinol Metab, 2011;96(12):3649–60. Erratum in: J Clin Endocrinol Metab, 2012;97(3):1064.
  6. Raverot G, Castinetti F, Jouanneau E, et al., Pituitary carcinomas and aggressive pituitary tumours: merits and pitfalls of temozolomide treatment, Clin Endocrinol (Oxf), 2012;76(6):769–75.
  7. Ortiz LD, Syro LV, Scheithauer BW, et al., Temozolomide in aggressive pituitary adenomas and carcinomas, Clinics (Sao Paulo), 2012;67(Suppl. 1):119–23.
  8. Lim S, Shahinian H, Maya MM, et al., Temozolomide: a novel treatment for pituitary carcinoma, Lancet Oncol, 2006;7(6):518–20.
  9. Fadul CE, Kominsky AL, Meyer LP, et al., Long-term response of pituitary carcinoma to temozolomide. Report of two cases, J Neurosurg, 2006;105(4):621–6.
  10. Syro LV, Uribe H, Penagos LC, et al., Antitumour effects of temozolomide in a man with a large, invasive prolactinproducing pituitary neoplasm, Clin Endocrinol (Oxf), 2006;65(4):552–3.
  11. Kovacs K, Horvath E, Syro LV, et al., Temozolomide therapy in a man with an aggressive prolactin-secreting pituitary neoplasm: Morphological findings, Hum Pathol, 2007;38(1):185–9.
  12. Neff LM, Weil M, Cole A, et al., Temozolomide in the treatment of an invasive prolactinoma resistant to dopamine agonists, Pituitary, 2007;10(1):81–6.
  13. Kovacs K, Scheithauer BW, Lombardero M, et al., MGMT immunoexpression predicts responsiveness of pituitary tumors to temozolomide therapy, Acta Neuropathol, 2008;115(2):261–2.
  14. Debono M, Bridgewater C, Ross R, Newell Price J, Treating an aggressive prolactinoma in a patient with MEN 1: beneficial response to temozolomide, Presented at: Society for Endocrinology BES 2008, Harrogate, UK, April 7–10, 2008; Endocrine Abstracts, 2008;15:188.
  15. Moyes VJ, Alusi G, Sabin HI, et al., Treatment of Nelson’s syndrome with temozolomide, Eur J Endocrinol, 2009;160(1):115–9.

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