Giuseppe Minniti, MD, PhD
UPMC Hillman Cancer Center, San Pietro, Roma, IT
Department of Medicine, Surgery, and Neuroscience, University of Siena, Siena, IT
IRCSS Neuromed, Pozzilli (IS), IT
Surgery, radiation therapy (RT), and medical therapies, are available treatments for patients with both nonfunctioning or secreting pituitary pituitary adenomas. Historically, transsphenoidal surgery has been recommended in the initialmanagementof pituitary tumors, with complete resection and biochemical normalization of hormone hypersecretion which is achieved in up to 80% of patients, depending on the size, location, and extension of the tumor, and with a low incidence of surgical complications. In the last two decades, medical treatment of GH-secreting, ACTH-secreting and prolactin-secreting adenomas has improved and several medicaltherapies are now available, including dopamine agonists, somatostatin analogs, and the GH-receptor antagonist pegvisomant with a reported normalization of hormone hypersecretion in more than 70% of patients, especially those with prolactinoma and acromegaly.
RT has been generally employed in the past for patients with residual or recurrent non-functioning pituitary adenomas after surgery to prevent tumour growth, resulting in local control of 90-95% at 5-10 years and variable normalization of hormonal hypersecretion for patients with GH-, ACTH-, and prolactin-secreting adenomas in the range of 40 to 80% at 5 years; however, its use has been limited because of concerns regarding potential late toxicity of radiation and delayed efficacy in normalization of hormone hypersecretion. Main complication of treatment is represented by the development or worsening of hypopituitarism occurring in 30-60% of patients 5-10 years after irradiation, while other toxicities, such as radiation-induced optic neuropathy, neurocognitive deterioration, cerebrovascular accidents, and secondary tumors that have been reported in less than 5% of patients. In the last decades, there have been advances in all aspects of radiation treatment, including more accurate immobilization, imaging, treatment planning and dose delivery. For patients with a pituitary adenoma, radiation techniques have evolved from 3D conformal RT to the stereotactic techniques, either stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT), with the aim of delivering high radiation doses with a steeper dose gradient between the tumor and the surrounding critical neurovascular structures, potentially reducing long-term adverse effects of radiation treatments.Stereotactic radiosurgery (SRS) delivered as either single-fraction or multi-fraction SRS (2-5 fractions) is frequently employed in patients with residual or recurrent pituitary adenoma. Currently, there are three types of equipment to deliver SRS: linear-accelerator based systems (X-Knife and Cyberknife), the cobalt-60 system Gamma Knife,and cyclotrons (Proton beam). Tumor control and normalization of hormone hypersecretion have been reported in 75-100% and 25-80% of patients, respectively. Hypopituitarism is the most commonly reported late complication of radiation treatment, whereas other toxicities occur less frequently.We have provided an overview of the recent available literature on SRS in patients with a pituitary adenoma. Single-fraction SRS represents an effective treatment for patients with a pituitary adenoma; however, caution should be used for lesions > 2.5-3 cm in size and/or involving the anterior optic pathway. The treatment for patients with aggressive tumors who recur after available standard reatment remains challenging in clinical practice and no standard of care exists. For them, few retrospective studies have suggested that a second course of radiation, either SRS or fractionated RT, is a feasible salvage therapy associated with high tumor control and relatively low toxicity.