2005

Stereotactic Radiosurgery for Patients With Pituitary Adenomas

Points to Remember

• Stereotactic radiosurgery is the precise, single-session delivery of radiation to an imaging-defined target.
• Biochemical remission is possible in approximately 80% of properly selected patients with hormone-producing pituitary adenomas.
• nTumor growth control is achieved in more than 95% of patients with nonfunctional pituitary adenomas.
• The majority of pituitary adenomas decrease in size after radiosurgery, although this typically occurs over months to years. For patients with symptomatic mass effect (visual decline), surgical resection is required.

Although medical therapy and surgical resection are the primary treatments for the majority of patients with pituitary adenomas, some patients do not respond to medical therapy and sometimes complete tumor resection is not possible. Fractionated radiotherapy has been used for patients who have unsuccessful medical and surgical treatment of their pituitary adenoma. In recent years, stereotactic radiosurgery has been increasingly used as an alternative to surgery or radiotherapy to manage patients with pituitary adenomas.

Stereotactic radiosurgery is the precise delivery of a single fraction (dose) of radiation to an imaging-defined target. Radiosurgery combines stereotactic localization techniques developed in neurosurgery with radiation physics to distribute energy (x-rays, gamma rays, protons) to lesions both intracranially and extracranially. Although the types of energy used in radiosurgery are the same as in radiotherapy, fundamental differences exist between the techniques and need to be appreciated.

In radiosurgery, modern equipment permits highly conformal dose plans that result in little radiation exposure to the adjacent tissues. Conversely, external beam radiotherapy (EBRT) plans are generally not as conformal, and more radiation is delivered to nearby structures. To reduce the likelihood of radiation injury after EBRT, dose fractionation is used. Each patient should be evaluated with an appreciation of the advantages and drawbacks of both radiosurgery and EBRT to decide which modality is most appropriate for the clinical situation. As our understanding of this technique has grown, we have seen a steady increase in the number of patients with pituitary adenomas having radiosurgery at our center over the past 15 years (Figure 1).

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Patient Selection

Proper patient selection is the most important factor associated with good outcomes after radiosurgery. As a rule, pituitary adenomas with considerable suprasellar extension are typically not considered good candidates for radiosurgery because patients with larger lesions often have visual loss related to mass effect. Although radiosurgery does result in growth control and size reduction in the majority of pituitary adenomas, these effects occur gradually over several years. Therefore, surgical resection is the preferred approach for patients with large pituitary adenomas. However, for many patients, it is recognized in advance that complete tumor removal is not possible because the tumor extends into the cavernous sinus. In these patients, radiosurgery can be part of a staged approach with microsurgery. Initially, the tumor is debulked to create a separation between the top surface of the tumor and the optic apparatus without an attempt at resection of the tumor involving the cranial nerves, major arteries, or dural venous sinuses. Radiosurgery can then be performed for the remaining tumor volume with little risk of cranial nerve deficits.

The dose plan of a patient with persistent acromegaly after prior transsphenoidal surgery

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Such multimodality treatment should result in reduced patient morbidity, with long-term tumor control. Our center and others have also determined that the results of pituitary adenoma radiosurgery are adversely affected by the use of pituitary suppressive medications (bromocriptine, cabergoline, octreotide) at the time of radiosurgery. Consequently, we now have patients discontinue these medications 4 to 8 weeks before radiosurgery.

Radiosurgery With the Gamma Knife

Radiosurgery is performed at Mayo Clinic using the Leksell Gamma Knife (Elekta Instruments, Norcross, Georgia). The Gamma Knife has been used for 35 years to treat more than 75,000 patients worldwide. Radiosurgery is an outpatient procedure, performed with the patient under local anesthesia, and requires virtually no recovery time. After placement of a stereotactic headframe, the patient has an MRI performed for dose-planning purposes. A dose plan is then created and reviewed by a neurologic surgeon, a radiation oncologist, and a radiation physicist (Figure 2).

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Since January 1990, 167 of more than 2,800 patients with pituitary adenomas have undergone stereotactic radiosurgery at Mayo Clinic. More than 90% of the 167 patients have undergone prior surgery; approximately 75% had tumors with extension into the cavernous sinus. To minimize the incidence of visual deficits after radiosurgery, we limit the radiation dose to the optic nerves to less than 12 Gy. Such dose prescription has resulted in visual morbidity of less than 2%. The tumor growth control rate for pituitary adenomas exceeds 95% with follow-up that now extends beyond 10 years. Figure 3 shows the MRIs of a patient with a recurrent nonfunctional pituitary adenoma after prior transsphenoidal surgery and following radiosurgery.

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Two factors appear to correlate with endocrine cure after radiosurgery: higher radiation doses and the absence of pituitary suppressive medications at the time of radiosurgery. Patients with hormoneproducing tumors not taking pituitary suppressive medications and who receive more than 20 Gy to the tumor margin have a greater than 80% chance of biochemical cure. The average time to endocrine normalization is between 1 and 3 years (Figure 4). The incidence of new anterior pituitary deficits ranges from about 10% for small tumors to as much as 50% for large tumors that fill the entire sella. The incidence of diabetes insipidus after radiosurgery is exceedingly rare.