Clinical Investigations
Initial clinical results of linac-based stereotactic radiosurgery and stereotactic radiotherapy for pituitary adenomas

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Abstract

Purpose: To retrospectively evaluate the initial clinical results of stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (SRT) for pituitary adenomas with regard to tumor and hormonal control and adverse effects of the treatment.

Subjects and Methods: Forty-eight patients with pituitary adenoma who underwent SRS or SRT between September 1989 and September 1995 were analyzed. Of these, 18 received SRS and 30 received SRT. The median tumor volumes were 1.9 cm3 for SRS and 5.7 cm3 for SRT. Eleven of the SRS and 18 of the SRT patients were hormonally active at the time of the initial diagnosis. Four of the SRS and none of the SRT patients had a history of prior radiation therapy. Both SRS and SRT were performed using a dedicated stereotactic 6-MV linear accelerator (LINAC). The dose and normalization used for the SRS varied from 1000 cGy at 85% of the isodose line to 1500 cGy at 65% of the isodose line. For SRT patients, a total dose of 4500 cGy at 90% or 95% of the isodose line was delivered in 25 fractions of 180 cGy daily doses.

Results: Disease control—The three year tumor control rate was 91.1% (100% for SRS and 85.3% for SRT). Normalization of the hormonal abnormality was achieved in 47% of the 48 patients (33% for SRS and 54% for SRT). The average time required for normalization was 8.5 months for SRS and 18 months for SRT. Adverse effects—The 3-year rate of freedom from central nervous system adverse effects was 89.7% (72.2% for SRS and 100% for SRT). Three patients who received SRS for a tumor in the cavernous sinus developed a ring enhancement in the temporal lobe as shown by follow-up magnetic resonance imaging. Two of these cases were irreversible and were considered to be radiation necrosis. None of the 48 patients developed new neurocognitive or visual disorders attributable to the irradiation. The incidence of endocrinological adverse effects were similar in the two groups, resulting in 3-year rates of freedom from newly initiated hormonal replacement of 78.4% (77.1% for SRS and 79.9% for SRT).

Conclusion: Considering the relatively high incidence of morbidity observed in the SRS group, we recommend SRT as the primary method of radiation therapy for pituitary tumors. When treating a lesion in the cavernous sinus with SRS, special attention should be paid to dose distribution in the adjacent brain parenchyma. Longer follow-up is necessary before drawing any conclusions about the advantages of these techniques over conventional external beam radiation therapy.

Introduction

Pituitary adenomas comprise about 10% of brain tumors (1). Although the majority of these tumors are histologically benign, they have the potential to severely deteriorate the patient’s quality of life by causing a visual disturbance and/or various clinical syndromes if they produce excessive pituitary hormones.

Medical management using bromocriptine or other drugs may provide temporary control of prolactinomas; however, this may have distressing side effects, and tumor relapse is uniformly seen after discontinuation of the drug treatment (2). In addition, this treatment is generally not effective for non-secreting adenomas, Cushing’s disease, or acromegaly (3).

For pituitary tumors larger than 1 cm in diameter, surgical removal is the treatment of choice (4). Almost all pituitary adenomas can be treated successfully by trans-sphenoidal surgery, which is generally less invasive and safer than craniotomy.

External beam radiation therapy (EBRT) has been used alone and as an adjunct to initial surgical debulking. In combination with surgery, conventional EBRT has been reported to provide 85% or higher tumor control over 10 years 5, 6, 7, 8, 9.

Stereotactic radiosurgery (SRS) has an advantage over conventional EBRT in that it can minimize the dose of radiation to the adjacent normal tissue by sharply focusing the dose distribution. In addition, stereotactic radiotherapy (SRT) is expected to have a further radiobiological advantage by fractionating the prescribed dose (10).

We herein report our initial clinical experience with SRS and SRT for pituitary adenomas, and we discuss the usefulness of these techniques in the treatment of pituitary adenomas.

Section snippets

Patient characteristics

Generally, radiation therapy for pituitary adenomas has been indicated for the following conditions: (a) Surgery is medically contraindicated or the patient refuses to undergo surgery; (b) the patient has a demonstrable re-growth of a non-functioning tumor after surgery; and (c) the patient has a residual functioning tumor which is likely to cause a persistent endocrine abnormality after surgery.

With these indications, 57 patients underwent radiation therapy for pituitary adenomas at the

Survival

The median follow-up for the whole patient population was 36 months (47 months for SRS and 34 months for SRT). There were 2 deaths among the 48 patients within the follow-up period. A 78-year-old male died of a massive cerebral hemorrhage in the frontal region 15 months after SRS, and an 81-year-old male died 33 months after SRS. The cause of his death was not documented. Consequently, the overall 3-year survival rate was 93.5% (84.4% for SRS and 100% for SRT) (Fig. 1 ). The 3-year survival

Discussion

Pituitary adenomas are best managed by a carefully considered combination of surgery, medical therapy, or radiation therapy. Radiation therapy in conjunction with initial surgical debulking has been repeatedly reported to further reduce the excessive hormonal secretion and lower the probability of recurrence 14, 15, 16, 17. The reported tumor control rates with postoperative EBRT range from 85% to 90% at 10 years 5, 6, 7, 8, 9. Although the 3-year tumor control rate of 91% in the present series

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    1

    Present address: Department of Radiology, Faculty of Medicine, Kyoto University, Kyoto 606-01, Japan.

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