Fractionated proton beam irradiation of pituitary adenomas

Purpose: Various radiation techniques and modalities have been used to treat pituitary adenomas. This report details our experience with proton treatment of these tumors.

Methods and Materials: Forty-seven patients with pituitary adenomas treated with protons, who had at least 6 months of follow-up, were included in this analysis. Forty-two patients underwent a prior surgical resection; 5 were treated with primary radiation. Approximately half the tumors were functional. The median dose was 54 cobalt-gray equivalent.

Results: Tumor stabilization occurred in all 41 patients available for follow-up imaging; 10 patients had no residual tumor, and 3 had greater than 50% reduction in tumor size. Seventeen patients with functional adenomas had normalized or decreased hormone levels; progression occurred in 3 patients. Six patients have died; 2 deaths were attributed to functional progression. Complications included temporal lobe necrosis in 1 patient, new significant visual deficits in 3 patients, and incident hypopituitarism in 11 patients.

Conclusion: Fractionated conformal proton-beam irradiation achieved effective radiologic, endocrinological, and symptomatic control of pituitary adenomas. Significant morbidity was uncommon, with the exception of postradiation hypopituitarism, which we attribute in part to concomitant risk factors for hypopituitarism present in our patient population.

Introduction

Pituitary adenomas comprise 10% to 12% of all intracranial tumors (1). They are classified as benign histologically but can cause morbidity and occasional mortality; these conditions may occur through hormonal imbalances and functional deficits via compression of adjacent structures, such as the optic chiasm and hypothalamus. For non–prolactin-secreting microadenomas, treatment has consisted primarily of surgery, usually via transsphenoidal resection (2, 3, 4, 5). Prolactin-secreting microadenomas are treated primarily with bromocriptine (6, 7). Macroadenomas are treated optimally with a multimodality approach, including postoperative radiotherapy and hormonal suppression for secreting tumors (8).

Treatment of pituitary adenomas with radiation dates back to the early 1900s (9). Although reports of good tumor control with primary radiotherapy exist in the literature (10), radiation is now more commonly used in a postoperative setting for macroadenomas that feature either macroscopic residuum or a high risk of recurrence (11). Various radiation techniques have been employed to treat these tumors, including external photon-beam irradiation by use of conventional fractionation regimens, (12, 13, 14, 15, 16) gamma knife and linear accelerator–based stereotactic radiosurgery or radiotherapy (17, 18, 19), and charged-particle radiosurgery (20, 21, 22, 23).

Comparative dosimetry studies have demonstrated that proton irradiation of small intracranial and paranasal sinus tumors can achieve greater target-dose conformity and sparing of organs at risk than can photon techniques (24, 25). One of these studies also found that proton irradiation achieved better target-dose uniformity than did 3D conformal, stereotactic arc, and intensity-modulated radiotherapy of a variety of small, benign intracranial tumors, including meningiomas, acoustic neuromas, and pituitary adenomas (24). From the late 1950s to the 1980s, pituitary adenomas were treated with proton and heavy-ion radiosurgery at several laboratory-based treatment centers abroad and in the United States, the latter at Harvard Cyclotron Laboratory and Lawrence Berkeley Laboratory (20, 21, 22, 23). However, with the advent of hospital-based proton treatment centers capable of treating large numbers of patients, treatment of pituitary adenomas and other small intracranial tumors with protons in standard fractionation regimens over 5 to 6 weeks has become practical.

From the outset of clinical proton treatments at Loma Linda University Medical Center in 1991, our practice has been to treat pituitary adenomas and other intracranial benign tumors with standard fractionation regimens (1.8–2 Gy per fraction). We have previously reported on our experience in the treatment of intracranial and base-of-skull tumors, including pituitary adenomas, with proton irradiation in pediatric patients (26). In this retrospective review, we detail the first reported clinical series of patients with pituitary adenomas treated with fractionated proton radiation over a period of 10 years.