Nancy A. Melville

April 28, 2017

LOS ANGELES — Treatment of residual nonfunctioning pituitary macroadenomas with Gamma Knife (Elekta) radiosurgery shows significantly greater benefit in reducing progression without an increase in endocrinopathies when used early after surgery compared with more than 6 months later in cases where clinicians opt for a "wait-and-watch" approach, according to new research.

"We found a significantly greater risk of tumor progression in the later stereotactic radiosurgery (SRS) cohort, and an equivalent and generally low risk of post-Gamma Knife radiosurgery endocrinopathy in the early as well as late cohorts," said Jason P. Sheehan, MD, PhD, a professor of neurological surgery and radiation oncology at the University of Virginia in Charlottesville.

He presented the findings here at the American Association of Neurological Surgeons (AANS) 2017 Annual Meeting.

Strong evidence supports the use of SRS in the treatment of residual or recurrent nonfunctioning pituitary macroadenomas, showing a control rate of more than 90% in some studies, the authors note. However, there is a lack of consensus on the timing of SRS and whether the radiosurgery should be performed early after surgery or delayed until signs of tumor progression emerge.

"There is concern of the risks of radiosurgery if it's not absolutely required, with radiation-induced endocrinopathies and notably hypopituitarism a significant risk with nonfunctioning macroadenomas," Dr Sheehan said.

In the current multicenter study, Dr Sheehan and colleagues evaluated outcomes of 222 patients with nonfunctioning pituitary macroadenomas who were treated with transsphenoidal surgery followed by Gamma Knife radiosurgery at nine centers between 1987 and 2015.

Patients were matched according to factors including age and sex, as well as adenoma and radiosurgical measures, and they were categorized according to whether they had early (less than 6 months after surgery) or late  (more than 6 months after surgery; both groups n = 111) SRS.

The results after a median follow-up period of 68.5 months showed that those in the late radiosurgical group had a significantly greater risk for tumor progression (P = .01) and residual tumor (P = .03) than the early radiosurgery group.

The groups meanwhile had no significant differences in the occurrence of postradiosurgery endocrinopathy (P = .68), with 30% of patients in the early SRS group and 27% in the late SRS group developing new endocrinopathies in the follow-up period (P = .84).

"We looked in detail at the endocrinopathies and, consistent with the literature, we found about a 30% risk of delayed endocrinopathy in both the early and delayed groups, while no differences were seen in the overall extent of endocrinopathy or in subtypes," Dr Sheehan said.

Resolution of endocrine dysfunction from the time of the original presentation was observed in 14% of patients in the early group and 25% in the late group, which also was not significantly different (P = .32).

"In essence, the findings indicate that the concern about complications arising from early radiosurgery seem to be unfounded," Dr Sheehan concluded.

Limitations of the study include variations in treatment approaches at the different treatment centers.

In terms of recommendations to patients, Dr Sheehan said that in general, early SRS treatment is a safe suggestion, with the caveat of consideration of certain patient situations.

"I would postulate that if a patient has a reasonable enough life expectancy and no appreciable comorbidities that would preclude SRS, such as concern about possible hypopituitarism at a time when they might, for instance, be trying to conceive, then there is probably no reason to delay SRS in the setting of a reasonably sized residual nonfunctioning adenoma after a reasonable attempt at resection with a transsphenoidal surgery approach."

He added that longer-term studies are nevertheless needed: In response to an audience member's question of whether the study's follow-up period is adequate when onset of hypopituitarism can occur as far as 10 years after SRS, Dr Sheehan agreed that the follow-up period is a limitation.

"One study has in fact shown the risk of endocrinopathies can be as high as 70% in patients even 15 years or more after SRS, so I agree that this is an insufficiently short follow-up, but it's unfortunately the best we can do right now."

The authors have disclosed no relevant financial relationships.

American Association of Neurological Surgeons (AANS) 2017 Annual Meeting. Abstract 839. Presented April 25, 2017.

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