October 30, 2018
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Long-term follow-up needed after gamma knife radiosurgery for acromegaly

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Among adults with acromegaly, gamma knife radiosurgery is an effective alternative to transsphenoidal surgery when pituitary surgery is either contraindicated or refused or tumor size is suitable; however, long-term follow-up is needed to watch for new-onset hypopituitarism and other complications, according to findings from a 30-year retrospective study published in Clinical Endocrinology.

Hugh P. Sims-Williams

Endocrine Society guidelines for the treatment of acromegaly recommend stereotactic radiosurgery over fractionated radiotherapy, provided the tumor target is small (< 35 mm in diameter) and in a position that allows less than 8 Gy radiation dose to the optic apparatus (usually at least 3 mm to 5 mm away), Hugh P. Sims-Williams, MSc, MBChB, MRCS, neurosurgical registrar in the department of neurosurgery, Royal Hallamshire Hospital in Sheffield, England, and colleagues wrote in the study background. The gamma knife has a targeting precision of less than 0.2 mm, they wrote.

“Transsphenoidal pituitary surgery remains the first-line treatment for acromegaly,” Sims-Williams told Endocrine Today. “It offers immediate correction of GH levels, thereby negating the long-term risks of raised GH levels. However, in cases where surgery is either contraindicated or refused by the patient, stereotactic radiosurgery offers an alternative permanent treatment. We have demonstrated significant latency to remission and new onset hypopituitarism.”

In a data review, Sims-Williams and colleagues analyzed data from 20 patients with acromegaly who underwent primary stereotactic radiosurgery at the National Centre for Radiosurgery in Sheffield between 1985 and 2015 (median age, 55 years). Researchers assessed biochemical control, hypopituitarism, morbidity and mortality. Biochemical remission was defined by two sets of criteria: guideline-based control (Endocrine Society guidelines for acromegaly) and pragmatic control for patients with only serum insulin-like growth factor I or growth hormone data available. Remission was also stratified as control on medication and control off medical treatment.

Researchers followed the cohort for a median of 166.5 months. Indications for primary stereotactic radiosurgery and treatment plans varied for the cohort, with a median marginal dose of 27.5 Gy.

At 20 years, researchers observed disease control in all patients on acromegaly-specific medication (n = 12) and in 75% of patients off medication. Time to achieve 50% control was 3 and 5 years, respectively, for patients on and off medication. Researchers observed a trend toward higher doses associated with faster control defined by guideline standards (P = .002) and pragmatic standards (P = .06); however, any effect was lost when using control on medication, according to researchers. Researchers did not observe a correlation between cavernous sinus invasion and time to control.

At a median follow-up of 146 months, 53% of patients developed new hypopituitarism. Of these, 50% developed new hypopituitarism by 12 years after stereotactic radiosurgery. Development of first-onset hypopituitarism occurred as late as 20 years after treatment, according to the researchers.

There were no deaths related to stereotactic radiosurgery; however, all but one death during follow-up (n = 7) were related to patient acromegaly.

The researchers noted that follow-up MRI was not routinely performed to confirm tumor volume reduction, although three patients required transsphenoidal pituitary surgery to achieve biochemical and symptom control.

“Stereotactic radiosurgery offers an alternative treatment for patients in whom transsphenoidal surgery is not an option,” Sims-Williams said. “We have provided outcome data that can guide clinic consultations. We have demonstrated the long-term potential for developing hypopituitarism after stereotactic radiosurgery and the need to monitor for this.”

by Regina Schaffer

For more information:

Hugh P. Sims-Williams, MSc, MBChB, MRCS, can be reached at Royal Hallamshire Hospital, Department of Neurosurgery, Glossop Rd., Sheffield S10 2JF, U.K.; email: simswilliams@doctors.org.uk.

Disclosures: The authors report no relevant financial disclosures.