By Ann Saul
LIEGE, Belgium -- September 26, 2010 -- Leksell gamma knife radiosurgery is effective for the treatment of Cushing's disease, researchers said here on September 22 at the 14th Congress of the European Neuroendocrine Association (ENEA).
Typical first-line treatment for Cushing's disease is usually transsphenoidal surgery, and the rate of remission following the initial surgery is between 70% to 90% in patients with microadenomas and 50% to 60% in patients with macroadenomas.
However, recurrence of the disease happened in approximately 10% to 30% of patients. In those cases, one of the treatment options is stereotactic radiosurgery with Leksell gamma knife (LGK).
"Leksell gamma knife is an integral part of the treatment approach in Cushing's disease," said Jana Jezkova, MD, Department of Medicine, First Medical Faculty, Charles University, Prague, Czech Republic. "LGK irradiation is used as a secondary treatment after surgery when a hormonally active residue is found or as a primary treatment in situations where surgery is contraindicated or is refused by the patient."
This study included 27 patients (24 females, 3 males) aged 16 to 65 years. They were followed for a mean period of 80.9 months (range, 24-168 months). Seventeen of the patients (63%) had previous neurosurgery, but none of them had conventional radiotherapy prior to LGK irradiation.
The target tumour volume for radiosurgery was between 13.4 to 2,700 mm3 with an average dose of 639.5 mm3 (median, 232 mm3). The central radiation dose range was 50 to 80 Gy, with an average dose of 68.3 Gy (media, 70 Gy). The minimal peripheral dose was 25 to 49 Gy, with an average dose of 37.2 Gy (median, 35 Gy). The dose for surrounding structures was 8 Gy for the edge of chiasma opticum and 14 Gy for the brainstem. The mean dose to the pituitary was 15 Gy.
Pituitary function was monitored at 6-month intervals post irradiation. The 3 criteria for hormonal normalisation included normalisation of 24-hour free urinary cortisol, suppressibility of plasma cortisol after an overnight dexamethasone (1 mg), and restitution of circadian variability of plasma cortisol levels.
At 1 year following treatment, 27 patients (25.9%) had achieved hormonal normalisation. After 3 years, 25 patients (36%) had achieved normalisation. Hormonal normalisation was achieved 5 years after LGK irradiation in 18 patients (66.7%) and 8 years later in 8 patients (75%).
The irradiation arrested the growth of all adenomas and caused the tumour to shrink in the majority of cases.
After 1 to 2 years, there was no change in 17.4% of tumours, a decrease in adenoma size in 69.7%, and disappearance of the adenoma in 13.0%. After 3 to 5 years, there was no change in only 13.3% of patients, 73.4% of adenomas had decreased, and 13.3% of adenomas had disappeared.
Three (11.1%) of the patients developed hypopituitarism within 12 to 72 months after LGK irradiation. However, hypopituitarism did not develop in patients who were irradiated with a mean dose to the pituitary of <15 Gy.
Until the effect of the irradiation is evident and the hormonal production halted, levels of excess hormones have to be suppressed pharmacologically. Keeping the mean radiation dose to the pituitary gland <15 Gy prevents the development of hypopituitarism, the researchers said.
[Presentation title: Gamma Knife Radiosurgery for Cushing's Disease. Abstract PC-118]