Pituitary insufficiency as a side effect after radiosurgery for pituitary adenomas: the role of the hypothalamus.

OBJECT: Causes of pituitary insufficiencies as a side effect of Gamma Knife surgery (GKS) following irradiation of the hypothalamopituitary axis are still under debate. In an investigation of pituitary insufficiencies after GKS, the authors' main focus is on what role can be attributed to the hypothalamus with regard to endocrinological changes in hypothalamopituitary function following GKS. METHODS: A total of 108 patients consecutively treated between April 1992 and July 2003 were included in this retrospective study. All patients had undergone either transsphenoidal or transcranial surgery prior to GKS. The spot dosimetry method was used to determine doses delivered to structures of the hypothalamopituitary axis. For statistical analyses, endocrine insufficiency and deterioration in pituitary function were defined as a decrease in hormonal blood levels below the normal range for 1 or more anterior pituitary lobe hormones. Additionally, an analysis of the rate of patients requiring hormone replacement therapy after GKS due to new endocrinopathies was performed. RESULTS: Complete patient records of 61 male and 47 female patients with a mean age of 51.9 years (range 9.1­81.2 years) were available for our investigation. The overall tumor control rate was 97% and the endocrinological cure rate was 61.2%. Mean treatment doses in patients with and without new endocrine insufficiencies (shown as with/without insufficiencies and followed by probability values) were as follows: 1.3/0.8 Gy to the hypothalamus(p = 0.2); 2.2/1.6 Gy to the median eminence (p = 0.1); 6.5/4.1 Gy to the pituitary stalk (p = 0.004); and 12.4/9.5Gy to the pituitary gland (p = 0.05). The median overall duration of follow-up after GKS was 6.7 years, with 84 patients(77.7%) whose follow-up was longer than 12 months. The median follow-up time after GKS in patients who developed a new pituitary dysfunction was 79.5 months (6.6 years, SD 3.8 years), and the median follow-up time inpatients with no new insufficiencies was 78.4 months (6.5 years, SD 4 years). CONCLUSIONS: Gamma Knife surgery is a safe and effective treatment for patients with residual and recurrent pituitary adenomas. The rate of pituitary insufficiencies after GKS is still lower than that after conventional radiotherapy.Very low radiation doses are directed to the hypothalamus, and thus this structure does not play a major role in the development of pituitary insufficiencies after GKS. The results of this study show that patients in whom the pituitary stalk and pituitary gland receive a high mean point dose are more likely to develop pituitary insufficiencies after GKS than those who receive a lower dose. (DOI: 10.3171/2010.8.GKS10959).

Volumetric follow up of brain metastases: a useful method to evaluate treatment outcome and predict survival after Gamma Knife surgery?

OBJECT: Brain metastases are diagnosed in 20 to 40% of all cancer patients and are associated with a considerable drop in life expectancy and often also in quality of life for these patients. Several treatment options are available including surgery, chemotherapy, whole-brain radiotherapy, stereotactic radiotherapy, stereotactic radiosurgery, and Gamma Knife surgery (GKS). However, management of brain metastases still presents a challenge and there is no general consensus on the best treatment strategy. The aim of the authors' study was to further evaluate the efficacy of GKS in the treatment of brain metastases and to evaluate the predictive value of volumetric tumor follow-up measurement. METHODS: Consecutive patients with controlled systemic cancer and variable numbers of brain metastases were included in this prospective study. Patients with severe symptoms of brain compression underwent surgery before GKS. Each follow-up examination included a thorough neurological examination and a neuroradiological quantitative volumetric tumor analysis. A total of 300 consecutive patients (mean age 58 years) with 703 brain metastases were treated between December 1998 and October 2005. The mean total tumor volume (TTV) was 2.1 cm3. The overall local tumor control rate was 84.5%. In 79% of all treated metastases a mean TTV reduction of 84.7% was achieved using a mean prescription dose of 21.8 Gy. Only few, mostly mild, side effects were observed during the mean follow-up period of 12.7 months. The overall mean progression-free survival period was 9.4 months. There was a statistically significant difference in survival of patients with one compared with multiple metastases, regardless of the histological type and preceding treatment. CONCLUSIONS: Gamma Knife surgery is a safe and effective treatment for patients with brain metastases regardless of the history of treatment and histological tumor type. It achieves excellent tumor control, significant TTV reduction without causing severe side effects, and accordingly, preserves quality of live. Volume changes after GKS did not serve as a predictor for treatment outcome and survival.

Intracranial glomus jugulare tumors: volume reduction with Gamma Knife surgery.

OBJECT: Glomus jugulare tumors (GJTs) are slow-growing benign tumors arising from paraganglion cells of the superior vagal ganglion. Involvement of cranial nerves and extensive erosion of the jugular foramen and petrous bone are typically seen in patients with GJTs. Advances in microsurgical techniques have improved patient outcomes, but tumors involving the petrous bone remain difficult to treat effectively. The aim of our study was to further evaluate the role of Gamma Knife surgery (GKS) in the management of intracranial GJTs. METHODS: Twelve consecutive patients (mean age 51.7 years) with intracranial GJTs were included in this study. The treatment strategy was either multimodal, with microsurgical tumor volume reduction followed by GKS in patients suffering from brainstem compression, or GKS as the only treatment. Follow-up examinations included thorough neurological examinations and neuroradiological quantitative volumetric tumor analysis. Five patients (41.6%) underwent microsurgery before GKS. Tumor volumes ranging from 1.6 to 24.8 cm3 were treated using prescription doses of 14 to 20 Gy (nine-28 isocenters). The achieved overall tumor control rate after GKS was 100% (33 months mean follow up) with only mild side effects observed. A tumor volume reduction (mean 41.1%; 3.2 cm3) was achieved in all patients. CONCLUSIONS: Gamma Knife surgery is a safe and effective treatment for intracranial GJTs. The tumor volume reductions achieved are comparable to those achieved using microsurgery but with a much lower rate of side effects. More studies with longer follow-up times are necessary to confirm these very promising results.

Evaluation of a new concept for the management of skull base chordomas and chondrosarcomas.

OBJECT: Chordomas and chondrosarcomas of the skull base are rare locally invasive tumors associated with high recurrence rates. The aim of this study was to evaluate the concept of microsurgical tumor volume reduction followed by early gamma knife surgery (GKS). METHODS: Thirteen patients with 15 tumors were treated between October 2000 and June 2003. There were three patients (23.1%) with chordomas and 10 (76.9%) with chondrosarcomas. There were nine men and four women who ranged in age between 19 and 69 years. All patients first underwent maximal tumor resection. Within 2 to 10 months after surgery they were treated with GKS. The mean postoperative tumor volume treated with GKS was 9.7 cm3 (range 1.4-20.3 cm3). Follow-up computerized tomography and magnetic resonance imaging examinations with volumetric tumor analysis were performed every 6 months after GKS. The mean treatment dose was 17 Gy and the mean isodose was 52%. The mean follow-up duration was 17 months during which there was only one tumor recurrence at the margin of the radiation field. The mean volume reduction was 35.4%. CONCLUSIONS: Results of this treatment strategy are encouraging but the efficacy of this multimodal treatment combining surgery and early GKS requires a longer follow up.