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Yoshimasa Mori, Tatsuya Kobayashi, and Yuta Shibamoto

Object

Metastases to the pituitary gland and cavernous sinus occasionally occur. Metastases of this nature are problematic because they are adjacent to eloquent structures such as cranial nerves, including the optic pathways and nerves for extraocular movement and facial sensation. Stereotactic radiosurgery has been reported to be safe and effective for metastases in various sites of brain parenchyma, providing the tumors are not large. Radiosurgery can be performed to treat a precisely defined target, and the risk of radiation side effects on the surrounding structures is reduced. The results of Gamma Knife surgery (GKS) for the treatment of metastases in the pituitary gland and the cavernous sinus are evaluated.

Methods

Among 623 patients with brain metastases treated by GKS, 13 patients (2.1%) had pituitary and/or cavernous metastases. The primary malignancies included lung cancer (five cases), breast cancer (two cases), parotid cancer (two cases), renal cell carcinoma, thyroid cancer, nasal cancer, and gastrointestinal stromal tumor (one case each). The location of the tumors was the pituitary gland (Type 1) in four patients, the cavernous sinus (Type 2) in five patients, and both the cavernous sinus and the sellar region (Type 3) in four patients. The patients' symptoms included dysfunction of the pituitary gland (two patients), visual disturbance (four patients), oculomotor palsy (one patient), abducent palsy (five patients), and trigeminal dysfunction (five patients). A margin dose of 12 to 12.3 Gy was delivered to pituitary metastases. A margin dose of 14.4 to 20 Gy was delivered to cavernous lesions. The dose selection depended on the spatial relationship between tumors and the cranial nerves. Imaging and clinical follow-up data have been obtained in nine of 13 patients for 2 to 12 months (median 4 months) after GKS. Three pituitary and/or cavernous tumors are stable in size, and six tumors have disappeared or decreased in size; full or partial improvement of visual function, extraocular movement, and facial sensation have been achieved in these six patients.

Conclusions

These preliminary results seem to indicate that GKS is a safe and effective treatment for pituitary and cavernous metastases, as it is effective for parenchymal metastases and promptly improved some patients' symptoms.

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Yoshihisa Kida, Tatsuya Kobayashi, and Yoshimasa Mori

Object. The purpose of this paper is to report the long-term results of gamma knife radiosurgery (GKS) for low-grade astrocytomas.

Methods. Fifty-one patients with low-grade astrocytomas treated with GKS and followed for more than 24 months are reported. Of the 51 patients, 12 harbored Grade I astrocytomas in and around the visual pathways and hypothalamus. The remaining 39 harbored Grade II astrocytomas. The mean patient age at time of GKS was 9.8 years for patient with Grade I and 30.9 years for those with Grade II astrocytomas. The mean tumor diameter was 25.4 mm for Grade I and 23.7 mm for Grade II tumors. The mean margin dose was 12.5 Gy for Grade I and 15.7 Gy for Grade II tumors.

In the mean follow-up period of 27.6 months, both Grade I and Grade II astrocytomas responded well to GKS. Grade I astrocytomas had a response rate of 50% and a control rate of 91.7%. Grade II astrocytomas had a 46.2% response rate and an 87.2% control rate. Statistical analyses concerning the efficacy and related factors showed a significantly better response for patients 10 years of age or older with Grade I and those with a follow-up period of more than 24 months. Complications included radiation-induced edema in 18 (35.3%) of 51 cases, cyst formation or enlargement in five (9.8%), and transient tumor enlargement in three (5.9%).

Conclusions. Radiosurgery can play an important role in the treatment of low-grade astrocytomas, and complete cure of these tumors is expected in at least some of the cases.

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Tatsuya Kobayashi, Yoshihisa Kida, and Yoshimasa Mori

Object. The authors sought to analyze the long-term outcome of patients with Cushing disease who underwent gamma knife radiosurgery (GKS) as either an adjuvant or primary treatment.

Methods. Twenty-five patients with Cushing disease were treated by GKS and followed for more than 2.5 years (mean 5.3 years).

The overall results showed a complete response rate of 30%, a response rate of 85%, and a tumor control rate of 100%. Tumor size and radiation dose were the most important factors related to the treatment response. The complete response rate for microadenomas and small adenomas was significantly higher than that for macroadenomas. An 83.2% complete response rate was obtained using a maximum dose of more than 55 Gy and/or a margin dose of more than 40 Gy. Serum adrenocorticotropic hormone and cortisol levels were normalized in 35% of patients, decreased significantly in 60%, and decreased in 85%. Fifty-one of 85 characteristic signs and symptoms of Cushing disease improved without any side effects. The overall outcome was excellent in seven cases, good in six, fair in four, and poor in four cases; one patient died. The initial treatment was GKS in four patients, two of whom had a complete response and two of whom had a partial response. Hormone levels returned to normal in the patients in whom there was a complete response. The results in the six patients in whom Nelson syndrome was present were less favorable; the response rate was only 33%, although the control rate was 100%. Hormone levels decreased in two patients.

Conclusions. Gamma knife radiosurgery is safe and effective for the treatment of Cushing disease as an adjuvant or initial therapy when selective and accurate dose planning is performed.

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Tatsuya Kobayashi, Yoshimasa Mori, Yukio Uchiyama, Yoshihisa Kida, and Shigeru Fujitani

Object. The authors conducted a study to determine the long-term results of gamma knife surgery for residual or recurrent growth hormine (GH)—producing pituitary adenomas and to compare the results with those after treatment of other pituitary adenomas.

Methods. The series consisted of 67 patients. The mean tumor diameter was 19.2 mm and volume was 5.4 cm3. The mean maximum dose was 35.3 Gy and the mean margin dose was 18.9 Gy. The mean follow-up duration was 63.3 months (range 13–142 months).

The tumor resolution rate was 2%, the response rate 68.3%, and the control rate 100%. Growth hormone normalization (GH < 1.0 ng/ml) was found in 4.8%, nearly normal (< 2.0 ng/ml) in 11.9%, significantly decreased (< 5.0 ng/ml) in 23.8%, decreased in 21.4%, unchanged in 21.4%, and increased in 16.7%. Serum insulin-like growth factor (IGF)—1 was significantly decreased (IGF-1 < 400 ng/ml) in 40.7%, decreased in 29.6%, unchanged in 18.5%, and increased in 11.1%, which was almost parallel to the GH changes.

Conclusions. Gamma knife surgery was effective and safe for the control of tumors; however, normalization of GH and IGF-1 secretion was difficult to achieve in cases with large tumors and low-dose radiation. Gamma knife radiosurgery is thus indicated for small tumors after surgery or medication therapy when a relatively high-dose radiation is required.

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Toshinori Hasegawa, Yoshihisa Kida, Tatsuya Kobayashi, Masayuki Yoshimoto, Yoshimasa Mori, and Jun Yoshida

Object. Gamma knife surgery (GKS) has been a safe and effective treatment for vestibular schwannomas in both the short and long term, although less is known about long-term outcomes in the past 10 years. The aim of this study was to clarify long-term outcomes in patients with vestibular schwannomas treated using GKS based on techniques in place in the early 1990s.

Methods. Eighty patients harboring a vestibular schwannoma (excluding neurofibromatosis Type 2) were treated using GKS between May 1991 and December 1993. Among these, 73 patients were assessed; seven were lost to follow up. The median duration of follow up was 135 months. The mean patient age at the time of GKS was 56 years old. The mean tumor volume was 6.3 cm3, and the mean maximal and marginal radiation doses applied to the tumor were 28.4 and 14.6 Gy, respectively. Follow-up magnetic resonance images were obtained in 71 patients. Forty-eight patients demonstrated partial tumor remission, 14 had tumors that remained stable, and nine demonstrated tumor enlargement or radiation-induced edema requiring resection. Patients with larger tumors did not fare as well as those with smaller lesions. The actuarial 10-year progression-free survival rate was 87% overall, and 93% in patients with tumor volumes less than 10 cm3. No patient experienced malignant transformation.

Conclusions. Gamma knife surgery remained an effective treatment for vestibular schwannomas for longer than 10 years. Although treatment failures usually occurred within 3 years after GKS, it is necessary to continue follow up in patients to reveal delayed tumor recurrence.

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Tatsuya Kobayashi, Yoshihisa Kida, Yoshimasa Mori, and Toshinori Hasegawa

Object

The authors analyzed the long-term outcomes of gamma knife surgery (GKS) for residual or recurrent craniopharyngiomas after microsurgery and the effects of dose reduction.

Methods

A total of 107 patients with craniopharyngiomas were treated with GKS at Komaki City Hospital during the past 12 years, and 98 patients were followed up for 6 to 148 months (mean 65.5 months). The mean tumor diameter and volume were 18.8 mm and 3.5 ml, respectively. These tumors were treated with a maximal dose of 21.8 Gy and a tumor margin dose of 11.5 Gy by using a mean of 4.5 isocenters. Final overall response rates were as follows: complete response 19.4%, partial response 67.4%, tumor control 79.6%, and tumor progression 20.4%. Reducing the tumor margin dose resulted in decreased therapeutic response and increased tumor progression, although the rate of visual and pituitary function loss also decreased. Among the factors examined, age (for adults) and the nature of the tumor (cystic or mixed) were statistically significant favorable and unfavorable prognostic factors, respectively. The actuarial 5- and 10-year survival rates were 94.1 and 91%, respectively. The progression-free survival rates were 60.8 and 53.8%, respectively. Patient outcomes were reportedly excellent in 45 cases, good in 23, fair in four, and poor in three; 16 patients died. Deterioration both in vision and endocrinological functions were documented as side effects in six patients (6.1%).

Conclusions

Stereotactic GKS is safe and effective, in the long term, as an adjuvant or boost therapy for residual or recurrent craniopharyngiomas after surgical removal and has minimal side effects. New treatment strategies must be devised to manage these tumors.