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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 Toshinori Hasegawa

Object

One hundred seven cases of craniopharyngiomas were treated using gamma knife surgery (GKS) at Komaki City Hospital during the past 12 years. The authors report the long-term results obtained in 100 patients who were followed for 6 to 148 months (mean 65.5 months).

Methods

All patients underwent GKS. The mean tumor diameter and volume were 18.8 mm and 5.8 ml, respectively; lesions were treated with a maximum dose of 21.8 Gy and marginal dose of 11.5 Gy (mean isocenters 4.5). Overall tumor responses were complete in 19, partial in 44, no change in 14, and disease progression in 23, yielding a complete response rate of 19%, overall response rate of 63%, control rate of 77%, and progression rate of 23%. Considering factors such as patient age, nature of the tumor (solid, mixed, cystic), frequency of previous treatments, and tumor size, the age and nature of the tumor were significant prognostic factors.

Changes in neurological and pituitary–hypothalamic symptoms after GKS were evaluated in 91 patients. Overall improvement was demonstrated in 17 (18.7%), no change in 59 (64.8%), and deterioration in 15 (16.5%). Outcome was documented in 93 cases: excellent in 42, good in 23, fair in seven, poor in three, and dead in 18 patients.

Conclusions

Stereotactic GKS is a safe and effective treatment as an adjuvant or boost therapy for postresection residual and/or recurrent craniopharyngiomas; the effects are durable and side effects acceptable.

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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, 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.

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Yoshihisa Kida, Tatsuya Kobayashi, Jun Yoshida, Kyouzou Kato and Naoki Kageyama

✓ Therapeutic results in 17 cases of alpha-fetoprotein (AFP)-secreting tumors of the central nervous system are reported. Twelve of the patients were male and five female. The patients' ages ranged from 5 years to 25 years (mean 13.6 years). The tumors originated in the pineal region in 10 cases, in the suprasellar region in four cases, and in both regions in one case; of the other two tumors, one originated in the basal ganglia and one in the sacrococcygeal region. Extraneural metastases or subarachnoid dissemination occurred in seven cases. Increased AFP titer in the serum or cerebrospinal fluid was verified in 13 cases. The patients were divided into two groups: those treated before (Group A) and those treated after (Group B) the introduction in 1980 of cisplatin as a chemotherapeutic agent. All seven Group A patients died, even after extensive therapy consisting of surgery, radiotherapy, and chemotherapy (ACNU or adriamycin) in some of the cases. The mean survival time following diagnosis for Group A was 23.7 months. Six of the 10 Group B patients died an average of 25.8 months after diagnosis; however, the other four were still alive and well an average of 25.3 months after diagnosis. The tumors responded well to chemotherapy consisting of cisplatin either alone or combined with bleomycin and vinblastine. The initial response rate to treatment in Group B was 100% and five cases had a complete remission, verified by computerized tomography or the serum AFP level. Once the tumor recurred, the response to cisplatin was markedly decreased. It is suggested that an effective therapy must still be sought for recurrent tumors.

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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, Jun Yoshida, Junzo Ishiyama, Satoshi Noda, Akira Kito and Yoshihisa Kida

✓ Antitumor activity against intracranial malignant teratoma by combination chemotherapy with cisplatin and etoposide was evaluated in experimental and clinical studies. A human teratoma cell line (Tera 2) was exposed in vitro to cisplatin and/or etoposide, after which cell growth inhibition and alterations of deoxyribonucleic acid (DNA) histograms were observed. The results indicated that a synergistic cytotoxic effect was achieved by use of both agents in combination. Four cases of recurrent intracranial germ-cell tumor (three malignant teratomas and one germinoma) were treated with cisplatin and etoposide. With this combinationtherapy, regression of the tumor was observed in all four cases (three complete and one partial), for a total response rate of 100%. During a follow-up period of 9 to 22 months, no recurrence or progression has been noted in three of these cases.

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Tatsuya Kobayashi, Naoki Kageyama, Yoshihisa Kida, Jun Yoshida, Naoki Shibuya and Kazuhiko Okamura

✓ Clinical characteristics of six cases of germinoma involving a unilateral basal ganglion and thalamus are summarized. The incidence was estimated as 10% of all intracranial germinomas. The average age at the onset was 10.5 years. The sex incidence showed a male dominance. The clinical course was slowly progressive, and the average duration between onset and diagnosis was 2 years 5 months. Common symptoms and signs were hemiparesis in all cases, fever of unknown origin and eye symptoms in most, mental deterioration and psychiatric signs in three, and convulsions, pubertas praecox, and diabetes insipidus in two. Signs of increased intracranial pressure were found in only two cases in the later state of the disease. Early diagnosis is difficult because of nonspecific symptomatology and slow progression. Carotid angiography and pneumoencephalography showed abnormal findings compatible with basal ganglia and thalamic tumors, but not specific to germinoma. Ipsilateral cortical atrophy and ventricular dilatation might be significant findings. Radioisotope scanning was useful. Computerized tomography scans were the best method of detecting the location and nature of this tumor, and repeat scans showed response to radiation therapy.