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Toshinori Hasegawa, Yoshihisa Kida, Takenori Kato, Hiroshi Iizuka, Shunichiro Kuramitsu and Takashi Yamamoto

Object

Little is known about long-term outcomes, including tumor control and adverse radiation effects, in patients harboring vestibular schwannomas (VSs) treated with stereotactic radiosurgery > 10 years previously. The aim of this study was to confirm whether Gamma Knife surgery (GKS) for VSs continues to be safe and effective > 10 years after treatment.

Methods

A total of 440 patients with VS (including neurofibromatosis Type 2) treated with GKS between May 1991 and December 2000 were evaluable. Of these, 347 patients (79%) underwent GKS as an initial treatment and 93 (21%) had undergone prior resection. Three hundred fifty-eight patients (81%) had a solid tumor and 82 (19%) had a cystic tumor. The median tumor volume was 2.8 cm3 and the median marginal dose was 12.8 Gy.

Results

The median follow-up period was 12.5 years. The actuarial 5- and ≥ 10-year progression-free survival was 93% and 92%, respectively. No patient developed treatment failure > 10 years after treatment. According to multivariate analysis, significant factors related to worse progression-free survival included brainstem compression with a deviation of the fourth ventricle (p < 0.0001), marginal dose ≤ 13 Gy (p = 0.01), prior treatment (p = 0.02), and female sex (p = 0.02). Of 287 patients treated at a recent optimum dose of ≤ 13 Gy, 3 (1%) developed facial palsy, including 2 with transient palsy and 1 with persistent palsy after a second GKS, and 3 (1%) developed facial numbness, including 2 with transient and 1 with persistent facial numbness. The actuarial 10-year facial nerve preservation rate was 97% in the high marginal dose group (> 13 Gy) and 100% in the low marginal dose group (≤ 13 Gy). Ten patients (2.3%) developed delayed cyst formation. One patient alone developed malignant transformation, indicating an incidence of 0.3%.

Conclusions

In this study GKS was a safe and effective treatment for the majority of patients followed > 10 years after treatment. Special attention should be paid to cyst formation and malignant transformation as late adverse radiation effects, although they appeared to be rare. However, it is necessary to collect further long-term follow-up data before making conclusions about the long-term safety and efficacy of GKS, especially for young patients with VSs.

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Toshinori Hasegawa, Yoshihisa Kida, Masayuki Yoshimoto, Hiroshi Iizuka, Dai Ishii and Kouta Yoshida

Object

The aim of this study was to evaluate the outcomes in patients with convexity, parasagittal, or falcine meningiomas treated using Gamma Knife surgery (GKS) and to determine management strategy considering a risk of radiation-induced edema.

Methods

One hundred twelve patients who harbored 125 convexity, parasagittal, or falcine meningiomas were assessed. Forty-six patients underwent GKS as the initial treatment. The median tumor diameter was 25 mm, and median tumor volume was 8 cm3. The median maximum and margin doses were 30 and 16 Gy, respectively.

Results

The median follow-up period was 72 months. The actuarial 5- and 10-year progression-free survival rates were 78% and 55%, respectively. The actuarial 5- and 10-year local tumor control rates were 87% and 71%, respectively. Of 29 tumors that developed postradiosurgical edema, 7 were symptomatic. The actuarial symptomatic radiation-induced edema rate was 7%. The incidence of this complication was significantly higher in patients who underwent GKS as the initial treatment. Six of 46 patients for whom GKS was the initial treatment had preradiosurgical edema. Of these 6 patients, 4 developed severe panhemispheric edema after GKS (2 patients with parasagittal tumors, 1 with a falx tumor, and 1 with a convexity tumor).

Conclusions

Gamma Knife surgery is an effective treatment for convexity, parasagittal, and falcine meningiomas as the initial or adjuvant treatment. However, GKS should be restricted to small- to medium-sized tumors, particularly in patients with primary tumors, because radiation-induced edema is more common in convexity, parasagittal, and falcine meningiomas than skull base meningiomas.

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Toshinori Hasegawa, Yoshihisa Kida, Masayuki Yoshimoto, Joji Koike, Hiroshi Iizuka and Dai Ishii

Object

The aim of this study was to evaluate long-term outcomes, including tumor control and neurological function, in patients with cavernous sinus meningiomas treated using Gamma Knife surgery (GKS).

Methods

One hundred fifteen patients with cavernous sinus meningiomas, excluding atypical or malignant meningiomas, were treated with GKS between 1991 and 2003. Forty-nine patients (43%) underwent GKS as the initial treatment. The mean tumor volume was 14 cm3, and the mean maximum and margin doses applied to the tumor were 27 and 13 Gy, respectively. The median follow-up period was 62 months. During the follow-up, 111 patients were able to be evaluated with neuroimaging.

Results

The actuarial 5- and 10-year progression-free survival rates were 87 and 73%, respectively. Similarly, the actuarial 5- and 10-year focal tumor control rates were 94 and 92%, respectively. Regarding functional outcomes, 43 patients (46%) experienced some degree of improvement, 40 (43%) remained stable, and 11 (12%) had worse preexisting or newly developed symptoms. Patients who underwent GKS as the initial treatment experienced significant improvement of their symptoms (p = 0.006).

Conclusions

Gamma Knife surgery is a safe and effective treatment over the long term in selected patients with cavernous sinus meningiomas. Tumor progression is more likely to occur from the lesion margin outside the treatment volume. In small to medium-sized tumors, GKS is an excellent alternative to resection, preserving good neurological function. For relatively large-sized tumors, low-dose radiosurgery (≤ 12 Gy) is acceptable for the prevention of tumor progression.

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Toshinori Hasegawa, Dai Ishii, Yoshihisa Kida, Masayuki Yoshimoto, Joji Koike and Hiroshi Iizuka

Object

The purpose of this study was to evaluate radiosurgical outcomes in skull base chordomas and chondrosarcomas, and to determine which tumors are appropriate for stereotactic radiosurgery as adjuvant therapy following maximum tumor resection.

Methods

Thirty-seven patients (48 lesions) were treated using Gamma Knife surgery (GKS); 27 had chordomas, seven had chondrosarcomas, and three had radiologically diagnosed chordomas. The mean tumor volume was 20 ml, and the mean maximum and marginal doses were 28 and 14 Gy, respectively. The mean follow-up period was 97 months from diagnosis and 59 months from GKS.

Results

The actuarial 5- and 10-year survival rates after GKS were 80 and 53%, respectively. The actuarial 5- and 10-year local tumor control (LTC) rates after single or multiple GKS sessions were 76 and 67%, respectively. All patients with low-grade chondrosarcomas achieved good LTC. A tumor volume of less than 20 ml significantly affected the high rate of LTC (p = 0.0182). No patient had adverse radiation effects, other than one in whom facial numbness worsened despite successful tumor control.

Conclusions

As an adjuvant treatment after resection, GKS is a reasonable option for selected patients harboring skull base chordomas or chondrosarcomas with a residual tumor volume of less than 20 ml. Dose planning with a generous treatment volume to avoid marginal treatment failure should be made at a marginal dose of at least 15 Gy to achieve long-term tumor control.

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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.

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Masaaki Yamamoto, Yoshihisa Kida, Seiji Fukuoka, Yoshiyasu Iwai, Hidefumi Jokura, Atsuya Akabane and Toru Serizawa

Object

Gamma Knife radiosurgery (GKS) is currently used for primary or postoperative management of cavernous sinus (CS) hemangiomas. The authors describe their experience with 30 cases of CS hemangioma successfully managed with GKS.

Methods

Thirty patients with CS hemangiomas, including 19 female and 11 male patients with a mean age of 53 years (range 19–78 years) underwent GKS at 7 facilities in Japan. Pathological entity was confirmed using surgical specimens in 17 patients, and neuroimaging diagnosis only in 13. Eight patients were asymptomatic before GKS, while 22 had ocular movement disturbances and/or optic nerve impairments. The mean tumor volume was 11.5 cm3 (range 1.5–51.4 cm3). The mean dose to the tumor periphery was 13.8 Gy (range 10.0–17.0 Gy).

Results

The mean follow-up period was 53 months (range 12–138 months). Among the 22 patients with symptoms prior to GKS, complete remission was achieved in 2, improvement in 13, and no change in 7. Hemifacial sensory disturbance developed following GKS in 1 patient. The most recent MR images showed remarkable shrinkage in 18, shrinkage in 11, and no change in 1 patient.

Conclusions

Gamma Knife radiosurgery proved to be an effective treatment strategy for managing CS hemangiomas. Given the diagnostic accuracy of recently developed neuroimaging techniques and the potentially serious bleeding associated with biopsy sampling or attempted surgical removal, the authors recommend that GKS be the primary treatment in most patients who have a clear neuroimaging diagnosis of this condition.

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Toshinori Hasegawa, Takenori Kato, Yoshihisa Kida, Motohiro Hayashi, Takahiko Tsugawa, Yoshiyasu Iwai, Mitsuya Sato, Hisayo Okamoto, Tadashige Kano, Seiki Osano, Osamu Nagano and Kiyoshi Nakazaki

OBJECT

The aim of this study was to explore the efficacy and safety of stereotactic radiosurgery for patients with facial nerve schwannomas (FNSs).

METHODS

This study was a multiinstitutional retrospective analysis of 42 patients with FNSs treated with Gamma Knife surgery (GKS) at 1 of 10 medical centers of the Japan Leksell Gamma Knife Society (JLGK1301). The median age of the patients was 50 years. Twenty-nine patients underwent GKS as the initial treatment, and 13 patients had previously undergone surgery. At the time of the GKS, 33 (79%) patients had some degree of facial palsy, and 21 (50%) did not retain serviceable hearing. Thirty-five (83%) tumors were solid, and 7 (17%) had cystic components. The median tumor volume was 2.5 cm3, and the median prescription dose to the tumor margin was 12 Gy.

RESULTS

The median follow-up period was 48 months. The last follow-up images showed partial remission in 23 patients and stable tumors in 19 patients. Only 1 patient experienced tumor progression at 60 months, but repeat GKS led to tumor shrinkage. The actuarial 3- and 5-year progression-free survival rates were 100% and 92%, respectively. During the follow-up period, 8 patients presented with newly developed or worsened preexisting facial palsy. The condition was transient in 3 of these patients. At the last clinical follow-up, facial nerve function improved in 8 (19%) patients, remained stable in 29 (69%), and worsened in 5 (12%; House-Brackmann Grade III in 4 patients, Grade IV in 1 patient). With respect to hearing function, 18 (90%) of 20 evaluated patients with a pure tone average of ≤ 50 dB before treatment retained serviceable hearing.

CONCLUSIONS

GKS is a safe and effective treatment option for patients with either primary or residual FNSs. All patients, including 1 patient who required repeat GKS, achieved good tumor control at the last follow-up. The incidence of newly developed or worsened preexisting facial palsy was 12% at the last clinical follow-up. In addition, the risk of hearing deterioration as an adverse effect of radiation was low. These results suggest that GKS is a safe alternative to resection.

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Toshinori Hasegawa, Takenori Kato, Yoshihisa Kida, Ayaka Sasaki, Yoshiyasu Iwai, Takeshi Kondoh, Takahiko Tsugawa, Manabu Sato, Mitsuya Sato, Osamu Nagano, Kotaro Nakaya, Kiyoshi Nakazaki, Tadashige Kano, Koichi Hasui, Yasushi Nagatomo, Soichiro Yasuda, Akihito Moriki, Toru Serizawa, Seiki Osano and Akira Inoue

OBJECTIVE

This study aimed to explore the efficacy and safety of stereotactic radiosurgery in patients with jugular foramen schwannomas (JFSs).

METHODS

This study was a multiinstitutional retrospective analysis of 117 patients with JFSs who were treated with Gamma Knife surgery (GKS) at 18 medical centers of the Japan Leksell Gamma Knife Society. The median age of the patients was 53 years. Fifty-six patients underwent GKS as their initial treatment, while 61 patients had previously undergone resection. At the time of GKS, 46 patients (39%) had hoarseness, 45 (38%) had hearing disturbances, and 43 (36%) had swallowing disturbances. Eighty-five tumors (73%) were solid, and 32 (27%) had cystic components. The median tumor volume was 4.9 cm3, and the median prescription dose administered to the tumor margin was 12 Gy. Five patients were treated with fractionated GKS and maximum and marginal doses of 42 and 21 Gy, respectively, using a 3-fraction schedule.

RESULTS

The median follow-up period was 52 months. The last follow-up images showed partial remission in 62 patients (53%), stable tumors in 42 patients (36%), and tumor progression in 13 patients (11%). The actuarial 3- and 5-year progression-free survival (PFS) rates were 91% and 89%, respectively. The multivariate analysis showed that pre-GKS brainstem edema and dumbbell-shaped tumors significantly affected PFS. During the follow-up period, 20 patients (17%) developed some degree of symptomatic deterioration. This condition was transient in 12 (10%) of these patients and persistent in 8 patients (7%). The cause of the persistent deterioration was tumor progression in 4 patients (3%) and adverse radiation effects in 4 patients (3%), including 2 patients with hearing deterioration, 1 patient with swallowing disturbance, and 1 patient with hearing deterioration and hypoglossal nerve palsy. However, the preexisting hoarseness and swallowing disturbances improved in 66% and 63% of the patients, respectively.

CONCLUSIONS

GKS resulted in good tumor control in patients with either primary or residual JFSs. Although some patients experienced some degree of symptomatic deterioration after treatment, persistent adverse radiation effects were seen in only 3% of the entire series at the last follow-up. Lower cranial nerve deficits were extremely rare adverse radiation effects, and preexisting hoarseness and swallowing disturbances improved in two-thirds of patients. These results indicated that GKS was a safe and reasonable alternative to surgical resection in selected patients with JFSs.