Katsuta Hospital Mito GammaHouse

Hitachi-Naka, Japan

Katsuta Hospital Mito GammaHouse

Hitachi-Naka, Japan
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Yamamoto M.,Katsuta Hospital Mito GammaHouse | Kida Y.,Komaki City Hospital | Fukuoka S.,Nakamura Memorial Hospital | Iwai Y.,Osaka City General Hospital | And 3 more authors.
Journal of Neurosurgery | Year: 2010

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.


Yamamoto M.,Katsuta Hospital Mito GammaHouse | Yamamoto M.,Tokyo Women's Medical University | Kawabe T.,Katsuta Hospital Mito GammaHouse | Kawabe T.,Kyoto Prefectural University of Medicine | And 6 more authors.
Journal of Neurosurgery | Year: 2013

Object. Although stereotactic radiosurgery (SRS) alone for patients with 4-5 or more tumors is not a standard treatment, a trend for patients with 5 or more tumors to undergo SRS alone is already apparent. The authors' aim in the present study was to reappraise whether SRS results for ≥ 5 tumors differ from those for 1-4 tumors. Methods. This institutional review board-approved retrospective cohort study used the authors' database of prospectively accumulated data that included 2553 consecutive patients who underwent SRS, not in combination with concurrent whole-brain radiotherapy, for brain metastases (METs) between 1998 and 2011. These 2553 patients were divided into 2 groups: 1553 with tumor numbers of 1-4 (Group A) and 1000 with ≥ 5 tumors (Group B). Because there was considerable bias in pre-SRS clinical factors between Groups A and B, a case-matched study was conducted. Ultimately, 1096 patients (548 each in Groups A and B) were selected. The standard Kaplan-Meier method was used to determine post-SRS survival and the post-SRS neurological death-free survival times. Competing risk analysis was applied to estimate cumulative incidences of local recurrence, repeat SRS for new lesions, neurological deterioration, and SRS-induced complications. Results. The post-SRS median survival time was significantly longer in the 548 Group A patients (7.9 months, 95% CI 7.0-8.9 months) than in the 548 Group B patients (7.0 months 95% [CI 6.2-7.8 months], HR 1.176 [95% CI 1.039-1.331], p = 0.01). However, incidences of neurological death were very similar: 10.6% in Group A and 8.2% in Group B (p = 0.21). There was no significant difference between the groups in neurological death-free survival intervals (HR 0.945, 95% CI 0.636-1.394, p = 0.77). Furthermore, competing risk analyses showed that there were no significant differences between the groups in cumulative incidences of local recurrence (HR 0.577, 95% CI 0.312-1.069, p = 0.08), repeat SRS (HR 1.133, 95% CI 0.910-1.409, p = 0.26), neurological deterioration (HR 1.868, 95% CI 0.608-1.240, p = 0.44), and major SRS-related complications (HR 1.105, 95% CI 0.490-2.496, p = 0.81). In the authors' cohort, age ≤ 65 years, female sex, a Karnofsky Performance Scale score ≥ 80%, cumulative tumor volume ≤ 10 cm3, controlled primary cancer, no extracerebral METs, and neurologically asymptomatic status were significant factors favoring longer survival equally in both groups. Conclusions. This retrospective study suggests that increased tumor number is an unfavorable factor for longer survival. However, the post-SRS median survival time difference, 0.9 months, between the two groups is not clinically meaningful. Furthermore, patients with 5 or more METs have noninferior results compared to patients with 1-4 tumors, in terms of neurological death, local recurrence, repeat SRS, maintenance of good neurological state, and SRS-related complications. A randomized controlled trial should be conducted to test this hypothesis. © AANS, 2013.


Yamamoto M.,Katsuta Hospital Mito GammaHouse | Yamamoto M.,Tokyo Women's Medical University | Sato Y.,Chiba University | Serizawa T.,Tokyo Gamma Unit Center | And 8 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2012

Purpose: Although the recursive partitioning analysis (RPA) class is generally used for predicting survival periods of patients with brain metastases (METs), the majority of such patients are Class II and clinical factors vary quite widely within this category. This prompted us to divide RPA Class II patients into three subclasses. Methods and Materials: This was a two-institution, institutional review board-approved, retrospective cohort study using two databases: the Mito series (2,000 consecutive patients, comprising 787 women and 1,213 men; mean age, 65 years [range, 19-96 years]) and the Chiba series (1,753 patients, comprising 673 female and 1,080 male patients; mean age, 65 years [range, 7-94 years]). Both patient series underwent Gamma Knife radiosurgery alone, without whole-brain radiotherapy, for brain METs during the same 10-year period, July 1998 through June 2008. The Cox proportional hazard model with a step-wise selection procedure was used for multivariate analysis. Results: In the Mito series, four factors were identified as favoring longer survival: Karnofsky Performance Status (90% to 100% vs. 70% to 80%), tumor numbers (solitary vs. multiple), primary tumor status (controlled vs. not controlled), and non-brain METs (no vs. yes). This new index is the sum of scores (0 and 1) of these four factors: RPA Class II-a, score of 0 or 1; RPA Class II-b, score of 2; and RPA Class II-c, score of 3 or 4. Next, using the Chiba series, we tested whether our index is valid for a different patient group. This new system showed highly statistically significant differences among subclasses in both the Mito series and the Chiba series (p < 0.001 for all subclasses). In addition, this new index was confirmed to be applicable to Class II patients with four major primary tumor sites, that is, lung, breast, alimentary tract, and urogenital organs. Conclusions: Our new grading system should be considered when designing future clinical trials involving brain MET patients. © 2012 Elsevier Inc. All rights reserved.


Yamamoto M.,Katsuta Hospital Mito GammaHouse | Yamamoto M.,Tokyo Women's Medical University | Kawabe T.,Katsuta Hospital Mito GammaHouse | Kawabe T.,Kyoto Prefectural University of Medicine | And 6 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2013

Purpose: Little is known about delayed complications after stereotactic radiosurgery in long-surviving patients with brain metastases. We studied the actual incidence and predictors of delayed complications. Patients and Methods: This was an institutional review board-approved, retrospective cohort study that used our database. Among our consecutive series of 2000 patients with brain metastases who underwent Gamma Knife radiosurgery (GKRS) from 1991-2008, 167 patients (8.4%, 89 women, 78 men, mean age 62 years [range, 19-88 years]) who survived at least 3 years after GKRS were studied. Results: Among the 167 patients, 17 (10.2%, 18 lesions) experienced delayed complications (mass lesions with or without cyst in 8, cyst alone in 8, edema in 2) occurring 24.0-121.0 months (median, 57.5 months) after GKRS. The actuarial incidences of delayed complications estimated by competing risk analysis were 4.2% and 21.2% at the 60th month and 120th month, respectively, after GKRS. Among various pre-GKRS clinical factors, univariate analysis demonstrated tumor volume-related factors: largest tumor volume (hazard ratio [HR], 1.091; 95% confidence interval [CI], 1.018-1.154; P=.0174) and tumor volume ≤10 cc vs >10 cc (HR, 4.343; 95% CI, 1.444-12.14; P=.0108) to be the only significant predictors of delayed complications. Univariate analysis revealed no correlations between delayed complications and radiosurgical parameters (ie, radiosurgical doses, conformity and gradient indexes, and brain volumes receiving >5 Gy and >12 Gy). After GKRS, an area of prolonged enhancement at the irradiated lesion was shown to be a possible risk factor for the development of delayed complications (HR, 8.751; 95% CI, 1.785-157.9; P=.0037). Neurosurgical interventions were performed in 13 patients (14 lesions) and mass removal for 6 lesions and Ommaya reservoir placement for the other 8. The results were favorable. Conclusions: Long-term follow-up is crucial for patients with brain metastases treated with GKRS because the risk of complications long after treatment is not insignificant. However, even when delayed complications occur, favorable outcomes can be expected with timely neurosurgical intervention. © 2013 Elsevier Inc.


Tamura K.,Tokyo Medical and Dental University | Aoyagi M.,Tokyo Medical and Dental University | Wakimoto H.,Tokyo Medical and Dental University | Ando N.,Tokyo Medical and Dental University | And 4 more authors.
Journal of Neurosurgery | Year: 2010

Object. Recent evidence suggests that a glioma stem cell subpopulation might contribute to radioresistance in malignant gliomas. To investigate this hypothesis, the authors examined recurrent malignant gliomas for histopathological changes after high-dose irradiation with Gamma Knife surgery (GKS) and external beam radiation therapy (EBRT). Methods. Thirty-two patients with malignant gliomas (Grade 3 in 8 patients, Grade 4 in 24) underwent GKS in combination with EBRT. Serial MR and L-[methyl-11C] methionine PET images were employed to assess remnant or recurrent tumors after GKS. Twelve patients underwent surgical removal after GKS and EBRT. Histological sections were subjected to immunohistochemistry for MIB-1, factor VIII, and stem cell markers, nestin and CD133. Results. The site of GKS treatment failure was local in 16 (76.2%) of 21 patients with glioblastomas showing progression; in 9 of these 16 patients, the recurrence clearly arose within the target lesion of GKS. Histopathological examination after GKS and EBRT showed variable mixtures of viable tumor tissues and necrosis. Viable tumor tissues exhibited high MIB-1 indices but reduced numbers of tumor blood vessels. There was marked accumulation of CD133-positive glioma cells, particularly in remnant tumors within the necrotic areas, in sections obtained after GKS plus EBRT, whereas CD133-positive cells appeared very infrequently in primary sections prior to adjuvant treatment. Conclusions. The results indicate that CD133-positive glioma stemlike cells can survive high-dose irradiation, leading to recurrence, despite prolonged damage to tumor blood vessels. This could be an essential factor limiting the effectiveness of GKS plus EBRT for malignant gliomas.


PubMed | St. Elizabeth Ziekenhuis, Katsuta Hospital Mito GammaHouse, National University Hospital Singapore, Karolinska University Hospital and West Virginia University
Type: | Journal: World neurosurgery | Year: 2016

To assess if modern management of extracranial malignant diseases has prolonged the survival times for patients with more than 2 brain metastases (BM).Data from 2385 patients treated with Gamma Knife surgery (GKS) for 3 BM between 1982 and 2011 were retrospectively analyzed. The patients were divided into 6 groups based on the treatment year and the median and 10% survival times were compared with the median and mean treatment dates in each group.The later the treatment date, the longer the median as well as the 10% survival times. The relation between the median treatment date and both the 10% and median survival times could be accurately expressed by a linear as well as an exponential curve fit. The median and 10% survival times increased by around 80% and 150%, respectively, between 1990 and2010.Both the median and 10% survival times have increased in recent years among patients with more than 2 BM treated with GKS. Both linear and exponential regressions accurately expressed the increase in both median and 10% survival times during the years 1990-2010. Findings from other published data support the observation of longer survival times among patients treated more recently, independent of the patients being treated with GKS or with whole-brain radiation therapy with or without radiosurgery. Thus, earlier findings of short survival times for patients with multiple BM are no longer valid, at least not for patients deemed suitable for radiosurgery. Aggressive management is thus warranted for these patients.


Little information is available on staged Gamma Knife surgery (GKS) with an interval of 3 years or more when used to treat arteriovenous malformations (AVMs) with volumes larger than 10 cm(3). The goal of this study was to increase knowledge in this area by reporting the authors' experience. The authors describe an institutional review board-approved retrospective study in which they examined databases including information on 250 patients who consecutively underwent GKS for cerebral AVMs during a 16-year period (1988-2004). Among the 250 patients the authors identified 31 patients (12.4%, 15 female and 16 male patients with a mean age of 29 years [range 10-63 years]) in whom 2-stage GKS was intentionally planned at the time of initial treatment because the volume of the AVM nidus was larger than 10 cm(3). The most common presentation was bleeding (14 patients), followed by seizures (9 patients), incidental findings (7 patients), and headache with scintillation (1 patient). One patient underwent GKS for the treatment of 2 AVMs simultaneously, and thus 32 AVMs are included in this study. The mean nidus volume was 16.2 cm(3) (maximum 55.8 cm(3)). In all 31 patients, relatively low radiation doses (12-16 Gy directed at the periphery of the lesion) were intentionally used for the first GKS. The second GKS was scheduled for at least 36 months after the first. Complete nidus obliteration was obtained after the first GKS in 1 patient. To date, 26 patients have undergone a second procedure with a post-GKS mean interval of 41 months (range 24-83 months); 2 other patients refused to undergo the second GKS, and no further treatment was given because of severe morbidity in 1 case and death due to bleeding in the other case. Among the 26 patients who did undergo a second procedure, 3 patients refused follow-up digital subtraction (DS) angiography, another is scheduled for follow-up DS angiography, and 2 patients died, one of bleeding and the other of an unknown cause. The remaining 20 patients underwent follow-up DS angiography. Complete nidus obliteration was confirmed in 13 patients (65.0%) and remarkable nidus shrinkage in the other 7 patients (35.0%). In 2 of these 7 patients, a third GKS achieved complete nidus obliteration. Therefore, the cumulative complete obliteration rate in this series was 76.2% (16 of 21 eligible patients). Seven patients (22.6%) experienced bleeding. The bleeding rates were 9.7%, 16.1%, 16.1%, and 26.1%, respectively, at 1, 2, 5, and 10 years post-GKS. There were 2 deaths and 3 cases of morbidity (persistent coma, mild hemimotor weakness, and hemianopsia in 1 patient each). Hemorrhage did not produce neurological deficits in the other 2 patients. During the mean post-GKS follow-up period of 105 months (range 42-229 months) to date, mild symptomatic GKS-related complications occurred in 2 patients (6.5%); these were classified as Radiation Oncology Group Neurotoxicity Grade 1 in 1 patient and Grade 2 in the other. Among various pre-GKS clinical factors, univariate analysis showed only patient age to impact complications (hazard ratio 0.675, 95% CI 0.306-0.942, p = 0.0085). The rate of complications in the pediatric cases was 33.3%, whereas that in the adolescent and adult cases was 0% (p = 0.0323). Although a final conclusion awaits further studies and patient follow-up, these results suggest 2-stage GKS to be beneficial even for relatively large AVMs.


Tamura K.,Tokyo Medical and Dental University | Aoyagi M.,Tokyo Medical and Dental University | Ando N.,Tokyo Medical and Dental University | Ogishimao T.,Tokyo Medical and Dental University | And 3 more authors.
Journal of Neurosurgery | Year: 2013

Object: Recent evidence suggests that a glioma stem cell subpopulation may determine the biological behavior of tumors, including resistance to therapy. To investigate this hypothesis, the authors examined varying grades of gliomas for stem cell marker expressions and histopathological changes between primary and recurrent tumors. Methods: Tumor samples were collected during surgery from 70 patients with varying grades of gliomas (Grade II in 12 patients, Grade III in 16, and Grade IV in 42) prior to any adjuvant treatment. The samples were subjected to immunohistochemistry for MIB-1, factor VIII, GFAP, and stem cell markers (CD133 and nestin). Histopathological changes were compared between primary and recurrent tumors in 31 patients after radiation treatment and chemotherapy, including high-dose irradiation with additional stereotactic radiosurgery. Results: CD133 expression on glioma cells was confined to de novo glioblastomas but was not observed in lower-grade gliomas. In de novo glioblastomas, the mean percentage of CD133-positive glioma cells in sections obtained at recurrence was 12.2% ± 10.3%, which was significantly higher than that obtained at the primary surgery (1.08% ± 1.78%). CD133 and Ki 67 dual-positive glioma cells were significantly increased in recurrent de novo glioblastomas as compared with those in primary tumors (14.5% ± 6.67% vs 2.16% ± 2.60%, respectively). In contrast, secondary glioblastomas rarely expressed CD133 antigen even after malignant progression following radiotherapy and chemotherapy. Conclusions: The authors' results indicate that CD133-positive glioma stem cells could survive, change to a proliferative cancer stem cell phenotype, and cause recurrence in cases with de novo glioblastomas after radiotherapy and chemotherapy. © AANS, 2013.


Yamamoto M.,Katsuta Hospital Mito GammaHouse | Kawabe T.,Katsuta Hospital Mito GammaHouse | Sato Y.,Katsuta Hospital Mito GammaHouse | Higuchi Y.,Katsuta Hospital Mito GammaHouse | And 3 more authors.
Journal of neurosurgery | Year: 2014

OBJECT: Although stereotactic radiosurgery (SRS) alone is not a standard treatment for patients with 4-5 tumors or more, a recent trend has been for patients with 5 or more, or even 10 or more, tumors to undergo SRS alone. The aim of this study was to reappraise whether the treatment results for SRS alone for patients with 10 or more tumors differ from those for patients with 2-9 tumors.METHODS: This was an institutional review board-approved, retrospective cohort study that gathered data from the Katsuta Hospital Mito GammaHouse prospectively accumulated database. Data were collected for 2553 patients who consecutively had undergone Gamma Knife SRS alone, without whole-brain radiotherapy (WBRT), for newly diagnosed (mostly) or recurrent (uncommonly) brain metastases during 1998-2011. Of these 2553 patients, 739 (28.9%) with a single tumor were excluded, leaving 1814 with multiple metastases in the study. These 1814 patients were divided into 2 groups: those with 2-9 tumors (Group A, 1254 patients) and those with 10 or more tumors (Group B, 560 patients). Because of considerable bias in pre-SRS clinical factors between groups A and B, a case-matched study, which used the propensity score matching method, was conducted for clinical factors (i.e., age, sex, primary tumor state, extracerebral metastases, Karnofsky Performance Status, neurological symptoms, prior procedures [surgery and WBRT], volume of the largest tumor, and peripheral doses). Ultimately, 720 patients (360 in each group) were selected. The standard Kaplan-Meier method was used to determine post-SRS survival times and post-SRS neurological death-free survival times. Competing risk analysis was applied to estimate cumulative incidence for local recurrence, repeat SRS for new lesions, neurological deterioration, and SRS-induced complications.RESULTS: Post-SRS median survival times did not differ significantly between the 2 groups (6.8 months for Group A vs 6.0 months for Group B; hazard ratio [HR] 1.133, 95% CI 0.974-1.319, p = 0.10). Furthermore, rates of neurological death were very similar: 10.0% for group A and 9.4% for group B (p = 0.89); neurological death-free survival times did not differ significantly between the 2 groups (HR 1.073, 95% CI 0.649-1.771, p = 0.78). The cumulative incidence of local recurrence (HR 0.425, 95% CI 0.0.181-0.990, p = 0.04) and repeat SRS for new lesions (HR 0.732, 95% CI 0.554-0.870, p = 0.03) were significantly lower for Group B than for Group A patients. No significant differences between the groups were found for cumulative incidence for neurological deterioration (HR 0.994, 95% CI 0.607-1.469, p = 0.80) or SRS-related complications (HR 0.541, 95% CI 0.138-2.112, p = 0.38).CONCLUSIONS: Post-SRS treatment results (i.e., median survival time; neurological death-free survival times; and cumulative incidence for local recurrence, repeat SRS for new lesions, neurological deterioration, and SRS-related complications) were not inferior (neither less effective nor less safe) for patients in Group B than for those in Group A. We conclude that carefully selected patients with 10 or more tumors are not unfavorable candidates for SRS alone. A randomized controlled trial should be conducted to test this hypothesis.


Kawabe T.,Katsuta Hospital Mito GammaHouse
Journal of neurosurgery | Year: 2012

Because brainstem metastases are not deemed resectable, stereotactic radiosurgery (SRS) is the only treatment modality expected to achieve a radical cure. The authors describe their treatment results, focusing particularly on how long patients can survive without neurological deterioration following SRS for brainstem metastases. This was an institutional review board-approved, retrospective cohort study in which the authors pulled from their database information on 2553 consecutive patients with brain metastases who underwent Gamma Knife surgery (GKS) at the Mito GammaHouse between July 1998 and July 2011. Among the 2553 patients, excluding cases in which there was meningeal dissemination, 200 cases of brainstem metastases (78 women and 122 men with a mean age of 64 years [range 36-86 years]) were identified and analyzed. The most common primary site was the lung (137 patients) followed by the gastrointestinal tract (24 patients), breast (17 patients), kidney (12 patients), and others (10 patients). Among the 200 patients, 15 patients (7.5%) harbored at least 2 tumors in the brainstem: 11 patients had 2 tumors, 2 patients had 3 tumors, and 1 patient each had 4 or 5 tumors. Therefore, a total of 222 tumors were irradiated. These 222 tumors were located in the pons (121 lesions), the midbrain (65 lesions), and the medulla oblongata (36 lesions). The mean and median tumor volumes were 1.3 and 0.2 cm(3) (range 0.005-10.7 cm(3)), and the median peripheral radiation dose was 18.0 Gy (range 12.0-25.0 Gy). The overall median survival time (MST) was 6.0 months. Distribution of MSTs across Recursive Partitioning Analysis (RPA) classes showed that the MSTs were 9.4 months in Class I (20 patients), 6.0 months in Class II (171 patients), and 1.9 months in Class III (9 patients). Better Karnofsky Performance Scale score, single metastasis, and well-controlled primary tumor were significant predictive factors for longer survival. The neurological and qualitative survival rates were 90.8% and 89.2%, respectively, at 24 months post-GKS. Better KPS score and smaller tumor volume tended to be associated with prolonged qualitative survival. Follow-up imaging studies were available for 129 patients (64.5%). The tumor control rate was 81.8% at 24 months post-GKS. Smaller tumor volume tended to contribute to tumor control. The present results indicate that GKS is effective in the treatment of brainstem metastases, particularly from the viewpoint of maintaining a good neurological condition in the patient.

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