Shigeo Matsunaga

Gamma knife radiosurgery for intracranial haemangioblastomas

SummaryBackground. The results of gamma knife radiosurgery for haemangioblastomas were retrospectively studied to assess the efficacy for tumour growth control and clarify the clinical indications for gamma knife radiosurgery in these tumours. Methods. The medical records of 22 patients with 67 tumours, 12 men and 10 women aged 20–73 years (mean 51.9 years), who underwent gamma knife radiosurgery for haemangioblastomas between January 1993 and January 2006, were retrospectively reviewed. Ten patients with 54 lesions had von Hippel-Lindau disease. The mean tumour volume was 1.69 cm3 (range 0.0097–16.4 cm3). Nineteen patients had undergone 1–4 open surgery procedures (mean 1.5) before gamma knife radiosurgery. Tumours without a cystic component, (the solid type), were found in 54 lesions and tumours associated with cyst, (the mural nodule with cyst type), in 13 lesions. The marginal dose was 8–30 Gy (mean 14.0 Gy). Findings. Follow-up magnetic resonance (MR) imaging was performed at 9–146 months (mean 63 months). The control rate for tumour growth was 83.6%. The only factor affecting tumour growth control was the presence of a cystic component at the time of gamma knife radiosurgery in both univariate and multivariate analysis. No complication such as radiation-induced peritumoural oedema or radiation necrosis occurred. Conclusion. The presence of cystic components at the time of gamma knife radiosurgery was the only factor significantly correlated with unfavourable tumour growth control by gamma knife radiosurgery for haemangioblastomas. Gamma knife radiosurgery is effective for solid type tumours, even if the marginal dose is relatively low. Surgical removal is recommended for mural nodule with cyst type tumours, when possible.

Gamma Knife surgery for metastatic brain tumors from primary breast cancer: treatment indication based on number of tumors and breast cancer phenotype

OBJECT The goal of this study was to analyze prognostic factors for local tumor control and survival and indications for initial treatment with the Gamma Knife in patients with up to 10 metastatic brain tumors from primary breast cancer. METHODS Outcomes were retrospectively reviewed in 101 women with a total of 600 tumors, who underwent Gamma Knife surgery (GKS) for metastatic brain tumors between April 1992 and December 2008 at 1 institution. The inclusion criteria were up to 10 brain metastases, maximum diameter of tumor < 3 cm, and total tumor volume < 15 cm(3). The exclusion criteria were poor systemic condition, presence of carcinomatous meningitis, and previous whole brain radiation treatment and/or craniotomy. RESULTS The mean tumor volume at GKS was 3.7 cm(3) (range 0.016-14.3 cm(3)). The mean margin dose was 19 Gy (range 8-30 Gy). Neuroimaging showed that the local tumor growth control rate was 97%, and the tumor response rate was 82.3%. Larger tumor volume (p = 0.001) and lower margin dose (p = 0.001) were significant adverse prognostic factors for local tumor growth control according to a multivariate analysis. The number of brain metastatic lesions was 4 or fewer in 76 patients and 5 or more in 25 patients. The median overall survival time was 13 months. Multivariate analysis revealed that the presence of extracranial metastases (p = 0.041) and lesions that were not the human epidermal growth factor receptor-2 (HER2)-positive type (p = 0.001) were significant adverse prognostic factors for overall survival. The number of brain metastases was not statistically significant, except for a single metastasis. The median new lesion-free survival time after initial GKS was 9 months. Five or more lesions at initial GKS (p = 0.007) and younger patient age (p = 0.008) reduced survival significantly. The prevention of neurological death after GKS was 93.9% at 1 year, and a lower Karnofsky Performance Scale score (p = 0.009) was the only unfavorable factor. Median overall survival associated with the HER2-positive phenotype was significantly longer than survival associated with the other phenotypes (luminal and triple-negative). There were no statistically significant differences between the 3 breast cancer phenotypes for the incidence of new brain metastases after initial GKS. CONCLUSIONS Initial GKS resulted in excellent local tumor control rates, which were associated with prolonged survival and a low risk of neurological death for patients with up to 10 metastatic brain tumors from primary breast cancer. The authors recommend periodic clinical and neuroradiological follow-up examinations after GKS in patients with 5 or more lesions at initial GKS, because they carry a high risk of development of new brain metastases, and in patients with the HER2-positive phenotype, because they tend to have a favorable prognosis in overall survival. Last, the authors recommend additional GKS or whole-brain radiation treatment for salvage treatment if new brain metastases occur.

Proposed mechanism for cyst formation and enlargement following Gamma Knife Surgery for arteriovenous malformations.

OBJECT The authors retrospectively studied the mechanism of cyst formation and enlargement after Gamma Knife surgery (GKS) for arteriovenous malformations (AVMs). METHODS Eighteen patients in whom cyst formation developed following GKS for AVM were retrospectively identified among 775 patients who underwent GKS for AVM at Yokohama Rosai Hospital. The study group was composed of 12 male and 6 female patients ranging in age from 17 to 47 years. RESULTS Chronic encapsulated expanding hematoma was associated with the cyst in 5 patients. The AVM nidus volume at the time of GKS ranged from 1.9 to 36 cm(3), and the prescription radiation dose was 18-25 Gy. Complete obliteration of the AVM nidus was obtained in 13 patients and partial obliteration in 5 patients. Cyst formation was detected between 2.6 and 15 years after GKS. Craniotomy was performed in 10 patients, including 2 patients in whom the incompletely obliterated nidus was removed at the same time, and an Ommaya reservoir was placed in 2 patients. Spontaneous regression of the cyst was observed in 1 patient. Serial MR imaging was performed in the other patients because the size of the cyst was stable or the lesion was asymptomatic. Histological examination of the cyst wall revealed linear hemosiderin deposits with gliosis. The nodular lesion, which was enhanced on MR images, contained granulation tissue with chronic hemorrhage from newly developed capillary vessels. CONCLUSIONS Cysts developing after GKS for AVM enlarge mainly due to repeated minor hemorrhages from a reddish nodular angiomatous lesion that develops within an adjacent brain area. Thus, the optimal treatment is wide opening of the cyst with removal of the associated angiomatous lesion by craniotomy.

Microsurgery for vestibular schwannoma after gamma knife radiosurgery

SummaryBackground. We evaluated the clinical characteristics of microsurgery for vestibular schwannoma (VS) after failed gamma knife radiosurgery (GKS). Method. Twelve patients, 5 men and 7 women aged 19 to 70 years (mean 54.5 years), who underwent microsurgery after failed GKS for VS were studied retrospectively. Findings. The median interval between GKS and microsurgery was 28.8 months (range, 6.6–120 months) and 4 patients had undergone previous microsurgery. The mean volume of tumour at GKS was 6.9 cm3 (range, 0.5–19.7 cm3) and the mean prescription dose to the tumour margin was 12.3 Gy. Microsurgery involved the lateral suboccipital approach in all patients. Tumour expansion involved solid enlargement in 7 patients, cystic enlargement in 3, and central necrosis in 2.Bleeding was slight in all patients except in one, probably because of the previous irradiation. Adhesion to the brain stem was severe in 7 patients. Identification of the facial nerve was easy in 5 operations and difficult in 7. Dissection of the tumour from the facial nerve was difficult in most interventions because of severe adhesions or colour change. Severe adhesions between the trigeminal nerve and the tumour was observed in 2 patients. The tumour was subtotally removed except around the internal auditory canal in most patients. Only one residual tumour increased in size and needed second GKS. The function of the facial nerve deteriorated in 3 patients, was unchanged in 7, and improved in 2. All patients had lost hearing on the affected side at the time of microsurgery. Conclusions. Microsurgery for VS after failed GKS presents some technical difficulties. Dissection of the tumour from the facial nerve or brain stem is likely to be difficult. We recommend subtotal resection without dissection of the facial nerve and tumour, because growth of the residual tumour was rare in our series.

Gamma Knife surgery for brain metastases from colorectal cancer: Clinical article

OBJECT The outcomes after Gamma Knife surgery (GKS) were retrospectively analyzed in patients with brain metastases from radioresistant primary colorectal cancer to evaluate the efficacy of GKS and the prognostic factors for local tumor control and overall survival. METHODS The authors reviewed the medical records of 152 patients with 616 tumors. The group included 102 men and 50 women aged 35-85 years (mean age 64.4 years), who underwent GKS for metastatic brain tumors from colorectal cancer between April 1992 and September 2008 at Yokohama Rosai Hospital. RESULTS The mean prescription dose to the tumor margin was 18.5 Gy (range 8-30 Gy). The mean tumor volume at GKS was 2.0 cm(3) (range 0.004-10.0 cm(3)). The primary tumors were located in the colon in 88 patients and the rectum in 64. The median interval between the diagnosis of primary lesions and the diagnosis of brain metastases was 27 months (range 0-180 months). The median neuroradiological follow-up period after GKS was 3 months (mean 6.4 months, range 1-93 months). The local tumor growth control rate, based on MR imaging, was 91.2%. The significant factors for unfavorable local tumor growth control, based on multivariate analysis, were larger tumor volume (p = 0.001) and lower margin dose (p = 0.016). The median overall survival time was 6 months. Lower Karnofsky Performance Scale (KPS) score (p = 0.026) and the presence of extracranial metastases (p = 0.004) at first GKS were significantly correlated with poor overall survival period in multivariate analysis. The cause of death was systemic disease in 112 patients and neurological disease in 13 patients. Leptomeningeal carcinomatosis was significantly correlated with a shorter duration of neurological survival in multivariate analysis (p < 0.0001). CONCLUSIONS Gamma Knife surgery is effective for suppression of local tumor growth in patients with brain metastases from radioresistant colorectal primary cancer. Therefore, clinical and radiological screening of intracranial metastases for patients with lower KPS scores and/or the presence of extracranial metastases as well as follow-up examinations after GKS for brain metastases should be performed periodically in patients with colorectal cancer, because the neurological prognosis is improved by initial and repeat GKS for newly diagnosed or recurrent tumors leading to a prolonged high-quality survival period.

Differentiation of Brain Tumor Recurrence from Post-Radiotherapy Necrosis with 11C-Methionine PET: Visual Assessment versus Quantitative Assessment

Purpose The aim of this multi-center study was to assess the diagnostic capability of visual assessment in L-methyl-11C-methionine positron emission tomography (MET-PET) for differentiating a recurrent brain tumor from radiation-induced necrosis after radiotherapy, and to compare it to the accuracy of quantitative analysis. Methods A total of 73 brain lesions (glioma: 31, brain metastasis: 42) in 70 patients who underwent MET-PET were included in this study. Visual analysis was performed by comparison of MET uptake in the brain lesion with MET uptake in one of four regions (around the lesion, contralateral frontal lobe, contralateral area, and contralateral cerebellar cortex). The concordance rate and logistic regression analysis were used to evaluate the diagnostic ability of visual assessment. Receiver-operating characteristic curve analysis was used to compare visual assessment with quantitative assessment based on the lesion-to-normal (L/N) ratio of MET uptake. Results Interobserver and intraobserver κ-values were highest at 0.657 and 0.714, respectively, when assessing MET uptake in the lesion compared to that in the contralateral cerebellar cortex. Logistic regression analysis showed that assessing MET uptake in the contralateral cerebellar cortex with brain metastasis was significantly related to the final result. The highest area under the receiver-operating characteristic curve (AUC) with visual assessment for brain metastasis was 0.85, showing no statistically significant difference with L/Nmax of the contralateral brain (AUC = 0.89) or with L/Nmean of the contralateral cerebellar cortex (AUC = 0.89), which were the areas that were the highest in the quantitative assessment. For evaluation of gliomas, no specific candidate was confirmed among the four areas used in visual assessment, and no significant difference was seen between visual assessment and quantitative assessment. Conclusion The visual assessment showed no significant difference from quantitative assessment of MET-PET with a relevant cut-off value for the differentiation of recurrent brain tumors from radiation-induced necrosis.

Semiquantitative analysis using thallium-201 SPECT for differential diagnosis between tumor recurrence and radiation necrosis after gamma knife surgery for malignant brain tumors.

PURPOSE Semiquantitative analysis of thallium-201 chloride single photon emission computed tomography (201Tl SPECT) was evaluated for the discrimination between recurrent brain tumor and delayed radiation necrosis after gamma knife surgery (GKS) for metastatic brain tumors and high-grade gliomas. METHODS AND MATERIALS The medical records were reviewed of 75 patients, including 48 patients with metastatic brain tumor and 27 patients with high-grade glioma who underwent GKS in our institution, and had suspected tumor recurrence or radiation necrosis on follow-up neuroimaging and deteriorating clinical status after GKS. Analysis of 201Tl SPECT data used the early ratio (ER) and the delayed ratio (DR) calculated as tumor/normal average counts on the early and delayed images, and the retention index (RI) as the ratio of DR to ER. RESULTS A total of 107 tumors were analyzed with 201Tl SPECT. Nineteen lesions were removed surgically and histological diagnoses established, and the other lesions were evaluated with follow-up clinical and neuroimaging examinations after GKS. The final diagnosis was considered to be recurrent tumor in 65 lesions and radiation necrosis in 42 lesions. Semiquantitative analysis demonstrated significant differences in DR (P=.002) and RI (P<.0001), but not in ER (P=.372), between the tumor recurrence and radiation necrosis groups, and no significant differences between metastatic brain tumors and high-grade gliomas in all indices (P=.926 for ER, P=.263 for DR, and P=.826 for RI). Receiver operating characteristics analysis indicated that RI was the most informative index with the optimum threshold of 0.775, which provided 82.8% sensitivity, 83.7% specificity, and 82.8% accuracy. CONCLUSIONS Semiquantitative analysis of 201Tl SPECT provides useful information for the differentiation between tumor recurrence and radiation necrosis in metastatic brain tumors and high-grade gliomas after GKS, and the RI may be the most valuable index for this purpose.

Surgical treatment for late complications following gamma knife surgery for arteriovenous malformations.

Background: To establish the surgical indications and strategy for late complications following gamma knife surgery (GKS) for arteriovenous malformations (AVMs). Methods: Ten male and 7 female patients aged 17–52 years (mean 28.0 years) were retrospectively identified among 686 patients who underwent GKS for AVM at our hospital. Ten patients showed cyst formation (group A), 2 patients had expanding hematoma (group B), and 5 patients had both cyst and expanding hematoma (group C). Results: The mean nidus volume was 10.1 ml (range 0.1–36 ml), and the mean prescription dose at the nidus margin was 19.9 Gy (range 18–28 Gy). Complete obliteration of the nidus was obtained in 12 patients, partial obliteration in 4, and no change in 1. Cyst formation (group A) was asymptomatic in 5 patients, and symptomatic in 5 patients, manifesting as headache, hemianopia, aphasia, and motor weakness. Expanding hematoma (groups B and C) was associated with surrounding brain edema and was symptomatic in all 7 patients. Cyst opening in 1 patient and placement of an Ommaya reservoir in 2 patients were necessary in group A. Both patients in group B underwent craniotomy. Four of the 5 patients in group C required craniotomy. Another patient in group C was lost to follow-up and the final outcome was unknown. Conclusions: Cyst formation is one of the late complications of GKS for AVM. Some cysts show spontaneous regression but others gradually increase in size and become symptomatic, although relatively large asymptomatic cysts are also known. Predicting the future course of a cyst is difficult. Surgery such as placement of an Ommaya reservoir should be considered for symptomatic cases. Expanding hematoma always increases in size and becomes symptomatic, so removal by craniotomy is necessary. Surrounding brain edema decreases rapidly after surgery and neurological symptoms quickly resolve.

Primary medulla oblongata germinoma in a male patient.

Germinoma mainly occurs in the pituitary stalk, pineal region, and basal ganglia. Sex predominance of the tumor in males in the pineal region and basal ganglia is well known. Primary germinoma of the medulla oblongata is rare, with only eight reports, mostly in females. We report the second male patient with primary medulla oblongata germinoma, without chromosomal abnormality, who was successfully treated with surgery, chemotherapy, and radiotherapy.

Gamma Knife Surgery for Metastatic Brain Tumors from Gynecologic Cancer.

OBJECTIVE The incidences of metastatic brain tumors from gynecologic cancer have increased. The results of Gamma Knife surgery (GKS) for the treatment of patients with brain metastases from gynecologic cancer (ovarian, endometrial, and uterine cervical cancers) were retrospectively analyzed to identify the efficacy and prognostic factors for local tumor control and survival. METHODS The medical records were retrospectively reviewed of 70 patients with 306 tumors who underwent GKS for brain metastases from gynecologic cancer between January 1995 and December 2013 in our institution. RESULTS The primary cancers were ovarian in 33 patients with 147 tumors and uterine in 37 patients with 159 tumors. Median tumor volume was 0.3 cm(3). Median marginal prescription dose was 20 Gy. The local tumor control rates were 96.4% at 6 months and 89.9% at 1 year. There was no statistically significant difference between ovarian and uterine cancers. Higher prescription dose and smaller tumor volume were significantly correlated with local tumor control. Median overall survival time was 8 months. Primary ovarian cancer, controlled extracranial metastases, and solitary brain metastasis were significantly correlated with satisfactory overall survival. Median activities of daily living (ADL) preservation survival time was 8 months. Primary ovarian cancer, controlled extracranial metastases, and higher Karnofsky Performance Status score were significantly correlated with better ADL preservation. CONCLUSIONS GKS is effective for control of tumor progression in patients with brain metastases from gynecologic cancer, and may provide neurologic benefits and preservation of the quality of life.