Shinji Matsuda

Gamma knife treatment for multiple metastatic brain tumors compared with whole-brain radiation therapy.

The purpose of this paper was to note a potential source of error in magnetic resonance (MR) imaging. Magnetic resonance images were acquired for stereotactic planning for GKS of a vestibular schwannoma in a female patient. The images were acquired using three-dimensional sequence, which has been shown to produce minimal distortion effects. The images were transferred to the planning workstation, but the coronal images were rejected. By examination of the raw data and reconstruction of sagittal images through the localizer side plate, it was clearly seen that the image of the square localizer system was grossly distorted. The patient was returned to the MR imager for further studies and a metal clasp on her brassiere was identified as the cause of the distortion.A-60-year-old man with medically intractable left-sided maxillary division trigeminal neuralgia had severe cardiac disease, was dependent on an internal defibrillator and could not undergo magnetic resonance imaging. The patient was successfully treated using computerized tomography (CT) cisternography and gamma knife radiosurgery. The patient was pain free 2 months after GKS. Contrast cisternography with CT scanning is an excellent alternative imaging modality for the treatment of patients with intractable trigeminal neuralgia who are unable to undergo MR imaging.The authors describe acute deterioration in facial and acoustic neuropathies following radiosurgery for acoustic neuromas. In May 1995, a 26-year-old man, who had no evidence of neurofibromatosis Type 2, was treated with gamma knife radiosurgery (GKS; maximum dose 20 Gy and margin dose 14 Gy) for a right-sided intracanalicular acoustic tumor. Two days after the treatment, he developed headache, vomiting, right-sided facial weakness, tinnitus, and right hearing loss. There was a deterioration of facial nerve function and hearing function from pretreatment values. The facial function worsened from House-Brackmann Grade 1 to 3. Hearing deteriorated from Grade 1 to 5. Magnetic resonance (MR) images, obtained at the same time revealed an obvious decrease in contrast enhancement of the tumor without any change in tumor size or peritumoral edema. Facial nerve function improved gradually and increased to House-Brackmann Grade 2 by 8 months post-GKS. The tumor has been unchanged in size for 5 years, and facial nerve function has also been maintained at Grade 2 with unchanged deafness. This is the first detailed report of immediate facial neuropathy after GKS for acoustic neuroma and MR imaging revealing early possibly toxic changes. Potential explanations for this phenomenon are presented.In clinical follow-up studies after radiosurgery, imaging modalities such as computerized tomography (CT) and magnetic resonance (MR) imaging are used. Accurate determination of the residual lesion volume is necessary for realistic assessment of the effects of treatment. Usually, the diameters rather than the volume of the lesion are measured. To determine the lesion volume without using stereotactically defined images, the software program VOLUMESERIES has been developed. VOLUMESERIES is a personal computer-based image analysis tool. Acquired DICOM CT scans and MR image series can be visualized. The region of interest is contoured with the help of the mouse, and then the system calculates the volume of the contoured region and the total volume is given in cubic centimeters. The defined volume is also displayed in reconstructed sagittal and coronal slices. In addition, distance measurements can be performed to measure tumor extent. The accuracy of VOLUMESERIES was checked against stereotactically defined images in the Leksell GammaPlan treatment planning program. A discrepancy in target volumes of approximately 8% was observed between the two methods. This discrepancy is of lesser interest because the method is used to determine the course of the target volume over time, rather than the absolute volume. Moreover, it could be shown that the method was more sensitive than the tumor diameter measurements currently in use. VOLUMESERIES appears to be a valuable tool for assessing residual lesion volume on follow-up images after gamma knife radiosurgery while avoiding the need for stereotactic definition.This study was conducted to evaluate the geometric distortion of angiographic images created from a commonly used digital x-ray imaging system and the performance of a commercially available distortion-correction computer program. A 12 x 12 x 12-cm wood phantom was constructed. Lead shots, 2 mm in diameter, were attached to the surfaces of the phantom. The phantom was then placed inside the angiographic localizer. Cut films (frontal and lateral analog films) of the phantom were obtained. The films were analyzed using GammaPlan target series 4.12. The same procedure was repeated with a digital x-ray imaging system equipped with a computer program to correct the geometric distortion. The distortion of the two sets of digital images was evaluated using the coordinates of the lead shots from the cut films as references. The coordinates of all lead shots obtained from digital images and corrected by the computer program coincided within 0.5 mm of those obtained from cut films. The average difference is 0.28 mm with a standard deviation of 0.01 mm. On the other hand, the coordinates obtained from digital images with and without correction can differ by as much as 3.4 mm. The average difference is 1.53 mm, with a standard deviation of 0.67 mm. The investigated computer program can reduce the geometric distortion of digital images from a commonly used x-ray imaging system to less than 0.5 mm. Therefore, they are suitable for the localization of arteriovenous malformations and other vascular targets in gamma knife radiosurgery.

Transient expansion of vestibular schwannoma following stereotactic radiosurgery

OBJECT The authors prospectively analyzed volume changes in vestibular schwannomas (VSs) after stereotactic radiosurgery. METHODS One hundred consecutive patients with unilateral VS treated with Gamma Knife surgery (GKS) at Chiba Cardiovascular Center between 1998 and 2006 were analyzed in this study. For each lesion the Gd-enhanced volume was measured serially every 3 months in the 1st year, then every 6 months thereafter, using volumetric software. The frequency and degree of transient tumor expansion were documented and possible prognostic factors were analyzed. Concurrently, neurological deterioration involving trigeminal, facial, and cochlear nerve functions were also assessed. RESULTS The mean observation period was 65 months (range 25-100 months). There were 32 men and 68 women, whose mean age was 59.1 years (range 29-80 years). Tumor volumes at GKS averaged 2.7 cm3 (range 0.1-13.2 cm3), and the lesions were irradiated at the mean 52.2% isodose line for the tumor margin (range 50-67%), with a mean dose of 12.2 Gy (range 10.5-13 Gy) at the periphery. The tumor volume was increased by 23% at 3 months and 27% at 6 months. Tumors shrank to their initial size over a mean period of 12 months. The maximum volume increase was < 10% (no significant increase) in 26 patients, 10-30% in 23, 30-50% in 22, 50-100% in 16, and > 100% in 13. The peak tumor expansion averaged 47% (range 0-613%). A high-dose (> or = 3.5 Gy/min) treatment appears to be the greatest risk factor for transient tumor expansion, although the difference did not reach statistical significance. Transient facial palsy and facial dysesthesia correlated strongly with tumor expansion, but only half of the hearing loss was coincident with this phenomenon. CONCLUSIONS Transient expansion of VSs after GKS was found to be much more frequent than previously reported, strongly suggesting a correlation with deterioration of facial and trigeminal nerve functions.

Three-staged stereotactic radiotherapy without whole brain irradiation for large metastatic brain tumors.

PURPOSE To evaluate the efficacy and toxicity of staged stereotactic radiotherapy with a 2-week interfraction interval for unresectable brain metastases more than 10 cm(3) in volume. PATIENTS AND METHODS Subjects included 43 patients (24 men and 19 women), ranging in age from 41 to 84 years, who had large brain metastases (> 10 cc in volume). Primary tumors were in the colon in 14 patients, lung in 12, breast in 11, and other in 6. The peripheral dose was 10 Gy in three fractions. The interval between fractions was 2 weeks. The mean tumor volume before treatment was 17.6 +/- 6.3 cm(3) (mean +/- SD). Mean follow-up interval was 7.8 months. The local tumor control rate, as well as overall, neurological, and qualitative survivals, were calculated using the Kaplan-Meier method. RESULTS At the time of the second and third fractions, mean tumor volumes were 14.3 +/- 6.5 (18.8% reduction) and 10.6 +/- 6.1 cm(3) (39.8% reduction), respectively, showing significant reductions. The median overall survival period was 8.8 months. Neurological and qualitative survivals at 12 months were 81.8% and 76.2%, respectively. Local tumor control rates were 89.8% and 75.9% at 6 and 12 months, respectively. Tumor recurrence-free and symptomatic edema-free rates at 12 months were 80.7% and 84.4%, respectively. CONCLUSIONS The 2-week interval allowed significant reduction of the treatment volume. Our results suggest staged stereotactic radiotherapy using our protocol to be a possible alternative for treating large brain metastases.

Diagnostic value of thallium-201 chloride single-photon emission computerized tomography in differentiating tumor recurrence from radiation injury after gamma knife surgery for metastatic brain tumors.

OBJECT The authors assessed the diagnostic value of 201Tl Cl single-photon emission computerized tomography (SPECT), performed after gamma knife surgery (GKS) for metastatic brain tumors in differentiating tumor recurrence from radiation injury. METHODS Of 6503 metastatic brain tumors treated with GKS, 201Tl SPECT was required in 72 to differentiate between tumor recurrence and radiation injury. When the Tl index was greater than 5, the lesion was diagnosed as a tumor recurrence. When the index was < 3.0 it was called radiation injury. In cases with a Tl index between 3 and 5, 201Tl SPECT was repeated once per month until the Tl index was greater than 5 or less than 3. If the Tl index fluctuated between 3 and 5 for 2 months, the lesion was diagnosed as radiation injury. The final diagnosis was based on histological examination or clinical course. The sensitivity of the method was 91%; thus 201Tl SPECT is effective for differentiating between tumor recurrence and radiation injury in metastatic brain tumors treated with GKS. Caution is necessary, however, for the following reasons: 1) simple interinstitutional comparisons of Tl indices are not possible because measurement methods are institute specific; 2) steroid administration decreases the Tl index to a variable degree; and 3) a severe radiation injury lesion, as is often seen after repeated GKS or very high dose GKS, may have a Tl index greater than 5. CONCLUSIONS Used with critical insight 201Tl Cl SPECT can be useful in distinguishing between tumor regrowth and radiation necrosis in patients with cerebral metastases.

Gamma Knife surgery as sole treatment for multiple brain metastases: 2-center retrospective review of 1508 cases meeting the inclusion criteria of the JLGK0901 multi-institutional prospective study

OBJECT The authors retrospectively reviewed the results of Gamma Knife surgery (GKS) used as the sole treatment for brain metastases in patients who met the eligibility criteria for the ongoing JLGK0901 multi-institutional prospective trial. They also discuss the anticipated results of the JLGK0901 study. METHODS Data from 1508 consecutive cases were analyzed. All of the patients were treated at the Gamma Knife House of Chiba Cardiovascular Center or the Mito Gamma House of Katsuta Hospital between 1998 and 2007 and met the following JLGK0901 inclusion criteria: 1) newly diagnosed brain metastases, 2) 1-10 brain lesions, 3) less than 10 cm(3) volume of the largest tumor, 4) no more than 15 cm(3) total tumor volume, 5) no findings of CSF dissemination, and 6) no impairment of activities of daily living (Karnofsky Performance Scale score < 70) due to extracranial disease. At the initial treatment, all visible lesions were irradiated with GKS without upfront whole-brain radiation therapy. Thereafter, gadolinium-enhanced MR imaging was performed every 2-3 months, and new distant lesions were appropriately retreated with GKS. Patients were divided into groups according to numbers of tumors: Group A, single lesions (565 cases); Group B, 2-4 tumors (577 cases); and Group C, 5-10 tumors (366 cases). The differences in overall survival (OS) were compared between groups. RESULTS The median age of the patients was 66 years (range 19-96 years). There were 963 men and 545 women. The primary tumors were in the lung in 1114 patients, gastrointestinal tract in 179, breast in 105, urinary tract in 66, and other sites in 44. The overall mean survival time was 0.78 years (0.99 years for Group A, 0.68 years for Group B, and 0.62 years for Group C). The differences between Groups A and B (p < 0.0001) and between Groups B and C (p = 0.0312) were statistically significant. Multivariate analysis revealed significant prognostic factors for OS to be sex (poor prognostic factor: male, p < 0.0001), recursive partitioning analysis class (Class I vs Class II and Class II vs III, both p < 0.0001), primary site (lung vs breast, p = 0.0047), and number of tumors (Group A vs Group B, p < 0.0001). However, no statistically difference was detected between Groups B and C (p = 0.1027, hazard ratio 1.124, 95% CI 0.999-1.265). CONCLUSIONS The results of this retrospective analysis revealed an upper CI of 1.265 for the hazard ratio, which was lower than the 1.3 initially set by the JLGK0901 study. The JLGK0901 study is anticipated to show noninferiority of GKS as sole treatment for patients with 5-10 brain metastases compared with those with 2-4 in terms of OS.

Comparison of the results of 2 targeting methods in Gamma Knife surgery for trigeminal neuralgia

OBJECT Gamma Knife surgery (GKS) is an effective treatment for intractable trigeminal neuralgia (TN). The authors compared results using two major GKS target points, the dorsal root entry zone and the retrogasserian portion, in a series of patients with intractable TN. METHODS One hundred patients with medically refractory TN underwent GKS between August 1998 and December 2007. Thirty-seven were men, and 63 were women. The median age at GKS was 74 years. With a single isocenter and use of a 4mm collimator, 51 patients received 80 Gy at the proximal trigeminal nerve (posterior group) and 7 patients received 80 Gy, 1 patient received 85 Gy, and 41 patients received 90 Gy at the retrogasserian portion (anterior group). Follow-up was obtained by clinic visits every 3-6 months after GKS. Data on pain control, complications, and pain recurrence were recorded. The relationships between pain control status, complications, recurrence, and the target portions (anterior vs posterior) were analyzed. RESULTS The median duration of follow-up was 30 months (range 3-88 months). Initially, 87 patients achieved pain-free status and 64 achieved complete remission. At the final follow-up visit, 68 patients were still in pain-free status and 42 were in complete remission. Recurrence of facial pain occurred in 15 patients. Forty-one patients developed some degree of trigeminal dysfunction. The rate of initial complete remission was higher in the posterior group than in the anterior group (p = 0.003). More complications were observed in the anterior group than in the posterior group (p = 0.009). CONCLUSIONS The posterior targeting group had better pain control and a lower complication rate. The authors recommend the posterior targeting method and use of 80 Gy for treatment of TN with GKS.

Gamma Knife surgery for metastatic brain tumors

OBJECT The authors compared results of Gamma Knife surgery (GKS) for brain metastases obtained at 2 institutions in Japan. METHODS They analyzed a consecutive series of 2390 patients with brain metastases who underwent GKS from 1998 through 2005 in 2 institutes (1,181 patients in Chiba; 1,209 in Mito). In the 2 facilities, 1 neurosurgeon each was responsible for diagnosis, patient selection, GKS procedures, and follow-up (T.S. in Chiba, M.Y. in Mito). Even if tumor numbers exceeded 4, all visible lesions were irradiated with a total skull integral dose (TSID) of <or= 10-12 J. No prophylactic whole-brain radiotherapy (WBRT) was applied. If new distant lesions were detected, salvage GKS was appropriately performed. RESULTS The distributions of patient and treatment factors did not differ between institutes. The most common primary tumors were lung cancer (1,572 patients), followed by gastrointestinal tract (316), breast (211), kidney (113), and other cancers (159). The median survival periods were 7.7 months in Chiba and 7.0 months in Mito (p = 0.0635). The significant poor prognostic factors for overall survival were active extracranial disease status, male sex, and low initial Karnofsky Performance Scale score on multivariate analysis (all p < 0.0001). The neurological survival rates at 1 year were 86.6% in Chiba and 84.2% in Mito (p = 0.3310). CONCLUSIONS This 2-institute study demonstrated no significant institutional differences in any of the treatment result items. Gamma Knife surgery for brain metastases without prophylactic WBRT prevents neurological death and allows a patient to maintain good brain condition. However, there is 1 important patient selection criterion: regardless of how many tumors there are, all lesions can be irradiated with a TSID of <or=12 J.

Robustness of the neurological prognostic score in brain metastasis patients treated with Gamma Knife radiosurgery

OBJECTIVE The neurological prognostic score (NPS) was recently proposed as a means for predicting neurological outcomes, such as the preservation of neurological function and the prevention of neurological death, in brain metastasis patients treated with Gamma Knife radiosurgery (GKRS). NPS consists of 2 groups: Group A patients were expected to have better neurological outcomes, and Group B patients were expected to have poorer outcomes. NPS robustness was tested in various situations. METHODS In total, 3040 patients with brain metastases that were treated with GKRS were analyzed. The cumulative incidence of the loss of neurological function independence (i.e., neurological deterioration) was estimated using competing risk analysis, and NPS was compared between Groups A and B by employing Grays model. NPS was tested to determine if it can be applied to 5 cancer categories-non-small cell lung cancer, small cell lung cancer, gastrointestinal tract cancer, breast cancer, and other cancers-as well as if it can be incorporated into the 5 major grading systems: recursive partitioning analysis (RPA), score index for stereotactic radiosurgery (SIR), basic score for brain metastases (BSBM), graded prognostic assessment (GPA), and modified-RPA (M-RPA). RESULTS There were 2263 patients in NPS Group A and 777 patients in Group B. Neurological deterioration was observed in 586 patients (19.2%). The cumulative incidences of neurological deterioration were 9.5% versus 21.0%, 14.1% versus 25.4%, and 17.6% versus 27.8% in NPS Groups A and B at 1, 2, and 5 years, respectively. Significant differences were detected between the NPS groups in all cancer categories. There were significant differences between NPS Groups A and B for all classes in terms of the BSBM, GPA, and M-RPA systems, but the differences failed to reach statistical significance in terms of RPA Class I and SIR Class 0 to 3. CONCLUSIONS The NPS was verified as being highly applicable to all cancer categories and almost all classes for the 5 grading systems in terms of neurological function independence. This NPS system appears to be quite robust in various situations for brain metastasis patients treated with GKRS.

Successful Selective Intra‐arterial Thrombolytic Therapy for Embolic Stroke in a Patient with Asplenia Syndrome and Unrepaired Cyanotic Congenital Heart Disease

We report successful selective local intra-arterial thrombolytic therapy for thromboembolic occlusion of right middle cerebral artery in a patient with asplenia syndrome and unrepaired cyanotic congenital heart disease.

Estimation of patient population fulfilling inclusion criteria for intravenous administration of recombinant tissue plasminogen activator for acute ischemic stroke-retrospective study-:retrospective study

Background and Purpose:Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) within 3 hours after onset of cerebral ischemia was approved in Japan in October 2005. Preceding using rt-PA for acute cerebral infarction, we built a simulation model of patient flow using inpatient data and clarified issues of in-hospital systems.Methods:We retrospectively analyzed consecutive 485 patients with acute ischemic stroke admitted in our center from May 2002 to October 2005. We analyzed the patients who arrived at our center within 120 minutes after the onset, because at least 60 minutes by the admission will be required for evaluating of patient status and informed consent. We estimate the ratio of patients who fulfilled inclusion criteria for intravenous administration of rt-PA in the patients with acute ischemic stroke. We also assessed interval from the arrival to the admission in these patients and factors related to the interval.Results:There were 148 patients (30.5%) who arrived at our center within 120 minutes after the onset of symptoms. There were 94 men and 54 women. Age was 73.9±10.0 years-old (Mean±SD). The time from the onset to the arrival was 78.8±39.8 minutes. Baseline National Institutes of Health Stroke Scale (NIHSS) was 12.4±9.6. In these patients, only 32 patients (21.6%) fulfilled criteria for the inclusion prior to the admission. The remaining patients were excluded due to the following reasons:unknown onset time, 55; regression of symptoms, 11; mild symptom (NIHSS54), 47; history of intracranial hemorrhage, 3;convulsion, 3; extensive early CT sign, 35 and other reasons, 8. In the included 32 patients, five patients needed more than 180 minutes from the onset to the admission. Finally, 27 patients (5.6% in the all patients) admitted within 180 minutes after the onset and fulfilled the inclusion criteria. In 148 patients, 81 patients were not admitted within 60 minutes after the arrival. Sixty-seven patients were admitted within 60 minutes after the arrival and had significant higher NIHSS than those admitted more than 60 minutes. Age, referral hospital, ambulance or arrival time was not significant factor for the interval from the arrival to the admission.Conclusion: We estimated the candidate for acute thrombolysis using intravenous rt-PA to be 5.6% of total patients with acute ischemic stroke. Patient evaluation frequently required more than 60 minutes prior to the admission, even if the patients arrived at our center within 120 minutes after the onset. We should establish the in-hospital system to reduce the time for patient evaluation.