Shigeo Inomori

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.

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.

Thrombotic occlusion of the middle cerebral artery

Background and Purpose: Epidemiological study of middle cerebral artery occlusion is important because the indication for extracranial-intracranial arterial bypass remains in dispute. To help clarify this issue, we investigated the prognosis of thrombotic middle cerebral artery occlusion in Japanese patients. Methods: We studied 40 patients with thrombotic middle cerebral artery occlusion who were selected on the basis of clinical features, computed tomographic findings, and angiographic findings. Patients with causes of embolism (i.e., cardiomyopathy, valvular heart disease, cardiac arrhythmia, and carotid ulceration) were excluded. The 40 patients were classified into three groups according to the site of middle cerebral artery occlusion: there were 13 patients with occlusion of the proximal portion of the Ml segment, 13 with distal Ml segment occlusion, and 14 with occlusion of the M2 segment. Results: Good collateral circulation was associated with improved outcomes both clinically and by computed tomography in patients with occlusion of the proximal and distal portions of the Ml segment but not in those with M2 occlusion. Conclusions: It is reasonable to assume that not only collateral circulation but also the site of occlusion plays an important role in the outcome of middle cerebral artery occlusion. Our finding that good collateral circulation improves the outcome for thrombotic occlusion of the proximal and distal Ml segments supports the possible benefits of such surgery.

Cyst formation following gamma knife surgery for intracranial meningioma

OBJECT The authors conducted a study to evaluate the clinical significance of cyst formation or enlargement after gamma knife surgery (GKS) for intracranial benign meningiomas. METHODS The medical records of 160 patients with 184 tumors were examined for those with follow-up data of more than 2 years among 270 patients who underwent GKS for intracranial meningiomas between February 1992 and November 2001. Cyst formation or enlargement following GKS was observed in five patients, one man and four women (mean age 61.2 years). The tumor location was the sphenoid ridge in one case, petroclival in two, tentorium in one, and parasagittal region in one. All patients underwent surgery before GKS. The mean tumor volume was 10.5 cm3, the mean margin dose was 13.4 Gy (median 14 Gy), and the mean maximum dose was 27.5 Gy (median 24.1 Gy). At the time of GKS three tumors were associated with cyst, of which two enlarged after radiosurgery. Three cysts developed de novo after GKS. Three of the five patients needed surgery to treat the cyst formation or enlargement. Histological examination demonstrated various findings such as tumor necrosis, proliferation of small vessels, vascular obliteration, and hemosiderin deposits. CONCLUSIONS New cyst formation following GKS for benign intracranial meningioma is relatively rare; however, both preexisting and newly developed cysts tend to enlarge after GKS and often require surgery.

Dose selection for optimal treatment results and avoidance of complications.

What is the optimal treatment for metastatic brain tumors (MBTs)? We present our experience with gamma knife (GK) treatments for patients with five or more MBTs. Our new formula for predicting patient survival time (ST), which was derived by combining tumor control probability (TCP) calculated by Colombos formula and normal tissue complication probability (NTCP) estimated by Flickingers integrated logistic formula, was also evaluated. ST=a*[(C-NTCP)*TCP]+b; a, b, C: const. Forty-one patients (23 male, 18 female) with more than five MBTs were treated between March 1992 and February 2000. The tumors originated in the lung in 15 cases, in the breast in 8. Four patients had previously undergone whole brain irradiation (WBI). Ten patients were given concomitant WBI. Thirteen patients had additional extracranial metastatic lesions. TCP and NTCP were calculated using Excel add-in software. Coxs proportional hazards model was used to evaluate correlations between certain variables and ST. The independent variables evaluated were patient factors (age in years and performance status), tumor factors (total volume and number of tumors in each patient), treatment factors (TCP, NTCP and marginal dose) and the values of (C-NTCP)*TCP. Total tumor number was 403 (median 7, range 5-56). The median total tumor volume was 9.8 cm3 (range 0.8-111.8 cm3). The marginal dose ranged from 8 to 22 Gy (median 16.0Gy), TCP from 0.0% to 83% (median 15%) and NTCP from 0.0% to 31% (median 6.0%). (0.39-NTCP)*TCP ranged from 0.0 to 0.21 (median 0.055). Follow-up was 0.2 to 26.2 months, with a median of 5.4 months. Multiple-sample tests revealed no differences in STs among patients with MBTs of different origins (p=0.50). The 50% STs of patients with MBTs originating from the breast, lung and other sites were 5.9, 7.8 and 3.5 months, respectively. Only TCP and (0.39-NTCP)*TCP were statistically significant covariates (p=0.014, 0.001, respectively), and the latter was a more important predictor of ST than the former (Beta= -2.2, -14.1, respectively). The relationship between (0.39-NTCP)*TCP and ST was significant. Linear regression analysis showed this value to predict ST (p=0.002, R2=0.22). The slope of the regression line for patients with MBTs originating from the breast was steeper (a=218.2, p=0.08, R2=0.41) than the slopes of regression lines for patients with tumors of other origins (lung; a=56.8, p=0.004, R2=0.49, others; a=50.4, p=0.03, R2=0.25). In treating multiple lesions, the maximum doses and dose distribution for individual lesions were often different. The formula described by Colombo is used to calculate the residual clonogenic cell number of every sub-volume of the tumor, with different doses. NTCP must also integrate every complication probability for each sub-volume of normal brain tissue in the relatively high dose area in proximity to the tumor. Herein, we present a method for determining the irradiation dose necessary for cases with multiple brain metastases. A personal computer-aided calculation is employed.