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PubMed1985

Modification of brain vascular eicosanoids after pharmacological treatment and ischemia in the rat: drugs and brain vascular eicosanoids.

Vascular eicosanoids (E) thromboxane (measured as T X B2) and prostacyclin (measured as 6-keto-PGF1 alpha) may modulate hemodynamic parameters in brain circulation. We have studied (a) the effects of the administration of vasoactive drugs, in the rat, on T X B2 and 6-keto-PGF1 alpha levels and release in brain cortex, and (b) changes of brain vascular E levels during hypoxia and recovery, in the same animal species. Administration of vasoactive drugs (papaverine, dipyridamole, the carbochromene derivative AD6 and nifedipine) to rats resulted in differential effects on endogenous levels and post-decapitation release of both compounds. Reduction of the T X B2/6-keto-PGF1 alpha balance in brain cortex was obtained with papaverine and AD6, whereas nifedipine reduced 6-keto-PGF1 alpha more than T X B2. During hypoxia there was no significant modification of brain vascular E, but during recovery both compounds were decreased. Thus pharmacological treatments during recovery from hypoxia may normalize brain vascular E levels.

6-Ketoprostaglandin F1 alpha↗

PubMed2005

Effectiveness of whole brain radiotherapy in the treatment of brain metastases: a systematic review.

BACKGROUND: Brain metastases are the most common intracranial tumour in adults, estimated to occur in up to 40% of patients with cancer. Despite being used in clinical practice for 50 years, the effectiveness of whole brain radiotherapy for the treatment of brain metastases remains uncertain. OBJECTIVES: To assess the effectiveness of whole brain radiotherapy (WBRT) on survival and quality of life. To identify whether patient performance status, number of brain metastases, extent of extracranial disease and primary site of cancer are important effect modifiers. DESIGN: Systematic literature review. METHODS: Electronic searches of four databases, augmented by hand searches of the most frequently encountered journal and assessment of the reference lists of consensus statements and all retrieved papers. Included papers underwent structured data extraction, assessment and qualitative synthesis. RESULTS: Thirty-two primary studies were included, with a range of study designs, methodological quality, pre-treatment variables, interventions and outcome measures. From the limited evidence available, survival appeared to increase when patients were selected by performance status (survival increasing from approximately three to seven months in high performance status groups, as defined by Karnofsky performance status or Recursive Partitioning Analysis classification). The evidence suggests no survival benefit when patients with poor performance status were treated with whole brain radiotherapy. No studies undertook direct measurement of patients' quality of life. Surrogate measures of patients' quality of life, such as improvement in neurological function or improvement/maintenance of KPS > or =70, produced response rates ranging from 7 to 90%. CONCLUSION: The heterogeneity of study designs, quality and outcomes necessitates caution in interpreting the review findings. WBRT appears to be of benefit in higher performance status patients but not in low performance status patients. This suggests a basis for current practice, however further robust trial evidence is required.

Brain Neoplasms↗

PubMed2002

Lead-in phase to randomized trial of motexafin gadolinium and whole-brain radiation for patients with brain metastases: centralized assessment of magnetic resonance imaging, neurocognitive, and neurologic end points.

PURPOSE: Motexafin gadolinium is a redox mediator that selectively targets tumor cells, is detectable by magnetic resonance imaging (MRI), and enhances the effect of radiation therapy. This lead-in phase to a randomized trial served to evaluate radiologic, neurocognitive, and neurologic progression end points and to evaluate the safety and radiologic response of motexafin gadolinium administered concurrently with 30 Gy in 10-fraction whole-brain radiation therapy for the treatment of brain metastases. PATIENTS AND METHODS: Motexafin gadolinium (5.0 mg/kg/d for 10 days) was administered before each radiation treatment in this prospective international trial. Patients were evaluated by MRI, neurologic examinations, and neurocognitive tests. Prospective criteria and centralized review procedures were established for radiologic, neurocognitive, and neurologic progression end points. RESULTS: Twenty-five patients with brain metastases from lung (52%) and breast (24%) cancer, recursive partitioning analysis class 2 (96%), and an average of 11 brain metastases were enrolled. Neurocognitive function was highly impaired at presentation. Motexafin gadolinium was well tolerated. Freedom from neurologic progression was 77% at 1 year. Median survival was 5.0 months. In 29% of patients, the cause of death was brain metastasis progression. The radiologic response rate was 68%. Motexafin gadolinium's tumor selectivity was established with MRI. CONCLUSION: (1) Centralized neurologic progression scoring that incorporated neurocognitive tests was implemented successfully. (2) Motexafin gadolinium was well tolerated. (3) Local control, measured by radiologic response rate, neurologic progression, and death caused by progression of brain metastasis, seemed to be improved compared with historical results. A randomized phase III trial using these methods for evaluation of efficacy has just been completed.

Adult↗

PubMed2004

Neurocognitive function and progression in patients with brain metastases treated with whole-brain radiation and motexafin gadolinium: results of a randomized phase III trial.

PURPOSE: To report the neurocognitive findings in a phase III randomized trial evaluating survival and neurologic and neurocognitive function in patients with brain metastases from solid tumors receiving whole-brain radiation therapy (WBRT) with or without motexafin gadolinium (MGd). PATIENTS AND METHODS: Patients were randomly assigned to receive WBRT 30 Gy in 10 fractions with or without MGd 5 mg/kg/d. Monthly neurocognitive testing for memory, executive function, and fine motor skill was performed. RESULTS: Four hundred one patients were enrolled (251 with non-small-cell lung cancer, 75 with breast cancer, and 75 with other cancers); 90.5% patients had impairment of one or more neurocognitive tests at baseline. Neurocognitive test scores of memory, fine motor speed, executive function, and global neurocognitive impairment at baseline were correlated with brain tumor volume and predictive of survival. There was no statistically significant difference between treatment arms in time to neurocognitive progression. Patients with lung cancer (but not other types of cancer) who were treated with MGd tended to have improved memory and executive function (P =.062) and improved neurologic function as assessed by a blinded events review committee (P =.048). CONCLUSION: Neurocognitive tests are a relatively sensitive measure of brain functioning; a combination of tumor prognostic variables and brain function assessments seems to predict survival better than tumor variables alone. Although the addition of MGd to WBRT did not produce a significant overall improvement between treatment arms, MGd may improve memory and executive function and prolong time to neurocognitive and neurologic progression in patients with brain metastases from lung cancer.

Adult↗

PubMed1980

Experimental exposure of the cat brain surface to neurosurgical irrigation fluids and air: study of blood-brain barrier damage.

Different fluids used in neurosurgery were tested for the production of blood-brain barrier dysfunction by applying them to the brain surface of the cat for 3 hours. Normal saline, Ringer's solution, and Elliott's Solution B induced no obvious damage either by closed subdural perfusion or when applied to the brain surface via pledgets for 3 hours. When perfusion with Ringer's solution for 2 hours and 45 minutes was preceded by 15 minutes of exposure to air, an intense extravasation of tracer was induced in the leptomeninges. When perfusion with Ringer's solution (2 hours and 45 minutes) was followed by irrigation with 3% hydrogen peroxide (5 minutes) and then brief perfusion (10 minutes) with Ringer's solution, thrombosis of leptomeningeal vessels and extensive extravasation of tracer were found in both the leptomeninges and the cortex down to the white matter. Elliott's Solution B seemed to provide better protection against these injuries than did Ringer's solution. Thee observations demonstrate the importance of immediate protection of the exposed brain surface against air by physiological fluids and show that these fluids provide effective protection against disturbance of the blood-brain barrier for at least 3 hours. Hydrogen peroxide proved unsuitable for application to the brain surface.

Animals↗

PubMed2003

Brain metastases treated with radiosurgery alone: an alternative to whole brain radiotherapy?

OBJECTIVE: Whole brain radiotherapy (WBRT) provides benefit for patients with brain metastases but may result in neurological toxicity for patients with extended survival times. Stereotactic radiosurgery in combination with WBRT has become an important approach, but the value of WBRT has been questioned. As an alternative to WBRT, we managed patients with stereotactic radiosurgery alone, evaluated patients' outcomes, and assessed prognostic factors for survival and tumor control. METHODS: One hundred seventy-two patients with brain metastases were managed with radiosurgery alone. One hundred twenty-one patients were evaluable with follow-up imaging after radiosurgery. The median patient age was 60.5 years (age range, 16-86 yr). The mean marginal tumor dose and volume were 18.5 Gy (range, 11-22 Gy) and 4.4 ml (range, 0.1-24.9 ml). Eighty percent of patients had solitary tumors. RESULTS: The overall median survival time was 8 months. The median survival time in patients with no evidence of primary tumor disease or stable disease was 13 and 11 months. The local tumor control rate was 87%. At 2 years, the rate of local control, remote brain control, and total intracranial control were 75, 41, and 27%, respectively. In multivariate analysis, advanced primary tumor status (P = 0.0003), older age (P = 0.008), lower Karnofsky Performance Scale score (P = 0.01), and malignant melanoma (P = 0.005) were significant for poorer survival. The median survival time was 28 months for patients younger than 60 years of age, with Karnofsky Performance Scale score of at least 90, and whose primary tumor status showed either no evidence of disease or stable disease. Tumor volume (P = 0.02) alone was significant for local tumor control, whereas no factor affected remote or intracranial tumor control. Eleven patients developed complications, six of which were persistent. Nineteen (16.5%) of 116 patients in whom the cause of death was obtained died as a result of causes related to brain metastasis. CONCLUSION: Brain metastases were controlled well with radiosurgery alone as initial therapy. We advocate that WBRT should not be part of the initial treatment protocol for selected patients with one or two tumors with good control of their primary cancer, better Karnofsky Performance Scale score, and younger age, all of which are predictors of longer survival.

Adolescent↗

PubMed1987

[The regulation system of brain aromatase activity; distribution and changes with age of the aromatase activity of the rat brain].

Sexual differentiation of brain structure and function is dependent on the hormonal environment during perinatal life. Recently, some studies have found the greatest aromatase activity in brain areas associated with sexual differentiation and sexual behavior, namely the hypothalamic and limbic structures. We have characterized the developmental and anatomical patterns of aromatase of aromatase activity in brains of fetal, neonatal, infantile and adult rats of both sexes. Aromatase activities in slices of brain were assayed by measuring the amount of 3H2O formed during the conversion of [1 beta-3H] androstenedione to estrogen. We have demonstrated major changes of the aromatase activity in the brain with age. Aromatase activities of both sexes reached peak values in the hypothalamus-preoptic area (HPOA) at least 3 days before birth. Thereafter, the activities declined to 3 weeks after birth. We have found the greatest amount of aromatase activity in HPOA and amygdala of both sexes. Aromatase activities in HPOA and amygdala of neonatal male rat were higher than adult male rat. The hippocampus, thalamus, pituitary, cerebral cortex and cerebellum all contained negligible aromatase activity. And, we studied HPOA in detail, aromatase activities in preoptic area and anterior part of hypothalamus were twice higher than that in posterior part of hypothalamus. Aromatase activity reached peak values at the critical period of the sexual differentiation of the brain in HPOA and amygdala, associated with sexual behavior and sexual differentiation. We have reported that aromatase activity was regulated by androgen. We suggested that aromatization didn't occur effectively in female rat, owing to scarcity of androgen, which was activator and substrate of aromatase.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed2004

Molecular neuro-oncology and the development of targeted therapeutic strategies for brain tumors. Part 3: brain tumor invasiveness.

Brain tumors are a diverse group of malignancies that remain refractory to conventional treatment approaches. Molecular neuro-oncology has now begun to clarify the transformed phenotype of brain tumors and identify oncogenic pathways that might be amenable to targeted therapy. Cellular invasion of surrounding brain is one of the key features of brain tumor behavior and is currently under evaluation for potential therapeutic targets. Tumor invasion occurs in the context of the extracellular matrix (ECM) of the brain and involves the interaction between cell-surface adhesion molecules, such as integrins and proteins embedded within the ECM. The overexpression of integrins is often associated with invasive behavior and can be inhibited by targeted approaches such as antibodies, antisense constructs and cyclic peptides. Tumor cell-secreted matrix metalloproteinases and serine proteinases degrade ECM proteins and provide space for movement and infiltration. The expression of proteinases positively correlates with tumor grade and infiltrative capacity. Proteinase activity can be reduced by several methods, including antibodies and small-molecule inhibitors such as marimastat. Early clinical trials suggest that marimastat may have activity in combination with traditional chemotherapy regimens. Further development of targeted therapies designed to inhibit tumor infiltration, and evaluation of these new agents in clinical trials, will be needed to improve survival and quality of life for patients with brain tumors.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1978

Compound impulse response for the brain stem derived through combinations of cochlear and brain stem recordings.

To overcome some of the problems involved in the application of brain stem evoked responses (BSER) in otoneurological diagnosis an approach is developed which combines cochlear and brain stem recordings. The activity of the cochlea and brain stem generators, as seen from the far-field recording electrode, is considered to be the output from a single system. The impulse response of this system can be derived through deconvolution of the brain stem evoked responses, BSER, with the compound action potential, AP, followed by appropriate filtering. This method is used on the recordings from 15 subjects with various degrees of cochlear hearing loss. The results show that the compound impulse response, CIR, for the brain stem consists of five recognizable peaks. From the individual subjects this response pattern is largely independent of intensity. By plotting the amplitude and latency of the individual peaks for all 15 subjects a set of normative data is retrieved. The variation in the data is small, probably because interfeerence from the periphery is eliminated and the separation of activity from the different brain stem generators is improved.

Audiometry↗

PubMed1993

Targeting anticancer drugs to the brain. I: Enhanced brain delivery of oxantrazole following administration in magnetic cationic microspheres.

A magnetic cationic microsphere delivery system, prepared from the polysaccharide chitosan and containing oxantrazole (OX), was examined for its ability to enhance brain delivery of OX compared to administration of OX in solution (OX-S). Magnetic chitosan microspheres containing OX (MCM-OX) and OX-S were administered intraarterially to male Fischer 344 rats at OX doses of 0.1 mg/kg and 0.5 mg/kg with a magnetic field of 6000 G applied to the brain for 30 min. Animals were sacrificed at 30 min and 120 min after MCM-OX and OX-S treatments, and multiple tissues were collected and analyzed for OX by HPLC. A statistical analysis of the effects of treatment, OX dose, and time on total OX in each sampled tissue was made. MCM-OX significantly increased OX brain concentrations compared to those achieved with OX-S treatments, concentrations after MCM-OX being a minimum of 100-fold greater. Within the MCM-OX treatment groups, ipsilateral OX concentrations were much greater, indicating target organ selectivity. A most interesting finding was that OX brain concentrations were similar at 120 min and 30 min after MCM-OX treatment. Thus, even in the absence of the magnetic field, MCM-OX were retained in the brain, possibly through cationic-anionic interactions with the blood-brain barrier.

Animals↗

PubMed2000

[A six year follow-up study on the influence of silent ischemic brain lesions on cognitive function and brain atrophy in elderly people].

METHODS: To investigate the influence of silent ischemic brain lesions (silent brain infarction (SBI) and periventricular hyperintensity (PVH) on cognitive function and brain atrophy, we studied MRI and cognitive tests in 27 healthy elderly people (above 65 years old) for 6 years. We examined Okabe's Scale for verbal intelligence, Koh's Block Design Test for performance intelligence and Zung's Self-rating Depression Scale (SDS). On MRI, lesions with high intensity on T2-weighted image and low intensity on T1-weighted image, and which were larger than 3 mm were diagnosed as SBI. The PVH was classified into 5 grades (0-4), and we divided the subjects into the PVH 0-1 group and the PVH 2-4 group. We evaluated brain atrophy using the ventricular area index (VAI) (the ratio of ventricular area to intracranial area at the level of lateral ventricle) on MRI by NIH image 1.55 (Macintosh). RESULTS: The SBI group and the PVH 2-4 group showed significant decline in Okabe's Score, and Koh's IQ, increase in SDS and VAI during six years. On the other hand, the non-SBI and the PVH 0-1 group showed a decline only in Okabe's score, and an increase in VAI. The rate of change in VAI was significantly higher in the subjects with SBI than those without it. However, there was no significant difference in the VAI change rate between the PVH 2-4 group and the PVH 0-1 group. CONCLUSION: Silent ischemic brain lesions such as SBI and PVH may have significant influence on decline of cognitive functions and progression of brain atrophy even in healthy elderly people.

Aged↗

PubMed1990

Diphtheria toxin effects on brain-tumor xenografts. Implications for protein-based brain-tumor chemotherapy.

A model was developed to determine whether protein-based chemotherapeutic agents can cross the blood-brain barrier and successfully treat brain tumors. The human small-cell lung carcinoma N417D was grown as a solid tumor in the nude rat brain, and diphtheria toxin (DT) was administered intravenously as therapy. Because rat cells lack functional DT receptors and are 1000 to 10,000 times less sensitive to DT than human cells, a therapeutic window exists between the implanted human tumor and the nude rat host. The pharmacokinetic and pharmacodynamic characteristics of DT were defined. Within 6 hours, more than 90% of the initial DT concentration was removed from the blood. The blood-to-tumor transfer constant Ki for DT in small N417D tumors was 0.49 microliters/gm-min, one-fourth to one-fifth the reported values for permeability to proteins in other experimental tumor models. Despite the toxin's short plasma half-life and the relatively intact blood-tumor barrier, DT administered intravenously as a single dose significantly extended animal survival. Untreated nude rats developed solid parenchymal tumors and died in 11 to 16 days (median 15 days). When administered at 0.1 micrograms/animal, DT increased the median survival time to 19 days (p less than 0.0016) while 1.0-microgram doses extended median survival times to 26.5 days (p less than 0.0002). A higher dose of DT (3.0 micrograms) had no further beneficial effect on survival (26.1 days). Blood-brain barrier constraints to successful monoclonal antibody-based therapies of brain tumors may have been overestimated since antibody conjugates have plasma half-lives longer than DT, and the permeability of N417D tumors to DT is equal to or less than the permeability of other experimental tumors to large proteins. Recently developed immunotoxins that have the higher potency of DT and a therapeutic window as wide as DT has in this nude rat/human tumor paradigm may be effective in treating brain tumors despite limited blood-tumor permeability.

Animals↗

PubMedDate not supplied

Laboratory investigations on neuroparalytic accidents associated with suckling mouse brain rabies vaccine. III. -- Preservation of vaccine potency after elimination of murine brain myelin by centrifugation.

Myelin, which has been found in nine day-old mouse brain, was eliminated from weanling mouse brain suspensions by centrifugation at 17,000 g for 10 min, as demonstrated by electron microscopy and guinea-pig inoculation tests for encephalitogenic activity. This centrifugation procedure did not affect the potency of seven batches of suckling mouse brain vaccine, when centrifuged and non-centrifuged samples of the same batches were compared by a modified NIH potency test (t = 0.17). The present results with weanling mouse brain preparations suggest that centrifugation at 17,000 g be used in the preparation of rabies suckling mouse brain vaccine instead of the 1,900 g currently employed, which does not eliminate myelin. This new procedure would be expected to reduce the number of postvaccinal reactions which are attributable to the small amount of myelin which remains in vaccines prepared with new-born animal brains following the current procedure.

Animals↗

PubMed1976

Significance of cranial circulation for the brain homeothermia in rabbits. I. The brain-arterial blood temperature gradient.

The hypothalamic-arterial blood temperature gradient (THpr-TAC difference) was studied on 10 freely moving rabbits at ambient temperatures between 0 and 42 degrees Celsius. In cold environment, below 10 degrees Celsius the THpt-TAC gradient varied considerably, but some distinct correlations were found between vasomotor responses of the nasal mucosa and fluctuations of brain temperature, as well as between vasomotor responses of the ear pinnas and changes of the arterial blood temperature. Vasodilatation of the nasal mucosa or the ear pinna caused respectively a drop in brain temperature or in arterial blood temperature. Opposite changes were induced by vasoconstriction in those areas. Variations in THpt-TAC gradient resulted from oppositely directed vasomotor responses in the nasal mucosa and in the ear pinnas. At high ambient temperatures above 35 degrees Celsius thermal panting was accompanied by selective brain cooling with respect to the arterial blood. Blocking the heat loss from the nasal mucosa caused an increase of the THpt-TAC difference, and under these conditions brain temperature was determined solely by arterial blood temperature. The assumed mechanism of the selective brain cooling in rabbits is the exchange of heat through the neurocranial bottom, between the ventral brain and the spacious splanchnocranial venous lakes supplied with blood from the nasal mucosa.

Animals↗

PubMed1999

An antibody-avidin fusion protein specific for the transferrin receptor serves as a delivery vehicle for effective brain targeting: initial applications in anti-HIV antisense drug delivery to the brain.

In the present study a novel Ab-avidin fusion protein has been constructed to deliver biotinylated compounds across the blood brain barrier. This fusion molecule consists of an Ab specific for the transferrin receptor genetically fused to avidin. The Ab-avidin fusion protein (anti-TfR IgG3-CH3-Av) expressed in murine myeloma cells was correctly assembled and secreted and showed both Ab- and avidin-related activities. In animal models, it showed much longer serum half-life than the chemical conjugate between OX-26 and avidin. Most importantly, this fusion protein demonstrated superior [3H]biotin uptake into brain parenchyma in comparison with the chemical conjugate. We also delivered a biotinylated 18-mer antisense peptide-nucleic acid specific for the rev gene of HIV-1 to the brain. Brain uptake of the HIV antisense drug was increased at least 15-fold when it was bound to the anti-TfR IgG3-CH3-Av, suggesting its potential use in neurologic AIDS. This novel Ab fusion protein should have general utility as a universal vehicle to effectively deliver biotinylated compounds across the blood-brain barrier for diagnosis and/or therapy of a broad range of CNS disorders such as infectious diseases, brain tumors as well as Parkinson's and Huntington's diseases.

Animals↗

PubMed2001

Drug transporters in the central nervous system: brain barriers and brain parenchyma considerations.

Drug transport in the central nervous system is highly regulated not only by the blood-brain and the blood-cerebrospinal fluid barriers but also in brain parenchyma. The novel localization of drug transporters in brain parenchyma cells, such as microglia and astrocytes, suggest a reconsideration of the present conceptualization of brain barriers as it relates to drug transport. That is, the cellular membranes of parenchyma cells act as a second "barrier" to drug permeability and express transporters whose properties appear similar to those localized at the conventional brain barriers. This review will focus on the molecular characteristics, localization, and substrate specificities of several classes of well known membrane drug transporters (i.e., the organic cation, organic anion, nucleoside, P-glycoprotein, and multidrug resistance proteins) in the brain. Comparisons to similar transporters localized within the peripheral system and clinical implications of the functional expression of specific drug transport families will be discussed when appropriate. Nutrient and neurotransmitter transporters, whose characteristics have been reviewed extensively elsewhere, will not be considered in this review.

Animals↗

PubMed2002

[Measurement of calcium fluorescent intensity in vital brain slice and mechanism of brain injury after circulatory arrest].

OBJECTIVE: To examine the calcium fluorescent intensity of vital brain slice and study the mechanism of brain injury after circulatory arrest. METHODS: Eight pigs underwent 90 minutes' deep hypothermic circulation arrest (DHCA) and eight pigs underwent retrograde cerebral perfusion (RCP) through superior vena cava and then rewarmed for 120 minutes. Vital brain slices were obtained and the calcium fluorescent intensity was examined with laser confocal scanning microscope (LCSM). The morphological change was examined with light microscope and electron microscope. RESULTS: The calcium fluorescent intensity of vital brain slice was lower in RCP group than in DHCA group. The calcium fluorescent intensity of vital brain slice is correlated with the level of moderate and severe eosinophilic degeneration of neuron (r = 0.86, P < 0.05). CONCLUSION: Calcium overload contributes to the injury of neuron after DHCA. RCP remarkably attenuates calcium overload, thus protecting the brain tissue.

Animals↗

PubMedDate not supplied

Whole-brain radiation therapy is not beneficial as an adjuvant therapy for brain metastases compared with localized irradiation.

BACKGROUND: We investigated the role of whole-brain radiation therapy (WBRT) which has been widely used as an adjuvant therapy for brain metastases. PATIENTS AND METHODS: The authors retrospectively reviewed 132 patients who underwent surgical resection for brain metastases. They were classified into five groups according to the dose of radiation therapy to the local brain (L) or to the whole-brain (W), independently; 0 Gy (Group A[L or W]), 20-29 Gy (Group B[L or W]), 30-39 Gy (Group C[L or W]), 40-49 Gy (Group D[L or W]) and 50 Gy or more (Group E[L or W]). RESULTS: Local recurrence rates and times to tumor progression (TTP) of the original tumor were 53% and 3 months for Group A(L), 25% and 6 months for Group C(L), 11% and 7 months for Group D(L) and 12% and 12 months for Group E(L). Median survival times (MST) were 6 months for Group A(L), 8 months for Group C(L), 8 months for Group D(L) and 11 months for Group E(L). Distant recurrence rates and the TTP of new lesions in the distant area were 27% and 7 months for Group A(W), 20% and 6 months for Group B(W), 8% and 9 months for Group C(W), 13% and 13 months for Group D(W) and 4% and 14 months for Group E(W). The MST were 11 months for Group A(W), 11 months for Group B(W), 10 months for Group C(W), 9 months for Group D(W) and 6 months for group E(W). CONCLUSION: The present results suggest that WBRT is unnecessary and that local radiation therapy of 40 Gy or more would be the primary choice of adjuvant therapy for the majority of patients treated with surgical resection for brain metastases.

Adult↗