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At least 19 recordsLinked to original sources

PubMed2006

Activation of stat3 in human melanoma promotes brain metastasis.

Brain metastasis is a major cause of morbidity and mortality in patients with melanoma. The molecular changes that lead to brain metastasis remain poorly understood. In this study, we developed a model to study human melanoma brain metastasis and found that Stat3 activity was increased in human brain metastatic melanoma cells when compared with that in cutaneous melanoma cells. The expression of activated Stat3 is also increased in human brain metastasis specimens when compared with that in the primary melanoma specimens. Increased Stat3 activation by transfection with a constitutively activated Stat3 enhanced brain metastasis, whereas blockade of Stat3 activation by transfection with a dominant-negative Stat3 suppressed brain metastasis of human melanoma cells in animal models. Furthermore, altered Stat3 activity profoundly affected melanoma angiogenesis in vivo and melanoma cell invasion in vitro and significantly affected the expression of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and matrix metalloproteinase-2 (MMP-2) in vivo and in vitro. Finally, Stat3 activity transcriptionally regulated the promoter activity of bFGF in addition to VEGF and MMP-2 in human melanoma cells. These results indicated that Stat3 activation plays an important role in dysregulated expression of bFGF, VEGF, and MMP-2 as well as angiogenesis and invasion of melanoma cells and contributes to brain metastasis of melanoma. Therefore, Stat3 activation might be a new potential target for therapy of human melanoma brain metastases.

Animals↗

PubMed1998

Clinical management of brain metastasis.

Brain metastasis is a common complication occurring in about 15-20% of all cancer patients. For the initial management, distinguishing between three types of presentation is essential: de novo brain metastasis, simultaneous presentation of both brain metastasis and the primary tumour (usually lung carcinoma), and the presentation of a patient known to have systemic cancer developing a brain metastasis. For de novo brain metastasis, surgery is required, and detecting the primary tumour is of limited value. For simultaneous presentation, both a craniotomy and a thoracotomy may be indicated and may lead to cure in a number of cases. For a sequential presentation, the outcome is determined by a number of independent prognostic factors: age, performance status, and the extent of metastatic disease. In relatively young patients with a single brain metastasis, good performance status and no progression of systemic disease, treatment by either surgery or radiosurgery in combination with whole brain radiation therapy is indicated. Otherwise, as in multiple brain metastases, radiation therapy only is the main treatment. For symptomatic therapy of brain oedema or increased intracranial pressure, dexamethasone is administered. The standard doses of dexamethasone may vary between 4 and 16 mg/day, depending on the severity of symptoms.

Anticonvulsants↗

PubMed1999

Cytopathologic evaluation of lung carcinomas presenting as brain metastasis.

Brain metastasis is an uncommon initial presentation of lung carcinoma. One arm of this analysis is a retrospective review of 137 cases of surgically diagnosed solitary brain metastasis, which were eventually found to be of lung origin, encountered at Hines VA Hospital during the period 1958 to 1996. The second arm is composed of fine-needle aspiration biopsy specimens of primary lung tumor in 23 patients with an initial clinical diagnosis of brain metastasis and without the benefit of surgery, seen from 1981 through 1996. Our results in both analyses indicate that pulmonary adenocarcinoma is the predominant primary tumor that initially manifests as a brain metastasis, approaching 76% (107 and 17 cases, respectively), followed by small-cell carcinoma at 20% (24 and five cases, respectively) and large-cell undifferentiated carcinoma and squamous-cell carcinoma at 2% each. The predominance of adenocarcinoma as a source of brain metastasis in lung cancer patients probably reflects its rising incidence overall of late. Collateral findings also suggest that surgical resection of a solitary and small brain metastasis as well as of a discrete lung primary, whenever feasible, as the most effective procedure to improve survival and quality of life of patients.

Adenocarcinoma↗

PubMed1986

Carcinoma of the prostate with brain metastasis.

Brain metastasis from prostatic carcinoma is considered rare and usually is diagnosed at postmortem examination. The authors reviewed the tumor registry of 1314 patients with proven diagnosis of prostatic carcinoma seen at Hines VA Hospital from January 1963 to December 1978 and found that 8 of the 1314 patients (0.6%) had brain metastasis. Six of eight patients (75%) were diagnosed having brain metastasis at premortem and of these, two patients presented with brain metastasis before diagnosis of prostatic carcinoma was made. Two of four patients who received palliative whole brain irradiation survived more than 1.5 years. It is our belief that patients with prostatic carcinoma who have symptoms of brain metastasis should be worked up and given palliative whole brain irradiation.

Adenocarcinoma↗

PubMed1999

The biology of melanoma brain metastasis.

Brain metastases are clinically diagnosed in the majority of patients with metastatic melanoma. The prognosis for patients with melanoma brain metastasis is poor with a median survival time of 6 months after diagnosis. Development of better therapies requires a better understanding of the biology of melanoma brain metastasis. The development of a relevant in vivo model offers this possibility. The intracarotid injection of different murine or human melanoma cells into syngeneic or nude mice produces metastases in different regions of the brain. This site-specific metastasis is not due to patterns of initial cell arrest, motility, or invasiveness, but rather to the ability of melanoma cells to proliferate in the brain parenchyma or the meninges. The blood-brain barrier is intact in metastases that are smaller than 0.25 mm in diameter. Although in larger metastases the blood-brain barrier is leaky, the lesions are resistant to many chemotherapeutic drugs. We have also analyzed the malignant behavior of several melanoma cell lines isolated from brain or visceral metastases of patients. The cells from brain metastases showed a slower growth rate and exhibited lower metastatic potential than cells from visceral metastases, indicating that brain metastases do not necessarily represent the end stage in the metastatic cascade. Rather, brain metastases are likely to originate from a unique subpopulation of cells within the primary neoplasm.

Animals↗

PubMed1996

Demographics of brain metastasis.

Brain metastases are the most common intracranial tumor, significantly out-numbering primary brain tumors. The apparent increase in the ratio of brain metastases to primary tumors may be the result of a number of factors, including the possibility of a CNS "pharmacologic sanctuary," an aging population, and improved imaging studies. Among adults, the most common origins of brain metastasis include primary tumors of the lung, breast, skin (melanoma), and gastrointestinal tract. Among patients under 21 years of age, brain metastases most often arise from the sarcomas and germ cell tumors.

Adolescent↗

PubMed2004

Survival in relation to radiotherapeutic modality for brain metastasis: whole brain irradiation vs. gamma knife radiosurgery.

The purpose of this report is to evaluate and compare the survival of patients with brain metastasis (BRM) treated by whole brain irradiation (WBI) using linear energy accelerator (LINAC) and by stereotactic radiosurgery using gamma knife. This study consists of a series of 67 patients with BRM treated with WBI between 1998 and 1999 and 53 patients with BRM treated with gamma knife radiosurgery (GKRS) between 2000 and 2001. A retrospective study of the data was performed and the overall survival between these 2 groups was analyzed. The comparability of these 2 groups was tested by chi2 and t test values. Log-rank test was used in the survival comparison. The 1-year survival rate was 26.3% and 22.6%, and corresponding mean survival was 7.8 months and 6.7 months for WBI and GKRS groups, respectively. There was no statistically significant difference between these 2 groups' survival. It was evident from imaging defined lesions that with GKRS the lesions were reduced, stabilized, or disappeared in 89% of cases. Survival of patients with BRM treated with WBI or GKRS was similar in these series. The present study suggests that good tumor response by GKRS does not translate in longer patient survival.

Adult↗

PubMed2006

Whole-brain radiotherapy in the management of brain metastasis.

Brain metastases are an important cause of morbidity and mortality, afflicting nearly 170,000 Americans annually. The prognosis for these patients is poor, with median survival times measured in months. In this review article, we present the standard treatment approach of whole-brain radiotherapy and discuss new directions, including the role of chemical modifiers and the management and prevention of neurocognitive deficits.

Brain Neoplasms↗

PubMed1995

The role of trophic factors and autocrine/paracrine growth factors in brain metastasis.

The brain is a unique microenvironment enclosed by the skull, lacking lymphatic drainage and maintaining a highly regulated vascular transport barrier. To metastasize to the brain malignant tumor cells must attach to microvessel endothelial cells, respond to brain-derived invasion factors, invade the blood-brain barrier and respond to survival and growth factors. Trophic factors are important in brain invasion because they can act to stimulate this process. In responsive malignant cells trophic factors such as neurotrophins can promote invasion by enhancing the production of basement membrane-degradative enzymes (such as type IV collagenase/gelatinase and heparanase) capable of locally destroying the basement membrane and the blood-brain barrier. We examined human melanoma cell lines that exhibit varying abilities to form brain metastases. These melanoma lines express low-affinity neurotrophin receptor p75NTR in relation to their brain-metastatic potentials but the variants do not express trkA, the gene encoding a high affinity nerve growth factor (NGF) tyrosine kinase receptor p140trkA. Melanoma cells metastatic to brain also respond to paracrine factors made by brain cells. We have found that a paracrine form of transferrin is important in brain metastasis, and brain-metastatic cells respond to low levels of transferrin and express high levels of transferrin receptors. Brain-metastatic tumor cells can also produce autocrine factors and inhibitors that influence their growth, invasion and survival in the brain. We found that brain-metastatic melanoma cells synthesize transcripts for the following autocrine growth factors: TGF beta, bFGF, TGF alpha and IL-1 beta. Synthesis of these factors may influence the production of neurotrophins by adjacent brain cells, such as oligodendrocytes and astrocytes. Increased amounts of NGF were found in tumor-adjacent tissues at the invasion front of human melanoma tumors in brain biopsies. Trophic factors, autocrine growth factors, paracrine growth factors and other factors may determine whether metastatic cells can successfully invade, colonize and grow in the central nervous system.

Amino Acid Sequence↗

PubMed2006

Nonsmall cell lung cancer presenting with synchronous solitary brain metastasis.

BACKGROUND: Solitary brain metastases occur in about 50% of patients with brain metastases from nonsmall cell lung cancer (NSCLC). The standard of care is surgical resection of solitary brain metastases, or stereotactic radiosurgery (SRS) plus whole brain radiation therapy (WBRT). However, the optimal treatment for the primary site of newly diagnosed NSCLC with a solitary brain metastasis is not well defined. The goal was to distinguish which patients might benefit from aggressive treatment of their lung primary in patients whose solitary brain metastasis was treated with surgery or SRS. METHODS: The cases of 84 newly diagnosed NSCLC patients presenting with a solitary brain metastasis and treated from December 1993 through June 2004 were retrospectively reviewed at The University of Texas M. D. Anderson Cancer Center. All patients had undergone either craniotomy (n = 53) or SRS (n = 31) for management of the solitary brain metastasis. Forty-four patients received treatment of their primary lung cancer using thoracic radiation therapy (median dose 45 Gy; n = 8), chemotherapy (n = 23), or both (n = 13). RESULTS: The median Karnofsky performance status score was 80 (range, 60-100). Excluding the presence of the brain metastasis, 12 patients had AJCC Stage I primary cancer, 27 had Stage II disease, and 45 had Stage III disease. The median follow-up was 9.7 months (range, 1-86 months). The 1-, 2-, 3-, and 5-year overall survival rates from time of lung cancer diagnosis were 49.8%, 16.3%, 12.7%, and 7.6%, respectively. The median survival times for patients by thoracic stage (I, II, and III) were 25.6, 9.5, and 9.9 months, respectively (P = .006). CONCLUSIONS: By applying American Joint Committee on Cancer staging to only the primary site, the thoracic Stage I patients in our study with solitary brain metastases had a more favorable outcome than would be expected and was comparable to Stage I NSCLC without brain metastases. Aggressive treatment to the lung may be justified for newly diagnosed thoracic Stage I NSCLC patients with a solitary brain metastasis, but not for locally advanced NSCLC patients with a solitary brain metastasis.

Adult↗

PubMed2004

Treatment of solitary brain metastasis. Resection followed by whole brain radiation therapy (WBRT) and a radiation boost to the metastatic site.

BACKGROUND: Whole brain radiation therapy (WBRT) is reported to improve local control after resection of brain metastases. Improvement of survival was only observed in patients with controlled extracranial disease. The optimum radiation schedule has yet to be defined. The authors' experience with a postoperative approach including WBRT and a radiation boost to the metastatic site is presented. PATIENTS AND METHODS: Criteria for inclusion into this retrospective analysis were solitary brain metastasis, Karnofsky performance status > or = 70%, and controlled extracranial disease. Two therapies were compared for local control and survival: surgery followed by 40 Gy WBRT (group A) versus surgery followed by 40 Gy WBRT and a 10 Gy boost (group B). Statistical analysis was performed using the Kaplan-Meier method and log-rank test. RESULTS: 33 patients were included (17 group A, 16 group B). The results suggested better local control (p = 0.0087) and survival (p = 0.0023) for group B. 17/17 patients (100%) of group A and 13/16 patients (81%) of group B showed progression of brain metastasis, 8/17 and 3/16 patients in the area of metastatic surgery. Median time to progression was 7 (1-22) months in group A and 12 (3-42) months in group B. The number of cancer-related deaths amounted to 17/17 (100%) in group A after a median interval of 9 (3-26) months, and to 9/16 (56%) in group B after 14 (4-46) months. CONCLUSION: After resection of solitary brain metastasis, a radiation boost in addition to WBRT seems to improve local control and survival when compared to postoperative WBRT alone. The results should be confirmed in a larger prospective trial.

Aged↗

PubMed1982

Brain metastasis in the natural history of small-cell lung cancer: 1972-1979.

The records of 134 patients with small-cell lung cancer who had been seen at Henry Ford Hospital between 1972-1979 were reviewed with emphasis on brain metastasis. Brain metastasis developed in 28% of the patients; 21% had brain metastasis at the time of diagnosis and in 7% it developed later (de novo). In 9%, the chief complaint was related to brain metastasis. Brain metastasis in only two of 109 patients developed after diagnosis (de novo) yet prior to initiation of prophylactic brain radiation. The frequency of de novo brain metastasis in those treated with intensive combination chemotherapy and those treated by other means was similar. Of the patients with brain metastasis, 73% died from other causes. Isolated brain metastasis in the absence of progressive systemic disease was rare.

Brain Neoplasms↗

PubMedDate not supplied

Patterns of brain metastasis in lung cancer.

Brain metastasis as the only site of spread in lung cancer was studied. Ninety-two (13.1%) of 701 lung cancer patients had brain metastasis at the time of diagnosis. Eighteen and 16 patients had small primary lesion and were N0-1 disease, respectively. Thirty-two patients had sole brain metastasis. Patients with sole brain metastasis had more favorable survival than patients with other metastatic sites (p=0.0165). Brain metastasis may occur even with small primary lesion and/or without regional lymph node involvement. Well-planned surgery or stereotactic radiosurgery will result in enhanced survival.

Adenocarcinoma↗

PubMed2000

Clinicopathological study of brain metastasis in gastric cancer patients.

Brain metastasis from cancers of the gastrointestinal tract is uncommon; brain metastasis from gastric cancer is rare and its incidence is low. Brain metastasis of gastric cancer is often difficult to treat and is resectable in only a few cases. We have treated three patients who had a solitary brain metastasis after a gastrectomy. These three cases are reviewed along with eight other previously reported cases of brain metastasis to clarify the clinicopathological features and to suggest guidelines for patients with metastatic brain tumors. The clinicopathological features of 11 cases of brain metastasis were analyzed. For comparison purposes, the 11 cases were classified into three groups as follows: a resection group, a chemoradiotherapy group, and a nontreatment group. All the patients had advanced gastric cancer of stage III or more. The resection group had the most survivors, and survival rates decreased in the order of the resection group, the chemoradiotherapy group, and the nontreatment group. There was a statistically significant difference between the resection group and the nontreatment group (P = 0.0177). Aggressive multidisciplinary treatment, including a resection, for brain metastasis should improve the quality of life and prolong life expectancy.

Adenocarcinoma↗

PubMed1998

Prognostic factors in lung cancer with brain metastasis.

BACKGROUND AND PURPOSE: Metastasis to the brain develops in 25% of all patients with lung cancer. Although the outcome is usually poor, there seems to be a subset of patients with favorable prognostic factors who may live longer. Prognostic factors were analyzed retrospectively in 103 patients with brain metastases from lung carcinoma to identify patients who would benefit from more intensive treatment strategies. MATERIALS AND METHODS: Between October 1991 and December 1994, 103 patients with brain metastasis from lung cancer were irradiated with palliative intent. Palliation was defined as 50% or more regression of neurological signs and symptoms 2 weeks after the completion of cranial radiotherapy. Local (related to the lung tumor) symptom status at the time of brain metastasis, the presence of metastases other than brain, multiplicity of brain metastases on CT scan and time of occurrence of brain metastasis were the factors which were evaluated with multivariate analysis. RESULTS: Palliation was accomplished in 85% of cases. Palliation duration ranged from 0.5 to 54 months (median 3 months). The overall median survival was 5 months. Only one patient is under follow-up without any symptoms related to the brain metastasis. According to the multivariate analysis survival was significantly decreased in the presence of symptoms related to the primary tumor (P = 0.001). CONCLUSION: The presence of symptoms related to the primary tumor at the time of brain metastasis is one of the factors that can be used to distinguish patients with a favorable outcome. In patients with favorable prognostic factors and thus longer survival probability, the role of boost dose after whole brain radiotherapy or surgical resection in suitable cases needs to be investigated.

Adenocarcinoma↗

PubMed1995

[VM-26 plus CCNU in the prevention of brain metastasis in lung cancer patients].

Brain metastasis is of frequent occurrence in patients with cancer of the lung. To ascertain if brain metastasis is preventable, 34 lung cancer patients without brain metastasis were treated with 4 cycles of VM-26 plus CCNU at 4-week intervals. As a control for comparison, an equal number of lung cancer patients free of brain metastasis were treated with chemotherapy protocol which did not include VM-26 and CCNU. The patients were monitored by clinical symptoms, signs and CT or MRI scan and were followed up for 4-12 months. The results indicate that none of the VM-26 plus CCNU-treated patients developed brain metastasis while brain metastasis occurred in 7 (20.5%) of 34 control patients. The difference was statistically significant (P < 0.05).

Adenocarcinoma↗

PubMed1998

Clinical study of renal cell carcinoma with brain metastasis.

BACKGROUND: The clinical outcome of patients with renal cell carcinoma with brain metastasis was analyzed. METHODS: Nine patients (median age, 60 years) with primary renal cell carcinoma and distant metastasis, including brain metastasis, were treated. The median time to the development of brain metastasis was 15 months after the initial visit. Patients with poor performance status or progressive disease were treated with interferon or conservative therapy alone. Patients with good performance status and other well-controlled metastatic foci were treated either with radiotherapy, or by tumorectomy of brain metastasis, or both. The median follow-up was 26 months after the initial visit. RESULTS: The 1-year, cause-specific survival rate was 17%. Of the 5 patients treated with alpha-interferon alone, all died of disease after the treatments, without improvement of performance status, 1 to 4 months after the diagnosis of brain metastasis. Two of 4 patients who underwent radiotherapy were treated with a combination of gamma-knife and tumorectomy of brain metastasis. They remained alive 10 and 22 months after diagnosis of brain metastasis. The 2 patients who underwent the combination treatment of gamma-knife and tumorectomy showed improvement of their performance status after these treatments for brain metastasis. CONCLUSION: Brain metastasis is an unfavorable prognostic factor in renal cell carcinoma. Although a larger number of patients would be necessary to demonstrate the definitive effects of gamma-knife treatment, our results suggest that the combination of gamma-knife and tumorectomy of brain metastases may be recommended for selected patients with good performance status and other well-controlled metastatic foci.

Aged↗

PubMed2004

Brain metastasis from esophageal carcinoma.

Brain metastasis from esophageal carcinoma is rare. In our center, among 301 cases of esophageal cancer referred for radiotherapy during a 14-year period, brain metastasis from esophageal carcinoma was detected in one case. An unusual case of esophageal carcinoma that presented with brain metastasis is reported.

Brain Neoplasms↗