Biomedical subjects

Frederick F Lang

Publications and source records attributed to Frederick F Lang.

At least 37 records · Page 2Linked to original sources

PubMed2005

Neurosurgical oncology at the university of Texas M. D. Anderson Cancer Center: its genesis and evolution.

The practice of neurosurgery at The University of Texas M. D. Anderson Cancer Center began in 1944 with one neurosurgeon among the 11 physicians present in a makeshift 16-room outpatient clinic at a temporary location. Neurosurgical oncology evolved as the hospital did, first as a neurosurgery service in 1951, then as the Section of Neurosurgery within the Department of Head and Neck Surgery in 1979, and finally, as the Department of Neurosurgery in 1990. Although M. D. Anderson is now one of the largest institutions in the world devoted exclusively to cancer patient care, research, education, and prevention, it has an unusual history, which is reviewed in terms of the institution's origin in 1941, its development under three presidents, and its fostering of neurosurgical oncology. We chronicle the growth and development of the department from 1990 to 2003 and describe the unique opportunities it presents for surgical innovation, for clinical and basic research, for training residents and fellows, and for multidisciplinary collaboration in neurosurgical oncology.

Hospitals, University↗

PubMed2005

Surgical resection of intrinsic insular tumors.

This report, with an accompanying videotape, details the authors' technique for performing radical resections of tumors intrinsic to the insular lobe. The resection technique takes advantage of the fact that many intrinsic insular tumors grow within the confines of the insula, usually without violating pial borders or invading the medial structures. The method described is based on an anatomic dissection of the insula that uses the internal boundaries of the region, particularly the peri-insular sulci, as guides for resection. The videotape provides a visual description of this method.

Adult↗

PubMed2005

Resection of brain metastases previously treated with stereotactic radiosurgery.

OBJECT: To date, no report has been published on outcomes of patients undergoing resection for brain metastases who were previously treated with stereotactic radiosurgery (SRS). Consequently, the authors reviewed their institutional experience with this clinical scenario to assess the efficacy of surgical intervention. METHODS: Sixty-one patients (each harboring three or fewer brain lesions), who were treated at a single institution between June 1993 and August 2002 were identified. Patient charts and their neuroimaging and pathological reports were retrospectively reviewed to determine overall survival rates, surgical complications, and recurrence rates. A univariate analysis revealed that patient preoperative recursive partitioning analysis (RPA) classification, primary disease status, preoperative Karnofsky Performance Scale score, type of focal treatment undergone for nonindex lesions, and major postoperative surgical complications were factors that significantly affected survival (p < or = 0.05). In contrast, only the RPA class and focal (conventional surgery or SRS) treatment of nonindex lesions significantly (or nearly significantly) affected survival in the multivariate analysis. Major neurological complications occurred in only 2% of patients. The median time to distant recurrence after resection was 8.4 months; that to local recurrence was not reached. The overall median survival time was 11.1 months, with 25% of patients surviving 2 or more years. Conventional surgery facilitated tapering of steroid administration. Conclusions. The complication, morbidity, survival, and recurrence rates are consistent with those seen after conventional surgery for recurrent brain metastases. Our results indicate that in selected patients with a favorable RPA class in whom nonindex lesions are treated with focal modalities, surgery can provide long-term control of SRS-treated lesions and positively affect overall survival.

Adult↗

PubMed2005

Chiari I malformation and acute acquired comitant esotropia: case report and review of the literature.

The authors describe a rare case of a Chiari I malformation presenting with acute acquired comitant esotropia (AACE) in a 5-year-old boy. A posterior fossa decompression with duraplasty and a C1-2 laminectomy were performed. There was an immediate postoperative improvement in the esotropia, which completely resolved by 7 months following surgery. The pertinent literature is discussed and reasons are presented for recommending posterior fossa decompression in certain patients, rather than strabismus surgery, as the initial treatment for esotropia. The authors suggest that in patients with AACE, even subtle symptoms and signs of Chiari I malformation should prompt imaging of the posterior fossa. Strong consideration should be given to performing posterior fossa decompression in patients with Chiari I malformation and AACE before strabismus surgery because the esotropia may completely resolve with decompression.

Acute Disease↗

PubMed2004

Stereotactic radiosurgical treatment in 103 patients for 153 cerebral melanoma metastases.

PURPOSE: To report on the outcome of patients with melanoma brain metastases treated with stereotactic radiosurgery (SRS). PATIENTS AND METHODS: One hundred three patients with 153 intracranial melanoma metastases consecutively underwent Linac-based SRS between November 1991 and October 2001. The Kaplan-Meier method, univariate comparisons with log-rank test, and multivariate analyses with classification and regression tree models were performed. Calculations were based on last imaging date rather than the date of the last visit. RESULTS: Median age was 51 years (range, 18-93 years). Median Karnofsky performance status was 90. Sixty-one patients (59%) had single brain metastasis at presentation. Treatment sequence was SRS alone (61 patients), SRS + whole-brain radiotherapy (WBRT) (12 patients), and salvage SRS after WBRT (30 patients). The median tumor volume was 1.9 cm(3) (range, 0.06-22.3 cm(3)). The median SRS minimum peripheral dose and isodose was 18 Gy (range, 10-24 Gy) and 85% (range, 60%-100%), respectively. The median follow-up was 6 months for all patients and 13 months (range, 2-46 months) for patients alive at the time of analysis. The 1-year local control (LC) for all patients treated with SRS was 49%. Among the patients treated with initial SRS alone, the 1-year LC was better for patients with tumors < or =2 cm(3) than with tumors >2 cm(3): 75.2% vs. 42.3% (p < 0.05). The 1-year distant brain metastasis-free survival incidence was 14.7% for the 73 patients receiving either initial SRS alone or SRS +WBRT. The initial number of brain lesions (single vs. multiple) was the only factor with a significant effect on distant brain metastasis-free survival at 1 year: 23.5% for single metastases and 0% for multiple lesions (p < 0.05). The 1-year overall survival was 25.2%. Stratification by Score Index for Radiosurgery (SIR) revealed a significant effect on survival, which was 29% at 1 year for SIR >6 and 10% for SIR <==6 (relative hazard ratio, 2.1; p < 0.05) in classification and regression-tree multivariate analysis involving age, Karnofsky performance status, primary tumor control, tumor volume, SRS dose, SIR (>6 vs. < or =6), and systemic disease status. CONCLUSIONS: Initial SRS alone was an effective treatment modality for smaller cerebral melanoma metastases, achieving a 75% incidence of 1-year LC for < or =2 cm(3) single brain metastases and should be considered in patients with SIR >6. The role of WBRT in melanoma brain metastases cannot be addressed, owing to retrospective bias toward administering this treatment to patients with more aggressive disease. A prospective study is needed to assess the role of WBRT in patients with melanoma brain metastasis.

Adolescent↗

PubMed2004

Conversion of myoblasts to physiologically active neuronal phenotype.

Repressor element 1 (RE1)-silencing transcription factor (REST)/neuron-restrictive silencer factor (NRSF) can repress several terminal neuronal differentiation genes by binding to a specific DNA sequence (RE1/neuron-restrictive silencer element [NRSE]) present in their regulatory regions. REST-VP16 binds to the same RE1/NRSE, but activates these REST/NRSF target genes. However, it is unclear whether REST-VP16 expression is sufficient to cause formation of functional neurons either from neural stem cells or from heterologous stem cells. Here we show that the expression of REST-VP16 in myoblasts grown under muscle differentiation conditions blocked entry into the muscle differentiation pathway, countered endogenous REST/NRSF-dependent repression, activated the REST/NRSF target genes, and, surprisingly, activated other neuronal differentiation genes and converted the myoblasts to a physiologically active neuronal phenotype. Furthermore, in vitro differentiated neurons produced by REST-VP16-expressing myoblasts, when injected into mouse brain, survived, incorporated into the normal brain, and did not form tumors. This is the first instance in which myoblasts were converted to a neuronal phenotype. Our results suggest that direct activation of REST/NRSF target genes with a single transgene, REST-VP16, is sufficient to activate other terminal neuronal differentiation genes and to override the muscle differentiation pathways, and they suggest that this approach provides an efficient way of triggering neuronal differentiation in myoblasts and possibly other stem cells.

Animals↗

PubMed2004

A novel E1A-E1B mutant adenovirus induces glioma regression in vivo.

Malignant gliomas are the most frequently occurring primary brain tumors and are resistant to conventional therapy. Conditionally replicating adenoviruses are a novel strategy in glioma treatment. Clinical trials using E1B mutant adenoviruses have been reported recently and E1A mutant replication-competent adenoviruses are in advanced preclinical testing. Here we constructed a novel replication-selective adenovirus (CB1) incorporating a double deletion of a 24 bp Rb-binding region in the E1a gene, and a 903 bp deleted region in the E1b gene that abrogates the expression of a p53-binding E1B-55 kDa protein. CB1 exerted a potent anticancer effect in vitro in U-251 MG, U-373 MG, and D-54 MG human glioma cell lines, as assessed by qualitative and quantitative viability assays. Replication analyses demonstrated that CB1 replicates in vitro in human glioma cells. Importantly, CB1 acquired a highly attenuated replicative phenotype in both serum-starved and proliferating normal human astrocytes. In vivo experiments using intracranially implanted D-54 MG glioma xenografts in nude mice showed that a single dose of CB1 (1.5 x 10(8) PFU/tumor) significantly improved survival. Immunohistochemical analyses of expressed adenoviral proteins confirmed adenoviral replication within the tumors. The CB1 oncolytic adenovirus induces a potent antiglioma effect and could ultimately demonstrate clinical relevance and therapeutic utility.

Adenovirus E1A Proteins↗

PubMed2004

Brain metastases in patients with ovarian carcinoma: prognostic factors and outcome.

Between January 1975 and April 2001, 8,225 patients with ovarian cancer were seen at The University of Texas M.D. Anderson Cancer Center. Brain metastases developed in 72 of these patients (0.9%). The medical records of these patients were reviewed to assess the incidence of these metastases and their correlates of survival, as well as to describe the various treatment modalities used against them and their respective outcomes. The mean age of patients at the time of brain metastasis diagnosis was 53.7 years. The median interval between the diagnosis of the primary cancer and brain metastasis was 1.84 years. Neurological deficit, headache, and seizure were the most common symptoms. The brain was the only site of metastasis in 43% of patients. Multiple metastases were seen in 65% of them, although this may be a slight underestimate, as brain metastases in 17% of patients were evaluated prior to the magnetic resonance imaging era. The median survival time after the diagnosis of brain metastases was 6.27 months (95% CI, 4.48-8.06 months). The combination of surgical resection and whole-brain radiation therapy (WBRT) resulted in a longer survival time (median, 23.07 months) than did WBRT alone (median, 5.33 months) or surgery alone (median, 6.90 months) (p < 0.01 in both instances, multivariate Cox proportional hazards model analysis). The prognosis for patients with brain metastases from ovarian cancer appears to be poor. The existence of systemic dissemination at the time of brain metastasis was associated with a worse survival trend. The only significant predictor of survival in our series was the treatment modality. In particular, the resection of brain metastasis from ovarian cancer followed by WBRT appeared to be superior to resection alone or WBRT alone.

Adenocarcinoma, Mucinous↗

PubMed2004

Brain metastases.

Explore the source record for details and available documents.

Antineoplastic Agents↗

PubMed2004

Cystic glioblastoma multiforme: survival outcomes in 22 cases.

OBJECT: The goal of this study was to determine whether the presence of a large tumor cyst was associated with improved outcome in patients undergoing surgery for newly diagnosed glioblastomas multiforme (GBMs) by comparing these patients with a matched cohort of patients with noncystic GBMs in clinical features, tumor imaging characteristics, survival, and time to tumor recurrence after surgery. METHODS: A retrospective analysis was conducted in 22 patients by using imaging information and chart reviews of operative reports of GBMs with large cysts (> or = 50% of tumor volume) at The University of Texas M. D. Anderson Cancer Center between 1993 and 2002. Clinical and neurosurgical outcomes and recurrence rates were studied. A statistical comparison was made with a matching cohort of 22 patients with noncystic GBMs. No significant differences in clinical variables were found between the cohort with cystic GBMs and the matched cohort with noncystic GBMs. To avoid bias in preoperative assessment of tumor volume, the tumor burden was compared in patients whose tumors had cysts (excluding the cystic mass) and in patients whose tumors did not contain cysts. There was no statistically significant difference between the two groups (p = 0.8). In patients with cystic GBMs the median survival time after surgery was 18.2 months (95% confidence interval [CI] 11.9-24.5 months) and at 2 years 43% of the patients were still alive. In comparison, in patients with noncystic GBMs, the median survival time was 14.3 months (95% CI 12.1-16.4 months) and only 16% of patients were alive at 2 years. The median time to tumor recurrence was 7.6 months (95% CI 0.01-18 months) in patients harboring cystic GBMs and 4.2 months (95% CI 1.8-6.6 months) in the matched cohort (log-rank test, p = 0.04). In the cystic GBM group, no recurrence was observed in 53% of patients at 6 months, 45% at 1 year, and 38% at 2 years after surgery, whereas the corresponding numbers for the noncystic group were 36, 14, and 9%, respectively. CONCLUSIONS: The results indicate that patients harboring a GBM that contains a large cyst survive longer and have a longer time to recurrence than those who lack such a cyst. This is the first such observation in the literature.

Adult↗

PubMed2004

Tumors of the skull base in children and adolescents.

OBJECT: Published data obtained in children with tumors of the skull base are sparse. In the majority of the available reports, the authors focus on the technical application of skull base approaches, but they contribute a paucity of information on the management of specific tumors, especially malignant skull base lesions. The purposes of this report are to increase the collective experience with the treatment of these tumors and to identify successful management paradigms. METHODS: The authors retrospectively reviewed the clinical records, pathological reports, and diagnostic images obtained in 24 children (< or = 19 years of age) with tumors arising from the cranial base in whom resection was part of their management between 1992 and 2002. Surgery-related complications and outcomes were analyzed with regard to tumor type and surgical approach. The median age of the group was 14 years. Tumors involved the anterior skull base in eight (33%), the middle skull base in 10 (42%), both the anterior and middle skull base in four (17%), and the posterior skull base in two patients (8%). Benign lesions were discovered in 11 patients (46%) and malignant neoplasms in 13 (54%). The tumors were most commonly of mesenchymal origin (21 [87.5%] of 24 tumors). Thirty surgical procedures were performed using a number of skull base approaches. A gross-total resection was achieved in 23 procedures (77%) and a subtotal resection in five (17%); a biopsy procedure was performed in one case; and the disease process could not be accessed in one case. One patient died in the perioperative period. Minor complications (Karnofsky Performance Scale score > or = 90, no prolongation of hospital stay, and no further surgery needed) occurred following 10 (33%) of the 30 surgical procedures. These affected 10 (42%) of the 24 patients and resulted in persistent or prolonged deficits in only five patients (21%). In nine patients (38%) the tumor recurred after a mean duration of 23 months. CONCLUSIONS: Skull base tumors in children affect mainly the anterior and middle cranial fossa. Sarcomas account for the majority of malignant tumors. Treatment of skull base tumors in children and adolescents needs to be tailored to patient age, tumor location, and tumor type.

Adolescent↗

PubMed2004

Differential activation of the Fas/CD95 pathway by Ad-p53 in human gliomas.

Adenoviral p53 gene transfer (Ad-p53) induces apoptosis in glioma cells expressing mutant p53, but fails in cells with wild-type p53. Endogenously, gliomas express varied levels of Fas/CD95, yet constitutively high levels of Fas/CD95 ligand. Because the mechanism behind the differential apoptotic response to Ad-p53 infection remains elusive, we examined how the Fas/CD95 pathway is involved in U87MG (wt-p53), D54 (wt-p53), U251MG (mutant-p53), and U373MG (mutant-p53) glioma cell lines. Ad-p53 infection did not alter the levels of Fas/CD95 ligand in either wild-type or mutant p53-expressing cell lines. In contrast, Ad-p53 infection led to an approximately 3-fold increase in Fas/CD95 mRNA expression in mutant p53-bearing cell lines but not in their wild-type (wt) counterparts, as assessed in an RNase protection assay. Fas/CD95 mRNA induction appeared to be regulated at the transcriptional level because Ad-p53 infection resulted in up to a 4-fold increase in Fas/CD95 promoter reporter activity. Subsequently, flow cytometric analysis revealed a 2- to 4-fold increase in surface Fas/CD95 expression following Ad-p53 infection in mutant-p53-containing cell lines. Use of the protein transport inhibitor Brefeldin A significantly inhibited Ad-p53-induced surface Fas/CD95 expression, but only partially inhibited apoptosis in mutant-p53 cell lines. These results suggest that p53 regulates Fas/CD95 expression at the transcriptional level and through protein trafficking in mutant-p53 cell lines. Fluorogenic activity assays demonstrated that induction of caspase-8 activity following Ad-p53 infection correlated with increases in Fas/CD95 expression. Incubating cells with a caspase-8-specific inhibitor Ac-IETD-CHO prior to Ad-p53 infection inhibited caspase-8 activity and apoptosis. Together, our results suggest that regulation of the Fas/CD95 pathway is partly responsible for Ad-p53-induced apoptosis in glioma cells, which depends on the p53 status of the involved cells. Additionally, the inability of Ad-p53 to activate the Fas/CD95 pathway in wt-p53 glioma cells coincides with their apoptotic-resistant phenotype. Further elucidation of the nature of this resistance could ultimately augment the efficacy of Ad-p53 gene therapy.

Adenoviridae↗

PubMed2003

IIp45, an insulin-like growth factor binding protein 2 (IGFBP-2) binding protein, antagonizes IGFBP-2 stimulation of glioma cell invasion.

Our previous studies have shown that insulin-like growth factor binding protein 2 (IGFBP-2) is frequently overexpressed in the highly invasive glioblastoma multiforme (GBM). By using a yeast two-hybrid system, we identified a gene, invasion inhibitory protein 45 (IIp45), whose protein product bound to IGFBP-2 through the thyroglobulin-RGD region of the C terminus of IGFBP-2. The IIp45 gene is located on chromosome 1p36 and has nine exons. The IIp45 protein has three SEG (segment of low compositional complexity) domains and an integrin-binding RGD motif. The IIp45 protein was not expressed in some GBMs. Functional studies showed that IIp45 inhibited GBM cell invasion both in vitro and in xenograft model. Gene expression profiling studies showed that IIp45 consistently inhibited the expression of cell invasion-associated genes, such as the transcriptional NFkappaB, and its downstream target gene, intercellular adhesion molecule 1. Thus, we report here the isolation and characterization of a gene, IIp45, whose protein product binds to IGFBP-2 and inhibits glioma cell invasion.

Adult↗

PubMed2003

Phase I trial of adenovirus-mediated p53 gene therapy for recurrent glioma: biological and clinical results.

PURPOSE: Advances in brain tumor biology indicate that transfer of p53 is an alternative therapy for human gliomas. Consequently, we undertook a phase I clinical trial of p53 gene therapy using an adenovirus vector (Ad-p53, INGN 201). MATERIALS AND METHODS: To obtain molecular information regarding the transfer and distribution of exogenous p53 into gliomas after intratumoral injection and to determine the toxicity of intracerebrally injected Ad-p53, patients underwent a two-stage approach. In stage 1, Ad-p53 was stereotactically injected intratumorally via an implanted catheter. In stage 2, the tumor-catheter was resected en bloc, and the postresection cavity was treated with Ad-p53. This protocol provided intact Ad-p53-treated biologic specimens that could be analyzed for molecular end points, and because the resection cavity itself was injected with Ad-p53, patients could be observed for clinical toxicity. RESULTS: Of fifteen patients enrolled, twelve underwent both treatment stages. In all patients, exogenous p53 protein was detected within the nuclei of astrocytic tumor cells. Exogenous p53 transactivated p21CIP/WAF and induced apoptosis. However, transfected cells resided on average within 5 mm of the injection site. Clinical toxicity was minimal and a maximum-tolerated dose was not reached. Although anti-adenovirus type 5 (Ad5) titers increased in most patients, there was no evidence of systemic viral dissemination. CONCLUSION: Intratumoral injection of Ad-p53 allowed for exogenous transfer of the p53 gene and expression of functional p53 protein. However, at the dose and schedule evaluated, transduced cells were only found within a short distance of the injection site. Although toxicity was minimal, widespread distribution of this agent remains a significant goal.

Adenoviridae↗

PubMed2003

Preclinical characterization of the antiglioma activity of a tropism-enhanced adenovirus targeted to the retinoblastoma pathway.

BACKGROUND: Oncolytic adenoviruses are promising therapies for the treatment of gliomas. However, untargeted viral replication and the paucity of coxsackie-adenovirus receptors (CARs) on tumor cells are major stumbling blocks for adenovirus-based treatment. We studied the antiglioma activity of the tumor-selective Delta-24 adenovirus, which encompasses an early 1 A adenoviral (E1A) deletion in the retinoblastoma (Rb) protein-binding region, and of the Delta-24-RGD adenovirus. Delta-24-RGD has an RGD-4C peptide motif inserted into the adenoviral fiber, which allows the adenovirus to anchor directly to integrins. METHODS: CAR and integrin expression were examined by flow cytometry in six glioma cell lines and in normal human astrocytes (NHAs). Adenoviral vectors containing green fluorescent protein (GFP) (AdGFP and AdGFP-RGD) were used to infect glioma cell lines with high or low CAR expression. Viability of glioma cells infected with different adenoviruses was assessed by trypan blue staining. Adenovirus replication was quantified with the infection-dose replication assay. Athymic mice carrying glioma xenografts received intratumoral injections of Delta-24-RGD or Delta-24 and were followed for survival, which was analyzed by the Kaplan-Meier method and the log-rank test. All statistical tests were two-sided. RESULTS: Half the glioma cell lines expressed low levels of CAR (defined as <50% of cells expressing detectable CAR); all lines expressed integrins in more than 50% of cells. Infection of U-87 MG cells (a low-CAR-expressing line) with AdGFP-RGD resulted in approximately six times more GFP-positive cells than infection with AdGFP. Delta-24-RGD was more cytopathic to both low- and high-CAR-expressing glioma lines than Delta-24, and it replicated more efficiently in both cell lines. In the xenografted mice, intratumoral injection of Delta-24-RGD was associated with longer survival than intratumoral injection of Delta-24 (P<.001, log-rank test). Furthermore, 60% of Delta-24-RGD-treated mice but only 15% of Delta-24-treated mice survived more than 4 months (difference = 45%, 95% CI = 21% to 68%). CONCLUSIONS: The antitumor activity of Delta-24-RGD suggests that it has the potential to be an effective agent in the treatment of gliomas.

Adenoviridae↗

PubMed2003

Surgical resection of metastatic intraventricular tumors.

The ventricle is a rare site of brain metastases. Renal cell carcinoma has a higher propensity to metastasize to the ventricle compared with more common metastatic tumors (e.g., lung cancer). The trigone is the predominant location for intraventricular metastases, presumably because of the high concentration of choroid plexus in this region. Surgical resection is an important component of the management of these lesions, particularly if there is only a single intraventricular lesion. Despite the deep location of these tumors within the ventricle, survival in patients undergoing surgery for them is comparable to that in patients receiving surgery for intraparenchymal metastases.

Adult↗

PubMed2003

Clinical trials of adenoviruses in brain tumors: a review of Ad-p53 and oncolytic adenoviruses.

Adenoviruses have been critical in the development of the molecular approaches to brain tumors. They have been engineered to function as vectors for delivering therapeutic genes in gene therapy strategies, and as direct cytotoxic agents in oncolytic viral therapies. This review outlines the uses of adenoviruses in brain tumor therapy by examining clinical trials of adenovirus-mediated p53 gene therapy and by reviewing the application of two conditionally replicative adenoviruses (CRAds) ONYX-015 and Delta 24 in brain tumors. The potential clinical use of CRAds that deliver trangenes, particularly p53, is also discussed.

Adenoviridae↗

PubMed2003

The role of tumor size in the radiosurgical management of patients with ambiguous brain metastases.

OBJECTIVE: To identify a size cutoff below which it is safe to observe obscure brain lesions suspected of being metastases so that treatment of nonmetastases can be avoided. METHODS: Medical records from patients who underwent linear accelerator-based radiosurgery from August 1991 to October 2001 were reviewed. Inclusion criteria were defined as brain metastasis tumor volume less than 5 cm(3) (diameter, thick similar 2.1 cm) treated with a dose of 20 Gy or more. One hundred thirty-five patients had 153 evaluable brain metastases with follow-up imaging that met inclusion criteria. Median age was 54 years (range, 18-79 yr). Lesion primaries were non-small-cell lung (n = 39), melanoma (n = 44), renal (n = 37), breast (n = 18), colon (n = 3), sarcoma (n = 5), other (n = 5), and unknown primary (n = 2). Median tumor volume was 0.67 cm(3) (range, 0.06-4.58 cm(3)). The minimum peripheral dose was 20 Gy (n = 132) or 21 to 24 Gy (n = 21). At the time of analysis, the median follow-up for all patients was 10 months (range, 0.2-99 mo). RESULTS: The 1- and 2-year actuarial local control rates for all of the lesions were 69 and 46%, respectively. For lesions of 1 cm (0.5 cm(3)) or less, the corresponding local control rates were 86 and 78%, respectively, which was significantly higher than the corresponding rates of 56 and 24%, respectively, for lesions larger than 1 cm (0.5 cm(3)) (P = 0.0016). CONCLUSION: A convincing brain metastasis measuring less than 1 cm should be pursued aggressively. If the suspected brain metastasis is ambiguous, observation is proposed up to a diameter of 1 cm. This is the first study in the literature to identify a 1-cm cutoff for radiosurgical control of small brain metastases, and validation by additional studies is required.

Actuarial Analysis↗