Minor head injury: CT-based strategies for management--a cost-effectiveness analysis.

PURPOSE: To compare the cost-effectiveness of using selective computed tomographic (CT) strategies with that of performing CT in all patients with minor head injury (MHI). MATERIALS AND METHODS: The internal review board approved the study; written informed consent was obtained from all interviewed patients. Five strategies were evaluated, with CT performed in all patients with MHI; selectively according to the New Orleans criteria (NOC), Canadian CT head rule (CCHR), or CT in head injury patients (CHIP) rule; or in no patients. A decision tree was used to analyze short-term costs and effectiveness, and a Markov model was used to analyze long-term costs and effectiveness. n-Way and probabilistic sensitivity analyses and value-of-information (VOI) analysis were performed. Data from the multicenter CHIP Study involving 3181 patients with MHI were used. Outcome measures were first-year and lifetime costs, quality-adjusted life-years, and incremental cost-effectiveness ratios. RESULTS: Study results showed that performing CT selectively according to the CCHR or the CHIP rule could lead to substantial U.S. cost savings ($120 million and $71 million, respectively), and the CCHR was the most cost-effective at reference-case analysis. When the prediction rule had lower than 97% sensitivity for the identification of patients who required neurosurgery, performing CT in all patients was cost-effective. The CHIP rule was most likely to be cost-effective. At VOI analysis, the expected value of perfect information was $7 billion, mainly because of uncertainty about long-term functional outcomes. CONCLUSION: Selecting patients with MHI for CT renders cost savings and may be cost-effective, provided the sensitivity for the identification of patients who require neurosurgery is extremely high. Uncertainty regarding long-term functional outcomes after MHI justifies the routine use of CT in all patients with these injuries.

SOX antibodies in small-cell lung cancer and Lambert-Eaton myasthenic syndrome: frequency and relation with survival.

PURPOSE: SOX1 antibodies are common in small-cell lung carcinoma (SCLC) with and without paraneoplastic syndrome (PNS) and can serve as serological tumor marker. Addition of other antibodies might improve its diagnostic power. We validated an enzyme-linked immunosorbent assay (ELISA) to assess the diagnostic value of serum antibodies in SCLC and Lambert-Eaton myasthenic syndrome (LEMS). Clinical outcome with respect to SOX antibodies was evaluated, as the SOX-related antitumor immune response might help to control the tumor growth. PATIENTS AND METHODS: We used recombinant SOX1, SOX2, SOX3, SOX21, HuC, HuD, or HelN1 proteins in an ELISA to titrate serum samples and validated the assay by western blot. We tested 136 consecutive SCLC patients, 86 LEMS patients (43 with SCLC), 14 patients with SCLC and PNS (paraneoplastic cerebellar degeneration or Hu syndrome), 62 polyneuropathy patients, and 18 healthy controls. RESULTS: Our ELISA was equally reliable as western blot. Forty-three percent of SCLC patients and 67% of SCLC-LEMS patients had antibodies to one of the SOX or Hu proteins. SOX antibodies had a sensitivity of 67% and a specificity of 95% to discriminate between LEMS with SCLC and nontumor LEMS. No difference in survival was observed between SOX positive and SOX negative SCLC patients. CONCLUSION: SOX antibodies are specific serological markers for SCLC. Our assay is suitable for high throughput screening, detecting 43% of SCLC. SOX antibodies have diagnostic value in discriminating SCLC-LEMS from nontumor LEMS, but have no relation to survival in patients with SCLC.

Cognitive rehabilitation in patients with gliomas: a randomized, controlled trial.

PURPOSE: Patients with gliomas often experience cognitive deficits, including problems with attention and memory. This randomized, controlled trial evaluated the effects of a multifaceted cognitive rehabilitation program (CRP) on cognitive functioning and selected quality-of-life domains in patients with gliomas. PATIENTS AND METHODS: One hundred forty adult patients with low-grade and anaplastic gliomas, favorable prognostic factors, and both subjective cognitive symptoms and objective cognitive deficits were recruited from 11 hospitals in the Netherlands. Patients were randomly assigned to an intervention group or to a waiting-list control group. The intervention incorporated both computer-based attention retraining and compensatory skills training of attention, memory, and executive functioning. Participants completed a battery of neuropsychological (NP) tests and self-report questionnaires on cognitive functioning, fatigue, mental health-related quality of life, and community integration at baseline, after completion of the CRP, and at 6-month follow-up. RESULTS: At the immediate post-treatment evaluation, statistically significant intervention effects were observed for measures of subjective cognitive functioning and its perceived burden but not for the objective NP outcomes or for any of the other self-report measures. At the 6-month follow-up, the CRP group performed significantly better than the control group on NP tests of attention and verbal memory and reported less mental fatigue. Group differences in other subjective outcomes were not significant at 6 months. CONCLUSION: The CRP has a salutary effect on short-term cognitive complaints and on longer-term cognitive performance and mental fatigue. Additional research is needed to identify which elements of the intervention are most effective.

Detection of brain metastases from small cell lung cancer: consequences of changing imaging techniques (CT versus MRI).

BACKGROUND: The aims of this study were to show 1) the effect of changing from computed tomography (CT) to magnetic resonance imaging (MRI) on the prevalence of detected brain metastases (BM) in patients with newly diagnosed small cell lung cancer (SCLC); 2) the difference in survival between patients with single and multiple BM; and 3) the effect of the change in patient labeling on eligibility for prophylactic brain irradiation. METHODS: From 1980 to 2004, 481 consecutive patients with SCLC were enrolled. Brain imaging was routinely performed after diagnosis of SCLC. At the start of 1991, MRI replaced CT in almost all patients. All patients were regularly examined by a neurologist. RESULTS: The prevalence of detected BM was 10% in the CT era and 24% in the MRI era. In the CT era, all detected BM were symptomatic, whereas in the MRI era, 11% were asymptomatic. In both periods, patients labeled as single BM survived longer than those labeled as multiple BM. For patients labeled as single BM or multiple BM, survival was longer in the MRI era than in the CT era. The proportion of patients who were eligible for prophylactic cranial irradiation was lower in the MRI era. CONCLUSIONS: The estimated prevalence of BM increases when MRI is used instead of CT. Patients with a detected single BM survive longer than patients with multiple BM. The apparently increased survival in the MRI era can be attributed to the "Will Rogers phenomenon". The use of MRI makes fewer patients eligible for prophylactic cranial irradiation.

Minor head injury: guidelines for the use of CT--a multicenter validation study.

PURPOSE: To prospectively and externally validate published national and international guidelines for the indications of computed tomography (CT) in patients with a minor head injury. MATERIALS AND METHODS: The study protocol was institutional review board approved. All patients implicitly consented to use of their deidentified data for research purposes. Between February 2002 and August 2004, data were collected in consecutive adult patients with blunt minor head injury (Glasgow Coma Scale score of 13-14 or 15) and a risk factor for neurocranial traumatic complications at presentation at four Dutch university hospitals. Primary outcome was any neurocranial traumatic CT finding. Secondary outcomes were clinically relevant traumatic CT findings and neurosurgical intervention. Sensitivity and specificity of each guideline for all outcomes and the number of patients needed to scan to detect one outcome (ie, the number of patients needed to undergo CT to find one patient with a neurocranial traumatic CT finding, a clinically relevant traumatic CT finding, or a CT finding that required neurosurgical intervention) were estimated. RESULTS: Data were available for 3181 patients. Only the European Federation of Neurological Societies guidelines reached a sensitivity of 100% for all outcomes. Specificity was 0.0%-0.5%. The Dutch guidelines had the lowest sensitivity (76.5%) for neurosurgical interventions. The best specificities for traumatic CT findings and neurosurgical interventions were reached with the criteria proposed by the United Kingdom National Institute for Clinical Excellence (NICE) (46.1% and 43.6%, respectively), albeit at relatively low sensitivities (82.1% and 94.1%, respectively). The number of patients needed to scan ranged from six to 13 for traumatic CT findings and from 79 to 193 for neurosurgical interventions. CONCLUSION: All validated guidelines demonstrated a trade-off between sensitivity and specificity. The lowest number of patients needed to scan for either of the outcomes was reached with the NICE criteria. SUPPLEMENTAL MATERIAL: radiology.rsnajnls.org/cgi/content/full/2452061509/DC1 (c) RSNA, 2007.

Predicting intracranial traumatic findings on computed tomography in patients with minor head injury: the CHIP prediction rule.

BACKGROUND: Prediction rules for patients with minor head injury suggest that the use of computed tomography (CT) may be limited to certain patients at risk for intracranial complications. These rules apply only to patients with a history of loss of consciousness, which is frequently absent. OBJECTIVE: To develop a prediction rule for the use of CT in patients with minor head injury, regardless of the presence or absence of a history of loss of consciousness. DESIGN: Prospective, observational study. SETTING: 4 university hospitals in the Netherlands that participated in the CT in Head Injury Patients (CHIP) study. PATIENTS: Consecutive adult patients with minor head injury (> or =16 years of age) with a Glasgow Coma Scale (GCS) score of 13 to 14 or with a GCS score of 15 and at least 1 risk factor. MEASUREMENTS: Outcomes were any intracranial traumatic CT finding and neurosurgical intervention. The authors performed logistic regression analysis by using variables from existing prediction rules and guidelines, with internal validation by using bootstrapping. RESULTS: 3181 patients were included (February 2002 to August 2004): 243 (7.6%) had intracranial traumatic CT findings and 17 (0.5%) underwent neurosurgical intervention. A detailed prediction rule was developed from which a simple rule was derived. Sensitivity of both rules was 100% for neurosurgical interventions, with an associated specificity of 23% to 30%. For intracranial traumatic CT findings, sensitivity and specificity were 94% to 96% and 25% to 32%, respectively. Potential CT reduction by implementing the prediction rule was 23% to 30%. Internal validation showed slight optimism for the model's performance. LIMITATION: External validation of the prediction model will be required. CONCLUSION: The authors propose the highly sensitive CHIP prediction rule for the selective use of CT in patients with minor head injury with or without loss of consciousness.

A pathology-based substrate for target definition in radiosurgery of brain metastases.

PURPOSE: To investigate the need of a margin other than for accuracy reasons in stereotactic radiosurgery (SRS) of brain metastases by means of histopathology. METHODS AND MATERIALS: Evaluation of 45 patients from two pathology departments having had brain metastases and an autopsy of the brain. Growth patterns were reviewed with a focus on infiltration beyond the metastases boundary and made visible with immunohistochemical staining: the metastasis itself with tumor-specific markers, surrounding normal brain tissue with a glial marker, and a possible capsule with a soft tissue marker. Measurements were corrected by a tissue-shrinkage correction factor taken from literature. Outcomes parameters for infiltration were mean and maximum depths of infiltration and number of measured infiltration sites. RESULTS: In 48 of 76 metastases, an infiltration was present. The largest group of metastases was lung cancer. Small-cell lung cancer (SCLC) and melanoma showed a maximum depth of infiltration of > or =1 mm, and other histologies <1 mm. For non-small-cell lung cancer (NSCLC), melanoma, and sarcoma, the highest number of infiltrative sites were observed (median, 2; range, 1-8). SCLC showed significantly larger infiltrative growth, compared with other diagnostic groups. In NSCLC, the highest percentage of infiltration was present (70%). CONCLUSIONS: Infiltrative growth beyond the border of the brain metastasis was demonstrated in 63% of the cases evaluated. Infiltrative growth, therefore, has an impact in defining the clinical target volume for SRS of brain metastases, and a margin of approximately 1 mm should be added to the visible lesion.

Response of asymptomatic brain metastases from small-cell lung cancer to systemic first-line chemotherapy.

PURPOSE: The purpose of this study was to investigate the radiologic response of asymptomatic brain metastases (BM) from small-cell lung cancer (SCLC) to first-line systemic chemotherapy. PATIENTS AND METHODS: From 1990 to 2003, 181 consecutive patients with SCLC were enrolled onto this study. Patients were examined by a neurologist on a regular basis. Magnetic resonance imaging (MRI) of the brain was performed routinely before (at diagnosis of SCLC) and after first-line systemic chemotherapy. Patients were treated with combination chemotherapy consisting of cyclophosphamide, doxorubicin, and etoposide. Clinically manifest BM were treated with whole-brain radiotherapy (WBRT). The response rate (RR) of BM was assessed by changes in the size or the number of enhanced lesions on MRI using standard criteria. RESULTS: Synchronous asymptomatic BM were found in 24 SCLC patients (13%). In six (27%) of the 22 assessable patients, the asymptomatic BM responded to systemic chemotherapy. A systemic response was found in 16 patients (73%). All patients became symptomatic during follow-up. The symptom-free survival did not differ between cranial responders and cranial nonresponders. CONCLUSION: The RR of asymptomatic BM from SCLC to systemic chemotherapy is 27% and evidently lower than the systemic RR. Future studies should focus on the possible beneficial effect of WBRT for patients with asymptomatic synchronous BM.

External validation of the Canadian CT Head Rule and the New Orleans Criteria for CT scanning in patients with minor head injury.

CONTEXT: Two decision rules for indications of computed tomography (CT) in patients with minor head injury, the Canadian CT Head Rule (CCHR) and the New Orleans Criteria (NOC), suggest that CT scanning may be restricted to patients with certain risk factors, which would lead to important reductions in the use of CT scans. OBJECTIVE: To validate and compare these 2 published decision rules in Dutch patients with head injuries. DESIGN, SETTING, AND PATIENTS: A prospective multicenter study conducted between February 11, 2002, and August 31, 2004, in 4 university hospitals in the Netherlands of 3181 consecutive adult patients with minor head injury who presented with a Glasgow Coma Scale (GCS) score of 13 to 14 or with a GCS score of 15 and at least 1 risk factor. MAIN OUTCOME MEASURES: Primary outcome was any neurocranial traumatic finding on CT scan. Secondary outcomes were neurosurgical intervention and clinically important CT findings. Sensitivity and specificity were estimated for each outcome for the CCHR and the NOC, using both rules as originally derived and also as adapted to apply to an expanded patient population. RESULTS: Of 3181 patients with a GCS score of 13 to 15, neurosurgical intervention was performed in 17 patients (0.5%); neurocranial traumatic CT findings were present in 312 patients (9.8%). Sensitivity for neurosurgical intervention was 100% for both the CCHR and the NOC. The NOC had a higher sensitivity for neurocranial traumatic findings and for clinically important findings (97.7%-99.4%) than did the CCHR (83.4%-87.2%). Specificities were very low for the NOC (3.0%-5.6%) and higher for the CCHR (37.2%-39.7%). The estimated potential reduction in CT scans for patients with minor head injury would be 3.0% for the adapted NOC and 37.3% for the adapted CCHR. CONCLUSIONS: For patients with minor head injury and a GCS score of 13 to 15, the CCHR has a lower sensitivity than the NOC for neurocranial traumatic or clinically important CT findings, but would identify all cases requiring neurosurgical intervention, and has greater potential for reducing the use of CT scans.

Leptomeningeal metastases from small cell lung carcinoma.

BACKGROUND: The current study was performed to investigate the frequency of leptomeningeal metastases (LMM) in patients with small cell lung carcinoma (SCLC) as well as the effect of LMM on survival, any correlation between the location of the LMM and survival, and a possible increased risk of LMM among patients with brain metastases (BM) located in the posterior fossa. METHODS: Between 1980-2003, 458 consecutive patients with SCLC were enrolled in the current study. Patients underwent regular neurologic examination and imaging of the brain before, during, and after treatment. The diagnosis of LMM was established by either the presence of malignant cells in the cerebrospinal fluid or positive clinical symptoms and signs supported by radiologic findings on magnetic resonance imaging. RESULTS: The group of patients in the current study had a 2% prevalence of LMM and the 2-year cumulative incidence of LMM was found to be 10%. The median survival after the diagnosis of LMM was reported to be 1.3 months. The median survival among patients with LMM located in the spinal cord was 2.4 months. The reported LMM-free survival 2 years after the diagnosis of SCLC was 78% for patients without BM and 61% for those patients with BM. Approximately 15% of the patients with BM located in the posterior fossa developed LMM, whereas only 10% of patients with cerebral BM did. CONCLUSIONS: The current prospective study found a 2-year cumulative incidence of LMM of 10%, with a prevalence of 2%. Patients with LMM located in the spinal cord appeared to survive longer than patients with cranial LMM. SCLC patients with BM located in the posterior fossa may be at a higher risk of developing LMM compared with patients with cerebral BM.

P/Q-type calcium channel antibodies, Lambert-Eaton myasthenic syndrome and survival in small cell lung cancer.

To assess the survival impact of the presence of P/Q-type calcium channel antibodies in patients with small cell lung carcinoma (SCLC), we examined the frequency of the antibodies and Lambert-Eaton myasthenic syndrome (LEMS) in 148 consecutive patients with SCLC, and in 30 patients with paraneoplastic cerebellar degeneration and SCLC, and studied their relation with survival. In both series, only patients with LEMS had a remarkably long survival, whereas presence of the antibodies without LEMS did not result in a better prognosis.

S-100B concentration is not related to neurocognitive performance in the first month after mild traumatic brain injury.

The serum concentration of S-100B is reported to reflect the severity of brain damage. The purpose of this study was to determine whether elevated serum S-100B concentrations were related to neuropsychological test performance of patients in the subacute phase of recovery from mild traumatic brain injury (TBI). S-100B concentrations were measured in blood samples taken within 6 h after TBI. Serum S-100B was estimated using an immunoluminometric assay. Cognitive speed and memory were assessed with neuropsychological tests at a median of 13 days (range 7-21 days) after injury. The two groups, formed on a median split of initial serum S-100B concentrations (>or<0.22 microg/l) did not differ in age or education. The neuropsychological performance of the TBI patients was also compared with that of a healthy control group. Cognitive speed and memory performance of mild TBI patients were inferior compared to those of healthy subjects. There were no significant differences within the TBI group when serum S-100B concentration was taken into consideration. The findings suggest that serum S-100B levels after mild TBI are not predictive of neuropsychological performance in the subacute stage of recovery.

Brain- and heart-type fatty acid-binding proteins in the brain: tissue distribution and clinical utility.

BACKGROUND: Detection of brain injury by serum markers is not a standard procedure in clinical practice, although several proteins, such as S100B, neuron-specific enolase (NSE), myelin basic protein, and glial fibrillary acidic protein, show promising results. We investigated the tissue distribution of brain- and heart-type fatty acid-binding proteins (B-FABP and H-FABP) in segments of the human brain and the potential of either protein to serve as plasma marker for diagnosis of brain injury. METHODS: B-FABP and H-FABP were measured immunochemically in autopsy samples of the brain (n = 6) and in serum samples from (a) patients with mild traumatic brain injury (MTBI; n = 130) and (b) depressed patients undergoing bilateral electroconvulsive therapy (ECT; n = 14). The protein markers S100B and NSE were measured for comparison. Reference values of B-FABP and H-FABP were established in healthy individuals (n = 92). RESULTS: The frontal, temporal, and occipital lobes, the striatum, the pons, and the cerebellum had different tissue concentrations of B-FABP and of H-FABP. B-FABP ranged from 0.8 microg/g wet weight in striatum tissue to 3.1 microg/g in frontal lobe. H-FABP was markedly higher, ranging from 16.2 microg/g wet weight in cerebellum tissue to 39.5 microg/g in pons. No B-FABP was detected in serum from healthy donors. H-FABP serum reference value was 6 microg/L. In the MTBI study, serum B-FABP was increased in 68% and H-FABP in 70% of patients compared with S100B (increased in 45%) and NSE (increased in 51% of patients). In ECT, serum B-FABP was increased in 6% of all samples (2 of 14 patients), whereas H-FABP was above its upper reference limit (6 microg/L) in 17% of all samples (8 of 14 patients), and S100B was above its upper reference limit (0.3 microg/L) in 0.4% of all samples. CONCLUSIONS: B-FABP and H-FABP patterns differ among brain tissues, with the highest concentrations in the frontal lobe and pons, respectively. However, in each part of the brain, the H-FABP concentration was at least 10 times higher than that of B-FABP. Patient studies indicate that B-FABP and H-FABP are more sensitive markers for minor brain injury than the currently used markers S100B and NSE.

Neurologic disorders in 432 consecutive patients with small cell lung carcinoma.

BACKGROUND: Neurologic complications are an important cause of morbidity and possibly also mortality in patients with small cell lung carcinoma (SCLC). The current study was undertaken to prospectively investigate survival and the frequency of neurologic disorders in patients with SCLC. METHODS: Between October 1980 and September 2001, 432 consecutive patients with microscopically proven SCLC were included in the current study. Patients underwent neurologic examinations on a regular basis prior to, during, and after treatment. Routine imaging of the brain (computed tomography or magnetic resonance imaging) was performed before and after systemic therapy. RESULTS: A neurologic disorder was diagnosed in approximately 56% of the SCLC patients. In nearly half of the cases, the neurologic disorder already was present at the time of diagnosis. Brain metastases (BM) were diagnosed most frequently. Seventy-four patients (18%) had BM at the time of diagnosis; in 20 of these patients, the BM did not demonstrate clinical signs. Another 101 patients developed BM during follow-up. The 2-year cumulative risk of BM reached 49% for patients with limited disease (LD) and 65% for patients with extensive disease (ED). Patients with BM as the only site of disease dissemination were found to have a poorer survival compared with LD patients. The majority of the nonmetastatic disorders preceded the diagnosis of SCLC. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) was diagnosed most frequently. CONCLUSIONS: In this prospective study, neurologic disorders were diagnosed in greater than half of the patients with SCLC. BM were detected most frequently. Approximately 18% of the patients were found to have BM at the time of diagnosis. In approximately 33% of the cases, these BM did not cause symptoms. BM were found to have a negative effect on survival in patients with SCLC.

10q25.3 (DMBT1) copy number changes in astrocytoma grades II and IV.

In the literature, it has been suggested that loss of the 10q25-26 region, including the DMBT1 gene (10q25.3), is correlated with initiation and/or malignant progression of astrocytomas, although the results of the studies on the loss of heterozygosity that led to this assumption are not unequivocal. For this reason, using double-target fluorescence in situ hybridization, we compared copy number changes of 10q25.3 to those of the pericentromeric region (10q12) in 10 cases each of astrocytoma grades II and IV. The same specimens were analyzed for copy number changes of chromosome 1, as a marker for polyploidy, and chromosome 7, which is often gained in astrocytomas of all grades. Our results show that selective loss of the 10q25.3 region was present in 2 of 10 specimens in both astrocytoma grade II and grade IV, occurring only in tumors with polysomy for 10q12. Furthermore, astrocytoma grade II often showed polyploidy for chromosomes 1, 7, and 10 (8 of 10 specimens). In addition, astrocytoma grade IV frequently exhibited losses of chromosome 10 in a high percentage of nuclei. Although based on a small number of cases, the results clearly show that loss of the 10q25.3 region is uncommon in astrocytoma grade II and mostly coincident with loss of chromosome 10 in grade IV tumors. These data indicate that selective loss of the 10q25.3 region, including the DMBT1 gene, is not an initiating event in the genesis of astrocytoma grade II.

Supratentorial grade II astrocytoma: biological features and clinical course.

Because of its unpredictable clinical course, treatment strategies for low-grade (grade II) astrocytoma vary from "wait and see" to gross tumour resection followed by immediate radiotherapy. Clinical studies on grade II astrocytoma show that 5-year-survival ranges from 27% to 85% of patients with very few consistent prognostic variables besides the patient's age and the presence of neurological deficit. There is no universally recognised choice of therapy for patients with astrocytoma grade II, partly because of the shortcomings of histological classification systems. Routine microscopy tends to underestimate malignancy grading of astrocytomas and in most cases cannot distinguish between indolent and progressive subtypes. Recent studies suggest that proliferation and genetic markers can be used to identify subgroups of astrocytoma grade II with a rapid progressive clinical course. Therefore these markers should be included in ongoing and future clinical studies of patients with astrocytoma grade II.

Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma.

BACKGROUND: The objective of this study was to report on the incidence of and factors related to the occurrence of central nervous system metastases in a cohort of patients who were diagnosed with colorectal, lung, breast, or kidney carcinoma or melanoma. METHODS: Using the population-based Maastricht Cancer Registry (MCR), a cohort was created of patients with colorectal carcinoma (n = 720 patients), lung carcinoma (n = 938 patients), breast carcinoma (n = 802 patients), renal carcinoma (n = 114 patients), and melanoma (n = 150 patients). The patients had to live in the catchment area of the University Hospital Maastricht (UHM) and had to have been diagnosed at the UHM during the period 1986-1995. Patients with brain metastases were searched for by linking the MCR to the Neuro-Oncology Registry of the UHM. Radiology files were checked as well. Follow-up lasted until December 31, 1998. RESULTS: Brain metastases were diagnosed in 232 patients (8.5%) in the cohort (n = 2724 patients). Of these patients, 84 patients were diagnosed with brain metastases within 1 month after their primary diagnosis, 82 patients were diagnosed with brain metastases within 1 year of their primary diagnosis, and 66 patients were diagnosed with brain metastases more than 1 year after their primary diagnosis. The cumulative incidence after 5 years was estimated at 16.3% in patients with lung carcinoma, 9.8% in patients with renal carcinoma, 7.4% in patients with melanoma, 5.0% in patients with breast carcinoma, and 1.2% in patients with colorectal carcinoma. The incidence was lower in patients age > or = 70 years compared with younger patients (breast and lung carcinoma), lower in patients who were diagnosed before 1991 compared with patients who were diagnosed after 1991 (breast and lung carcinoma), and lower in patients who had nonsmall cell lung carcinoma compared with patients who had small cell lung carcinoma. CONCLUSIONS: The frequency of brain metastases in this cohort was highest in patients with lung carcinoma, followed by patients with renal carcinoma. There was no evidence of an increasing incidence of brain metastasis in patients with carcinoma of the breast or lung.

Gain of chromosome 7, as detected by in situ hybridization, strongly correlates with shorter survival in astrocytoma grade 2.

The clinical course of astrocytoma grade 2 (A2) is highly variable and is not reflected by morphological characteristics. Earlier studies using small series of A2 cases suggest that in situ hybridization (ISH) with chromosome-specific DNA probes allows for frequent detection of aneusomy 1, trisomy 7, and monosomy 10. The role of trisomy 7 in astrocytoma carcinogenesis is disputed, however, because of its presence in non-neoplastic brain tissue, as detected by karyotyping. Our objective was to investigate whether there was a correlation between chromosomal aberrations and survival in a series of 47 cases of A2. All cases were evaluated for numerical aberrations of chromosomes 1, 7, and 10 by ISH. Chromosomal aberrations were detected in 68% of cases of A2. Trisomy/polysomy 7 was seen in 31 cases (66%), 22 of which (47%) had a high percentage of this numerical aberration. Only 11 of these 22 cases also showed aneusomy for 1 or 10. No cells or only a few cells with aberrations were detected in non-neoplastic control samples. Using Kaplan-Meier analysis, trisomy/polysomy 7 correlated significantly with shorter survival. Hence, as determined by ISH, trisomy/polysomy 7 is absent in non-neoplastic brain tissue and is frequently detected in A2, correlating with the malignant progression of the disease.