Wednesday, January 30, 2013

"Women who smoke like men, die like men"

N Engl J Med2013;368:341-50N Engl J Med2013;368:351-64Smoking has become substantially riskier for women during the past 50 years, say researchers. Analyses from two historical and five contemporary...







Júlio Leonardo B. Pereira
Phone: (+1) 424-2301706
Linkedin:http://www.linkedin.com/in/juliommais 
Site: www.neurocirurgiabr.com
Postado por No comments:

Thursday, January 24, 2013

Long-term survival of patients with glioblastoma multiforme (GBM)

Available online 23 January 2013
Publication year: 2013
Source:Journal of Clinical Neuroscience

Long-term survival is an often used, yet poorly defined, concept in the study of glioblastoma multiforme (GBM). This study suggests a method to define a time-point for long-term survival in patients with GBM. Data for this study were obtained from the Surveillance, Epidemiology and End-Results database, which was limited to the most recent data using the period approach. Relative survival measures were used and modelled using piecewise constant hazards to describe the survival profile of long-term survivors of GBM. For patients with GBM, the first quarter of the second year (5th quarter) post-diagnosis is considered to be the peak incidence of mortality with an excess hazard ratio of 7.58 (95% confidence interval=6.54, 8.78) and the risk of death due to GBM decreases to half of its rate at 2.5years post-diagnosis. The 2.5-year cumulative relative survival (CRS) for all patients is approximately 8%, with a CRS of approximately 2% at 10years. Using the definition of long-term survival suggested here, the results indicate that long-term survivors are patients who survive at least 2.5years post-diagnosis. The most likely time period for patients with GBM to die is the 5th quarter post-diagnosis.






Postado por No comments:

Tweet to Learn

@thomascmurray: I learn more on Twitter in one week than I did in ANY grad course, which by the way, I paid for. Who's with me? #edtech #edchat #satchat @sjunkins: Twitter is everything a teachers lounge should be... Inspiring educators with engaging ideas. #iaedchat [More]

Add to digg Add to StumbleUpon Add to Reddit Add to Facebook Add to del.icio.us Email this Article





Postado por No comments:

Saturday, January 19, 2013

Diffusion-Weighted MR Imaging and MGMT Methylation Status in Glioblastoma: A Reappraisal of the Role

Published online before print December 28, 2012, doi: 10.3174/ajnr.A3467
AJNR 2013 34: E10-E11

A. Guptaa
aDepartment of Radiology
Weill Cornell Medical College/New-York Presbyterian Hospital
New York, New York

A. Pragerb and R.J. Youngb
bDepartment of Radiology

W. Shic
cDepartment of Epidemiology and Biostatistics

A.M.P. Omurod
dDepartment of Neurology
Memorial Sloan-Kettering Cancer Center
New York, New York

J.J. Grabere
eDepartment of Neurology
Montefiore Medical Center
New York, New York

Methylation of the DNA repair enzyme O6-methylguanine-DNA-methyltransferase (MGMT) has been well described as one the most significant biomarkers of glioblastoma (GBM) patient prognosis and response to standard first-line chemotherapy treatment with temozolomide.1 As such, we read with great interest the recent study published in AJNR in May 2011 entitled "Apparent Diffusion Coefficient Histogram Analysis Stratifies Progression-Free Survival in Newly Diagnosed Bevacizumab-Treated Glioblastoma" by Dr. Pope and colleagues.2

A significant conclusion of this study was that "lower ADC is associated with tumor MGMT promoter methylation." This is a finding of significant interest to radiologists and oncologists alike as it suggests that ADC measures can potentially function as both a prognostic and predictive imaging biomarker and thereby act as a surrogate for the reference standard pathologic determination of MGMT methylation status. The authors arrived at this conclusion based on a pixel-by-pixel ADC histogram analysis with bi-modal curve fitting of enhancing tumor in 89 patients with GBM with pathologically confirmed methylation status. This analysis showed a mean ADC of 1071 × 10−6mm2/s for 36 methylated tumors versus 1183 × 10−6mm2/s for 53 unmethylated tumors, with a P value of .01 between the groups.

To assess the applicability of these findings to our own patients, we retrospectively performed blinded quantitative ADC measurements in 105 treatment naïve, preoperative patients with GBM with pathologically confirmed MGMT promoter methylation status determined through real-time methylation specific polymerase chain reaction. Our goal was to build on the work of Pope et al2 by using an ADC quantification technique readily available from a popular vendor and applicable to daily clinical practice. We performed region of interest analysis by using an off-line commercially available workstation (Advantage; GE Healthcare, Milwaukee, Wisconsin) and software (FuncTools 9.04b; GE Healthcare) to calculate quantititative ADC metrics. We drew ROIs around the contrast enhancing tumor and derived ADCmean, ADCmin, and ADCmax values. In addition, by using a validated and commonly used standardized technique,3,4 we manually placed 4 small circular ROIs (30–50 mm2) in the enhancing tumor to select the region of maximal ADC hypointensity and recorded this minimum value as ADCregion of interest. We also obtained ADCratios by dividing ADCregion of interest by ADCnormal with a region of interest placed in normal contralateral brain. Results after Wilcoxon rank-sum tests are summarized in the Table.

Unlike Pope et al, 2 in our slightly larger series (n = 105 versus n = 89) by using more widely available postprocessing tools (ADC region of interest analysis on commercially available software versus ADC histogram analysis), we were not able to find a correlation between ADC values and MGMT promoter status (P values >.12). Although our divergent conclusions may in part be related to differences in methods, we suggest that the role of DWI and ADC quantification to predict glioblastoma prognosis and MGMT promoter status requires more investigation and validation before wide adoption into routine clinical practice.

Acknowledgments

The authors gratefully thank Drs. Akash D. Shah, Andrew D. Schweitzer, Jason Huse, and Zhigang Zhang for their contributions to this project.

References

  1. Kim YS, Kim SH, Cho J, et al. MGMT gene promoter methylation as a potent prognostic factor in glioblastoma treated with temozolomide-based chemoradiotherapy: a single-institution study. Int J Radiat Oncol Biol Phys 2012;84:661–67 » CrossRef » Medline
  2. Pope WB, Lai A, Mehta R, et al. Apparent diffusion coefficient histogram analysis stratifies progression-free survival in newly diagnosed bevacizumab-treated glioblastoma. AJNR Am J Neuroradiol 2011;32:882–89 » Abstract/FREE Full Text
  3. Law M, Young R, Babb J, et al. Histogram analysis versus region of interest analysis of dynamic susceptibility contrast perfusion MR imaging data in the grading of cerebral gliomas. AJNR Am J Neuroradiol 2007;28:761–66 » Abstract/FREE Full Text
  4. Wetzel SG, Cha S, Johnson G, et al. Relative cerebral blood volume measurements in intracranial mass lesions: interobserver and intraobserver reproducibility study. Radiology 2002;224:797–803 » Abstract/FREE Full Text

Reply

W. Popea
aDepartment of Radiological Sciences
David Geffen School of Medicine at UCLA
Los Angeles, California

We agree that the differences in technique (2-curve histogram modeling versus minimum ADC region-of-interest analysis) may account for the discrepant conclusions, meriting further investigation in larger datasets.






Postado por No comments:

Phase II trial of continuous low-dose temozolomide for patients with recurrent malignant glioma

Background

In this phase II trial, we investigated the efficacy of a metronomic temozolomide schedule in the treatment of recurrent malignant gliomas (MGs).

Methods

Eligible patients received daily temozolomide (50 mg/m2) continuously until progression. The primary endpoint was progression-free survival rate at 6 months in the glioblastoma cohort (N = 37). In an exploratory analysis, 10 additional recurrent grade III MG patients were enrolled. Correlative studies included evaluation of 76 frequent mutations in glioblastoma (iPLEX assay, Sequenom) aiming at establishing the frequency of potentially "drugable" mutations in patients entering recurrent MG clinical trials.

Results

Among glioblastoma patients, median age was 56 y; median Karnofsky Performance Score (KPS) was 80; 62% of patients had been treated for ≥2 recurrences, including 49% of patients having failed bevacizumab. Treatment was well tolerated; clinical benefit (complete response + partial response + stable disease) was seen in 10 (36%) patients. Progression-free survival rate at 6 months was 19% and median overall survival was 7 months. Patients with previous bevacizumab exposure survived significantly less than bevacizumab-naive patients (median overall survival: 4.3 mo vs 13 mo; hazard ratio = 3.2; P = .001), but those patients had lower KPS (P = .04) and higher number of recurrences (P < .0001). Mutations were found in 13 of the 38 MGs tested, including mutations of EGFR (N = 10), IDH1 (N = 5), and ERBB2 (N = 1).

Conclusions

In spite of a heavily pretreated population, including nearly half of patients having failed bevacizumab, the primary endpoint was met, suggesting that this regimen deserves further investigation. Results in bevacizumab-naive patients seemed particularly favorable, while results in bevacizumab-failing patients highlight the need to develop further treatment strategies for advanced MG.

Clinical trials.gov identifier

NCT00498927 (available at http://clinicaltrials.gov/ct2/show/NCT00498927)






Postado por No comments:

Endoscopic Transsphenoidal Surgery for Cushing Disease: Techniques, Outcomes, and Predictors of Rem

imageBACKGROUND: The efficacy of endoscopic transsphenoidal surgery (ETS) for Cushing disease has not been clearly established. OBJECTIVE: To assess efficacy of a pure endoscopic approach for treatment of Cushing disease and determine predictors of remission. METHODS: A prospectively acquired database of 61 patients undergoing ETS was reviewed. Remission was defined as postoperative morning serum cortisol of <5 μg/dL or normal or decreased 24-hour urine-free cortisol level in follow-up. RESULTS: Overall, hypercortisolemia resolved in 58 of 61 patients (95%) by discharge. Tumor size did not predict resolution of hypercortisolemia at discharge (microadenomas [97%], magnetic resonance imaging-negative Cushing [100%], macroadenomas [87%]). At 2- to 3-month evaluations, 45 of 49 patients (91.8%) were in remission. Fifty patients were followed for at least 12 months (mean, 28 months; range, 12-72). Forty-two (84%) achieved remission from a single ETS. In these patients, there was no significant difference in remission rates between microadenomas (93%), magnetic resonance imaging-negative (70%), and macroadenomas (77%). Patients with history of previous surgery (n = 14, 23%) were 9 times less likely to achieve follow-up remission (P = .021). In-house cortisol level of <5.7 μg/dL provided the best prediction of follow-up remission (sensitivity 88.6%, specificity 83.3%). Postoperative diabetes insipidus occurred transiently in 7 patients (9%) and permanently in 3 (5%). One patient experienced postoperative cerebrospinal fluid leak that resolved with further surgery. CONCLUSION: ETS for Cushing disease provides high rates of remission with low rates of complications regardless of size. Although patients with a history of previous surgery are less likely to achieve remission, the majority can still achieve remission following treatment. ABBREVIATIONS: CTH, adrenocorticotropic hormone CD, Cushing disease DI, diabetes insipidus ETS, endoscopic transsphenoidal surgery GKRS, gamma knife stereotactic radiosurgery IGF-1, insulin-like growth factor 1 UFC, urine-free cortisol





Postado por No comments:

A Web-based communication aid for patients with cancer

Abstract

BACKGROUND:

Cancer patients and their oncologists often report differing perceptions of consultation discussions and discordant expectations regarding treatment outcomes. CONNECT, a computer-based communication aid, was developed to improve communication between patients and oncologists.

METHODS:

CONNECT includes assessment of patient values, goals, and communication preferences; patient communication skills training; and a preconsultation physician summary report. CONNECT was tested in a 3-arm, prospective, randomized clinical trial. Prior to the initial medical oncology consultation, adult patients with advanced cancer were randomized to the following arms: 1) control; 2) CONNECT with physician summary; or 3) CONNECT without physician summary. Outcomes were assessed with postconsultation surveys.

RESULTS:

Of 743 patients randomized, 629 completed postconsultation surveys. Patients in the intervention arms (versus control) felt that the CONNECT program made treatment decisions easier to reach (P = .003) and helped them to be more satisfied with these decisions (P < .001). In addition, patients in the intervention arms reported higher levels of satisfaction with physician communication format (P = .026) and discussion regarding support services (P = .029) and quality of life concerns (P = .042). The physician summary did not impact outcomes. Patients with higher levels of education and poorer physical functioning experienced greater benefit from CONNECT.

CONCLUSIONS:

This prospective randomized clinical trial demonstrates that computer-based communication skills training can positively affect patient satisfaction with communication and decision-making. Measurable patient characteristics may be used to identify subgroups most likely to benefit from an intervention such as CONNECT. Cancer 2013. © 2013 American Cancer Society.






Postado por No comments:

Clinical outcomes of treatment for spinal cord compression due to primary non-Hodgkin lymphoma

Available online 18 January 2013
Publication year: 2013
Source:The Spine Journal

Background context Primary non-Hodgkin lymphoma of the spine (PNHLS) with spinal cord compression is an extremely rare disease in clinical practice. The optimal treatment options for this disease have been controversial and pose a challenge for the clinicians. Purpose To provide some useful insight into the treatments, outcomes, and prognostic factors of PNHLS. Study design Retrospective analysis. Patient sample The authors collected 40 patients' data with primary non-Hodgkin lymphoma at the mobile spine, and these patients presented with spinal cord compression as a first symptom between 1998 and 2010. Outcome measures The posttreatment neurologic status, general status, local recurrence, and survival were noted according to the telephone calls, letters, or follow-up visits in the outpatient department. Methods Multidisciplinary treatments, including surgical intervention, chemotherapy, and radiotherapy, were performed in this series. Follow-ups regarding treatment outcomes, local recurrence, and survival rates were carried out and analyzed. The prognostic factors including age, neurologic status, general status, vertebrae involvement, and treatment outcomes were determined. Results The median age of the patients was 52 years (range, 13–79 years). After treatments, 30 patients (75%) reached a complete remission (CR). The 5-year overall survival (OS) of all patients was 72.9%. Patients who were younger than 60 years, with single vertebra involvement, or had CR after treatment had higher 5-year OS (p<.05). In multivariate analysis, CR after treatment and involvement of a single vertebra were identified as favorable prognostic factors for OS. Conclusions Patients with PNHLS with neurologic compression had distinct clinical features. Regarding treatment, the authors emphasized the importance of multidisciplinary management and the optimal operating juncture. Patients with excellent response to the treatment and single vertebra involvement had better survival.






Postado por No comments:

Monday, January 14, 2013

FREE: Neurosurgery Blog App


Neurosurgery Blog

The goal of Neurosurgery blog is promote an international dialogue about Neurosurgery. 



Postado por No comments:

Sunday, January 13, 2013

Role of resection of malignant peripheral nerve sheath tumors in patients with neurofibromatosis Typ

Journal of Neurosurgery, Volume 118, Issue 1, Page 142-148, January 2013.
Object Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas that often arise from major peripheral nerves. Approximately half of MPNSTs arise in patients with neurofibromatosis Type 1 (NF1) who, in comparison with patients without NF1, present at younger ages and with larger tumors that are commonly associated with extensive plexiform neurofibromas. These tumors therefore pose a particularly difficult treatment challenge because of the morbidity often associated with attempted gross-total resection (GTR). Here, the authors aim to examine what role the extent of resection and other covariates play in the long-term survival of patients with NF1 in the setting of MPNST. Methods The authors retrospectively reviewed the records of 23 adult patients with NF1 who underwent surgery for MPNSTs at their institution between 1991 and 2008. The primary end points of the study were mortality, local recurrence, and metastasis. Kaplan-Meier survival curves were evaluated for all patients. Differences for each of the primary end points were evaluated based on cause-specific covariates, which included tiered tumor size, tumor location, grade, resection margin status, postoperative weakness, and use of chemotherapy and radiation therapy. Multivariate analysis was performed using Cox proportional hazards models. Results Gross-total resection (p = 0.01) and surgical margin status (p = 0.034) had a statistically important role in prolonging overall survival in patients with NF1 by univariate analysis. When tumor size, location, grade, postoperative weakness, and radiation therapy were also taken into account using multivariate analysis, GTR continued to be a significant prognostic factor (p = 0.035). Conclusions These findings suggest that GTR offers significant long-term benefit on survival in patients with NF1. Benefit on survival occurred independently of all other covariates, suggesting that complete resection should be the principal goal of treatment in this patient population.





Postado por No comments:
Subscribe to: Posts (Atom)