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
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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.






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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]

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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.






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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)






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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





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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.






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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.






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Monday, January 14, 2013

FREE: Neurosurgery Blog App


Neurosurgery Blog

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



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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.





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A systematic review of published evidence on expanded endoscopic endonasal skull base surgery and th

February 2013
Publication year: 2013
Source:Journal of Clinical Neuroscience, Volume 20, Issue 2

Although postoperative seizure is an acknowledged risk following transcranial surgery, the incidence of seizure after removal of intradural pathology via an expanded endoscopic endonasal approach is not well defined. The current study was performed to systematically review the risk of seizure in patients undergoing endoscopic endonasal skull base (EESB) surgery. Embase (1980 to 9 March 2012) and Medline (1950 to 9 March 2012) were searched using a search strategy designed to include any studies that report the perioperative outcomes following EESB surgery. Outcomes of patients undergoing a simple closure of cerebrospinal fluid fistulae or encephaloceles and transellar approaches for pituitary or intrasellar lesions were excluded because this review is focused on large skull base defects. A title search selected those articles relevant to clinical series on expanded endoscopic approaches. A subsequent search of abstracts selected for manuscripts of any report that documented the presence or absence of postoperative seizure. A total of 2234 manuscripts were selected initially and full text analysis produced 67 studies with extractable data regarding the perioperative outcomes for EESB surgery. Of these manuscripts, seven reported the incidence of seizure following EESB procedures. Two of these studies were excluded due to duplication of authorship and institutional data. The overall risk of postoperative seizure following EESB surgery was estimated at 1.1% (six of 530). Subgroup analyses of data revealed that the risk of seizure following an endoscopic endonasal to the anterior cranial base was 2.3% (one patient of 43). For a posterior cranial base approach, the risk of seizure was indeterminate due to deficiency of reporting in the current literature. We concluded that the risk of seizure following an EESB procedure appears to be low (1%). However, the lack of reporting on the incidence of seizures or the use of antiepileptic prophylaxis following EESB procedure is a key limitation. Future EESB studies will need to include seizure as an outcome to accurately define this risk.






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Paediatric germ cell tumours of the central nervous system: Results and experience from a tertiary-r

Available online 11 January 2013
Publication year: 2013
Source:Journal of Clinical Neuroscience

A retrospective analysis was conducted on consecutive patients with intracranial germ cell tumours diagnosed and treated from 1 January 1997 to 31 December 2007 to assess and determine demographic factors and treatment outcomes of children with these tumours treated in a major paediatric referral hospital in Australia. In this study, intracranial germ cell tumours represented 4.8% of paediatric brain tumours seen. Of the 21 patients identified, 15 (71.4%) were diagnosed with pure germinoma and six (28.6%) with non-germinomatous germ cell tumours (NGGCT) or mixed tumours. One patient received chemotherapy alone, two patients were treated with radiation alone and the remaining 18 received a combination of chemotherapy and radiotherapy. A total of 33 neurosurgical operations were performed with 15 biopsies via open, endoscopic or transphenoidal means; nine open resections; and nine procedures for hydrocephalus comprising seven third ventriculostomies and two ventriculoperitoneal shunts. For patients with pure germinomas, the 5-year disease-free rate (DFS) was 93.3%, and overall survival (OS) rate was 100% compared to NGGCT or mixed tumours (DFS 50%; OS 50%) (DFS p =0.019, OS p =0.004). The data presented show that pure germinomas carry a favourable prognosis. The data also support that treatment with induction chemotherapy followed by dose-attenuated radiotherapy is an effective alternative with results comparable to historical controls treated with craniospinal irradiation. Although chemoradiotherapy has become the mainstay of treatment in intracranial germ cell tumours, surgery remains integral to the management of this condition. Surgery remains important in establishing the histological diagnosis, as well as in the treatment of hydrocephalus. Furthermore, debulking procedures may be advocated in NGGCT as they are often resistant to chemotherapy.






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Surgical technique for the prevention of CSF leakage after bifrontal craniotomy

Available online 10 January 2013
Publication year: 2013
Source:World Neurosurgery

Background Cerebrospinal fluid leakage and meningitis caused by frontal sinus exposure are characteristic complications of bifrontal craniotomy used for treating skull base tumors and anterior communicating artery aneurysms. Prevention of these complications is of utmost importance. Objective We describe in detail our procedure for sealing exposed frontal sinuses during bifrontal craniotomy and present the results and outcomes of the procedure. Subjects and Methods: A total of 51 consecutive patients who had undergone bifrontal craniotomy for tuberculum sellae meningiomas, craniopharyngiomas, anterior cerebral artery aneurysms, or other frontal skull base lesions at our institute were selected for the study. Our technique for sealing exposed frontal sinuses is described below. The mucosa was sterilized using surgical cotton dipped in iodine. After craniotomy, the exposed mucosa was sealed using 7-0 nylon sutures, whereas gelfoam with fibrin glue was used to ensure watertight closure. The exposed portions of the frontal sinuses were covered by bone covers made of internal table bone and sealed. As a final layer, frontal periosteal flaps were sutured to the frontal basedura mater. Results/Conclusion Postoperative cerebrospinal fluid leakage or meningitis did not occur in any of our patients, indicating the effectiveness of our technique in the prevention of frontal sinus-related postoperative complications.






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Transcranial Magnetic Stimulation Following Spinal Cord Injury

Available online 12 January 2013
Publication year: 2013
Source:World Neurosurgery

Objective to review the basic principles and techniques of transcranial magnetic stimulation and provide information and evidence regarding its applications in spinal cord injury clinical rehabilitation. Methods A review of the available current and historical literature regarding transcranial magnetic stimulation and a discussion of its potential use in spinal cord injury rehab was conducted. Results TMS provides reliable information about the functional integrity and conduction properties of the corticospinal tracts and motor control in the diagnostic and prognostic assessment of various neurological disorders. It allows one to follow the evolution of motor control and to evaluate the effects of different therapeutic procedures. MEPs can be useful in follow-up evaluation of motor function during treatment and rehabilitation, specifically in spinal cord injury and stroke patients. While studies regarding somatomotor functional recovery after spinal cord injury have shown promise, it will require further trials to provide strong and substantial evidence. Conclusions TMS is a promising non-invasive tool for the treatment of spasticity, neuropathic pain and somatomotor deficit following SCI. Further investigation is needed to demonstrate whether different protocols and applications of stimulation, as well as alternative cortical sites of stimulation may induce more pronounced and beneficial clinical effects.






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Conservative management of presumed low-grade gliomas in the asymptomatic pediatric population

Available online 12 January 2013
Publication year: 2013
Source:World Neurosurgery

Objectives Optimal management of asymptomatic children with small, nonenhancing intracranial lesions, presumed to be low-grade gliomas (LGG) is not entirely clear in the literature. However, surgical intervention via resection or biopsy is not without risk and is of questionable long-term benefit in children with stable lesions. We present a series of twelve patients with incidentally detected, small, nonenhancing, intracranial lesions that were managed with watchful waiting and serial MRIs. Methods We retrospectively reviewed a series of twelve cases (8 male, 4 female) of children with T1 hypointense and T2 hyperintense intracranial lesions less than 2 cm without enhancement or surrounding edema. Results Most patients (n=5, 41.7%) received MRI studies after suffering a traumatic injury with evidence of an abnormality seen on computed tomography (CT) scan. Others received MRI scan as part of headache work-up (n=4, 33.3%). The majority of lesions were located infratentorially (n=8, 66.7%), while other locations included the frontal lobe and thalamus. The median age of the patients upon identification of the intracranial abnormality was 10 years (range 1-19 years of age). Patients were followed for a median of 16.7 months (range 2.7-59.5 months). The most common diagnosis based on clinical and radiographic features of these lesions consisted of LGG. No patient underwent surgery, radiation therapy or chemotherapy except one patient, in whom the lesion grew in size. Surgical pathologic diagnosis in this case confirmed WHO grade II astrocytoma. Conclusions Our case series suggests that conservative management and close follow-up of incidental radiographic lesions consistent with LGGs is a safe and effective initial strategy in the pediatric population. In cases where lesion size or quality changes, surgical resection may be necessary to confirm diagnosis. Further studies that include a larger number of patients and longer follow-up period are required to compare outcomes between this approach and initial surgical, radiation, or chemotherapy management strategies.






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Thursday, January 10, 2013

The art of gene therapy for glioma: a review of the challenging road to the bedside

Glioblastoma multiforme (GBM) is a highly invasive brain tumour that is unvaryingly fatal in humans despite even aggressive therapeutic approaches such as surgical resection followed by chemotherapy and radiotherapy. Unconventional treatment options such as gene therapy provide an intriguing option for curbing glioma related deaths. To date, gene therapy has yielded encouraging results in preclinical animal models as well as promising safety profiles in phase I clinical trials, but has failed to demonstrate significant therapeutic efficacy in phase III clinical trials. The most widely studied antiglioma gene therapy strategies are suicide gene therapy, genetic immunotherapy and oncolytic virotherapy, and we have attributed the challenging transition of these modalities into the clinic to four major roadblocks: (1) anatomical features of the central nervous system, (2) the host immune system, (3) heterogeneity and invasiveness of GBM and (4) limitations in current GBM animal models. In this review, we discuss possible ways to jump these hurdles and develop new gene therapies that may be used alone or in synergy with other modalities to provide a powerful treatment option for patients with GBM.






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The art of gene therapy for glioma: a review of the challenging road to the bedside

Glioblastoma multiforme (GBM) is a highly invasive brain tumour that is unvaryingly fatal in humans despite even aggressive therapeutic approaches such as surgical resection followed by chemotherapy and radiotherapy. Unconventional treatment options such as gene therapy provide an intriguing option for curbing glioma related deaths. To date, gene therapy has yielded encouraging results in preclinical animal models as well as promising safety profiles in phase I clinical trials, but has failed to demonstrate significant therapeutic efficacy in phase III clinical trials. The most widely studied antiglioma gene therapy strategies are suicide gene therapy, genetic immunotherapy and oncolytic virotherapy, and we have attributed the challenging transition of these modalities into the clinic to four major roadblocks: (1) anatomical features of the central nervous system, (2) the host immune system, (3) heterogeneity and invasiveness of GBM and (4) limitations in current GBM animal models. In this review, we discuss possible ways to jump these hurdles and develop new gene therapies that may be used alone or in synergy with other modalities to provide a powerful treatment option for patients with GBM.






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Wednesday, January 9, 2013

Childhood cancer: Incidence and early deaths in Argentina, 2000–2008

January 2013
Publication year: 2013
Source:European Journal of Cancer, Volume 49, Issue 2

Introduction Knowledge on the epidemiology of childhood cancer in Latin America is limited. The Argentinean Oncopaediatric Registry (ROHA) has been active since 2000. Data for 2000–2008 are described in the present work. Materials and methods ROHA is fed from a network of paediatric units and population-based cancer registries. Cases are coded by the International Classification of Childhood Cancer. Results A total of 11447 children aged 0–14 diagnosed with cancer were reported. Histologically verified cases and cases identified only through death certificates were respectively 91% and 6%. The annual age of standardised incidence rate of all cancers was 128.5 per million. Proportions of leukaemia's, lymphoma's and Central Nervous System tumours were 37%, 13% and 18%. The distribution of rates of acute lymphatic leukaemia by the year of age showed a peak around age 3. Eighty percent of the patients are treated in public hospital and around 35% migrate for some of the treatment. Deaths within a month of diagnosis were 5% in 2000 and 3% in 2008. Conclusions Childhood cancer incidence in Argentina is somewhat lower than in North American and in Western European countries: the deficit is mainly due to tumours of the Central Nervous system and other solid tumours. Childhood cancer incidence did not show any tendency to increase. The possible excess of Hodgkin lymphoma in the Northeast region requires additional studies. Early deaths after diagnosis indicate an unsatisfactory state of the overall organisation of childhood cancer care. Data from ROHA are used for decision making at local and national levels.






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Successful Onyx Embolization of a Giant Glomus Jugulare: Case Report and Review of Nonsurgical Treat

Available online 9 January 2013
Publication year: 2013
Source:World Neurosurgery

Background Otorrhagia is an uncommon but severe symptom of patients with large glomus jugulare tumors that erode through the tympanic membrane. In this case report we describe the use of transarterial embolization for long-term palliative management of otorrhagia in a patient with an unresectable glomus jugulare tumor. Case description A 53-year-old female presented with intermittent otorrhagia 10 years after subtotal resection of a glomus jugulare tumor. Follow-up MRI showed progressive enlargement of the tumor with significant extension into the posterior fossa. Resection was thought to be impractical, so transarterial embolization was offered as a palliative measure to help reduce the frequency and severity of bleeding episodes. Results Long-term control of otorrhagia was achieved after three rounds of intra-arterial embolization. In round one, the tumor was embolized from multiple ECA feeding branches using PVA particles. In round two, the ICA was sacrificed by embolizing the cavernous and petrous segments with coils. In round three, persistent feeders from the cervical ICA were embolized with Onyx. In 6 years of clinical follow-up, the patient has had no otorrhagia or new neurological deficits. Serial MRI shows there has been no significant interval tumor growth. Conclusion Long-term control of otorrhagia from glomus jugulare tumors can be safely achieved by intravascular embolization with Onyx.






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Population-based outcomes after brain radiotherapy in patients with brain metastases from breast can

Purpose: To evaluate the survival of patients with human epidermal growth factor receptor 2 (HER2) positive and negative metastatic breast cancer irradiated for brain metastases before and after the availability of trastuzumab (T).Materials and methods: Women diagnosed with brain metastasis from breast cancer in two eras between 2000 and 2007 (T-era, n = 441) and 1986 to 1992 (PreT-era, n = 307), treated with whole brain radiotherapy (RT) were identified. In the T-era, HER2 testing was part of routine clinical practice, and in the preT-era 128/307 (42%) cases had HER2 testing performed retrospectively on tissue microarrays. Overall survival (OS) was estimated using the Kaplan-Meier method and comparisons between eras used log-rank tests. Results: In the preT- and T-era cohorts, the rate of HER2 positivity was 40% (176/441) and 26% (33/128) (p < 0.001). The median time from diagnosis to brain RT was longer in the preT-era (3.3 years versus 2.3 years, p < 0.001). Survival after brain RT was improved in the T-era compared to the preT-era (1-year OS 26% versus 12%, p < 0.001). The 1-year OS rate for HER2 negative patients was 20% in both eras (p = 0.97). Among HER2 positive patients, the 1-year OS in the preT-era was 5% compared to 40% in the T-era (p < 0.001). Conclusions: Distinct from patients with HER2 negative disease in whom no difference in survival after brain RT was observed over time, patients with HER2 positive brain metastases experienced significantly improved survival subsequent to the availability of trastuzumab.





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Use of Stereotactic Radiosurgery for Brain Metastases From Non-Small Cell Lung Cancer in the United

Purpose: The indications for treatment of brain metastases from non-small cell lung cancer (NSCLC) with stereotactic radiosurgery (SRS) remain controversial. We studied patterns, predictors, and cost of SRS use in elderly patients with NSCLC.Methods and Materials: Using the Surveillance, Epidemiology, and End Results-Medicare (SEER-Medicare) database, we identified patients with NSCLC who were diagnosed with brain metastases between 2000 and 2007. Our cohort included patients treated with radiation therapy and not surgical resection as initial treatment for brain metastases.Results: We identified 7684 patients treated with radiation therapy within 2 months after brain metastases diagnosis, of whom 469 (6.1%) cases had billing codes for SRS. Annual SRS use increased from 3.0% in 2000 to 8.2% in 2005 and varied from 3.4% to 12.5% by specific SEER registry site. After controlling for clinical and sociodemographic characteristics, we found SRS use was significantly associated with increasing year of diagnosis, specific SEER registry, higher socioeconomic status, admission to a teaching hospital, no history of participation in low-income state buy-in programs (a proxy for Medicaid eligibility), no extracranial metastases, and longer intervals from NSCLC diagnosis. The average cost per patient associated with radiation therapy was 2.19 times greater for those who received SRS than for those who did not.Conclusions: The use of SRS in patients with metastatic NSCLC increased almost 3-fold from 2000 to 2005. In addition, we found significant variations in SRS use across SEER registries and socioeconomic quartiles. National practice patterns in this study suggested both a lack of consensus and an overall limited use of the approach among elderly patients before 2008.





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Management of Pediatric Myxopapillary Ependymoma: The Role of Adjuvant Radiation

Introduction: Myxopapillary ependymoma (MPE) is a rare tumor in children. The primary treatment is gross total resection (GTR), with no clearly defined role for adjuvant radiation therapy (RT). Published reports, however, suggest that children with MPE present with a more aggressive disease course. The goal of this study was to assess the role of adjuvant RT in pediatric patients with MPE.Methods: Sixteen patients with MPE seen at Johns Hopkins Hospital (JHH) between November 1984 and December 2010 were retrospectively reviewed. Fifteen of the patients were evaluable with a mean age of 16.8 years (range, 12-21 years). Kaplan-Meier curves and descriptive statistics were used for analysis.Results: All patients received surgery as the initial treatment modality. Surgery consisted of either a GTR or a subtotal resection (STR). The median dose of adjuvant RT was 50.4 Gy (range, 45-54 Gy). All patients receiving RT were treated at the involved site. After a median follow-up of 7.2 years (range, 0.75-26.4 years), all patients were alive with stable disease. Local control at 5 and 10 years was 62.5% and 30%, respectively, for surgery alone versus 100% at both time points for surgery and adjuvant RT. Fifty percent of the patients receiving surgery alone had local failure. All patients receiving STR alone had local failure compared to 33% of patients receiving GTR alone. One patient in the surgery and adjuvant RT group developed a distant site of recurrence 1 year from diagnosis. No late toxicity was reported at last follow-up, and neurologic symptoms either improved or remained stable following surgery with or without RT.Conclusions: Adjuvant RT improved local control compared to surgery alone and should be considered after surgical resection in pediatric patients with MPE.





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Hypofractionation vs Conventional Radiation Therapy for Newly Diagnosed Diffuse Intrinsic Pontine Gl

Purpose: Despite conventional radiation therapy, 54 Gy in single doses of 1.8 Gy (54/1.8 Gy) over 6 weeks, most children with diffuse intrinsic pontine glioma (DIPG) will die within 1 year after diagnosis. To reduce patient burden, we investigated the role of hypofractionation radiation therapy given over 3 to 4 weeks. A 1:1 matched-cohort analysis with conventional radiation therapy was performed to assess response and survival.Methods and Materials: Twenty-seven children, aged 3 to 14, were treated according to 1 of 2 hypofractionation regimens over 3 to 4 weeks (39/3 Gy, n=16 or 44.8/2.8 Gy, n=11). All patients had symptoms for ≤3 months, ≥2 signs of the neurologic triad (cranial nerve deficit, ataxia, long tract signs), and characteristic features of DIPG on magnetic resonance imaging. Twenty-seven patients fulfilling the same diagnostic criteria and receiving at least 50/1.8 to 2.0 Gy were eligible for the matched-cohort analysis.Results: With hypofractionation radiation therapy, the overall survival at 6, 9, and 12 months was 74%, 44%, and 22%, respectively. Progression-free survival at 3, 6, and 9 months was 77%, 43%, and 12%, respectively. Temporary discontinuation of steroids was observed in 21 of 27 (78%) patients. No significant difference in median overall survival (9.0 vs 9.4 months; P=.84) and time to progression (5.0 vs 7.6 months; P=.24) was observed between hypofractionation vs conventional radiation therapy, respectively.Conclusions: For patients with newly diagnosed DIPG, a hypofractionation regimen, given over 3 to 4 weeks, offers equal overall survival with less treatment burden compared with a conventional regimen of 6 weeks.





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Oncology Scan—High-Grade Gliomas

In this edition's Oncology Scan, I have chosen to focus attention on a common problem in the world of radiation oncology—the frail, elderly patient with glioblastoma for whom the most appropriate management has been poorly defined. I have selected 3 recent, high-quality studies, 2 of them randomized trials, that shed new light on the care of patients with this disease and that point us in new directions. Six weeks of radiation therapy, which has been the standard management choice for decades, is now being challenged either by abbreviated radiation treatment or by temozolomide alone. Radiation oncologists would be well advised to stay abreast of this rapidly changing landscape.





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Teuto - Aplicativos médicos #medicina

Algumas Sugestões de Aplicativos do Blog Dr. Teuto.

http://www.drteuto.com.br/aplicativos?busca=&categoria=7
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Tuesday, January 8, 2013

MRI diffusion tensor tractography: Evaluation of anatomical accuracy of different fiber tracking sof

Available online 4 January 2013
Publication year: 2013
Source:World Neurosurgery

Objective DTI based tractography has become an integral part of pre-operative diagnostic imaging in many neurosurgical centers and also other non surgical specialties depend increasingly on DTI tractography as a diagnostic tool. It was the aim of this study to analyze the anatomical accuracy of visualized white matter fiber pathways using different, readily available DTI tractography software programs. Methods MRI scans of the head of twenty healthy volunteers were acquired using a Siemens Symphony TIM, 1.5 T scanner and a 12 channel head array coil. 12 diffusion directions and 5mm slices were selected for the standard settings of the scans in this study. The fornices were chosen as an anatomical structure for the comparative fiber tracking. Identical data sets were loaded into nine different fiber tracking packages which used different algorithms. The nine software packages and algorithms used were: NeuroQLab (modified TEND algorithm), Sörensen DTI task card (modified STT algorithm), Siemens DTI module (modified 4th order Runge-Kutta algorithm), six different software packages from Trackvis (interpolated streamline algorithm, interpolated streamline algorithm, 2nd order Runge Kutta algorithm, Q-ball -> FACT algorithm, tensorline algorithm, Q-ball -> 2nd order Runge Kutta algorithm), DTI Query (modified STT algorithm), Medinria (modified TEND algorithm), Brainvoyager (modified TEND algorithm ), DTI Studio modified FACT algorithm) and the BrainLab DTI module based on the modified Runge Kutta-algorithm. Three examiners (a neuroradiologist, a MRI physicist and a neurosurgeon) served as examiners. They were double blinded with respect to the test subject and the fiber tracking software used in the presented images. A total of 301 images were evaluated from each examiner. They were instructed to evaluate screenshots from the different programs based on 2 main criteria: 1. anatomical accuracy of the course of the displayed fibers and 2. the number of fibers displayed outside the anatomical boundaries. Results The mean overall grade for anatomical accuracy was 2.2 (range 1.1 – 3.6) with a standard deviation (SD) of 0.9. The mean overall grade for incorrectly displayed fibers was 2.5 (range 1.6 – 3.5) with a SD of 0.6. The mean grade of the overall program ranking was 2.3 with a SD of 0.6. The overall mean grade of the program ranked number one (NeuroQLab) was 1.7 (range 1.5 – 2.8). The mean overall grade of the program ranked last (BrainLab iPlan Cranial 2.6 DTI Module) was 3.3 (range 1.7 – 4). The difference between the mean grades of these two programs was statistically highly significant (p<0.0001). There was no statistically significant difference between the programs ranked 1 – 3, NeuroQLab, Sörensen DTI Task Card and Siemens DTI module. Conclusion The results of this study show that there is a statistically significant difference in the anatomical accuracy of the tested DTI fiber tracking programs. While incorrectly displayed fibers could lead to wrong conclusions in the field of neurosciences which relies heavily on this non invasive imaging technique, in neurosurgery incorrectly displayed fibers could lead to surgical decisions potentially harmful for the patient if used without intra-operative cortical stimulation. DTI fiber tracking presents a valuable non-invasive preoperative imaging tool which requires further validation after important standardization of the acquisition and processing techniques currently available.






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Thursday, January 3, 2013

Outcome and molecular characteristics of adolescent and young adult patients with newly diagnosed pr

Background

Young age is a favorable prognostic factor for patients with glioblastoma multiforme (GBM). We reviewed the outcomes and molecular tumor characteristics of adolescent and young adult patients with GBM treated in 2 Austrian centers.

Patients and Methods

Data on patients with histologically proven primary GBM diagnosed from 18 through 40 years of age were retrospectively analyzed. All patients were treated with standard first-line therapy. The primary end points were overall survival (OS) and time to progression (TTP). IDH1-R132H mutation status was analyzed using immunohistochemistry, and MGMT promoter methylation was assessed using methylation-specific polymerase chain reaction.

Results

We included 70 patients (36 men and 34 women) with a median age of 33 years. IDH1-R132H mutations were detected in 22 (39.3%) of 56 cases and MGMT promoter methylation in 33 (61.1%) of 54 cases with available tissue samples. In patients with wild-type IDH, median TTP was 8.2 months and median OS was 24 months, compared with 18 months and 44 months, respectively, observed in patients with mutated IDH. Neither IDH1 nor MGMT status showed a statistically significant association with TTP or OS. Of note, the social and economical situation of the young patients with GBM was alarming, because only 17% succeeded in staying employed after receiving the diagnosis.

Conclusions

We found a high frequency of IDH1 mutations and MGMT promoter methylation among young adult patients with primary GBM that may contribute to the generally favorable outcome associated with young age. The social and economic coverage of patients with glioma remains an unsolved socio-ethical problem.






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Screening for major depressive disorder in adults with cerebral glioma: an initial validation of 3 s

No depression screening tool is validated for use in cases of cerebral glioma. To address this, we studied the operating characteristics of the Hospital Anxiety and Depression Scale (Depression subscale) (HAD-D), the Patient Health Questionnaire–9 (PHQ-9), and the Distress Thermometer (DT) in glioma patients.We conducted a twin-center prospective observational cohort study of major depressive disorder (MDD), according to the Diagnostic and Statistical Manual, 4th edition, in adults with a new diagnosis of cerebral glioma receiving active management or "watchful waiting." At each of 3 interviews over a 6-month period, patients completed the screening questionnaires and received a structured clinical interview to diagnose MDD. Internal consistency, area under the receiver operating characteristics curve (AUC), sensitivity, specificity, positive predictive value, and positive likelihood ratio were calculated. A maximum of 154 patients completed the DT, 133 completed the HAD-D, and 129 completed the PHQ-9. The HAD-D and PHQ-9 showed good internal consistency (α ≥ 0.77 at all timepoints). Median AUCs were 0.931 ± 0.074 for the HAD-D and 0.915 ± 0.055 for the PHQ-9. The optimal threshold was 7+ for the HAD-D, but 8+ had similar operating characteristics. There was no consistently optimal PHQ-9 threshold, but 10+ was optimal in the largest sample. The DT was inferior to the multi-item instruments. Clinicians can screen for depression in well-functioning glioma patients using the HAD-D at the existing recommended lower threshold of 8+, or the PHQ-9 at a threshold of 10+. Due to a modest positive predictive value of either instrument, patients scoring above these thresholds need a clinical assessment to diagnose or exclude depression.






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Survival and secondary tumors in children with medulloblastoma receiving radiotherapy and adjuvant c

The purpose of the trial was to determine the survival and incidence of secondary tumors in children with medulloblastoma receiving radiotherapy plus chemotherapy. Three hundred seventy-nine eligible patients with nondisseminated medulloblastoma between the ages of 3 and 21 years were treated with 2340 cGy of craniospinal and 5580 cGy of posterior fossa irradiation. Patients were randomized between postradiation cisplatin and vincristine plus either CCNU or cyclophosphamide. Survival, pattern of relapse, and occurrence of secondary tumors were assessed. Five- and 10-year event-free survivals were 81 ± 2% and 75.8 ± 2.3%; overall survivals were 87 ± 1.8% and 81.3 ± 2.1%. Event-free survival was not impacted by chemotherapeutic regimen, sex, race, age at diagnosis, or gender. Seven patients had disease relapse beyond 5 years after diagnosis; relapse was local in 4 patients, local plus supratentorial in 2, and supratentorial alone in 1. Fifteen patients experienced secondary tumors as a first event at a median time of 5.8 years after diagnosis (11 >5 y postdiagnosis). All non-CNS solid secondary tumors (4) occurred in regions that had received radiation. Of the 6 high-grade gliomas, 5 occurred >5 years postdiagnosis. The estimated cumulative 10-year incidence rate of secondary malignancies was 4.2% (1.9%–6.5%). Few patients with medulloblastoma will relapse ≥5 years postdiagnosis; relapse will occur predominantly at the primary tumor site. Patients are at risk for development of secondary tumors, many of which are malignant gliomas. This may become an increasing issue as more children survive.






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Relationship of glioblastoma multiforme to the subventricular zone is associated with survival

The subventricular zone (SVZ) lines the lateral ventricles and represents the origin of neural and some cancer stem cells. Tumors contacting the SVZ may be more invasive with higher potential to recruit migratory progenitor cells. Our specific aim was to determine whether SVZ involvement in glioblastoma multiforme (GBM) is associated with a higher recurrence rate and shorter overall survival. MR imaging and clinical data from 91 patients with GBM treated at our institution were retrospectively reviewed. Tumors were classified as type I if the contrast-enhancing lesion contacted both the SVZ and cortex on pre-operative MRI, type II if only the SVZ was involved, type III if only cortex was involved, and type IV if the lesion did not contact either the SVZ or cortex. Progression-free survival (PFS) and overall survival were estimated based on Kaplan-Meier calculations. When comparing type I tumors with types II-IV, only 39% of patients with type I tumors were free of recurrence and alive at 6 months, significantly fewer than for all other types combined (67%; P = .01). PFS at 6 months was also less, at only 47% among patients with SVZ-positive tumors, compared with 69% in the SVZ-negative group (P = .002). Patients with SVZ involvement also demonstrated a more rapid time to progression, compared with those not involving the SVZ (P = .003). Patients with GBM involving the SVZ have decreased overall survival and PFS, which may have prognostic and therapeutic implications.






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MicroRNA profiling in pediatric pilocytic astrocytoma reveals biologically relevant targets, includi

Pilocytic astrocytoma (PA) is a World Health Organization grade I glioma that occurs most commonly in children and young adults. Specific genetic alterations have been described in PA, but the pathogenesis remains poorly understood. We studied microRNA (miRNA) alterations in a large cohort of patients with PA. A total of 43 PA, including 35 sporadic grade I PA, 4 neurofibromatosis-1 (NF1)–associated PA, and 4 PA with pilomyxoid features, as well as 5 nonneoplastic brain controls were examined. BRAF fusion status was assessed in most cases. RNA was examined using the Agilent Human miRNA Microarray V3 platform. Expression of miRNA subsets was validated using quantitative real-time PCR (qRT-PCR) with Taqman probes. Validation of predicted protein targets was performed on tissue microarrays with the use of immunohistochemistry. We identified a subset of miRNAs that were differentially expressed in pediatric PAs versus normal brain tissue: 13 miRNAs were underexpressed, and 20 miRNAs were overexpressed in tumors. Differences were validated by qRT-PCR in a subset, with mean fold change in tumor versus brain of -17 (miR-124), -15 (miR-129), and 19.8 (miR-21). Searching for predicted protein targets in Targetscan, we identified a number of known and putative oncogenes that were predicted targets of miRNA sets relatively underexpressed in PA. Predicted targets with increased expression at the mRNA and/or protein level in PA included PBX3, METAP2, and NFIB. A unique miRNA profile exists in PA, compared with brain tissue. These miRNAs and their targets may play a role in the pathogenesis of PA.






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Detection of glioblastoma response to temozolomide combined with bevacizumab based on {micro}MRI and

The individualized care of glioma patients ought to benefit from imaging biomarkers as precocious predictors of therapeutic efficacy. Contrast enhanced MRI and [18F]-fluorodeoxyglucose (FDG)–PET are routinely used in clinical settings; their ability to forecast the therapeutic response is controversial. The objectives of our preclinical study were to analyze sensitive µMRI and/or µPET imaging biomarkers to predict the efficacy of anti-angiogenic and/or chemotherapeutic regimens. Human U87 and U251 orthotopic glioma models were implanted in nude rats. Temozolomide and/or bevacizumab were administered. µMRI (anatomical, diffusion, and microrheological parameters) and µPET ([18F]-FDG and [18F]-fluoro-l-thymidine [FLT]–PET) studies were undertaken soon (t1) after treatment initiation compared with late anatomical µMRI evaluation of tumor volume (t2) and overall survival. In both models, FDG and FLT uptakes were attenuated at t1 in response to temozolomide alone or with bevacizumab. The distribution of FLT, reflecting intratumoral heterogeneity, was also modified. FDG was less predictive for treatment efficacy than was FLT (also highly correlated with outcome, P < .001 for both models). Cerebral blood volume was significantly decreased by temozolomide + bevacizumab and was correlated with survival for rats with U87 implants. While FLT was highly predictive of treatment efficacy, a combination of imaging biomarkers was superior to any one alone (P < .0001 in both tumors with outcome). Our results indicate that FLT is a sensitive predictor of treatment efficacy and that predictability is enhanced by a combination of imaging biomarkers. These findings may translate clinically in that individualized glioma treatments could be decided in given patients after PET/MRI examinations.






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Standards of care for treatment of recurrent glioblastoma--are we there yet?

Newly diagnosed glioblastoma is now commonly treated with surgery, if feasible, or biopsy, followed by radiation plus concomitant and adjuvant temozolomide. The treatment of recurrent glioblastoma continues to be a moving target as new therapeutic principles enrich the standards of care for newly diagnosed disease. We reviewed PubMed and American Society of Clinical Oncology abstracts from January 2006 to January 2012 to identify clinical trials investigating the treatment of recurrent or progressive glioblastoma with nitrosoureas, temozolomide, bevacizumab, and/or combinations of these agents. At recurrence, a minority of patients are eligible for second surgery or reirradiation, based on appropriate patient selection. In temozolomide-pretreated patients, progression-free survival rates at 6 months of 20%–30% may be achieved either with nitrosoureas, temozolomide in various dosing regimens, or bevacizumab. Combination regimens among these agents or with other drugs have not produced evidence for superior activity but commonly produce more toxicity. More research is needed to better define patient profiles that predict benefit from the limited therapeutic options available after the current standard of care has failed.






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Description of selected characteristics of familial glioma patients – Results from the Gliogene Cons

Available online 4 January 2013
Publication year: 2013
Source:European Journal of Cancer

Background While certain inherited syndromes (e.g. Neurofibromatosis or Li-Fraumeni) are associated with an increased risk of glioma, most familial gliomas are non-syndromic. This study describes the demographic and clinical characteristics of the largest series of non-syndromic glioma families ascertained from 14 centres in the United States (US), Europe and Israel as part of the Gliogene Consortium. Methods Families with 2 or more verified gliomas were recruited between January 2007 and February 2011. Distributions of demographic characteristics and clinical variables of gliomas in the families were described based on information derived from personal questionnaires. Findings The study population comprised 841 glioma patients identified in 376 families (9797 individuals). There were more cases of glioma among males, with a male to female ratio of 1.25. In most families (83%), 2 gliomas were reported, with 3 and 4 gliomas in 13% and 3% of the families, respectively. For families with 2 gliomas, 57% were among 1st-degree relatives, and 31.5% among 2nd-degree relatives. Overall, the mean (±standard deviation [SD]) diagnosis age was 49.4 (±18.7) years. In 48% of families with 2 gliomas, at least one was diagnosed at <40y, and in 12% both were diagnosed under 40y of age. Most of these families (76%) had at least one grade IV glioblastoma multiforme (GBM), and in 32% both cases were grade IV gliomas. The most common glioma subtype was GBM (55%), followed by anaplastic astrocytoma (10%) and oligodendroglioma (8%). Individuals with grades I–II were on average 17y younger than those with grades III–IV. Interpretation Familial glioma cases are similar to sporadic cases in terms of gender distribution, age, morphology and grade. Most familial gliomas appear to comprise clusters of two cases suggesting low penetrance, and that the risk of developing additional gliomas is probably low. These results should be useful in the counselling and clinical management of individuals with a family history of glioma.






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