Thursday, August 30, 2012

Volume Changes After Stereotactic LINAC Radiotherapy in Vestibular Schwannoma: Control Rate and Grow

Purpose: The purpose of this study was to evaluate the control rate of vestibular schwannomas (VS) after treatment with linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) or radiotherapy (SRT) by using a validated volumetric measuring tool. Volume-based studies on prognosis after LINAC-based SRS or SRT for VS are reported scarcely. In addition, growth patterns and risk factors predicting treatment failure were analyzed.Materials and Methods: Retrospectively, 37 VS patients treated with LINAC based SRS or SRT were analyzed. Baseline and follow-up magnetic resonance imaging scans were analyzed with volume measurements on contrast enhanced T1-weighted magnetic resonance imaging. Absence of intervention after radiotherapy was defined as "no additional intervention group, " absence of radiological growth was defined as "radiological control group. " Significant growth was defined as a volume change of 19.7% or more, as calculated in a previous study.Results: The cumulative 4-year probability of no additional intervention was 96.4% ± 0.03; the 4-year radiological control probability was 85.4% ± 0.1). The median follow-up was 40 months. Overall, shrinkage was seen in 65%, stable VS in 22%, and growth in 13%. In 54% of all patients, transient swelling was observed. No prognostic factors were found regarding VS growth. Previous treatment and SRS were associated with transient swelling significantly.Conclusions: Good control rates are reported for LINAC based SRS or SRT in VS, in which the lower rate of radiological growth control is attributed to the use of the more sensitive volume measurements. Transient swelling after radiosurgery is a common phenomenon and should not be mistaken for treatment failure. Previous treatment and SRS were significantly associated with transient swelling.





Outcome of Patients With Pilocytic Astrocytoma and Leptomeningeal Dissemination

Purpose: To determine the patient, tumor, and treatment characteristics of patients with pilocytic astrocytoma (PA) and leptomeningeal dissemination (LMD).Methods and Materials: A PubMed search of English-language studies pertaining to PA with LMD was performed using a combination of keywords that included juvenile pilocytic astrocytoma, low-grade astrocytoma, low-grade glioma, leptomeningeal dissemination, neuraxis spread, and radiotherapy. We found 26 studies with 58 patients between 1976 and 2005 that met these criteria.Results: The median survival for PA patients with LMD was 65 months. The 1-, 2-, and 5-year overall survival (OS) rate after the diagnosis of LMD was 81.1%, 75.7%, and 55.5%. The 1-, 2-, and 5-year progression-free survival (PFS) rate after the diagnosis of LMD was 69.3%, 66.5%, and 34.6%, respectively. Age, gender, primary site location, timing of LMD presentation (synchronous vs. metachronous), and LMD location did not significantly influence OS or PFS. No statistically significant difference was found in OS or PFS between the chemotherapy and radiotherapy groups. Likewise, no difference was found in OS or PFS according to the use of craniospinal irradiation vs. less extensive RT fields.Conclusions: Approximately one-half of PA patients were alive 5 years after the diagnosis of LMD. Both chemotherapy and radiotherapy have efficacy against LMD. Although the use of craniospinal irradiation did not have an effect on PFS, the patient numbers were small and a larger number treated with craniospinal irradiation is needed to determine its efficacy.





Stereotactic Radiosurgery of the Postoperative Resection Cavity for Brain Metastases: Prospective Ev

Purpose: Given the neurocognitive toxicity associated with whole-brain irradiation (WBRT), approaches to defer or avoid WBRT after surgical resection of brain metastases are desirable. Our initial experience with stereotactic radiosurgery (SRS) targeting the resection cavity showed promising results. We examined the outcomes of postoperative resection cavity SRS to determine the effect of adding a 2-mm margin around the resection cavity on local failure (LF) and toxicity.Patients and Methods: We retrospectively evaluated 120 cavities in 112 patients treated from 1998-2009. Factors associated with LF and distant brain failure (DF) were analyzed using competing risks analysis, with death as a competing risk. The overall survival (OS) rate was calculated by the Kaplan-Meier product-limit method; variables associated with OS were evaluated using the Cox proportional hazards and log rank tests.Results: The 12-month cumulative incidence rates of LF and DF, with death as a competing risk, were 9.5% and 54%, respectively. On univariate analysis, expansion of the cavity with a 2-mm margin was associated with decreased LF; the 12-month cumulative incidence rates of LF with and without margin were 3% and 16%, respectively (P=.042). The 12-month toxicity rates with and without margin were 3% and 8%, respectively (P=.27). On multivariate analysis, melanoma histology (P=.038) and number of brain metastases (P=.0097) were associated with higher DF. The median OS time was 17 months (range, 2-114 months), with a 12-month OS rate of 62%. Overall, WBRT was avoided in 72% of the patients.Conclusion: Adjuvant SRS targeting the resection cavity of brain metastases results in excellent local control and allows WBRT to be avoided in a majority of patients. A 2-mm margin around the resection cavity improved local control without increasing toxicity compared with our prior technique with no margin.





Wednesday, August 29, 2012

Acoustic neurinoma



Lucas Alverne F. Albuquerque

Medical Apps iPhone, iPad and Android




We started in February this year (2012) the construction of medical applications for iPhone, iPad and Android with a team of residents and preceptors of the Santa Casa de Belo Horizonte, Minas Gerais. In August we have had over 6,000 downloads, new apps come soon. We hope you are being useful.
 
Distimo Monitor, the free web-based app store analytics tool for app developers.
 
 
 


 

Gene Might Predict Brain Tumors' Aggressiveness

Scientists zero in on DNA sequence associated with gliomas

HealthDay news image

Source: HealthDay





[Review] Epilepsy meets cancer: when, why, and what to do about it?

The lifetime risk of having epileptic seizures is profoundly increased in patients with cancer: about 20% of all patients with systemic cancer may develop brain metastases. These patients and those with primary brain tumours have a lifetime risk of epilepsy of 20–80%. Moreover, exposure to chemotherapy or radiotherapy to the brain, cancer-related metabolic disturbances, stroke, and infection can provoke seizures. The management of epilepsy in patients with cancer includes diagnosis and treatment of the underlying cerebral pathological changes, secondary prophylaxis with antiepileptic drugs, and limiting of the effect of epilepsy and its treatment on the efficacy and tolerability of anticancer treatments, cognitive function, and quality of life.





[Articles] Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in

Standard radiotherapy was associated with poor outcomes, especially in patients older than 70 years. Both temozolomide and hypofractionated radiotherapy should be considered as standard treatment options in elderly patients with glioblastoma. MGMT promoter methylation status might be a useful predictive marker for benefit from temozolomide.





Current status of boron neutron capture therapy of high grade gliomas and recurrent head and neck ca

Boron neutron capture therapy (BNCT) is a biochemically targeted radiotherapy based on the nuclear capture and fission reactions that occur when non-radioactive boron-10, which is a constituent of natural elemental boron, is irradiated with low energy thermal neutrons to yield high linear energy transfer alpha particles and recoiling lithium-7 nuclei. Clinical interest in BNCT has focused primarily on the treatment of high grade gliomas, recurrent cancers of the head and neck region and either primary or metastatic melanoma. Neutron sources for BNCT currently have been limited to specially modified nuclear reactors, which are or until the recent Japanese natural disaster, were available in Japan, United States, Finland and several other European countries, Argentina and Taiwan. Accelerators producing epithermal neutron beams also could be used for BNCT and these are being developed in several countries. It is anticipated that the first Japanese accelerator will be available for therapeutic use in 2013. The major hurdle for the design and synthesis of boron delivery agents has been the requirement for selective tumor targeting to achieve boron concentrations in the range of 20 mug/g. This would be sufficient to deliver therapeutic doses of radiation with minimal normal tissue toxicity. Two boron drugs have been used clinically, a dihydroxyboryl derivative of phenylalanine, referred to as boronophenylalanine or "BPA", and sodium borocaptate or "BSH" (Na2B12H11SH). In this report we will provide an overview of other boron delivery agents that currently are under evaluation, neutron sources in use or under development for BNCT, clinical dosimetry, treatment planning, and finally a summary of previous and on-going clinical studies for high grade gliomas and recurrent tumors of the head and neck region. Promising results have been obtained with both groups of patients but these outcomes must be more rigorously evaluated in larger, possibly randomized clinical trials. Finally, we will summarize the critical issues that must be addressed if BNCT is to become a more widely established clinical modality for the treatment of those malignancies for which there currently are no good treatment options.





Tuesday, August 28, 2012

MEDICINA PERSONALIZADA GANHA FORÇA COM AVANÇOS DA TECNOLOGIA GENÔMICA

Fonte: Estadão

por Herton Escobar / O Estado de S. Paulo



 Anamaria Camargo, Fabiana Betoni , Paula Asprima e Fernada Koyama, na sala dos sequenciadores no Centro de Oncologia Molecular do Hospital Sírio-libanês. FOTO: CLAYTON DE SOUZA/AE


As amostras de DNA entregues a Frederico e Griselda (dois aparelhos sequenciadores, de US$ 600 mil cada, que dão apoio às pesquisas de medicina





A rare case of primary extranodal, extradural histiocytic sarcoma of the thoracic spine and review o

Ashis Patnaik, Sudhansu S Mishra, Satya B Senapati

Surgical Neurology International 2012 3(1):96-96

Background: Histiocytic sarcoma (HS) is a rare aggressive malignant neoplasm of hematopoietic cell origin showing features of fever, weight loss, adenopathy, hepatosplenomegaly, and pancytopenia. Primary histiocytic sarcoma of spine without involvement of lymph nodes, bone marrow or systemic features is very rare. Due to highly malignant, aggressive behavior and frequent local and distant metastases, prognosis of histocytic sarcoma is poor. Case description: We report a case of primary extranodal variety of histiocytic sarcoma without involvement of bone marrow at extradural location of thoracic spine. Immunohistochemistry panel ruled out other more common lesions in this location. We could not find such presentation of extradural histiocytic sarcoma at the thoracic region in the literature. Conclusion: Primary involvement of extradural space by histiocytic sarcoma could arise from the proliferation of multipotent hematopoietic stem cells which are left in this space embroyologically.





Ventriculoperitoneal shunting versus endoscopic third ventriculostomy in the treatment of patients w

David D Gonda, Teddy E Kim, Peter C Warnke, Ekkehard M Kasper, Bob S Carter, Clark C Chen

Surgical Neurology International 2012 3(1):97-97

Background: Between 2005 and 2010, we treated patients with hydrocephalus related to cerebral metastases, who were not good candidates for surgical resection by either endoscopic third ventriculostomy (ETV) or ventriculoperitoneal shunting (VPS). Patients were excluded from ETV if they had a clinical history suggestive of non-obstructive hydrocephalus, including: (1) history of infection or ventricular hemorrhage and (2) leptomeningeal carcinomatosis. The rest of the patients were treated with VPS. Methods: We analyzed the clinical outcome of these patient cohorts, to determine whether the efficacy of VPS was compromised due to a history of infection, ventricular hemorrhage, or leptomeningeal carcinomatosis, and compared these results to those patients who underwent ETV. Results: Sixteen patients were treated with ETV and 36 patients were treated with VPS. The overall efficacy of symptomatic palliation was comparable in the ETV and VPS patients (ETV = 69%, VPS = 75%). In both groups, patients with more severe hydrocephalic symptoms such as nausea, vomiting, and lethargy were more likely to benefit from the procedure. The overall complication rate for the two groups was comparable (ETV = 12.6%, VPS = 19.4%), although the spectrum of complications differed. The overall survival, initial Karnofsky performance status (KPS), and three-month KPS, were similarly comparable (median survival: ETV 3 months, VPS 5.5 months; initial KPS: ETV = 66 ± 7, VPS = 69 ± 12; 3 months KPS: ETV = 86 ± 7, KPS = 84 ± 12). Conclusion: VPS remains a reasonable option for poor RPA grade metastasis patients with hydrocephalus, even in the setting of a previous infection, hemorrhage, or in those with leptomeningeal disease. Optimal treatment of this population will involve the judicious consideration of the relative merits of VPS and ETV.





Posterior fossa immature teratoma in an infant with trisomy 21: A case report and review of the lite

Yuriz Bakhtiar, Hajime Yonezawa, Manoj Bohara, Ryosuke Hanaya, Yasuhiro Okamoto, Kazuhiko Sugiyama, Takako Yoshioka, Kazunori Arita

Surgical Neurology International 2012 3(1):100-100

Background: Intracranial teratoma associated with Down syndrome is rare. With only three previously reported cases, our case is the first one presenting an immature component. Case Description: A 2-month-old boy with trisomy 21 presented with lethargy and head enlargement. A magnetic resonance imaging (MRI) study showed an obstructive hydrocephalus with 0.5 cm posterior fossa tumor compressing the cerebellum. The tumor revealed a mixed intensity on T1- and T2-weighted MRI images and was surrounded by peritumoral cysts. It was heterogeneously enhancing and showed multinodular mass. The tumor was gross totally removed via suboccipital craniotomy and histologically diagnosed as immature teratoma. Four cycles of chemotherapy consisting of cisplatin and etoposide followed the surgery. The radiotherapy was withheld due to infancy. Recurrent lesions in the tumor bed were noted 10 months later. They were removed in the second surgery and histologically identified as mature teratoma. Conclusion: Maturation of immature teratoma may be a result of natural conversion of multipotent embryonal cells into mature tissues and following chemotherapy.





Prospective technical validation and assessment of intra-tumour heterogeneity of a low density array

Publication year: 2012
Source:European Journal of Cancer
Guy N.J. Betts, Amanda Eustace, Shalini Patiar, Helen R. Valentine, Joely Irlam, Anassuya Ramachandran, Ashirwad Merve, Jarrod J. Homer, Carla Möller-Levet, Francesca M. Buffa, Gillian Hall, Crispin J. Miller, Adrian L. Harris, Catharine M.L. West
Background and purpose Tumour hypoxia is associated with a poor prognosis in head and neck squamous cell carcinoma (HNSCC), however there is no accepted method for assessing hypoxia clinically. We aimed to conduct a technical validation of a hypoxia gene expression signature using the TaqMan Low Density Array (TLDA) platform to investigate if this approach reliably identified hypoxic tumours. Materials and methods Tumour samples (n =201) from 80 HNSCC patients were collected prospectively from two centres. Fifty-three patients received pimonidazole prior to surgery. TaqMan Low Density Array-Hypoxia Scores (TLDA-HS) were obtained by quantitative real-time PCR (qPCR) using a 25-gene signature and customised TLDA cards. Assay performance was assessed as coefficient of variation (CoV). Results The assay was sensitive with linear reaction efficiencies across a 4log10 range of inputted cDNA (0.001–10ng/μl). Intra- (CoV=6.9%) and inter- (CoV=2.0%) assay reproducibility were excellent. Intra-tumour heterogeneity was lower for TLDA-HS (23.2%) than for pimonidazole (67.2%) or single gene measurements of CA9 (62.2%), VEGFA (45.0%) or HIG2 (39.4%). TLDA-HS in HNSCC cell lines increased with decreasing pO2. TLDA-HS correlated with Affymetrix U133 Plus 2.0 microarray HS (p <0.01) and positive pimonidazole scores (p =0.005). Conclusions Gene expression measurements of hypoxia using a 25-gene signature and TLDA cards are sensitive, reproducible and associated with lower intra-tumour heterogeneity than assaying individual genes or pimonidazole binding. The approach is suitable for further assessment of prognostic and predictive capability in clinical trial material.






Outcome of elderly patients with primary CNS lymphoma in the G-PCNSL-SG-1 trial

Objective:

To assess the outcome of elderly patients with primary CNS lymphoma (PCNSL) treated within the G-PCNSL-SG-1 trial.

Methods:

We reviewed response, toxicity, and survival of patients with PCNSL aged 70 or more enrolled in the G-PCNSL-SG-1 trial.

Results:

A total of 126 of the 526 eligible patients (24%) and 66 of 318 patients (21%) in the per protocol population were aged 70 or more. Among all eligible patients, the rate of complete and partial responses (CR+PR) to HD-MTX-based chemotherapy was 44% in the elderly vs 57% in the younger patients (p = 0.016). Toxicity was age-independent except for a higher rate of grade III/IV leukopenia in the elderly (34% vs 21%, p = 0.007). Death on therapy was more frequent (18% vs 11%; p = 0.027), and progression-free survival (PFS) (4.0 vs 7.7 months, p = 0.014) and overall survival (12.5 vs 26.2 months, p < 0.001) inferior, in the elderly. A striking difference between younger and elderly patients was the PFS of CR patients of 35.0 in the younger vs 16.1 in the elderly patients (p = 0.024). Elderly patients were treated less often and less aggressively at salvage. However, age was not associated with survival from salvage whole brain radiotherapy in patients progressing during primary HD-MTX-based chemotherapy (p = 0.633).

Conclusions:

Lower response rate and higher mortality on HD-MTX-based chemotherapy as well as lower PFS of CR patients and less salvage therapy contribute to the poor prognosis of elderly patients with PCNSL.






Glutamate is associated with a higher risk of seizures in patients with gliomas

Objective:

To investigate the relationship of glutamate and glutamate transporter expression in human gliomas and surrounding peritumoral brain to the presence of tumor-associated seizures (TAS).

Methods:

We studied a retrospective (group 1: 190 patients) and then a prospective (group 2: 98 patients) cohort of patients who underwent a craniotomy for a supratentorial glioma. Tumor and peritumor tissue specimens were assayed for glutamate concentration and expression of glial glutamate transporters. Differences between the seizure (TAS) and seizure-free (non-TAS) groups were compared.

Results:

A total of 42% of patients had TAS, with 95% of seizures first occurring preoperatively. Clinical factors independently associated with risk of TAS were younger age, temporal lobe location, and tumors with oligodendroglial components. Molecular features in tumor specimens associated with TAS were higher glutamate concentrations, reduced EAAT2 expression, and increased system Xc expression. In group 2, these results were also replicated in the peritumor tissue. Logistic regression analysis identified raised glutamate concentrations in tumor and peritumor tissue, increased expression of peritumor system Xc, younger age, temporal lobe location, and tumors with oligodendroglial components as independently predictive of preoperative seizures.

Conclusion:

Relative increased glutamate concentration in gliomas, and altered glutamate transporter expression, are associated with the presence of TAS and may play a mechanistic role in their pathogenesis.






Genomic Variant Discovered That Increases Risk Of Brain Tumors

People who carry a "G" instead of an "A" at a specific spot in their genetic code have roughly a six-fold higher risk of developing certain types of brain tumors, a Mayo Clinic and University of California, San Francisco study has found...





Saturday, August 25, 2012

Chemosensitized radiosurgery for recurrent brain metastases

Abstract  
Temozolomide is known to penetrate the blood–brain barrier and sensitize brain tumors to radiation and has been used clinically to sensitize fractionated external beam radiotherapy. However, there are limited prospective clinical data available on the safety of temozolomide as a chemosensitizing agent administered with stereotactic radiosurgery. This is a phase I trial of previously irradiated patients with one to four progressive brain metastases and Karnofsky performance scale score ≥60 % enrolled in three sequential cohorts: temozolomide 100, 150 or 200 mg/(m2 day) administered for 5 days. Stereotactic radiosurgery (SRS) was administered on day 5. The SRS dose was dependent on target diameter: 15 Gy (31–40 mm), 18 Gy (21–30 mm) or 21 Gy (<20 mm). The primary endpoint was safety of increasing temozolomide doses. Secondary endpoints included local control and survival. 26 subjects were enrolled and 49 total metastatic lesions were treated. The median number of brain metastases was 1.5, with a median target diameter of 21 mm. The most common grade 1–2 adverse events irrespective of causality were vomiting (23 %), nausea (23 %), edema (12 %), seizure (8 %), psychosis (4 %) and thrombocytopenia (4 %). The frequency of nausea and vomiting did not appear to be dose-dependent. Grade 3–4 toxicities were not observed. Median overall survival was 10.2 months. Crude local control was 87.5 %, with a radiological response seen in eight of 24 evaluable patients (33.3 %), and stable disease >6 months in 13 of 24 patients (54.2 %). Temozolomide, at doses up to 200 mg/(m2 day) × 5 days, prior to SRS is well tolerated, with no dose-limiting toxicities in patients with recurrent brain metastases. Local control of target lesions was >80 %.

  • Content Type Journal Article
  • Category Clinical Study
  • Pages 1-6
  • DOI 10.1007/s11060-012-0965-6
  • Authors
    • David Roberge, Department of Radiation Oncology, Montreal General Hospital, Montreal, QC, Canada
    • Luis Souhami, Department of Radiation Oncology, Montreal General Hospital, Montreal, QC, Canada
    • Marie-Andrée Fortin, Departement de Radio-Oncologie, Hôpital Notre-Dame de Montreal, TS-33661560, rue Sherbrooke est, Montreal, QC H2L 4M1, Canada
    • Jean-François Pouliot, Merck Canada, Kirkland, QC, Canada





A DNA methylation signature associated with aberrant promoter DNA hypermethylation of DNMT3B in huma

Publication year: 2012
Source:European Journal of Cancer, Volume 48, Issue 14
Covadonga Huidobro, Rocío G. Urdinguio, Ramón María Rodríguez, Cristina Mangas, Vincenzo Calvanese, Pablo Martínez-Camblor, Cecilia Ferrero, Adolfo Parra-Blanco, Luis Rodrigo, Álvaro J. Obaya, Laura Suárez-Fernández, Aurora Astudillo, Henar Hernando, Esteban Ballestar, Agustín F. Fernández, Mario F. Fraga
Altered promoter DNA methylation, one of the most important molecular alterations in cancer, is proposed to correlate with deregulation of DNA methyltransferases, although the molecular mechanisms implicated are still poorly understood. Here we show that the de novo DNA methyltransferase DNMT3B is frequently repressed in human colorectal cancer cell lines (CCL) and primary tumours by aberrant DNA hypermethylation of its distal promoter. At the epigenome level, DNMT3B promoter hypermethylation was associated with the hypomethylation of gene promoters usually hypermethylated in the healthy colon. Forced DNMT3B overexpression in cancer cells restored the methylation levels of these promoters in the healthy colon. Our results show a new molecular mechanism of aberrant DNMT3B regulation in colon cancer and suggest that its expression is associated with the methylation of constitutively hypermethylated promoters in the healthy colon.






Thursday, August 23, 2012

Clinical review of pediatric pilocytic astrocytomas treated at a tertiary care hospital in Pakistan

Muhib A Khan, Saniya S Godil, Halima Tabani, Sukaina A Panju, Syed A Enam

Surgical Neurology International 2012 3(1):90-90

Background: Pilocytic Astrocytoma (PA) is a common type of brain tumor in the pediatric population. They have a fairly good prognosis. This study describes PAs in detail, with a focus on the demographic factors, presenting features, management and prognosis, and aims, to identify the negative outcome predictors in our population, which can affect the course of the disease. This article will add to the understanding of PAs from a third world perspective. Methods: The Aga Khan University medical records (1995 - 2007) were reviewed, to study the clinical features, management, and outcome of patients (0 - 15 years) with Pilocytic Astrocytomas (PAs) in our population. After a thorough review of the medical records, all the PAs diagnosed on the basis of histopathology at our Pathology Laboratory, during this period, were included in the study. Results: Twenty-two patients were included with a mean age of 9.25 years. Male-to-female ratio was 1 : 1. The most common presenting feature was a sign of increased intracranial pressure. The most common location was the cerebellum followed by the cerebrum. Fifteen patients underwent maximum surgical resection. Three had recurrence, despite no residual tumor. There were 10 Intensive Care Unit (ICU) admissions and one inpatient mortality. Fifteen patients followed up in the clinic: Eight had recurrence and four underwent repeat surgery (three showed clinical improvement). Hydrocephalus was a predictor of ICU admission. Solid consistency was found to be a marker of recurrence. Conclusion: Pilocytic Astrocytomas are the most common pediatric brain tumors in our population, commonly located in the cerebellum. Complete resection is the best treatment option, but some tumors are aggressive and recurrence is not uncommon. The possible negative outcome predictors are age, source of admission, extent of resection, hydrocephalus, and solid consistency.





Primary CNS germ cell tumors in Japan and the United States: an analysis of 4 tumor registries

Intracranial germ cell tumors (GCTs) are relatively rare. Their incidence has been considered to be higher in East Asia than in the United States. This study estimates the incidence of CNS GCTs in Japan and the United States, investigates gender discrepancies in each country, and describes treatment outcomes. Data on primary CNS GCTs from 4 databases were utilized: population-based malignant incidence data from (1) the Japan Cancer Surveillance Research Group (2004–2006; 14 registries), malignant and nonmalignant incidence data from (2) the Surveillance, Epidemiology, and End Results Program (2004–2008; 17 registries), and hospital-based observed survival data from (3) the Brain Tumor Registry of Japan (1984–2000) and (4) the US National Cancer Data Base (1990–2003). Incidence rates per 100 000 for malignant GCTs were not statistically significantly different between Japan (males = 0.143, females = 0.046) and the United States (males = 0.118, females = 0.030). The malignant incidence-rate ratio was higher for pineal GCTs versus nonpineal (ie, the rest of the brain) GCTs in Japan (11.5:1 vs 1.9:1, respectively) and the United States (16.0:1 vs 1.7:1, respectively). In general, 5-year survival estimates were high: over 75% for all GCTs, and over 81% for germinomas, regardless of the type of treatment in either Japan or the United States. The incidence of primary GCTs is similar between Japan and the United States and has the same gender-based patterns by location. High rates of survival were observed in both countries.






White matter integrity is associated with cognitive processing in patients treated for a posterior f

Children treated for posterior fossa tumors experience reduced cognitive processing speed and, after imaging, show damage to white matter (WM) tracts in the brain. This study explores relationships between white matter microstructure, assessed by fractional anisotropy (FA), and speed of cognitive processing using tract-based spatial statistics (TBSS). At 36 months after treatment with radiotherapy and chemotherapy, 40 patients completed an MRI examination and neuropsychological evaluation. Patients were matched with healthy control subjects based on age, sex, and race. Individual FA values were extracted from examinations for all voxels identified as having significant association between processing speed and FA using TBSS. The regions were labeled anatomically, and fiber tracts were grouped into larger fiber bundle categories based on their anatomical and functional associations. Analyses were performed between mean skeletal FA values in each of the fiber bundles and each of the cognitive processing scores controlling for age. Children 3 years after treatment for posterior fossa brain tumors demonstrate significantly lower processing speed associated with decreased FA, compared with their healthy peers. Commissural fibers in the corpus callosum were negatively affected by disease and therapy with detrimental consequence on patients' cognitive processing. Diffusion tensor imaging of the white matter tracts in the brain is relevant to determining potential mechanisms underlying clinically meaningful change in cognitive performance. Neuroprotective strategies are needed to preserve critical functions.






Phase II trial of lapatinib in adult and pediatric patients with neurofibromatosis type 2 and progre

This single-institution phase II study was performed to estimate the response rate to lapatinib in neurofibromatosis type 2 (NF2) patients with progressive vestibular schwannoma (VS). Twenty-one eligible patients were enrolled. Brain and spine MRIs, including 3-dimensional volumetric tumor analysis, and audiograms were performed once at baseline and again every 12 weeks. The primary response end point was evaluable in 17 patients and defined as ≥15% decrease in VS volume. Hearing was evaluable as a secondary end point in 13 patients, with responses defined as an improvement in the pure tone average of at least 10 dB  or a statistically significant increase in word recognition scores. Four of 17 evaluable patients experienced an objective volumetric response (23.5%; 95% confidence interval [CI], 10%–47%), with median time to response of 4.5 months (range, 3–12). In responders, reduction in VS volumes ranged from –15.7% to –23.9%. Four of 13 patients evaluable for hearing met hearing criteria for response (30.8%; 95% CI, 13%–58%). One sustained response exceeded 9 months in duration. Median time to overall progression (ie, volumetric progression or hearing loss) was 14 months. The estimated overall progression-free survival and volumetric progression-free survival at 12 months were 64.2% (95% CI, 36.9%–82.1%) and 70.6% (95% CI, 43.1%–86.6%), respectively. Toxicity was generally minor, and no permanent dose modifications were required. Lapatinib carries minor toxicity and has objective activity in NF2 patients with progressive VS, including volumetric and hearing responses. Future studies could explore combination therapy with other molecular targeted agents such as bevacizumab.






Endoscopic approaches to the trigeminal nerve and clinical consideration for trigeminal schwannomas:

Journal of Neurosurgery, Volume 0, Issue 0, Page 1-7, Ahead of Print.
Object The course of the trigeminal nerve straddles multiple fossae and is known to be very complex. Comprehensive anatomical knowledge and skull base techniques are required for surgical management of trigeminal schwannomas. The aims of this study were to become familiar with the endoscopic anatomy of the trigeminal nerve and to develop a minimally invasive surgical strategy for the treatment of trigeminal schwannomas. Methods Ten fresh cadavers were studied using 5 endoscopic approaches with the aid of 4-mm 0° and 30° endoscopes to identify surgical landmarks associated with the trigeminal nerve. The endoscopic approaches included 3 transcranial keyhole approaches (the extradural supraorbital, extradural subtemporal, and retrosigmoid approaches), and 2 endonasal approaches (the transpterygoid and the transmaxillary transpterygoid approaches). Results The trajectories of the extradural supraorbital, transpterygoid, and extradural subtemporal approaches corresponded with the course of the first, second, and third divisions of the trigeminal nerve, respectively. The 3 approaches demonstrated each division in intra- and extracranial spaces, as well as the Meckel cave in the middle cranial fossa. The interdural space at the lateral wall of the cavernous sinus was exposed by the extradural supraorbital and subtemporal approaches. The extradural subtemporal approach with anterior petrosectomy and the retrosigmoid approach visualized the trigeminal sensory root and its neighboring neurovascular structures in the posterior cranial fossa. The transmaxillary transpterygoid approach revealed the course of the third division in the infratemporal fossa. Conclusions The 5 endoscopic approaches effectively followed the course of the trigeminal nerve with minimal invasiveness. These approaches could provide alternative options for the management of trigeminal schwannoma.





Tuesday, August 21, 2012

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Increased risk of cancer after Bell’s palsy: a 5-year follow-up study

Abstract  
Reactivation of latent herpes simplex virus (HSV) type I or varicella-zoster virus (VZV) has been recognized as the most common pathomechanism underlying Bell's palsy. There is also increased reactivation of HSV or VZV in patients with immunosuppressed states and in cancer patients. The purpose of this study was to investigate the risk for cancer during a 5-year follow-up period after diagnosis of Bell's palsy by using a population-based dataset in Taiwan. We used data from the "Longitudinal Health Insurance Database". We identified 2,618 patients with Bell's palsy as the study cohort and randomly selected 13,090 patients to be used as a comparison cohort. Cox proportional hazards regression was performed to compare the 5-year risk of subsequent cancer between the study and comparison cohorts. We found that the incidence of cancer was 1.55 (95 % CI 1.35–1.78) per 100 person-years for patients with Bell's palsy and 1.09 (95 % CI 1.02–1.18) per 100 person-years for comparison patients. After censoring cases that died from non-cancer causes during the follow-up period and adjusting for urbanization, monthly income, geographic region, and diabetes, the hazard ratio (HR) for cancer during the 5-year follow-up period for patients with Bell's palsy was 1.43 times that for comparison patients (95 % CI 1.22–1.73). There was a particularly increased risk of oral cancer (HR = 2.49; 95 % CI 1.54–4.03) for patients with Bell's palsy compared with the other patients. We conclude that patients with Bell's palsy were at significant risk of cancer during a 5-year follow-up period after diagnosis.

  • Content Type Journal Article
  • Category Clinical Study
  • Pages 1-6
  • DOI 10.1007/s11060-012-0954-9
  • Authors
    • Jau-Jiuan Sheu, Department of Neurology, Taipei Medical University Hospital, Taipei, Taiwan
    • Joseph J. Keller, School of Public Health, Taipei Medical University, Taipei, Taiwan
    • Herng-Ching Lin, School of Health Care Administration, College of Medicine, Taipei Medical University, 250 Wu-Hsing St., Taipei, 110 Taiwan





Sunday, August 19, 2012

Malignant Brain Cancer Antigens Targeted By Vaccine Which Significantly Lengthens Survival

An experimental immune-based therapy more than doubled median survival of patients diagnosed with the most aggressive malignant brain tumor, Cedars-Sinai Medical Center researchers reported in Cancer Immunology, Immunotherapy, published online. Median survival in a Phase I clinical trial at Cedars-Sinai's Johnnie L. Cochran, Jr. Brain Tumor Center was 38...





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Saturday, August 18, 2012

Application of diffusion tensor tractography in pediatric optic pathway glioma

Journal of Neurosurgery: Pediatrics, Volume 0, Issue 0, Page 1-8, Ahead of Print.
Object Magnetic resonance imaging is commonly used in diagnosis and surveillance for optic pathway glioma (OPG). The authors investigated the role of diffusion tensor (DT) tractography in assessing the location of visual pathway fibers in the presence of tumor. Methods Data in 10 children with OPG were acquired using a 3T MRI generalized autocalibrating parallel acquisitions DT–echo planar imaging sequence (25 isotropic directions with a b value of 1000 seconds/mm2, slice thickness 3 mm). Fiber tractography was performed, with seed regions placed within the optic chiasm and bilateral nerves on the coronal plane, including the tumor and surrounding normal-appearing tissue. Tracking was performed with a curvature threshold of 30°. Results For prechiasmatic lesions, fibers either stopped abruptly at the tumor or traversed abnormally dilated nerve segments. Similar findings were seen with chiasmatic lesions, with an additional arrangement in which fibers diverged around the tumor. For each patient, DT tractography provided additional information about visual fiber arrangement in relation to the tumor that was not evident by using conventional MRI methods. Retrospective reconstruction of visual fibers in 1 patient with new postoperative hemianopia revealed an unexpected superior displacement of the optic tract that might have been helpful information had it been applied to preoperative planning or surgical navigation. Conclusions Optic pathway DT tractography is feasible in patients with OPG and provides new information about the arrangement of visual fibers in relation to tumors that could be incorporated into surgical navigation for tumor biopsy or debulking procedures.





Giant anterior clinoidal meningiomas: surgical technique and outcomes

Journal of Neurosurgery, Volume 0, Issue 0, Page 1-12, Ahead of Print.
Object Surgery for giant anterior clinoidal meningiomas that invade vital neurovascular structures surrounding the anterior clinoid process is challenging. The authors present their skull base technique for the treatment of giant anterior clinoidal meningiomas, defined here as globular tumors with a maximum diameter of 5 cm or larger, centered around the anterior clinoid process, which is usually hyperostotic. Methods Between 2000 and 2010, the authors performed 23 surgeries in 22 patients with giant anterior clinoidal meningiomas. They used a skull base approach with extradural unroofing of the optic canal, extradural clinoidectomy (Dolenc technique), transdural debulking of the tumor, early optic nerve decompression, and early identification and control of key neurovascular structures. Results The mean age at surgery was 53.8 years. The mean tumor diameter was 59.2 mm (range 50–85 mm) with cavernous sinus involvement in 59.1% (13 of 22 patients). The tumor involved the prechiasmatic segment of the optic nerve in all patients, invaded the optic canal in 77.3% (17 of 22 patients), and caused visual impairment in 86.4% (19 of 22 patients). Total resection (Simpson Grade I or II) was achieved in 30.4% of surgeries (7 of 23); subtotal and partial resections were each achieved in 34.8% of surgeries (8 of 23). The main factor precluding total removal was cavernous sinus involvement. There were no deaths. The mean Glasgow Outcome Scale score was 4.8 (median 5) at a mean of 56 months of follow-up. Vision improved in 66.7% (12 of 18 patients) with consecutive neuroophthalmological examinations, was stable in 22.2% (4 of 18), and deteriorated in 11.1% (2 of 18). New deficits in cranial nerve III or IV remained after 8.7% of surgeries (2 of 23). Conclusions This modified surgical protocol has provided both a good extent of resection and a good neurological and visual outcome in patients with giant anterior clinoidal meningiomas.





Radiation-associated meningiomas in children: clinical, pathological, and cytogenetic characteristic

Journal of Neurosurgery: Pediatrics, Volume 0, Issue 0, Page 1-10, Ahead of Print.
Object Radiation-associated meningiomas (RAMs) arise after treatment with radiation to the cranium and are recognized as clinically separate from sporadic meningiomas. Compared with their sporadic counterparts, RAMs are often aggressive or malignant, likely to be multiple, and have a high recurrence rate. However, limited information exists about the clinical, pathological, and cytogenetic features of RAMs in pediatric patients. The authors report the findings in 9 children with meningiomas following therapeutic radiation to the cranium. In addition, they performed a critical review of the English language literature on pediatric RAMs. Methods Medical files were searched for patients who demonstrated meningiomas after a history of radiation to the brain. Only those patients in whom a meningioma occurred before the age of 18 years were included in this study. Clinical and demographic data along with the MIB-1 labeling index and cytogenetic studies were evaluated. Results The patients consisted of 5 males and 4 females with a median age of 5 years (range 2–10 years) at radiation therapy. The latency period was a median of 10 years after radiation therapy (range 6–13 years). The MIB-1 labeling index was a median of 6.6% (range 4%–10%). Five patients (55.6%) displayed multiple meningiomas at the first presentation. Histological types included clear cell meningioma in 1 patient, fibroblastic meningioma in 2, chordoid meningioma in 2, meningothelial meningioma in 7 (atypical in 2 cases), xanthomatous meningioma in 1, and chordoid meningioma in 1. Cytogenetic studies showed that the loss of 22q12.2 was the most common abnormality (3 patients), followed by complex cytogenetic abnormalities (2 patients) and rearrangements between chromosomes 1 and 12 (1 patient) and a 1p deletion (1 patient). Conclusions In contrast to RAMs occurring in adults, those in pediatric patients show an increased incidence of multiplicity on first presentation and unusual histological variants, some of which are described here for the first time. There was no difference in the MIB-1 labeling index in children with RAMs as compared with that in children with non-RAMs.





Progressive symptomatic increase in the size of choroidal fissure cysts

Journal of Neurosurgery: Pediatrics, Volume 0, Issue 0, Page 1-4, Ahead of Print.
Cysts of the choroidal fissure are often incidentally identified. Symptoms from such cysts appear to be exceedingly rare. Herein, the authors report a case series of symptomatic enlargement of choroidal fissure cysts that were surgically treated. Although cysts of the choroidal fissure do not normally become symptomatic, the neurosurgeon should be aware of such a complication. Based on the authors' experience, surgical fenestration of such cysts has good long-term results.





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Friday, August 17, 2012

Longitudinal Analysis of Visual Outcomes After Surgical Treatment of Adult Craniopharyngiomas

imageBACKGROUND: Craniopharyngiomas (CRPs) often cause visual deterioration (VD) due to the close vicinity of the optic apparatus. OBJECTIVE: To evaluate longitudinal visual outcomes after surgery of CRP and determine the prognostic factors thereof. METHODS: One hundred forty-six adult patients who underwent surgery for newly diagnosed CRP were retrospectively reviewed. There were 87 male patients (60%), and the median age was 41 years (range, 18-75). The mean follow-up duration was 88.7 months (range, 24-307). A visual impairment score was used to assess the short-term (<1 month) and long-term (>2 years) visual outcomes. RESULTS: Gross total removal was performed in 53 patients (36%), and tumor recurrence occurred in 40 patients (27%). The average preoperative, short- and long-term visual impairment scores were 44.4, 38.5, and 38.1, respectively, on a 0- to 100-point scale (with 100 indicating the worst vision). Short- and long-term VD occurred in 28 (19%) and 39 patients (27%), respectively. Subtotal removal (STR) alone (P = .010; OR = 4.8), short-term VD (P < .001; OR = 39.7), and tumor recurrence (P < .001; OR = 28.2) were significant risk factors for long-term VD in the multivariate analysis. Patients undergoing STR alone had higher tumor recurrence rates in comparison with those who underwent gross total removal or STR with adjuvant therapy (P < .001). CONCLUSION: Short-term VD secondary to the surgical insult and the recurrence of the tumor were strong predictors of long-term visual outcomes after surgical treatment for CRP. STR alone may be an ineffective strategy for achieving tumor control and optimal visual outcomes in patients with CRP. ABBREVIATIONS: CI, confidence interval CRP, craniopharyngioma GTR, gross total removal STR, subtotal removal VA, visual acuity VD, visual deterioration VF, visual field VIS, visual impairment score





Endoscopic Endonasal Approach for Resection of Cranial Base Chordomas: Outcomes and Learning Curve

imageBACKGROUND: Gross total resection (GTR) of cranial base chordomas represents a surgical challenge because of the location, invasiveness, and tumor extension. In the past decade, the endoscopic endonasal approach (EEA) has been used with notable outcomes. OBJECTIVE: To present the endoscopic endonasal experience in the treatment of cranial base chordomas at our institution. METHODS: From April 2003 to March 2011, 60 patients underwent an EEA for primary (n = 35) or previously treated (n = 25) cranial base chordomas. We evaluated the degree of GTR and complications. We studied the factors that influenced outcomes and compared our surgical results in the early and late years of our experience. RESULTS: The overall rate of GTR of cranial base chordomas was 66.7% (82.9% in primary and 44% in previously treated patients). The most important limitations for GTR were tumor volume greater than 20 cm3 (P = .042), tumor location in the lower clivus with lateral extension (P = .022), and previously treated disease (P = .002). The learning curve had a significant impact on GTR, increasing the success rate to 88.9% (92.6% in primary patients and 63.6% in previously treated patients) during recent years (P < .0001). The most frequent complication was cerebrospinal fluid leak (20%) resulting in meningitis in 3.3%. Carotid injuries occurred in 2 patients without any resulting deficit. Neurological complications included new cranial neuropathies (6.7%) and long tract deficits (1.7%). There was no operative mortality in our series. CONCLUSION: For the treatment of cranial base chordomas, the EEA is a competitive alternative to transcranial approaches with minimal morbidity and high success rates of GTR when performed by experienced cranial base surgeons. ABBREVIATIONS: CN, cranial nerve EEA, endoscopic endonasal approach GTR, gross total resection ICA, internal carotid artery LOS, length of hospital stay





Single-Fraction Radiosurgery of Benign Intracranial Meningiomas

imageBACKGROUND: Stereotactic radiosurgery (SRS) of benign intracranial meningiomas is an accepted management option for well-selected patients. OBJECTIVE: To analyze patients who had single-fraction SRS for benign intracranial meningiomas to determine factors associated with tumor control and neurologic complications. METHODS: Retrospective review was performed of 416 patients (304 women/112 men) who had single-fraction SRS for imaging defined (n = 252) or confirmed World Health Organization grade I (n = 164) meningiomas from 1990 to 2008. Excluded were patients with radiation-induced tumors, multiple meningiomas, neurofibromatosis type 2, and previous or concurrent radiotherapy. The majority of tumors (n = 337; 81%) involved the cranial base or tentorium. The median tumor volume was 7.3 cm3; the median tumor margin dose was 16 Gy. The median follow-up was 60 months. RESULTS: The disease-specific survival rate was 97% at 5 years and 94% at 10 years. The 5- and 10-year local tumor control rate was 96% and 89%, respectively. Male sex (hazard ratio [HR]: 2.5, P = .03), previous surgery (HR: 6.9, P = .002) and patients with tumors located in the parasagittal/falx/convexity regions (HR: 2.8, P = .02) were negative risk factors for local tumor control. In 45 patients (11%) permanent radiation-related complications developed at a median of 9 months after SRS. The 1- and 5-year radiation-related complication rate was 6% and 11%, respectively. Risk factors for permanent radiation-related complication rate were increasing tumor volume (HR: 1.05, P = .008) and patients with tumors of the parasagittal/falx/convexity regions (HR: 3.0, P = .005). CONCLUSION: Single-fraction SRS at the studied dose range provided a high rate of tumor control for patients with benign intracranial meningiomas. Patients with small volume, nonoperated cranial base or tentorial meningiomas had the best outcomes after single-fraction SRS. ABBREVIATIONS: BMRS, benign meningioma radiosurgery score CI, confidence interval DSS, disease-specific survival EBRT, external beam radiation therapy LTC, local tumor control PFS, progression-free survival RRC, radiation-related complication SRS, stereotactic radiosurgery WHO, World Health Organization





Tuesday, August 14, 2012

Presentation, management, and outcome of elderly patients with newly-diagnosed anaplastic astrocytom

Abstract  
Few studies have assessed the presentation, management, and outcome of anaplastic astrocytoma (AA) in elderly patients in the temozolomide era. We retrospectively reviewed 42 consecutive patients aged >65 years with newly-diagnosed AA who underwent surgical resection or biopsy between 2003 and 2008. Median age and KPS score were 73 years (range, 66–88) and 80 (range, 50–90), respectively. Thirty-two patients (76 %) presented with focal deficits. Twenty patients (48 %) experienced seizures before surgery. Tumor enhanced diffusely in 24 patients (57 %) and sparsely in 18 patients (43 %). Biopsy (79 %) was more common than resection. Post-operatively, new persistent neurological deficits and hemorrhage were seen in two (4.8 %) and three (7.1 %) patients, respectively. Complete follow-up data regarding adjuvant treatment was available in 31 patients. Sixteen patients (52 %) received temozolomide and radiation therapy (RT), while nine patients (29 %) received RT alone. Chemotherapy-related grade 3/4 hematologic complication rate was 17.6 %. Median overall survival (OS) was 6.5 months (12 months with resection; 3.5 months with biopsy). Resection (P = 0.007, risk ratio = 0.21) and sparse enhancement (P = 0.007, risk ratio = 0.13) were associated with longer OS in multivariate analysis. Similarly, chemoradiation was associated with longer survival compared to RT alone (OS: P = 0.01, progression-free survival (PFS): P = 0.02) after adjusting for age, KPS, enhancement, and surgery. Resection was associated with longer survival among elderly patients with AA, although this could reflect selection bias. Similarly, adding chemotherapy to RT was associated with prolonged survival but carried important complication risks. In appropriately selected AA patients, aggressive treatments with radical resection and chemoradiation may be appropriate even in this age group.

  • Content Type Journal Article
  • Category Clinical Study
  • Pages 1-9
  • DOI 10.1007/s11060-012-0956-7
  • Authors
    • Shota Tanaka, Department of Neurological Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
    • Fredric B. Meyer, Department of Neurological Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
    • Jan C. Buckner, Department of Medical Oncology, Mayo Clinic, Rochester, MN 55905, USA
    • Joon H. Uhm, Department of Neuro-Oncology, Mayo Clinic, Rochester, MN 55905, USA
    • Elizabeth S. Yan, Department of Radiation Oncology, Mayo Clinic, Rochester, MN 55905, USA
    • Ian F. Parney, Department of Neurological Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA





Supratentorial pure cortical ependymoma

Publication year: 2012
Source:Journal of Clinical Neuroscience
Satoshi Nakamizo, Takashi Sasayama, Takeshi Kondoh, Satoshi Inoue, Ryoji Shiomi, Hirotomo Tanaka, Masamitsu Nishihara, Katu Mizukawa, Keiichiro Uehara, Yu Usami, Eiji Kohmura
Ependymoma usually occurs in the lateral or the fourth ventricle. Supratentorial extraventricular ependymoma is relatively rare. However, extraventricular ependymoma located at the cerebral cortex is extremely rare. We treated a 20-year-old woman who presented with generalized seizures. Cranial CT scan revealed a calcified mass in the left precentral gyrus. MRI confirmed an extraventricular, 12-mm-diameter intracortical mass. After gadolinium injection, tumor enhancement was mild and heterogeneous. The tumor was totally resected without neurological deterioration. Histological features were consistent with ependymoma, forming perivascular pseudorosettes without anaplastic figures. Immunohistochemistry showed positive staining for glial fibrillary acidic protein, S-100, and epithelial membrane antigen. A diagnosis of ependymoma of World Health Organization grade II was made. The patient has not had a seizure since the operation. There has been no clinical or radiologic evidence of recurrence during a 16-month postoperative follow-up.