| 1: Arch Neurol.
2006 May;63(5):763-5. |
|
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Nontuberculous mycobacterial infection of a metastatic
brain neoplasm in an immunocompromised patient.
Little AA, Gebarski SS, Blaivas M.
Department of Neurology, University of Michigan Medical Center, 1924 Taubman
Center, 1500 E. Medical Center Drive, Ann Arbor, MI 48109, USA. alitt@umich.edu
BACKGROUND: Nontuberculous mycobacterial infections occur in
immunocompromised patients but so rarely involve the central nervous system
(CNS) that they may not be included in a differential diagnosis of CNS
lesions in such patients. OBJECTIVE: To illustrate a putative mechanism for
nontuberculous mycobacterial infection of the CNS via breakdown of the
blood-brain barrier by metastatic neoplasm. RESULTS: A 56-year-old man who
had undergone renal transplantation in February 2003 and was taking an
immunosuppressive regimen of mycophenolate mofetil and cyclosporine was seen
in the emergency department after a syncopal episode. Head computed
tomography revealed a single focal occipital lesion with vasogenic edema.
Hospital admission and further workup led to diagnosis of metastatic
carcinoma infected with nontuberculous mycobacteria in the setting of a
disseminated nontuberculous mycobacterial infection. CONCLUSION: This case
illustrates that breakdown of the blood-brain barrier by metastatic neoplasm
may provide a route of access for a pathogen that is not normally seen in
the CNS.
Publication Types:
PMID: 16682548 [PubMed - indexed for MEDLINE]
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| 2: Br J Cancer.
2006 Jun 27; [Epub ahead of print] |
|
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A pilot clinical study of Delta(9)-tetrahydrocannabinol
in patients with recurrent glioblastoma multiforme.
Guzman M, Duarte MJ, Blazquez C, Ravina J, Rosa
MC, Galve-Roperh I, Sanchez C, Velasco G, Gonzalez-Feria
L.
1Department of Biochemistry and Molecular Biology I, School of Biology,
Complutense University, Madrid 28040, Spain.
Delta(9)-Tetrahydrocannabinol (THC) and other cannabinoids inhibit tumour
growth and angiogenesis in animal models, so their potential application as
antitumoral drugs has been suggested. However, the antitumoral effect of
cannabinoids has never been tested in humans. Here we report the first
clinical study aimed at assessing cannabinoid antitumoral action,
specifically a pilot phase I trial in which nine patients with recurrent
glioblastoma multiforme were administered THC intratumoraly. The patients
had previously failed standard therapy (surgery and radiotherapy) and had
clear evidence of tumour progression. The primary end point of the study was
to determine the safety of intracranial THC administration. We also
evaluated THC action on the length of survival and various tumour-cell
parameters. A dose escalation regimen for THC administration was assessed.
Cannabinoid delivery was safe and could be achieved without overt
psychoactive effects. Median survival of the cohort from the beginning of
cannabinoid administration was 24 weeks (95% confidence interval: 15-33).
Delta(9)-Tetrahydrocannabinol inhibited tumour-cell proliferation in vitro
and decreased tumour-cell Ki67 immunostaining when administered to two
patients. The fair safety profile of THC, together with its possible
antiproliferative action on tumour cells reported here and in other studies,
may set the basis for future trials aimed at evaluating the potential
antitumoral activity of cannabinoids.British Journal of Cancer advance
online publication, 27 June 2006; doi:10.1038/sj.bjc.6603236
www.bjcancer.com.
PMID: 16804518 [PubMed - as supplied by publisher]>>>
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| 3: Br J
Neurosurg. 2006 Jun;20(3):129-38. |
|
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Surgical management of tuberculum sellae meningioma: Role
of selective extradural anterior clinoidectomy.
Otani N, Muroi C, Yano H, Khan N, Pangalu A,
Yonekawa Y.
Department of Neurosurgery.
A retrospective analysis of 32 patients with tuberculum sellae meningiomas
who underwent surgery via a unilateral pterional approach was performed. A
selective extradural anterior clinoidectomy (SEAC) technique was added in 20
patients. All patients had visual dysfunction preoperatively.
Macroscopically complete removal with Simpson grade II was performed in 28
patients (87.5%). The postoperative visual function improved in 25 (78.1%),
did not change in 3 (9.4%), and worsened in 4 patients (12.5%). The SEAC
technique was effective, especially for removal of the tumour extending into
the sellae/pituitary stalk (9 patients), the optic canal (4 patients) and
hypothalamus (4 patients) with preservation of the visual and
endocrinological function. These results were superior to those of surgery
without SEAC technique. This technique is therefore recommended for complete
resection of the tuberculum sellae meningiomas extending to the surrounding
anatomical structures as the SEAC procedure reduces the risk of
intraoperative optic nerve injury considerably.
PMID: 16801044 [PubMed - in process]
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| 4: Childs
Nerv Syst. 2006 Jun 28; [Epub ahead of print] |
|
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A report of nine newborns with congenital brain tumours.
Carstensen H, Juhler M, Bogeskov L, Laursen H.
Department of Pediatrics, Copenhagen University Hospital (Rigshospitalet),
Copenhagen, Denmark.
BACKGROUND: Although rare, brain tumours represent one of the relatively
larger groups of congenital neoplasias. Most studies on congenital
neoplastic disease deal with several types of neoplasms and are dominated by
leukaemias, retinoblastomas and systemic solid tumours. Few studies are
dedicated to congenital brain tumours. We present nine newborns (four boys
and five girls) who were diagnosed with congenital brain tumours during the
8-year period 1 January 1992-31 December 1999 at our institution, which
covers all paediatric neuro-oncology cases for Eastern Denmark. EPIDEMIOLOGY:
Two of the cases were referred from Western Denmark for surgery, and were
therefore excluded from the calculation of incidence. During the same
period, a total of 172 children below the age of 15 years were diagnosed as
having primary central nervous system tumours. The seven remaining
congenital cases thus represent 4% of all paediatric brain tumour cases in
the area (95% confidence interval 1.7-8.3%). The population of the referral
area is 2.383x10(6), and based on the total number of living births, the
incidence of congenital brain tumour was calculated to be 2.9 per 100,000
live births. The ages of the mothers were 28-33 years, corresponding to the
present mean age of 31 years for Danish primipara. The gestational age
varied between 35 and 42 weeks, and the birth weights were 3,044-4,790 g.
RISK FACTORS: Two patients with p53-related glioblastoma multiforme (GBM)
had relatives with p53-related neoplasms. In one case, the mother was
treated for cancer of the ovary with surgery and chemotherapy 2 months
before conception. CLINICAL FEATURES: In five of the cases, brain
abnormality was suspected antenatally. The clinical features of the newborns
were limited to enlarged head circumferences, associated hydrocephalus, and
asymmetric skull growth. DIAGNOSIS AND TREATMENT: Three babies were treated
with complete tumour resection. In the remaining six cases, a guided or open
biopsy to obtain histology was made after CT/MRI imaging. The histological
diagnoses were teratoma in four cases, GBM in two cases, anaplastic
astrocytoma in two cases and, finally, haemangioma capillare in one case.
OUTCOME: Four of the patients (44%) are still alive, including two patients
with totally resected combined orbital/intracranial teratomas, one patient
with a totally resected haemangioma and one patient with anaplastic
astrocytoma who did not receive any treatment apart from supportive care.
The survival lengths of the five neonates who died varied between 1 day and
51 days.
PMID: 16804715 [PubMed - as supplied by publisher]>>>
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| 5: Childs
Nerv Syst. 2006 Jun 28; [Epub ahead of print] |
|
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A report of nine newborns with congenital brain tumors.
Rekate H.
Barrow Neurological Institute, 2910 North Third Avenue, Phoenix, AZ,
85013-4473, USA, harold.rekate@bnaneuro.net.
PMID: 16804714 [PubMed - as supplied by publisher]
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| 6: Eur
J Cancer. 2006 Jun 27; [Epub ahead of print] |
|
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Prognostic factors for progression of childhood optic
pathway glioma: A systematic review.
Opocher E, Kremer LC, Da Dalt L, van de Wetering MD,
Viscardi E, Caron HN, Perilongo G.
Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical
Center (AMC), University of Amsterdam, The Netherlands.
A systematic literature review was carried out to evaluate best existing
evidence on prognostic factors for progression of childhood optic pathway
glioma. Databases were searched for relevant articles and articles selected
independently by two authors. Information about study design, population,
treatment, outcome and prognostic analysis were abstracted and the quality
of each article was assessed. A total of 23 articles met the inclusion
criteria. Many studies had important methodological limitations, regarding
external and internal validity. Eleven studies evaluated possible prognostic
factors in a multivariate analysis. Three high-quality studies indicated
age<1 year as an independent prognostic factor for a worse
progression-free survival. Three studies with multivariate analysis,
including one high-quality study, found that children with neurofibromatosis
type 1 (NF-1) have a better progression-free survival than those without
NF-1. Two studies with multivariate analysis found tumour site to be a
prognostic factor, both with some methodological limitations. In conclusion,
this systematic review demonstrates that only a few of the prognostic
factors proposed have been proven to be clinically relevant. Age<1 year
is a clear and independent prognostic factor for progression-free survival.
Other prognostic factors, such as NF-1, tumour site and others, are
suggested, but are still without solid evidence and need further
high-quality studies to be clearly proven.
PMID: 16809032 [PubMed - as supplied by publisher]>>>
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| 7: Int
J Radiat Oncol Biol Phys. 2006 Jun 1;65(2):608-16. |
|
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Dosimetric comparisons of helical tomotherapy treatment
plans and step-and-shoot intensity-modulated radiosurgery treatment plans in
intracranial stereotactic radiosurgery.
Han C, Liu A, Schultheiss TE, Pezner RD, Chen
YJ, Wong JY.
Department of Radiation Physics, City of Hope National Medical Center,
Duarte, CA 91010, USA. chan@coh.org
PURPOSE: To evaluate dose conformity, dose homogeneity, and dose gradient in
helical tomotherapy treatment plans for stereotactic radiosurgery, and
compare results with step-and-shoot intensity-modulated radiosurgery (IMRS)
treatment plans. METHODS AND MATERIALS: Sixteen patients were selected with
a mean tumor size of 14.65 +/- 11.2 cm3. Original step-and-shoot IMRS
treatment plans used coplanar fields because of the constraint of the beam
stopper. Retrospective step-and-shoot IMRS plans were generated using
noncoplanar fields. Helical tomotherapy treatment plans were generated using
the tomotherapy planning station. Dose conformity index, dose gradient score
index, and homogeneity index were used in plan intercomparisons. RESULTS:
Noncoplanar IMRS plans increased dose conformity and dose gradient, but not
dose homogeneity, compared with coplanar IMRS plans. Tomotherapy plans
increased dose conformity and dose gradient, yet increased dose
heterogeneity compared with noncoplanar IMRS plans. The average dose
conformity index values were 1.53 +/- 0.38, 1.35 +/- 0.15, and 1.26 +/- 0.10
in coplanar IMRS, noncoplanar IMRS, and tomotherapy plans, respectively. The
average dose homogeneity index values were 1.15 +/- 0.05, 1.13 +/- 0.04, and
1.18 +/- 0.09 in coplanar IMRS, noncoplanar IMRS, and tomotherapy plans,
respectively. The mean dose gradient score index values were 1.37 +/- 19.08,
22.32 +/- 19.20, and 43.28 +/- 13.78 in coplanar IMRS, noncoplanar IMRS, and
tomotherapy plans, respectively. The mean treatment time in tomotherapy was
42 +/- 16 min. CONCLUSIONS: We were able to achieve better dose conformity
and dose gradient in tomotherapy plans compared with step-and-shoot IMRS
plans for intracranial stereotactic radiosurgery. However, tomotherapy
treatment time was significantly larger than that in step-and-shoot IMRS.
Publication Types:
PMID: 16690442 [PubMed - indexed for MEDLINE]>>>
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| 8: Int
J Radiat Oncol Biol Phys. 2006 Jun 1;65(2):481-5. Epub 2006 Mar
10. |
|
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Low-dose prophylactic craniospinal radiotherapy for
intracranial germinoma.
Schoenfeld GO, Amdur RJ, Schmalfuss IM, Morris CG,
Keole SR, Mendenhall WM, Marcus RB Jr.
Department of Radiation Oncology, University of Florida College of Medicine,
Gainesville, Florida 32610-0385, USA.
PURPOSE: To report outcomes of patients with localized intracranial
germinoma treated with low-dose craniospinal irradiation (CSI) followed by a
boost to the ventricular system and primary site. METHODS AND MATERIALS:
Thirty-one patients had pathologically confirmed intracranial germinoma and
no spine metastases. Low-dose CSI was administered in 29 patients: usually
21 Gy of CSI, 9.0 Gy of ventricular boost, and a 19.5-Gy tumor boost, all at
1.5 Gy per fraction. Our neuroradiologist recorded three-dimensional tumor
size on magnetic resonance images before, during, and after radiotherapy.
RESULTS: With a median follow-up of 7.0 years, 29 of 31 patients (94%) are
disease free. One failure had nongerminomatous histology; the initial
diagnosis was a sampling error. Of 3 patients who did not receive CSI, 1
died. No patient developed myelopathy, visual deficits, dementia, or
skeletal growth problems. In locally controlled patients, tumor response
according to magnetic resonance scan was nearly complete within 6 months
after radiotherapy. CONCLUSIONS: Radiotherapy alone with low-dose
prophylactic CSI cures almost all patients with localized intracranial
germinoma. Complications are rare when the daily dose of radiotherapy is
limited to 1.5 Gy and the total CSI dose to 21 Gy. Patients without a
near-complete response to radiotherapy should undergo resection to rule out
a nongerminomatous element.
PMID: 16530341 [PubMed - indexed for MEDLINE]>>>
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| 9: Int
J Radiat Oncol Biol Phys. 2006 Jun 1;65(2):486-92. Epub 2006
Mar 10. |
|
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Limited-field radiation for bifocal germinoma.
Lafay-Cousin L, Millar BA, Mabbott D, Spiegler B,
Drake J, Bartels U, Huang A, Bouffet E.
Pediatric Brain Tumor Program, Hospital for Sick Children, Toronto, Ontario,
Canada. lucie.lafay-cousin@sickkids.ca
PURPOSE: To report the incidence, characteristics, treatment, and outcomes
of bifocal germinomas treated with chemotherapy followed by focal radiation.
METHODS AND MATERIALS: This was a retrospective review. Inclusion criteria
included radiologic diagnosis of bifocal germinoma involving the pineal and
neurohypophyseal region, no evidence of dissemination on spinal MRI,
negative results from cerebrospinal fluid cytologic evaluation, and negative
tumor markers. RESULTS: Between 1995 and 2004, 6 patients (5 male, 1 female;
median age, 12.8 years) fulfilled the inclusion criteria. All had symptoms
of diabetes insipidus at presentation. On MRI, 4 patients had a pineal and
suprasellar mass, and 2 had a pineal mass associated with abnormal
neurohypophyseal enhancement. All patients received chemotherapy followed by
limited-field radiation and achieved complete remission after chemotherapy.
The radiation field involved the whole ventricular system (range,
2,400-4,000 cGy) with or without a boost to the primary lesions. All
patients remain in complete remission at a median follow-up of 48.1 months
(range, 9-73.4 months). CONCLUSIONS: This experience suggests that bifocal
germinoma can be considered a locoregional rather than a metastatic disease.
Chemotherapy and focal radiotherapy might be sufficient to provide excellent
outcomes. Staging refinement with new diagnostic tools will likely increase
the incidence of the entity.
PMID: 16530340 [PubMed - indexed for MEDLINE]>>>
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| 10: Int
J Radiat Oncol Biol Phys. 2006 Jun 1;65(2):499-508. Epub 2006
Mar 6. |
|
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Cerebral radiation necrosis: incidence, outcomes, and
risk factors with emphasis on radiation parameters and chemotherapy.
Ruben JD, Dally M, Bailey M, Smith R, McLean
CA, Fedele P.
William Buckland Radiotherapy Centre, Melbourne, Australia.
PURPOSE: To investigate radiation necrosis in patients treated for glioma in
terms of incidence, outcomes, predictive and prognostic factors. METHODS AND
MATERIALS: Records were reviewed for 426 patients followed up until death or
for at least 3 years. Logistic regression analysis was performed to identify
predictive and prognostic factors. Multivariate survival analysis was
conducted using Cox proportional hazards regression. Separate analyses were
performed for the subset of 352 patients who received a biologically
effective dose (BED) > or =85.5 Gy2 (> or =45 Gy/25 fractions) who
were at highest risk for radionecrosis. RESULTS: Twenty-one patients
developed radionecrosis (4.9%). Actuarial incidence plateaued at 13.3% after
3 years. In the high-risk subset, radiation parameters confirmed as risk
factors included total dose (p < 0.001), BED (p < 0.005), neuret (p
< 0.001), fraction size (p = 0.028), and the product of total dose and
fraction size (p = 0.001). No patient receiving a BED <96 Gy2 developed
radionecrosis. Subsequent chemotherapy significantly increased the risk of
cerebral necrosis (p = 0.001) even when adjusted for BED (odds ratio [OR],
5.8; 95% confidence interval [CI], 1.6-20.3) or length of follow-up (OR,
5.4; 95% CI, 1.5-19.3). Concurrent use of valproate appeared to delay the
onset of necrosis (p = 0.013). The development of radionecrosis did not
affect survival (p = 0.09). CONCLUSIONS: Cerebral necrosis is unlikely at
doses below 50 Gy in 25 fractions. The risk increases significantly with
increasing radiation dose, fraction size, and the subsequent administration
of chemotherapy.
PMID: 16517093 [PubMed - indexed for MEDLINE]>>>
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| 11: J Neurooncol.
2006 Jun 29; [Epub ahead of print] |
|
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Effectiveness of novel combination chemotherapy,
consisting of 5-fluorouracil, vincristine, cyclophosphamide and etoposide,
in the treatment of low-grade gliomas in children.
Lee MJ, Ra YS, Park JB, Goo HW, Ahn SD, Khang
SK, Song JS, Kim YJ, Ghim TT.
Department of Pediatrics, Asan Medical Center, University of Ulsan College
of Medicine, Seoul, Korea.
Low-grade gliomas (LGG), which account for about 30% of brain tumors in
children, are usually treated with surgical excision and/or radiotherapy.
For patients who have significant residual tumor after resection or relapse
after radiation, the proper chemotherapy regimen has not yet been
identified. Thirteen children diagnosed with LGG outside the cerebellum
between January 1999 and December 2004, all of whom had significant residual
tumor after surgical resection, relapsed after radiation or showed visual
deterioration, were treated for 18 months with a multi-drug regimen of
vincristine, etoposide, cyclophosphamide and 5-fluorouracil. Of the 7
patients who completed chemotherapy, 1 showed complete response (CR), 5
showed partial response (PR), and 1 had stable disease (SD). In 5 patients,
chemotherapy was prematurely discontinued; 4 of these patients showed tumor
progression and 1 had SD. One patient is still undergoing treatment. The
side effects of chemotherapy were manageable. The median time to tumor
response was 34 months (range, 2-82 months). The progression free survival
was 67.3%. Pediatric LGG patients with residual tumor after surgery or who
undergo relapse(s) may be successfully treated using our combination
chemotherapy regimen.
PMID: 16807782 [PubMed - as supplied by publisher]>>>
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| 12: J Neurooncol.
2006 Jun 29; [Epub ahead of print] |
|
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Intelligence and adaptive function in children diagnosed
with brain tumour during infancy.
Stargatt R, Rosenfeld JV, Anderson V, Hassall T,
Maixner W, Ashley D.
Department of Psychology, Murdoch Childrens' Research Institute, Royal
Children's Hospital, Melbourne, Vic, Australia.
BACKGROUND: Late effects of treatment in children diagnosed and treated for
brain tumours in infancy is a major concern. Assessment of infants
presenting with brain tumours is difficult and there is little information
available regarding the development of infants prior to treatment and hence
the impact of the tumour itself on developmental outcomes. AIM: To describe
the development of children diagnosed with brain tumours in infancy and to
document their cognitive and adaptive function at school entry. METHOD:
Infants were psychologically evaluated at the time of diagnosis of a brain
tumour and during their fifth or sixth year in preparation for school entry.
RESULTS: Children diagnosed with brain tumours in infancy display
developmental delays in a number of areas of adaptive function. By the time
these children are school age they display further compromise in cognitive
and academic skills and adaptive behaviour. Higher levels of deficit at
follow-up were associated with tumour location in the supratentorium,
younger age at diagnosis and longer time since diagnosis. The effect of
radiotherapy could not be determined because of differing degrees of
developmental compromise in the treatment groups at baseline. CONCLUSION:
Brain tumours in infancy confer a risk of poor developmental progress at the
time of diagnosis. These children display additional compromise of
development by the time they reach school age. Research protocols evaluating
the impact of treatment in infants diagnosed with brain tumours need to take
account of the developmental status of the child at diagnosis.
PMID: 16807781 [PubMed - as supplied by publisher]>>>
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| 13: J Neurooncol.
2006 Jun 29; [Epub ahead of print] |
|
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Medical management of patients with brain tumors.
Wen PY, Schiff D, Kesari S, Drappatz J, Gigas
DC, Doherty L.
Division of Neuro-Oncology, Department of Neurology, Brigham and Women's
Hospital and Center for Neuro-Oncology, Dana-Farber Brigham and Women's
Cancer Center, SW430D, 44 Binney Street, Boston, MA, 02115, USA, pwen@partners.org.
The most common medical problems in brain tumor patients include the
management of seizures, peritumoral edema, medication side effects, venous
thromboembolism (VTE), fatigue and cognitive dysfunction. Despite their
importance, there are relatively few studies specifically addressing these
issues. There is increasing evidence that brain tumor patients who have not
had a seizure do not benefit from prophylactic antiepileptic medications.
Patients on corticosteroids are at greater risk of Pneumocystis jerovecii
pneumonia and may benefit from prophylactic therapy. There is also growing
evidence suggesting that anticoagulation may be more effective than inferior
vena cava IVC) filtration devices for treating VTE in brain tumor patients
and the risk of hemorrhage with anticoagulation is relatively small.
Low-molecular weight heparin may be more effective than coumadin.
Medications such as modafinil and methylphenidate have assumed an increasing
role in the treatment of fatigue, while donepezil and memantine may be
helpful with memory loss.
PMID: 16807780 [PubMed - as supplied by publisher]>>>
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| 14: Neurol Res.
2006 Jul;28(5):542-8. |
|
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Convection-enhanced delivery in the treatment of
malignant glioma.
Lopez KA, Waziri AE, Canoll PD, Bruce JN.
Gabriele Bartoli Brain Tumor Laboratory, Department of Neurological Surgery,
Columbia University Medical Center, New York, NY, USA.
Despite advancements in glioma therapy, median survival remains low because
of rapid post-resection recurrence. A regional method of drug delivery to
address local invasion may improve clinical outcomes. Convection-enhanced
delivery (CED) is a novel therapy that allows distribution of substances
throughout the interstitium via positive-pressure infusion. Studies using
various agents have investigated the parameters that affect CED including
infusion rate, cannula size, infusion volume, extracellular space, particle
characteristics and tumor tissue structure. We review models of small animal
glioma that have been successfully treated using different substances
administered through CED, particularly our favorable results using topotecan
in a C6 rat glioma model. We also review Phase I/II trials utilizing CED
which have shown promising response rates and acceptable safety profiles.
Future studies should include prospective clinical trials and investigation
of novel antitumor agents that are ineffective with systemic delivery.
Development of a large animal glioma model would enhance pre-clinical
investigation of CED. Clinically, methods to monitor distribution of
therapeutic agents and real-time patient response should likewise be
explored.
PMID: 16808887 [PubMed - in process]>>>
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| 15: Neurol Res.
2006 Jul;28(5):538-41. |
|
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Molecular markers of gliomas: a clinical approach.
Eoli M, Silvani A, Pollo B, Bianchessi D, Menghi
F, Valletta L, Broggi G, Boiardi A, Bruzzone MG,
Finocchiaro G.
Neurological Institute 'C. Besta', Via Caloria 11, Milan, Italy.
Over the last decade, the knowledge on the molecular genetic background of
gliomas has dramatically increased. This information provides the basis for
the molecular target therapies and molecular tests serve to complement the
subjective nature of histopathologic criteria and add useful data regarding
response to treatments and prognosis. In particular, the use of loss of
heterozygosity (LOH) and methylation specific polymerase chain reaction (PCR)
(MSP) based testing of gliomas is already in place and used clinically in
several centers. This paper provides a brief overview of these molecular
genetic aberrations and discusses the clinical utility, as well as the
advantages and disadvantages of such approach.Newly developed molecular
techniques, such as LOH testing, fluorescence in situ hybridization (FISH),
DNA sequencing and MSP, are currently being employed in assessment of
gliomas in some laboratories. However, the clinical use of some markers and
the context in which the information obtained should be used are still not
entirely understood. Therefore, this paper will focus on validation and
implementation of molecular testing in gliomas, with emphasis on LOH on
chromosomes 1p, 19q, 17p and 10q and O(6)-methylguanine-DNA
methyltransferase (MGMT) methylation status.
PMID: 16808886 [PubMed - in process]>>>
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| 16: Neurol Res.
2006 Jul;28(5):532-7. |
|
-
Telomerase inhibition impairs tumor growth in
glioblastoma xenografts.
Falchetti ML, Fiorenzo P, Mongiardi MP, Petrucci G,
Montano N, Maira G, Pierconti F, Larocca LM, Levi
A, Pallini R.
Institute of Neurobiology and Molecular Medicine, CNR, Rome, Italy.
Telomerase is a specialized DNA polymerase that is required to replicate the
ends of linear chromosomes, the telomeres. The majority of human cancers
express high levels of telomerase activity that is permissive for tumor
growth because it provides cells with an extended proliferative potential.
Additionally, telomerase exerts cell growth promoting functions and favors
cell survival. Human glioblastoma multiforme (GBM) cells express high level
of telomerase activity owing to the overexpression of human telomerase
reverse transcriptase (hTERT), the limiting subunit of the enzyme. Here we
used retroviral mediated RNA interference to dampen down telomerase activity
in two distinct human GBM cell lines, U87MG and TB10. Substantial decrease
of hTERT mRNA and telomerase activity had only minimal effects on telomere
length maintenance, cell growth and survival in vitro. On the contrary,
development of tumors upon subcutaneously grafting of U87MG and TB10 cells
and intracranial implantation of U87MG cells in nude athymic mice was
strongly reduced by telomerase inhibition.
PMID: 16808885 [PubMed - in process]>>>
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| 17: Neurol Res.
2006 Jul;28(5):527-31. |
|
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Dendritic cells pulsed with glioma lysates induce
immunity against syngeneic intracranial gliomas and increase survival of
tumor-bearing mice.
Pellegatta S, Poliani PL, Corno D, Grisoli M, Cusimano
M, Ubiali F, Baggi F, Bruzzone MG, Finocchiaro G.
Department of Experimental Neuro-Oncology, Istituto Nazionale Neurologico
Besta, Milano, Italy.
In recent years, the use of dendritic cells (DC), the most powerful antigen
presenting cells, has been proposed for the creation of vaccines against
gliomas. This approach has been demonstrated to be safe and non-toxic in
phase I or I-II trials (2, 3). Immunotherapy plays a central role in the
search for new treatments for glioblastoma multiforme (GBM). In particular,
several phase I studies have been performed using DC pulsed by GBM proteins
as a vaccine for patients with relapsing GBM. The studies demonstrated that
DC vaccination is safe and may produce a significant increase in overall
survival. As the first step in the preparation of appropriate conditions for
a clinical evaluation in Italy, we have performed pre-clinical experiments
on immune-competent mice injected intra-cerebrally with syngeneic GL261GBM
cells and treated subcutaneously and intra-tumorally with DC loaded with a
GL261 homogenate. These results show that vaccination with DC pulsed with a
tumor lysate increases considerably survival in mice bearing intracranial
glioblastomas and supports the development of DC-based clinical trials for
patients with glioblastomas that do not respond to standard therapies.
PMID: 16808884 [PubMed - in process]>>>
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| 18: Neurol Res.
2006 Jul;28(5):518-22. |
|
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Radioimmunotherapy of brain tumor.
Paganelli G, Bartolomei M, Grana C, Ferrari M, Rocca
P, Chinol M.
Division of Nuclear Medicine, European Institute of Oncology, Milano, Italy.
Despite years of intensive research, the prognosis of high-grade gliomas (HGG)
remains poor, as these tumors are highly resistant to currently available
therapies. Therefore, there is a need for the development of new therapeutic
strategies, such as the use of monoclonal antibodies (MoAbs) in association
with radioisotopes, in order to achieve better responses and prognosis. This
article describes our experience in radioimmunotherapy (RIT) with MoAbs and
tumor pre-targeting with the avidin-biotin system, either in systemic or
locoregional administrations. This therapy offers the exciting prospect of
increasing the specificity of tumor cell irradiation with radioisotopes. We
suggest that RIT, both systemic and locoregional, should be used as part of
a combined modality approach: in combination with surgery, radiotherapy and
chemotherapy.
PMID: 16808882 [PubMed - in process]>>>
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| 19: Neurol Res.
2006 Jul;28(5):482-7. |
|
-
Intraoperative visualization for resection of gliomas:
the role of functional neuronavigation and intraoperative 1.5 T MRI.
Nimsky C, Ganslandt O, Buchfelder M, Fahlbusch R.
Department of Neurosurgery, University Erlangen-Nuremberg, Erlangen,
Germany.
OBJECTIVE: To investigate how functional neuronavigation and intraoperative
high-field magnetic resonance imaging (MRI) influence glioma
resection.METHODS: One hundred and thirty-seven patients [World Health
Organization (WHO) grade I: 20; II: 19; III: 41; IV: 57] underwent resection
for supratentorial gliomas in an operative suite equipped with
intraoperative high-field MRI and microscope-based neuronavigation. Besides
standard anatomical image data including T1- and T2-weighted sequences,
various functional data from magnetoencephalography (n=37), functional MRI
(n=65), positron emission tomography (n=8), MR spectroscopy (n=28) and
diffusion tensor imaging (n=55) were integrated in the navigational
setup.RESULTS: Intraoperative MRI showed primary complete resection in 27%
of all patients (I: 50%; II: 53%; III: 2%; IV: 28%). In 41% of all patients
(I: 40%; II: 26%; III: 66%; IV: 28%) the resection was extended owing to
intraoperative MRI increasing the percentage of complete resections to 40%
(I: 70%; II: 58%; III: 17%; IV: 40%). Integrated application of functional
navigation resulted in low post-operative morbidity with a transient new
neurological deficit in 10.2% (paresis: 8.8% and speech disturbance: 1.4%)
decreasing to a permanent deficit in 2.9% (four of 137 patients with a new
or increased paresis).CONCLUSIONS: The combination of intraoperative MRI and
functional navigation allows safe extended resections in glioma surgery.
However, despite extended resections, still in the majority of the grade III
and IV gliomas no gross total resection could be achieved owing to the
extension of the tumor into eloquent brain areas. Intraoperative MRI data
can be used to localize the tumor remnants reliably and compensate for the
effects of brain shift.
PMID: 16808876 [PubMed - in process]>>>
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| 20: Neurol Res.
2006 Jul;28(5):471-3. |
|
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Advances in biology and treatment of malignant brain
gliomas: Stem cells and neurosciences.
Maira G, Fernandez E.
Department of Neurosurgery, Catholic University School of Medicine, Largo A.
Gemelli 8, Rome 00168, Italy.
PMID: 16808874 [PubMed - in process]
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| 21: Neurology. 2006 Jun
27;66(12):1899-906. |
|
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Diagnostic performance of spectroscopic and perfusion MRI
for distinction of brain tumors.
Weber MA, Zoubaa S, Schlieter M, Juttler E, Huttner
HB, Geletneky K, Ittrich C, Lichy MP, Kroll A,
Debus J, Giesel FL, Hartmann M, Essig M.
Department of Radiology, German Cancer Research Center, Im Neuenheimer Feld
280, D-69120 Heidelberg, Germany. m.a.weber@dkfz.de
OBJECTIVE: To assess the value of spectroscopic and perfusion MRI for glioma
grading and for distinguishing glioblastomas from metastases and from CNS
lymphomas. METHODS: The authors examined 79 consecutive patients with first
detection of a brain neoplasm on nonenhanced CT scans and no therapy prior
to evaluation. Spectroscopic MRI; arterial spin-labeling MRI for measuring
cerebral blood flow (CBF); first-pass dynamic, susceptibility-weighted,
contrast-enhanced MRI for measuring cerebral blood volume; and T1-weighted
dynamic contrast-enhanced MRI were performed. Receiver operating
characteristic analysis was performed, and optimum thresholds for tumor
classification and glioma grading were determined. RESULTS: Perfusion MRI
had a higher diagnostic performance than spectroscopic MRI. Because of a
significantly higher tumor blood flow in glioblastomas compared with CNS
lymphomas, a threshold value of 1.2 for CBF provided sensitivity of 97%,
specificity of 80%, positive predictive value (PPV) of 94%, and negative
predictive value (NPV) of 89%. Because CBF was significantly higher in
peritumoral nonenhancing T2-hyperintense regions of glioblastomas compared
with metastases, a threshold value of 0.5 for CBF provided sensitivity,
specificity, PPV, and NPV of 100%, 71%, 94%, and 100%. Glioblastomas had the
highest tumor blood flow values among all other glioma grades. For
discrimination of glioblastomas from grade 3 gliomas, sensitivity was 97%,
specificity was 50%, PPV was 84%, and NPV was 86% (CBF threshold value of
1.4), and for discrimination of glioblastomas from grade 2 gliomas,
sensitivity was 94%, specificity was 78%, PPV was 94%, and NPV was 78% (CBF
threshold value of 1.6). CONCLUSION: Perfusion MRI is predictive in
distinguishing glioblastomas from metastases, CNS lymphomas and other
gliomas vs MRI and magnetic resonance spectroscopy.
PMID: 16801657 [PubMed - in process]>>>
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| 22: Neurology. 2006 May
23;66(10):1609-10; author reply 1609-10. |
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Comment on:
- Neurology. 2005 Oct 11;65(7):1120-2.
CSF levels of angiogenesis-related proteins in patients
with leptomeningeal metastases.
Groves MD.
Publication Types:
PMID: 16717241 [PubMed - indexed for MEDLINE]
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Volume 5, Number 27 - 3 July 2006