-
Intensity-modulated stereotactic radiotherapy (IMSRT) for
skull-base meningiomas.
Yenice
KM, Narayana
A, Chang
J, Gutin
PH, Amols
HI.
Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New
York, NYUSA.
PURPOSE: To investigate the potential benefits of a micromultileaf
collimator (muMLC) -based intensity-modulated stereotactic radiotherapy
(IMSRT) in skull-base meningiomas. METHODS AND MATERIALS: Seven patients
with inoperable or recurrent small-volume (1.7-15.5 cc) skull-base
meningiomas were treated with IMSRT to 54 Gy in 30 fractions using a muMLC
in the dynamic mode. IMSRT plan quality was evaluated in comparison with the
conformal stereotactic radiotherapy technique, using the same beam
arrangement and static delivery with the muMLC. Plans were compared using
multiple dose distributions and dose-volume histograms for the planning
target volume and organs at risk. The conformity and uniformity metrics, as
well as normal-tissue complication probabilities, were calculated for the
two techniques. Follow-up with MRI and clinical examination was performed at
regular intervals. RESULTS: With a mean follow-up of 17 months, local
control has been achieved in all cases, and no treatment-related toxicities
have been noted. For cavernous sinus tumors overlapping with optic
apparatus, IMSRT has improved the dose uniformity within the target on
average by 8%, which resulted in a reduction of the estimated chiasm
normal-tissue complication probability by up to 65%. CONCLUSIONS:
Intensity-modulated stereotactic radiotherapy can be safely delivered to
improve the dose distributions in select skull-base meningiomas with an
appreciable concomitant dose reduction to involved critical structures.
Longer follow-up with a larger patient group is necessary to demonstrate
sustained tumor control and low morbidity with IMSRT for small inoperable,
recurrent, or subtotally resected meningiomas.
PMID: 16376488 [PubMed - as supplied by publisher]
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Spinal Cord Gliomas: A Multi-Institutional Retrospective
Analysis.
Abdel-Wahab
M, Etuk
B, Palermo
J, Shirato
H, Kresl
J, Yapicier
O, Walker
G, Scheithauer
BW, Shaw
E, Lee
C, Curran
W, Thomas
T, Markoe
A.
Department of Radiation Oncology, University of Miami, Miami FL.
PURPOSE: To determine the impact of postoperative radiation therapy (POXRT)
on outcome in spinal cord gliomas. PATIENTS AND METHODS: Data from 242
patients were collected retrospectively from six institutions using a
standardized data sheet. Pathology specimens, when available, were centrally
reviewed. RESULTS: A total of 183 patients were analyzed: 82 received
surgery alone as initial treatment, whereas 101 had surgery and POXRT.
Demographic, diagnostic, and treatment factors were analyzed for impact on
progression-free (PFS) and overall survival (OS). PFS in ependymoma patients
was 74%, 60%, and 35% at 5, 10, 15 years, respectively, and was
significantly influenced by treatment type, race, age, tumor grade, and type
of surgery on univariate analysis, with age being the only significant
factor on multivariate analysis (MVA) (p = 0.01). OS of ependymoma patients
was 91%, 84%, and 75% at 5, 10, and 15 years, respectively, and was
significantly influenced by both complete resection (p = 0.04) and age (p =
0.03) on MVA. In astrocytomas, PFS was 42%, 29%, and 15% at 5, 10, and 15
years, and was significantly influenced by POXRT in low- and
intermediate-grade tumors on MVA (p = 0.02). OS at 5, 10, and 15 years was
59%, 53%, and 32%, respectively, and was significantly influenced by grade
on MVA (p < 0.01). CONCLUSION: Postoperative radiation therapy reduced
disease progression in low- and moderate-grade astrocytomas. In ependymomas,
complete resection significantly influenced OS.
PMID: 16373081 [PubMed - as supplied by publisher]
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Utility of cranial boost in addition to total body
irradiation in the treatment of high risk acute lymphoblastic leukemia.
Alexander
BM, Wechsler
D, Braun
TM, Levine
J, Herman
J, Yanik
G, Hutchinson
R, Pierce
LJ.
Department of Radiation Oncology, University of Michigan, Ann Arbor, MI
48109-0010, USA.
PURPOSE: Total body irradiation (TBI) as part of a conditioning regimen
before hematopoietic stem cell transplant (HSCT) is an important component
in the management of acute lymphoblastic leukemia (ALL) that has relapsed or
has other certain high-risk features. Controversy exists, however, as to
whether a cranial boost in addition to TBI is necessary to prevent central
nervous system (CNS) recurrences in these high-risk cases. Previous national
trials have included a cranial boost in the absence of data to justify its
use. Therefore, the aim of this study was to assess risk of CNS recurrence
in ALL patients treated with TBI, to identify subsets of these high-risk
patients at an increased or decreased risk of CNS recurrence after TBI, and
to investigate whether regimens with higher doses of cranial irradiation
further reduce the risk of CNS recurrence. METHODS AND MATERIALS: Charts of
67 consecutively treated patients with ALL who received TBI before HSCT were
reviewed. Data including patient demographics, clinical features at
presentation, conditioning regimen, donor source, use of a cranial boost,
remission stage at transplant, histologic subtype, cytogenetics, and
extramedullary site of presentation were retrospectively collected and
correlated with the risk of subsequent CNS recurrence. RESULTS: At the time
of analysis, 30 (45%) patients were alive with no evidence of disease, 8
(12%) were alive with recurrence of leukemia, 7 (10.5%) had recurrent ALL
but with successful salvage, 7 (11%) died subsequent to recurrence, 14 (21%)
died from complications related to HCST, and 1 patient was lost to follow-up
(1.5%). Of the patients who recurred after HSCT, the relapses were
hematologic in 13 (57%), CNS with or without simultaneous marrow involvement
in 3 (13%), and other sites in 7 (30%). Forty-one (61%) patients did not
receive an extracranial boost of irradiation with TBI. Two of these patients
(4.9%) suffered CNS failures compared with 1 of 26 (3.8%) who received a
cranial boost (p = 0.84). None of the 40 patients who presented only with
hematologic disease developed a CNS recurrence despite the fact that only 13
of 40 of these patients received a cranial boost after TBI. Cranial boost
was therefore not associated with a reduction in CNS recurrence, especially
in patients with only hematologic disease at presentation for which there
were no failures regardless of the use of additional cranial radiotherapy.
CONCLUSIONS: Patients who present with hematologic disease only at the time
of HSCT have a low risk of CNS recurrence after TBI regardless of the use of
a cranial boost, suggesting that a cranial boost may not be necessary in
these patients.
Publication Types:
PMID: 15978741 [PubMed - indexed for MEDLINE]
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Salvage radioimmunotherapy with murine iodine-131-labeled
antitenascin monoclonal antibody 81C6 for patients with recurrent primary
and metastatic malignant brain tumors: phase II study results.
Reardon
DA, Akabani
G, Coleman
RE, Friedman
AH, Friedman
HS, Herndon
JE 2nd, McLendon
RE, Pegram
CN, Provenzale
JM, Quinn
JA, Rich
JN, Vredenburgh
JJ, Desjardins
A, Guruangan
S, Badruddoja
M, Dowell
JM, Wong
TZ, Zhao
XG, Zalutsky
MR, Bigner
DD.
Department of Surgery, Division of Neurosurgery, Duke University Medical
Center, Durham, NC, 27710, USA. reard003@mc.duke.edu
PURPOSE: To assess the efficacy and toxicity of intraresection cavity
iodine-131-labeled murine antitenascin monoclonal antibody 81C6 (131I-m81C6)
among recurrent malignant brain tumor patients. PATIENTS AND METHODS: In
this phase II trial, 100 mCi of 131I-m81C6 was injected directly into the
surgically created resection cavity (SCRC) of 43 patients with recurrent
malignant glioma (glioblastoma multiforme [GBM], n = 33; anaplastic
astrocytoma [AA], n = 6; anaplastic oligodendroglioma [AO], n = 2;
gliosarcoma [GS], n = 1; and metastatic adenocarcinoma, n = 1) followed by
chemotherapy. RESULTS: With a median follow-up of 172 weeks, 63% and 59% of
patients with GBM/GS and AA/AO tumors were alive at 1 year. Median overall
survival for patients with GBM/GS and AA/AO tumors was 64 and 99 weeks,
respectively. Ten patients (23%) developed acute hematologic toxicity. Five
patients (12%) developed acute reversible neurotoxicity. One patient (2%)
developed irreversible neurotoxicity. No patients required reoperation for
radionecrosis. CONCLUSION: In this single-institution phase II study,
administration of 100 mCi of 131I-m81C6 to recurrent malignant glioma
patients followed by chemotherapy is associated with a median survival that
is greater than that of historical controls treated with surgery plus
iodine-125 brachytherapy. Furthermore, toxicity was acceptable.
Administration of a fixed millicurie dose resulted in a wide range of
absorbed radiation doses to the SCRC. We are now conducting a phase II
trial, approved by the US Food and Drug Administration, using
patient-specific 131I-m81C6 dosing, to deliver 44 Gy to the SCRC followed by
standardized chemotherapy. A phase III multicenter trial with
patient-specific dosing is planned.
PMID: 16382120 [PubMed - in process]
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Comment on:
Radiotherapy alone or surgery in spinal cord compression?
The choice depends on accurate patient selection.
Maranzano
E, Bellavita
R, Rossi
R.
Publication Types:
PMID: 16278484 [PubMed - indexed for MEDLINE]
-
Comment on:
Radiation dose in spinal cord compression.
Macbeth
F, Stephens
R, Hoskin
P.
Publication Types:
PMID: 16278483 [PubMed - indexed for MEDLINE]
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-
Leptomeningeal metastases from solid malignancy: a
review.
Taillibert
S, Laigle-Donadey
F, Chodkiewicz
C, Sanson
M, Hoang-Xuan
K, Delattre
JY.
Federation de Neurologie, Batiment Mazarin, Groupe hospitalier
Pitie-Salpetriere, 47-83 bd de l'Hopital, 75013, Paris, France.
Leptomeningeal metastases (LMM) consist of diffuse involvement of the
leptomeninges by infiltrating cancer cells. In solid tumors, the most
frequent primary sites are lung and breast cancers, two tumors where the
incidence of LMM is apparently increasing. Careful neurological examination
is required to demonstrate multifocal involvement of the central nervous
system (CNS), cranial nerves, and spinal roots, which constitute the
clinical hallmark of the disease. Cerebro-spinal fluid (CSF) analysis is
almost always abnormal but only a positive cytology or demonstration of
intrathecal synthesis of tumor markers is diagnostic. T1-weighted
gadolinium-enhanced sequence of the entire neuraxis (brain and spine) plays
an important role in supporting the diagnosis, demonstrating the involved
sites and guiding treatment. Radionuclide CSF flow studies detect CSF
compartmentalization and are useful for treatment planning. Standard therapy
relies mainly on focal irradiation and intrathecal or systemic chemotherapy.
Studies using other therapeutic approaches such as new biological or
cytotoxic compounds are ongoing. The overall prognosis remains grim and
quality of life should remain the priority when deciding which treatment
option to apply. However, a sub-group of patients, tentatively defined here,
may benefit from an aggressive treatment.
Publication Types:
PMID: 16215819 [PubMed - indexed for MEDLINE]
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-
Dural metastases.
Laigle-Donadey
F, Taillibert
S, Mokhtari
K, Hildebrand
J, Delattre
JY.
Federation de Neurologie Mazarin, Groupe Hospitalier Pitie-Salpetriere, 47
boulevard de l'hopital, 75651, Paris Cedex 13, France.
Dural metastases are found at autopsy in 8-9% of patients with advanced
systemic cancer. They arise either by direct extension from skull metastases
or by hematogeneous spread. Dural metastases are often clinically
asymptomatic but they may produce progressive neurological deficits and
sometimes subdural hematomas. MRI may be misleading when the metastasis
simulates a meningioma or when a subdural hematoma masks the underlying
tumor. Whenever possible, surgical removal is the most appropriate
treatment. The prognosis is poor because of the progressive systemic cancer
but prolonged survival has been reported in operated patients, when the
systemic cancer was controlled.
Publication Types:
PMID: 16215816 [PubMed - indexed for MEDLINE]
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-
Metastasis to nervous system: spinal epidural and
intramedullary metastases.
Mut
M, Schiff
D, Shaffrey
ME.
Department of Neurosurgery, University of Virginia, Charlottesville
22908-0432, USA.
Spinal cord epidural metastasis (SEM) is a common complication of systemic
cancer with an increasing incidence. Prostate, breast and lung cancer are
the most common offenders. Metastasis usually arises in the posterior aspect
of vertebral body with later invasion of epidural space.
Pathophysiologically, vascular insufficiency is more important than direct
spinal cord compression. The most common complaint is pain, and two thirds
of patients with SEM have motor signs at initial diagnosis. Currently
magnetic resonance imaging is the most sensitive diagnostic tool. The
optimal management of SEM is still arguable, but recent advances in surgical
management of SEM and higher complication rate of surgery following
radiotherapy should persuade clinicians to consider de novo surgery where
possible. Radiotherapy has an important role, particularly in treatment of
radiosensitive tumors and in patients who are not candidates for surgery.
Novel approaches such as stereotactic radiosurgery are promising; however,
response to chemotherapy depends on inherent properties of primary tumor.
Recurrent SEM is a substantial problem for which surgery or repeat
radiotherapy may be options. Intramedullary metastasis is rare but should be
considered in patients with systemic malignancy and asymmetrical
presentation of myelopathic symptoms. The prognosis is usually poor and
preferred modality of treatment is radiotherapy.
Publication Types:
PMID: 16215815 [PubMed - indexed for MEDLINE]
-
-
Metastatic tumors of the nervous system.
Taillibert
S, Delattre
JY.
Publication Types:
PMID: 16215810 [PubMed - indexed for MEDLINE]
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Effect of trichostatin A, a histone deacetylase
inhibitor, on glioma proliferation in vitro by inducing cell cycle arrest
and apoptosis.
Wetzel
M, Premkumar
DR, Arnold
B, Pollack
IF.
Department of Neurological Surgery, University of Pittsburgh School of
Medicine, Pennsylvania, USA.
OBJECT: Trichostatin A (TSA) is a histone deacetylase inhibitor that causes
growth inhibition of malignant cells. The authors' goal was to evaluate its
effect on cell growth and cell cycle regulation in a large panel of glioma
cell lines, as well as in human astrocytes, fibroblasts, and endothelial
cells. METHODS: Cell growth in response to TSA was evaluated using a
tetrazolium colorimetric assay and a clonogenic assay. Cell cycle effects
were examined using flow cytometry. A DNA fragmentation assay was used to
evaluate induction of apoptosis. Histone acetylation status and the
expression of p21WAF1, phosphorylated retinoblastoma protein (Rb),
poly(adenosine diphosphate-ribose) polymerase (PARP), and caspase-3 were
studied using Western blot analysis. In the glioma cell lines, there was
significant inhibition of cell growth and detection of increased levels of
acetylated histones after TSA treatment. The mechanisms underlying the
growth inhibition include cell cycle arrest at the G2/M phase and apoptosis
induction. The expression of p21WAF1 was activated, with a temporally
related decrease in levels of phosphorylated Rb. Apoptosis was preceded by
detection of cleaved PARP and activated caspase-3. The effects of TSA were
less pronounced or absent in human astrocytes, fibroblasts, and endothelial
cells. CONCLUSIONS: The TSA caused inhibition of glioma cell growth by both
cell cycle arrest and apoptosis. Cell cycle arrest was associated with an
increase in p21WAF1 expression and a decrease in phosphorylated Rb.
Apoptosis was mediated at least partly through the activation of caspase-3.
Because of the differential effects in glioma cells compared with
nonneoplastic cells, TSA may provide a novel strategy for achieving tumor
growth inhibition and cytotoxicity. Further investigation is warranted.
PMID: 16383255 [PubMed - in process]
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Central nervous system meningiomas in the first two
decades of life: a clinicopathological analysis of 87 patients.
Rushing
EJ, Olsen
C, Mena
H, Rueda
ME, Lee
YS, Keating
RF, Packer
RJ, Santi
M.
Department of Neuropathology, Armed Forces Institute of Pathology,
Washington, DC 20306-6000, USA. rushinge@afip.osd.mil
OBJECT: The occurrence of meningiomas in children younger than 20 years of
age is rare, accounting for less than 3% of all childhood tumors of the
central nervous system. The authors of this study sought to add to the
limited available information regarding clinicopathological factors that
influence outcome, disease progression, and survival in children with
meningiomas. METHODS: Eighty-seven cases of childhood meningiomas were
identified and classified according to World Health Organization (WHO) 2000
criteria. In addition to the WHO classification, the following potential
prognostic factors were analyzed: age, sex, extent of resection, history of
radiotherapy, diagnosis of neurofibromatosis Type 2 (NF2) or other inherited
syndromes, and the presence of a comorbidity. There was a sex predilection
for male patients (35 females and 52 males). Patient age ranged from 5
months to 20 years (mean 14 years). The most common clinical presentations
were seizures (33%), headaches (13%), ataxia (10%), and hemiparesis (10%).
Nine patients had NF2 and two had Gorlin syndrome. Seven patients had
undergone radiotherapy for a prior neoplasm. Tumor location was
supratentorial in 64% of the patients, infratentorial in 16%,
intraventricular in 12%, and spinal in 8%. Fifty-three patients (62%)
underwent gross-total resection and 28 (33%) underwent subtotal resection.
Histopathological analysis revealed 62 (71%) WHO Grade I, 21 (24%) Grade II,
and four (5%) Grade III meningiomas. One patient received adjuvant
chemotherapy and four received radiotherapy. CONCLUSIONS: Using survival
data from this unique patient cohort, the authors found that recurrence-free
survival time was significantly related to WHO grade (p = 0.002), but
overall survival time was not significantly linked to any of the potential
prognostic factors considered in this study (p = 0.06).
PMID: 16383246 [PubMed - in process]
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Long-term results of gamma knife surgery for the
treatment of craniopharyngioma in 98 consecutive cases.
Kobayashi
T, Kida
Y, Mori
Y, Hasegawa
T.
Nagoya Radiosurgery Center, Nagoya Kyoritsu Hospital, Japan.
ttkobayashi@kaikou.or.jp
OBJECT: The authors analyzed the long-term outcomes of gamma knife surgery
(GKS) for residual or recurrent craniopharyngiomas after microsurgery and
the effects of dose reduction. METHODS: A total of 107 patients with
craniopharyngiomas were treated with GKS at Komaki City Hospital during the
past 12 years, and 98 patients were followed up for 6 to 148 months (mean
65.5 months). The mean tumor diameter and volume were 18.8 mm and 3.5 ml,
respectively. These tumors were treated with a maximal dose of 21.8 Gy and a
tumor margin dose of 11.5 Gy by using a mean of 4.5 isocenters. Final
overall response rates were as follows: complete response 19.4%, partial
response 67.4%, tumor control 79.6%, and tumor progression 20.4%. Reducing
the tumor margin dose resulted in decreased therapeutic response and
increased tumor progression, although the rate of visual and pituitary
function loss also decreased. Among the factors examined, age (for adults)
and the nature of the tumor (cystic or mixed) were statistically significant
favorable and unfavorable prognostic factors, respectively. The actuarial 5-
and 10-year survival rates were 94.1 and 91%, respectively. The
progression-free survival rates were 60.8 and 53.8%, respectively. Patient
outcomes were reportedly excellent in 45 cases, good in 23, fair in four,
and poor in three; 16 patients died. Deterioration both in vision and
endocrinological functions were documented as side effects in six patients
(6.1%). CONCLUSIONS: Stereotactic GKS is safe and effective, in the long
term, as an adjuvant or boost therapy for residual or recurrent
craniopharyngiomas after surgical removal and has minimal side effects. New
treatment strategies must be devised to manage these tumors.
PMID: 16383245 [PubMed - in process]
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Retargeting of adenoviral vector using basic fibroblast
growth factor ligand for malignant glioma gene therapy.
Wang
W, Zhu
NL, Chua
J, Swenson
S, Costa
FK, Schmitmeier
S, Sosnowski
BA, Shichinohe
T, Kasahara
N, Chen
TC.
Department of Pediatrics, University of Southern California School of
Medicine, Los Angeles 90033, USA.
OBJECT: Adenovirus vector (AdV)-mediated gene delivery has been recently
demonstrated in clinical trials as a novel potential treatment for malignant
gliomas. Combined coxsackievirus B and adenovirus receptor (CAR) has been
shown to function as an attachment receptor for multiple adenovirus
serotypes, whereas the vitronectin integrins (alphavbeta3 and alphavbeta5)
are involved in AdV internalization. In resected glioma specimens, the
authors demonstrated that malignant gliomas have varying levels of CAR,
alphavbeta3, and alphavbeta5 expression. METHODS: A correlation between CAR
expression and the transduction efficiency of AdV carrying the green
fluorescent protein in various human glioblastoma multiforme (GBM) cell
lines and GBM primary cell lines was observed. To increase transgene
activity in in vitro glioma cells with low or deficient levels of CAR, the
authors used basic fibroblast growth factor (FGF2) as a targeting ligand to
redirect adenoviral infection through its cognate receptor, FGF receptor 1
(FGFR1), which was expressed at high levels by all glioma cells. These
findings were confirmed by in vivo study data demonstrating enhanced
transduction efficiency of FGF2-retargeted AdV in CAR-negative intracranial
gliomas compared with AdV alone, without evidence of increased angiogenesis.
CONCLUSIONS: Altogether, the results demonstrated that AdV-mediated gene
transfer using the FGF2/FGFR system is effective in gliomas with low or
deficient levels of CAR and suggested that FGF2-retargeting of AdV may be a
promising approach in glioma gene therapy.
PMID: 16381193 [PubMed - in process]
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Resection of parietal lobe gliomas: incidence and
evolution of neurological deficits in 28 consecutive patients correlated to
the location and morphological characteristics of the tumor.
Russell
SM, Elliott
R, Forshaw
D, Kelly
PJ, Golfinos
JG.
Department of Neurosurgery, New York University School of Medicine, New
York, USA. russes01@yahoo.com
OBJECT: The goal of this study is to report the incidence and clinical
evolution of neurological deficits in patients who underwent resection of
gliomas confined to the parietal lobe. METHODS: Patient demographics,
findings of serial neurological examinations, tumor location and
neuroimaging characteristics, extent of resection, and surgical outcomes
were tabulated by reviewing inpatient and office records, as well as all
pre- and postoperative magnetic resonance (MR) images obtained in 28
consecutive patients who underwent resection of a glial neoplasm found on
imaging studies to be confined to the parietal lobe. Neurological deficits
were correlated with hemispheric dominance, location of the lesion within
the superior or inferior parietal lobules, subcortical extension, and
involvement of the postcentral gyrus. The tumors were located in the
dominant hemisphere in 18 patients (64%); had a mean diameter of 39 mm
(range 14-69 mm); were isolated to the superior parietal lobule in six
patients (21%) and to the inferior parietal lobule in eight patients (29%);
and involved both lobules in 14 patients (50%). Gross-total resection,
documented by MR imaging, was achieved in 24 patients (86%).
Postoperatively, nine patients (32%) experienced new neurological deficits,
whereas seven (25%) had an improvement in their preoperative deficit. A
correlation was noted between larger tumors and the presence of neurological
deficits both before and after resection. Postoperatively higher-level
(association) parietal deficits were noted only in patients with tumors
involving both the superior and inferior parietal lobules in the dominant
hemisphere. At the 3-month follow-up examination, five of nine new
postoperative deficits had resolved. CONCLUSIONS: Neurological deterioration
and improvement occur after resection of parietal lobe gliomas. Parietal
lobe association deficits, specifically the components of Gerstmann
syndrome, are mostly associated with large tumors that involve both the
superior and inferior parietal lobules of the dominant hemisphere. New
hemineglect or sensory extinction was not noted in any patient following
resection of lesions located in the nondominant hemisphere. Nevertheless,
primary parietal lobe deficits (for example, a visual field loss or cortical
sensory syndrome) occurred in patients regardless of hemispheric dominance.
PMID: 16381187 [PubMed - in process]
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Modified boron neutron capture therapy for malignant
gliomas performed using epithermal neutron and two boron compounds with
different accumulation mechanisms: an efficacy study based on findings on
neuroimages.
Miyatake
S, Kawabata
S, Kajimoto
Y, Aoki
A, Yokoyama
K, Yamada
M, Kuroiwa
T, Tsuji
M, Imahori
Y, Kirihata
M, Sakurai
Y, Masunaga
S, Nagata
K, Maruhashi
A, Ono
K.
Department of Neurosurgery, Osaka Medical College, Takatsuki City, Japan.
neu070@poh.osaka-med.ac.jp
OBJECT: To improve the effectiveness of boron neutron capture therapy (BNCT)
for malignant gliomas, the authors used epithermal rather than thermal
neutrons for deep penetration and two boron compounds-sodium borocaptate
(BSH) and boronophenylalanine (BPA)-with different accumulation mechanisms
to increase the boron level in tumors while compensating for each other's
faults. METHODS: Thirteen patients, 10 of whom harbored a glioblastoma
multiforme (GBM), one a gliosarcoma, one an anaplastic astrocytoma, and one
an anaplastic oligoastrocytoma, were treated using this modified BNCT
between January 2002 and December 2003. Postoperatively, neuroimaging
revealed that only one patient with a GBM had no lesion enhancement
postoperatively. The patients underwent 18F-BPA positron emission
tomography, if available, to assess the accumulation and distribution of BPA
before neutron radiotherapy. The neutron fluence rate was estimated using
the Simulation Environments for Radiotherapy Applications dose-planning
system before irradiation. The patients' volume assessments were performed
using magnetic resonance (MR) imaging or computerized tomography (CT)
scanning. Improvements in the disease as seen on neuroimages were assessed
between 2 and 7 days after irradiation to determine the initial effects of
BNCT; its maximal effects were also analyzed on serial neuroimages. The mean
tumor volume before BNCT was 42.3 cm3. Regardless of the pre-BNCT tumor
volume, in every patient harboring an assessable lesion, improvements on MR
or CT images were recognized both at the initial assessment (range of volume
reduction rate 17.4-71%, mean rate 46.4%) and at follow-up assessments
(range of volume reduction rates 30.3-87.6%, mean rate 58.5%). More than 50%
of the contrast-enhanced lesions disappeared in eight of the 12 patients
during the follow-up period. CONCLUSIONS: This modified BNCT produced a good
improvement in malignant gliomas, as seen on neuroimages.
PMID: 16381186 [PubMed - in process]
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ADAM22, expressed in normal brain but not in high-grade
gliomas, inhibits cellular proliferation via the disintegrin domain.
D'Abaco
GM, Ng
K, Paradiso
L, Godde
NJ, Kaye
A, Novak
U.
Department of Surgery, Royal Melbourne Hospital, Parkville, Australia.
OBJECTIVE: To study the expression and function of the brain-specific
proteinase deficient disintegrins, ADAM11 and ADAM22 (a disintegrin and
metalloproteinase). METHODS: Specimens of low- and high-grade gliomas and
normal brain were analyzed for ADAM11 and ADAM22 expression using Western
blotting. The effects of overexpression of ADAM11 and ADAM22 in glioma cells
on growth were analyzed using bromodeoxyuridine incorporation linked to
immunocytochemistry. Similarly analyzed were the effects on cell
proliferation of bacterially expressed glutathione S-transferase fusion
proteins with the disintegrin domain of ADAM11 and ADAM22. RESULTS: ADAM22
is expressed in normal brain and some low-grade gliomas, but not in
high-grade gliomas, whereas ADAM11 is expressed in all low- and high-grade
gliomas. In vitro, ADAM22 inhibits cellular proliferation of glioma derived
astrocytes. The growth inhibition appears to be mediated by interactions
between the disintegrin domain of ADAM22 and specific integrins expressed on
the cell surface. This growth inhibition can be avoided by over-expression
of integrin linked kinase. CONCLUSION: ADAM22, a brain-specific cell surface
protein, mediates growth inhibition using an integrin dependent pathway. It
is expressed in normal brain but not in high-grade gliomas. A related
protein, ADAM11, has only a minor effect on cell growth, and its expression
is unchanged in low- and high-grade gliomas.
PMID: 16385342 [PubMed - in process]
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Gamma-knife radiosurgery for cranial base meningiomas:
experience of tumor control, clinical course, and morbidity in a follow-up
of more than 8 years.
Zachenhofer
I, Wolfsberger
S, Aichholzer
M, Bertalanffy
A, Roessler
K, Kitz
K, Knosp
E.
Department of Neurosurgery, Medical University of Vienna, Vienna, Austria.
iris.zachenhofer@meduniwien.ac.at
OBJECTIVE: Surgical resection of cranial base meningiomas is often limited
owing to involvement of crucial neural structures. Within the last 2 decades
Gamma Knife radiosurgery (GKRS) has gained increasing importance as an
adjunct treatment after incomplete resection and as an alternative treatment
to open surgery. However, reports of long-term results are still sparse. We
therefore performed this study to analyze the long-term results of GKRS
treatment of cranial base meningiomas, following our previously published
early follow-up experience. METHODS: A retrospective analysis of the medical
files for Gamma Knife and surgical treatments, clinicoradiological findings,
and outcome was carried out focusing on tumor control, clinical course, and
morbidity. RESULTS: Between 1992 and 1995, we treated 36 patients with
cranial base meningiomas using GKRS (male:female ratio, 1:5; mean age, 59
yr; range, 44-89 yr). Twenty-five patients were treated with GKRS after open
surgery, and 11 patients received GKRS alone. Tumor control, neurological
outcomes, and adverse effects were analyzed after a long-term follow-up
period (mean, 103 mo; range, 70-133 mo) and compared with our previous
results after an early follow-up period (mean, 48 mo; range, 36-76 mo).
Control of tumor growth was achieved in 94% of patients. Compared with the
early follow-up period, the late neuroradiological effects of GKRS on
cranial base meningiomas were continuing tumor shrinkage in 11 patients
(33%), stable tumor size in 20 patients (64%) and tumor progression in two
meningiomas (6%). The neurological status improved in 16 patients (44%),
remained stable in 19 patients (52%), and deteriorated in one patient (4%).
Adverse side effects of GKRS were found only during the early follow-up
period. CONCLUSION: Our data confirm that GKRS is not only a safe and
effective treatment modality for cranial base meningiomas in short-term
observation, but also in a mean long-term follow-up period of more than 8
years. Tumor shrinkage and clinical improvement also continued during the
longer follow-up period.
PMID: 16385326 [PubMed - in process]
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Roles of the Rac1 and Rac3 GTPases in human tumor cell
invasion.
Chan
AY, Coniglio
SJ, Chuang
YY, Michaelson
D, Knaus
UG, Philips
MR, Symons
M.
Institute for Medical Research at North Shore-LIJ, Manhasset, NY 11030, USA.
Members of the Rho family of small GTPases have been shown to be involved in
tumorigenesis and metastasis. Currently, most of the available information
on the function of Rho proteins in malignant transformation is based on the
use of dominant-negative mutants of these GTPases. The specificity of these
dominant-negative mutants is limited however. In this study, we used small
interfering RNA directed against either Rac1 or Rac3 to reduce their
expression specifically. In line with observations using dominant-negative
Rac1 in other cell types, we show that RNA interference-mediated depletion
of Rac1 strongly inhibits lamellipodia formation, cell migration and
invasion in SNB19 glioblastoma cells. Surprisingly however, Rac1 depletion
has a much smaller inhibitory effect on SNB19 cell proliferation and
survival. Interestingly, whereas depletion of Rac3 strongly inhibits SNB19
cell invasion, it does not affect lamellipodia formation and has only minor
effects on cell migration and proliferation. Similar results were obtained
in BT549 breast carcinoma cells. Thus, functional analysis of Rac1 and Rac3
using RNA interference reveals a critical role for these GTPases in the
invasive behavior of glioma and breast carcinoma cells.
PMID: 16027728 [PubMed - indexed for MEDLINE]
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Intracranial involvement in Hodgkin's disease.
Akyuz
C, Yalcin
B, Atahan
IL, Varan
A, Kutluk
MT, Buyukpamukcu
M.
Hacettepe University Institute of Oncology, Department of Pediatric
Oncology, Ankara, Turkey. cakyuz@hacettepe.edu.tr
The authors report 3 cases of Hodgkin's disease with intracranial
involvement. The patients were 4, 12, and 15 years old (male/female=1/2).
Initially, they were treated with ABVD or COPP chemotherapies and low-dose
involved field radiotherapy. Intracranial recurrences occurred 27, 40, and
42 months after initial diagnosis, respectively. Two patients experienced
convulsions and the other complained of diplopia. The metastatic lesions
were located supratentorially with CT or MRI. Despite initial response
achieved following systemic chemotherapy and external irradiation to cranial
lesions, all patients died with disseminated disease. In patients with
intracranial involvement of Hodgkin's disease, prolonged disease-free
survival may be achieved by combined modality treatment.
Publication Types:
PMID: 16166052 [PubMed - indexed for MEDLINE]
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Everyday Cognitive Function After Craniopharyngioma in
Childhood.
Waber
DP, Pomeroy
SL, Chiverton
AM, Kieran
MW, Scott
RM, Goumnerova
LC, Rivkin
MJ.
Division of Psychology, Department of Psychiatry, Children's Hospital
Boston, Boston, Massachusetts; Department of Psychiatry, Harvard Medical
School, Boston, Massachusetts.
Despite clinical impressions that cognitive complaints are prominent in
patients with a history of craniopharyngioma, formal neuropsychologic
documentation is inconsistent. This study assessed everyday cognitive
complaints and neuropsychologic test performance to evaluate the prevalence
of problems and the relationship of these domains to one another in patients
treated for craniopharyngioma in childhood or adolescence. Ten patients
treated for craniopharyngioma completed measures of everyday cognitive
function (Cognitive Failures Questionnaire, Rivermead Behavioural Memory
Test) and a battery of standard neuropsychologic tests. The prevalence of
problems was ascertained for each measure. Most patients demonstrated
significant deficits in everyday memory (Cognitive Failures Questionnaire,
9/10 patients; Rivermead Behavioural Memory Test, 7/10 patients). Scores
were within normal limits, however, for intelligence quotient, achievement,
attention, verbal memory, and spatial working memory. Processing speed was
slow (5/10 patients). Spatial working memory predicted Cognitive Failures
Questionnaire (P < 0.07), as did somatic symptoms from the Beck
Depression Inventory (P < 0.01), but these associations appeared
independent. Adolescents and young adults with treated craniopharyngioma
experience deficits in everyday cognitive functions, many involving memory,
that are not easily detected by standard neuropsychologic testing. The
extent of self-rated cognitive problems is related to spatial working memory
and somatic concerns.
PMID: 16376272 [PubMed - as supplied by publisher]
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A long-term ventricular drainage for patients with germ
cell tumors or medulloblastoma.
Matsumoto
J, Kochi
M, Morioka
M, Nakamura
H, Makino
K, Hamada
J, Kuratsu
J, Ushio
Y.
Department of Neurosurgery, Kumamoto University School of Medicine, Kumamoto
860-8556, Japan.
BACKGROUND: Hydrocephalus associated with intracranial germ cell tumors or
disseminated medulloblastoma has been treated with ventriculoperitoneal
shunt. However, this procedure has a potential risk of intraperitoneal
metastasis of these brain tumors. To prevent this potential risk and to
minimize the risk of infection, we developed a percutaneous long-tunneled
ventricular drainage (PLTVD). To confirm the effectiveness, we
retrospectively analyzed the results of this procedure. METHODS: From 1979
to 2003, we have treated 96 patients with germ cell tumors and
medulloblastoma in our hospital. Of 96 patients, 59 (germ cell tumor, 31;
medulloblastoma, 28) had hydrocephalus and 13 needed long-term cerebrospinal
fluid drainage to manage the obstructive hydrocephalus due to persistent
tumor or communicating hydrocephalus due to dissemination. We performed
PLTVD for these cases using a flow-controlled shunt device and percutaneous
long-tunneled shunt tube (peritoneal catheter) exiting at the upper abdomen
and connecting to a closed drainage system. The occurrence of extraneural
metastasis and the incidence of infection were evaluated. RESULTS: The
average duration of drainage was 74 days (range, 34-115 days). All 13 cases
received full-dose chemotherapy and radiotherapy without infectious
complications or extraneural metastasis. CONCLUSIONS: Percutaneous
long-tunneled ventricular drainage was an effective method to manage
long-lasting obstructive or communicating hydrocephalus with germ cell
tumors and medulloblastoma.
PMID: 16378864 [PubMed - in process]
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Fractionated stereotactic radiotherapy in the treatment
of exclusive cavernous sinus meningioma: functional outcome, local control,
and tolerance.
Brell
M, Villa
S, Teixidor
P, Lucas
A, Ferran
E, Marin
S, Acebes
JJ.
Neurosurgery Department, Hospital Universitari de Bellvitge, L'Hospitalet,
Barcelona, Spain 08907.
BACKGROUND: Fractionated stereotactic radiotherapy (FSRT) combines the
precision of stereotactic positioning with the radiobiologic advantage of
dose fractionation. METHODS: From June 1997 to June 2001, 30 patients with
cavernous sinus meningiomas were treated with FSRT using fixed noncoplanar
conformal fields. Patient skull fixation was achieved using the BrainLAB
mask (20 patients) or Beverly frame (10 patients). The Cosman-Roberts-Wells
coordinate frame was used for stereotactic space definition. In selected
cases before 1999, and in all cases afterward, gadolinium-enhanced MRI for
image fusion was performed. The median radiation dose was 52 Gy, with a
daily fraction of 2 Gy. Patients were regularly followed up analyzing
symptoms, tumor progression, and side effects. Neurocognitive function was
evaluated retrospectively for 26 patients using Mini-Mental State
Examination. RESULTS: Median follow-up period was 50 months (range,
28.2-74.5 months). Preexisting neurologic symptoms improved in 50% of the
patients and worsened in 2 patients. Only 2 patients progressed and the
actuarial local progression free survival was 93% at 4 years. Tolerance was
good with 2 cases of late radiation toxicity which consisted of moderate
short-term memory loss and dysphasia in one case and neuropsychologic
deficit with seizures in the other. Postradiotherapy Mini-Mental State
Examination results showed a median score of 28 (range, 16-30). CONCLUSIONS:
Fractionated stereotactic radiotherapy is a high-precision technique. It is
safe and feasible in the primary and adjuvant treatment of cavernous sinus
meningiomas. Fractionated stereotactic radiotherapy allowed local control in
more than 90% of patients.
PMID: 16378847 [PubMed - in process]
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Neuropsychological findings in patients with
intraventricular tumors.
Buhl
R, Huang
H, Gottwald
B, Mihajlovic
Z, Mehdorn
HM.
Department of Neurosurgery, University of Kiel, 24105 Kiel, Germany.
buhlr@nch.uni-kiel.de
BACKGROUND: Intraventricular tumors are quite rare and become symptomatic
with hydrocephalus-related signs such as headache, double vision, and
seizures. Also, most of the patients show neuropsychological deficits,
especially memory problems and lack of attention. METHODS: We reviewed the
charts and computed tomographic/magnetic resonance images of 15 patients
with tumors of the lateral and third ventricle, who were also examined by a
neuropsychologist pre- and postoperatively. Neuropsychological testing
included tests of attention, memory, executive functions, and concentration.
RESULTS: Between 1995 and 2003, 7 patients with colloid cysts of the third
ventricle (3 men, 4 women; mean age, 38 years), 5 patients with meningiomas
of the lateral ventricle (2 men, 3 women; mean age, 51 years), and 3
patients with astrocytomas and ependymoma (2 men, 1 woman; mean age, 38
years) were treated. All patients with colloid cysts and meningiomas showed
mental changes, especially attention and memory deficits. Symptoms improved
markedly after surgical intervention. The 3 patients with astrocytoma and
ependymoma showed normal results pre- and postoperatively. CONCLUSION:
Neuropsychological testing is very useful in patients with intraventricular
lesions and important for follow-up examinations. It should be included in
every workup examination in this small patient group.
PMID: 16293462 [PubMed - indexed for MEDLINE]
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Volume 5, Number 1 - 1
January 2006