J Neurooncol (2011) 104:545551

DOI 10.1007/s11060-010-0512-2

Ventriculoperitoneal shunt for hydrocephalus caused by central

nervous system metastasis
Seung Hoon Lee Doo Sik Kong Ho Joon Seol Do-Hyun Nam Jung-Il Lee

Received: 1 September 2010/Accepted: 20 December 2010/Published online: 28 January 2011

Springer Science+Business Media, LLC. 2011 adequate cancer treatment after VPS may provide the best
means of improving survival.
Keywords Ventriculoperitoneal shunt CNS
Abstract The development of better diagnostic tools and
metastasis Risk factor Survival
therapeutic modalities has increased the incidence of central
nervous system (CNS) metastasis in malignant tumor
patients. Hydrocephalus can result from CNS metastasis and
Introduction
frustrate cancer treatment. The authors sought to investigate
the outcomes and the roles of ventriculoperitoneal shunts
Approximately 2535% of cancer patients will develop
(VPS) in patients with CNS metastasis. The medical records
brain metastasis [1]. The incidence of metastasis to the CNS
of 50 consecutive patients who underwent VPS for
is likely to increase due to introduction of better diagnostic
hydrocephalus related to CNS metastasis were analyzed
tools, which enable earlier detection, and to the development
retrospectively. Data included features of primary
of more efficient therapeutic modalities, which enable
malignancies, CNS involvement, clinical course and
longer systemic control and longer survival. Furthermore,
surgical outcome. Median patient age was 55.0 years (range
regardless of brain parenchymal metastasis, LMS (also
2577), and 30 female and 20 male patients were included
known as meningeal carcinomatosis, neoplastic meningitis,
in the study. At the time of VPS, 10 patients had
and carcinomatous meningitis) is in itself a devastating
parenchymal metastases only and 40 patients had
complication of cancer that affects 58% of patients with
leptomeningeal seeding (LMS). Symptom improvement
solid tumors [25].
was observed postoperatively in 40 patients (80%), mean
Of the various clinical manifestations of secondary CNS
Karnofsky performance status (KPS) scale change was from
malignancies, hydrocephalus may result from the
37.8 to 46.0, and median survival from VPS was 3.0 months
obstruction of a CSF pathway by a large mass or from the
(2 days to 54 months). A ventricular opening pressure of[30
dissemination of metastatic cells in the subarachnoid space
cmH2O (HR 6.44, 95% CI 1.2632.9,P= 0.02) andfurther
inducing CSF malabsorption. Symptoms of hydrocephalus,
cancer treatmentafter VPS (HR 0.17, 95% CI 0.070.42,
such as headache, nausea, vomiting, gait disturbance,
P\0.0001) were found to be independent risk factors of
urinary incontinence, cranial nerve palsy, and even mental
poorer and better survival, respectively. Hydrocephalus in
change, are disabling enough to prevent systemic cancer
CNS metastasis requiring VPS is commonly associated with
treatments [3]. In this paper, we present the clinical features
LMS. VPS is an effective palliative measure and an
and outcomes of our patients with advanced stage
Materials and methods
S. H. Lee D. S. Kong H. J. Seol D.-H. Nam
In this retrospective study, we enrolled 50 consecutive
J.-I. Lee (&)
Department of Neurosurgery, Samsung Medical Center, patients with a diagnosis of CNS metastasis who underwent
Sungkyunkwan University School of Medicine, VPS between March 2003 and March 2010. Patients with a
Seoul, Republic of Korea e-mail: primary brain tumor were excluded. All patient records were
jilee@skku.edu
reviewed for presenting symptoms, type of primary
CNS metastasis and hydrocephalus after VPS. malignancy, onset of CNS involvement, presence of LMS,

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type of hydrocephalus, ventricular opening
pressure, symptom improvement after VPS,
Karnofsky performance status (KPS) scale
change, procedure-related complications, cancer
treatments before and after VPS, systemic
disease status at time of death, and post-VPS and
overall survival.
CNS metastasis was diagnosed based on
magnetic resonance image (MRI) findings,
pathologic findings, or both. The presence of
LMS at the time of VPS was diagnosed by MRI,
by the presence of malignant cells in CSF, or
both. Our definition of positive MRI finding is
contrastenhancement of diffuse or localized
areas such as meninges, ependyma, tentorium,
basal cistern and sulci. Since CSF cytology test
for malignant cells has a 4050% falsenegative
rate, three serial spinal taps were performed to
reduce such a high rate. After cytospin
preparations, cells were evaluated, and if
malignant cells were confirmed in CSF, we could
define cytologically positive LMS.
Hydrocephalus was classified as obstructive
hydrocephalus with a large parenchymal or
intraventricular mass obstructing the CSF
pathway or as communicating hydrocephalus
with leptomeningeal enhancement by MRI or
positive CSF cytology (Fig. 1). We also
documented the time intervals between initial
primary tumor diagnosis, CNS involvement, and
VPS. In cases positive for LMS, the time
intervals between brain parenchymal metastasis,
Fig. 1 Image findings of a breast
cancer patient with CNS
involvement. Left axial CT scan
shows ventriculomegaly,
periventricular low density, and
bilateral sulci obliteration. Post-
VPS CT scan (right) shows
much relieved
ventriculomegaly, loss of
periventricular low density, and
reappearance of bilateral sulci
LMS, and VPS were included. The indications of
VPS were (1) an uncontrollable increase in
intracranial pressure (ICP) despite aggressive
ICP management, or (2) progressive
ventriculomegaly with neurological deficits.
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J Neurooncol (2011) 104:545551
We placed VPSs in a routine manner and used a pressure
adjustable programmable valve (The CODMAN HAKIM
Programmable Valve System or The MIETHKE proGAV
Shunt System) or a fixed-pressure valve (The CODMAN
HAKIM Precision Fixed Pressure valve). High pressure
valves were used in all cases (Fig. 1).
We measured the height of CSF in the catheter from
external auditory canal when we inserted the proximal
catheter into the ventricle. We defined this height as the
opening pressure. In our institution, endotracheal general
anesthesia was maintained with neck position enabling good
venous drainage, no positive end expiratory pressure
(PEEP), end tidal CO2 around 3035 mmHg, using
osmotherapy (e.g., mannitol), and using propofol instead of
gas anesthetics as much as possible.
The outcomes of VPS were analyzed with respect to the
following risk factors; age ([55 versus B55 years), sex, type
of primary malignancy (lung cancer versus breast cancer
versus others), onset of CNS involvement (synchronous
versus metachronous), systemic disease status (progressive
versus non-progressive), hydrocephalus type
(communicating versus obstructive), ventricular opening
pressure ([30 versus 1530 versus B15 cmH2O), and
additional cancer treatment after VPS. Univariate analysis
was used to identify potential risk factors associated with
post-VPS survival, and the KaplanMeier method was used
to evaluate survival rates for different risk factors. The Log
rank test was used to compare group survival curves, and
multivariate analysis was performed using the Cox
proportional hazards model to identify independent risk
factors.
Results
The median age of the 50 adult patients (male:female =
20:30) was 55.0 years (range 2577). The most common
presenting symptom was a headache (70%) followed by
J Neurooncol (2011) 104:545551
mental change (24%), gait disturbance (14%),
cognitive dysfunction (e.g., memory
impairment) (10%), urinary incontinence (10%),
seizure (4%), and cranial nerve palsy (2%).
CNS metastasis was from a hematologic
malignancy (diffuse large B-cell lymphoma) in 1
patient and from solid tumors in 49. Regarding
the solid tumors, the primary diagnosis was lung
cancer in 32 patients (non-small cell lung cancer
in 29, small cell lung cancer in 2, and mixed in 1
patient), breast cancer (invasive ductal
carcinoma) in 8, colorectal cancer in 3, renal cell
carcinoma in 2, and other cancers (gastric cancer,
cervix cancer, ovarian cancer, and cancer of
unknown origin) in 5.
Thirty-seven patients were found to have CNS
involvement of metachronous onset and the
remaining 13 patients synchronous onset. At the
time of hydrocephalus diagnosis and VPS, 10
patients had parenchymal metastases only and 40
patients had coexistent LMS. In these 40 LMS
positive patients, 18 patients had parenchymal
metastases prior to LMS and 22 patients were
found to have brain parenchymal involvement
and LMS simultaneously. Primary diseases of
LMS positive patients were 25 non-small cell
lung cancer, 8 breast cancer, 2 colorectal cancer,
and 5 other cancers. (gastric cancer, cervix
cancer, ovarian cancer, and cancer of unknown
origin) And among them, synchronous
development of LMS and intraparenchymal
metastases was from 14 non-small cell lung
cancer, 1 small cell lung cancer, 3 breast cancer,
and other cancers. (1 gastric cancer, 1 colon
cancer, 1 diffuse large B-cell lymphoma, and 1
unknown origin) In terms of hydrocephalus type,
37 were of the communicating type and 13 were
of the obstructive type, and of these 13, 6 were
blocked by a supratentorial and 7 by an
infratentorial lesion.
Before VPS, patients had been treated for
CNS lesions using various modalities; 23 by
whole-brain radiotherapy (WBRT), 24 by
radiosurgery, 23 by intrathecal chemotherapy,
and 5 by tumor resection. During surgery,
ventricular opening pressure was B15 cmH2O in
5 patients, 1530 cmH2O in 22, and [30 cmH2O
in 23. After VPS, symptoms improved in 40
patients, and most of these improvements
involved relief from headache, nausea, and/ or
vomiting, and an improved level of
547
consciousness. Cognitive function and urinary incontinence
did not respond as well to VPS (only 2 of 5 patients
improved) (Table 1). Most of the patients were relieved from
symptoms within 12 days after the operation. Complication
rate was 10%. Four patients experienced a valve pressure
adaptation failure, increased ICP, an overdrain, or
uncontrolled hydrocephalus and underwent revision to
change the valve type. One death was attributed to
intracerebral hematoma probably provoked by multiple
ventricular puncture because of an inadequate initial
trajectory. There were no coagulation disorders, abnormal
vascular structures, or tumor which was blocking the
catheter trajectory for this patient. And no other shunt-
related complication, such as infection, valve malfunction,
or peritoneal carcinomatosis, was observed during the study
period.
After VPS, further systemic chemotherapy, WBRT,
radiosurgery, and tumor resection performed in 11, 6, 4, and
1 patients, respectively. Intrathecal chemotherapy after VPS
was not considered because an onoff valve was not
available and we did not believe it would work at that stage
of disease with an extremely high ICP and a blockage of
CSF flow. Five patients remained alive at the end of this
study in May 2010. At the time of death, we found that
systemic malignant tumor status had progressed in 27, but
no definitive progression was observed in 23. Deaths were
attributed to an increased ICP due to CNS lesion progression
in 10 patients, and to an aggravated general condition or an
organ failure in 35.
Median time from initial primary malignancy diagnosis
to CNS involvement was 10.5 months (range 0106), and
from CNS involvement to VPS was 3.5 months (023). In
40 patients with LMS, median time from brain parenchymal
metastasis to LMS was 0 months (023), and from LMS to
VPS was 1.0 month (2 days to 13 months). There were 2
patients who had developed hydrocephalus and underwent
VPS before LMS appeared, 1 and 2 months
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Table 1 Presenting symptom and improvement after VPS

Presenting symptom No. of Clinical improvement
patients (%) after VPS (%)

Headache 35 (70) 30 (86)

Mental change 12 (24) 10 (83)

Gait disturbance 7 (14) 5 (71)
Cognitive dysfunction 5 (10) 2 (40)
Urinary incontinence 5 (10) 2 (40)
Seizure 2 (4) 2 (100)

Fig. 2 Overall survival after VPS in patients with CNS metastasis.

ahead respectively. Median overall survival after primary
malignancy diagnosis was 21.0 months (1113). Median
survivals after the diagnosis of CNS involvement, LMS, and
VPS (Fig. 2) were 7.5 months (155), 3.5 months (028),
and 3.0 months (2 days to 54 months), respectively (Table
2).
Univariate analysis revealed that further treatment after
VPS, including systemic chemotherapy, WBRT,
radiosurgery, or tumor resection, conferred a survival
advantage (P= 0.0002), whereas age, sex, type of primary
malignancy, onset of CNS involvement (synchronous or
metachronous), type of hydrocephalus, ventricular opening
pressure, and systemic disease status were not found to be
significant prognostic factors (Table 3; Fig. 3). Multivariate
analysis showed that a ventricular opening pressure of [30
cmH2O influenced survival negatively (HR 6.44, 95% CI
1.2632.9, P= 0.02) and further cancer treatment after VPS
Actuarial survivals were 52% at 3 months and 10% at 1 year after VPS
did so positively (HR 0.17, 95% CI 0.070.42, P\0.0001) for
better survival (Table 4; Fig. 4).
Discussion
Disseminated cancer cells result in multi-organ failure
finally experienced by end-stage cancer patients. CNS
involvement including LMS with an uncontrollable
increased ICP is considered a feature of the final stage. The
diagnosis of LMS, however, is sometimes equivocal in MRI
or false-negative result by cytology [6], and few treatment
choices are available. Furthermore, treatment response rate
is very low when LMS is present: one study found that 52%
failed to respond. Omuro et al. pointed out the importance
of suspicion of intracranial hypertension in patients with
LMS, and our study confirms the frequent
No. of patients (%)

Age (years) 55.0 (range, 2577)

Sex: female/male 30 (60)/20 (40)

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Table 2 Characteristics of the patients Primary malignancy
Lung cancer [NSCLC/SCLC/Mixed] 32 (64) [29 (58)/2 (4)/1 (2)]
Breast cancer 8 (16)

Colorectal cancer 3 (6)

Renal cell carcinoma 2 (8)

Others 5 (10)

Onset of CNS involvement

Metachronous/synchronous
37 (74)/13 (26)
Presence of LMS at the time of VPS
Yes/No 40 (80)/10(20)
Type of hydrocephalus
Communicating/obstructive
37 (74)/13 (26)
Ventricular opening pressure: B15 cmH2O/1530 cmH2O/[30 cmH2O 5 (10)/22 (44)/23 (46)

Treatment before/after VPS

WBRT 23 (46)/6 (12)
Systemic chemotherapy 43 (86)/11 (22)

Radiosurgery 24 (48)/4 (8)

Intrathecal chemotherapy 23 (46)/0 (0)

Craniotomy and tumor resection 5 (10)/1 (2)

Systemic disease status at the time of death

NSCLC non-small cell lung cancer, Progressive/Non-progressive 27 (54)/23 (46)
SCLC small cell lung cancer, DLBL Cause of death
diffuse large B-cell lymphoma, LMS
Uncontrolled ICP
leptomeningeal seeding, VP 10 (20)
ventriculoperitoneal, WBRT whole-
Aggravated general condition 35 (70)
brain radiotherapy, ICP intracranial
pressure, Dx diagnosis Median time interval between
Table 3 Univariate analysis of Initial primary malignancy Dx and CNS involve 10.5 months (0106)
prognostic factors for survival after
VP shunt insertion CNS involve and VPS 3.5 months (023)

Brain parenchymal metastasis and LMS 0 month (023)

LMS and VPS 1.0 month (013)

P value

Age[55 versus B55 years 0.59

LCA lung cancer, BCA breast
Sex: M versus F 0.79
cancer
Primary malignancy: LCA versus BCA versus others 0.93
Onset of CNS involvement: synchronous versus metachronous 0.40
Systemic disease status: progressive versus non-progressive 0.39
Type of hydrocephalus: communicating versus obstructive 0.60
Ventricular opening pressure: [30 versus 1530 versus B15 cmH2O 0.12
Further treatment after VPS: yes versus no 0.0002

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Fig. 3 Post-VPS survival in patients who received additional cancer Fig. 4 Post-VPS survival in patients according to ventricular opening
treatment versus those who received conservative management only. pressure. After VPS, the hazard ratio for patients with a ventricular
After VPS, the hazard ratio for death of patients who received further opening pressure[30 cmH2O versus those with a pressure B15 cmH2O
cancer treatment versus those who received supportive care alone was was 6.44 (95% CI 1.2632.9, P = 0.02)
0.17 (95% CI 0.070.42, P\0.0001)
associations between LMS and hydrocephalus or anesthesia and of various shunt-related complications [9
intracranial hypertension. In the present study, 80% of 11], and improves survival and favorably affects quality of
hydrocephalus patients who underwent VPS were found to life
have coexistent LMS. The dominant type of hydrocephalus [4].
was the communicating type associated with LMS, and the A median survival time of 1.85.8 months after a
median time interval between the diagnosis of LMS and diagnosis of LMS [2, 4, 5, 1214] and of 2.0 months
VPS was only 2.2 months. Accordingly, we recommend a
thorough investigation for LMS be undertaken when a
cancer patient develops neurological symptoms and signs of
hydrocephalus and/or images of ventriculomegaly. If LMS
is confirmed, its treatment should be actively pursued
without delay before VPS. The early diagnosis of LMS is
important because the opportunity to administer intrathecal
chemotherapy might be missed after VPS for
hydrocephalus. Furthermore, if hydrocephalus persists,
intrathecal chemotherapy cannot provide a viable treatment
option because CSF flow is inhibited, that is, CSF
compartmentalization and prohibits intrathecal
chemoagents being delivered effectively [2, 5, 7, 8].
In the present study, 80% of patients experienced
immediate post-operative symptom relief. A headache was
the most common symptom, and was resolved by surgery in
85.7% of cases. On the other hand, cognitive function and
urinary incontinence were improved in less than a half of
cases by VPS (40%). Unlike cancer treatment itself, the
treatment of intracranial hypertension is not optional
because of its debilitating consequences. When relief of the
symptoms and signs of increased ICP are of major concern,
VPS helps enormously despite the risks of general

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Table 4 Results of multivariate Cox
regression analysis
Age: [55 versus B55 years
Sex: M versus F
Primary malignancy
LCA versus others
BCA versus others
Onset of CNS involvement: synchronous versus metachronous
Systemic disease status: progressive versus non-progressive
Type of hydrocephalus: cCommunicating versus obstructive
Ventricular opening pressure: [30 versus B15 cmH2O
Further treatment after VPS: yes versus no
(2 days to 3.6 years) after VPS [3] have been reported, which
concur with our findings (3.5 months of median survival
after a diagnosis of LMS and 3.0 months after VPS).
Approximately 2434% of CNS metastasis patients
succumb to LMS alone, 2225% to LMS and progressive
systemic cancer, 1944% to systemic progressive disease,
and up to 10% to other causes [1518]. In the present study,
the majority of patients succumbed to aggravated systemic
disease progression (70%), which included systemic cancer
progression and an aggravated general condition mainly due
to an infection, like pneumonia.
Furthermore, overall outcome was in line with that found
previously, although it is noteworthy that five patients
(10%) survived after VPS for more than 1 year and one
patient on continuing systemic cancer treatment survived 54
months. These patients who achieved long-term survival
after VPS support the notion that LMS development and
VPS do not necessarily mean the end of the further cancer
treatment. Aggressive treatments in patients with CNS
metastasis have been reported to substantially increase
survival [2, 46, 1315, 1921]. We also found that further
aggressive cancer treatment after VPS was a prognostic
factor of better survival time by univariate and multivariate
analysis. The most reasonable explanation for this result is
that we selected patients with a better performance status
and a lower tumor burden, which increased the likelihood of
eligibility for further systemic or local cancer treatment.
Furthermore, this finding strengthens the hypothesis that the
bloodbrain barrier is made more permeable by infiltrative
tumor cells and that systemic chemotherapy agents can
penetrate into the CSF space more easily, which may
favorably affect survival after VPS. Multivariate analysis
also identified an independent risk factor that negatively
affected survival after VPS, namely a ventricular opening
pressure of [30 cmH2O. An elevated ventricular opening
551
Hazard ratio (95% CI) P value
0.88 (0.411.88) 0.73
1.27 (0.552.94) 0.57
0.65 (0.172.48) 0.94
0.45 (0.102.05) 0.48
0.73 (0.281.88) 0.51
0.78 (0.391.55) 0.47
1.24 (0.413.74) 0.70
6.44 (1.2632.9) 0.02
0.17 (0.070.42) \0.0001
pressure, which reflects an increased ICP, probably
indicates severe distortion of CSF dynamics due to a long-
standing, heavy tumor burden in the CNS when it is from a
communicating hydrocephalus, and although VPS can
effectively relieve an elevated ICP, a poor prognosis is
expected due to the progression of the underlying disease.
When the hydrocephalus is obstructive, the lesion is usually
deep-seated around the third or fourth ventricle. Surgical
resection could be incomplete and even impossible, and this
affects the survival unfavorably.
In a previous study, it was found that primary tumor
histology has a significant impact on survival after a
diagnosis of LMS. The longest median survival was
observed in breast cancer (3.1 months), and the shortest in
lung cancer (0.8 months) [5]. However, we failed to find any
significant relationship between primary malignancy type
and survival after VPS; for example, median survival times
after VPS in lung cancer, breast cancer, and other primary
malignancies were 3.0, 2.0, and 2.5 months, respectively
(P= 0.93). Our findings could be explained by the fact that
CNS involvement with LMS represents the most advanced
stage of cancer irrespective of the nature of the primary
malignancy, and that short life expectancies do not allow
survival differences to be attributed to different histologies.
To improve survival, further research should be focused
on improving diagnostic and therapeutic tools. More
sensitive diagnostic tools are needed to overcome the high
falsenegative rates of imaging and cytology findings.
Furthermore, personalized and tumor-specific therapeutic
regimens should be established. At present, systemic or
intrathecal chemotherapies based on methotrexate,
cytarabine, liposomal cytarabine, or thiotepa and on several
emerging drugs, such as mafosfamide, diaziquone,
topotecan, gemcitabine, and temozolomide, are being
investigated to identify regimens best suited for particular
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types of malignant tumors [2, 6, 15]. In addition, novel
therapeutic modalities for LMS are required, such as agents
that can overcome CSF flow stagnation and a VPS valve
system that enables both CSF shunting and intrathecal
chemotherapy.
As post-operative survival gets longer, unanticipated side
effects may be unveiled such as shunt infection, malfunction
and even rarer peritoneal carcinomatosis. Considering
reports from primary malignant brain tumors disseminating
through peritoneal catheter, it is likely that the same risk
exist in the patients with LMS who undergo CSF diversion.
The main reason why we could not find the patient with
peritoneal carcinomatosis seems to be the short survival
period of the patients after VPS. Recently, we experienced a
case not included in analysis of this manuscript in which
malignant ascites developed 1 month after VPS for the
hydrocephalus with LMS. If survival of the patient is
prolonged after VPS, it is expected that the risk of peritoneal
seeding will get higher.
Lastly, a comparative study with patients who had not
undergone VPS to look for the difference in survival in both
groups will be performed in the near future and be able to
define the role of VPS further, if there were no practical
limitation nor ethical problems.
Conclusions
Hydrocephalus related to CNS metastasis requiring VPS is
commonly associated with LMS. Though the prognosis of
CNS metastasis and subsequent hydrocephalus is dismal,
VPS is an effective palliative measure, and adequate cancer
treatment after VPS may offer the best means of improving
survival. Effective diagnostic and therapeutic modalities are
required to control LMS and improve outcome.
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