SYSTEMATIC REVIEW

Brain metastasis from gastrointestinal cancers: a

systematic review
M. Esmaeilzadeh,1 A. Majlesara,2 A. Faridar,2 M. Hafezi,2 B. Hong,1 H. Esmaeilnia-Shirvani,2
B. Neyazi,1 A. Mehrabi,2 M. Nakamura1

1
Department of Neurosurgery,
Hannover Medical School,
Hannover, Germany
2
Department of General,
Visceral and Transplantation
Surgery, University of
Heidelberg, Heidelberg,
Germany
Correspondence to:
Dr M. Esmaeilzadeh,
Department of Neurosurgery,
Hannover Medical School, Carl-
Neuberg Street. Nr. 1, 30625
Hannover, Germany
Tel.: + 49 511532 6651
Fax: + 49 511532 5864
Email: esmaeilzadeh_majid@
mh-hannover.de
Disclosures
The authors declare that they
have no competing interests.
SUMMARY
Background: Brain metastases (BM) from the gastrointestinal tract (GIT) cancers
are relatively rare. Despite those advances in diagnostic and treatment options, life
expectancy and quality of life in these patients are still poor. In this review, we
present an overview of the studies which have been previously performed as well
as a comprehensive strategy for the assessment and treatment of BM from the
GIT cancers. Method: To obtain information on brain metastases from GIT, we
performed a systematic review of Medline, EMBASE and the Cochrane Central
Register of Controlled Trials (CENTRAL). The collected data included patient char-
acteristics, primary tumor data and brain metastases data. Result: In our search
of the literature, we found 74 studies between 1980 and 2011, which included
2538 patients with brain metastases originated from gastrointestinal cancer.
Analysis of available data showed that among 2538 patients who had brain
metastases from GIT, a total of 116 patients (4.57%) had esophageal cancer, 148
patients (5.83%) had gastric cancer, 233 patients (9.18%) had liver cancer, 13
patients had pancreas cancer (0.52%) and 2028 patients (79.90%) had colorectal
cancer. The total median age of the patients was 58.9 years. Conclusion: Brain
metastases have been considered the most common structural neurological compli-
cation of systemic cancer. Due to poor prognosis they influence the survival rate
as well as the quality of life of the patients. The treatment of cerebral metastasis
depends on the patients’ situation and the decisions of the treating physicians.
The early awareness of a probable metastasis from GI to the brain will have a
great influence on treatment outcomes as well as the survival rate and the
quality-of-life of the patients.
Review criteria
A systematic literature search was performed to
identify potential articles on the association between
brain metastases and gastrointestinal cancers in
PubMed, EMBASE and Cochrane Library, within a
range of published years from 1980 to 2011.
Reference lists of retrieved relevant articles were
screened for other studies. We excluded studies
which in languages other than English or German as
well as review articles. Furthermore, we excluded
studies which only published in abstract form,
relating to animal or in vitro experiments.
Messages for the clinic
• Early brain scans should been suggested even in
asymptomatic patients, for whom earlier
diagnosis may lead to improved survival rate and
quality of life.
• Clinicians should consider the extent of the
systemic disease, primary histology, patient age,
Karnofsky score, and the number, size, and
location of the brain metastases as main factors
for the selection of a managing strategy.
• The use of whole brain radiotherapy (WBRT) in
combination with other treatment modalities
such as stereotactic radiosurgery (SRS) seems to
be the optimal approach in patients with multiple
brain metastases.
• Lesions > 3 cm in maximum diameter are
regularly treated with resection and when
needed, followed by WBRT.
• SRS has been shown to be effective for small
brain metastases.

Early brain scans have been suggested even in asymp-

Introduction
Brain metastases (BM) are the most common struc-
tural neurological complications of systemic cancer
and they correlate with a poor prognosis in 20–40%
of systemic cancers (1,2). BM from the gastrointesti-
nal tract (GIT) are relatively rare (4–6% of patients)
(3,4). However, the actual frequency of BM originat-
ing from GIT is underestimated because usually brain
imaging is not performed as a routine evaluation and
also asymptomatic brain lesions may be overlooked.
tomatic patients, for whom earlier diagnosis may lead
to improved survival rate and quality of life (5,6).
Over the last two decades, the management of
patients with BM has improved in consequence of
advances in diagnostic methods, a better knowledge
of prognostic factors (7), and continuously improv-
ing therapeutic options such as surgical techniques,
whole brain radiotherapy (WBRT), stereotactic
radiosurgery (SRS) and chemotherapy, either alone
or in combination. Despite those advances in diag-

ª 2014 John Wiley & Sons Ltd

890 Int J Clin Pract, July 2014, 68, 7, 890–899. doi: 10.1111/ijcp.12395

nostic and treatment options, life expectancy and
quality of life in these patients are still poor (8). The
median survival time is only a few months (9); the
percentage of 2-year survival rate is under 10% (10);
and cures are rare enough to be the subject of
patient reports (11). In this systematic review, we
focus on BM from GIT cancers and present an over-
view of the studies which have been previously per-
formed. In addition, in order to draw attention to
this still underestimated issue we present a compre-
hensive strategy for the assessment and treatment of
BM from GIT cancers.
Methods
Search strategy
We performed a systematic review of Medline
(1980–2011), EMBASE (1985–2011) and the Cochra-
ne Central Register of Controlled Trials (CENTRAL)
(The Cochrane Library Issue 3, 2011) for relevant
citations. Search terms used in electronic searching
included: ‘brain metastasis’, ‘gastrointestinal cancer’,
‘esophageal cancer’, ‘gastric cancer’, ‘pancreatic can-
cer’, ‘liver cancer’ and ‘colorectal cancer’. These
terms were combined with the terms ‘WBRT’, ‘sur-
gery’, ‘SRS’ and ‘chemotherapy’ in brain metastasis.
Reference lists of retrieved relevant articles were
screened for other studies.
Study selection and data extraction
All studies which reported brain metastasis from GIT
were eligible for inclusion. We excluded studies which
in languages other than English or German as well as
review articles. Furthermore, we excluded studies
which only published in abstract form, relating to ani-
mal or in vitro experiments. One reviewer (ME)
screened all titles and abstracts to assess whether they
were potentially eligible for inclusion and whether full
text was required. Then abstracts and full texts for all
potentially eligible studies were reviewed by two
researchers (AF and AMs), who independently evalu-
ated these articles and extracted their data. Any dis-
agreement during study selection and the data
extraction process was resolved by discussion with a
third author (AM). According to our search of the
medical literature, after application of our ‘Inclusion
and Exclusion Criteria’, 74 studies were reported
between 1980 and 2011. The collected data included
patient characteristics (age, gender), primary tumour
data (presenting symptom, site of tumour, pathologi-
cal type of tumour) and BM data (time between the
primary tumour and BM, neurological symptoms,
type of therapy and survival). In our analysis, we focus
on BM from GIT cancers and present an overview of
the studies which have been previously performed.
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Brain metastasis from gastrointestinal cancers 891
Statistical analysis
The statistical analysis was performed using SPSS 14.0
software for Windows (Stata Corp., College Station,
TX). All statistical data regarding patient age,
interval time from the time of diagnosis of the primary
tumour and survival time were expressed as median.
Results
Figure 1 summarises the process of literature identi-
fication and selection. In Table 1, we summarise the
74 reported studies with BM originated from gastro-
intestinal cancer.
Patient characteristics
We evaluated 74 studies done between 1980 and
2011, which included 2538 patients with BM origi-
nated from gastrointestinal cancer. Analysis of avail-
able data showed that among 2538 patients who
had BM from GIT, a total of 116 patients (4.57%)
had oesophageal cancer, 148 patients (5.83%) had
gastric cancer, 233 patients (9.18%) had liver can-
cer, 13 patients had pancreas cancer (0.52%) and
2028 patients (79.90%) had colorectal cancer. The
total median age of the patients was 58.9 years
(Table 1).
Oesophagus cancer
The median age of patients with oesophageal cancer
was 61.5 years (range 48–84). The most common
presenting symptoms of oesophagus malignancies
were dysphagia and weight loss. Primary work-ups
included oesophagogram, endoscopic guided biopsy,
transoesophageal ultrasonography and lab tests such
as alpha-fetoprotein. The sites of involvement were
68% in middle third of oesophagus, 21% in lower
third and 11% in upper third. Treatment of oesoph-
ageal tumours is based on surgical resection, radio-
therapy and chemotherapy (mainly with Cisplatin
and 5FU). Almost all the patients underwent CT
scan or a combination of CT and MRI for a follow
up. The median interval time from the time of diag-
nosis of the primary tumour to the development of
BM was 13 months. Neurological symptoms leading
to a diagnosis of brain metastasis were in the order
of prevalence: headache, motor deficit, gait distur-
bance, speech deficit, personality changes, nausea,
visual defects, sensory deficit, cranial nerve deficit
and emesis. Basic treatment for brain metastasis was
WBRT, as single treatment or following surgical
resection and chemotherapy. Secondary follow-up
work-ups included CT scan, MRI and oesophagecto-
my. Median survival time after treatment was about
7 months.

892 Brain metastasis from gastrointestinal cancers
Figure 1 Flow chart of abstracts and articles identified and evaluated during the review process
Gastric cancer
The median age of patients with gastric cancer was
52.2 years (range 16–78). Primary sites of gastric
tumour were 37% in cardia and the first one-third
of corpus, 30% middle third of corpus, and 33%
antrum and distal third. The median survival time
after diagnosis of primary tumour was 7 months.
The median interval from the time of diagnosis of
the primary tumour to the development of BM was
12 months. Metastases involved all parts of brain
with no specific regional preference. About 81% of
patients also suffered metastasis in other organs
including lung, liver and lymph node. Neurological
signs and symptoms were in the order of prevalence:
headache, muscular weakness and visual troubles.
Treatment was based on chemotherapy followed by
WBRT and/or surgery. The median survival time
after treatment of metastasis was about 3 months.
Cause of death was mainly because of progression of
the primary tumour.
Liver cancer
The median age of patient with liver cancer was
51.3 years (range 14–82). The median time interval
between the diagnosis of the primary tumour and
the development of brain metastasis was about
19 months. CT scan and MRI were employed for
diagnosis of brain metastasis. A percentage of 14.7%
of patients presented initially signs of brain metasta-
sis. It was noticed that singular brain metastasis was
more common and in addition to brain metastasis
patients also suffered from other organ metastases
such as lung, portal vein, lymph node and bone.
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Neurological signs in the order of prevalence were:
mental change, headache, vomiting, hemiplegia and
nerve palsy. Treatment of brain metastasis was based
on WBRT  steroid therapy, surgery, and in some
cases, conservative therapy. Median survival time after
diagnosis of brain metastasis was about 3.9 months.
Pancreatic cancer
There were 13 patients, with a median age of
47.7 years (range 7–66). The most common present-
ing symptoms of pancreas cancer were fatigue,
weight loss, and epigastric and pain in right upper
quadrant of abdomen. Primary work-ups included
abdominal sonography and CT scan in addition to
laboratory tests such as CA-125 and CA 19-91. Ade-
nocarcinoma was the dominant histological finding
of primary pancreas malignancy. Treatment of pan-
creatic tumour was based on surgery (if it was possi-
ble) in addition to chemotherapy. The first median
time of appearance of brain metastasis was
9.6 months. All patients with metastatic lesion
underwent CT scan and MRI for follow-up. Metasta-
sis involved all parts of the brain with no specific
regional preference. Treatment of brain metastasis
included WBRT alone or following resection and
chemotherapy. The median survival time after diag-
nosis of brain metastasis was about 4 months.
Colorectal cancer
From 2028 reported patients, 1001 patients were
reported by Smedby et al. (12) in a population-based
cohort study. The median age of the patients was
58.02 years old. Other studies reported 1051 patients
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Brain metastasis from gastrointestinal cancers 893

Table 1 An overview of the reported studies Table 1 Continued

Year of Number of Year of Number of

First author publication patients First author publication patients

Oesophageal cancer Colorectal cancer

Smith et al. (79) 2011 7 Kye et al. (44) 2012 39
Agrawal et al. (80) 2009 1 Noura et al. (43) 2012 29
Da Silva et al. (81) 2009 5 Jiang et al. (41) 2011 60
Kim et al. (82) 2009 1 Jung et al. (119) 2011 126
Yoshida (83) 2007 17 Heisterkamp et al. (120) 2010 53
Kasler et al. (84) 2006 1 Smedby et al. (12) 2009 1001
Weinberg et al. (19) 2003 27 Tan et al. (5) 2009 27
Ogawa et al. (17) 2002 36 Nieder et al. (121) 2009 35
Gabrielsen et al. (18) 1995 15 Aprile et al. (122) 2009 30
Koga et al. (85) 1991 4 Crncevic-Urek et al. (123) 2009 1
Odaimi et al. (86) 1986 1 Mongan et al. (124) 2009 39
Averbuch et al. (87) 1983 1 Gomez Raposo et al. (125) 2007 1
Pancreatic cancer Aoyama et al. (71) 2006 17
Lemke et al. (36) 2011 2 Amichetti et al. (126) 2005 23
Marepally et al. (35) 2009 1 D’andrea et al. (127) 2004 44
Voutsadakis et al. (88) 2009 1 Bartelt et al. (20) 2004 47
Naugler et al. (89) 2008 1 Maiuri et al. (128) 2004 1
Szerlip et al. (90) 2007 1 €
Uskent et al. (129) 2003 1
Park et al. (91) 2003 4 Schoeggl et al. (130) 2002 35
Ferreira Filho et al. (92) 2001 1 Zulkowski et al. (131) 2002 13
Kuratsu et al. (93) 1990 2 Wronski et al. (132) 1999 73
Gastric cancer Hammoud et al. (133) 1996 100
Park et al. (94) 2011 56 Farnell et al. (134) 1996 150
Han et al. (95) 2010 11 Alden et al. (48) 1996 19
Zhang et al. (96) 2007 1 Salvati et al. (135) 1995 24
Lee et al. (97) 2007 1 Cascino et al. (136) 1983 40
Braeuninger 2005 1
et al. (98)
Lee et al. (99) 2004 19
Lisenko et al. (100) 2003 8 with BM from colorectal cancer with the median age
Perri et al. (101) 2001 1 of 58.2 years (range 29–93). Primary signs of colo-
Kasakura et al. (23) 2000 11 rectal malignancy were constipation and rectal bleed-
York et al. (102) 1999 24 ing. The most common primary site of colorectal
Kim et al. (103) 1999 13 tumour was ascending colon, followed by transverse
Nomura et al. (104) 1997 1 colon, descending colon and rectosigmoid. The most
Bitoh et al. (105) 1985 1
common histological finding was adenocarcinoma.
Liver cancer
Surgery was the main treatment of colorectal
Chan et al. (106) 2009 28
involvement. The majority of the patients suffered
Hsieh et al. (107) 2009 42
Choi et al. (29) 2009 62 also from metastases in other organs. Brain metasta-
Hiraoka et al. (108) 2008 1 sis involved all parts of the brain. Diagnosis of brain
Toshikuni et al. (109) 2007 1 metastasis was based on CT scan and MRI. The
Seinfeld et al. (110) 2006 1 median interval from the time of diagnosis of the
Natsuizaka et al. (111) 2005 5 primary tumour and the development of BM was
Franca et al. (112) 2004 1 26 months. Neurological signs and symptoms in the
Tunc et al. (28) 2004 1 order of prevalence were headache, hemiparesis, sei-
Chang et al. (113) 2004 45 zure, dizziness and ataxia. Treatment of brain metas-
Kim et al. (114) 1998 8
tasis was based on WBRT  chemotherapy and
Robertson et al. (115) 1997 1
surgery. The median survival time after treatment of
Yen et al. (116) 1995 33
metastasis was 5.2 months. The most common cause
Tanabe et al. (117) 1994 2
Shuangshoti et al. (118) 1988 1 of death was mainly because of progression of pri-
Bitoh et al. (105) 1985 1 mary tumour. The median survival time after diag-
nosis of the primary tumour was 37 months.

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894 Brain metastasis from gastrointestinal cancers
Discussion
What is already known about gastrointestinal
cancers and BM?
Oesophageal cancer
The incidence of oesophageal cancer has recently
shown an increase owing to improvements in diag-
nostic techniques (13). Surgery still remains the
only potentially therapeutic option (14). Transhiatal
and transthoracic oesophagectomy are the tech-
niques which are most frequently employed, fol-
lowed by chemotherapy and radiation therapy as
adjuvant treatment (15). Despite the advances in
diagnosis and treatment of this cancer, the 5-year
survival rate is only 20–30% (16). Patients with
large primary tumours (mean primary tumour
length ≥ 8.5 cm) (17), local invasion and lymph
node metastases (18) are in higher risk of BM. Met-
astatic brain tumours originating from oesophageal
cancer are, however, relatively rare (1–5%) (19).
Because symptoms of increased intracranial pressure
such as nausea and vomiting can also be attributed
to the primary tumour itself (20), clinicians should
always consider the occurrence of BM as a differen-
tial diagnosis.
Gastric cancer
Gastric cancer is the second leading cause of cancer-
related death (21) and one of the most common
types of cancer in Asian countries. Curative treat-
ment consists of surgery followed by chemotherapy.
The stage of disease has a strong influence on patient
survival rate (22), thus patients with late stage dis-
ease have poor prognosis (21). The development of
BM from gastric cancer is very rare, occurring in
0.16–0.69% of the patients (23). Response to treat-
ment is poor among patients with brain metastasis
arising from gastric cancer (22).
Liver cancer
Hepatocellular carcinomas (HCC) present the most
common malignancies (24) which accounts for
500,000–600,000 deaths per year (25). Surgical resec-
tion is the primary treatment for HCC. High fre-
quency of tumour recurrence (26) and tumour
resistance against common chemotherapy and radio-
therapy (27) extensively limit the survival rate. Intra-
cranial metastases originating from HCC represent
1.3–2.9% of all intracranial metastatic tumours (28).
Because of hypervascularization of HCC and a possi-
ble coagulopathy caused by the underlying liver cir-
rhosis, BM from HCC often present with
haemorrhage and extracranial symptoms (29).
Because of the low incidence of these metastases, no
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effective treatment has been reported so far. With
the mean survival period of 3 months after diagnosis
of brain metastasis, the overall prognosis of these
patients is very poor (28).
Pancreatic cancer
Pancreatic cancer is relatively rare, but is known as
one of the major causes of cancer mortality (30). To
date, most cancers have already metastasis at the
time of diagnosis. Therefore, to improve outcomes
early detection is crucial. The treatment of pancreatic
cancer even with recent improvements in surgical
techniques and adjuvant therapies is usually ineffec-
tive (31). Chemotherapy is nowadays the standard
therapy to control disease-related symptoms and to
prolong the survival rate of patients with metastasis
(32). Because of the silent nature and late presenta-
tion of symptoms (33), the prognosis of pancreatic
cancer remains poor with a 5-year survival rate of
< 4% (32,34). The incidence of brain metastasis from
pancreatic cancer is extremely low (0.1–0.3%)
(35,36). Most patients with metastatic brain tumours
died from the primary tumour before developing
neurological symptoms.
Colorectal cancer
Colorectal cancer is the second most common
malignant disease in developing countries. Every
year, nearly 600,000 patients are diagnosed world-
wide (37,38) and 500,000 deaths occur annually
(39). Surgical resection (open or laparoscopic) is
the only curative treatment (40). Adjuvant chemo-
therapy can decrease the risk of recurrence (41,42).
The 5-year survival rate has improved from 33%
in 1970s to 60% in recent years (38,43). BM are
rare with a reported incidence of < 4% (44,45).
Colorectal tumours larger than 2 cm in size have a
high risk of brain metastasis (46). The intracranial
metastasis arising from different regions of the
colorectal system are as follows: rectum (33%), sig-
moid colon (23%), caecum and ascending colon
(15%), rectosigmoid colon (9%), descending colon
(4%) and transverse colon (1%) (47). Most
patients diagnosed with BM suffered simultaneously
from lung and/or liver metastases (5). The degree
of neurological impairment is directly related to
the survival rate of patients (5). As reported by
Alden et al. (48), the survival rate of patients with
BM from colorectal cancer is poorer in comparison
to patients with BM originating from lung, breast
and skin.
Management of brain metastasis from GIT
The management of patients with brain metastasis is
based on two strategies: definitive therapy and sup-
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portive therapy. Definitive therapy aims at treatment
of systemic malignancy, restoration of neurological
function and improvement of patient survival. In
general, surgery, WBRT, SRS and chemotherapy
either as single treatment or in combination are usu-
ally used as the definitive therapy. Supportive ther-
apy offers management of complications caused by
the metastatic tumour such as seizures, cerebral
oedema, psychiatric abnormalities, as well as deep
vein thrombosis (49). The best treatment strategy for
each patient depends on various aspects such as
prognostic factors, the tumour’s response to previous
therapies, and its assumed response to further treat-
ment (50). Since the strategies offering management
of BM are generally not related to and do not deal
with the primary tumour, the most important treat-
ment options for the management of BM will be
reviewed here.
Local therapy
The major aims of a surgical intervention, along with
the establishment of histological diagnosis, are
improvement of neurological symptoms, local con-
trol of the metastatic disease, and survival prolonga-
tion (51,52). Surgical skill, tumour location, extent
of resection needed, use of immediate post-operative
imaging as well as the frequency of follow-up imag-
ing are the most important factors for the local con-
trol (53). Patients with favourable prognostic factors
such as solitary lesion and uncertain histology are
ideal candidates for surgical resection (3). Two pro-
spective randomised trials conducted by Patchell
et al. (54) and Vecht et al. (55) demonstrated that
the surgical approach is the method of choice in
patients with a single metastasis. Patients who pres-
ent with multiple lesions are considered poor candi-
dates for resection. However, a large and
symptomatic lesion in patients with multiple BM
should also be resected in order to correct neurologi-
cal symptoms.
Whole brain radiation therapy is one of the treat-
ment options frequently used in patients with active
extracranial disease and/or multiple intracranial
lesions (56,57) and with poor prognosis. This treat-
ment can increase local and loco-regional control
and improve median survival rate in comparison
with supportive care or steroids therapy alone (58).
In addition, WBRT may prevent the occurrence of
new metastasis, decrease neurological deficits, reduce
the need for salvage therapy (53) and control the
micro-metastases which are not seen on MRI (59).
To avoid long-term toxicity and cognitive problems,
WBRT is usually not used as an initial therapy. The
generally accepted WBRT regimens are 30 Gy given
in 10 fractions or 40 Gy given in 20 fractions (56).
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Brain metastasis from gastrointestinal cancers 895
Stereotactic radiosurgery is a technique of external
irradiation employing multiple conventional beams
to direct a high single dose of radiation to a prede-
fined target volume (7) using either multiple radio-
active cobalt-60 sources [gamma knife radiosurgery
(GKRS)] or particle accelerator which speeds up
charged particles in a linear (linear accelerator/Linac)
or spiral fashion (7). As a result of a rapid decline of
radiation dose in the surroundings of the target vol-
ume, the risk of nervous tissue damage can be
reduced. It is well known that the efficacy of SRS is
related to tumour size. The required dose of irradia-
tion is inversely related to tumour diameter and vol-
ume (60). The GKRS is a standard radiosurgery
device mostly used for intracranial lesions (61). In
addition, the cyber knife radiosurgery uses a new
frameless SRS device which can be better tolerated
by the target and is also used for extracranial lesions
(61,62). It has been shown, however, that the use of
SRS alone for the treatment of singular brain metas-
tasis significantly increases the risk of local tumour
recurrence and is associated with neurological deficits
(63–65). However, this could be an appropriate
treatment option for these lesions, especially in
patients with surgical contraindications (66).
Chemotherapy is typically used when other treatment
modalities have failed. Because of the blood-brain
barrier and the blood-tumour barrier, chemotherapy is
generally not considered to be effective in treating
BM and therefore it is not a first-line treatment (67).
The most important factor for a supposed response
of BM is the primary tumour’s sensitivity to
chemotherapy (68).
Combination therapy
WBRT + surgery/SRS
In multiple lesions, surgery is employed for the larg-
est lesion followed by WBRT. The EORTC Radio-
therapy and Brain Tumour Groups reported that
after SRS or surgery of 1–3 BM, the frequency of
intracranial relapses and neurological deaths is
reduced by adjuvant WBRT (69). In order to com-
pare the effectiveness of WBRT plus SRS with sur-
gery plus WBRT, Rades et al. (70) performed a
matched pair analysis for patients with one to three
BM. WBRT plus SRS appeared to be at least as effec-
tive as surgery plus WBRT since 1-year survival was
56% after WBRT plus SRS and 47% after surgery
plus WBRT (p = 0.034) and local tumour control
was 82% and 66% (p = 0.006), respectively (70). A
randomised controlled trial by Aoyama et al. showed
that in patients who received WBRT plus SRS, local
tumour recurrence after 1 year was significantly
lower in comparison with patients receiving SRS

896 Brain metastasis from gastrointestinal cancers
Figure 2 Recommendations for the management of brain metastases
alone (WBRT + SRS: 47% vs. SRS: 76%) but 1-year
overall patient survival was not significantly different
in two groups (WBRT + SRS: 38.5% vs. SRS: 28.4%)
(71). In a small phase III randomised trial, the local
control was not statistically different in patients with
tumours < 3 cm between surgery/WBRT vs. SRS
alone. However, in the surgery with WBRT group,
the 2-year local control was numerically inferior to
the SRS alone (65% vs. 90%, p = 0.06) (72).
SRS + surgery
Some studies reported a decrease in local relapse
rates and an increase in median survival in patients
undergoing resection followed by SRS (73,74). SRS
provides effective local control of the tumour after
resection in most patients with BM (75). In contrast,
some studies show an equal success rate for these
two treatment options in control of BM (76,77). As
reported by Quigley et al. (78), patients with four or
more BM undergoing resection with SRS had a bet-
ter survival rate compared with patients treated with
SRS alone (19.6 months vs. 10.3 months).
What does this study recommend?
Finding the optimal therapy for management of
patients with BM is beset with difficulties. Clinicians
should consider the extent of the systemic disease,
primary histology, patient age, Karnofsky score, and
the number, size and location of the BM as main
factors for the selection of a managing strategy.
Lesions > 3 cm in maximum diameter are regularly
treated with resection and when needed, followed by
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WBRT. In this group, surgical resection proposes to
relieve symptoms and prolong survival. In addition,
surgical resection improves the survival rate and
quality of life in patients with recurrent metastases.
SRS, in turn, has been shown to be effective for small
BM, while the use of SRS for the treatment of singu-
lar lesions with the maximum diameter of more than
3 cm is still controversial.
Patients with multiple lesions are poor candidates
for surgical resection alone, but surgical resection of
progressive BM followed by WBRT for patients with
one to three BM and resections preceded by SRS in
patients with four or more BM can provide a signifi-
cant improvement in survival rates. SRS is frequently
employed as initial treatment in a single lesion or as
an adjuvant therapy to surgery, while WBRT is used
in patients with multiple BM. The use of WBRT in
combination with other treatment modalities such as
SRS seems to be the optimal approach in patients
with multiple BM, but it should be optimised to
ensure the best outcomes with regard to tumour con-
trol and functional status. The prognosis depends on
the type of primary tumour, number of BM (single
vs. multiple), the time interval between the primary
tumour diagnosis and the occurrence of brain metas-
tasis, as well as the presence of other systemic metas-
tasis. This means that the time interval between the
diagnosis of primary tumour and the diagnosis of
brain metastasis should be shortened and physicians
as well as patients should pay special attention to any
subtle neurological symptoms. However, as has been
shown above, the selection of the best approach
ª 2014 John Wiley & Sons Ltd
Int J Clin Pract, July 2014, 68, 7, 890–899
 17421241, 2014, 7, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/ijcp.12395 by Gerencia Regional De Salud, Wiley Online Library on [19/09/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Brain metastasis from gastrointestinal cancers 897

depends on a patient’s general condition and the
opinion of the treating physicians (Figure 2).
Limitations of the review
This review faced two main limitations. Because of a
retrospective character of individual studies, these
results might be biased and therefore should be
interpreted with caution. Furthermore, another limi-
tation of this review is a lack of certain data. For
example, we have no evidence to compare the effec-
tiveness of methods described in different studies. It
is clear that a great deal needs to be learnt in order
to select an appropriate treatment in patients with
BM, but the lack of statistical data about the effec-
tiveness still limits our knowledge as to which meth-
ods work best for BM.
Conclusions
Brain metastases have been considered the most
common structural neurological complication of sys-
temic cancer. Because of poor prognosis they influ-
ence the survival rate as well as the quality of life of
the patients. The treatment of cerebral metastasis
depends on the patients’ situation and the decisions
of the treating physicians who choose among surgical
resection, whole brain radiation, chemotherapy and
SRS. The early awareness of a probable metastasis
from GI to the brain will have a great influence on
treatment outcomes as well as the survival rate and
the quality of life of the patients.
Authors’ contributions
ME, AMa, AM and MN participated in the design of
the study and reviewed articles. ME, AF, MH and
BH participated in the design of the study and
drafted the manuscript. AF, HES and BN performed
the statistical analysis and revised the manuscript.
ME, AMa, BN, BH and HES were involved in draft-
ing the manuscript or revising it critically for impor-
tant intellectual content. ME, AM and MN revised
the manuscript and gave final approval of the version
to be published. All authors read and approved the
final manuscript.

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Paper received June 2013, accepted December 2013