Brain metastases in soft tissue sarcomas: case report and literature review.
ABSTRACT Background and purpose: Brain metastasis is a relatively uncommon event in the natural history of soft tissue sarcomas. The increasing use of chemotherapy may have caused a reduction in local relapses as well as distant failures leading to an improvement in survival, thereby allowing metachronous seeding of the brain, a sanctuary site. The purpose of this report is to increase awareness amongst clinicians regarding such a possibility.Patients and methods: A review of the departmental sarcoma database following the presentation of this index case in the clinic.Results and discussion: An adolescent male who had previously been treated with surgery and radiotherapy for a spindle cell sarcoma of the left thigh developed a space-occupying lesion in the brain within 6 months of treatment of the primary tumor. He subsequently underwent resection of the presumed solitary brain metastasis followed by whole brain radiotherapy. On radiation he was detected to have pulmonary metastases too, for which he was offered palliative chemotherapy. The patient died of brain metastasis within 4 months. A review of the departmental sarcoma database, restricted to soft tissue sarcomas purely, maintained prospectively from 2000 till date, could not identify any other such case.Conclusion: Brain metastases from soft tissue sarcomas are rare. Patients with neurological symptoms, however, should be appropriately investigated. Surgical resection of brain metastasis could be considered for solitary brain metastasis in non-eloquent areas. Palliative radiotherapy is appropriate for patients with multiple brain metastases or co-existing extra-cranial disease.
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ABSTRACT: Eleven cases of brain metastases that developed in 114 sarcoma patients are presented. Two of 11 patients presented with brain metastasis at the time of diagnosis and the other nine developed them later. The high incidence of brain metastases in patients with rhabdomyosarcoma (26%) and malignant fibrous histiocytoma (27%), two types of tumor which supposedly metastasize rarely to the brain, is remarkable. The increased incidence of brain metastases may be related to longer survival of sarcoma patients and to the inability of AMN and other drugs used in the treatment of sarcomas to cross the blood-brain barrier. Preventive treatment of brain metastases with drugs active in the CNS or with radiotherapy following the diagnosis of pulmonary metastases, could be useful, especially in patients with rhabdomyosarcoma and malignant fibrous histiocytoma.Cancer 02/1980; 45(2):377-80. · 4.77 Impact Factor
Cancer 06/1964; 17:558-63. · 4.77 Impact Factor
Advances in neurology 02/1978; 19:579-92.
Brain metastases in soft tissue sarcomas: Case report and
TEJPAL GUPTA, SIDDHARTHA LASKAR, SUMEET GUJRAL, &
MARY ANN MUCKADEN
Tata Memorial Centre, Institute Tata Memorial Centre, Mumbai, India
Background and purpose: Brain metastasis is a relatively uncommon event in the natural history of soft tissue sarcomas.
The increasing use of chemotherapy may have caused a reduction in local relapses as well as distant failures leading to an
improvement in survival, thereby allowing metachronous seeding of the brain, a sanctuary site. The purpose of this report is
to increase awareness amongst clinicians regarding such a possibility.
Patients and methods: A review of the departmental sarcoma database following the presentation of this index case in the
Results and discussion: An adolescent male who had previously been treated with surgery and radiotherapy for a spindle cell
sarcoma of the left thigh developed a space-occupying lesion in the brain within 6 months of treatment of the primary
tumor. He subsequently underwent resection of the presumed solitary brain metastasis followed by whole brain
radiotherapy. On radiation he was detected to have pulmonary metastases too, for which he was offered palliative
chemotherapy. The patient died of brain metastasis within 4 months. A review of the departmental sarcoma database,
restricted to soft tissue sarcomas purely, maintained prospectively from 2000 till date, could not identify any other such
Conclusion: Brain metastases from soft tissue sarcomas are rare. Patients with neurological symptoms, however, should
be appropriately investigated. Surgical resection of brain metastasis could be considered for solitary brain metastasis
in non-eloquent areas. Palliative radiotherapy is appropriate for patients with multiple brain metastases or co-existing
Keywords: Brain metastases, pulmonary metastases, soft tissue sarcomas
Background and purpose
Brain metastasis is a relatively uncommon event
in the natural history of soft tissue sarcomas (STS),
more so in the absence of pulmonary metastases.
round cell sarcomas (rhabdomyosarcomas) and
alveolar soft part sarcomas (ASPS) have a relatively
increased propensity to metastasize to the brain. The
increasing use of systemic chemotherapy in high-
grade STS has improved outcome. It is associated
with a significant reduction in local relapses as well
as distant metastases. This may have led to a con-
sequential improvement in disease-free survival and
overall survival. This increase in survival could
potentially provide an opportunity for metachronous
seeding of the brain, a pharmacological sanctuary site
. The authors report on one such rare occurrence.
The purpose of this report is to increase the
awareness amongst clinicians regarding the possi-
bility of such an occurrence and conduct a review
of the sarcoma database maintained prospectively in
the Department of Radiation Oncology since 2000.
Patient and methods
review of the departmental sarcoma database was
Correspondence: Dr Tejpal Gupta, MD, DNB, Department of Radiation Oncology, Clinical Research Centre, Advanced Centre for Treatment Research
& Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, 410208, India. Tel: 912227405057. Fax: 912227412894.
Sarcoma, September/December 2005; 9(3/4): 147–150
ISSN 1357–714X print/ISSN 1369–1643 online/05/(03-04)0147-4 ? 2005 Taylor & Francis
carried out. Since 2000 to date, patients with non-
prospectively in a database maintained in the
Department of Radiation Oncology. The medical
records of all such registered patients were searched
electronically. Patients with soft tissue sarcomas
alone (excluding extra-skeletal Ewing’s family of
tumors, and sarcomas of uncertain histogenesis such
as ASPS) were selected from the database and their
case files retrieved to document the occurrence of
An 18-year-old boy presented with complaints of
recent onset headache and vomiting. These central
nervous system (CNS) symptoms prompted a con-
trast-enhanced computed tomography (CECT) of
the brain, which revealed a heterogenously enhanc-
ing mixed density space-occupying lesion in the
right temporo-parietal region with moderate perifo-
cal edema and mass effect with midline shift
(Figure 1). Six months prior the patient had under-
gone wide excision of a soft tissue tumor of the
left thigh that was reported as a pleomorphic spindle
cell sarcoma of low to intermediate grade. He
had also received postoperative adjuvant radiation
to the tumor bed to a dose of 60Gy/30 fractions/
6 weeks and was locally controlled. In view of the
antecedent history, the diagnosis of a solitary brain
metastasis was favored. Until that time there was no
evidence of pulmonary metastases on a chest radio-
graph (CXR). The patient underwent right tem-
poral craniotomy with gross total resection of the
lesion. Histopathology revealed it to be a metastatic
high-grade spindle cell sarcoma consistent with
a known primary STS. Slide review of the pre-
vious surgery (wide excision of the left thigh swell-
ing) established that the lesion in the brain was
indeed metastatic from that primary. Subsequently
brain radiotherapy (WBRT) to a dose of 30Gy/
10 fractions/2 weeks with parallel opposed portals on
a telecobalt unit. While on radiation he developed
a cough for which he was adequately investigated.
Although the CXR was still negative, a CECT of
the thorax showed multiple lung nodules sugges-
tive of bilateral pulmonary metastases. He was
offered palliative chemotherapy that he declined.
Subsequently the patient died of disseminated
disease within 4 months of the diagnosis of brain
non-rhabdomyosarcoma STS from 2000 to date.
After excluding extra-skeletal Ewing’s family of
tumors and ASPS (higher propensity to involve
the brain), 307 patients with pure soft tissue
sarcomas were identified. None of these 307
patients with pure STS, excepting the index patient
described in this report had a documented brain
metastasis on retrospective case file review.
with registered 368
The prognosis of patients with brain metastases is
generally poor, the median survival of untreated
patients being 1–2 months. The overall median
survival increases to 4–6 months with therapy.
Neurosurgical resection of a solitary brain metas-
tasis is a good palliative procedure with low
morbidity in experienced hands. It is also associated
with better intra-cranial control and potentially
improved survival. However, its role in multiple
brain metastases or in patients with co-existing
extra-cranial disease remains largely speculative.
Given the resource implications and the question-
able efficacy, open craniotomy could possibly be
therapy offered to these patients with limited life
Brain metastasisis thought
tively uncommon event in the natural history of
STS, particularly in the absence of pulmonary
metastases. It is highly likely that this patient had
asymptomatic pulmonary metastases prior to the
to bea rela-
Figure 1. CT scan of the brain showing a heterogenously
enhancing mixed density SOL in right temporo-parietal region
with moderate perilesional edema and mass effect.
T. Gupta et al.
development of brain metastasis, which was missed
on a CXR. Had a CECT thorax been done instead
of CXR, one would have been more circumspect
in going ahead with a major neurosurgical pro-
cedure in the setting of disseminated lung metas-
tases. The true incidence of symptomatic brain
metastases in STS is not clearly known. It occurs
in a small minority with a reported prevalence
of 1–6%. The available literature is limited to
autopsy series [2,3], few retrospective studies [4–6],
small surgical series [7–9] and one recently pub-
lished prospective study  (Table I). The issue is
confounded by the fact that most of published series
and round cell sarcomas (e.g., rhabdomyosarcomas
or Ewing’s sarcomas) with non-round cell sarcomas.
The surgical case series suffer from an inherent
In a retrospective review of 411 patients with
various types of sarcomas, Postovsky et al. 
identified 18 patients with brain metastases, an
overall incidence of 4.3%. Soft tissue tumors had
lesser (2.3%) CNS involvement as compared to
bone sarcomas (5.9%), with Ewing’s sarcoma being
the most common. All these 18 patients with
brain metastases had some neurological symptoms
for which they were investigated appropriately. The
management of brain metastatic disease was indi-
vidualized and consisted of surgery, radiotherapy,
chemotherapy, best supportive care or a combina-
tion of the above depending upon the general
condition of the patient. The outcome of these
patients was particularly bad with a median survival
of 5 months from the diagnosis of brain metastases,
despite aggressive therapy. Paulino and colleagues
 reported a 4.9% incidence of brain metas-
tases (30 patients) in pediatric solid tumors from
the medical records of 611 children treated at
University of Iowa Hospital over a 35-year period.
Neuroblastoma (8%), rhabdomyosarcoma (6.7%),
Ewing’s sarcoma (5.7%) and osteosarcoma (4.7%)
had a higher incidence of CNS metastases as
compared to non-round cell soft tissue sarcoma
(2.4%) and Wilm’s tumor (1%). Of these 30 chil-
dren, four were diagnosed to have brain metastases
only at autopsy, whereas the remaining 26 non-
prompted neuro-imaging for radiological confirma-
tion. Majority of the patients had concurrent distant
disease either in the form of lung or bone metastases.
The treatment strategy was very varied for these
patients and the median survival after diagnosis of
brain metastases was only 4 months with a 6-month
and 1-year survival of 27 and 11.5%, respectively.
On multivariate analysis, use of radiotherapy was the
only factor that was associated with an improved
freedom from neurological progression (P¼0.005)
and a trend towards improved overall survival
(P¼0.07). Ogose et al. , in a retrospective
review of their institutional sarcoma database,
identified 20 cases of symptomatic brain metastases
from 480 patients treated and followed-up for at least
a year (4.2%). Of these, 15 cases of brain metastases
were recorded from 268 soft tissue tumors and five
cases from 212 bone sarcomas. ASPS (3/4), extra-
(2/13) tended to show a relatively high incidence of
CNS involvement. The majority (16/20) of these
patients had pulmonary metastases too. These
patients were variably treated with surgical resection,
WBRT, palliative chemotherapy or best supportive
care with the mean survival after the diagnosis of
brain metastases being 5.1 months.
Bindal et al.  reported on a series of 21 patients
treated with surgical resection of intraparenchymal
brain metastases from osteosarcoma (seven patients),
leiomyosarcoma (four patients), malignant fibrous
histiocytoma (three patients), alveolar soft part
sarcoma (two patients), Ewing’s sarcoma (three
patients), and unclassified sarcomas (two patients).
The median survival of the entire group after
craniotomy was 11.8 months with pre-operative
Table I. Selected series of brain metastases in sarcomas/pediatric solid tumors.
Total no. of
Patients detected with
metastases MS (months)
Postovsky et al. 411 14/236 (bone sarcomas)
Paulino et al.  61129/304
Ogose et al.  48015/268 (STS)
5/212 (bone sarcomas)
Bindal et al. – Not known11.8
Wronski et al. 670 25 19/257
Salvati et al. – 159/15 9.3
Espat et al. 3829 4018/197
MS, median survival; STS, soft tissue sarcomas; ASPS, alveolar soft part sarcoma; RMS, rhabdomyosarcoma.
STS brain metastases
performance status and completeness of resection
being the only factors associated with outcome. The
presence of lung metastases did not impact upon
survival and the authors concluded that it should
not be regarded as a contra-indication to brain
metastasectomy. In another surgical series, Wronski
et al.  reported a 4% prevalence of sarcoma brain
metastases (25 patients) in a group of 670 patients
undergoing brain metastasectomy. Osteosarcomas
and embryonal rhabdomyosarcomas were the com-
monest tumors of skeletal and non-skeletal origin,
Pulmonary metastases were present in the majority
(19/25) of these patients, 12 of whom underwent
pulmonary metastasectomy also in addition to the
resection of brain metastases. The median survival
post-craniotomy was 7 months with a 2-year
estimated overall survival of 16%. The authors
were unable to identify an association between
improved survival for patients undergoing surgical
resection of brain metastases and previous pulmo-
nary metastasectomy. Salvati et al.  reported on
15 patients surgically treated for brain metastases
from sarcoma, including six osteosarcomas, five
leiomyosarcomas, two malignant fibrous histio-
cytomas, and two alveolar soft part sarcomas. The
median survival of the entire group was 9.3 months
following craniotomy. Performance status was the
only factor significantly impacting upon outcome
(median survival of 12.8 months in good perfor-
mance status patients versus 5.3 months in poor
In the only prospective study cohort, Espat et al.
 could identify 40 patients with brain metas-
tases from a total of 3829 STS patients (1%)
registered in a prospective database over a 20-year
period. The most frequent subtype of STS metas-
tasizing to the brain was leiomyosarcoma (eight
patients), liposarcoma (five patients), rhabdomyo-
sarcomas (four patients) and malignant fibrous
histiocytomas (four patients). Of the 19 patients
who developed brain metastases metachronously,
18 had lung metastases as the immediate prior site
of disease. Such high frequency of pulmonary
metastases is consistent with the preponderance
of truncal or extremity sarcomas in this cohort.
The first site of distant metastases for truncal or
extremity STS is mostly the lung. In contrast patients
with retroperitoneal or visceral STS die of local
failure rather than surviving to develop distant
metastases. Brain metastasectomy was done in
27 of the 40 patients and was significantly associated
with the initial site of disease; 20 of the 27 patients
who underwent resection versus two of the 13
patients not undergoing resection had extremity or
truncal STS (P<0.001). There was no association
between parenchymal versus leptomeningeal site of
metastases and any outcome measure. The 1- and
2-year disease-specific survival for the entire cohort
of 40 patients was 55 and 25%, respectively, with
a median survival of 15 months. The 1- and 2-year
post-metastases survival rates were 34 and 20%,
respectively, with a median survival of 7 months.
Surgical resection of metastasis was associated
with an improvement in survival (9.6 vs. 2.7
months for unresected patients, p<0.01) and the
authors concluded that metastasectomy may be
appropriate treatment for selected patients with
Although brain metastases from STS are rare,
symptomatic patients should
investigated. Neurosurgical resection may be con-
sidered for solitary brain metastasis confined to non-
eloquent cortex associated with significant mass
effect. WBRT should be appropriate palliative
treatment for patients with multiple brain metas-
tases or co-existing extra-cranial disease. CECT
thorax is needed to rule out pulmonary metastases
definitely. In case of synchronous lung metastases,
palliative chemotherapy may be offered. The outlook
of these patients continues to remain grim despite
Conflict of interest
1. Espana P, Chang P, Wiernik PH. Increased incidence of
brain metastasesin sarcoma
2. Aronson SM, Garcia JH, Aronson BE. Metastatic neoplasms
of the brain: Their frequency in relation to age. Cancer
3. Posner JB, Chernik NL. Intracranial metastases from systemic
cancer. Adv Neurol 1978;19:579–592.
4. Postovsky S, Ash S, Ramu IN, Yaniv Y, Zaizov R,
in children with sarcoma. Oncology 2003;65:118–124.
5. Paulino AC, Nguyen T, Barker JL Jr. Brain metastases
in children with sarcoma, neuroblastoma and Wilm’s tumor.
Int J Radiat Oncol Biol Phys 2003;57(1):177–183.
6. Ogose A, Morita T, Hotta T, Kobayashi H, Otsuka H,
Hirata Y, Yoshida S. Brain metastases in musculoskeletal
sarcomas. Jpn J Clin Oncol 1999;29(5):245–247.
7. Bindal RK,Sawaya RE,
Guinee VF. Sarcoma metastatic to the brain: Results of
surgical treatment. Neurosurgery 1994;35:185–190.
8. Wronski M, Arbit E, Burt M, Perino G, Galicich JH,
Brennan MF. Resection of brain metastases from sarcoma.
Ann Surg Oncol 1995;2:392–395.
9. Salvati M, Cervoni L, Caruso R, Gagliardi FM, Delfini R.
Sarcoma metastatic to the brain: A series of 15 cases.
Surg Neurol 1998;49:441–444.
10. Espat JN, Bilsky M, Lewis JJ, Leung D, Brennan MF.
Soft tissue sarcoma brain metastases: Prevalence in a cohort
of 3829 patients. Cancer 2002;94:2706–2711.
Leavens ME,Taylor SH,
T. Gupta et al.