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Brain Metastases: General Information
written and compiled by doctordee
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Introduction
How to Use This Page

This page deals with Brain Metastases. There is a general discussion, followed by treatment techniques with illustrative annotated citations of medical journal articles, dealing with LMS or sarcoma if possible. [For further discussion of some of the treatment techniques like Chemotherapy or Radiation, see another section of this website.]

Should you be interested in a specific technique, abstracts can be highlighted and copied, and then printed out and taken with you to your doctor for further discussion. Furthermore searches on Pubmed or on ASCO may provide further information on the technique, and places where it is done, for you and your doctor.
[ ] will indicate editorial comment by the compiler. Some sentences are highlighted in bold, again chosen by the compiler.



Leiomyosarcoma & Brain Metastases
Metastasis is the spread of cancer. Cancer that begins in other parts of the body may spread to the brain and cause secondary tumors. These tumors are not the same as primary brain tumors. Cancer that spreads to the brain is the same disease and has the same name as the original (primary) cancer. For example, if lung cancer spreads to the brain, the disease is called metastatic lung cancer because the cells in the secondary tumor resemble abnormal lung cells, not abnormal brain cells.

Treatment for secondary brain tumors depends on the kind of cancer it is, and the extent of the spread as well as other factors, including the patient's age, general health, and response to previous treatment.
While brain metastases were an unusual development in leiomyosarcoma, there is now an increased incidence of brain metastases in sarcoma patients with prolonged survival from chemotherapy. Brain metastases from sarcoma usually occur with or after lung metastasis. Long-term survival is possible with treatment in some patients. [1,2,7,8, 9]


Letter posted to the L-M-Sarcoma Mailing List at ACOR, August 2002

Alfrida,

I am so sorry to hear of your symptoms. By now, you most likely know the outcome of your MRI. I just wanted you to know that I had brain mets and had them removed in Dec. 1999. I lived a full life afterwards and then found last summer that more had returned. Once again I had brain surgery back in July last year. Unfortunately, my latest scan showed two more, but this time they are small and I am receiving stereotactic radiosurgery, which is a kind of radiation. If I have slowed down my activities a bit lately, it is more due to painful tumors in my foot rather than the brain tumors.
I just wanted you to know that I am still out here and fighting. My heart goes out to you, and hopefully this will not be your diagnosis. If it is, you can do this. One step at a time.

Hugs, Maria (New Jersey)
Uterine LMS 29 year survivor. Surgery, radiation.
Next occurrence 21 years later, 1994. Lung VAT procedure.
Next occurrence 5 years later, 1999, brain. 3 chemos.
Many mets, several surgeries. Radiation presently.
Symptoms

Read What you Need to Know About Brain Tumors
from the www.cancer.gov site of the National Cancer Institute [NCI]


Symptoms of Brain Tumors

The symptoms of brain tumors depend mainly on their size and their location in the brain. Symptoms are caused by damage to vital tissue and by pressure on the brain as the tumor grows within the limited space in the skull. They also may be caused by swelling and a buildup of fluid around the tumor, a condition called edema. Symptoms may also be due to hydrocephalus, which occurs when the tumor blocks the flow of cerebrospinal fluid and causes it to build up in the ventricles. If a brain tumor grows very slowly, its symptoms may appear so gradually that they are overlooked for a long time.

The most frequent symptoms of brain tumors include:
Headaches that tend to be worse in the morning and ease during the day,
Seizures (convulsions or fits),
Nausea or vomiting,
Weakness or loss of feeling in the arms or legs,
Stumbling or lack of coordination in walking (ataxic gait),
Abnormal eye movements or changes in vision,
Drowsiness,
Changes in personality or memory, and
Changes in speech.
These symptoms may be caused by brain tumors or by other problems.
Only a doctor can make the diagnosis.


Diagnosis


To find the cause of a person's symptoms, the doctor asks about the patient's personal and family medical history and performs a complete physical examination. In addition to checking general signs of health, the doctor does a neurologic exam. This includes checks for alertness, muscle strength, coordination, reflexes, and response to pain. The doctor also examines the eyes to look for swelling caused by a tumor pressing on the nerve that connects the eye and the brain.

Depending on the results of the physical and neurologic examinations, the doctor may request one or both of the following:

A CT (or CAT) scan is a series of detailed pictures of the brain. The pictures are created by a computer linked to an x-ray machine. In some cases, a special dye is injected into a vein before the scan. The dye helps to show differences in the tissues of the brain.

MRI (magnetic resonance imaging) gives pictures of the brain, using a powerful magnet linked to a computer. MRI is especially useful in diagnosing brain tumors because it can "see" through the bones of the skull to the tissue underneath. A special dye may be used to enhance the likelihood of detecting a brain tumor.

The doctor may also request other tests such as:

A skull x-ray can show changes in the bones of the skull caused by a tumor. It can also show calcium deposits, which are present in some types of brain tumors.

A brain scan reveals areas of abnormal growth in the brain and records them on special film. A small amount of a radioactive material is injected into a vein. This dye is absorbed by the tumor, and the growth shows up on the film. (The radiation leaves the body within 6 hours and is not dangerous.)

An angiogram, or arteriogram, is a series of x-rays taken after a special dye is injected into an artery (usually in the area where the abdomen joins the top of the leg). The dye, which flows through the blood vessels of the brain, can be seen on the x-rays. These x-rays can show the tumor and blood vessels that lead to it.

A myelogram is an x-ray of the spine. A special dye is injected into the cerebrospinal fluid in the spine, and the patient is tilted to allow the dye to mix with the fluid. This test may be done when the doctor suspects a tumor in the spinal cord.
About Treatment

Brain tumors are usually treated with surgery, radiation therapy, and/or chemotherapy. Depending on the patient's needs, several methods may be used. The patient may be referred to doctors who specialize in different kinds of treatment and work together as a team. This medical team often includes a neurosurgeon, a medical oncologist, a radiation oncologist, a nurse, a dietitian, and a social worker. The patient may also work with a physical therapist, an occupational therapist, and a speech therapist.

Before treatment begins, most patients are given steroids, which are drugs that relieve swelling (edema). They may also be given anticonvulsant medicine to prevent or control seizures. If hydrocephalus is present, the patient may need a shunt to drain the cerebrospinal fluid.

As always with leiomyosarcoma, surgical resection is the treatment of choice. Direct neurosurgical excision, with or without other treatments, is usually recommended if it is possible. Surgery is the usual treatment for most brain tumors. To remove a brain tumor, a neurosurgeon makes an opening in the skull. This operation is called a craniotomy. Whenever possible, the surgeon attempts to remove the entire tumor. However, if the tumor cannot be completely removed without damaging vital brain tissue, the doctor removes as much of the tumor as possible. Partial removal (debulking) helps to relieve symptoms by reducing pressure on the brain and reduces the amount of tumor to be treated by radiation therapy or chemotherapy.

Radiation in some form [intraoperative, whole brain irradiation, stereotactic or gamma knife, proton or other particle beam, or radioisotope insertion] is often used alone or in conjunction with surgery or possibly other treatments. Cognitive defects may occur after whole brain irradiation, and possibly with other treatments. Radionecrosis of the brain-the development of multiple and increasing areas of dead and dying brain tissue-is a serious complication of radiation treatment.
Radiation therapy is the use of high-powered rays to damage cancer cells and stop them from growing. It is often used to destroy tumor tissue that cannot be removed with surgery or to kill cancer cells that may remain after surgery. Radiation therapy is also used when surgery is not possible.

Radiation therapy may be given in two ways. External radiation comes from a large machine. Generally, external radiation treatments are given 5 days a week for several weeks. The treatment schedule depends on the type and size of the tumor and the age of the patient. Giving the total dose of radiation over an extended period helps to protect healthy tissue in the area of the tumor.

Radiation can also come from radioactive material placed directly in the tumor (implant radiation therapy). Depending on the material used, the implant may be left in the brain for a short time or permanently. Implants lose a little radioactivity each day. The patient stays in the hospital for several days while the radiation is most active.

External radiation may be directed just to the tumor and the tissue close to it or, less often, to the entire brain. (Sometimes the radiation is also directed to the spinal cord.) When the whole brain is treated, the patient often receives an extra dose of radiation to the area of the tumor. This boost can come from external radiation or from an implant.

Stereotactic radiosurgery is another way to treat brain tumors. Doctors use the techniques described in the Surgery section to pinpoint the exact location of the tumor. Treatment is given in just one session; high-energy rays are aimed at the tumor from many angles. In this way, a high dose of radiation reaches the tumor without other brain tissue becoming badly damaged.

Chemotherapy is the use of drugs to kill cancer cells. The doctor may use just one drug or a combination, usually giving the drugs by mouth or by injection into a blood vessel or muscle. Intrathecal chemotherapy involves injecting the drugs into the cerebrospinal fluid.

Chemotherapy is usually given in cycles: a treatment period followed by a recovery period, then another cycle. Patients often do not need to stay in the hospital for treatment. Most drugs can be given in the doctor's office or the outpatient clinic of a hospital. However, depending on the drugs used, the way they are given, and the patient's general health, a short hospital stay may be necessary.

Chemotherapy is not very successful in treating brain tumors, because of something called the "blood brain barrier" [BBB], which prevents chemotherapy agents, present in the blood, from migrating into or penetrating brain tissue. There are substances and conditions that do break down the BBB, and allow permeation of the brain, but these are in experimental use at this time. We do know that trauma and radiation and certain substances can cause disruption of the BBB. [3,4,6] Were chemotherapy agents able to pass the blood brain barrier, would their neurotoxicity become the limiting factor for treatment? [5]

Radio frequency ablation has also been used to treat brain metastases. As has hyperthermia.

Generally, aggressive treatment of treatable brain metastases is indicated where conditions are favorable, with failures coming from local recurrence of the treated brain metastases, emergence of new brain metastases, or progression of other systemic disease. [2]

Aggressive treatment of brain metastases is recommended if a person's functioning is good. [1,2] In a sense, this depends upon the location [whether near vital centers] and the size of the tumor, so it is worthwhile being alert to the possibility of brain metastasis, and being scanned if there is a suspicion, to diagnose them early. MRI scans are more accurate for this purpose than CT scans.

Search Pubmed for Brain Metastases and Treatment
Clinical Trials

Researchers are looking for treatment methods that are more effective against brain tumors and have fewer side effects. When laboratory research shows that a new method has promise, doctors use it to treat cancer patients in clinical trials. These trials are designed to answer scientific questions and to find out whether the new approach is both safe and effective. Patients who take part in clinical trials make an important contribution to medical science and may have the first chance to benefit from improved treatment methods.

Many clinical trials of new treatments for brain tumors are under way. Doctors are studying new types and schedules of radiation therapy, new anticancer drugs, new drug combinations, and combinations of chemotherapy and radiation.

Scientists are trying to increase the effectiveness of radiation therapy by giving treatments twice a day instead of once. Also, they are studying drugs called radiosensitizers. These drugs make the cancer cells more sensitive to radiation. Another method under study is hyperthermia, in which the tumor is heated to increase the effect of radiation therapy.
Many drugs cannot reach brain cells because of the blood-brain barrier, a network of blood vessels and cells that filters blood going to the brain. Researchers continue to look for new drugs that will pass through the blood-brain barrier. Studies are under way using different techniques to temporarily disrupt the barrier so that drugs can reach the tumor.
In other studies, scientists are exploring new ways to give the drugs. Drugs may be injected into an artery leading to the brain or may be put directly into the ventricles. Doctors are also studying the effectiveness of placing tiny wafers containing anticancer drugs directly into the tumor.

Biological therapy is a new way of treating brain tumors that is currently under study. This type of treatment is an attempt to improve the way the body's immune system fights disease.

Patients interested in taking part in a clinical trial should discuss this option with their doctor. They may want to read about clinical trials on the National Cancer Institute website. This resource contains information about cancer treatment and about clinical trials in progress all over the country.

It also has a service listing clinical trials that is searchable.
Online Resources and Annotated Citations

The Virtual Trials Website
This excellent section of the virtual trials website attempts to explain the latest brain tumor treatments that are in general use in plain English, with a brief overview of each, then details on the treatments and where to find them. Unlike the rest of the "Clinical Trials & Noteworthy Treatments For Brain Tumors" site, this section is only the author's OPINIONS of the material. Use it for general information, to get ideas of what is available out there, but then discuss it with your own doctors.



Radiation URLs


Staten Island, NY University Hospital Radiosurgery

Oncolink Article About Radiosurgery

Fermi National Accelerator Laboratory Neutron Beam

Massachusetts General Hospital, Harvard Medical School Proton Beam

Loma Linda, CA, University Medical Center Proton Beam

Gamma Knife Radiosurgery

Kansas City

San Diego

Arkansas



Brain Anatomy


Brain Anatomy

More Brain Anatomy

Brain Functions and Map




Annotated References for this section:


1. Surg Neurol 2000 Aug;54(2):160-4
Brain metastasis in patients with sarcoma: an analysis of histological subtypes, clinical characteristics, and outcomes.
Yoshida S, Morii K, Watanabe M, Saito T. Department of Neurosurgery, Niigata Cancer Center Hospital, Niigata, Japan.

"... Brain metastasis was found in 27 (5.6%) of 480 patients with systemic sarcoma (7.2% soft part sarcoma, 3.5% bone sarcoma, 15.1% distant metastasis). Of these 27 sarcoma patients with brain metastases, lung metastasis occurred in 16 patients (59.3%). Out of 10 patients surgically treated, 8 patients survived more than 16 months. Median survival period after craniotomy was 25.4 months."
"...We recommend aggressive treatment for those patients with brain metastases whose performance scores are over 70."
Fetch PMID: 11077098


2. Neurochirurgie 1999 Dec;45(5):382-92
[Cerebral metastases: radiotherapy and chemotherapy]. [Article in French]
Helfre S, Pierga J. Institut Curie, 26, rue d'Ulm, 75005 Paris, France.

"Brain metastases are common events in adult patients with solid tumors. The choice of the optimal therapy is still challenging and controversial. Whole brain radiotherapy (WBRT) is a standard practice in most patients with an excellent palliative effect. Boost to gross disease has also been advocated without a clear benefit. Moreover following extended irradiation, a substantial proportion of the long term survivors (>6 months), will present documented cognitive impairments. Patients with favorable prognostic factors can benefit from more aggressive therapy: local resection, mono or multifractionated irradiation with or without radiosensitizing agents, stereotactic radiotherapy, brachytherapy. Although brain metastases of solid tumors occur in the presence of progressive widespread disease, chemotherapy has played a limited role in their treatment. Poor drug penetration across the normal blood-brain barrier of chemotherapy agents is not a limiting factor because of the neovascularization in the tumor. [?] The few prospective studies that have addressed this issue, especially in lung and breast tumors, are reviewed."
Fetch PMID: 10717587


3. Neuro-oncol 2001 Jan;3(1):46-54
Importance of dose intensity in neuro-oncology clinical trials: summary report of the Sixth Meeting of the Blood-Brain Barrier Disruption Consortium.
Doolittle ND, Anderson CP, Bleyer WA, Cairncross JG, Cloughesy T, Eck
SL, Guastadisegni P, Hall WA, Muldoon LL, Patel SJ, Peereboom D, Siegal
T, Neuwelt EA.
Dept of Neurology, Oregon Health Sciences University, Portland 97201-3098, USA.

" Therapeutic options for the treatment of malignant brain tumors have been limited, in part, because of the presence of the blood-brain barrier. For this reason, the Sixth Annual Meeting of the Blood-Brain
Barrier Disruption Consortium, the focus of which was the "Importance of Dose Intensity in Neuro-Oncology Clinical Trials," was convened ...This meeting...brought together clinicians and basic scientists from across the U.S. to discuss the role of dose intensity and enhanced chemotherapy delivery in the treatment of malignant brain tumors and to design multicenter clinical trials. "
"Optimizing chemotherapy delivery to the CNS is crucial, particularly in view of recent progress identifying certain brain tumors as chemosensitive. The discovery that specific constellations of genetic alterations can predict which tumors are chemoresponsive, and can therefore more accurately predict prognosis, has important implications for delivery of intensive, effective chemotherapy regimens with acceptable toxicities. This report summarizes the discussions, future directions, and key questions regarding dose-intensive treatment of ... metastatic cancer of the brain. The promising role of cytoenhancers and chemoprotectants as part of dose-intensive regimens for chemosensitive brain tumors and development of improved gene therapies ... are discussed."
Publication Types: Congresses
Fetch PMID: 11305417


4. Curr Oncol Rep 2000 Sep;2(5):445-53
Cytotoxic chemotherapy: advances in delivery, pharmacology, and testing.
Ciordia R, Supko J, Gatineau M, Batchelor T.
Brain Tumor Center, Massachusetts General Hospital Cancer Center, Harvard Medical School, Cox 315, 100 Blossom Street, Boston, MA 02114, USA.

"... A major factor in the failure of iv chemotherapy [for treatment of brain tumors] is the blood-brain barrier (BBB), a physiologic impediment to the delivery of cytotoxic chemotherapeutic drugs to the central nervous system (CNS). Intra-arterial and intrathecal infusion, blood-brain barrier disruption, high-dose chemotherapy, intratumoral administration, and convection-enhanced delivery are methods developed to overcome the BBB. Although some of these methods may increase the local concentration-time profile, improvement in clinical outcomes has yet to be definitively established. New methods for assessment of drug delivery to the brain tumor will assume increasing importance in the study of new cytotoxic chemotherapeutic drugs for these types of cancer. Pharmacokinetic studies are critical components of these clinical trials and allow assessment of drug delivery to the CNS and brain tumor. Additionally, pharmacokinetic studies will remain an important component of early clinical trials, particularly for identifying significant drug interactions involving the various supporting medications that are typically used in this patient population."
Fetch PMID: 11122877



5. Neurosurgery 2000 Jul;47(1):199-207
Unexpected neurotoxicity of etoposide phosphate administered in combination with other chemotherapeutic agents after blood-brain barrier modification to enhance delivery, using propofol for general anesthesia, in a rat model.
Fortin D, McCormick CI, Remsen LG, Nixon R, Neuwelt EA.
Dept of Neurology, Oregon Health Sciences University, and Veterans Administration Medical Center, Portland, USA.

"... Osmotic blood-brain barrier disruption (BBBD) increases brain and brain tumor delivery of chemotherapeutic agents, which results in increased efficacy against brain tumors. We previously noted that the use of propofol anesthesia for BBBD increased the percentage of successful disruptions, resulting in delivery of increased amounts of chemotherapeutic drugs. This study evaluated the neurotoxicity of combination chemotherapeutic administration with this enhanced delivery system."...
"Neurotoxicity was significantly increased for etoposide phosphate combination groups, particularly when both drugs were administered IA after BBBD. This increase in neurotoxicity may reflect on increase in drug delivery observed with propofol anesthesia. ..."
Fetch PMID: 10917363


6. Clin Pharmacol Ther 2000 Jun;67(6):631-41
Pharmacokinetics of methotrexate in cerebrospinal fluid and serum after osmotic blood-brain barrier disruption in patients with brain lymphoma.
Zylber-Katz E, Gomori JM, Schwartz A, Lossos A, Bokstein F, Siegal T.
Division of Medicine, the Neuro-Oncology Center, Hadassah University Hospital, Jerusalem, Israel. esterzk@hadassah.org.il

"... Enhanced methotrexate delivery to the central nervous system can be attained by intra-arterial administration combined with osmotic disruption of the blood-brain barrier compared with simple intra-arterial or intravenous administration."
Fetch PMID: 10872645


7. Cancer 1988 Feb 1;61(3):593-601
Sarcoma metastatic to the brain.
Lewis AJ.
Department of Pathology, University of Toronto, Ontario, Canada.

"...Reportedly, most types of sarcomas are able to metastasize to the brain, and are represented in these 94 patients. ... There may be a group of tumors, including ...perhaps leiomyosarcoma ... in which the incidence of brain metastases has increased with improved sarcoma chemotherapy ... In this group particularly... the presence of lung metastases may increase the probability of brain metastasis occurring subsequently.
Fetch PMID: 3276383


8. Med Pediatr Oncol 1985;13(5):280-92
Sarcoma metastatic to the central nervous system parenchyma: a review of the literature.
Sarno JB, Wiener L, Waxman M, Kwee J.

Sarcoma metastatic to cerebral parenchyma, although rare, occurs more frequently than generally recognized. With increased duration of survival due to multi-modal therapy, more CNS metastases are being
found. A literature search occasioned by a patient with metastatic sarcoma has produced some interesting results.

Fetch PMID: 3897818


9. Cancer 1975 Nov;36(5):1843-51
Increased incidence of cerebral metastases in sarcoma patients with prolonged survival from chemotherapy. Report of cases of leiomyosarcoma and chondrosarcoma.
Gercovich FG, Luna MA, Gottlieb JA.

Soft tissue and bony sarcomas rarely metastasize to the central nervous system, particularly to the cerebral hemispheres. In 456 patients with metastatic sarcoma, only 6 (1.3%) had cerebral metastases documented by brain scan at the time of referral for chemotherapy. Adriamycin-containing combination chemotherapeutic regimens have led to a significant increase in the median survival of patients from the start of chemotherapy (18 + months for responders compared, to 7 months in nonresponders). Of 14 patients relapsing after a response or stabilization of disease of 6 months or greater, the cause of relapse was the development of cerebral metastases in 5 (36%). Two of these cases, one a patient with leiomyosarcoma and one with chondrosarcoma, were documented by autopsy and are reported in detail because of their rarity in the medical literature. Although the numbers are small, the increased incidence of cerebral metastases in the group relapsing after a lengthy response suggests that improved chemotherapy for sarcomas resulting in improved survival may be changing the pattern of metastatic disease, and may require new therapeutic approaches.
Fetch PMID: 1192369
Sarcoma and Brain Metastases


"The autopsy findings of 73 patients with uterine sarcoma were studied to determine the sites and possible modes of metastasis. [26% of the tumor types were LMS] The peritoneal cavity and omentum were the most frequently involved sites (59%), followed by the lung (52%), pelvic lymph nodes (41%), paraaortic lymph nodes (38%), and liver parenchyma (34%). The presence of lung metastasis was not associated with pelvic or paraaortic node metastasis or intraperitoneal disease. Metastasis to other distant sites including the brain, heart, kidney, and bone were independent of pelvic and paraaortic nodal metastasis or intraperitoneal disease. Metastatic sites were not different among various histologic types. Distant metastatic sites were statistically associated with lung metastasis. Hematogenous metastasis best explains this metastatic pattern..."[12]

Soft tissue and bony sarcomas rarely metastasize to the brain. [1,2,5,6,8,9,18] Data concerning the treatment and results of therapy are sparse [5] Sarcoma and leiomyosarcoma metastatic to the brain is uncommon and rarely occurs as the initial manifestation of tumor. Central nervous system metastases are an unusual sequela of leiomyosarcoma. The incidence of brain metastases from systemic sarcoma has been reported as 7% or less. [2]

If sarcoma does metastasize to the brain, it is often after lung metastases [approximately 60% of those with brain metastases will have had or have lung metastases. [1,5] Although the numbers are small, the increased incidence of cerebral metastases in the group relapsing after a lengthy response suggests that improved chemotherapy for sarcomas resulting in improved survival may be changing the pattern of metastatic disease, and may require new therapeutic approaches.[18]

"Treatment allowing longer survival may be allowing brain metastases to become noticeable. With increased duration of survival due to multi-modal therapy, more CNS metastases are being found. A literature search occasioned by a patient with metastatic sarcoma has produced some interesting results" [14]

" In 456 patients with metastatic sarcoma, only 6 (1.3%) had cerebral metastases documented by brain scan at the time of referral for chemotherapy. Adriamycin-containing combination chemotherapeutic regimens have led to a significant increase in the median survival of patients from the start of chemotherapy (18 + months for responders compared, to 7 months in nonresponders). Of 14 patients relapsing after a response or stabilization of disease of 6 months or greater, the cause of relapse was the development of cerebral metastases in 5 (36%). Two of these cases, one a patient with leiomyosarcoma and one with chondrosarcoma, were documented by autopsy and are reported in detail because of their rarity in the medical literature." [18]

"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" [17]

"There may be a group of tumors, including malignant fibrous histiocytoma, rhabdomyosarcoma, and perhaps leiomyosarcoma and osteosarcoma, in which the incidence of brain metastases has increased with improved sarcoma chemotherapy (CT). In this group particularly, but also in alveolar soft-part sarcoma and others, the presence of lung metastases may increase the probability of brain metastasis occurring subsequently." [13]

"Since brain metastases from sarcoma are refractory to alternative treatment, surgical excision is indicated when feasible". [5]

"In one series where sarcoma was surgically resected, one-year survival was 36% and 2-year survival was 18%. Three patients (12%) survived over 5 years. "[5]

"Out of 10 patients surgically treated, 8 patients survived more than 16 months. Median survival period after craniotomy was 25.4 months. ... We recommend aggressive treatment for those patients with brain metastases whose performance scores are over 70."[1]

"We report on 21 patients surgically treated for intraparenchymal brain metastasis from sarcoma, including ... four leiomyosarcomas, .... Median survival after craniotomy was 11.8 months. Patients with a preoperative Karnofsky performance score of > 70 survived for 15.7 versus 6.6 months for those with a Karnofsky performance score < or = 70. Patients undergoing complete resection survived 14.0 versus 6.2 months for patients undergoing incomplete resection. Patients with evidence of lung metastases at the time of surgery survived 11.8 months, which was similar to the 10.5-month survival for patients with disease limited to the brain. .... We conclude that surgery is effective in treating selected patients with sarcoma metastatic to the brain and that patients with metastasis from alveolar soft-part sarcoma may have a relatively good prognosis if they are surgically treated. The complete removal of all brain metastases and a Karnofsky performance score > 70 are associated with a favorable prognosis, whereas the presence of concurrent lung metastases is not a contraindication to surgery."[7]

"Of 480 sarcoma patients, 179 had distant metastases, including 20 patients with brain metastases (4.2%). ,,, Three patients underwent surgical treatment and two of them survived over 1 year. Mean survival after diagnosis of brain metastasis was 5.1 months".[2]

In a series of sarcoma brain metastases: "Median survival after craniotomy was 9.3 months. Patients with a preoperative Karnofsky performance score of > 70 survived for 12.8 versus 5.3 months for those with a Karnofsky performance score < 70 (p=0.03). Patients with evidence of only lung metastases at the time of surgery (nine cases) survived 8.6 months, which was similar to the 10.4-month survival for patients with disease limited to the brain (p=0.1). ,,,". [3]
"...We conclude that surgery is effective in treating selected patients with sarcoma metastatic to the brain ,,,. The complete removal of all brain metastases and a Karnofsky performance score > 70 are associated with a favorable prognosis; the presence of concurrent lung metastases is not a contraindication to surgery.[3]
Annotated Citations
Brain Metastases and Sarcoma

1. Surg Neurol 2000 Aug;54(2):160-4
Brain metastasis in patients with sarcoma: an analysis of histological subtypes, clinical characteristics, and outcomes.
Yoshida S, Morii K, Watanabe M, Saito T. Department of Neurosurgery, Niigata Cancer Center Hospital, Niigata, Japan.

... We examined the incidence and the characteristics of brain metastasis in patients with sarcomas. ... All sarcoma patients treated at our institution from 1975 to 1998 were reviewed for brain metastasis. ... Brain metastasis was found in 27 (5.6%) of 480 patients with systemic sarcoma (7.2% soft part sarcoma, 3.5% bone sarcoma, 15.1% distant metastasis). Of these 27 sarcoma patients with brain metastases, lung metastasis occurred in 16 patients (59.3%). Out of 10 patients surgically treated, 8 patients survived more than 16 months. Median survival period after craniotomy was 25.4 months. ... We recommend aggressive treatment for those patients with brain metastases whose performance scores are over 70.
Fetch PMID: 11077098


2. Jpn J Clin Oncol 1999 May;29(5):245-7
Brain metastases in musculoskeletal sarcomas.
Ogose A, Morita T, Hotta T, Kobayashi H, Otsuka H, Hirata Y, Yoshida S.
Department of Orthopaedic Surgery, Niigata Cancer Center Hospital, Japan.

...In musculoskeletal sarcomas, brain metastases are rare, but severely affect quality of life. ... All patients with musculoskeletal sarcomas who were treated at our institutions from 1975 to 1997 were reviewed for examples of brain metastasis.
...Of 480 sarcoma patients, 179 had distant metastases, including 20 patients with brain metastases (4.2%). Alveolar soft part sarcoma (3/4), extraskeletal Ewing's sarcoma (2/8), rhabdomyosarcoma (2/13) and bone Ewing's sarcoma (2/18) tended to metastasize to the brain. All 20 patients had distant or local relapses and 16 of the 20 patients had pulmonary metastases. Three patients underwent surgical treatment and two of them survived over 1 year. Mean survival after diagnosis of brain metastasis was 5.1 months...: Patients with alveolar soft part sarcoma, Ewing's sarcoma, rhabdomyosarcoma and pulmonary metastases have a high risk of brain metastasis.
Fetch PMID: 10379335



3. Surg Neurol 1998 Apr;49(4):441-4
Sarcoma metastatic to the brain: a series of 15 cases.
Salvati M, Cervoni L, Caruso R, Gagliardi FM, Delfini R. Department of Neurosurgery, Neurological Mediterranean Neuromed Institute, IRCCS, Pozzilli (IS), Italy.

We report on 15 patients surgically treated for intraparenchymal brain metastases from sarcoma, including six osteosarcomas, five leiomyosarcomas, two malignant fibrous histiocytomas, and two alveolar soft-part sarcomas (ASPS).
...Median survival after craniotomy was 9.3 months. Patients with a preoperative Karnofsky performance score of > 70 survived for 12.8 versus 5.3 months for those with a Karnofsky performance score < 70 (p=0.03). Patients with evidence of only lung metastases at the time of surgery (nine cases) survived 8.6 months, which was similar to the 10.4-month survival for patients with disease limited to the brain (p=0.1). The two patients with alveolar soft-part sarcomas are alive at 15 and 20 months after surgery.
...We conclude that surgery is effective in treating selected patients with sarcoma metastatic to the brain and that patients with metastasis from ASPS may have a relatively good prognosis if they are surgically treated. The complete removal of all brain metastases and a Karnofsky performance score > 70 are associated with a favorable prognosis; the presence of concurrent lung metastases is not a contraindication to surgery.
Fetch PMID: 9537665


4.Am J Clin Oncol 1996 Aug;19(4):351-5
Late onset of isolated central nervous system metastasis of liposarcoma--a case report.
Arepally G, Kenyon LC, Lavi E.
Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia 19104, USA.

Metastatic soft-tissue sarcoma of the central nervous system (CNS) is exceedingly rare,,,
Fetch PMID: 8677903


5. Chir Narzadow Ruchu Ortop Pol 1995;60(1):55-60
[Surgical treatment of brain metastases from sarcoma]. [Article in Polish]
Wronski M. Oddzialu Neurochirurgii Centrum Onkologii im. Sloana-Ketteringa w Nowym Jorku.

Brain metastases from sarcoma are rare, and data concerning the treatment and results of therapy are sparse. ,,, Median time from primary diagnosis to diagnosis of brain metastasis was 26.7 months. Lung metastases were present in 21 patients (76%) (8 synchronous with the brain lesion). Pulmonary metastases were resected in 14 patients (50%). The overall median survival time from diagnosis of primary sarcoma was 38.8 months, and from craniotomy was 6.6 months. The presence or absence of lung lesion did not change the median survival calculated from diagnosis of brain metastasis (7 mos and 4.5 mos, respectively, p < 0.48, log-rank test). ,,,. One-year survival was 36% and 2-year survival was 18%. Three patients (12%) survived over 5 years. Since brain metastases from sarcoma are refractory to alternative treatment, surgical excision is indicated when feasible. Brain metastases from sarcoma are uncommon and usually occur in association with or following lung metastasis. Long term survival is possible in a small percentage of patients.
Fetch PMID: 7736836


6.Gynecol Oncol 1994 Aug;54(2):237-41
Leiomyosarcoma of the uterus metastatic to brain: a case report and a review of the literature.
Wronski M, de Palma P, Arbit E. Neurosurgery Service, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.

Central nervous system metastases are an unusual sequela of uterine sarcomas. ,,, Only seven other cases of uterus leiomyosarcoma metastatic to the brain have been published. Review of reported cases
Fetch PMID: 8063254


7. Neurosurgery 1994 Aug;35(2):185-90; discussion 190-1
Sarcoma metastatic to the brain: results of surgical treatment.
Bindal RK, Sawaya RE, Leavens ME, Taylor SH, Guinee VF.
Department of Neurosurgery, University of Texas M.D. Anderson Cancer Center, Houston.

We report on 21 patients surgically treated for intraparenchymal brain metastasis from sarcoma, including ... four leiomyosarcomas, .... Median survival after craniotomy was 11.8 months. Patients with a preoperative Karnofsky performance score of > 70 survived for 15.7 versus 6.6 months for those with a Karnofsky performance score < or = 70. Patients undergoing complete resection survived 14.0 versus 6.2 months for patients undergoing incomplete resection. Patients with evidence of lung metastases at the time of surgery survived 11.8 months, which was similar to the 10.5-month survival for patients with disease limited to the brain. The two patients with alveolar soft-part sarcoma are alive at 16 and 25 months after surgery. We conclude that surgery is effective in treating selected patients with sarcoma metastatic to the brain and that patients with metastasis from alveolar soft-part sarcoma may have a relatively good prognosis if they are surgically treated. The complete removal of all brain metastases and a Karnofsky performance score > 70 are associated with a favorable prognosis, whereas the presence of concurrent lung metastases is not a contraindication to surgery.
Fetch PMID: 7969824


8. Neurosurgery 1994 Jan;34(1):168-70
Metastatic alveolar soft part sarcoma presenting as a dural-based cerebral mass.
Perry JR, Bilbao JM.
Division of Neurology, St. Michael's Hospital, Toronto, Ontario, Canada.

Sarcoma metastatic to the brain is uncommon and rarely occurs as the initial manifestation of tumor. ....
Fetch PMID: 8121554


9. Br J Radiol 1993 Nov;66(791):1009-15
Survival, patterns of spread and prognostic factors in uterine sarcoma: a study of 76 patients.
Moskovic E, MacSweeney E, Law M, Price A.
Department of Radiology, Royal Marsden Hospital, London, UK.

We have analysed the medical records and diagnostic imaging of 76 patients presenting to this hospital for treatment of uterine sarcoma between 1970 and 1990. ,,, Bone and brain metastases were uncommon (< 10%). Following diagnosis of relapse, the median survival was 9 months, with the outcome significantly worse if multiple metastatic sites were involved (p < 0.001). No survival benefit was demonstrated from either local radiotherapy or combination chemotherapy once relapse had occurred. Prognostic factors and current policies for the diagnosis and management of uterine sarcomas are discussed.
Fetch PMID: 8281375


10. J Heart Lung Transplant 1993 May-Jun;12(3):527-30
Heart transplantation for cardiac angiosarcoma: should its indication be questioned?
Crespo MG, Pulpon LA, Pradas G, Serrano S, Segovia J, Vegazo I, Salas C, Espana P, Silva L, Burgos R, et al.
Heart Transplant Unit, Clinica Puerta de Hierro, Madrid, Spain.

Two men, aged 31 and 32 years, respectively, underwent orthotopic heart transplantation, in both cases to treat primary cardiac angiosarcoma of the right atrium. Total removal of the tumor was performed, and no evidence was found of distant dissemination at the time of surgery. Their postoperative progress was good; however, the patients died 8 and 9 months after transplantation, respectively, of multiple brain metastases. We do not consider heart transplantation to be indicated in the management of malignant cardiac tumors.
Fetch PMID: 8329433


11. Thorac Cardiovasc Surg 1992 Feb;40(1):48-51
Leiomyosarcoma of the pulmonary hilar vessels.
Berney CR, Roche B, Kurt AM, Spiliopoulos A, Megevand R.
Institute of Pathology, University Hospital, Geneva, Switzerland.

Fetch PMID: 1631867


12. Cancer 1989 Mar 1;63(5):935-8
Patterns of metastasis in uterine sarcoma. An autopsy study.
Rose PG, Piver MS, Tsukada Y, Lau T.
Department of Gynecologic Oncology, Roswell Park Memorial Institute, Buffalo, NY 14263.

The autopsy findings of 73 patients with uterine sarcoma were studied to determine the sites and possible modes of metastasis. Homologous mixed mesodermal tumors were the most frequent (41%) followed by leiomyosarcoma (26%), heterologous mixed mesodermal tumor (18.3%), stromal sarcoma (12%), and endolymphatic stromal myosis (3%). The peritoneal cavity and omentum were the most frequently involved sites (59%), followed by the lung (52%), pelvic lymph nodes (41%), paraaortic lymph nodes (38%), and liver parenchyma (34%). The presence of lung metastasis was not associated with pelvic or paraaortic node metastasis or intraperitoneal disease. Metastasis to other distant sites including the brain, heart, kidney, and bone were independent of pelvic and paraaortic nodal metastasis or intraperitoneal disease. Metastatic sites were not different among various histologic types. Distant metastatic sites were statistically associated with lung metastasis. Hematogenous metastasis best explains this metastatic pattern and adjuvant systemic therapy seems indicated.
Fetch PMID: 2914299


13. Cancer 1988 Feb 1;61(3):593-601
Sarcoma metastatic to the brain. Lewis AJ.
Department of Pathology, University of Toronto, Ontario, Canada.

,,, Reportedly, most types of sarcomas are able to metastasize to the brain, and are represented in these 94 patients. ,,, There may be a group of tumors, including malignant fibrous histiocytoma, rhabdomyosarcoma, and perhaps leiomyosarcoma and osteosarcoma, in which the incidence of brain metastases has increased with improved sarcoma chemotherapy (CT). In this group particularly ,,, the presence of lung metastases may increase the probability of brain metastasis occurring subsequently. Review, multicase
Fetch PMID: 3276383


14. Med Pediatr Oncol 1985;13(5):280-92
Sarcoma metastatic to the central nervous system parenchyma: a review of the literature.
Sarno JB, Wiener L, Waxman M, Kwee J.

Sarcoma metastatic to cerebral parenchyma, although rare, occurs more frequently than generally recognized. With increased duration of survival due to multi-modal therapy, more CNS metastases are being found. ,,,
Fetch PMID: 3897818


15. Cancer 1985 Mar 15;55(6):1382-8
Surgical treatment of brain metastases. Clinical and computerized tomography evaluation of the results of treatment.
Sundaresan N, Galicich JH.
Fetch PMID: 3971308


16. Arch Surg 1983 Aug;118(8):915-8
Metastatic patterns in soft-tissue sarcomas.
Vezeridis MP, Moore R, Karakousis CP.

In 242 patients with recurrent soft-tissue sarcomas, the most common sites of initial recurrence were the primary site in 47.5% of patients and the lungs in 38% of patients. Further recurrences in the course of the disease concerned the lungs, bones, liver, and brain. Total survival and survival after recurrence were influenced by the histologic type, which also affected the site of recurrence. In the management of local recurrence, a five-year disease-free survival rate of 38% was achieved with surgical treatment, while radiation or chemotherapy alone was ineffective. Local recurrences resulted in significantly higher survival rates than those involving other organs. The disease-free interval was a significant prognostic indicator of subsequent survival in the whole group of patients and among those with local recurrence.
Fetch PMID: 6307217


17. Cancer 1980 Jan 15;45(2):377-80
Increased incidence of brain metastases in sarcoma patients.
Espana P, Chang P, Wiernik PH.

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,,,
Fetch PMID: 6243247


18. Cancer 1975 Nov;36(5):1843-51
Increased incidence of cerebral metastases in sarcoma patients with prolonged survival from chemotherapy. Report of cases of leiomyosarcoma and chondrosarcoma.
Gercovich FG, Luna MA, Gottlieb JA.

Soft tissue and bony sarcomas rarely metastasize to the central nervous system, particularly to the cerebral hemispheres. In 456 patients with metastatic sarcoma, only 6 (1.3%) had cerebral metastases documented by brain scan at the time of referral for chemotherapy. Adriamycin-containing combination chemotherapeutic regimens have led to a significant increase in the median survival of patients from the start of chemotherapy (18 + months for responders compared, to 7 months in nonresponders). Of 14 patients relapsing after a response or stabilization of disease of 6 months or greater, the cause of relapse was the development of cerebral metastases in 5 (36%). ,,,. Although the numbers are small, the increased incidence of cerebral metastases in the group relapsing after a lengthy response suggests that improved chemotherapy for sarcomas resulting in improved survival may be changing the pattern of metastatic disease, and may require new therapeutic approaches.
Fetch PMID: 1192369



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