This study will compare the effectiveness of craniotomy to that of stereotactic surgery
(SRS) for the treatment of metastatic brain tumors - tumors that first develop elsewhere in
the body and then travel to the brain. Craniotomy is surgical removal of the tumors through
an operation. SRS consists of highly focused radiation doses to the tumors. Neither
treatment is experimental and both have shown benefits to patients with metastatic brain
tumors. This study will determine whether one treatment is superior to the other in
prolonging patient survival.
Patients 21 years of age and older with one to three metastatic brain tumors may be eligible
for this study. Participants will have a medical history and physical examination, blood and
urine tests, an electrocardiogram, and chest x-ray. They will then be randomly assigned to
undergo either surgery or SRS. Before either procedure, patients will have a magnetic
resonance imaging (MRI) scan. MRI uses a strong magnetic field and radio waves to obtain
images of the brain. Patients scheduled for SRS will have a computed tomography (CT) scan in
addition to the MRI. CT uses X-rays to obtain images of the brain. During the CT, a contrast
agent is injected through an IV tube placed in a vein to enhance the CT images. For both the
MRI and CT tests, the patient lies on a table that slides into a cylindrical scanner. The
MRI usually lasts between 45 and 90 minutes, while the CT scan lasts for about 30 to 60
Patients scheduled for surgery will have general anesthesia or local anesthesia with
sedation. They will be in intensive care after the surgery until their condition is stable.
Before being discharged home, they will have another MRI scan. The surgical sutures or
staples will be removed 7 to 10 days after surgery.
Patients scheduled for SRS will have their scalp numbed with medicine and their head will be
placed in a head frame. A CT scan will be done on the morning of the procedure to plan the
treatment. Around noon, the treatment, which consists of brief exposures to radiation, will
be administered with the patient positioned comfortably on a treatment couch. The treatment
will be completed in 1 to 2 hours, after which the head frame will be removed. After a brief
period of observation, the patient will be discharged home.
Patients will return to NIH for follow-up visits within 4 weeks after surgery or SRS and
then every 3 months after that for a medical history, physical examination, and MRI scan,
and to complete a quality of life questionnaire.
Introduction: Metastatic brain tumors occur more frequently than primary brain tumors and
occur in approximately 25% of patients who die of cancer each year. The main treatment
goals for patients with brain metastases are the relief of neurological symptoms and
long-term control of the tumors. Glucocorticoids and external beam whole brain radiation
therapy (WBRT) comprise the current standard of care and increase median survival from one
month to three to six months. Patients with three or less tumors (greater than 70% of
patients) also commonly undergo surgery or stereotactic radiosurgery (SRS) with the goal of
lengthening survival. Two prospective randomized trials have shown a significant survival
benefit for patients undergoing surgical resection of single tumors in combination with WBRT
compared to patients receiving WBRT alone. Although there have been no prospective
randomized studies comparing SRS and WBRT to WBRT alone, there have been numerous large
retrospective series reporting a significant survival benefit from SRS. To date, a
prospective randomized trial comparing surgery to SRS has not been reported. Despite the
lack of rigorous data, there are proponents for each of these treatment modalities. Those
in favor of surgery cite the ability to achieve a complete resection in most cases, the
almost immediate relief of symptoms, and the low rate of local recurrence. Those in favor
of SRS cite an equivalent degree of local tumor control compared to surgery, the relative
ease of the one day outpatient procedure, and the ability to treat lesions in deeper brain
Objectives: We plan to determine in a prospective randomized manner if surgery is superior
to SRS for prolonging survival in patients with one to three surgically accessible brain
Study Population: Patients aged twenty one years and older with one to three brain
metastases will be assessed for enrollment in this study.
Design: Patients who meet eligibility criteria will be randomly assigned to undergo either
surgery or SRS for their tumors. Patients will then be followed at regularly scheduled
intervals for the duration of their disease.
Outcome measures: The primary outcome measure will be time of survival following
treatment. Among the secondary outcomes that will be measured over time are tumor
recurrence or progression, neurologic sign or symptom development, functional independence,
steroid and anticonvulsant use, and overall quality of life.
1. be 21 years of age or older.
2. have a histologically confirmed primary malignancy.
3. be able to undergo an MRI scan of the brain.
4. have one to three intraparenchymal brain metastases as identified on a brain MRI scan
with intravenous contrast.
5. have contrast enhancing tumor(s) that are well circumscribed and less than or equal
to 4.0 cm in any dimension.
6. be appropriate for either procedure as determined by both a neurosurgeon and a
Patients must not:
1. have tumor(s) in the midbrain, pons, or medulla - patients undergoing surgical
resections in these areas are highly likely to develop significant neurological
deficits or death.
2. have tumors within 10 millimeters of the optic apparatus (nerves and chiasm) or the
area postrema - patients undergoing SRS to these areas are at significant risk of
developing permanent blindness or intractable nausea.
3. be poor operative candidates from an anesthetic point of view secondary to other
major medical illnesses - the risk of undergoing general anesthesia outweighs the
potential benefit of undergoing surgical resection of a brain metastasis.
4. have a coagulopathy demonstrated by an abnormal prothrombin time, activated partial
thromboplastin time, or thrombocytopenia (platelet count less that 150,000
platelets/mm3) - the risk of developing uncontrollable intra-operatively bleeding
outweighs the potential benefit of undergoing surgical resection of a brain
5. have radiographic or cerebrospinal fluid specimen evidence of widespread
leptomeningeal metastasis - neither surgery nor SRS is a useful treatment modality
for this condition.
6. significant psychiatric impairments which, in the opinion of the investigators, will
interfere with the proper administration or completion of the protocol - self
7. acute or untreated infections (viral, bacterial or fungal) - patients with active
infections are highly likely to have spread of their infections to the brain as a
result of a craniotomy.
8. be pregnant at the time of the randomized treatment - general anesthesia and surgery
may subject the fetus to unacceptable risks. Also, the NIH does not offer full
obstetrical services in the event that medical care to the mother and/or fetus is
required. Pregnant women presenting with brain metastases will be referred to
facilities offering OB/GYN services.
9. be prisoners or other institutionalized individuals - these individuals are at risk
of being susceptible to undue influences to participate in a research protocol
against their free will.
10. have a diagnosis of germ cell tumor, lymphoma or small cell lung cancer - these
tumors are highly radiosensitive and should therefore be treated with radiation.
11. have any of the following: aneurysm clip, implanted neural stimulator, implanted
cardiac pacemaker or auto defibrillator, cochlear implant, ocular foreign body or
implant [e.g. metal shavings, retinal clips], or insulin pump as these items would be
contra-indications to undergoing an MRI scan.
12. have an allergy to iodine or shellfish or have previously had an allergic reaction to
iodinated-contrast agents as this is a contra-indication to undergoing a contrast
enhanced CT of the brain - a contrast enhanced CT of the brain is required for the
planning of SRS.