Surgery Versus Radiosurgery to Treat Metastatic Brain Tumors
Surgery Versus Radiosurgery to Treat Metastatic Brain Tumors
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 minutes.

 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 structures.

 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 tumors.

 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.
INCLUSION CRITERIA:

 Patients must:

 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
 radiation oncologist.

 EXCLUSION CRITERIA:

 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
 metastasis.

 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
 explanatory.

 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.