The purpose of this study is to determine the effectiveness and efficiency of Single Isocenter Multi-target Stereotactic Radiosurgery (SIMT SRS) in patients with four or more brain metastases

Forty patients with four or more brain metastases will be enrolled prior to radiosurgery. A planning MRI brain scan will be performed with GD-DPTA within one week prior to radiosurgery, per the standard of care. Neurocognitive (Mini-Mental Status Examination (MMSE), Trail-making test A&B, Hopkins Learning Verbal (HVLT)) and functional assessment of cancer therapy-brain (FACT- Br) will be obtained prior to radiosurgery. Dose will be prescribed to the maximum isodose line encompassing the resulting PTV using the dose guidelines as described below.

The primary endpoint will be the proportion of patients who live longer than predicted based on the diagnosis-specific GPA score. The Kaplan-Meier estimator will be used to describe the survival of all patients treated with SIMT SRS. Secondary endpoints will be the rate of recurrence at the treated metastases sites, the rate of new brain metastases at a site different from the SRS-treated metastases sites, the rate of death due to neurological causes, and the prevalence of significant adverse events. Exploratory endpoints include change over time in neurocognition and quality of life, quantification of dosimetric measures, the rate of salvage therapy, the rate of radionecrosis at the SRS treatment sites, and the rate and intensity of steroid-usage post-SRS.

All patients will be evaluated for neurocognitive function via MMSE, HVLT, and Trail-making tests A & B, quality of life via FACT-Br, and for local recurrence via MRI every 3 months over the course of the study. These evaluations will be done at regular follow-up evaluations or when local recurrence is suspected on the basis of symptoms. Distant recurrence is defined as the appearance of new brain metastases at a site different from that of the original metastases. Recurrence will further be defined as a new area of enhancement that measures greater than 5 millimeters in the axial plane on MRI. The length of time to recurrence of the original brain metastases will be calculated from the date of the brain metastases radiosurgery to the date that a recurrence was detected by MRI. Patients with suspected recurrent tumor and/or who are symptomatic may undergo a stereotactic biopsy to evaluate for radionecrosis versus recurrent brain metastases, as is standard of care.

Inclusion Criteria:

1. A contrast-enhanced MRI scan showing = or > 4 brain metastases.
2. Age >/=18 years of age.
3. KPS >/= 70
4. Patient must have a graded prosnostic score (GPA) score 0.5 or greater
5. Life expectancy of at least 3 months
6. Postoperative patients with resected brain metastases are eligible.
7. Largest lesion < 4cm diameter
8. Must be a candidate for MRI imaging
9. Previous cranial stereotactic radiosurgery (SRS) or whole brain radiation therapy (WBRT) is allowed if > 3 months prior to SIMT
10. Must be capable of providing informed consent

Exclusion Criteria:

1. Primary lesion with radiosensitive histology (i.e., small cell carcinoma, germ-cell tumors, lymphoma, leukemia, and multiple myeloma).
2. Metastases within 2 mm of the optic apparatus
3. Patients unable to obtain MRI
4. Evidence of leptomeningeal disease
5. Greater than 10 brain metastases
6. Pregnant women are excluded

2 years

Serious Adverse Events were only collected if they were grade 3, 4, or 5 event and were deemed by the Principal Investigator to be probably, possibly, or definitely related to the SRS treatment.