Dose Escalation Trial of Neoadjuvant Radiosurgery for the Treatment of Metastatic Brain Tumors

Radiosurgery is a non-surgical radiation therapy that can deliver targeted radiation to small
brain tumors. Radiosurgery is considered to be part of standard of care. Typically for
standard of care, radiosurgery is given after a patient has healed from neurosurgery, in an
attempt to destroy any cancer cells that may be left after surgery. Patients who agree to
participate in this research study will receive radiosurgery before their neurosurgery.

The timing of radiosurgery (pre-operatively) and the dosing to determine the safest dose is
considered experimental.

By giving radiation the typical way, after surgery, a larger area of the brain must be
covered, which means healthy brain tissue also receives radiation, whereas radiation before
surgery will specifically target the tumor.

Inclusion Criteria:

- Patients with prior histopathological diagnosis of cancer other than small cell lung
cancer, lymphoma, and germ cell histologies.

- MR imaging of the brain with findings strongly suggestive of metastatic tumor(s) as
assessed by the radiologist.

- MR evidence of at least one brain lesion ≤ 40 mm in maximal diameter that is deemed to
be surgically resectable as evaluated by the neurosurgeon and appropriate for SRS. All
other brain lesions must be appropriate for SRS alone and treated according to
physician preference. Prior neurosurgery and/or prior SRS at a non-overlapping
location are permitted at the discretion of the treating physician.

- Written informed consent obtained from subject, or a legally designated power of
attorney and ability for subject to comply with the requirements of the study.

- Negative pregnancy test in women of childbearing potential (WOCBP) within 30 days of
radiation. WOCBP is a female patient less than 50 years of age or who has menstruated
within the last 12 months.

- Patients aged ≥ 18 years.

- Life expectancy ≥ 3 months

- Non-acute KPS ≥ 60%

Exclusion Criteria:

- Patients deemed medically unfit to undergo surgical resection of brain metastasis,
such as those who are neurologically or hemodynamically unstable despite appropriate
medical interventions.

- Patients who have had prior whole brain radiation.

- Patients with >4 brain metastases.

- Active or prior: documented inherited hypersensitivity syndromes, certain autoimmune
diseases, and certain collagen vascular diseases. For example, any radiation
hypersensitivity syndrome, including, but not limited to, ataxia-telangiectasia,
Gorlin syndrome, multiple sclerosis, scleroderma, and systemic lupus erythematosus.

- Radiographic or cytologic evidence of leptomeningeal disease.

- Patients receiving methotrexate, adriamycin, epirubicine, or navelbin for one week
prior to or concurrently with SRS. Note: All other systemic anti-cancer therapies will
be reviewed on a case-by-case basis by study PI to determine if appropriate for study
treatment and documented within the research record or EMR.