This phase I/II trial studies the side effects and the best dose of stereotactic radiosurgery and to see how well it works in treating patients with large brain metastases. Radiosurgery can send x-rays directly to the tumor and cause less damage to normal tissue.

PRIMARY OBJECTIVES:

I. To determine the incidence of acute and long-term toxicities with increasing dose of stereotactic radiosurgery (SRS). (Phase I) II. To determine if local control may be improved with increasing doses of SRS. (Phase II)

SECONDARY OBJECTIVES:

I. To determine the risk of acute and long-term toxicity with increasing dose of SRS. (Phase II) II. To determine if there is increased neurocognitive toxicity with increased dose of SRS.

III. To determine the rate of radiation necrosis/steroid dependency. IV. To determine if quality of life is affected more by tumor recurrence versus radiation necrosis. This includes assessment of progression free survival, overall survival, local failure, and number of patients who receive bevacizumab, laser interstitial thermal therapy, or surgery for presumed radiation necrosis.

OUTLINE: This is a phase I dose-escalation study followed by a phase II study.

Patients undergo SRS guided by computer tomography (CT) and magnetic resonance imaging (MRI).

After completion of treatment, patients are followed up at 1-2, 3, 6, 9, and 12 months, every 3 months for 2 years, and then every 4 months thereafter.

Inclusion Criteria:

• Any patient undergoing SRS for brain metastases

• Lesions to be treated under this protocol must be > 2 cm, but =< 4.0 cm in diameter

• Patients may have had prior therapy including:

  • Whole brain radiation therapy (WBRT) > 3 months ago
  • SRS to other brain metastases

• Patients with newly diagnosed brain metastases are eligible as long as they are not planned for WBRT upfront

• Any primary is eligible with exception of small cell lung cancer, lymphoma, and germ cell histologies

• Patient must be able to provide written informed consent

Exclusion Criteria:

• Patients receiving SRS to resection bed
• Planned concurrent WBRT
• Leptomeningeal metastases
• Small cell lung cancer, lymphoma, and germ cell histologies
• Inability to participate in study activities due to physical or mental limitations
• Inability or unwillingness to return for all the required follow-up visits
• Conformality index 2.0 or less cannot be achieved, or homogeneity index is > 2.0
• Unable to deliver 10 Gray (Gy) or less to optic nerve/chiasm
• Brainstem location is excluded from this study