Stereotactic Radiosurgery Dose Escalation for Brain Metastases

Inclusion Criteria:

- Clinically confirmed brain metastases by CT or MRI criteria. If there is evidence of
extra-cranial metastatic disease, it is preferable that the lesions be pathologically
confirmed (see section 4.2.5 for excluded histologies) and reviewed by a University of
Utah or Huntsman Cancer Hospital pathologist if the initial review was done at an
outside facility.

- Prior brain surgery is allowed, although a lesion situated in the operative bed would
not be selected to receive an experimental dose of SRS treatment. SRS should be
delivered 4-6 weeks post-surgery if the patient had a craniotomy for resection of a
lesion. Enrollment of a patient with the goal of performing SRS outside of the 4-6
post-craniotomy window is at the PI's discretion.

- Patients must have 1-5 brain metastases total.

- Equivalent tumor diameter ≤ 40 mm by CT or MRI measurement at the time of
consultation/screening (for each metastatic lesion present in the brain).

- All metastatic lesions must be separated by a minimum of 3 cm as measured from the
peripheral edges of the lesions which are in closest proximity to one another. If
multiple lesions are present and are not all ≥ 3 cm away from each other, the patient
will be deemed ineligible.

- Prior systemic therapy is allowed, although appropriate washout is required for
patients who have been on BRAF inhibitors (at least 7 days).

- For subjects currently on active systemic cancer therapy, the treating medical
oncologist should be consulted to ensure proper washout (if appropriate) periods prior
to SRS.

- Patients must be at least 18 years of age.

- Karnofsky Performance Status (KPS) ≥ 60.

- Able to provide informed consent and have signed an approved consent form that
conforms to federal and institutional guidelines.

- Women of child-bearing potential must have a negative pregnancy test within 10 days of
study enrollment and must agree to use an acceptable method of birth control while
receiving radiation and for 3 months after radiation. Women of non-childbearing
potential may be included if they are either surgically sterile or have been
postmenopausal for >1 year.

- Men who are able to father a child must agree to use an acceptable method of birth
control while receiving radiation, and for 3 months after radiation.

Exclusion Criteria:

- Prior whole/partial brain irradiation or stereotactic radiosurgery

- Brain lesions with an equivalent diameter of > 40 mm in size on MRI imaging at the
time of consultation/screening for protocol eligibility.

- Lesions located in anatomic regions that are not amendable to SRS (e.g., optic nerve)

- Brain lesions located in the brain stem.

- Radiographic or cytologic evidence of leptomeningeal disease

- Primary lesion with radiosensitive histology that includes the following: small cell
carcinoma, germ cell tumors, lymphoma, leukemia, or multiple myeloma

- Women of child-bearing potential who are pregnant or breast feeding

- Patients with multiple lesions, which by size criteria would be enrolled in a cohort
which is full at the time of enrollment and the 12 weeks DLT period has not been
reached.