Neurocognitive Decline in Patients With Brain Metastases

On review of our experience with treatment for brain metastases since 2009, the investigators
have treated over 100 patients with 6 or more metastases in a single radiosurgery session. In
the past year and a half (2015-16) there have been approximately 50 patients treated with six
or more metastases, indicating that there has been a shift in management of intracranial
metastatic disease with increasing preference for radiosurgery despite the presences of
greater metastatic burden. The phase I component will accrue 7-15 patients at each dose
cohort until the maximal tolerated dose (MTD) is determined. Once the MTD is reached, the
phase II component will commence with a total of 50 patients total enrolled at the MTD, with
a study time of 3 years. The primary endpoint of the phase I component is toxicity. The
primary endpoint of the phase II component is the change in neurocognitive function, defined
by a decline in the Hopkins Verbal Learning Test- Revised delayed recall.

Inclusion Criteria:

- Age ≥ 18 years.

- ECOG Performance Score of 2 or better.

- Biopsy-proven non-hematopoietic malignancy, except for germ cell cancer. Small cell
lung carcinoma is eligible for this study

- Six or more metastases on diagnostic or treatment planning imaging, which include
either CT or MR imaging.

- Largest tumor <4 cm

- No prior SRS to the lesions which will be treated on protocol.

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry, and
for the duration of protocol treatment.

- Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria:

- Prior whole brain radiotherapy

- Patients with leptomeningeal metastasis.

- Patients with life expectancy < 4 months

- Psychiatric illness/social situations that would limit compliance with study
requirements.