Pre-operative SRS or Post-operative SRS in Treating Cancer Patients With Brain Metastases

PRIMARY OBJECTIVES:

I. To investigate the 1 year leptomeningeal disease (LMD)-free rate among patients with
surgically resectable metastatic brain lesions randomized to post-operative stereotactic
radiosurgery (SRS) (standard care) versus pre-operative SRS followed by surgery (experimental
arm).

SECONDARY OBJECTIVES:

I. To investigate the local control (LC), distant brain metastasis rate, overall survival
(OS) and neuro-cognitive impact of pre-operative (pre-op) versus (vs) post-operative
(post-op) SRS in patients with brain metastasis. This aim includes an evaluation of the
impact of the method used for stereotactic radiosurgery including, Gamma Knife single
fraction, Gamma Knife fractionated with ICON, or LINAC (linear accelerator) based
fractionated SRS, as well as an assessment on the impact of tumor volume and cavity volume.

EXPLORATORY OBJECTIVES:

I. To assess the reliability of different imaging features by using a combination of patient
data and phantom data to quantify the uncertainties associated with using magnetic resonance
imaging (MRI) for radiomics studies.

II. To assess the correlation of imaging-pathology correlates using multiparametric imaging
that characterize the tumor and peri-tumoral microenvironment including features such as
tumor vascular characteristics, cellular density, oxygenation and presence of
inflammation/immune reactivity.

OUTLINE: Patients are randomized to 1 of 2 groups.

GROUP I (PRE-OPERATIVE SRS): Patients undergo SRS within 15 days of randomization followed by
surgery within 15 days. Patients may undergo additional SRS if disease returns after
treatment.

GROUP II (POST-OPERATIVE SRS): Patients undergo surgery within 15 days of randomization
followed by standard of care SRS within 30 days. Patients may undergo additional SRS if
disease returns after treatment.

After completion of study treatment, patients are followed up periodically.

Inclusion Criteria:

- The primary posterior fossa lesion pre-operatively or the post-operative resection
cavity must have a maximum diameter of =< 4 cm for single fraction and =< 8 cm for
multifraction (will be determined by the study radiologist)

- Additional unresected brain metastases must have a maximum diameter of =< 4 cm for
single fraction and =< 8 cm for multifraction

- Patients must be considered candidates for SRS within +/- 30 days of surgical
resection as defined by either history and physical (H&P) or presentation at brain
metastasis tumor board conference note

- Patients must have a Karnofsky performance scores >= 70 or Eastern Cooperative
Oncology Group (ECOG) >= 2 within 30 days of enrollment

- Patients must agree to randomization as documented by signing the Institutional Review
Board (IRB) approved consent form

- No radiographic evidence of leptomeningeal disease on MD Anderson Cancer Center
(MDACC) departmental radiology report or study neuro-radiologist review

- Documented history of malignancy

Exclusion Criteria:

- Patients who have received prior radiation therapy to the brain for any reason

- The primary tumor is small-cell lung cancer, lymphoma, leukemia, or multiple myeloma

- For females, if they are pregnant or breast-feeding (The exclusion is made because
gadolinium may be teratogenic in pregnancy)