PRIMARY OBJECTIVE:
I. To determine if salvage stereotactic radiosurgery (SRS) plus whole brain radiotherapy with
hippocampal avoidance (HA-WBRT) in patients with brain metastasis velocity >= 4 new brain
metastases/year at time of first or second distant brain failure following upfront SRS
prolongs time to neurologic death as compared to salvage SRS alone.
SECONDARY OBJECTIVES:
I. To determine if salvage SRS + HA-WBRT in patients with brain metastasis velocity >= 4 new
brain metastases/year at time of first or second distant brain failure following upfront SRS
prolongs overall survival as compared to salvage SRS alone.
II. To evaluate if salvage SRS + HA-WBRT in patients with brain metastasis velocity >= 4 new
brain metastases/year at time of first or second distant brain failure following upfront SRS
prolongs intracranial progression-free survival as compared to salvage SRS alone.
III. To evaluate if salvage SRS + HA-WBRT in patients with brain metastasis velocity >= 4 new
brain metastases/year at time of first or second distant brain failure following upfront SRS
improves brain metastasis velocity at subsequent relapse as compared to salvage SRS alone.
IV. To assess perceived difficulties in cognitive abilities, symptom burden and health status
after salvage SRS + HA-WBRT, as compared to salvage SRS alone, in patients with brain
metastasis velocity >= 4 new brain metastases/year at time of first or second distant brain
failure following upfront SRS.
V. To compare neurocognitive function outcomes following salvage SRS + HA-WBRT, as compared
to salvage SRS alone, in patients with brain metastasis velocity >= 4 new brain
metastases/year at time of first or second distant brain failure following upfront SRS.
VI. To tabulate and descriptively compare the adverse events associated with the
interventions.
VII. To tabulate and descriptively compare the number of salvage procedures used to manage
recurrent intracranial disease following the interventions.
EXPLORATORY OBJECTIVES:
I. To collect serum, plasma, and whole blood for translational research analyses.
II. To collect baseline and all follow-up magnetic resonance (MR) imaging for hippocampal
volume, memory center substructures, axial T2 volumes, and quantitative texture analysis.
III. To collect baseline and follow-up MR imaging to extract whole brain volume, white matter
volume and volume of metastatic disease to correlate with cognitive change at 4 months.
IV. To evaluate dose-volume histogram parameters to correlate with radiation toxicity.
V. To assess in patients receiving immunotherapy or targeted therapy, if salvage SRS +
HA-WBRT in patients with brain metastasis velocity >= 4 new brain metastases/year at time of
first or second distant brain failure following upfront SRS improves brain metastasis
velocity and/or overall survival at subsequent relapse as compared to salvage SRS.
VI. To compare the estimated cost of brain-related therapies and quality-adjusted life years
in patients who receive salvage SRS + HA-WBRT, as compared to salvage SRS alone, in patients
with metastasis velocity >= 4 new brain metastases/year at time of first or second distant
brain failure following upfront SRS.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients undergo HA-WBRT daily (5 times weekly) for 2 weeks for a total of 10
fractions in the absence of disease progression or unacceptable toxicity. Within 1 week prior
to or following HA-WBRT, patients undergo salvage SRS. Prior to HA-WBRT or no later than the
4th treatment, patients also receive memantine orally (PO) once daily (QD) or twice daily
(BID) for 24 weeks in the absence of disease progression or unacceptable toxicity.
ARM II: Patients undergo salvage SRS.
After completion of study treatment, patients are followed up every 2-3 months for at least 1
year.