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.