Neurocognitive Outcome of Bilateral or Unilateral Hippocampal Avoidance WBRT With Memantine for Brain Metastases
Status:
Recruiting
Trial end date:
2025-02-28
Target enrollment:
Participant gender:
Summary
Brain metastases are the most common brain tumors in adults. It is estimated that around
10-30% of cancer patients would develop brain metastases during the course of their illness.
Whole brain radiotherapy (WBRT) is the treatment of choice for the majority of patients with
brain metastases. WBRT yields high radiologic response rate (27~56%) and is effective in
rapid palliation of neurologic symptoms as well as prolongs time to neurocognitive function
decline caused by intracranial lesions. By using conventional fractionation, more than one-
third of patients developed late neurocognitive toxicity while memory impairment was the most
common symptom. The incidence is even higher when a formal and sensitive neurocognitive
assessment was prospectively evaluated. With more long-term survivors nowadays, it has become
increasingly important to minimize neurocognitive function decline and maintain quality of
life in patients with brain metastasis.
The function of hippocampus is cooperation in learning, consolidation and retrieval of
information and essential for formation of new memories. Bilateral and unilateral radiation
injury of the hippocampus is known to alter learning and memory formation. Several
preclinical studies support the hypothesis of hippocampus-mediated cognitive dysfunction by
ionizing radiation. Clinical studies show increase in radiation dose to hippocampus is
associated with subsequent neurocognitive function impairment in adult and pediatric
patients. Furthermore, the result of phase III randomized trials suggested hippocampal
avoidance plus Memantine significantly reduce the risk of neurocognitive impairment at 6
months from 68.2% in control arm with standard WBRT to 59.5% in experimental arm. In the
investigator's prior investigation, patients received conformal WBRT with bilateral
hippocampal avoidance also had significant less declines in verbal memory at 6 months.
Previous studies showed the right and left hippocampus exert different neurocognitive
functions. Several retrospective studies also demonstrated that the radiation dose to the
left hippocampus is more related to neurocognitive impairment. Planning study and
investigation showed that by avoiding the left hippocampus alone, the radiation dose to the
spared unilateral hippocampus is further decreased. In present study, a single blind
randomized phase II trial is designed to investigate the effectiveness of neurocognitive
function preservation using conformal WBRT with bilateral or unilateral hippocampal avoidance
and memantine.