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. Author manuscript; available in PMC: 2018 Oct 1.
Published in final edited form as: Semin Radiat Oncol. 2017 Oct;27(4):332–339. doi: 10.1016/j.semradonc.2017.04.006

Table 1.

Randomized trials to prevent or minimize CNS radiation toxicity.

Trial Intervention Mechanism Administration Result
RTOG 910421 Hyperfractionation Altered fractionation 54.4 Gy/1.6 Gy BID vs. 30 Gy/3 Gy
  • -

    No significant difference on MMSE at 3 months

  • -

    Tumor control correlated to better MMSE scores
RTOG 093342 Hippocampal sparing Preservation of hippocampal neurogenesis Intensity modulated radiation therapy (IMRT) delivered as 30 Gy in 10 fractions
  • -

    Reduced mean relative decline in the HVLT-R DR (7% vs. 30%, p<0.001)
N057443 SRS vs. WBRT Reduction of treatment volume SRS (18–24 Gy) +/− Whole brain irradiation (30 Gy/12 fractions)
  • -

    SRS alone associated with less cognitive decline at 3 months (63.5% vs. 91.3%, p<0.001)

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    For long-term survivors, SRS alone benefitted cognitive function both 3 months (45.5% vs. 94.1%, p=0.007) and at 12 months (60% vs. 94.4%, p=0.04)
RTOG 061446 Memantine NMDA receptor antagonist 20 mg/day given during radiation and for 24 weeks post-radiation
  • -

    Increased time to cognitive decline (HR 0.78, p=0.01)

  • -

    Reduced probability of cognitive function failure at 24 weeks (53.8% vs. 64.9%)
Wake Forest47 Donepezil Acetylcholine esterase inhibitor 5–10 mg/day for 24 weeks beginning at least 6 months after partial or whole brain irradiation
  • -

    No difference in composite score

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    Improved memory (p<0.05)

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    Improved motor speed and dexterity (p=0.016)

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    Greater benefit with baseline neurologic impairments