Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial

Brown, Paul D.; Pugh, Stephanie L.; Laack, Nadia N.; Wefel, Jeffrey S.; Khuntia, Deepak; Meyers, Christina A.; Choucair, Ali; Fox, Sherry; Suh, John H.; Roberge, David; Kavadi, Vivek S.; Bentzen, Søren M.; Mehta, Minesh P.; Bruner, Deborah Watkins

doi:10.1093/neuonc/not114

Cited by 807 publications

(539 citation statements)

References 30 publications

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“…In a phase iii study of adult patients with brain metastases, the addition of memantine to whole-brain rt was associated with a delay in the decline of cognitive function 46 . The use of novel neuroprotectants in conjunction with whole-brain rt remains an active area of investigation, and to our knowledge, no such trials have investigated the use of such agents in sclc patients undergoing pci.…”

Section: Influencing Factormentioning

confidence: 99%

Management of Small-Cell Lung Cancer with Radiotherapy—A Pan-Canadian Survey of Radiation Oncologists

et al. 2016

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Section: Influencing Factormentioning

confidence: 99%

Management of Small-Cell Lung Cancer with Radiotherapy—A Pan-Canadian Survey of Radiation Oncologists

et al. 2016

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“…In adults, impairments occur in up to 50%-90% of patients within 3-6 months after fractionated whole-brain radiation therapy (WBRT). 8,24 Long-term survivors of childhood brain radiotherapy are most severely affected, experiencing double-digit declines in IQ, vocational restriction, and an elevated incidence of psychiatric impairments. 45,52,53 Neurooncology outcomes have historically focused on survival.…”

mentioning

confidence: 99%

Radiation-induced brain injury: low-hanging fruit for neuroregeneration

Burns

Awad

et al. 2016

FOC

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Brain radiation is a fundamental tool in neurooncology to improve local tumor control, but it leads to profound and progressive impairments in cognitive function. Increased attention to quality of life in neurooncology has accelerated efforts to understand and ameliorate radiation-induced cognitive sequelae. Such progress has coincided with a new understanding of the role of CNS progenitor cell populations in normal cognition and in their potential utility for the treatment of neurological diseases. The irradiated brain exhibits a host of biochemical and cellular derangements, including loss of endogenous neurogenesis, demyelination, and ablation of endogenous oligodendrocyte progenitor cells. These changes, in combination with a state of chronic neuroinflammation, underlie impairments in memory, attention, executive function, and acquisition of motor and language skills. Animal models of radiation-induced brain injury have demonstrated a robust capacity of both neural stem cells and oligodendrocyte progenitor cells to restore cognitive function after brain irradiation, likely through a combination of cell replacement and trophic effects. Oligodendrocyte progenitor cells exhibit a remarkable capacity to migrate, integrate, and functionally remyelinate damaged white matter tracts in a variety of preclinical models. The authors here critically address the opportunities and challenges in translating regenerative cell therapies from rodents to humans. Although valiant attempts to translate neuroprotective therapies in recent decades have almost uniformly failed, the authors make the case that harnessing human radiation-induced brain injury as a scientific tool represents a unique opportunity to both successfully translate a neuroregenerative therapy and to acquire tools to facilitate future restorative therapies for human traumatic and degenerative diseases of the central nervous system.

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“…The administration of memantine at the time of radiotherapy could reduce cognitive disorder. Memantine is inexpensive and tolerable, and thus could be widely applied [18][19][20][21]. In addition, whole brain radiotherapy keeping away from hippocampal synapse could protect the neural stem cells in hippocampal synapse, which is helpful to improve the prognosis, relieve hypomnesia [22][23] and improve QOL.…”

Section: It Is Recommended By National Comprehensive Cancermentioning

confidence: 99%

Clinical study of the treatment of multiple brain metastases from adenocarcinoma of the lung by simultaneous integrated boost intensity-modulated radiotherapy

Shao¹,

S²,

Wang³

et al. 2018

J Cancer Res Ther.

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Objective: To investigate the effects of simultaneous integrated boost intensity-modulated radiotherapy (SIB) and sequential boost conformal radiotherapy (CRT) in treatment of multiple brain metastases from lung adenocarcinoma. Methods: Forty-two patients with multiple brain metastases from lung adenocarcinoma were analyzed. The epidermal growth factor (EGFR) mutations were negative, ECOG (Eastern Cooperative Oncology Group) were not more than two, the diameters of brain metastases were from 0.5cm to 3.0cm and the numbers of brain metastases were from three to five. The target volume of radiotherapy included whole brain and brain metastatic tumor. The radiation models were divided into SIB in 26 cases and CRT in 16 cases. The median radiation dose of whole brains in SIB and CRT groups were 40Gy, and the brain metastases tumor were 55Gy, 60Gy respectively, and the median number of radiotherapy for 22 times, 30 times. Thirty one patients followed by pemetrexed maintenance chemotherapy (PMC) or docetaxel maintenance chemotherapy (DMC) and 11 patients received no maintenance chemotherapy (NMC). Results: The 1-, 3-, and 5-year survival rates of whole group were 92.8%, 23.8%, and 4.8%, respectively. The median survival time of SIB and CRT groups were 36 months, 29 months, respectively. The SIB group was better than CRT group, and PMC was better than DMC or NMC. Multiple factors analyses showed ECOG, dose and times of brain metastatic tumor radiotherapy, and cycles of PMC were independent risk factors for survival time. The late main adverse reaction was hypomnesia. Conclusion: SIB was superior to CRT, and PMC could improve survival time.

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Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial

Cited by 807 publications

References 30 publications

Management of Small-Cell Lung Cancer with Radiotherapy—A Pan-Canadian Survey of Radiation Oncologists

Management of Small-Cell Lung Cancer with Radiotherapy—A Pan-Canadian Survey of Radiation Oncologists

Radiation-induced brain injury: low-hanging fruit for neuroregeneration

Clinical study of the treatment of multiple brain metastases from adenocarcinoma of the lung by simultaneous integrated boost intensity-modulated radiotherapy

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