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Strategies to Preserve Cognition in Patients With Brain Metastases: A Review.

ABSTRACT: Brain metastases are common to the natural history of many advanced malignancies. Historically, whole brain radiation therapy (WBRT) has played a key role in the management of brain metastases, especially for patients with multiple lesions. However, prospective trials have demonstrated consistent neurocognitive toxicities after WBRT, and various pharmacologic and anatomic strategies designed to mitigate these toxicities have been studied in recent years. Memantine, an NMDA receptor antagonist, taken during and after WBRT improved cognitive preservation in a randomized trial over placebo. Deliberate reductions in radiation dose to the hippocampus, via hippocampal-avoidance (HA)-WBRT, resulted in improved cognition over historic controls in a phase II trial, and follow-up randomized trials are now ongoing to evaluate cognitive outcomes with HA vs. conventional brain radiation techniques. Nevertheless, some of the most promising strategies currently available to reduce the cognitive effects of brain radiation may be found in efforts to avoid or delay WBRT administration altogether. Stereotactic radiosurgery (SRS), involving focused, high-dose radiation to central nervous system (CNS) lesions with maximal sparing of normal brain parenchyma, has become the standard for limited brain metastases (classically 1-3 or 4 lesions) in the wake of multiple randomized trials demonstrating equivalent survival and improved cognition with SRS alone compared to SRS plus WBRT. Today, there is growing evidence to support SRS alone for multiple (?4) brain metastases, with comparable survival to SRS alone in patients with fewer lesions. In patients with small-cell lung cancer, the routine use of prophylactic cranial irradiation (PCI) for extensive-stage disease has been also been challenged following the results of a randomized trial supporting an alternative strategy of MRI brain surveillance and early salvage radiation for the development of brain metastases. Moreover, new systemic agents are demonstrating increasing CNS penetration and activity, with the potential to offer greater control of widespread and microscopic brain disease that was previously only achievable with WBRT. In this review, we endeavor to put these clinical data on cognition and brain metastases into historical context and to survey the evolving landscape of strategies to improve future outcomes.

SUBMITTER: Robin TP

PROVIDER: S-EPMC6189295 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Strategies to Preserve Cognition in Patients With Brain Metastases: A Review.

Robin Tyler P TP Rusthoven Chad G CG

Frontiers in oncology 20181009

Brain metastases are common to the natural history of many advanced malignancies. Historically, whole brain radiation therapy (WBRT) has played a key role in the management of brain metastases, especially for patients with multiple lesions. However, prospective trials have demonstrated consistent neurocognitive toxicities after WBRT, and various pharmacologic and anatomic strategies designed to mitigate these toxicities have been studied in recent years. Memantine, an NMDA receptor antagonist, t ...[more]

PMID: 30356657

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Project description:ObjectiveTo broadly review the modern management of brain metastases.BackgroundBrain metastases are the commonest neurological manifestation of cancer and a major cause of morbidity in cancer patients. Brain metastases are increasing in frequency, as a result of longer life expectancy of cancer patients, more sensitive methods for brain metastasis detection and an ageing population. The proportional incidence of brain metastases according to cancer of origin, from greatest to least, is lung cancer, melanoma, renal, breast and colorectal cancers. Patients with lung cancer and melanoma are most likely to have brain metastases at diagnosis. Brain metastases cause a variety of symptoms, depending on their size and location, whether they cause mass effect and oedema, compression of the brain parenchyma, or focal neurological deficits. The major differential diagnoses of brain metastases include primary tumours and vascular/inflammatory lesions. Prognosis is dependent on the site, number and volume of lesions, the patients' performance status, age and the activity and extent of extracranial disease.MethodsEnglish literature articles in PubMed from 1950 to June 2021 were reviewed. Article bibliographies provided further references.ConclusionsTreatment of brain metastasis patients has moved from considering them as a homogenous population of patients, to individualised treatment. In those brain metastases patients of satisfactory performance status with a solitary lesion, especially one in a non-eloquent/accessible area causing significant mass effect and/or raised intracranial pressure or for whom the diagnosis is in doubt (histology needed), surgical resection is usually the treatment of choice. For multiple brain metastases, radiotherapy with or without systemic therapies are usually employed. For relatively fit patients with limited numbers of brain metastases (e.g., 4 or less), stereotactic radiosurgery is standard of care. Current clinical trials are testing the efficacy of stereotactic treatment alone for >4 brain metastases (although it is increasingly used for such patients in many centres) as well as integration of local therapies with targeted and immunological therapies in appropriately selected cases. In certain circumstances, cranial irradiation can be omitted.

Dataset Information

Strategies to Preserve Cognition in Patients With Brain Metastases: A Review.

Publications

Strategies to Preserve Cognition in Patients With Brain Metastases: A Review.

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