Brain metastases: increasingly precision medicine—a narrative review

Abstract

Objective: To broadly review the modern management of brain metastases.Background: Brain 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.Methods: English literature articles in PubMed from 1950 to June 2021 were reviewed. Article bibliographies provided further references.Conclusions: Treatment 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.

The sparing effect of FLASH-RT on synaptic plasticity is maintained in mice with standard fractionation

“…Here we report on the capability of FLASH-RT delivered in a clinically used standard fractionation protocol to preserve LTP, in marked contrast to the inhibition of LTP found under CONV-RT. In the clinic, whole brain RT is used under an identical fractionation regimen for the control of multiple brain metastasis [ 13 , 14 ]. Cognitive endpoints have been used in multiple recent clinical trials of whole brain RT [ 15 , 16 ], in which most patients develop measurable cognitive decline by 4 months after irradiation.…”

Uncovering the Protective Neurologic Mechanisms of Hypofractionated FLASH Radiotherapy

“…To safely implement FLASH-RT into the clinic the convergence of multiple expertise and continued research is needed. To that end, we have focused on delivering a high total fractionated dose to the brain, close to the standard of care currently used for the treatment of brain metastasis ( 27, 28 ) in efforts to establish a link between critical functional outcomes and key cellular, molecular, and structural mediators of neurotransmission. Our initial focus was to critically evaluate the long-term capability of hypofractionated FLASH-RT to spare neurocognition using an expanded behavioral battery by the inclusion of a cross-species relevant OUL task and an extended (24 hours) NOR task in tumor-free animals.…”

Recent Trends in Synchronous Brain Metastasis Incidence and Mortality in the United States: Ten-Year Multicenter Experience

“…Minimally invasive surgery is increasingly being performed to acquire tissue for examination. Undoubtedly, BMs are now receiving more individualized care rather than being treated as a homogenous group of patients [ 43 ]. First-generation EGFR tyrosine kinase inhibitors (TKIs) (e.g., gefitinib and erlotinib) and second-generation TKIs (e.g., neratinib and dacomitinib) were shown to prolong overall survival in BMs from non-small cell lung cancer (NSCLC) with EGFR mutations [ 44 , 45 ].…”