Current approaches to the treatment of metastatic brain tumours

Key Points

  • An increased understanding of the molecular biology of metastatic processes, including cell migration, blood–brain barrier penetration, angiogenesis and tumour proliferation, is providing new opportunities for the development of targeted therapies

  • Advances in MRI, incorporating spectroscopy and perfusion techniques, and tracers unique to metastases, provide additional information on responses to treatment and enable the earlier detection of new tumours

  • Improvements in intraoperative tumour identification using MRI and fluorescent agents maximize the likelihood of complete tumour resection and minimize injury to normal tissue

  • Reduction of radiation-induced cerebral injury and cognitive decline through repeated use of stereotactic radiosurgery or hippocampal-avoidance whole-brain radiotherapy provide useful options for individuals with advanced cerebral metastatic disease

  • Targeted therapy is beneficial in molecularly-selected tumours, including erlotinib in EGFR-mutant lung tumours, crizotinib in lung carcinomas with EML4ALK translocations, trastuzumab in HER2+ breast cancer and dabrafenib in BRAF-mutant melanoma

Abstract

Metastatic tumours involving the brain overshadow primary brain neoplasms in frequency and are an important complication in the overall management of many cancers. Importantly, advances are being made in understanding the molecular biology underlying the initial development and eventual proliferation of brain metastases. Surgery and radiation remain the cornerstones of the therapy for symptomatic lesions; however, image-based guidance is improving surgical technique to maximize the preservation of normal tissue, while more sophisticated approaches to radiation therapy are being used to minimize the long-standing concerns over the toxicity of whole-brain radiation protocols used in the past. Furthermore, the burgeoning knowledge of tumour biology has facilitated the entry of systemically administered therapies into the clinic. Responses to these targeted interventions have ranged from substantial toxicity with no control of disease to periods of useful tumour control with no decrement in performance status of the treated individual. This experience enables recognition of the limits of targeted therapy, but has also informed methods to optimize this approach. This Review focuses on the clinically relevant molecular biology of brain metastases, and summarizes the current applications of these data to imaging, surgery, radiation therapy, cytotoxic chemotherapy and targeted therapy.

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Figure 1: The key molecular alterations in the primary cancers that most commonly metastasize to the brain.

Change history

  • 06 March 2014

    In the version of this article initially published online, details of Jack Arbiser’s primary affiliation were omitted from the correspondence section, and should have included 'Atlanta Veterans Administration Medical Center'. The error has been corrected for the print, HTML and PDF versions of the article.

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T.K.O., J.A., A.Z., A.R. and M.K.M. researched the data for this article. T.K.O., J.A., A.Z., H.-K.G.S., A.M.R., S.N.K. and J.J.O. made substantial contributions to all other stages of the preparation of the manuscript for submission. In addition, T.R. and K.M.E. contributed substantially to discussion of content and the writing of the article. T.G.W., B.S., N.L.T. and M.K.M. also made considerable contributions to the writing of the article.

Correspondence to Jeffrey J. Olson.

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Owonikoko, T., Arbiser, J., Zelnak, A. et al. Current approaches to the treatment of metastatic brain tumours. Nat Rev Clin Oncol 11, 203–222 (2014) doi:10.1038/nrclinonc.2014.25

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