Current approaches to the management of brain metastases

Abstract

Brain metastases are a very common manifestation of cancer that have historically been approached as a single disease entity given the uniform association with poor clinical outcomes. Fortunately, our understanding of the biology and molecular underpinnings of brain metastases has greatly improved, resulting in more sophisticated prognostic models and multiple patient-related and disease-specific treatment paradigms. In addition, the therapeutic armamentarium has expanded from whole-brain radiotherapy and surgery to include stereotactic radiosurgery, targeted therapies and immunotherapies, which are often used sequentially or in combination. Advances in neuroimaging have provided additional opportunities to accurately screen for intracranial disease at initial cancer diagnosis, target intracranial lesions with precision during treatment and help differentiate the effects of treatment from disease progression by incorporating functional imaging. Given the numerous available treatment options for patients with brain metastases, a multidisciplinary approach is strongly recommended to personalize the treatment of each patient in an effort to improve the therapeutic ratio. Given the ongoing controversies regarding the optimal sequencing of the available and expanding treatment options for patients with brain metastases, enrolment in clinical trials is essential to advance our understanding of this complex and common disease. In this Review, we describe the key features of diagnosis, risk stratification and modern paradigms in the treatment and management of patients with brain metastases and provide speculation on future research directions.

Key points

  • Many patient-related and disease-related prognostic criteria have incorporated molecular profiling into the classification schema and should be considered when estimating a patient’s prognosis following a diagnosis of brain metastases.

  • Genomic profiling of brain metastases has yielded important information about potentially actionable genomic alterations that may not be detected in the primary tumour or extracranial metastases.

  • Evolving radiotherapy techniques, such as hippocampal avoidance whole-brain radiotherapy (WBRT), mitigate the risk of neurocognitive decline following treatment.

  • Stereotactic radiosurgery (SRS) is now the primary treatment for patients with either limited or multiple brain metastases, with potential synergistic effects when combined with certain immunotherapeutic agents or targeted therapies.

  • Postoperative SRS is an alternative to WBRT for patients who undergo resection of brain metastases, with a reduced risk of neurocognitive decline; however, preoperative SRS might be favoured given the lower risks of radiation necrosis and leptomeningeal disease.

  • Developments in targeted therapies and immunotherapies for patients with non-small-cell lung cancer, breast cancer and melanoma have dramatically transformed the treatment of patients with brain metastases.

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Fig. 1: Key features of brain metastases from five common solid tumour types.
Fig. 2: Whole-exome sequencing of brain metastases matched with primary tumours, other brain metastases and extracranial metastases1.
Fig. 3: Radiation exposures during WBRT.
Fig. 4: Potential role of CEST–MRI in the management of brain metastases.

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Correspondence to John H. Suh.

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J.H.S. has acted as a consultant of AbbVie. R.K. has received honoraria from Accuray, Elekta AB, Elsevier and Novocure, and has served on the advisory board of Accuray and Novocure. S.T.C. has received honoraria from Varian Medical Systems. M.S.A. has acted as a consultant of AbbVie, Bayer, Elsevier, Flatiron, Karyopharm, Varian Medical Systems and VBI vaccines, has received royalties from Wiley, fees for contracted research from AbbVie, AstraZeneca, Bayer, BMS, Incyte, Merck, Novocure and Pharmacyclics, and owns stocks in Doctible and Mimivax. A.S. has acted as a consultant of AbbVie, BrainLAB, Elekta (Gamma Knife Icon), Merck, Roche and Varian, has served on the advisory board of VieCure and the International Stereotactic Radiosurgery Society (ISRS), has conducted educational seminars on behalf of Accuray, BrainLAB, Elekta AB and Varian (CNS Teaching Faculty), has received a research grant from Elekta AB, has received travel and accommodation fees from BrainLAB, Elekta and Varian, and is a member of the Elekta MR Linac, Elekta Spine, Oligometastases and Linac-based SRS consortia. E.L.C. declares no competing interests.

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Suh, J.H., Kotecha, R., Chao, S.T. et al. Current approaches to the management of brain metastases. Nat Rev Clin Oncol (2020). https://doi.org/10.1038/s41571-019-0320-3

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