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Role of Whole-Brain Radiotherapy

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Central Nervous System Metastases

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Abstract

Whole-brain radiotherapy (WBRT) has been integral to the management of brain metastases for several decades. Early studies demonstrated the efficacy of WBRT in relieving neurologic symptoms related to intracranial disease and improving survival for patients with brain metastases. However, concerns over cognitive side effects with conventional WBRT and improvements in local treatment techniques have led to a shifting dynamic in how and when WBRT is used. As a result, focal therapies involving stereotactic radiosurgery (SRS) with or without surgical resection have been increasingly used as an alternative to conventional WBRT in patients with limited brain metastases at a cost of increased risk of distant brain relapse and use of salvage therapies. Subsequent trials demonstrating cognitive preservation using neuroprotective strategies of prophylactic memantine and hippocampal avoidance have led to efforts seeking to redefine the role of WBRT, especially since prior trials comparing cognitive outcomes between focal therapy and WBRT did not include these neuroprotective strategies and no longer apply in the modern WBRT era.

In recent years, multiple attempts have been made to optimize the efficacy of WBRT. The most common dose prescription for WBRT is 30 Gy in 10 fractions, though other dosing regimens have been studied without proven superiority. The use of systemic agents during and following WBRT has also been studied extensively. Although enthusiasm for radiosensitizers was sparked by studies of motexafin gadolinium showing benefits in non-small cell lung cancer, other radiosensitizers have failed to show added value. The use of targeted agents and immune checkpoint inhibitors with WBRT remain areas of active study.

Radiation-related toxicity secondary to conventional WBRT manifests as early, early-delayed, and late delayed forms, with the last one being the most permanent. This toxicity ranges from mild cognitive impairment to rarely dementia and can be a concern for patients and clinicians alike. However, practice-changing clinical trials have demonstrated that prophylactic memantine, combined with minimal radiation dose to the hippocampal neural stem cell compartment (hippocampal avoidance), prevents cognitive toxicity in patients undergoing WBRT. This chapter traces the course of the research that established the use of WBRT and discusses the evolving role and delivery of WBRT in contemporaneous management of brain metastases. In order to improve care for patients requiring WBRT, knowledge of the optimal candidates for WBRT and techniques for safer delivery of WBRT are important.

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Authors and Affiliations

  1. Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Connor Lynch

  2. Department of Radiation Oncology, Northwestern University, Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, USA

    Jeffrey P. Gross

  3. Brain and Spine Tumor Center, Department of Radiation Oncology, Northwestern Medicine Cancer Center Warrenville, Warrenville, IL, USA

    Vinai Gondi

  4. Northwestern Medicine Chicago Proton Center, Warrenville, IL, USA

    Vinai Gondi

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  1. Connor Lynch
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Correspondence to Vinai Gondi .

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Editors and Affiliations

  1. Department of Neurological Surgery, NewYork-Presbyterian Hospital/Weill Cornell Medicine, Director - Brain Metastases Program, New York, NY, USA

    Rohan Ramakrishna

  2. Department of Neurology, NewYork-Presbyterian Hospital/Weill Cornell Medicine, New York, NY, USA

    Rajiv S. Magge

  3. Department of Neurological Surgery, NewYork-Presbyterian Hospital/Weill Cornell Medicine, New York, NY, USA

    Ali A. Baaj

  4. Department of Radiation Oncology, NewYork-Presbyterian Hospital/Weill Cornell Medicine, New York, NY, USA

    Jonathan P.S. Knisely

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Lynch, C., Gross, J.P., Gondi, V. (2020). Role of Whole-Brain Radiotherapy. In: Ramakrishna, R., Magge, R., Baaj, A., Knisely, J. (eds) Central Nervous System Metastases. Springer, Cham. https://doi.org/10.1007/978-3-030-42958-4_20

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