Management of Complications From Brain Metastasis Treatment

A Narrative Review

Kevin Diao; Alan J. Sosa; Gabriel Zada; Seema Nagpal; Eric L. Chang


Chin Clin Oncol. 2022;11(2):11 

In This Article

Abstract and Introduction


Objective: To describe the range of potential side effects associated with modern brain metastasis treatment and provide evidenced-based guidance on the effective management of these side effects.

Background: Brain metastases are the most commonly diagnosed malignant intracranial tumor and have historically been associated with very poor prognosis. The standard treatment for brain metastases until the 1990s was whole-brain radiation therapy (WBRT) alone. Since then, however, numerous advances have established the role of neurosurgical resection, stereotactic radiosurgery (SRS), targeted systemic therapy, and immunotherapy in the multidisciplinary management of brain metastases and led to improvements in intracranial control, survival, and neurocognitive preservation among patients with brain metastases. As a result, however, brain metastasis treatment is associated with a wider range of potential side effects than ever before, and clinicians are tasked with the challenge of effectively managing these side effects without compromising cancer outcomes.

Methods: We performed a narrative review of peer-reviewed articles related to the management of side effects from multidisciplinary brain metastasis treatment and synthesized the data in the context of our clinical experience and practice.

Conclusions: In this review, we summarize the major complications from intracranial radiotherapy, neurosurgical resection, and brain metastasis directed systemic therapy with corresponding evidenced-based, modern management principles to guide the practicing oncologist.


Brain metastases represent the most commonly diagnosed malignant intracranial tumor,[1] occurring in up to half of all patients with cancer.[2] The incidence of brain metastases is increasing because of improved imaging modalities allowing for more accurate detection of brain metastases, better awareness among oncologists leading to more frequent surveillance imaging, and improved cancer therapies which have led to longer periods of time during which brain metastases may develop.[3,4] In addition, improved systemic therapies used in the metastatic setting may not achieve the same effects in the central nervous system (CNS) due to the blood-brain barrier.[5]

Historically, brain metastases were near-uniformly associated with poor outcomes. The standard treatment for brain metastases until the 1990s was whole-brain radiation therapy (WBRT) alone, which was associated with a median survival of 3–6 months.[6] Since then, however, a plethora of research and treatment advances has fundamentally transformed the landscape of brain metastasis management. Level I data showed the addition of surgical resection to WBRT for patients with a single brain metastasis improved overall survival (OS), and the addition of WBRT to surgical resection improved local and distant brain control and neurologic death, establishing the role of selective surgical resection in patients with brain metastases.[6,7] Multiple trials compared stereotactic radiosurgery (SRS) versus SRS + WBRT for patients with limited brain metastases and found similar OS but better neurocognitive preservation and health-related quality-of-life (QOL) with SRS alone.[8–11] Two trials examined the role of post-operative SRS which found improved local control (LC) compared to observation[12] and better QOL compared to WBRT.[13]

More recently, targeted systemic agents and immunotherapy have demonstrated clinically meaningful intracranial activity in patients with certain cancer histologies.[2,14–17] In some carefully selected patients with brain metastases, systemic agents can be used as a frontline treatment option. Certain novel immunotherapy agents are postulated to have a synergistic effect with radiotherapy and may offer an intracranial control and OS benefit when combined with SRS.[18,19]

As patients survive longer following brain metastasis treatment, however, late neurologic complications from brain metastasis directed therapy are also becoming more likely. Furthermore, due to the number of treatment options now available, clinicians are faced with a wide range of potential treatment-related complications in patients with brain metastases from radiotherapy, surgical resection, and systemic therapy and managing these complications appropriately is increasingly complex. In this review, we aim to describe the major potential complications from brain metastasis treatment with an emphasis on modern, evidenced-based clinical management. We present the following article in accordance with the Narrative Review reporting checklist (available at