Brain metastases and treatment: multiplying cognitive toxicities

ABSTRACT

Introduction: Thirty per cent of cancer patients develop brain metastases, with multiple combination or sequential treatment modalities available, to treat systemic or central nervous system (CNS) disease. Most patients experience toxicities as a result of these treatments, of which cognitive impairment is one of the adverse events most commonly reported, causing major impairment of the patient’s quality of life.

Areas covered: This article reviews the role of cancer treatments in cognitive decline of patients with brain metastases: surgery, radiotherapy, chemotherapy, targeted therapies, immunotherapies and hormone therapy. Pathological and molecular mechanisms, as well as future directions for limiting cognitive toxicities are also presented. Other causes of cognitive impairment in this population are discussed in order to refine the benefit-risk balance of each treatment modality.

Expert opinion: Cumulative cognitive toxicity should be taken into account, and tailored to the patient’s cognitive risk in the light of the expected survival benefit. Standardization of cognitive assessment in this context is needed in order to better appreciate each treatment’s responsibility in cognitive impairment, keeping in mind disease itself impacts cognition in this context.

KEYWORDS:

• Brain metastases
• cognitive decline
• toxicity
• cancer
• radiotherapy
• neurology
• dementia

Article highlights

• Cancer related cognitive impairment in the context of BM should not be neglected when evaluating treatment toxicities on cognition

• Lack of consistency in cognitive assessment through clinical trials, with difficulty to compare results.

• Thorough standardized consensus guidelines evaluation of cognition are needed, with a realistic approach towards less time-consuming assessments.

• Early referral to a neurologist for correct risk assessment is recommended for assessment of the cognitive cumulative risk

• Limit whole brain radiotherapy (WBRT) indications as much as possible, which is what clinical practice is heading to. Hippocampal avoidance is a promising technique under evaluation.

• All treatment modalities are potentially toxic, with inter-activeness of different treatments.

• Within each class of treatment, different molecules probably pertain different levels of cognitive toxicity: WBRT seems to be more toxic than stereotactic radiotherapy, anthracyclines seem to pertain more cognitive toxicity than other chemotherapies, lorlatinib is an ALK inhibitor molecule with proven cognitive toxicity, TDM1 in association with radiotherapy warrants further evaluation, all hormone therapies are probably not equally neurotoxic.

• Inclusion in clinical trials of preventive or curative measures of cognitive impairment should be more frequent

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.