Chapter 12 - Neurocognitive aspects of brain metastasis
Introduction
Patients with brain metastasis represent a very heterogeneous and large patient population: upwards of 17% of all cancer patients eventually develop disease in the brain (Nayak et al., 2012). Improvements in diagnosis and efficacy of systemic therapies will likely result in an even higher incidence of brain metastasis in the future. Treatment of patients with metastatic cancer can be complicated by the need to address disease both within and outside the central nervous system (CNS). Although many systemically administered therapies are believed to have limited penetration across the bloodābrain barrier, CNS toxicities have been observed and some agents have demonstrated efficacy in terms of disease control and/or response within the CNS compartment. The historic mainstays of treatment for patients with brain metastasis have been surgery, radiosurgery, and whole-brain radiation therapy (WBRT). All of these approaches carry potential risks of off-target as well as on-targetāoff-tumor adverse effects that can be manifest as neurocognitive dysfunction.
Section snippets
Impact of prior therapies: chemotherapy-related neurocognitive impairment
The most common primary cancers that metastasize to the brain include lung, breast, melanoma, renal, and colorectal. However, there is variation in when during a patient's disease course brain metastasis is diagnosed. For example, patients with lung cancer frequently develop brain metastasis at the time of diagnosis or shortly thereafter; in contrast, patients with breast and renal cancer often develop brain metastasis years after initial diagnosis and treatment (Nayak et al., 2012). Given this
Impact of tumor: neurocognitive function in brain metastasis patients at diagnosis
The impact of a brain mass on neurocognitive function is primarily related to the location of the lesion, its size, rate of growth, and the extent of surrounding edema. Neurocognitive evaluation prior to any treatment has demonstrated that these baseline deficits are common in patients with brain metastasis (Sherman et al., 2002; Herman et al., 2003; Mehta et al., 2003; Meyers et al., 2004; Chang et al., 2009). Prevalence rates vary among studies, based primarily on the sensitivity of
Surgery
The resection of a single brain metastasis is frequently considered the best treatment option in patients with accessible lesions causing mass effect, good performance status, and well-controlled systemic disease (Vogelbaum and Suh, 2006). The hallmark study conducted by Patchell and colleagues (1990) randomized 48 patients with single brain metastases to surgery and WBRT (25 patients) compared with WBRT alone (23 patients) and evaluated local recurrence and survival rates. The addition of
Neurocognitive function in clinical trials: performance-based tests
Past and current clinical trials described below have used the clinical trial battery (Wefel et al., 2011a) of neurocognitive tests that includes the Hopkins Verbal Learning Test ā Revised (Benedict et al., 1998), Trail Making Test (Tombaugh, 2004), and Multilingual Aphasia Examination Controlled Oral Word Association (Ruff et al., 1996). This core battery of tests has been reviewed in detail elsewhere and recommended for inclusion in trials assessing neurocognition (van den Bent et al., 2011;
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Cited by (22)
Neurological complications of breast cancer
2022, Neurological Complications of Systemic Cancer and Antineoplastic TherapyBrain metastasis models: What should we aim to achieve better treatments?
2021, Advanced Drug Delivery ReviewsCitation Excerpt :Additionally, metastatic outgrowth in the brain frequently impairs patient neurocognition [88], which is a major contributor to the morbidity of this type of metastasis and might also involve additional therapeutic strategies and cognitive rehabilitation [57]. Although this problem is clinically well-documented and there are established tests to evaluate neurocognitive decline in patients with brain metastasis [286], there is no knowledge on the underlying pathophysiology rather than the mass effect, which does not always explain the variability among patients regarding the degree of cognitive impact [111]. Emerging interests to understand this aspect that applies to many brain tumors could generate additional organ-specific strategies to improve the prognosis of patients with brain metastasis [170].
Initial Approach to the Patient with Multiple Newly Diagnosed Brain Metastases
2020, Neurosurgery Clinics of North AmericaCitation Excerpt :However, reduced rates of intracranial relapse do not translate into significant prolongation of overall survival or functionally independent survival in patients treated with WBRT in addition to SRS, versus SRS alone.15ā18 Furthermore, WBRT is associated with significant neurocognitive decline.19 Post-WBRT patients show decreased performance on a battery of cognitive tests, such as delayed recall,20 with greater than 90% of patients showing cognitive decline in the 3 months following WBRT + SRS versus 63.5% who underwent SRS alone.16
Death Anxiety in Patients With Metastatic Non-Small Cell Lung Cancer With and Without Brain Metastases
2020, Journal of Pain and Symptom ManagementCitation Excerpt :The shortened life expectancy and adverse neurological sequelae associated with brain metastases may increase death anxiety. Cognitive decline is common in both central nervous system and non-central nervous system cancers, but the development of brain metastases and their treatment increase the risk for such decline.20ā25 Cognitive decline can significantly impede daily functioning and may be a signal of disease progression to patients, heightening their death anxiety.26
Radiosurgery and Immunotherapy in the Treatment of Brain Metastases
2019, World NeurosurgeryCitation Excerpt :Strategies in this scenario differ considerably. The available evidence in patients with more than 4 brain metastases indicates that whole brain radiotherapy enhances brain control, but this occurs at the expense of neurocognitive deterioration and is associated with questionable survival benefit.2,5,6 Because of these drawbacks, many offer SRS to patients with more than 4 brain metastases as a first-choice treatment.7-11