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INTRODUCTION

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Advances in multimodal therapy have resulted in increased success in the management of many cancers. However, as many anticancer therapies are not highly specific, healthy tissues are also placed at risk. While traditional measures of treatment outcome have generally focused on survival time, progression-free survival, tumor response, and physiological toxicities, additional indices, including cognitive functioning and quality of life, are receiving increasing recognition as important and viable clinical endpoints. The following chapter presents evidence regarding the presence and nature of cancer- and treatment-related neurobehavioral symptoms in adult cancer patients as well as information regarding the interventions that are currently being employed against those side effects.

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COGNITIVE IMPAIRMENT

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Cancer-related Cognitive Impairment

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In order to determine whether or not cancer therapies are associated with the development of cognitive impairment, it is essential to understand the presence and pattern of these symptoms prior to the initiation of treatment. Patients with brain tumors may present with a variety of cognitive complaints as tumors destroy, crowd, and infiltrate brain tissue; the nature and severity of cognitive impairments varies in association with lesion location and lesion momentum, or the rate at which tumors grow. In non-central nervous system (CNS) cancers, several studies have demonstrated cancer-related cognitive dysfunction. For example, cognitive dysfunction in at least a subgroup of women with breast cancer has been demonstrated prior to initiation of chemotherapy, with estimates ranging from 11% 35% of patients.1,2,3,4 The first of these studies revealed particularly frequent (18–25%) difficulties on measures assessing verbal learning and memory.1 Pretreatment cognitive dysfunction has also been found in other patient populations, including acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS), in whom pretreatment impairments have been demonstrated in learning and memory (41–44%), cognitive processing speed (28%), aspects of executive dysfunction (29%), and upper extremity fine motor dexterity (37%).5 Patients with small cell lung cancer have also been shown to exhibit pretreatment cognitive impairments; Meyers et al6 demonstrated that 70% to 80% of patients with small cell lung cancer exhibited memory deficits, 38% had deficits in executive functions, and 33% showed impaired motor coordination before treatment was initiated.

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Treatment-related Cognitive Impairment

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In addition to the potential for cognitive impairment related to cancer itself, cancer therapies may have an untoward impact on cognitive functioning. This chapter will focus on the effects of chemotherapies and other agents; it is important to note that other treatment modalities, including surgery and radiation, may also result in neurobehavioral changes. In patients with brain tumors, surgery may result in damage to normal tissue that surrounds the tumor, and yield more focal cognitive impairments that may resolve over time. There is also evidence that radiation therapy may be associated with the development of neurobehavioral symptoms both during and after treatment. The acute phase develops during treatment and is characterized by transient symptoms of headache, ...

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