Brain metastases
Section snippets
Epidemiologic features of brain metastases
Approximately 1.3 million individuals will be diagnosed with cancer each year in the United States.1 It has been estimated that between 100,000 and 170,000 of those patients will develop brain metastases.2, 3 Metastatic brain tumors represent the most common neurological complication of systemic cancer4 and are taking on increasing significance in clinical neuro-oncology. Approximately 10% to 15% of cancer patients will actually be diagnosed with brain metastases during their lifetimes.5 The
Molecular biology of brain metastasis and invasion
As mentioned previously, evidence indicates that the overall incidence of brain metastasis is rising because of improved cancer therapy for the systemic disease.20 Many of these new therapies (in particular, targeted antibodies) may fail to penetrate the blood-brain barrier (BBB), thereby providing a “safe harbor” for tumor recurrence in the CNS.
The possibility that microscopic seeding of distant sites has already occurred at the time of diagnosis of the primary cancer site cannot be excluded
Pathologic features of brain metastases
The intracranial and intraspinal contents may be directly involved as the result of hematogenous metastases. Alternatively, the CNS may be implicated secondarily by continuity with metastatic lesions to the adjacent bones. The great majority of metastases (approximately 80%) occur in the cerebral hemispheres; the cerebellum and brainstem are less involved (10% to 15% and 2% to 3%, respectively).62 A higher incidence (37%) of cerebral hemispheric metastases occur in the border zones of the
Diagnosis and initial management
The clinical presentation of brain metastases can be similar to that of any intracranial mass lesions and two thirds of patients with brain metastases will develop neurological symptoms during the course of their illness.70 A metachronous presentation of brain metastases should be suspected in any patient with a known primary cancer who has developed new neurological signs or symptoms. Signs and symptoms of brain metastases can be roughly divided into a “generalized” category, typically related
Imaging of brain metastases
Advances in imaging and image guidance technology have improved our ability both to diagnose and to treat metastatic brain tumors. In this section we summarize the methods used to image metastatic brain tumors and then describe the development and current use of surgical navigation technology.
MRI with gadolinium enhancement is by far the most sensitive imaging modality for both diagnosis and follow-up of patients with brain metastases.85 T2-weighted images are used to estimate the extent of
Surgery for single brain metastasis
Patients with a single brain metastasis are often best treated by surgical resection followed by adjuvant radiotherapy. In fact, gross total resection of a single brain lesion in the absence of extracranial metastases often results in long-term, high-quality survival if the primary tumor is treated aggressively. Patients who are experiencing significant, medically refractory symptoms related to brain metastases often require craniotomy for tumor removal regardless of the status of their
Surgery for multiple metastases
Surgery to resect multiple brain metastases is a relatively new concept in neuro-oncology. Traditionally, the identification of multiple brain metastases was considered a contraindication to surgical intervention, and most patients with multiple brain metastases were treated exclusively with WBRT.114, 115 Resection of multiple metastases was undertaken only in the case of life-threatening lesions or in cases in which the diagnosis was in question.62 Although WBRT is still a mainstay of
Whole-brain radiation therapy
Whole-brain radiation therapy (WBRT) has been used for decades in the management of patients with brain metastases. Early clinical trials focused on various dose and timing schedules, but no single schedule has proved superior in terms of overall survival. The recognition of potential late neurotoxicity with WBRT and the development of better imaging and focal therapies, such as microsurgical resection and radiosurgery, have shifted the research focus to study which patients are best treated
Radiosurgery for brain metastases
Stereotactic radiosurgery (SRS) is a specialized technique that utilizes beams of high-energy photons to deposit a high dose of radiation to the metastasis with relatively little radiation delivered to the surrounding normal brain. SRS is a technique that offers many of the benefits of conventional open surgery without some of the limitations. SRS does not cause the physiological stress of an open operation and can be performed in the outpatient setting. SRS may be used to treat multiple
Chemotherapy for brain metastases
Intuitively, the notion of chemotherapy for brain metastases offers appeal. Most patients who develop brain metastases have active systemic cancer, which focal brain-directed strategies do not address. Systemic failure is the cause of death in the majority of patients with brain metastases. The great majority of patients with brain metastases have multiple brain metastases. Like WBRT, chemotherapy can treat all brain metastases. Moreover, although it is unproven that chemotherapy has no
Local delivery of radiotherapy and chemotherapy at the time of surgery
The importance of focused therapies in the treatment of brain metastases has been discussed elsewhere in this monograph. Surgery and SRS are frequently utilized treatment modalities and can significantly prolong survival in many patients with metastatic brain cancer. Although patients who undergo surgical resection are thought to benefit from subsequent treatment with radiation, potential neurotoxicities associated with WBRT have led clinicians to consider other forms of adjuvant therapies such
Targeted therapies and future directions for brain metastases
Many clinical trials that evaluate novel agents for patients with refractory cancer specifically exclude patients with brain metastases because of the poor survival expectations. As a result, specific prospective clinical trials addressing the efficacy of drug therapies in patients with brain metastases are lacking. Consequently, there is a great need for the prospective evaluation of novel treatment approaches that demonstrate efficacy in targeting metastatic tumor cells (whether located in
Quality of life
Many patients with brain metastases present initially with neurocognitive impairment195, 196 along with other symptoms, although it is not uncommon for this impairment to go unrecognized. Treatments (eg, surgery, radiation, and chemotherapy) have the potential to increase or palliate neurocognitive deficits. However, studies of quality of life (QOL) and neurocognitive sequelae in patients with brain metastases are significantly underrepresented in the literature. Treatment-induced
Conclusions: survival can be extended beyond acceptable QOL
Baseline QOL has been suggested to be a significant predictor of survival in metastatic brain tumor patients,199 probably through complicated relationships among such issues as self-care, help-seeking behavior, social and caregiver support, and neurocognitive impairment of the patient. A better understanding of the interaction between QOL and survival is crucial to guide ethical decision making by physicians and families, particularly at end-of-life.
Awareness that QOL is at least as important
Recommendations
Clinical follow-up of brain tumor patients should include routine patient-oriented assessments of depression and neurocognitive impairment, and these areas should also be evaluated in clinical trials. The lack of information about tradeoffs between survival and QOL limits the ability to weigh the risks and benefits of new therapies.262 An increased understanding of the potential neurocognitive impairment in patients with brain metastases is crucial for understanding and improving QOL in this
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