Radiosurgery for brain metastases and cerebral edema

Abstract

The objective of this study was to assess reduction in cerebral edema following linear accelerator radiosurgery (LINAC) as first line therapy for brain metastasis. We reviewed the medical records of all patients who underwent LINAC radiosurgery for brain metastasis at our institution during 2010–2012, and who had not previously undergone either surgery or whole brain radiotherapy. Data were analyzed for 55 brain metastases from 46 patients (24 males), mean age 59.9 years. During the 2 months following LINAC radiosurgery, the mean steroid dose decreased from 4.8 to 2.6 mg/day, the mean metastasis volume decreased from 3.79 ± 4.12 cc to 2.8 ± 4.48 cc (p = 0.001), and the mean edema volume decreased from 16.91 ± 30.15 cc to 12.85 ± 24.47 cc (p = 0.23). The 17 patients with reductions of more than 50% in brain edema volume had single metastases. Edema volume in the nine patients with two brain metastases remained stable in five patients (volume change <10%, 0–2 cc) and increased in four patients (by >10%, 2–14 cc). In a subanalysis of eight metastases with baseline edema volume greater than 40 cc, edema volume decreased from 77.27 ± 37.21 cc to 24.84 ± 35.6 cc (p = 0.034). Reductions in brain edema were greater in metastases for which non-small-cell lung carcinoma and breast cancers were the primary diseases. Overall, symptoms improved in most patients. No patients who were without symptoms or who had no signs of increased intracranial pressure at baseline developed signs of intracranial pressure following LINAC radiosurgery. In this series, LINAC stereotactic radiosurgery for metastatic brain lesions resulted in early reduction in brain edema volume in single metastasis patients and those with large edema volumes, and reduced the need for steroids.

Introduction

Metastases are the most common tumors of the central nervous system. The most common primary cancers associated with brain metastases are lung, breast, melanoma, renal and colorectal cancers [1]. The prognosis of patients with brain metastases is generally poor; the median survival ranges from 2.3 to 7.1 months [2]. Thus, the treatment of brain metastases is mainly palliative.

Several hypotheses of tumor related edema have been postulated, including secretion of vascular endothelial growth factor, inflammatory cytokines, arachidonic acid metabolites, and destruction of the blood–brain barrier by the tumor itself [3]. Edema adds to the mass of the tumor, increases intracranial pressure (ICP), and disrupts tissue homeostasis by reducing local blood flow [4]. The symptoms of edema can be related to its location, resulting in hemiparesis, epilepsy, visual field defect, aphasia and other focal neurological deficits; or related to increased ICP, with headache worsening in the morning, nausea and vomiting, abnormal eye movements, and impaired consciousness [5]. Reducing tumor related edema may be as important to quality of life as controlling the tumor.

Stereotactic radiosurgery (SRS) plays a substantial role in brain metastasis tumor control and affords many patients improved survival and quality of life. Radiosurgery can be used to treat multiple metastases during the same procedure and permits treatment of deep deposits considered surgically inaccessible [3], [6], [7]. SRS enables delivery of a high dose of radiation, precisely focused to the tumor, while minimizing the radiation absorbed by normal surrounding brain tissue. In contrast with whole brain radiotherapy (WBRT), SRS is less likely to cause neurological toxicity. In contrast with surgery, SRS is a minimally invasive outpatient procedure that does not require general anesthesia, has wide applicability, lower costs, shorter recovery time, and lower post-treatment morbidity [2]. SRS has become an increasingly popular procedure, as a first-line therapy, as a repeated therapy, and as an adjunctive therapy to surgery and WBRT.

Linear accelerator (LINAC) is an SRS technique that has demonstrated effectiveness in controlling brain tumor size [8], [9], [10], and in prolonging survival [11]. Nevertheless, only a few studies have investigated the effects of SRS on cerebral edema. Reduction in cerebral edema following Gamma Knife (Elekta AB, Stockholm, Sweden) radiosurgery (RS) was found to be associated with improved quality of life outcomes, though not with prolonged survival [3]. For meningioma, SRS treatment demonstrated a low incidence of toxicity; risk factors for increased post-treatment edema were large tumor volumes and single-fraction SRS treatment [12].

In this study, we assessed the reduction in cerebral edema following LINAC SRS as a first line therapy for brain metastasis.