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Rajesh K. Bindal, Raymond Sawaya, Milam E. Leavens and J. Jack Lee

establish a diagnosis. 28, 35 For all other patients with multiple metastases, treatment is largely limited to steroids and whole-brain radiation therapy; life expectancy for these patients is 3 to 6 months. Although these represent the majority of patients with brain metastases, no previous study has specifically attempted to determine the effectiveness of aggressive surgical treatment. Clinical Material and Methods The records of 56 patients with multiple brain metastases who underwent surgical resection of one or more lesions between January, 1984, and January

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Jinyu Xue, Gregory J. Kubicek, Jimm Grimm, Tamara LaCouture, Yan Chen, H. Warren Goldman and Ellen Yorke

lesion receives up to twice the prescription dose. A dose delivered in a single fraction has a greater biological efficacy than the same dose cumulated over multiple fractions. Because of the tight targeting in SRS, normal tissues outside a treated lesion receive radiation doses that drop off fast, so the doses the tissues receive are much lower (often less than 50%) than the prescribed dose. There are 2 major concerns about using SRS rather than WBRT for treating multiple brain metastases. One is that the presence of multiple clinically detectable metastases implies

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Steven D. Chang and John R. Adler Jr.

The management of patients with multiple brain metastases remains a difficult challenge for neurosurgeons. This patient population has a poor prognosis when compared with those harboring a solitary brain metastasis, and historically treatment has generally consisted of administering whole-brain radiotherapy once the diagnosis of multiple brain metastases is made. Resection can be useful in a subset of patients with multiple metastases in whom one or two of the lesions are symptomatic, as this may provide rapid reduction of mass effect and edema. Furthermore, the authors of recent studies have shown that stereotactic radiosurgery can be used in certain patients with multiple brain metastases as part of the treatment regimen. In this review the authors outline the treatment options and indications as well as a management strategy for the treatment of patients with multiple brain metastases.

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Steven D. Chang, Elizabeth Lee, Gordon T. Sakamoto, Nalani P. Brown and John R. Adler Jr.

Object

Patients with multiple brain metastases are often treated primarily with fractionated whole-brain radiation therapy (WBRT). In previous reports the authors have shown that patients with four or fewer brain metastases can benefit from stereotactic radiosurgery in addition to fractionated WBRT. In this paper the authors review their experience using linear accelerator stereotactic radiosurgery to treat patients with multiple brain metastases.

Methods

Fifty-three patients with 149 brain metastases underwent stereotactic radiosurgery. The mean age of patients was 53.1 years (range 20–78 years). There were 23 men and 30 women. The primary tumor location was lung (27 patients), melanoma (10), breast (six), ovary (six), and other (four). All patients harbored at least two metastatic tumors treated with radiosurgery; 27 patients (51%) harbored two lesions, 17 (32%) three lesions, eight (15%) four lesions, and one patient (2%) harbored five lesions. The mean radiation dose administered was 19.6 Gy (range 14–30 Gy), and the mean secondary collimator size was 15.7 mm (range 7.5–40 mm). One hundred thirty-two (89%) of the 149 treated tumors were available for review on magnetic resonance (MR) imaging at 3 months posttreatment. Fifty-two percent were smaller in size, 31% were stable, 9% had increased in size, and 8% had disappeared. New metastatic tumors appeared in 12 (23%) of the 53 patients on MR imaging within 6 months posttreatment. Radiation-induced necrosis occurred at the site of eight (5.4%) of the 149 tumors at 6 months. Seven tumors (4.7%) subsequently required surgical resection for either tumor progression (four cases) or worsening edema from radiation-induced necrosis (three cases). Median actuarial survival was 9.6 months.

Conclusions

Stereotactic radiosurgery can be used to treat patients with up to four brain metastases with a 91% rate of either decrease or stabilization in tumor size and a low rate of radiation-induced necrosis. In the authors' study only a small number of patients subsequently required surgical resection of a treated lesion.

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Douglas Kondziolka, Atul Patel, L. Dade Lunsford and John C. Flickinger

Object

Multiple brain metastases are a common health problem, frequently found in patients with cancer. The prognosis, even after treatment with whole-brain radiation therapy (WBRT), is poor, with an average expected survival time of less than 6 months. Investigators at numerous centers have evaluated the role of stereotactic radiosurgery in retrospective case series of patients harboring solitary or multiple tumors. Tumor resection is used mainly for patients with large tumors that cause acute neurological syndromes. The authors conducted a randomized trial in which they compared radiosurgery combined with WBRT with WBRT alone.

Methods

Twenty-seven patients were randomized (14 to recieve WBRT alone and 13 to receive WBRT combined with radiosurgery). The rate of local failure at 1 year was 100% after WBRT alone but only 8% in patients in whom boost radiosurgery was performed. The median time to local failure was 6 months after WBRT alone (95% confidence interval (CI) 3.5–8.5) in comparison to 36 months (95% CI 15.6–57) after WBRT and radiosurgery (p = 0.0005). The median time to the development of any brain failure was improved in the combined modality group (p = 0.002). Survival was shown to be related to the extent of extracranial disease (p = 0.02).

Conclusions

Combined WBRT and radiosurgery for the treatment of patients with two to four brain metastases significantly improves control of brain disease. Whole-brain radiation therapy alone does not provide lasting and effective care when treating most patients. Surgical resection remains important for patients with large symptomatic tumors and in whom limited extracranial disease has been demonstrated.

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Berndt Wowra, Michael Siebels, Alexander Muacevic, Friedrich Wilhelm Kreth, Andreas Mack and Alfons Hofstetter

%) due to uncontrolled intracerebral progression (new metastases), and five (7%) due to either final tumor progression to the entire body (including the brain) or an unknown cause. Maximum length of survival after GKS was 60.7 months (minimum 10 days). Median survival time ± SE after the initial GKS was 11.1 ± 3.2 months, whereas the MST after initial diagnosis of renal cell carcinoma was 4.5 ± 1.1 years. TABLE 3 Therapeutic results and outcome in 75 patients after GKS for multiple brain metastases from renal cell carcinoma * Factor No. of

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Kwan H. Cho, Walter A. Hall, Bruce J. Gerbi and Patrick D. Higgins

Object

The authors evaluated the role of stereotactic radiosurgery (SRS) in patients with multiple brain metastases by analyzing prognostic factors that predict survival.

Methods

Between March 1991 and January 1999, 83 patients with multiple brain metastases underwent SRS in which they used a 6 mV linear accelerator. The median radiation dose of 15 Gy (range 6–50 Gy) was delivered to the 40 to 90% (median 87%) isodose line encompassing the target. Actuarial overall survival was calculated from the date of SRS by using the Kaplan–Meier method. Univariate comparisons of survival between different groups were performed using a log-rank test. All 83 patients were included in the calculation of overall survival. Actuarial overall survival was 22% at 1 year and 13% at 2 years, and a median survival of 5.4 months (range, 0.3–28.8 months) was demonstrated. Variables that predicted survival were Karnofsky Performance Scale (KPS) score, extracranial disease status, and the number of intracranial metastases. Median survival in patients with a KPS score greater than as compared with less than 70 was 9.1 and 2.7 months, respectively (p = 0.002). Median survival when comparing absence and presence of extracranial disease was 9.9 and 4.1 months, respectively (p = 0.02). Median survival in patients harboring two, three, or four or more lesions was 6.6 months, 5.4 months, and 2.7 months, respectively (p = 0.02). In patients with a KPS score greater than or equal to 70 and with three or fewer lesions, median survival was 7 months or longer. In patients with four or more lesions median survival was 7.4 months for those with no extracranial disease and 2.4 months for those with extracranial disease. Other variables tested (sex, histological tumor type, previous resection, location of metastases, treatment modality, and tumor status) did not influence outcome.

Conclusions

The absence of extracranial disease, a KPS score greater than or equal to 70, and fewer number of metastases were shown to be significant predictors of longer survival. Stereotactic radiosurgery appears to be a reasonable therapeutic option in patients with up to three lesions when their KPS score is greater than or equal to 70, regardless of extracranial disease status. In those with four or more metastases, however, SRS should be limited to those with no extracranial disease.

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Won Seok Chang, Hae Yu Kim, Jin Woo Chang, Yong Gou Park and Jong Hee Chang

for treatment of multiple brain metastases, the survival rate in our patients with more than 15 metastases appears to be good, even if this study was not a randomized or case-control study. The progression-free survival time for Group 4 was statistically shorter than those for the other groups. Given that there was no statistical difference in the local control rate between Group 4 and Groups 1, 2, and 3, the cause of the shorter progression-free survival time for Group 4 could be mainly due to more frequent remote tumor progression. Several authors have reported

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Daniel McDonald, John Schuler, Istvan Takacs, Jean Peng, Joseph Jenrette and Kenneth Vanek

H istorically , the appearance of multiple brain metastases indicated a dismal prognosis, and options for simultaneous treatment of these metastases were limited. Resection has been shown to improve quality of life and increase overall survival for patients with a single, accessible symptomatic lesion. 17 In addition, removal of 2–3 metastases exerting a mass effect has proven appropriate because the benefits of the resulting decompression are immediate. Although Bindal et al. 2 found resection of multiple lesions to be beneficial, none of the patients they

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Albertus T. C. J. van Eck and Gerhard A. Horstmann

). The MR images did not demonstrated any radiation-related side effects. Twelve months after the first GKS, local tumor control was achieved in all brain metastases. The patient complained of intermittently occurring dizziness. Until his death from pneumonia 14 months after the first GKS, the patient's neurological status remained stable and he remained in good functional condition (Karnofsky Performance Scale Score 70). Discussion We have presented the case of a patient who harbored multiple brain metastases from a very rare tumor. To the best of our knowledge ours