Clinical investigation: central nervous system
Metastatic melanoma to the brain: prognostic factors after gamma knife radiosurgery

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Abstract

Purpose: To identify important prognostic factors predictive of survival and tumor control in patients with metastatic melanoma to the brain who underwent gamma knife radiosurgery.

Methods and Materials: A total of 122 consecutive patients with 332 intracranial melanoma metastases underwent gamma knife radiosurgery over a 5-year period. Of these, 39 (32%) also received whole-brain irradiation (WBI). The median tumor volume was 0.8 cm3 (range: 0.02–30.20 cm3), and the median prescribed dose was 20 Gy (range: 14–24 Gy). Median follow-up was 6.8 months. Univariate and multivariate analyses of survival and freedom from progression were performed using the following parameters: status of systemic disease, intracranial tumor volume, number of lesions, tumor location, Karnofsky performance status, gender, age, and WBI.

Results: Overall median survival was 7.0 months from time of radiosurgery and 9.1 months from the onset of brain metastasis. In multivariate analysis, improved survival was noted in patients with total intracranial tumor volume <3 cm3 (p = 0.003) and inactive systemic disease (p = 0.0065), whereas other parameters studied were of lesser importance (tumor location, p = 0.056, and Karnofsky performance status, p = 0.086), or of no significance (number of lesions, WBI, age, and gender). Freedom from subsequent brain metastasis depended on intracranial tumor volume (p = 0.0018) and status of systemic disease (p = 0.034).

Conclusions: Stereotactic radiosurgery is an effective treatment modality for patients with intracranial metastatic melanoma. Tumor volume and status of systemic disease are good independent predictors of survival and freedom from tumor progression.

Introduction

For the past few decades, there has been a steady increase in the incidence and mortality of patients with melanoma 1, 2. Melanoma is of major importance for the development of brain metastases, because it represents the third most common cause of this disease after primary tumors of the lung and breast 3, 4, 5. Melanoma metastasis to the brain is a serious problem, because affected patients experience a sharp decrease in quality of life and poor survival 2, 3, 6, 7, 8. Rapid deterioration and death resulting from progressive central nervous system disease is a norm in untreated patients. In one report, median survival for patients with untreated intracranial melanoma was <1 month (8). Various treatment modalities have been used individually and in combination in the management of patients with melanoma metastatic to the brain. These treatment modalities include the following: surgical resection with and without whole-brain irradiation (WBI) 9, 10, 11, 12, 13, 14, 15, 16, WBI 17, 18, 19, 20, chemotherapy (2), immunotherapy (21), and stereotactic radiosurgery 22, 23, 24, 25, 26. Despite earlier detection of frequently asymptomatic metastatic disease with the use of contemporary imaging modalities, the prognosis in patients with intracranial metastatic melanoma remains poor. The reported median survival ranges from 2 to 8 months 2, 4, 5, 6, 8, 27.

In this report, we have assessed the influence of multiple prognostic factors on survival and freedom from progression (FFP) in a series of consecutive patients treated with stereotactic radiosurgery in a single medical center during a 5-year period.

Section snippets

Patients

Between August 1994 and October 1999, a total of 122 consecutive patients with metastatic intracranial melanomaunderwent gamma knife stereotactic radiosurgery (GK) at the University of Southern California Keck School of Medicine. There were 167 radiosurgery sessions used to treat 332 brain metastases. Most (70%) patients were males, with a median age of 55 years. A total of 61 (50%) patients presented with a solitary lesion, whereas 26 (21%) had two lesions at diagnosis (Table 1). Median tumor

Results

Overall median survival was 7 months, and the 1-year survival was 26% (Fig. 1). The median survival from the onset of brain metastasis was 9.1 months and from the original diagnosis of melanoma was 46.7 months. At the end of this study, 107 (88%) patients were known to have died, 10 (8%) were alive, and 5 (4%) were lost to follow-up. The cause of death could be determined in 86 of the patients known to have died during the data capture period. Death from systemic disease occurred in 49 (46%)

Discussion

Fractionated radiotherapy has been widely accepted as a treatment of choice for patients with brain metastases since the reports of its effectiveness in the early 1950s (18). The reported median survival after WBI for patients with tumors such as melanoma metastatic to the brain was only 10–14 weeks (30). Several retrospective studies evaluating treatment efficacy in patients with this disease showed an improvement in median survival from 3.3 to 8.4 months after surgical resection followed by

Conclusion

Stereotactic radiosurgery is a safe, minimally invasive, and effective treatment modality for patients with intracranial metastatic melanoma. Total intracranial tumor volume was the most important predictor of survival, local tumor control, and freedom from subsequent brain metastasis. A routine screening for brain metastasis in asymptomatic, high-risk patients with melanoma may be of relevance. Application of early therapy for lower-volume lesions should be expected to result in improved

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