Clinical investigation: brain
Stereotactic radiosurgical treatment in 103 patients for 153 cerebral melanoma metastases

Presented at the 12th Annual ECCO Meeting, September 21–25, 2003 in Copenhagen, Denmark.
https://doi.org/10.1016/j.ijrobp.2003.12.037Get rights and content

Abstract

Purpose

To report on the outcome of patients with melanoma brain metastases treated with stereotactic radiosurgery (SRS).

Patients and methods

One hundred three patients with 153 intracranial melanoma metastases consecutively underwent Linac-based SRS between November 1991 and October 2001. The Kaplan-Meier method, univariate comparisons with log–rank test, and multivariate analyses with classification and regression tree models were performed. Calculations were based on last imaging date rather than the date of the last visit.

Results

Median age was 51 years (range, 18–93 years). Median Karnofsky performance status was 90. Sixty-one patients (59%) had single brain metastasis at presentation. Treatment sequence was SRS alone (61 patients), SRS + whole-brain radiotherapy (WBRT) (12 patients), and salvage SRS after WBRT (30 patients). The median tumor volume was 1.9 cm3 (range, 0.06–22.3 cm3). The median SRS minimum peripheral dose and isodose was 18 Gy (range, 10–24 Gy) and 85% (range, 60%–100%), respectively. The median follow-up was 6 months for all patients and 13 months (range, 2–46 months) for patients alive at the time of analysis. The 1-year local control (LC) for all patients treated with SRS was 49%. Among the patients treated with initial SRS alone, the 1-year LC was better for patients with tumors ≤2 cm3 than with tumors >2 cm3: 75.2% vs. 42.3% (p < 0.05). The 1-year distant brain metastasis–free survival incidence was 14.7% for the 73 patients receiving either initial SRS alone or SRS +WBRT. The initial number of brain lesions (single vs. multiple) was the only factor with a significant effect on distant brain metastasis–free survival at 1 year: 23.5% for single metastases and 0% for multiple lesions (p < 0.05). The 1-year overall survival was 25.2%. Stratification by Score Index for Radiosurgery (SIR) revealed a significant effect on survival, which was 29% at 1 year for SIR >6 and 10% for SIR ≤6 (relative hazard ratio, 2.1; p < 0.05) in classification and regression-tree multivariate analysis involving age, Karnofsky performance status, primary tumor control, tumor volume, SRS dose, SIR (>6 vs. ≤6), and systemic disease status.

Conclusions

Initial SRS alone was an effective treatment modality for smaller cerebral melanoma metastases, achieving a 75% incidence of 1-year LC for ≤2 cm3 single brain metastases and should be considered in patients with SIR >6. The role of WBRT in melanoma brain metastases cannot be addressed, owing to retrospective bias toward administering this treatment to patients with more aggressive disease. A prospective study is needed to assess the role of WBRT in patients with melanoma brain metastasis.

Introduction

Melanoma is the third most common cause of cerebral metastasis. Incidences of metastasis to the central nervous system ranging from 8% to 46% have been reported in clinical series and from 55% to 75% in autopsy series 1, 2, 3. Melanoma cerebral metastases tend to be multiple 4, 5, and the cause of death in most patients seems to be central nervous system disease rather than extracranial systemic disease 4, 6, 7. Series addressing cerebral melanoma metastases but not necessarily focusing on stereotactic radiosurgery (SRS) show that the prognosis remains poor despite treatment with a median survival of 2–5 months 2, 8, 9, 10, 11.

Reports documenting the effectiveness of SRS in treating cerebral metastases have involved primarily patients with brain metastases arising mainly from carcinoma and only a few with cerebral melanomas (12). Results of such studies may not be directly applicable to the study of cerebral melanoma metastases. Thus, large studies that focus exclusively on SRS in the treatment of cerebral melanoma metastases are needed. Previously reported SRS series focusing exclusively on patients with melanoma cerebral metastases have been relatively small 13, 14, 15, 16, 17.

To our knowledge, the present study is one of the largest SRS melanoma experiences and the largest Linac-based SRS series in melanoma that has been reported in the medical literature to date.

Section snippets

Study group

The study group comprised 103 patients who were diagnosed with melanoma metastasis to the brain. A total of 153 cerebral melanoma metastases were treated using Linac-based SRS between November 1991 and October 2001 at The University of Texas M. D. Anderson Cancer Center. For the purpose of this retrospective analysis, we identified these patients by searching our database and reviewing the patients' records. Seventy-three patients were treated initially with SRS. In addition, 30 patients were

Patient characteristics

The median age of the study population was 51 years (range, 18–93 years), and median KPS at the time of treatment was 90. Sixty-one patients (59%) presented with a single brain metastasis. According to the Radiation Therapy Oncology Group recursive partitioning analysis, 93 (90%) patients are RPA class II, 4 (4%) are RPA class III, and 6 (6%) are RPA class I. SIR, which is based on the classification system of Weltman et al. (18), was used to stratify 49 (48%) patients as ≤6 and 54 (52%)

SRS local control for melanoma brain metastases

In recent years, the use of SRS has been advocated as part of the initial management of cerebral melanoma metastases when indicated. For local control, the use of SRS has improved the reported results obtained with WBRT alone. Mori et al. reported a heterogeneous experience with a crude local control rate of 90% in that 22% of 60 patients underwent surgical resection before SRS, and 60% had adjuvant WBRT (15). Brown et al. reported on a radioresistant series that included 23 melanoma patients

Conclusion

Initial SRS alone is an effective treatment modality for cerebral melanoma when applied to selected patients with small lesions. Cerebral melanoma metastases are controlled at a rate of 75% at 1 year for single brain metastasis ≤2 cm3. The expected 1-year WBRT-free survival with this approach is approximately 60%. Initial SRS should be considered in patients with lesions ≤2 cm3 and SIR >6, because of the better prognosis. The role of WBRT in melanoma brain metastases cannot be adequately

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