Clinical investigation
Brain
Gamma-Knife radiosurgery in the management of melanoma patients with brain metastases: A series of 106 patients without whole-brain radiotherapy

https://doi.org/10.1016/j.ijrobp.2006.01.024Get rights and content

Purpose: To assess retrospectively a strategy that uses Gamma-Knife radiosurgery (GKR) in the management of patients with brain metastases (BMs) of malignant melanoma (MM).

Methods: GKR without whole-brain radiotherapy (WBRT) was performed for patients with Karnofsky Performance Status (KPS) of 60 or above who harbored 1 to 4 BMs of 30 mm or less and was repeated as often as needed. Survival was assessed in the whole population, whereas local-control rates were assessed for patients with follow-up longer than 3 months.

Results: A total of 221 BMs were treated in 106 patients; 61.3% had a single BM. Median survival from the time of GKR was 5.09 months. Control rate of treated BMs was 83.7%, with 14% of complete response (14 BMs), 42% of partial response (41 BMs), and 43% of stabilization (43 BMs). In multivariate analysis, survival prognosis factors retained were KPS greater than 80, cortical or subcortical location, and Score Index for Radiosurgery (SIR) greater than 6. On the basis of KPS, BM location, and age, a score called MM-GKR, predictive of survival in our population, was defined.

Conclusion: Gamma-Knife radiosurgery provides a surgery-like ability to obtain control of a solitary BM and could be consider as an alternative treatment to the combination of GKR+WBRT as a palliative strategy. MM-GKR classification is more adapted to MM patients than are SIR, RPA and Brain Score for Brain Metastasis.

Introduction

Radiosurgery (RS) is a stereotaxic noninvasive procedure that allows treatment of cerebral lesions by focal delivery of a single high dose of radiation by use of multiple narrow beams. Gamma-Knife radiosurgery (GKR) involves the strict convergence of 201 γ-rays arising from a 60Co source. This procedure allows obtaining a rapid dose falloff and minimizes risk of damage to surrounding healthy brain cells. The first series of RS treatments that focused on brain metastasis (BM) date from the 1980s (1, 2, 3, 4). They raised a lot of interest because they provided an alternative to surgery with minimal invasiveness, low morbidity, low impact on the quality of life, and similar local-control rates (5, 6, 7, 8). They also offer the possibility to treat several lesions simultaneously (9).

Malignant melanoma (MM) is reported to be the third cause of BM after lung and breast tumors, with an incidence of 6% to 43% in clinical series and of 12% to 74% in autopsy series (10). Lesions are multifocal in 66% of cases (11), and median survival time without treatment is about 3 to 8 weeks (12, 13, 14, 15). Because of the usual resistance of MM cells to radiotherapy, patients with isolated or localized small-volume BM are usually considered for surgical resection with 5 to 22 months median survival time (10). For patients with multiple BMs, palliative therapeutic options are whole-brain radiotherapy (WBRT), chemotherapy with fotemustine, eldisine, or temozolomide, or WBRT plus chemotherapy. However, the efficacy of these procedures is quite limited, with median survival of 12 to 20 weeks (16).

Several retrospective studies have described the effects of treatment that combines GKR and WBRT in patients with BM of MM (4, 11, 17, 18, 19, 20, 21, 22). This strategy gives local control rates of 80% to 90% (23), similar to surgical procedures, with the possibility to treat a higher proportion of patients, that is, patients usually contraindicated for surgery and those with multiple or inaccessible BMs (24). In the context of low and uncertain efficacy of WBRT, we used GKR alone, to avoid additional restriction in the patient life for an uncertain additive benefit and to prevent the development of cognitive deleterious effects of WBRT, such as memory loss and low-grade dementia.

We report retrospectively the results of the GKR treatment of 106 patients with BM of MM. Our main objective was to study the overall survival after GKR in the whole population and the factors that best predicted it. A secondary objective was to assess the local-control rate of BM in patients with sufficient follow-up.

Section snippets

Patient’s selection

All MM patients with BM from the dermatology departments treated at the Neurosurgery-Radiosurgery Department (Hôpital La Timone) in Marseille, France, between 1997 and 2003 were included in the study. Selection criteria for GKR treatment were the presence of 1 to 4 BMs detectable on a CT-scan, with maximal diameter under 30 mm, Karnofsky Performance Status (KPS) of 60 or higher, and absence of immediately life-threatening metastases elsewhere. Furthermore, patients should not have been included

Patients and metastatic disease

A total of 106 patients were treated with GKR during the study. Population and BM characteristics at the time of first GKR treatment are summarized in Table 1. Among the 106 patients, 65 (61.3%) presented with a single BM, which was solitary in 22 patients (20.7%) (i.e., single BM without other visceral metastasis). Among the 41 patients (38.7%) with multiple BMs, 12 (11.3%) were also free of other visceral metastasis.

Forty patients (38%) presented with neurologic symptoms related to BM: 13

Discussion

This series of melanoma BM is one of the largest treated by GKR (4, 11, 17, 18, 19, 20, 22, 34, 35) and the largest that used RS alone without WBRT. This study confirms a high rate of local control close to that of surgical series, with minimal restriction in the patient life, even if a long survival was observed only in a minority of patients. Moreover, GKR was repeated as often as required, with survival results comparing favorably with those of previous series that used a combination of GKR

Acknowledgments

The authors are grateful to J. Gouvernet for statistical support and to Dr. C. Delsanti for radiologic assistance.

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