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Single brain metastases from melanoma: remarks on a series of 84 patients

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Abstract

The authors report on 84 patients with single melanoma brain metastasis surgically treated from 1997 to 2007. There were 46 males and 38 females; mean age was 41 years (range 24–58 years). All patients were surgically treated, and 52 of them received postoperative adjuvant therapy consisting of whole-brain radiation therapy (36), radiosurgery (9), or a combination of these two techniques (7). Brain recurrences were observed in 44 cases, of which 9 were local. Of the latter, seven were re-operated while the remaining two were treated by radiosurgery. At 1-year follow-up, the survival rate was 52% (32 patients) whereas only 12 patients (14%) were still alive after 2 years. None of the patients in which removal was subtotal survived for more than 6 months after surgical treatment. Three years after the onset of the brain metastasis, five patients (6%) were still alive. Survival was significantly influenced by treatment with regard to overall survival reported in other series. A review of literature, together with our own series, suggests that radical surgical treatment of the lesion possibly employing the internal no-touch technique has significantly increased survival in our patients (p < 0.05) and that the association of postoperative radiotherapy and re-operation in the event of recurrent metastatic lesions is advisable even though statistical significance was not reached (p > 0.05).

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Authors and Affiliations

  1. Neurosurgery INM–Neuromed, Pozzilli (IS), University of Rome “Sapienza”, Via Cardinal Agliardi 15, 00165, Rome, Italy

    Maurizio Salvati & Alessandro Frati

  2. General Surgery–Policlinico Umberto I, University of Rome “Sapienza”, Rome, Italy

    Maurizio Fazi

  3. Department of Neurological Sciences–Neurosurgery, Policlinico Umberto I, University of Rome “Sapienza”, Rome, Italy

    Alessandro D’Elia, Lorenzo Pescatori, Manolo Piccirilli, Andrea Pietrantonio & Antonio Santoro

Authors
  1. Maurizio Salvati
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  2. Alessandro Frati
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  3. Alessandro D’Elia
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  4. Lorenzo Pescatori
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  5. Manolo Piccirilli
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  6. Andrea Pietrantonio
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  7. Maurizio Fazi
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  8. Antonio Santoro
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Correspondence to Maurizio Salvati.

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Comments

Silvia Hofer, Zürich, Switzerland

The authors report about a remarkable cohort of patients (n = 84) with single brain metastases from melanoma histology only. This retrospective series confirms that WBRT might be omitted as an adjuvant postoperative treatment since it does not affect overall survival. This has already been demonstrated in a large randomized trial by the European Organisation for Research and Treatment of Cancer (EORTC) in patients with one to three brain metastases of solid tumors [1]. Furthermore, the series demonstrates that patients with single brain metastases but with systemic disease do worse compared to solitary brain metastases (brain disease only) as we know from large RTOG trials for brain metastases of any histology using RPA, a prognostic index [2].

In line with results from other and one recently published retrospective cohort (n = 240), median survival in patients with single brain metastases from melanoma is around 7 months, which is slightly better than in patients with multiple brain metastases, most probably due to more effective local treatment (surgery and stereotactic radiosurgery) [3]. Neuroradiological follow-up for patients at high risk for CNS recurrence from melanoma, as suggested by the authors, seems not reasonable with currently available tools. The ESMO guidelines 2010 state that there is no consensus on the frequency and use of imaging techniques in the follow-up of a melanoma patient. Rising serum S-100 levels are the most accurate blood test in the follow-up of melanoma patients, if any blood test is recommended at all [4]. Although still in clinical trials, BRAF-Inhibitors and ipilimumab are worth mentioning as therapeutic options, even in the context of brain metastases in metastatic melanoma (www.clinicaltrials.gov).

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Gabriele Schackert, Dresden, Germany

The publication by Salvati and colleagues covers the important issue of treatment of cerebral metastases. The authors focus on brain metastases of the malignant melanoma, which is known to be the primary tumor with the highest incidence for cerebral seeding.

Eighty-six patients were included in the study. All patients had only one single cerebral lesion, and all were treated by surgery. Adjuvant therapy comprised radiotherapy, radiosurgery, or a combination of these two modalities.

An important finding was that none of the patients, in which removal was subtotal, survived more than 6 months. Patients benefit from complete resection, employing the no-touch technique. Thirty-two patients were treated by surgery alone, 36 patients by adjuvant radiotherapy, 9 by adjuvant radiosurgery, and the remaining by a combination of both techniques.

At 1-year follow-up, the survival rate was 52% (32 patients); at 2 years, only 12 patients were still alive; at 3 years, 5 patients. In 52.3% (44 patients), death was related to neurological causes.

The paper has three messages:

1. Complete removal of a metastasis can lead to prolonged survival. The overall diameter of the lesion and the quantity of peritumoral edema were found to be the fundamental parameters for the outcome of the patients. Lesions bigger than 3 cm3 were considered as an absolute indication for surgical treatment. Smaller lesions were optional. The authors point out that the “en bloc” resection is crucial for the avoidance of a local recurrence. This has been also published by Patel and collegues recently in 2010 [1]. However, Salvati and colleagues do not discuss the presence of an infiltration zone around the lesion, which has also been shown previously [2]. The microscopic resection including a safety zone of half a centimeter around the lesion can lead to a significant better local tumor control [3]. If we want to improve our surgical results, both aspects—en bloc resection and infiltration zone—should be respected.

2. Radiotherapy as an adjunct did not improve the overall survival; however it reduced significantly the incidence of recurrence at local and distant sites. This already has been shown by several prospective randomized trials, covering metastases of different origin. Melanoma metastases are known to be low radiosensitive. Therefore, the decision against adjuvant postsurgical WBRT might be logical. We have the same regimen in the treatment of single cerebral metastasis in our institution. We rely on the postoperative MRI. If no residual tumor can be demonstrated, adjuvant radiotherapy will not be applied. In case of residual tumor, we go for WBRT or radiosurgery.

3. In case of recurrence, the authors favor active treatment, e.g., re-operation of local or distant metastases, which improves survival and quality of life. This again is our experience. The decision for active treatment of recurrent lesions: re-operation, radiosurgery, or radiotherapy, however, should mainly depend on prognostic factors, e.g., the KPS and the progress of the extracranial tumor burden.

References

1. Patel AJ et al. (2010) Factors influencing the risk of local recurrence after resection of a single brain metastasis. J Neurosurg 113:181–189

2. Baumert BG et al. (2006) A pathology-based substrate for target definition of brain metastases. Int J Radiat Oncol Biol Phys 66:187–194

3. Yoo H et al. (2009) Reduced local recurrence of a single brain metastasis through microscopic total resection. J Neurosurg 110:730–736

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Salvati, M., Frati, A., D’Elia, A. et al. Single brain metastases from melanoma: remarks on a series of 84 patients. Neurosurg Rev 35, 211–218 (2012). https://doi.org/10.1007/s10143-011-0348-z

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