Summary of recommendations and practice points: Treatment approaches to brain metastases for patients with melanoma
Evidence summary: systematic drug therapy
|Combined therapy with BRAF and MEK inhibitors induces an intracranial response of 58% in patients with asymptomatic untreated brain metastases whose melanoma has a V600E BRAF mutation.||III-1|||
|Anti-PD-1 monotherapy in drug treatment-naïve patients induces an intracranial response in at least 20% of patients with active melanoma brain metastases.||III-1||, |
|Combined ipilimumab and nivolumab in drug treatment-naïve patients induces an intracranial response in approximately 55% of patients with active brain metastases. (In drug treatment-naïve patients, phase II studies demonstrated 56% and 55% intracranial response rates in the Australian Brain Collaboration and the CheckMate 204 studies, respectively, with 6-month PFS rates of 53% and 67%, respectively).||III-1||, |
Evidence summary: surgical approaches
|Local control rates after surgical resection are very high, in the order of 80–93%||I, III-2||, , , , |
|Surgery is highly effective in relieving symptoms and improving functional outcome.||I, III-2||, , , |
|Perioperative surgical mortality is approximately 2% whilst complications occur in 6–8% of patients.||III-2||, |
Brain metastases that are symptomatic or generate mass effect at presentation are best treated with surgery, with resultant rapid relief of symptoms and maintenance of functional independence.
Evidence summary: radiotherapy
|Stereotactic radiosurgery (SRS) to melanoma brain metastases achieves a high rate of local control.||III-2||, , , , |
|Stereotactic radiosurgery (SRS) may be considered for patients with single or a small number of brain metastases to maximise local control.||C|
|For patients with multiple brain metastases, whole brain radiation therapy may provide some palliative benefits.||C|
All melanoma patients with brain metastases should be reviewed at a multidisciplinary team meeting to ensure optimal drug, surgery and radiotherapy treatment combination and sequencing.
Patients with single or a small number of brain metastases should be given the opportunity to discuss the option of adjuvant radiotherapy to the surgical cavity and/or the whole brain after local treatment of the individual metastases.
- Davies MA, Saiag P, Robert C, Grob JJ, Flaherty KT, Arance A, et al. Dabrafenib plus trametinib in patients with BRAFV600-mutant melanoma brain metastases (COMBI-MB): a multicentre, multicohort, open-label, phase 2 trial. Lancet Oncol 2017 Jul;18(7):863-873 Available from: http://www.ncbi.nlm.nih.gov/pubmed/28592387.
- Goldberg SB, Gettinger SN, Mahajan A, Chiang AC, Herbst RS, Sznol M, et al. Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. Lancet Oncol 2016 Jul;17(7):976-983 Available from: http://www.ncbi.nlm.nih.gov/pubmed/27267608.
- Long GV, Atkinson V, Lo S, Sandhu S, Guminski AD, Brown MP, et al. Combination nivolumab and ipilimumab or nivolumab alone in melanoma brain metastases: a multicentre randomised phase 2 study. Lancet Oncol 2018 Mar 27 Available from: http://www.ncbi.nlm.nih.gov/pubmed/29602646.
- Tawbi HA-H, Forsyth PAJ, Algazi AP, Hamid O, Hodi FS, Moschos SJ, et al. Efficacy and safety of nivolumab (NIVO) plus ipilimumab (IPI) in patients with melanoma (MEL) metastatic to the brain: Results of the phase II study CheckMate 204. J Clin Oncol 2017;35:(suppl; abstr 9507).
- Patchell RA, Tibbs PA, Walsh JW, Dempsey RJ, Maruyama Y, Kryscio RJ, et al. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 1990 Feb 22;322(8):494-500 Available from: http://www.ncbi.nlm.nih.gov/pubmed/2405271.
- Salvati M, Frati A, D'Elia A, Pescatori L, Piccirilli M, Pietrantonio A, et al. Single brain metastases from melanoma: remarks on a series of 84 patients. Neurosurg Rev 2012 Apr;35(2):211-7; discussion 217-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/21915621.
- Lonser RR, Song DK, Klapper J, Hagan M, Auh S, Kerr PB, et al. Surgical management of melanoma brain metastases in patients treated with immunotherapy. J Neurosurg 2011 Jul;115(1):30-6 Available from: http://www.ncbi.nlm.nih.gov/pubmed/21476810.
- Miller D, Zappala V, El Hindy N, Livingstone E, Schadendorf D, Sure U, et al. Intracerebral metastases of malignant melanoma and their recurrences--a clinical analysis. Clin Neurol Neurosurg 2013 Sep;115(9):1721-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23643143.
- Carrubba CJ, Vitaz TW. Factors affecting the outcome after treatment for metastatic melanoma to the brain. Surg Neurol 2009 Dec;72(6):707-11 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19604550.
- Fife KM, Colman MH, Stevens GN, Firth IC, Moon D, Shannon KF, et al. Determinants of outcome in melanoma patients with cerebral metastases. J Clin Oncol 2004 Apr 1;22(7):1293-300 Available from: http://www.ncbi.nlm.nih.gov/pubmed/15051777.
- Paek SH, Audu PB, Sperling MR, Cho J, Andrews DW. Reevaluation of surgery for the treatment of brain metastases: review of 208 patients with single or multiple brain metastases treated at one institution with modern neurosurgical techniques. Neurosurgery 2005 May;56(5):1021-34; discussion 1021-34 Available from: http://www.ncbi.nlm.nih.gov/pubmed/15854250.
- Schödel P, Schebesch KM, Brawanski A, Proescholdt MA. Surgical resection of brain metastases-impact on neurological outcome. Int J Mol Sci 2013 Apr 24;14(5):8708-18 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23615466.
- Zacest AC, Besser M, Stevens G, Thompson JF, McCarthy WH, Culjak G. Surgical management of cerebral metastases from melanoma: outcome in 147 patients treated at a single institution over two decades. J Neurosurg 2002 Mar;96(3):552-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/11883841.
- Nieder C, Grosu AL, Gaspar LE. Stereotactic radiosurgery (SRS) for brain metastases: a systematic review. Radiat Oncol 2014 Jul 12;9:155 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25016309.
- Bernard ME, Wegner RE, Reineman K, Heron DE, Kirkwood J, Burton SA, et al. Linear accelerator based stereotactic radiosurgery for melanoma brain metastases. J Cancer Res Ther 2012 Apr;8(2):215-21 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22842364.
- Christ SM, Mahadevan A, Floyd SR, Lam FC, Chen CC, Wong ET, et al. Stereotactic radiosurgery for brain metastases from malignant melanoma. Surg Neurol Int 2015;6(Suppl 12):S355-65 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26392919.
- Rades D, Sehmisch L, Huttenlocher S, Blank O, Hornung D, Terheyden P, et al. Radiosurgery alone for 1-3 newly-diagnosed brain metastases from melanoma: impact of dose on treatment outcomes. Anticancer Res 2014 Sep;34(9):5079-82 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25202094.
- Bates JE, Youn P, Usuki KY, Walter KA, Huggins CF, Okunieff P, et al. Brain metastasis from melanoma: the prognostic value of varying sites of extracranial disease. J Neurooncol 2015 Nov;125(2):411-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26354772.