Summary of recommendations and practice points: Treatment approaches to brain metastases for patients with melanoma

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Clinical practice guidelines for the diagnosis and management of melanoma > Summary of recommendations and practice points: Treatment approaches to brain metastases for patients with melanoma


Evidence summary: systematic drug therapy

Evidence summary Level References
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 [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 [2], [3]
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 [3], [4]


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Systemic drug therapy is effective in untreated melanoma brain metastases, and can be considered as first line treatment (as an alternative to local brain therapy) in asymptomatic patients with multidisciplinary support from a radiation oncologist and a neurosurgeon.

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Evidence summary: surgical approaches

Evidence summary Level References
Local control rates after surgical resection are very high, in the order of 80–93% I, III-2 [5], [6], [7], [8], [9]
Surgery is highly effective in relieving symptoms and improving functional outcome. I, III-2 [5], [10], [11], [12]
Perioperative surgical mortality is approximately 2% whilst complications occur in 6–8% of patients. III-2 [13], [11]


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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.


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Surgical resection of brain metastases provides safe, durable local control. The use of the operating microscope, neuro navigation and en bloc resection technique are recommended. The integration of surgery with systemic therapy and radiotherapy should be discussed by a multidisciplinary team

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Evidence summary: radiotherapy

Evidence summary Level References
Stereotactic radiosurgery (SRS) to melanoma brain metastases achieves a high rate of local control. III-2 [14], [15], [16], [17], [18]
Evidence-based recommendationQuestion mark transparent.png Grade
Stereotactic radiosurgery (SRS) may be considered for patients with single or a small number of brain metastases to maximise local control.
C


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For patients with multiple brain metastases, whole brain radiation therapy may provide some palliative benefits.
C



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There are no randomised controlled trials comparing surgery with SRS for local control and quality of life. Management of brain metastases should be discussed by a multidisciplinary team. Surgical resection of brain metastases is recommended for metastases in non-eloquent areas >= 1cm or symptomatic metastases. Stereotactic radiosurgery is recommended for small (< 1cm, but maximum size to 3 cm) or multiple metastases.


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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.


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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.

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References

  1. 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 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/28592387.
  2. 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 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/27267608.
  3. 3.0 3.1 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 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/29602646.
  4. 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).
  5. 5.0 5.1 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 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/2405271.
  6. 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 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21915621.
  7. 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 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21476810.
  8. 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 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23643143.
  9. Carrubba CJ, Vitaz TW. Factors affecting the outcome after treatment for metastatic melanoma to the brain. Surg Neurol 2009 Dec;72(6):707-11 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19604550.
  10. 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 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15051777.
  11. 11.0 11.1 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 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15854250.
  12. 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 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23615466.
  13. 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 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/11883841.
  14. Nieder C, Grosu AL, Gaspar LE. Stereotactic radiosurgery (SRS) for brain metastases: a systematic review. Radiat Oncol 2014 Jul 12;9:155 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/25016309.
  15. 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 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22842364.
  16. 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 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/26392919.
  17. 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 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/25202094.
  18. 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 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/26354772.

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