Outcome predictors of Gamma Knife surgery for melanoma brain metastases

Clinical article

Restricted access


To evaluate the role of stereotactic radiosurgery (SRS) in the management of brain metastases from melanoma, the authors assessed clinical outcomes and prognostic factors for survival and tumor control.


The authors reviewed 333 consecutive patients with melanoma who underwent SRS for 1570 brain metastases from cutaneous and mucosal/acral melanoma. The patient population consisted of 109 female and 224 male patients with a median age of 53 years. Two hundred eleven patients (63%) had multiple metastases. One hundred eighteen patients (35%) underwent whole-brain radiation therapy (WBRT). The target volume ranged from 0.1 cm3 to 37.2 cm3. The median marginal dose was 18 Gy.


Actuarial survival rates were 70% at 3 months, 47% at 6 months, 25% at 12 months, and 10% at 24 months after radiosurgery. Factors associated with longer survival included controlled extracranial disease, better Karnofsky Performance Scale score, fewer brain metastases, no prior WBRT, no prior chemotherapy, administration of immunotherapy, and no intratumoral hemorrhage before radiosurgery. The median survival for patients with a solitary brain metastasis, controlled extracranial disease, and administration of immunotherapy after radiosurgery was 22 months. Sustained local tumor control was achieved in 73% of the patients. Sixty-four (25%) of 259 patients who had follow-up imaging after SRS had evidence of delayed intratumoral hemorrhage. Sixteen patients underwent a craniotomy due to intratumoral hemorrhage. Seventeen patients (6%) had asymptomatic and 21 patients (7%) had symptomatic radiation effects. Patients with ≤ 8 brain metastases, no prior WBRT, and the recursive partitioning analysis Class I had extended survivals (median 54.3 months).


Stereotactic radiosurgery is an especially valuable option for patients with controlled systemic disease even if they have multiple metastatic brain tumors.

Abbreviations used in this paper: HFS = hemorrhage-free survival; HR = hazard ratio; KPS = Karnofsky Performance Scale; OS = overall survival; PFS = progression-free survival; RPA = recursive partitioning analysis; SIR = score index of radiosurgery; SRS = stereotactic radiosurgery; WBRT = whole-brain radiation therapy.

Article Information

* Drs. Liew and Kano contributed equally to this work.

Address correspondence to: L. Dade Lunsford, M.D., Department of Neurological Surgery, University of Pittsburgh, Suite B-400, UPMC Presbyterian, 200 Lothrop Street, Pittsburgh, Pennsylvania 15213. email: lunsfordld@upmc.edu.

Please include this information when citing this paper: published online June 4, 2010; DOI: 10.3171/2010.5.JNS1014.

© AANS, except where prohibited by US copyright law.



  • View in gallery

    Kaplan-Meier plot showing OS from the time of radiosurgery for the entire patients.

  • View in gallery

    Kaplan-Meier plot showing PFS after radiosurgery.

  • View in gallery

    Kaplan-Meier plot showing the proportion of patients without new brain metastases after radiosurgery.

  • View in gallery

    Kaplan-Meier plot showing the proportion patients without intratumoral hemorrhage after radiosurgery.

  • View in gallery

    Treatment algorithm proposed for the management of melanoma brain metastases. +/-= with or without.


  • 1

    Atkins MBSosman JAAgarwala SLogan TClark JIErnstoff MS: Temozolomide, thalidomide, and whole brain radiation therapy for patients with brain metastasis from metastatic melanoma: a phase II Cytokine Working Group study. Cancer 113:213921452008

  • 2

    Bafaloukos DGogas H: The treatment of brain metastases in melanoma patients. Cancer Treat Rev 30:5155202004

  • 3

    Bamias AAravantinos GDeliveliotis CBafaloukos DKalofonos CXiros N: Docetaxel and cisplatin with granulocyte colony-stimulating factor (G-CSF) versus MVAC with G-CSF in advanced urothelial carcinoma: a multicenter, randomized, phase III study from the Hellenic Cooperative Oncology Group. J Clin Oncol 22:2202282004

  • 4

    Bhatnagar AKFlickinger JCKondziolka DLunsford LD: Stereotactic radiosurgery for four or more intracranial metastases. Int J Radiat Oncol Biol Phys 64:8989032006

  • 5

    Brown PDBrown CAPollock BEGorman DAFoote RL: Stereotactic radiosurgery for patients with “radioresistant” brain metastases. Neurosurgery 62:Suppl 27908012008

  • 6

    Buchsbaum JCSuh JHLee SYChidel MAGreskovich JFBarnett GH: Survival by radiation therapy oncology group recursive partitioning analysis class and treatment modality in patients with brain metastases from malignant melanoma: a retrospective study. Cancer 94:226522722002

  • 7

    Chang ELSelek UHassenbusch SJ IIIMaor MHAllen PKMahajan A: Outcome variation among “radioresistant” brain metastases treated with stereotactic radiosurgery. Neurosurgery 56:9369452005

  • 8

    Christopoulou ARetsas SKingsley DPaddick ILindquist C: Integration of gamma knife surgery in the management of cerebral metastases from melanoma. Melanoma Res 16:51572006

  • 9

    DiLuna MLKing JT JrKnisely JPChiang VL: Prognostic factors for survival after stereotactic radiosurgery vary with the number of cerebral metastases. Cancer 109:1351452007

  • 10

    Doss LLMemula N: The radioresponsiveness of melanoma. Int J Radiat Oncol Biol Phys 8:113111341982

  • 11

    Eisenhauer EATherasse PBogaerts JSchwartz LHSargent DFord R: New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:2282472009

  • 12

    Ellerhorst JStrom ENardone EMcCutcheon I: Whole brain irradiation for patients with metastatic melanoma: a review of 87 cases. Int J Radiat Oncol Biol Phys 49:93972001

  • 13

    Fife KMColman MHStevens GNFirth ICMoon DShannon KF: Determinants of outcome in melanoma patients with cerebral metastases. J Clin Oncol 22:129313002004

  • 14

    Gaudy-Marqueste CRegis JMMuracciole XLaurans RRichard MABonerandi JJ: Gamma-Knife radiosurgery in the management of melanoma patients with brain metastases: a series of 106 patients without whole-brain radiotherapy. Int J Radiat Oncol Biol Phys 65:8098162006

  • 15

    Geara FBAng KK: Radiation therapy for malignant melanoma. Surg Clin North Am 76:138313981996

  • 16

    Gieger MWu JKLing MNWazer DTsai JSEngler MJ: Response of intracranial melanoma metastases to stereotactic radiosurgery. Radiat Oncol Investig 5:72801997

  • 17

    Grooms GAEilber FRMorton DL: Failure of adjuvant immunotherapy to prevent central nervous system metastases in malignant melanoma patients. J Surg Oncol 9:1471531977

  • 18

    Guirguis LMYang JCWhite DESteinberg SMLiewehr DJRosenberg SA: Safety and efficacy of high-dose interleukin-2 therapy in patients with brain metastases. J Immunother 25:82872002

  • 19

    Hara WTran PLi GSu ZPuataweepong PAdler JR Jr: Cyberknife for brain metastases of malignant melanoma and renal cell carcinoma. Neurosurgery 64:2 SupplA26A322009

  • 20

    Herfarth KKIzwekowa OThilmann CPirzkall ADelorme SHofmann U: Linac-based radiosurgery of cerebral melanoma metastases. Analysis of 122 metastases treated in 64 patients. Strahlenther Onkol 179:3663712003

  • 21

    Jensen RLShrieve AFSamlowski WShrieve DC: Outcomes of patients with brain metastases from melanoma and renal cell carcinoma after primary stereotactic radiosurgery. Clin Neurosurg 55:1501592008

  • 22

    Koc MMcGregor JGrecula JBauer CJGupta NGahbauer RA: Gamma Knife radiosurgery for intracranial metastatic melanoma: an analysis of survival and prognostic factors. J Neurooncol 71:3073132005

  • 23

    Kondziolka DBernstein MResch LTator CHFleming JFVanderlinden RG: Significance of hemorrhage into brain tumors: clinicopathological study. J Neurosurg 67:8528571987

  • 24

    Korn ELLiu PYLee SJChapman JANiedzwiecki DSuman VJ: Meta-analysis of phase II cooperative group trials in metastatic stage IV melanoma to determine progression-free and overall survival benchmarks for future phase II trials. J Clin Oncol 26:5275342008

  • 25

    Kouvaris JRMiliadou AKouloulias VEKolokouris DBalafouta MJPapacharalampous XN: Phase II study of temozolomide and concomitant whole-brain radiotherapy in patients with brain metastases from solid tumors. Onkologie 30:3613662007

  • 26

    Lagerwaard FJLevendag PCNowak PJEijkenboom WMHanssens PESchmitz PI: Identification of prognostic factors in patients with brain metastases: a review of 1292 patients. Int J Radiat Oncol Biol Phys 43:7958031999

  • 27

    Lavine SDPetrovich ZCohen-Gadol AAMasri LSMorton DLO'Day SJ: Gamma knife radiosurgery for metastatic melanoma: an analysis of survival, outcome, and complications. Neurosurgery 44:59661999

  • 28

    Lorenzoni JDevriendt DMassager NDavid PRuíz SVanderlinden B: Radiosurgery for treatment of brain metastases: estimation of patient eligibility using three stratification systems. Int J Radiat Oncol Biol Phys 60:2182242004

  • 29

    Manon RO'Neill AKnisely JWerner-Wasik MLazarus HMWagner H: Phase II trial of radiosurgery for one to three newly diagnosed brain metastases from renal cell carcinoma, melanoma, and sarcoma: an Eastern Cooperative Oncology Group study (E 6397). J Clin Oncol 23:887088762005

  • 30

    Mathieu DKondziolka DCooper PBFlickinger JCNiranjan AAgarwala S: Gamma knife radiosurgery in the management of malignant melanoma brain metastases. Neurosurgery 60:4714822007

  • 31

    Meier SBaumert BGMaier TWellis GBurg GSeifert B: Survival and prognostic factors in patients with brain metastases from malignant melanoma. Onkologie 27:1451492004

  • 32

    Mingione VOliveira MPrasad DSteiner MSteiner L: Gamma surgery for melanoma metastases in the brain. J Neurosurg 96:5445512002

  • 33

    Mori YKondziolka DFlickinger JCKirkwood JMAgarwala SLunsford LD: Stereotactic radiosurgery for cerebral metastatic melanoma: factors affecting local disease control and survival. Int J Radiat Oncol Biol Phys 42:5815891998

  • 34

    Noël GSimon JMValery CACornu PBoisserie GLedu D: Linac radiosurgery for brain metastasis of melanoma. Stereotact Funct Neurosurg 79:2452552002

  • 35

    Ott PAChang JLOratz RJones AFarrell KMuggia F: Phase II trial of dacarbazine and thalidomide for the treatment of metastatic melanoma. Chemotherapy 55:2212272009

  • 36

    Powell JWChung CTShah HRCanute GWHodge CJBassano DA: Gamma Knife surgery in the management of radioresistant brain metastases in high-risk patients with melanoma, renal cell carcinoma, and sarcoma. J Neurosurg 109:Suppl1221282008

  • 37

    Radbill AEFiveash JFFalkenberg ETGuthrie BLYoung PEMeleth S: Initial treatment of melanoma brain metastases using gamma knife radiosurgery: an evaluation of efficacy and toxicity. Cancer 101:8258332004

  • 38

    Redmond AJDiluna MLHebert RMoliterno JADesai RKnisely JP: Gamma Knife surgery for the treatment of melanoma metastases: the effect of intratumoral hemorrhage on survival. J Neurosurg 109:Suppl991052008

  • 39

    Saha SMeyer MKrementz ETHoda SCarter RDMuchmore J: Prognostic evaluation of intracranial metastasis in malignant melanoma. Ann Surg Oncol 1:38441994

  • 40

    Samlowski WEWatson GAWang MRao GKlimo P JrBoucher K: Multimodality treatment of melanoma brain metastases incorporating stereotactic radiosurgery (SRS). Cancer 109:185518622007

  • 41

    Sampson JHCarter JH JrFriedman AHSeigler HF: Demographics, prognosis, and therapy in 702 patients with brain metastases from malignant melanoma. J Neurosurg 88:11201998

  • 42

    Savas BArslan GGelen TKarpuzoglu GOzkaynak C: Multidrug resistant malignant melanoma with intracranial metastasis responding to immunotherapy. Anticancer Res 19:5C441344201999

  • 43

    Selek UChang ELHassenbusch SJ IIIShiu ASLang FFAllen P: Stereotactic radiosurgical treatment in 103 patients for 153 cerebral melanoma metastases. Int J Radiat Oncol Biol Phys 59:109711062004

  • 44

    Seung SKSneed PKMcDermott MWShu HKLeong SPChang S: Gamma knife radiosurgery for malignant melanoma brain metastases. Cancer J Sci Am 4:1031091998

  • 45

    Sin AHCardenas RJVannemreddy PNanda A: Gamma Knife stereotactic radiosurgery for intracranial metastases from conventionally radioresistant primary cancers: outcome analysis of survival and control of brain disease. South Med J 102:42442009

  • 46

    Sloan AENock CJEinstein DB: Diagnosis and treatment of melanoma brain metastasis: a literature review. Cancer Control 16:2482552009

  • 47

    Somaza SKondziolka DLunsford LDKirkwood JMFlickinger JC: Stereotactic radiosurgery for cerebral metastatic melanoma. J Neurosurg 79:6616661993

  • 48

    Tarhini AAAgarwala SS: Management of brain metastases in patients with melanoma. Curr Opin Oncol 16:1611662004

  • 49

    Tarhini AAKirkwood JMGooding WEMoschos SAgarwala SS: A phase 2 trial of sequential temozolomide chemotherapy followed by high-dose interleukin 2 immunotherapy for metastatic melanoma. Cancer 113:163216402008

  • 50

    Tsao HAtkins MBSober AJ: Management of cutaneous melanoma. N Engl J Med 351:99810122004

  • 51

    Weltman ESalvajoli JVBrandt RAde Morais Hanriot RPrisco FECruz JC: Radiosurgery for brain metastases: a score index for predicting prognosis. Int J Radiat Oncol Biol Phys 46:115511612000

  • 52

    Wroński MArbit E: Surgical treatment of brain metastases from melanoma: a retrospective study of 91 patients. J Neurosurg 93:9182000

  • 53

    Yu CChen JCApuzzo MLO'Day SGiannotta SLWeber JS: Metastatic melanoma to the brain: prognostic factors after gamma knife radiosurgery. Int J Radiat Oncol Biol Phys 52:127712872002

  • 54

    Zacest ACBesser MStevens GThompson JFMcCarthy WHCuljak G: Surgical management of cerebral metastases from melanoma: outcome in 147 patients treated at a single institution over two decades. J Neurosurg 96:5525582002




All Time Past Year Past 30 Days
Abstract Views 359 359 74
Full Text Views 198 198 3
PDF Downloads 158 158 2
EPUB Downloads 0 0 0


Google Scholar