Timing and risk factors for new brain metastasis formation in patients initially treated only with Gamma Knife surgery

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  • Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia
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Object

Stereotactic radiosurgery has been shown to afford a reasonable chance of local tumor control. However, new brain metastasis can arise following successful local tumor control from radiosurgery. This study evaluates the timing, number, and risk factors for development of subsequent new brain metastasis in a group of patients treated with stereotactic radiosurgery alone.

Methods

One hundred seventeen patients with histologically confirmed metastatic cancer underwent Gamma Knife surgery (GKS) to treat all brain metastases demonstrable on MR imaging. Patients were followed clinically and radiologically at approximately 3-month intervals for a median of 14.4 months (range 0.37–51.8 months). Follow-up MR images were evaluated for evidence of new brain metastasis formation. Statistical analyses were performed to determine the timing, number, and risk factors for development of new brain metastases.

Results

The median time to development of a new brain metastasis was 8.8 months. Patients with 3 or more metastases at the time of initial radiosurgery or those with cancer histologies other than non–small cell lung carcinoma were found to be at increased risk for early formation of new brain metastasis (p < 0.05). The mean number of new metastases per patient was 1.6 (range 0–11). Those with a higher Karnofsky Performance Scale score at the time of initial GKS were significantly more likely to develop a greater number of brain metastases by the last follow-up evaluation.

Conclusions

The timing and number of new brain metastases developing in patients treated with GKS alone is not inconsequential. Those with 3 or more metastases at the time of radiosurgery and those with cancer histology other than non–small cell lung carcinoma were at greater risk of early formation of new brain metastasis. Frequent follow-up evaluations, such as at 3-month intervals, appears appropriate in this patient population, particularly in high-risk patients. When detected early, salvage treatments including repeat radiosurgery can be used to treat new brain metastasis.

Abbreviations used in this paper:

GKS = Gamma Knife surgery; KPS = Karnofsky Performance Scale; NSCLC = non–small cell lung carcinoma; WBRT = whole-brain radiation therapy.

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Contributor Notes

Address correspondence to: Jason P. Sheehan, M.D., Ph.D., Department of Neurological Surgery, University of Virginia Health System, Box 800212, Charlottesville, Virginia 22908. email: jps2f@virginia.edu.

Please include this information when citing this paper: published online March 12, 2010; DOI: 10.3171/2010.2.JNS091539.

  • 1

    Andrews DW, , Scott CB, , Sperduto PW, , Flanders AE, , Gaspar LE, & Schell MC, et al. : Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet 363:16651672, 2004

    • Search Google Scholar
    • Export Citation
  • 2

    Aoyama H, , Shirato H, , Tago M, , Nakagawa K, , Toyoda T, & Hatano K, et al. : Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. JAMA 295:24832491, 2006

    • Search Google Scholar
    • Export Citation
  • 3

    Aoyama H, , Tago M, , Kato N, , Toyoda T, , Kenjyo M, & Hirota S, et al. : Neurocognitive function of patients with brain metastasis who received either whole brain radiotherapy plus stereotactic radiosurgery or radiosurgery alone. Int J Radiat Oncol Biol Phys 68:13881395, 2007

    • Search Google Scholar
    • Export Citation
  • 4

    Atkins MB, , Sosman JA, , Agarwala S, , Logan T, , Clark JI, & Ernstoff MS, et al. : Temozolomide, thalidomide, and whole brain radiation therapy for patients with brain metastasis from metastatic melanoma: a phase II Cytokine Working Group study. Cancer 113:21392145, 2008

    • Search Google Scholar
    • Export Citation
  • 5

    Brown PD, , Brown CA, , Pollock BE, , Gorman DA, & Foote RL: Stereotactic radiosurgery for patients with “radioresistant” brain metastases. Neurosurgery 62:Suppl 2 790801, 2008

    • Search Google Scholar
    • Export Citation
  • 6

    Chang EL, , Wefel JS, , Hess KR, , Allen PK, , Lang FF, & Kornguth DG, et al. : Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol 10:10371044, 2009

    • Search Google Scholar
    • Export Citation
  • 7

    Ellerhorst J, , Strom E, , Nardone E, & McCutcheon I: Whole brain irradiation for patients with metastatic melanoma: a review of 87 cases. Int J Radiat Oncol Biol Phys 49:9397, 2001

    • Search Google Scholar
    • Export Citation
  • 8

    Higuchi Y, , Serizawa T, , Nagano O, , Matsuda S, , Ono J, & Sato M, et al. : Three-staged stereotactic radiotherapy without whole brain irradiation for large metastatic brain tumors. Int J Radiat Oncol Biol Phys 74:15431548, 2009

    • Search Google Scholar
    • Export Citation
  • 9

    Jawahar A, , Matthew RE, , Minagar A, , Shukla D, , Zhang JH, & Willis BK, et al. : Gamma knife surgery in the management of brain metastases from lung carcinoma: a retrospective analysis of survival, local tumor control, and freedom from new brain metastasis. J Neurosurg 100:842847, 2004

    • Search Google Scholar
    • Export Citation
  • 10

    Kihlström L, , Karlsson B, & Lindquist C: Gamma Knife surgery for cerebral metastases. Implications for survival based on 16 years experience. Stereotact Funct Neurosurg 61:Suppl 1 4550, 1993

    • Search Google Scholar
    • Export Citation
  • 11

    Kondziolka D, , Martin JJ, , Flickinger JC, , Friedland DM, , Brufsky AM, & Baar J, et al. : Long-term survivors after gamma knife radiosurgery for brain metastases. Cancer 104:27842791, 2005

    • Search Google Scholar
    • Export Citation
  • 12

    Lee DH, , Han JY, , Kim HT, , Yoon SJ, , Pyo HR, & Cho KH, et al. : Primary chemotherapy for newly diagnosed nonsmall cell lung cancer patients with synchronous brain metastases compared with whole-brain radiotherapy administered first: result of a randomized pilot study. Cancer 113:143149, 2008

    • Search Google Scholar
    • Export Citation
  • 13

    Lee WY, , Cho DY, , Lee HC, , Chuang HC, , Chen CC, & Liu JL, et al. : Outcomes and cost-effectiveness of gamma knife radiosurgery and whole brain radiotherapy for multiple metastatic brain tumors. J Clin Neurosci 16:630634, 2009

    • Search Google Scholar
    • Export Citation
  • 14

    Lutterbach J, , Cyron D, , Henne K, & Ostertag CB: Radiosurgery followed by planned observation in patients with one to three brain metastases. Neurosurgery 62:Suppl 2 776784, 2008

    • Search Google Scholar
    • Export Citation
  • 15

    Meyers CA, , Smith JA, , Bezjak A, , Mehta MP, , Liebmann J, & Illidge T, et al. : Neurocognitive function and progression in patients with brain metastases treated with whole-brain radiation and motexafin gadolinium: results of a randomized phase III trial. J Clin Oncol 22:157165, 2004

    • Search Google Scholar
    • Export Citation
  • 16

    Moscetti L, , Nelli F, , Felici A, , Rinaldi M, , De Santis S, & D'Auria G, et al. : Up-front chemotherapy and radiation treatment in newly diagnosed nonsmall cell lung cancer with brain metastases: survey by Outcome Research Network for Evaluation of Treatment Results in Oncology. Cancer 109:274281, 2007

    • Search Google Scholar
    • Export Citation
  • 17

    Muacevic A, , Kreth FW, , Horstmann GA, , Schmid-Elsaesser R, , Wowra B, & Steiger HJ, et al. : Surgery and radiotherapy compared with gamma knife radiosurgery in the treatment of solitary cerebral metastases of small diameter. J Neurosurg 91:3543, 1999

    • Search Google Scholar
    • Export Citation
  • 18

    Regine WF, , Huhn JL, , Patchell RA, , St Clair WH, , Strottmann J, & Meigooni A, et al. : Risk of symptomatic brain tumor recurrence and neurologic deficit after radiosurgery alone in patients with newly diagnosed brain metastases: results and implications. Int J Radiat Oncol Biol Phys 52:333338, 2002

    • Search Google Scholar
    • Export Citation
  • 19

    Regine WF, , Scott C, , Murray K, & Curran W: Neurocognitive outcome in brain metastases patients treated with accelerated-fractionation vs. accelerated-hyperfractionated radiotherapy: an analysis from Radiation Therapy Oncology Group Study 91-04. Int J Radiat Oncol Biol Phys 51:711717, 2001

    • Search Google Scholar
    • Export Citation
  • 20

    Rossi A, , Maione P, , Colantuoni G, , Ferrara C, , Rossi E, & Guerriero C, et al. : Recent developments of targeted therapies in the treatment of non-small cell lung cancer. Curr Drug Discov Technol 6:91102, 2009

    • Search Google Scholar
    • Export Citation
  • 21

    Sawrie SM, , Guthrie BL, , Spencer SA, , Nordal RA, , Meredith RF, & Markert JM, et al. : Predictors of distant brain recurrence for patients with newly diagnosed brain metastases treated with stereotactic radiosurgery alone. Int J Radiat Oncol Biol Phys 70:181186, 2008

    • Search Google Scholar
    • Export Citation
  • 22

    Sheehan JP, , Sun MH, , Kondziolka D, , Flickinger J, & Lunsford LD: Radiosurgery for non-small cell lung carcinoma metastatic to the brain: long-term outcomes and prognostic factors influencing patient survival time and local tumor control. J Neurosurg 97:12761281, 2002

    • Search Google Scholar
    • Export Citation
  • 23

    Sneed PK, , Lamborn KR, , Forstner JM, , McDermott MW, , Chang S, & Park E, et al. : Radiosurgery for brain metastases: is whole brain radiotherapy necessary?. Int J Radiat Oncol Biol Phys 43:549558, 1999

    • Search Google Scholar
    • Export Citation
  • 24

    Sneed PK, , Suh JH, , Goetsch SJ, , Sanghavi SN, , Chappell R, & Buatti JM, et al. : A multi-institutional review of radiosurgery alone vs. radiosurgery with whole brain radiotherapy as the initial management of brain metastases. Int J Radiat Oncol Biol Phys 53:519526, 2002

    • Search Google Scholar
    • Export Citation
  • 25

    Stevens G, , Firth I, & Coates A: Cerebral metastases from malignant melanoma. Radiother Oncol 23:185191, 1992

  • 26

    Tiseo M, , Bartolotti M, , Gelsomino F, & Ardizzoni A: First-line treatment in advanced non-small-cell lung cancer: the emerging role of the histologic subtype. Expert Rev Anticancer Ther 9:425435, 2009

    • Search Google Scholar
    • Export Citation
  • 27

    Tsao MN, , Lloyd N, , Wong R, , Chow E, , Rakovitch E, & Laperriere N: Whole brain radiotherapy for the treatment of multiple brain metastases. Cochrane Database Syst Rev 3:CD003869, 2006

    • Search Google Scholar
    • Export Citation
  • 28

    Varlotto JM, , Flickinger JC, , Niranjan A, , Bhatnagar A, , Kondziolka D, & Lunsford LD: The impact of whole-brain radiation therapy on the long-term control and morbidity of patients surviving more than one year after gamma knife radiosurgery for brain metastases. Int J Radiat Oncol Biol Phys 62:11251132, 2005

    • Search Google Scholar
    • Export Citation
  • 29

    Varlotto JM, , Flickinger JC, , Niranjan A, , Bhatnagar AK, , Kondziolka D, & Lunsford LD: Analysis of tumor control and toxicity in patients who have survived at least one year after radiosurgery for brain metastases. Int J Radiat Oncol Biol Phys 57:452464, 2003

    • Search Google Scholar
    • Export Citation
  • 30

    Wen PY, & Loeffler JS: Brain metastases. Curr Treat Options Oncol 1:447458, 2000

  • 31

    Yen CP, , Sheehan J, , Patterson G, & Steiner L: Gamma knife surgery for metastatic brainstem tumors. J Neurosurg 105:213219, 2006

  • 32

    Yu C, , Chen JC, , Apuzzo ML, , O'Day S, , Giannotta SL, & Weber JS, et al. : Metastatic melanoma to the brain: prognostic factors after gamma knife radiosurgery. Int J Radiat Oncol Biol Phys 52:12771287, 2002

    • Search Google Scholar
    • Export Citation

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