Journal of Neuro-Oncology

, Volume 75, Issue 1, pp 31–42 | Cite as

Radiotherapy and chemotherapy of brain metastases

  • R. SoffiettiEmail author
  • A. Costanza
  • E. Laguzzi
  • M. Nobile
  • R. Rudà


The authors have reviewed the results, the indications and the controversies regarding radiotherapy and chemotherapy of patients with newly diagnosed and recurrent brain metastases. Whole-brain radiotherapy, radiosurgery, hypofractionated stereotactic radiotherapy, brachytherapy and chemotherapy are the available options. New radiosensitizers and cytotoxic or cytostatic agents are being investigated. Adjuvant whole brain radiotherapy, either after surgery or radiosurgery, and prophylactic cranial irradiation in small-cell lung cancer are discussed, taking into account local control, survival, and risk of late neurotoxicity. Increasingly, the different treatments are tailored to the different prognostic subgroups, as defined by Radiation Therapy Oncology Group RPA Classes.


brain metastases chemotherapy prophylactic cranial irradiation radiosurgery whole brain radiotherapy 


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  1. 1.
    Diener-West, M, Dobbins, TW, Phillips, TL, Nelson, DF 1989Identification of an optimal subgroup for treatment evaluation of patients with brain metastases using RTOG Study 7916Int J Radiat Oncol Biol Phys16669673PubMedGoogle Scholar
  2. 2.
    Gaspar, L, Scott, C, Rotman, M, Asbell, S, Phillips, T, Wasserman, T, McKenna, WG, Byhardt, R 1997Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trialsInt J Radiat Oncol Biol Phys37745751CrossRefPubMedGoogle Scholar
  3. 3.
    Lagerwaard, FJ, Levendag, PC, Nowak, PJ, Eijkenboom, WM, Hanssens, PE, Schmitz, PI 1999Identification of prognostic factors in patients with brain metastases: a review of 1292 patientsInt J Radiat Oncol Biol Phys43795803CrossRefPubMedGoogle Scholar
  4. 4.
    Chidel, MA, Suh, JH, Reddy, CA, Chao, ST, Lundbeck, MF, Barnett, GH 2000Application of recursive partitioning analysis and evaluation of the use of whole-brain radiation among patients treated with stereotactic radiosurgery for newly diagnosed brain metastasesInt J Radiat Oncol Biol Phys47993999CrossRefPubMedGoogle Scholar
  5. 5.
    Gaspar, L, Scott, C, Murray, K, Curran, W 2000Validation of the RTOG recursive partitioning analysis (RPA) classification for brain metastasesInt J Radiat Oncol Biol Phys4710011006CrossRefPubMedGoogle Scholar
  6. 6.
    Nieder, C, Nestle, U, Motaref, B, Walter, K, Niewald, M, Schnabel, K 2000Prognostic factors in brain metastases: should patients be selected for aggressive treatment according to recursive partitioning analysis (RPA) classesInt J Radiat Oncol Biol Phys46297302CrossRefPubMedGoogle Scholar
  7. 7.
    Weltman, E, Salvajoli, JV, Brandt, RA, Morais Hanriot, R, Prisco, FE, Cruz, JC, Oliveira Borges, R, Lagatta, M, Ballas Wajsbrot, D 2001Radiosurgery for brain metastases: who may not benefitInt J Radiat Oncol Biol Phys5113201327CrossRefPubMedGoogle Scholar
  8. 8.
    Murray, KJ, Scott, C, Zachariah, B, Michalski, JM, Demas, W, Vora, NL, Whitton, A, Movsas, B 2000Importance of the Mini-Mental Status Examination in the treatment of patients with brain metastases: a report from the Radiation Therapy Oncology Group protocolInt J Radiat Oncol Biol Phys485964CrossRefPubMedGoogle Scholar
  9. 9.
    Maesawa, S, Kondziolka, D, Thompson, TP, Flickinger, JC, Dade, L 2000Brain metastases in patients with no known primary tumorThe role of stereotactic radiosurgery. Cancer8910951101Google Scholar
  10. 10.
    Nguyen, LN, Maor, MH, Oswald, MJ 1998Brain metastases as the only manifestation of an undetected primary tumorCancer8321812184CrossRefPubMedGoogle Scholar
  11. 11.
    Rudà, R, Borgognone, M, Benech, F, Vasario, E, Soffietti, R 2001Brain metastases from unknown primary tumorA prospective study. J Neurol248394398Google Scholar
  12. 12.
    Bartelt, S, Lutterbach, J 2003Brain metastases in patients with cancer of unknown primaryJ Neurooncol64249253CrossRefPubMedGoogle Scholar
  13. 13.
    Macdonald, DR, Cascino, T, Schold, SC, Cairncross, JG 1990Response criteria for Phase II studies of malignant gliomaJ Clin Oncol812771280PubMedGoogle Scholar
  14. 14.
    Regine, WF, Scott, C, Murray, K, Curran, W 2001Neurocognitive outcome in brain metastases patients treated with accelerated-fractionation vs accelerated-hyperfractionated radiotherapy: an analysis from Radiation Therapy Oncology Group study 91–04Int J Radiat Oncol Biol Phys51711717CrossRefPubMedGoogle Scholar
  15. 15.
    Mehta, MP, Shapiro, WR, Glantz, MJ, Patchell, RA, Weitzner, MA, Meyers, CA, Schultz, CJ, Roa, WH, Leibenhaut, M, Ford, J, Curran, W, Phan, S, Smith, JA, Miller, RA, Renschler, MF 2002Lead-in phase to randomized trial of motexafin gadolinium and whole-brain radiation for patients with brain metastases: centralized assessment of magnetic resonance imaging, neurocognitive, and neurologic end pointsJ Clin Oncol2034453453CrossRefPubMedGoogle Scholar
  16. 16.
    Zimm, S, Wampler, GL, Stablein, D, Hazra, T, Young, HF 1981Intracerebral metastases in solid-tumor patients: natural history and results of treatmentCancer48384394PubMedGoogle Scholar
  17. 17.
    Posner JB: Brain metastases. In: Posner JB (ed) Neurologic Complications of Cancer. FA Davis Co, Philadelphia, pp 78–95.Google Scholar
  18. 18.
    Cairncross, JG, Chernik, NL, Kim, JH, Posner, JB 1979Sterilization of cerebral metastases by radiation therapyNeurology2911951202PubMedGoogle Scholar
  19. 19.
    Borgelt, BB, Gelber, RD, Kramer, S, Brady, LW, Chang, CH, Davis, LW, Perez, CA, Hendrickson, FR 1980The palliation of brain metastases: final results of the first two studies by the Radiation Therapy Oncology GroupInt J Radiat Oncol Biol Phys619PubMedGoogle Scholar
  20. 20.
    Hoskin, PJ, Brada, M 2001Radiotherapy for brain metastasesClin Oncol139194Google Scholar
  21. 21.
    Bezjak, A, Adam, J, Barton, R, Panzarella, T, Laperriere, N, Wong, CS, Mason, W, Buckley, C, Levin, W, McLean, M, Wu, JSY, Sia, M, Kirkbride, P 2002Symptom response after palliative radiotherapy for patients with brain metastasesEur J Cancer38487496CrossRefPubMedGoogle Scholar
  22. 22.
    Kurtz, JM, Gelber, R, Brady, LW, Carella, RJ, Cooper, JS 1981The palliation of brain metastases in a favorable patient population: a randomized clinical trial by the Radiation Therapy Oncology GroupInt J Radiat Oncol Biol Phys7891895PubMedGoogle Scholar
  23. 23.
    Borgelt, B, Gelber, R, Larson, M, Hendrickson, F, Griffin, T, Roth, R 1981Ultra-rapid high dose irradiation schedules for the palliation of brain metastases: final results of the first two studies by the Radiation Therapy Oncology GroupInt J Radiat Oncol Biol Phys716331638PubMedGoogle Scholar
  24. 24.
    Murray, KJ, Scott, C, Greenberg, H, Emami, B, Seider, M, Vora, NL, Olson, C, Whitton, A, Movsas, B, Curran, W 1997A randomized phase III study of accelerated hyperfractionated versus standard radiation in patients with unresected brain metastases: a report of the Radiation Therapy Oncology Group (RTOG) 9104Int J Radiat Oncol Biol Phys39571574CrossRefPubMedGoogle Scholar
  25. 25.
    Hoskins, PJ, Crow, J, Ford, HT 1990The influence of extent and local management on the outcome of radiotherapy for brain metastasesInt J Radiat Oncol Biol Phys19111115PubMedGoogle Scholar
  26. 26.
    Eyre, HJ, Ohlsen, JD, Frank, J, LoBuglio, AF, McCracken, JD, Weatherall, TJ, Mansfield, CM 1984Randomized trial of radiotherapy versus radiotherapy plus metronidazole for the treatment metastatic cancer to brain. A Southwest Oncology Group study. J Neurooncol2325330CrossRefPubMedGoogle Scholar
  27. 27.
    Angelis, LM, Currie, VE, Kim, JH, Krol, G, O'Hehir, MA, Farag, FM, Young, CW, Posner, JB 1989The combined use of radiation therapy and lonidamine in the treatment of brain metastasesJ Neurooncol7241247PubMedGoogle Scholar
  28. 28.
    Komarnicky, LT, Phillips, TL, Martz, K, Asbell, S, Isaacson, S, Urtasun, R 1991A randomized phase III protocol for the evaluation of misonidazole combined with radiation in the treatment of patients with brain metastases (RTOG-7916)Int J Radiat Oncol Biol Phys205358PubMedGoogle Scholar
  29. 29.
    Phillips, TL, Scott, CB, Leibel, SA, Rotman, M, Weigensberg, IJ 1995Results of a randomized comparison of radiotherapy and bromodeoxyuridine with radiotherapy alone for brain metastases: report of RTOG trial 89–05Int J Radiat Oncol Biol Phys33339348CrossRefPubMedGoogle Scholar
  30. 30.
    Carde, P, Timmerman, R, Mehta, MP, Koprowski, CD, Ford, J, Tishler, RB, Miles, D, Miller, RA, Renschler, MF 2001Multicenter phase Ib/II trial of the radiation enhancer motefaxin gadolinium in patients with brain metastasesJ Clin Oncol1920742083PubMedGoogle Scholar
  31. 31.
    Mehta, MP, Rodrigus, P, Terhaard, CH, Rao, A, Suh, J, Roa, W, Souhami, L, Bezjak, A, Leibenhaut, M, Komaki, R, Schultz, C, Timmerman, R, Curran, W, Smith, J, Phan, SC, Miller, RA, Renschler, MF 2003Survival and neurologic outcomes in a randomized trial of motexafin gadolinium and whole-brain radiation therapy in brain metastasesJ Clin Oncol2125292536CrossRefPubMedGoogle Scholar
  32. 32.
    Shaw, E, Scott, C, Suh, J, Kadish, S, Stea, B, Hackman, J, Pearlman, A, Murray, K, Gaspar, L, Mehta, M, Curran, W, Gerber, M 2003RSR13 plus cranial radiation therapy in patients with brain metastases: comparison with the Radiation Therapy Oncology Group Recursive Partitioning Analysis Brain Metastases DatabaseJ Clin Oncol2123642371CrossRefPubMedGoogle Scholar
  33. 33.
    Hazuka, MB, Kinzie, JJ 1988Brain metastases: results and effects of re-irradiationInt J Radiat Oncol Biol Phys15433437CrossRefPubMedGoogle Scholar
  34. 34.
    Wong, WW, Schild, SE, Sawyer, TE, Shaw, EG 1996Analysis of outcome in patients reirradiated for brain metastasesInt J Radiat Oncol Biol Phys34585590CrossRefPubMedGoogle Scholar
  35. 35.
    Angelis, LM, Delattre, JY, Posner, JB 1989Radiation-induced dementia in patients cured of brain metastasesNeurology39789796PubMedGoogle Scholar
  36. 36.
    Nieder, C, Schwerdtfeger, K, Steudel, WI, Schnabel, K 1998Patterns of relapse and late toxicity after resection and whole-brain radiotherapy for solitary brain metastasesStrahlenther Onkol174275278PubMedGoogle Scholar
  37. 37.
    Noordijk, EM, Vecht, CJ, Haaxma-Reiche, H, Padberg, GW, Voormolen, JH, Hoekstra, FH, Tans, JT, Lambooij, N, Metsaars, JA, Wattendorff, AR 1994The choice of treatment of single brain metastasis should be based on extracranial tumor activity and ageInt J Radiat Oncol Biol Phys29711717PubMedGoogle Scholar
  38. 38.
    Adler, JR, Cox, RS, Kaplan, I, Martin, DP 1992Stereotactic radiosurgical treatment of brain metastasesJ Neurosurg76444449PubMedGoogle Scholar
  39. 39.
    Mehta, MP, Rozenthal, JM, Levin, B, Mackie, TR, Kubsad, SS, Gehring, MA, Kinsella, TJ 1992Defining the role of radiosurgery in the management of brain metastasesInt J Radiat Oncol Biol Phys24619625PubMedGoogle Scholar
  40. 40.
    Engenhardt, RB, Kimmig, N, Hover, KH, Wowra, B, Romahn, J, Lorenz, WJ, Kaick, G, Wannenmacher, M 1993Long-term follow-up for brain metastases treated by percutaneous single high dose irradiationCancer7113531361PubMedGoogle Scholar
  41. 41.
    Flickinger, JC, Kondziolka, D, Lunsford, LD, Coffey, RJ, Goodman, ML, Shaw, EG, Hudgins, WR, Weiner, R, Harsh, GR IV, Sneed, PK 1994A multi-institutional experience with stereotactic radiosurgery for solitary brain metastasisInt J Radiat Oncol Biol Phys28797802PubMedGoogle Scholar
  42. 42.
    Alexander, E, Moriarty, TM, Davis, RB, Wen, PY, Fine, HA, Black, PM, Kooy, HM, Loeffler, JS 1995Stereotactic radiosurgery for the definitive, noninvasive treatment of brain metastasesJ Natl Cancer Inst873440PubMedGoogle Scholar
  43. 43.
    Auchter, RM, Lamond, JP, Alexander, E, Buatti, JM, Chappell, R, Friedman, WA, Kinsella, TJ, Levin, AB, Noyes, WR, Schultz, CJ, Loeffler, JS, Mehta, MP 1996A multi-institutional outcome and prognostic factor analysis of radiosurgery for resectable single brain metastasisInt J Radiat Oncol Biol Phys352735CrossRefPubMedGoogle Scholar
  44. 44.
    Shiau, CY, Sneed, PK, Shu, HK, Lamborn, KR, McDermott, MW, Chang, S, Nowak, P, Petti, PL, Smith, V, Verhey, LJ, Ho, M, Park, E, Wara, WM, Gutin, PH, Larson, DA 1997Radiosurgery for brain metastases: relationship of dose and pattern of enhancement to local controlInt J Radiat Oncol Biol Phys37375383CrossRefPubMedGoogle Scholar
  45. 45.
    Maor, MH, Dubey, P, Tucker, SL, Shiu, AS, Mathur, BN, Sawaya, R, Lang, FF, Hassenbusch, SJ 2000Stereotactic radiosurgery for brain metastases: results and prognostic factorsInt J Cancer90157162CrossRefPubMedGoogle Scholar
  46. 46.
    Joseph, J, Adler, JR, Cox, RS, Hancock, SL 1996Linear accelerator-based stereotaxic radiosurgery for brain metastases: the influence of number of lesions on survivalJ Clin Oncol1410851092PubMedGoogle Scholar
  47. 47.
    Cho, KH, Hall, WA, Gerbi, BJ, Higgins, PD, Bohen, M, Clark, HB 1998Patient selection criteria for the treatment of brain metastases with stereotactic radiosurgeryJ Neurooncol407386CrossRefPubMedGoogle Scholar
  48. 48.
    Sneed, PK, Lamborn, KR, orstner, JM, McDermott, MW, Chang, S, Park, E, Gutin, PH, Phillips, TL, Wara, WM, Larson, D 1999Radiosurgery for brain metastases: is whole brain radiotherapy necessaryInt J Radiat Oncol Biol Phys3549558CrossRefGoogle Scholar
  49. 49.
    Kondziolka, D, Patel, A, Lunsford, LD, Kassam, A, Flickinger, JC 1999Stereotactic radiosurgery plus whole-brain radiotherapy versus radiotherapy alone for patients with multiple brain metastasesInt J Radiat Oncol Biol Phys45427434CrossRefPubMedGoogle Scholar
  50. 50.
    Yamamoto, M, Ide, M, Nishio, S, Urakawa, Y 2002Gamma knife radiosurgery for numerous brain metastases: is this a safe treatmentInt J Radiat Oncol Biol Phys5312791283CrossRefPubMedGoogle Scholar
  51. 51.
    Kihlstrom, L, Karlsson, B, Lindquist, C 1993Gamma knife surgery for cerebral metastases. Implications for survival based on 16 years experienceStereotact Funct Neurosurg61 (Suppl 1)4550Google Scholar
  52. 52.
    Pirzkall, A, Debus, J, Lohr, F, Fuss, M, Rhein, B, Engenhart-Cabillic, R, Wannenmacher, M 1998Radiosurgery alone or in combination with whole-brain radiotherapy for brain metastasesJ Clin Oncol1635633569PubMedGoogle Scholar
  53. 53.
    Mori, Y, Kondziolka, D, Flickinger, JC, Kirkwood, JM, Agarwala, S, Lunsford, LD 1998Stereotactic radiosurgery for cerebral metastatic melanoma: factors affecting local disease control and survivalInt J Radiat Oncol Biol Phys42581589CrossRefPubMedGoogle Scholar
  54. 54.
    Peterson, AM, Meltzer, CC, Evanson, EJ, Flickinger, JC, Kondziolka, D 1999MR imaging response of brain metastases after gamma knife stereotactic radiosurgeryRadiology211807814PubMedGoogle Scholar
  55. 55.
    Noel, G, Simon, JM, Valery, CA, Cornu, P, Boisserie, G, Hasboun, D, Ledu, D, Tep, B, Delattre, JY, Marsault, C, Baillet, F, Mazeron, JJ 2003Radiosurgery for brain metastasis: impact of CTV on local controlRadiother Oncol681521CrossRefPubMedGoogle Scholar
  56. 56.
    Levine, SD, Petrovich, Z, Cohen-Gadol, AA, Masri, LS, Morton, DL, O'Day, SJ, Essner, R, Zelman, V, Yu, C, Luxton, G, Apuzzo, ML 1999Gamma knife radiosurgery for metastatic melanoma: an analysis of survival, outcome, and complicationsNeurosurgery445964CrossRefPubMedGoogle Scholar
  57. 57.
    Yu, C, Chen, JC, Apuzzo, ML, O'Day, S, Giannotta, SL, Weber, JS, Petrovich, Z 2002Metastatic melanoma to the brain: prognostic factors after gamma knife radiosurgeryInt J Radiat Oncol Biol Phys5212771287CrossRefPubMedGoogle Scholar
  58. 58.
    Schoeggl, A, Kitz, K, Reddy, M, Zauner, C 2002Stereotactic radiosurgery for brain metastases from colorectal cancerInt J Colorectal Dis17150155CrossRefPubMedGoogle Scholar
  59. 59.
    Sheehan, JP, Sun, MH, Kondziolka, D, Flickinger, J, Lunsford, LD 2003Radiosurgery in patients with renal cell carcinoma metastasis to the brain: long-term outcomes and prognostic factors influencing survival and local tumor controlJ Neurosurg98342349PubMedGoogle Scholar
  60. 60.
    Huang, CF, Kondziolka, D, Flickinger, JC, Lunsford, LD 1999Stereotactic radiosurgery for brainstem metastasesJ Neurosurg84563568Google Scholar
  61. 61.
    Buatti, JM, Friedman, WA, Meeks, SL, Bova, FJ 2000RTOG 90–05: the real conclusionInt J Radiat Oncol Biol Phys47269271CrossRefPubMedGoogle Scholar
  62. 62.
    Huber, PE, Hawighorst, H, Fuss, M, Kaick, G, Wannenmacher, MF, Debus, J 2001Transient enlargement of contrast uptake on MRI after linear accelerator (LINAC) stereotactic radiosurgery for brain metastasesInt J Radiat Oncol Biol Phys4913391349CrossRefPubMedGoogle Scholar
  63. 63.
    Sanghavi, SN, Miranpuri, SS, Chappell, R, Buatti, JM, Sneed, PK, Suh, JH, Regine, WF, Weltman, E, King, VJ, Goetsch, SJ, Breneman, JC, Sperduto, PW, Scott, C, Mabanta, S, Mehta, MP 2001Radiosurgery for patients with brain metastases: a multi-institutional analysis, stratified by the RTOG recursive partitioning analysis methodInt J Radiat Oncol Biol Phys51426434CrossRefPubMedGoogle Scholar
  64. 64.
    Chougule, PB, Burton-Williams, M, Saris, S 2000Randomized treatment of brain metastases with gamma knife radiosurgery, whole-brain radiotherapy or both.Int J Radiat Oncol Biol Phys48(Suppl)114CrossRefGoogle Scholar
  65. 65.
    Sperduto, PW, Scott, C, Andrews, D 2000Preliminary report of RTOG 9508: a phase III trial comparing whole-brain irradiation alone versus whole-brain irradiation plus stereotactic radiosurgery for patients with two or three unresected brain metastases.Int J Radiat Oncol Biol Phys48(Suppl)113CrossRefGoogle Scholar
  66. 66.
    Muacevic, A, Kreth, FW, Horstmann, GA, Schmid-Elsaesser, R, Wowra, B, Steiger, HJ, Reulen, HJ 1999Surgery and radiotherapy compared with gamma knife radiosurgery in the treatment of solitary cerebral metastases of small diameterJ Neurosurg913543PubMedGoogle Scholar
  67. 67.
    O'Neill, BP, Iturria, NJ, Link, MJ, Pollock, BE, Ballman, KV, O'Fallon, JR 2003A comparison of surgical resection and stereotactic radiosurgery in the treatment of solitary brain metastasesInt J Radiat Oncol Biol Phys5511691176CrossRefPubMedGoogle Scholar
  68. 68.
    Bindal, AK, Bindal, RK, Hess, KR, Shiu, A, Hassenbusch, SJ, Shi, WM, Sawaya, R 1996Surgery versus radiosurgery in the treatment of brain metastasisJ Neurosurg84748754PubMedGoogle Scholar
  69. 69.
    Loeffler, JS, Kooy, HM, Wen, PY, Fine, HA, Cheng, CW, Mannarino, EG, Tsai, JS, Alexander, E 1990The treatment of recurrent brain metastases with stereotactic radiosurgeryJ Clin Oncol8576582PubMedGoogle Scholar
  70. 70.
    Chen, JCT, Petrovich, Z, Giannotta, SL, Yu, C, Apuzzo, ML 2000Radiosurgical salvage therapy for patients presenting with recurrence of metastatic disease to the brainNeurosurgery46860867CrossRefPubMedGoogle Scholar
  71. 71.
    Shaw, E, Scott, C, Souhami, L, Dinapoli, R, Kline, R, Loeffler, J, Farnan, N 2000Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: final report of RTOG protocol 90–05Int J Radiat Oncol Biol Phys47291298CrossRefPubMedGoogle Scholar
  72. 72.
    McKenzie, MR, Souhami, L, Caron, JL, Olivier, A, Villemure, JG, Podgorsak, EB 1993Early and late complications following dynamic stereotactic radiosurgery and fractionated stereotactic radiotherapyCan J Neurol Sci20279285PubMedGoogle Scholar
  73. 73.
    Gelblum, DY, Lee, H, Bilsky, M, Pinola, C, Longford, S, Wallner, K 1998Radiographic findings and morbidity in patients treated with stereotactic radiosurgeryInt J Radiat Oncol Biol Phys42391395CrossRefPubMedGoogle Scholar
  74. 74.
    Chao, ST, Suh, JH, Raja, S, Lee, SY, Barnett, G 2001The sensitivity and specificity of FDG PET in distinguishing recurrent brain tumor from radionecrosis in patients treated with stereotactic radiosurgeryInt J Cancer96191197CrossRefPubMedGoogle Scholar
  75. 75.
    Rutigliano, MJ, Lunsford, LD, Kondziolka, D, Strauss, MJ, Khanna, V, Green, M 1995The cost effectiveness of stereotactic radiosurgery versus surgical resection in the treatment of solitary matastatic brain tumorsNeurosurgery37445455PubMedGoogle Scholar
  76. 76.
    Mehta, M, Noyes, W, Craig, B, Lamond, J, Auchter, R, French, M, Johnson, M, Levin, A, Badie, B, Robbins, I, Kinsella, T 1997A cost-effectiveness and cost-utility analysis of radiosurgery vsresection for single-brain metastases. Int J Radiat Oncol Biol Phys39445454CrossRefGoogle Scholar
  77. 77.
    Laing, RW, Warrington, AP, Hines, F, Graham, JD, Brada, M 1993Fractionated stereotactic external beam radiotherapy in the management of brain metastasesEur J Cancer2913871391CrossRefGoogle Scholar
  78. 78.
    Manning, MA, Cardinale, RM, Benedict, SH, Kavanagh, BD, Zwicker, RD, Amir, C, Broaddus, WC 2000Hypofractionated stereotactic radiotherapy as an alternative to radiosurgery for the treatment of patients with brain metastasesInt J Radiat Oncol Biol Phys47603608CrossRefPubMedGoogle Scholar
  79. 79.
    Aoyama, H, Shirato, H, Onimaru, R, Kagei, K, Ikeda, J, Ishii, N, Sawamura, Y, Miyasaka, K 2003Hypofractionated stereotactic radiotherapy alone without whole-brain irradiation for patients with solitary and oligo brain metastasis using noninvasive fixation of the skullInt J Radiat Oncol Biol Phys56793800CrossRefPubMedGoogle Scholar
  80. 80.
    Bernstein, M, Cabantog, A, Laperriere, N, Leung, P, Thomason, C 1995Brachytherapy for recurrent single brain metastasisCan J Neurol Sci221316PubMedGoogle Scholar
  81. 81.
    McDermott, MW, Cosgrove, GR, Larson, DA, Sneed, PK, Gutin, PH 1996Interstitial brachytherapy for intracranial metastasesNeurosurg Clin North Am7485495Google Scholar
  82. 82.
    Bogart, JA, Ungureanu, C, Shihadeh, E, Chung, TC, King, GA, Ryu, S, Kent, C, Winfield, JA 1999Resection and permanent I-125 brachytherapy without whole brain irradiation for solitary brain metastasis from non-small cell lung carcinomaJ Neurooncol445357CrossRefPubMedGoogle Scholar
  83. 83.
    Rock, JP, Shaw, E, Sills, A, Vogelbaum, M, Ewend, M, Rogers, LR 2003Initial results of a phase 2 trial of resection and gliasite brachytherapy for a single brain metastasisNeuro-Oncology5345Google Scholar
  84. 84.
    Mintz, A, Cairncross, JG 1998Treatment of a single brain metastasisThe role of radiation following surgical resection. JAMA28015271529Google Scholar
  85. 85.
    Smalley, SR, Schray, MF, Laws, ER, O'Fallon, JR 1987Adjuvant radiation therapy after surgical resection of solitary brain metastasis: association with pattern of failure and survivalInt J Radiat Oncol Biol Phys1316111616PubMedGoogle Scholar
  86. 86.
    Angelis, LM, Mandell, LR, Thaler, HT, Kimmel, DW, Galicich, JH, Fuks, Z, Posner, JB 1989The role of postoperative radiotherapy after resection of single brain metastasesNeurosurgery24798805PubMedGoogle Scholar
  87. 87.
    Patchell, RA, Tibbs, PA, Regine, WF, Dempsey, RJ, Mohiuddin, M, Kryscio, RJ, Markesbery, WR, Foon, KA, Young, B 1998Postoperative radiotherapy in the treatment of single metastases to the brainJAMA28014851489CrossRefPubMedGoogle Scholar
  88. 88.
    Fuller, BG, Kaplan, ID, Adler, J, Cox, RS, Bagshaw, MA 1992Stereotactic radiosurgery for brain metastases: the importance of adjuvant whole-brain irradiationInt J Radiat Oncol Biol Phys23413418PubMedGoogle Scholar
  89. 89.
    Shirato, H, Takamura, A, Tomita, M, Suzuki, K, Nishioka, T, Isu, T, Kato, T, Sawamura, Y, Miyamachi, K, Abe, H, Miyasaka, K 1997Stereotactic irradiation without whole-brain irradiation for single brain metastasisInt J Radiat Oncol Biol Phys37385391CrossRefPubMedGoogle Scholar
  90. 90.
    Li, B, Yu, J, Suntharalingam, M, Kennedy, AS, Amin, PP, Chen, Z, Yin, R, Guo, S, Han, T, Wang, Y, Yu, N, Song, G, Wang, L 2000Comparison of three treatment options for single brain metastasis from lung cancerInt J Cancer903745CrossRefPubMedGoogle Scholar
  91. 91.
    Hasegawa, T, Kondziolka, D, Flickinger, JC, Germanwala, A, Lunsford, LD 2003Brain metastases treated with radiosurgery alone: an alternative to whole-brain radiotherapyNeurosurgery5213181326CrossRefPubMedGoogle Scholar
  92. 92.
    Regine, WF, Huhn, JL, Patchell, RA, St Clair, WH, Strottmann, J, Meigooni, A, Sanders, M, Young, AB 2002Risk of symptomatic brain tumor recurrence and neurologic deficit after radiosurgery alone in patients with newly diagnosed brain metastases: results and implicationsInt J Radiat Oncol Biol Phys52333338CrossRefPubMedGoogle Scholar
  93. 93.
    Lutterbach, J, Cyron, D, Henne, K, Ostertag, CB 2003Radiosurgery followed by planned observation in patients with one to three brain metastasesNeurosurgery5210661074CrossRefPubMedGoogle Scholar
  94. 94.
    Withers, HR, Suwinski, R 1998Radiation dose response for subclinical metastasesSemin Radiat Oncol8224228PubMedGoogle Scholar
  95. 95.
    Einhorn, LH 1995The case against prophylactic cranial irradiation in limited small cell lung cancerSemin Radiat Oncol55760PubMedGoogle Scholar
  96. 96.
    Vines, EF, Pechoux, C, Arriagada, R 2003Prophylactic cranial irradiation in small-cell lung cancerSemin Oncol303846CrossRefGoogle Scholar
  97. 97.
    Auperin, A, Arriagada, R, Pignon, JP, Pechoux, C, Gregor, A, Stephens, RJ, Kristjansen, PE, Johnson, BE, Ueoka, H, Wagner, H, Aisner, J 1999Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group. N Engl J Med341476484CrossRefPubMedGoogle Scholar
  98. 98.
    Meert, AP, Paesmans, M, Berghmans, T, Martin, B, Mascaux, C, Vallot, F, Verdebout, JM, Lafitte, JJ, Sculier, JP 2001Prophylactic cranial irradiation in small-cell lung cancer: a systematic review of the literature with meta-analysisBMC Cancer15CrossRefPubMedGoogle Scholar
  99. 99.
    Robnett, TJ, Machtay, M, Stevenson, JP, Algazy, KM, Hahn, SM 2001Factors affecting the risk of brain metastases after definitive chemoradiation for locally advanced non-small-cell lung carcinomaJ Clin Oncol1913441349PubMedGoogle Scholar
  100. 100.
    Lesser, GJ 1996Chemotherapy of cerebral metastases from solid tumorsNeurosurgery Clin North Am7527536Google Scholar
  101. 101.
    Postmus, PE, Smit, EF 1999Chemotherapy for brain metastases of lung cancer: a reviewAnn Oncol10753759CrossRefPubMedGoogle Scholar
  102. 102.
    Kristensen, CA, Kristjansen, PE, Hansen, HH 1992Systemic chemotherapy of brain metastases from SCLC: a reviewJ Clin Oncol1014981502PubMedGoogle Scholar
  103. 103.
    Grossi, F, Scolaro, T, Tixi, L, Loprevite, M, Ardizzoni, A 2001The role of systemic chemotherapy in the treatment of brain metastases from small-cell lung cancerCrit Rev Oncol Hematol376167PubMedGoogle Scholar
  104. 104.
    Korfel, A, Oehm, C, Pawel, J, Keppler, U, Deppermann, M, Kaubitsch, S, Thiel, E 2002Response to topotecan of symptomatic brain metastases of small-cell lung cancer also after whole-brain irradiation: a multicentre phase II studyEur J Cancer3817241729CrossRefPubMedGoogle Scholar
  105. 105.
    Postmus, PE, Haaxma-Reiche, H, Smit, EF, Groen, HJM, Karnicka, H, Lewinski, T, Meerbeeck, J, Clerico, M, Gregor, A, Curran, D, Sahmoud, T, Kirkpatrick, A, Giaccone, G 2000Treatment of brain metastases of small-cell lung cancer: comparing teniposide and teniposide with whole-brain radiotherapy–a phase III study of the European Organization for the Research and Treatment of Cancer, Lung Cancer Cooperative GroupJ Clin Oncol1834003408PubMedGoogle Scholar
  106. 106.
    Kaba, SE, Kyritsis, AP, Hess, K, Yung, WK, Mercier, R, Dakhil, S, Jaeckle, KA, Levin, VA 1997TPDC-FuHu chemotherapy for the treatment of recurrent metastatic brain tumorsJ Clin Oncol1510631070PubMedGoogle Scholar
  107. 107.
    Crino, L, Scagliotti, GV, Ricci, S, Marinis, G, Rinaldi, M, Gridelli, C, Ceribelli, A, Bianco, R, Marangolo, M, Costanzo, F, Sassi, M, Barni, S, Ravaioli, A, Adamo, V, Portalone, L, Cruciani, G, Masotti, A, Ferrara, G, Gozzelino, F, Tonato, M 1999Gemcitabine and cisplatin versus mitomycin, ifosfamide, and cisplatin in advanced non-small-cell lung cancer: a randomized phase III study of the Italian Lung Cancer ProjectJ Clin Oncol1735223530PubMedGoogle Scholar
  108. 108.
    Franciosi, V, Cocconi, G, Michiara, M, Di Costanzo, F, Fosser, V, Tonato, M, Carlini, P, Boni, C, Di Sarra, S 1999Front-line chemotherapy with cisplatin and etoposide for patients with brain metastases from breast, NSCLC or malignant melanoma: a prospective studyCancer8515991605CrossRefPubMedGoogle Scholar
  109. 109.
    Cortes, J, Rodriguez, J, Aramendia, JM, Salgado, E, Gurpide, A, Garcia-Foncillas, J, Aristu, JJ, Claver, A, Bosch, A, Lopez-Picazo, JM, Martin-Algarra, S, Brugarolas, A, Calvo, E 2003Front-line paclitaxel/cisplatin-based chemotherapy in brain metastases from non-small-cell lung cancerOncology642835CrossRefPubMedGoogle Scholar
  110. 110.
    Abrey, LE, Olson, JD, Raizer, JJ, Mack, M, Rodavitch, A, Boutros, DY 2001A phase II trial of temozolomide for patients with recurrent or progressive brain metastasesJ Neuro-Oncol53259265CrossRefGoogle Scholar
  111. 111.
    Christodoulou, C Bafaloukos, D Kosmidis, P Samantas, E Bamias, A Papakostas, P Karabelis, A Bacoyiannis, C Skarlos DV for the Hellenic Cooperative Oncology Group2001Phase II study of temozolomide in heavily pretreated cancer patients with brain metastasesAnn Oncol12249254CrossRefPubMedGoogle Scholar
  112. 112.
    Dziadziuszko, R Ardizzoni, A Postmus, PE Smit, EF Price, A Debruyne, C Legrand, C Giaccone G on behalf of the EORTC Lung Cancer Group2003Temozolomide in patients with advanced non-small-cell lung cancer with and without brain metastases: a phase II study of the EORTC Lung Cancer Group (08965)Eur J Cancer3912711276CrossRefPubMedGoogle Scholar
  113. 113.
    Ushio, Y, Arita, N, Hayakawa, T, Mogami, H, Hasegawa, H, Bitoh, S, Oku, Y, Ikeda, H, Kanai, N, Kanoh, M 1991Chemotherapy of brain metastases from lung carcinoma: a controlled randomized studyNeurosurgery28201205CrossRefPubMedGoogle Scholar
  114. 114.
    Robinet, G, Thomas, P, Breton, JL, Lena, H, Gouva, S, Dabouis, G, Bennouna, J, Souquet, PJ, Balmes, P, Thiberville, L, Fournel, P, Quoix, E, Riou, R, Rebattu, P, Perol, M, Paillotin, D, Mornex, F 2001Results of a phase III study of early versus delayed whole brain radiotherapy with concurrent cisplatin and vinorelbine combination in inoperable brain metastases of non-small-cell lung cancer: Groupe Francais de Pneumocancerologie (GFPC) protocol 95-1Ann Oncol125967CrossRefPubMedGoogle Scholar
  115. 115.
    Antonadou, D, Paraskevaidis, M, Sarris, G, Coliarakis, N, Economou, I, Karageorgis, P, Throuvalas, N 2002Phase II randomized trial of temozolomide and concurrent radiotherapy in patients with brain metastasesJ Clin Oncol2036443650CrossRefPubMedGoogle Scholar
  116. 116.
    Cappuzzo, F, Ardizzoni, A, Soto-Parra, H, Gridelli, C, Maione, P, Tiseo, M, Calandri, C, Bartolini, S, Santoro, A, Crinò, L 2003Epidermal growth factor receptor targeted therapy by ZD 1839 (Iressa) in patients with brain metastases from non-small-cell lung cancer (NSCLC)Lung Cancer41227231CrossRefPubMedGoogle Scholar
  117. 117.
    Rozner, D, Nemoto, T, Lane, WW 1986Chemotherapy induces regression of brain metastases in breast carcinomaCancer58832839PubMedGoogle Scholar
  118. 118.
    Boogerd, W, Dalesio, O, Bais, EM, Sande, JJ 1992Response of brain metastases from breast cancer to systemic chemotherapyCancer69972980PubMedGoogle Scholar
  119. 119.
    Cocconi, G, Lottici, R, Bisagni, G, Bacchi, M, Tonato, M, Passalacqua, R, Boni, C, Belsanti, V, Bassi, P 1990Combination therapy with platinum and etoposide of brain metastases from breast carcinomaCancer Invest8327334PubMedGoogle Scholar
  120. 120.
    Colleoni, M, Graiff, C, Nelli, P, Vicario, G, Sgarbossa, G, Pancheri, F, Manente, P 1997Activity of combination chemotherapy in brain metastases from breast and lung adenocarcinomaAm J Clin Oncol20303307CrossRefPubMedGoogle Scholar
  121. 121.
    Siegelmann-Danieli, N, Stein, M, Bar-Ziv, J 2003Complete response of brain metastases originating in breast cancer to capecitabine therapyIsr Med Assoc J5833834PubMedGoogle Scholar
  122. 122.
    Carey, RW, Davis, JM, Zervas, NT 1981Tamoxifen-induced regression of cerebral metastases in breast carcinomaCancer Treat Rep65793795PubMedGoogle Scholar
  123. 123.
    Pors, H, Eyben, FE, Sorensen, OS, Larsen, M 1991Longterm remission of multiple brain metastases with tamoxifenJ Neurooncol10173177CrossRefPubMedGoogle Scholar
  124. 124.
    Salvati, M, Cervoni, L, Innocenzi, G, Bardella, L 1993Prolonged stabilization of multiple and single brain metastases from breast cancer with tamoxifenReport of three cases. Tumori79359362Google Scholar
  125. 125.
    Gaast, A, Alexieva-Figusch, J, Vecht, C, Verweij, J, Stoter, G 1990Complete remission of a brain metastasis to third-line hormonal treatment with megestrol acetateAm J Clin Oncol13507509PubMedGoogle Scholar
  126. 126.
    Lissoni, P, Barni, S, Ardizzoia, A, Tancini, G, Conti, A, Maestroni, G 1994A randomized study with the pineal hormone melatonin versus supportive care alone in patients with brain metastases due to solid neoplasmsCancer73699701PubMedGoogle Scholar
  127. 127.
    Bendell, JC, Domchek, SM, Burstein, HJ, Harris, L, Younger, J, Kuter, I, Bunnell, C, Rue, M, Gelman, R, Winer, E 2003Central nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinomaCancer9729722977CrossRefPubMedGoogle Scholar
  128. 128.
    Shmueli, E, Wigler, N, Inbar, M 2004Central nervous system progression among patients with metastatic breast cancer responding to trastuzumab treatmentEur J Cancer40379382CrossRefPubMedGoogle Scholar
  129. 129.
    Kirsch, DG, Hochberg, FH 2003Targeting HER2 in brain metastases from breast cancerClin Cancer Res954355436PubMedGoogle Scholar
  130. 130.
    Fossa, SD, Bokemeyer, C, Gerl, A, Culine, S, Jones, WG, Mead, GM, Germa-Luch, JR, Pont, J, Schmoll, HJ, Tjulandin, S 1999Treatment outcome of patients with brain metastases from malignant germ cell tumorsCancer85988997CrossRefPubMedGoogle Scholar
  131. 131.
    Newlands, ES, Bagshawe, KD, Begent, RH, Rustin, GJ, Holden, L 1991Results with the EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) regimen in high risk gestational trophoblastic tumours, 1979 to 1989Br J Obstet Gynaecol98550557PubMedGoogle Scholar
  132. 132.
    Cooper, KG, Kitchener, HC, Parkin, DE 1994Cerebral metastases from epithelial ovarian carcinoma treated with carboplatinGynecol Oncol55318323CrossRefPubMedGoogle Scholar
  133. 133.
    Abrey, LE, Dalmau, JO 1999Neurologic complications of ovarian carcinomaCancer85127133CrossRefPubMedGoogle Scholar
  134. 134.
    Jacquillat, C, Khayat, D, Banzet, P, Weil, M, Fumoleau, P, Avril, MF, Namer, M, Bonneterre, J, Kerbrat, P, Bonerandi, JJ 1990Final report of the French multicenter phase II study of the nitrosourea fotemustine in 153 evaluable patients with disseminated malignant melanoma including patients with cerebral metastasesCancer6618731878PubMedGoogle Scholar
  135. 135.
    Middleton, MR, Grob, JJ, Aaronson, N, Fierlbeck, G, Tilgen, W, Seiter, S, Gore, M, Aamdal, S, Cebon, J, Coates, A, Dreno, B, Henz, M, Schadendorf, D, Kapp, A, Weiss, J, Fraass, U, Statkevich, P, Muller, M, Thatcher, N 2000Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanomaJ Clin Oncol18158166PubMedGoogle Scholar
  136. 136.
    Biasco, G, Pantaleo, MA, Casadei, S 2001Treatment of brain metastases of malignant melanoma with temozolomideN Eng J Med345621622CrossRefGoogle Scholar
  137. 137.
    Nakagawa, H, Fujita, T, Izumimoto, S, Miyawaki, Y, Kubo, S, Nakajima, Y, Tsuruzono, K, Kodama, K, Higashiyama, M, Doi, O 1993cis-diamminedichloroplatinum (CDDP) therapy for brain metastasis of lung cancerII: Clinical effects. J Neurooncol166976Google Scholar
  138. 138.
    Soffietti, R, Ruda, R, Mutani, R 2002Management of brain metastasesJ Neurol24913571369CrossRefPubMedGoogle Scholar

Copyright information

© Springer 2005

Authors and Affiliations

  • R. Soffietti
    • 1
    Email author
  • A. Costanza
    • 1
  • E. Laguzzi
    • 1
  • M. Nobile
    • 1
  • R. Rudà
    • 1
  1. 1.Neuro-Oncology Service, Department of NeuroscienceUniversity and San Giovanni Battista HospitalTorinoItaly

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