Skip to main content

Advertisement

Log in

A systematic approach to the management of patients with brain metastases of known or unknown primary site

  • Mini Review
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

To establish an empirical systematic approach for the management of brain metastases from a variety of cancers.

Methods

The English literature was reviewed from 2000 to 2011 and all clinical trials (phase II, phase III and retrospective studies) regarding therapy of brain metastases were selected for more detailed review. Some key articles published prior to 2000 were also included in the review as are supplemental recommendations based on our clinical experience.

Results

Patients with brain metastases from small cell lung cancer (SCLC) at the initial cancer diagnosis can be treated with concomitant whole-brain radiation therapy (WBRT) and chemotherapy or first with chemotherapy followed by WBRT. In all other cases, brain metastases are currently treated independently of the management of the extracranial disease with surgery or radiosurgery followed by WBRT. In radioresistant tumors (melanoma, sarcoma, renal cell carcinoma), WBRT may be omitted initially but administered at recurrence. Where surgery or radiosurgery is not an option for patients, WBRT should be administered. Prophylactic WBRT should be given in patients with SCLC and considered in patients with non-small cell lung cancer. Apart from its use in SCLC, chemotherapy for the treatment of brain metastases is reserved for patients enrolled in clinical trials.

Conclusion

Brain metastases should be treated aggressively and independently of the primary site tumor especially if the performance status of the patient is good. The role of chemotherapy should be addressed in the context of clinical trials.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Aragon-Ching JB, Zujewski JA (2007) CNS metastasis: an old problem in a new guise. Clin Cancer Res 13(6):1644–1647. doi:10.1158/1078-0432.CCR-07-0096

    Article  PubMed  CAS  Google Scholar 

  2. Walker AE, Robins M, Weinfeld FD (1985) Epidemiology of brain tumors: the national survey of intracranial neoplasms. Neurology 35(2):219–226

    PubMed  CAS  Google Scholar 

  3. Eichler AF, Chung E, Kodack DP, Loeffler JS, Fukumura D, Jain RK (2011) The biology of brain metastases-translation to new therapies. Nat Rev Clin Oncol. doi:10.1038/nrclinonc.2011.58

    PubMed  Google Scholar 

  4. Nussbaum ES, Djalilian HR, Cho KH, Hall WA (1996) Brain metastases. Histology, multiplicity, surgery, and survival. Cancer 78(8):1781–1788

    Article  PubMed  CAS  Google Scholar 

  5. Gremmer R, Schroder ML, Ten Huinink WW, Brandsma D, Boogerd W (2008) Successful management of brain metastasis from malignant germ cell tumours with standard induction chemotherapy. J Neurooncol 90(3):335–339. doi:10.1007/s11060-008-9668-4

    Article  PubMed  CAS  Google Scholar 

  6. Levin V, Giglio P, Kyritsis AP (2005) The management of gliomas, medulloblastoma, CNS germ cell tumors, and carcinomas metastatic to the CNS. In: Cavalli F, Hansen H, Kaye S (eds) Textbook of medical oncology. Martin Dunitz, London, pp 415–430

    Google Scholar 

  7. Campos S, Davey P, Hird A, Pressnail B, Bilbao J, Aviv RI, Symons S, Pirouzmand F, Sinclair E, Culleton S, Desa E, Goh P, Chow E (2009) Brain metastasis from an unknown primary, or primary brain tumour? A diagnostic dilemma. Curr Oncol 16(1):62–66

    PubMed  CAS  Google Scholar 

  8. Giannopoulos S, Kyritsis AP (2010) Diagnosis and management of multifocal gliomas. Oncology 79(3–4):306–312. doi:10.1159/000323492

    Article  PubMed  Google Scholar 

  9. Kyritsis AP, Yung WK, Leeds NE, Bruner J, Gleason MJ, Levin VA (1992) Multifocal cerebral gliomas associated with secondary malignancies. Lancet 339(8803):1229–1230

    Article  PubMed  CAS  Google Scholar 

  10. Bondy M, Wiencke J, Wrensch M, Kyritsis AP (1994) Genetics of primary brain tumors: a review. J Neurooncol 18(1):69–81

    Article  PubMed  CAS  Google Scholar 

  11. Kyritsis AP, Bondy ML, Rao JS, Sioka C (2010) Inherited predisposition to glioma. Neuro Oncol 12(1):104–113. doi:10.1093/neuonc/nop011

    Article  PubMed  CAS  Google Scholar 

  12. Kyritsis AP, Levin VA, Yung WK, Leeds NE (1993) Imaging patterns of multifocal gliomas. Eur J Radiol 16(3):163–170

    Article  PubMed  CAS  Google Scholar 

  13. Sperduto PW (2010) What is your patient’s GPA and why does it matter? Managing brain metastases and the cost of hope. Int J Radiat Oncol Biol Phys 77(3):643–644. doi:10.1016/j.ijrobp.2010.02.038

    Article  PubMed  Google Scholar 

  14. Gaspar L, Scott C, Rotman M, Asbell S, Phillips T, Wasserman T, McKenna WG, Byhardt R (1997) Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys 37(4):745–751

    Article  PubMed  CAS  Google Scholar 

  15. Sperduto PW, Berkey B, Gaspar LE, Mehta M, Curran W (2008) A new prognostic index and comparison to three other indices for patients with brain metastases: an analysis of 1, 960 patients in the RTOG database. Int J Radiat Oncol Biol Phys 70(2):510–514. doi:10.1016/j.ijrobp.2007.06.074

    Article  PubMed  Google Scholar 

  16. Sperduto PW, Chao ST, Sneed PK, Luo X, Suh J, Roberge D, Bhatt A, Jensen AW, Brown PD, Shih H, Kirkpatrick J, Schwer A, Gaspar LE, Fiveash JB, Chiang V, Knisely J, Sperduto CM, Mehta M (2010) Diagnosis-specific prognostic factors, indexes, and treatment outcomes for patients with newly diagnosed brain metastases: a multi-institutional analysis of 4, 259 patients. Int J Radiat Oncol Biol Phys 77(3):655–661. doi:10.1016/j.ijrobp.2009.08.025

    Article  PubMed  Google Scholar 

  17. Sperduto PW, Kased N, Roberge D, Xu Z, Shanley R, Luo X, Sneed PK, Chao ST, Weil RJ, Suh J, Bhatt A, Jensen AW, Brown PD, Shih HA, Kirkpatrick J, Gaspar LE, Fiveash JB, Chiang V, Knisely JP, Sperduto CM, Lin N, Mehta M (2011) Effect of tumor subtype on survival and the graded prognostic assessment for patients with breast cancer and brain metastases. Int J Radiat Oncol Biol Phys. doi:10.1016/j.ijrobp.2011.02.027

    PubMed  Google Scholar 

  18. Alexiou GA, Bokharhii JA, Kyritsis AP, Polyzoidis KS, Fotopoulos AD (2006) Tc-99 m Tetrofosmin SPECT for the differentiation of a cerebellar hemorrhage mimicking a brain metastasis from a renal cell carcinoma. J Neurooncol 78(2):207–208. doi:10.1007/s11060-005-9074-0

    Article  PubMed  CAS  Google Scholar 

  19. Hochstenbag MM, Twijnstra A, Wilmink JT, Wouters EF, ten Velde GP (2000) Asymptomatic brain metastases (BM) in small cell lung cancer (SCLC): MR-imaging is useful at initial diagnosis. J Neurooncol 48(3):243–248

    Article  PubMed  CAS  Google Scholar 

  20. Glantz MJ, Cole BF, Friedberg MH, Lathi E, Choy H, Furie K, Akerley W, Wahlberg L, Lekos A, Louis S (1996) A randomized, blinded, placebo-controlled trial of divalproex sodium prophylaxis in adults with newly diagnosed brain tumors. Neurology 46(4):985–991

    PubMed  CAS  Google Scholar 

  21. Glantz MJ, Cole BF, Forsyth PA, Recht LD, Wen PY, Chamberlain MC, Grossman SA, Cairncross JG (2000) Practice parameter: anticonvulsant prophylaxis in patients with newly diagnosed brain tumors. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 54(10):1886–1893

    PubMed  CAS  Google Scholar 

  22. Sirven JI, Wingerchuk DM, Drazkowski JF, Lyons MK, Zimmerman RS (2004) Seizure prophylaxis in patients with brain tumors: a meta-analysis. Mayo Clin Proc 79(12):1489–1494

    Article  PubMed  Google Scholar 

  23. Sioka C, Kyritsis AP (2009) Central and peripheral nervous system toxicity of common chemotherapeutic agents. Cancer Chemother Pharmacol 63(5):761–767. doi:10.1007/s00280-008-0876-6

    Article  PubMed  CAS  Google Scholar 

  24. Aoyama H, Tago M, Kato N, Toyoda T, Kenjyo M, Hirota S, Shioura H, Inomata T, Kunieda E, Hayakawa K, Nakagawa K, Kobashi G, Shirato H (2007) 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(5):1388–1395. doi:10.1016/j.ijrobp.2007.03.048

    Article  PubMed  Google Scholar 

  25. DeAngelis LM, Delattre JY, Posner JB (1989) Radiation-induced dementia in patients cured of brain metastases. Neurology 39(6):789–796

    PubMed  CAS  Google Scholar 

  26. Li J, Bentzen SM, Renschler M, Mehta MP (2007) Regression after whole-brain radiation therapy for brain metastases correlates with survival and improved neurocognitive function. J Clin Oncol 25(10):1260–1266. doi:10.1200/JCO.2006.09.2536

    Article  PubMed  Google Scholar 

  27. Wong J, Hird A, Kirou-Mauro A, Napolskikh J, Chow E (2008) Quality of life in brain metastases radiation trials: a literature review. Curr Oncol 15(5):25–45

    Article  PubMed  CAS  Google Scholar 

  28. Welzel G, Fleckenstein K, Schaefer J, Hermann B, Kraus-Tiefenbacher U, Mai SK, Wenz F (2008) Memory function before and after whole brain radiotherapy in patients with and without brain metastases. Int J Radiat Oncol Biol Phys 72(5):1311–1318. doi:10.1016/j.ijrobp.2008.03.009

    Article  PubMed  Google Scholar 

  29. Jenkinson MD, Haylock B, Shenoy A, Husband D, Javadpour M (2011) Management of cerebral metastasis: evidence-based approach for surgery, stereotactic radiosurgery and radiotherapy. Eur J Cancer 47(5):649–655. doi:10.1016/j.ejca.2010.11.033

    Article  PubMed  Google Scholar 

  30. Li J, Bentzen SM, Renschler M, Mehta MP (2008) Relationship between neurocognitive function and quality of life after whole-brain radiotherapy in patients with brain metastasis. Int J Radiat Oncol Biol Phys 71(1):64–70. doi:10.1016/j.ijrobp.2007.09.059

    Article  PubMed  Google Scholar 

  31. Sun A, Bae K, Gore EM, Movsas B, Wong SJ, Meyers CA, Bonner JA, Schild SE, Gaspar LE, Bogart JA, Werner-Wasik M, Choy H (2011) Phase III trial of prophylactic cranial irradiation compared with observation in patients with locally advanced non-small-cell lung cancer: neurocognitive and quality-of-life analysis. J Clin Oncol 29(3):279–286. doi:10.1200/JCO.2010.29.6053

    Article  PubMed  Google Scholar 

  32. Grosshans DR, Meyers CA, Allen PK, Davenport SD, Komaki R (2008) Neurocognitive function in patients with small cell lung cancer : effect of prophylactic cranial irradiation. Cancer 112(3):589–595. doi:10.1002/cncr.23222

    Article  PubMed  Google Scholar 

  33. Le Pechoux C, Laplanche A, Faivre-Finn C, Ciuleanu T, Wanders R, Lerouge D, Keus R, Hatton M, Videtic GM, Senan S, Wolfson A, Jones R, Arriagada R, Quoix E, Dunant A (2011) Clinical neurological outcome and quality of life among patients with limited small-cell cancer treated with two different doses of prophylactic cranial irradiation in the intergroup phase III trial (PCI99-01, EORTC 22003-08004, RTOG 0212 and IFCT 99-01). Ann Oncol 22(5):1154–1163. doi:10.1093/annonc/mdq576

    Article  PubMed  Google Scholar 

  34. Weitzner MA, Meyers CA, Valentine AD (1995) Methylphenidate in the treatment of neurobehavioral slowing associated with cancer and cancer treatment. J Neuropsychiatry Clin Neurosci 7(3):347–350

    PubMed  CAS  Google Scholar 

  35. Spathis A, Dhillan R, Booden D, Forbes K, Vrotsou K, Fife K (2009) Modafinil for the treatment of fatigue in lung cancer: a pilot study. Palliat Med 23(4):325–331. doi:10.1177/0269216309102614

    Article  PubMed  CAS  Google Scholar 

  36. Kyritsis A (1998) Evaluation and treatment of CNS neoplasms. In: Lechtenberg R, Schutta HS (eds) Neurology practice guidelines. Marcel Dekker, New York, pp 473–496

    Google Scholar 

  37. Gonzalez J, Kumar AJ, Conrad CA, Levin VA (2007) Effect of bevacizumab on radiation necrosis of the brain. Int J Radiat Oncol Biol Phys 67(2):323–326. doi:10.1016/j.ijrobp.2006.10.010

    Article  PubMed  CAS  Google Scholar 

  38. Levin VA, Bidaut L, Hou P, Kumar AJ, Wefel JS, Bekele BN, Prabhu S, Loghin M, Gilbert MR, Jackson EF (2010) Randomized double-blind placebo-controlled trial of bevacizumab therapy for radiation necrosis of the central nervous system. Int J Radiat Oncol Biol Phys 79(5):1487–1495. doi:10.1016/j.ijrobp.2009.12.061

    Google Scholar 

  39. Al-Shamy G, Sawaya R (2009) Management of brain metastases: the indispensable role of surgery. J Neurooncol 92(3):275–282. doi:10.1007/s11060-009-9839-y

    Article  PubMed  Google Scholar 

  40. Soffietti R, Ruda R, Trevisan E (2008) Brain metastases: current management and new developments. Curr Opin Oncol 20(6):676–684. doi:10.1097/CCO.0b013e32831186fe00001622-200811000-00012

    Article  PubMed  Google Scholar 

  41. Narita Y, Shibui S (2009) Strategy of surgery and radiation therapy for brain metastases. Int J Clin Oncol 14(4):275–280. doi:10.1007/s10147-009-0917-0

    Article  PubMed  Google Scholar 

  42. Rao RD, Brown PD, Buckner JC (2007) Innovation in the management of brain metastases. Oncology (Williston Park) 21(4):473–481. discussion 482, 484, 489

  43. Patchell RA, Regine WF, Renschler M, Loeffler JS, Sawaya R, Chin LS, Andrews DW (2006) Comments about the prospective randomized trial by Aoyama et al. Surg Neurol 66(5):459–460. doi:10.1016/j.surneu.2006.08.003

    Article  PubMed  Google Scholar 

  44. Rades D, Kieckebusch S, Haatanen T, Lohynska R, Dunst J, Schild SE (2008) Surgical resection followed by whole brain radiotherapy versus whole brain radiotherapy alone for single brain metastasis. Int J Radiat Oncol Biol Phys 70(5):1319–1324. doi:10.1016/j.ijrobp.2007.08.009

    Article  PubMed  Google Scholar 

  45. Rodrigus P, de Brouwer P, Raaymakers E (2001) Brain metastases and non-small cell lung cancer. Prognostic factors and correlation with survival after irradiation. Lung Cancer 32(2):129–136

    Article  PubMed  CAS  Google Scholar 

  46. Rogers LR, Rock JP, Sills AK, Vogelbaum MA, Suh JH, Ellis TL, Stieber VW, Asher AL, Fraser RW, Billingsley JS, Lewis P, Schellingerhout D, Shaw EG (2006) Results of a phase II trial of the GliaSite radiation therapy system for the treatment of newly diagnosed, resected single brain metastases. J Neurosurg 105(3):375–384. doi:10.3171/jns.2006.105.3.375

    Article  PubMed  Google Scholar 

  47. Cohen ZR, Suki D, Weinberg JS, Marmor E, Lang FF, Gershenson DM, Sawaya R (2004) Brain metastases in patients with ovarian carcinoma: prognostic factors and outcome. J Neurooncol 66(3):313–325

    Article  PubMed  Google Scholar 

  48. Rajendra T, Ann Lee K, Thomas J, Hong A, Chan C (2003) Results of surgical treatment for cerebral metastases. J Clin Neurosci 10(2):190–194

    Article  PubMed  Google Scholar 

  49. Roberge D, Petrecca K, El Refae M, Souhami L (2009) Whole-brain radiotherapy and tumor bed radiosurgery following resection of solitary brain metastases. J Neurooncol 95(1):95–99. doi:10.1007/s11060-009-9899-z

    Article  PubMed  Google Scholar 

  50. Ewend MG, Brem S, Gilbert M, Goodkin R, Penar PL, Varia M, Cush S, Carey LA (2007) Treatment of single brain metastasis with resection, intracavity carmustine polymer wafers, and radiation therapy is safe and provides excellent local control. Clin Cancer Res 13(12):3637–3641. doi:10.1158/1078-0432.CCR-06-2095

    Article  PubMed  CAS  Google Scholar 

  51. Patel AJ, Suki D, Hatiboglu MA, Abouassi H, Shi W, Wildrick DM, Lang FF, Sawaya R (2010) Factors influencing the risk of local recurrence after resection of a single brain metastasis. J Neurosurg 113(2):181–189. doi:10.3171/2009.11.JNS09659

    Article  PubMed  Google Scholar 

  52. Suki D, Hatiboglu MA, Patel AJ, Weinberg JS, Groves MD, Mahajan A, Sawaya R (2009) Comparative risk of leptomeningeal dissemination of cancer after surgery or stereotactic radiosurgery for a single supratentorial solid tumor metastasis. Neurosurgery 64(4):664–674; discussion 674–666. doi:10.1227/01.NEU.0000341535.53720.3E

    Google Scholar 

  53. Bindal RK, Sawaya R, Leavens ME, Lee JJ (1993) Surgical treatment of multiple brain metastases. J Neurosurg 79(2):210–216. doi:10.3171/jns.1993.79.2.0210

    Article  PubMed  CAS  Google Scholar 

  54. Ruda R, Borgognone M, Benech F, Vasario E, Soffietti R (2001) Brain metastases from unknown primary tumour: a prospective study. J Neurol 248(5):394–398

    Article  PubMed  CAS  Google Scholar 

  55. Mehta MP, Tsao MN, Whelan TJ, Morris DE, Hayman JA, Flickinger JC, Mills M, Rogers CL, Souhami L (2005) The American Society for Therapeutic Radiology and Oncology (ASTRO) evidence-based review of the role of radiosurgery for brain metastases. Int J Radiat Oncol Biol Phys 63(1):37–46. doi:10.1016/j.ijrobp.2005.05.023

    Article  PubMed  Google Scholar 

  56. Pantazis G, Trippel M, Birg W, Ostertag CB, Nikkhah G (2009) Stereotactic interstitial radiosurgery with the Photon Radiosurgery System (PRS) for metastatic brain tumors: a prospective single-center clinical trial. Int J Radiat Oncol Biol Phys 75(5):1392–1400. doi:10.1016/j.ijrobp.2009.01.022

    Article  PubMed  Google Scholar 

  57. Mahmoud-Ahmed AS, Kupelian PA, Reddy CA, Suh JH (2002) Brain metastases from gynecological cancers: factors that affect overall survival. Technol Cancer Res Treat 1(4):305–310

    PubMed  Google Scholar 

  58. Raizer JJ, Hwu WJ, Panageas KS, Wilton A, Baldwin DE, Bailey E, von Althann C, Lamb LA, Alvarado G, Bilsky MH, Gutin PH (2008) Brain and leptomeningeal metastases from cutaneous melanoma: survival outcomes based on clinical features. Neuro Oncol 10(2):199–207. doi:10.1215/15228517-2007-058

    Article  PubMed  Google Scholar 

  59. Lutterbach J, Cyron D, Henne K, Ostertag CB (2008) Radiosurgery followed by planned observation in patients with one to three brain metastases. Neurosurgery 62(Suppl 2):776–784. doi:10.1227/01.neu.0000316281.07124.ea00006123-200802001-00033

    PubMed  Google Scholar 

  60. Gupta T (2005) Stereotactic radiosurgery for brain oligometastases: good for some, better for all? Ann Oncol 16(11):1749–1754. doi:10.1093/annonc/mdi392

    Article  PubMed  CAS  Google Scholar 

  61. 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 (2001) Radiosurgery for patients with brain metastases: a multi-institutional analysis, stratified by the RTOG recursive partitioning analysis method. Int J Radiat Oncol Biol Phys 51(2):426–434

    Article  PubMed  CAS  Google Scholar 

  62. Kocher M, Maarouf M, Bendel M, Voges J, Muller RP, Sturm V (2004) Linac radiosurgery versus whole brain radiotherapy for brain metastases. A survival comparison based on the RTOG recursive partitioning analysis. Strahlenther Onkol 180(5):263–267. doi:10.1007/s00066-004-1180-y

    Article  PubMed  Google Scholar 

  63. Aoyama H, Shirato H, Tago M, Nakagawa K, Toyoda T, Hatano K, Kenjyo M, Oya N, Hirota S, Shioura H, Kunieda E, Inomata T, Hayakawa K, Katoh N, Kobashi G (2006) Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. JAMA 295(21):2483–2491. doi:10.1001/jama.295.21.2483

    Article  PubMed  CAS  Google Scholar 

  64. Andrews DW, Scott CB, Sperduto PW, Flanders AE, Gaspar LE, Schell MC, Werner-Wasik M, Demas W, Ryu J, Bahary JP, Souhami L, Rotman M, Mehta MP, Curran WJ Jr (2004) 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(9422):1665–1672. doi:10.1016/S0140-6736(04)16250-8S0140-6736(04)16250-8

    Article  PubMed  Google Scholar 

  65. Simonova G, Liscak R, Novotny J Jr, Novotny J (2000) Solitary brain metastases treated with the Leksell gamma knife: prognostic factors for patients. Radiother Oncol 57(2):207–213

    Article  PubMed  CAS  Google Scholar 

  66. Noel G, Medioni J, Valery CA, Boisserie G, Simon JM, Cornu P, Hasboun D, Ledu D, Tep B, Delattre JY, Marsault C, Baillet F, Mazeron JJ (2003) Three irradiation treatment options including radiosurgery for brain metastases from primary lung cancer. Lung Cancer 41(3):333–343

    Article  PubMed  Google Scholar 

  67. Selek U, Chang EL, Hassenbusch SJ III, Shiu AS, Lang FF, Allen P, Weinberg J, Sawaya R, Maor MH (2004) Stereotactic radiosurgical treatment in 103 patients for 153 cerebral melanoma metastases. Int J Radiat Oncol Biol Phys 59(4):1097–1106. doi:10.1016/j.ijrobp.2003.12.037

    Article  PubMed  Google Scholar 

  68. Amendola BE, Wolf AL, Coy SR, Amendola M, Bloch L (2000) Brain metastases in renal cell carcinoma: management with gamma knife radiosurgery. Cancer J 6(6):372–376

    PubMed  CAS  Google Scholar 

  69. Hoshi S, Jokura H, Nakamura H, Shintaku I, Ohyama C, Satoh M, Saito S, Fukuzaki A, Orikasa S, Yoshimoto T (2002) Gamma-knife radiosurgery for brain metastasis of renal cell carcinoma: results in 42 patients. Int J Urol 9(11):618–625; discussion 626; author reply 627

    Google Scholar 

  70. Noel G, Simon JM, Valery CA, Cornu P, Boisserie G, Hasboun D, Ledu D, Tep B, Delattre JY, Marsault C, Baillet F, Mazeron JJ (2003) Radiosurgery for brain metastasis: impact of CTV on local control. Radiother Oncol 68(1):15–21

    Article  PubMed  Google Scholar 

  71. Muacevic A, Wowra B, Siefert A, Tonn JC, Steiger HJ, Kreth FW (2008) Microsurgery plus whole brain irradiation versus Gamma Knife surgery alone for treatment of single metastases to the brain: a randomized controlled multicentre phase III trial. J Neurooncol 87(3):299–307. doi:10.1007/s11060-007-9510-4

    Article  PubMed  Google Scholar 

  72. Ernst-Stecken A, Ganslandt O, Lambrecht U, Sauer R, Grabenbauer G (2006) Phase II trial of hypofractionated stereotactic radiotherapy for brain metastases: results and toxicity. Radiother Oncol 81(1):18–24. doi:10.1016/j.radonc.2006.08.024

    Article  PubMed  Google Scholar 

  73. Franzin A, Vimercati A, Picozzi P, Serra C, Snider S, Gioia L, Ferrari da Passano C, Bolognesi A, Giovanelli M (2008) Stereotactic drainage and Gamma Knife radiosurgery of cystic brain metastasis. J Neurosurg 109(2):259–267. doi:10.3171/JNS/2008/109/8/0259

    Article  PubMed  Google Scholar 

  74. Noel G, Proudhom MA, Valery CA, Cornu P, Boisserie G, Hasboun D, Simon JM, Feuvret L, Duffau H, Tep B, Delattre JY, Marsault C, Philippon J, Fohanno D, Baillet F, Mazeron JJ (2001) Radiosurgery for re-irradiation of brain metastasis: results in 54 patients. Radiother Oncol 60(1):61–67

    Article  PubMed  CAS  Google Scholar 

  75. Fortin D, Gendron C, Boudrias M, Garant MP (2007) Enhanced chemotherapy delivery by intraarterial infusion and blood-brain barrier disruption in the treatment of cerebral metastasis. Cancer 109(4):751–760. doi:10.1002/cncr.22450

    Article  PubMed  CAS  Google Scholar 

  76. Chen G, Huynh M, Chen A, Fehrenbacher L, Gandara D, Lau D (2008) Chemotherapy for brain metastases in small-cell lung cancer. Clin Lung Cancer 9(1):35–38

    Article  PubMed  CAS  Google Scholar 

  77. 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 (2001) Results of a phase III study of early versus delayed whole brain radiotherapy with concurrent cisplatin and vinorelbine combination in inoperable brain metastasis of non-small-cell lung cancer: Groupe Francais de Pneumo-Cancerologie (GFPC) Protocol 95-1. Ann Oncol 12(1):59–67

    Article  PubMed  CAS  Google Scholar 

  78. Ma S, Xu Y, Deng Q, Yu X (2009) Treatment of brain metastasis from non-small cell lung cancer with whole brain radiotherapy and Gefitinib in a Chinese population. Lung Cancer 65(2):198–203. doi:10.1016/j.lungcan.2008.10.028

    Article  PubMed  Google Scholar 

  79. Kaba SE, Kyritsis AP, Hess K, Yung WK, Mercier R, Dakhil S, Jaeckle KA, Levin VA (1997) TPDC-FuHu chemotherapy for the treatment of recurrent metastatic brain tumors. J Clin Oncol 15(3):1063–1070

    PubMed  CAS  Google Scholar 

  80. Kyritsis AP (2010) Management of primary intracranial germ cell tumors. J Neurooncol 96(2):143–149. doi:10.1007/s11060-009-9951-z

    Article  PubMed  Google Scholar 

  81. Kyritsis AP, Levin VA (2011) An algorithm for chemotherapy treatment of recurrent glioma patients after temozolomide failure in the general oncology setting. Cancer Chemother Pharmacol 67(5):971–983. doi:10.1007/s00280-011-1617-9

    Article  PubMed  CAS  Google Scholar 

  82. Kouvaris JR, Miliadou A, Kouloulias VE, Kolokouris D, Balafouta MJ, Papacharalampous XN, Vlahos LJ (2007) Phase II study of temozolomide and concomitant whole-brain radiotherapy in patients with brain metastases from solid tumors. Onkologie 30(7):361–366. doi:10.1159/0000102557

    Article  PubMed  CAS  Google Scholar 

  83. Addeo R, Caraglia M, Faiola V, Capasso E, Vincenzi B, Montella L, Guarrasi R, Caserta L, Del Prete S (2007) Concomitant treatment of brain metastasis with whole brain radiotherapy [WBRT] and temozolomide [TMZ] is active and improves quality of life. BMC Cancer 7:18

    Article  PubMed  CAS  Google Scholar 

  84. Addeo R, De Rosa C, Faiola V, Leo L, Cennamo G, Montella L, Guarrasi R, Vincenzi B, Caraglia M, Del Prete S (2008) Phase 2 trial of temozolomide using protracted low-dose and whole-brain radiotherapy for nonsmall cell lung cancer and breast cancer patients with brain metastases. Cancer 113(9):2524–2531. doi:10.1002/cncr.23859

    Article  PubMed  CAS  Google Scholar 

  85. Margolin K, Atkins B, Thompson A, Ernstoff S, Weber J, Flaherty L, Clark I, Weiss G, Sosman J, IIS W, Dutcher P, Gollob J, Longmate J, Johnson D (2002) Temozolomide and whole brain irradiation in melanoma metastatic to the brain: a phase II trial of the Cytokine Working Group. J Cancer Res Clin Oncol 128(4):214–218. doi:10.1007/s00432-002-0323-8

    Article  PubMed  CAS  Google Scholar 

  86. Boogerd W, de Gast GC, Dalesio O (2007) Temozolomide in advanced malignant melanoma with small brain metastases: can we withhold cranial irradiation? Cancer 109(2):306–312. doi:10.1002/cncr.22411

    Article  PubMed  CAS  Google Scholar 

  87. Hofmann M, Kiecker F, Wurm R, Schlenger L, Budach V, Sterry W, Trefzer U (2006) Temozolomide with or without radiotherapy in melanoma with unresectable brain metastases. J Neurooncol 76(1):59–64. doi:10.1007/s11060-005-2914-0

    Article  PubMed  CAS  Google Scholar 

  88. Atkins MB, Sosman JA, Agarwala S, Logan T, Clark JI, Ernstoff MS, Lawson D, Dutcher JP, Weiss G, Curti B, Margolin KA (2008) Temozolomide, thalidomide, and whole brain radiation therapy for patients with brain metastasis from metastatic melanoma: a phase II Cytokine Working Group study. Cancer 113(8):2139–2145. doi:10.1002/cncr.23805

    Article  PubMed  CAS  Google Scholar 

  89. Mikkelsen T, Anderson J, Doyle TJ, Croteau D, Avedissian R, Ryu S, Schultz L (2010) Phase I/II dose escalation trial of concurrent temozolomide and whole brain radiation therapy for multiple brain metastasis. J Neurooncol 100(2):241–247. doi:10.1007/s11060-010-0187-8

    Article  PubMed  CAS  Google Scholar 

  90. Arriagada R, Le Chevalier T, Riviere A, Chomy P, Monnet I, Bardet E, Santos-Miranda JA, Le Pehoux C, Tarayre M, Benhamou S, Laplanche A (2002) Patterns of failure after prophylactic cranial irradiation in small-cell lung cancer: analysis of 505 randomized patients. Ann Oncol 13(5):748–754

    Article  PubMed  CAS  Google Scholar 

  91. Pugh TJ, Gaspar LE (2007) Prophylactic cranial irradiation for patients with lung cancer. Clin Lung Cancer 8(6):365–368

    Article  PubMed  Google Scholar 

  92. Le Pechoux C, Dunant A, Senan S, Wolfson A, Quoix E, Faivre-Finn C, Ciuleanu T, Arriagada R, Jones R, Wanders R, Lerouge D, Laplanche A (2009) Standard-dose versus higher-dose prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer in complete remission after chemotherapy and thoracic radiotherapy (PCI 99-01, EORTC 22003-08004, RTOG 0212, and IFCT 99-01): a randomised clinical trial. Lancet Oncol 10(5):467–474. doi:10.1016/S1470-2045(09)70101-9

    Article  PubMed  Google Scholar 

  93. Law A, Karp DD, Dipetrillo T, Daly BT (2001) Emergence of increased cerebral metastasis after high-dose preoperative radiotherapy with chemotherapy in patients with locally advanced nonsmall cell lung carcinoma. Cancer 92(1):160–164. doi:10.1002/1097-0142(20010701)92:1<160:AID-CNCR1304>3.0.CO;2-X

    Article  PubMed  CAS  Google Scholar 

  94. Blanchard P, Le Pechoux C (2010) Prophylactic cranial irradiation in lung cancer. Curr Opin Oncol 22(2):94–101. doi:10.1097/CCO.0b013e32833500ef

    Article  PubMed  Google Scholar 

  95. Andre F, Grunenwald D, Pujol JL, Girard P, Dujon A, Brouchet L, Brichon PY, Westeel V, Le Chevalier T (2001) Patterns of relapse of N2 nonsmall-cell lung carcinoma patients treated with preoperative chemotherapy: should prophylactic cranial irradiation be reconsidered? Cancer 91(12):2394–2400. doi:10.1002/1097-0142(20010615)91:12<2394:AID-CNCR1273>3.0.CO;2-6

    Article  PubMed  CAS  Google Scholar 

  96. Gore EM, Bae K, Wong SJ, Sun A, Bonner JA, Schild SE, Gaspar LE, Bogart JA, Werner-Wasik M, Choy H (2011) Phase III comparison of prophylactic cranial irradiation versus observation in patients with locally advanced non-small-cell lung cancer: primary analysis of radiation therapy oncology group study RTOG 0214. J Clin Oncol 29(3):272–278. doi:10.1200/JCO.2010.29.1609

    Article  PubMed  Google Scholar 

  97. Scorsetti M, Facoetti A, Navarria P, Bignardi M, De Santis M, Ninone SA, Lattuada P, Urso G, Vigorito S, Mancosu P, Del Vecchio M (2009) Hypofractionated stereotactic radiotherapy and radiosurgery for the treatment of patients with radioresistant brain metastases. Anticancer Res 29(10):4259–4263

    PubMed  Google Scholar 

  98. Clarke JW, Register S, McGregor JM, Grecula JC, Mayr NA, Wang JZ, Li K, Gupta N, Kendra KL, Olencki TE, Cavaliere R, Sarkar A, Lo SS (2010) Stereotactic radiosurgery with or without whole brain radiotherapy for patients with a single radioresistant brain metastasis. Am J Clin Oncol 33(1):70–74. doi:10.1097/COC.0b013e31819ccc8c

    Article  PubMed  Google Scholar 

  99. Powell JW, Chung CT, Shah HR, Canute GW, Hodge CJ, Bassano DA, Liu L, Mitchell L, Hahn SS (2008) Gamma Knife surgery in the management of radioresistant brain metastases in high-risk patients with melanoma, renal cell carcinoma, and sarcoma. J Neurosurg 109(Suppl):122–128. doi:10.3171/JNS/2008/109/12/S19

    PubMed  Google Scholar 

  100. Choi HJ, Cho BC, Sohn JH, Shin SJ, Kim SH, Kim JH, Yoo NC (2009) Brain metastases from hepatocellular carcinoma: prognostic factors and outcome: brain metastasis from HCC. J Neurooncol 91(3):307–313. doi:10.1007/s11060-008-9713-3

    Article  PubMed  Google Scholar 

  101. Mahmoud-Ahmed AS, Suh JH, Kupelian PA, Klein EA, Peereboom DM, Dreicer R, Barnett GH (2002) Brain metastases from bladder carcinoma: presentation, treatment and survival. J Urol 167(6):2419–2422

    Article  PubMed  Google Scholar 

  102. Zigouris A, Pahatouridis D, Mihos E, Alexiou GA, Nesseris J, Zikou AK, Argyropoulou MI, Goussia A, Voulgaris S (2009) Solitary cystic cerebral metastasis from transitional cell carcinoma of the bladder. Acta Neurol Belg 109(4):322–325

    PubMed  Google Scholar 

  103. Tremont-Lukats IW, Bobustuc G, Lagos GK, Lolas K, Kyritsis AP, Puduvalli VK (2003) Brain metastasis from prostate carcinoma: The M. D. Anderson Cancer Center experience. Cancer 98(2):363–368. doi:10.1002/cncr.11522

    Article  PubMed  Google Scholar 

  104. Agazzi S, Pampallona S, Pica A, Vernet O, Regli L, Porchet F, Villemure JG, Leyvraz S (2004) The origin of brain metastases in patients with an undiagnosed primary tumour. Acta Neurochir (Wien) 146(2):153–157. doi:10.1007/s00701-003-0188-x

    Article  CAS  Google Scholar 

  105. Klee B, Law I, Hojgaard L, Kosteljanetz M (2002) Detection of unknown primary tumours in patients with cerebral metastases using whole-body 18F-flouorodeoxyglucose positron emission tomography. Eur J Neurol 9(6):657–662

    Article  PubMed  CAS  Google Scholar 

  106. D’Ambrosio AL, Agazzi S (2007) Prognosis in patients presenting with brain metastasis from an undiagnosed primary tumor. Neurosurg Focus 22(3):E7

    PubMed  Google Scholar 

  107. Bartelt S, Lutterbach J (2003) Brain metastases in patients with cancer of unknown primary. J Neurooncol 64(3):249–253

    Article  PubMed  Google Scholar 

  108. Rades D, Bohlen G, Lohynska R, Veninga T, Stalpers LJ, Schild SE, Dunst J (2007) Whole-brain radiotherapy with 20 Gy in 5 fractions for brain metastases in patients with cancer of unknown primary (CUP). Strahlenther Onkol 183(11):631–636. doi:10.1007/s00066-007-1763-5

    Article  PubMed  Google Scholar 

  109. Niranjan A, Kano H, Khan A, Kim IY, Kondziolka D, Flickinger JC, Lunsford LD (2010) Radiosurgery for brain metastases from unknown primary cancers. Int J Radiat Oncol Biol Phys 77(5):1457–1462. doi:10.1016/j.ijrobp.2009.07.012

    Article  PubMed  Google Scholar 

  110. Kargiotis O, Markoula S, Kyritsis AP (2011) Epilepsy in the cancer patient. Cancer Chemother Pharmacol 67(3):489–501. doi:10.1007/s00280-011-1569-0

    Article  PubMed  CAS  Google Scholar 

  111. Sioka C, Fotopoulos A, Kyritsis AP (2010) Paraneoplastic neurological syndromes and the role of PET imaging. Oncology 78(2):150–156. doi:10.1159/000312657

    Article  PubMed  Google Scholar 

  112. Aoyama H, Shirato H, Onimaru R, Kagei K, Ikeda J, Ishii N, Sawamura Y, Miyasaka K (2003) Hypofractionated stereotactic radiotherapy alone without whole-brain irradiation for patients with solitary and oligo brain metastasis using noninvasive fixation of the skull. Int J Radiat Oncol Biol Phys 56(3):793–800

    Article  PubMed  Google Scholar 

  113. Kargiotis O, Geka A, Rao JS, Kyritsis AP (2010) Effects of irradiation on tumor cell survival, invasion and angiogenesis. J Neurooncol 100(3):323–338. doi:10.1007/s11060-010-0199-4

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Athanassios P. Kyritsis.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kyritsis, A.P., Markoula, S. & Levin, V.A. A systematic approach to the management of patients with brain metastases of known or unknown primary site. Cancer Chemother Pharmacol 69, 1–13 (2012). https://doi.org/10.1007/s00280-011-1775-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-011-1775-9

Keywords

Navigation