Skip to main content
SpringerLink
Log in

Central Nervous System Malignancies

  • Chapter
  • First Online:
Practical Medical Oncology Textbook

Part of the book series: UNIPA Springer Series ((USS))

  • 3304 Accesses

Abstract

The primitive neoplasms of the central nervous system (CNS) are a rare and heterogeneous group of malignancies. Brain metastases (BMs) are the most frequent intracranial tumor, and their incidence is rising in the last few decades. Primary tumors more often complicated by BMs are lung cancer, breast cancer, and melanoma. Neuroimaging techniques, mainly magnetic resonance imaging (MRI), play a key role for the diagnosis of BMs. The management of BMs is based on a multimodal approach, including symptomatic treatment, local treatment, such as surgery, stereotactic radiosurgery (SRS), and whole brain radiotherapy (WBRT), and systemic therapy, such as chemotherapy, target therapy, or immunotherapy. Despite active treatment, however, BMs still have an adverse impact on survival and quality of life.

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

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 179.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

Primary Brain Tumors

  1. Lowery FJ, YU D. Brain metastasis: unique challenges and open opportunities. Biochim Biophys Acta Rev Cancer. 2017;1867(1):49–57.

    Google Scholar 

  2. Wrensch M, Minn Y, Chew T, Bondy M, Berger MS. Epidemiology of primary brain tumors: current concepts and review of the literature. Neuro-Oncology. 2002;4(4):278–99.

    Google Scholar 

  3. Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, et al. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2016;131(6):803–20.

    Google Scholar 

  4. Perkins A, Liu G. Primary brain tumors in adults: diagnosis and treatment. Am Fam Physician. 2016;93(3):211–7.

    Google Scholar 

  5. Weller M, van den Bent M, Tonn JC, Stupp R, Preusser M, et al. European Association for Neuro-Oncology (EANO) guideline on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas. Lancet Oncol. 2017;18(6):e315–29.

    Google Scholar 

  6. van den Bent MJ, Baumert B, Erridge SC, Vogelbaum MA, Nowak AK, Sanson M, et al. Interim results from the CATNON trial (EORTC study 26053-22054) of treatment with concurrent and adjuvant temozolomide for 1p/19q non-co-deleted anaplastic glioma: a phase 3, randomised, open-label intergroup study. Lancet. 2017;390(10103):1645–53.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987–96.

    Article  CAS  PubMed  Google Scholar 

  8. Weller M, Stupp R, Reifenberger G, Brandes AA, van den Bent MJ, Wick W, et al. MGMT promoter methylation in malignant gliomas: ready for personalized medicine? Nat Rev Neurol. 2010;6(1):39–51.

    Article  CAS  PubMed  Google Scholar 

  9. Lu VM, O’Connor KP, Shah AH, Eichberg DG, Luther EM, et al. The prognostic significance of CDKN2A homozygous deletion in IDH-mutant lower-grade glioma and glioblastoma: a systematic review of the contemporary literature. J Neuro-Oncol. 2020;148:221.

    Google Scholar 

  10. Davis ME. Glioblastoma: overview of disease and treatment. Clin J Oncol Nurs. 2016;20(5 Suppl):S2–8.

    Google Scholar 

  11. Glas M, Kebir S. Regorafenib in glioblastoma recurrence: how to deal with conflicting ‘real-life’ experiences? Ther Adv Med Oncol. 2019;11:1758835919887667.

    Google Scholar 

  12. Sanson M, Cartalat-Carel S, Taillibert S, Napolitano M, Djafari L, Cougnard J, et al. Initial chemotherapy in gliomatosis cerebri. Neurology. 2004;63(2):270–5.

    Article  CAS  PubMed  Google Scholar 

  13. Baumert BG, Hegi ME, van den Bent MJ, von Deimling A, Gorlia T, Hoang-Xuan K, et al. Temozolomide chemotherapy versus radiotherapy in high-risk low-grade glioma (EORTC 22033-26033): a randomised, open-label, phase 3 intergroup study. Lancet Oncol. 2016;17(11):1521–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Metellus P, Guyotat J, Chinot O, Durand A, Barrie M, Giorgi R, et al. Adult intracranial WHO grade II ependymomas: long-term outcome and prognostic factor analysis in a series of 114 patients. Neuro-Oncology. 2010;12(9):976–84.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Reni M, Gatta G, Mazza E, Vecht C. Ependymoma. Crit Rev Oncol Hematol. 2007;63(1):81–9.

    Article  PubMed  Google Scholar 

  16. Oya N, Shibamoto Y, Nagata Y, Negoro Y, Hiraoka M. Postoperative radiotherapy for intracranial ependymoma: analysis of prognostic factors and patterns of failure. J Neuro-Oncol. 2002;56(1):87–94.

    Article  Google Scholar 

  17. Franceschi E, Bartolotti M, Paccapelo A, Marucci G, Agati R, Volpin L, et al. Adjuvant chemotherapy in adult medulloblastoma: is it an option for average-risk patients? J Neuro-Oncol. 2016;128(2):235–40.

    Article  CAS  Google Scholar 

  18. Brandes AA, Pasetto LM, Lumachi F, Monfardini S. Endocrine dysfunctions in patients treated for brain tumors: incidence and guidelines for management. J Neuro-Oncol. 2000;47(1):85–92.

    Article  CAS  Google Scholar 

  19. Wiemels J, Wrensch M, Claus EB. Epidemiology and etiology of meningioma. J Neuro-Oncol. 2010;99(3):307–14.

    Article  Google Scholar 

  20. Buerki RA, Horbinski CM, Kruser T, Horowitz PM, James CD, Lukas RV. An overview of meningiomas. Future Oncol. 2018;14(21):2161–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Melean G, Sestini R, Ammannati F, Papi L. Genetic insights into familial tumors of the nervous system. Am J Med Genet C Semin Med Genet. 2004;129C(1):74–84.

    Google Scholar 

  22. Galanti D, Inno A, La Vecchia M, et al. Current treatment options for HER2-positive breast cancer patients with brain metastases. Crit Rev Oncol Hematol. 2021;161:103329. https://doi.org/10.1016/j.critrevonc.2021.103329.

Brain Metastases

  1. Walker AE, Robins M, Weinfeld FD. Epidemiology of brain tumors: the national survey of intracranial neoplasms. Neurology. 1985;35:219–26.

    Article  CAS  PubMed  Google Scholar 

  2. Counsell CE, Collie DA, Grant R. Incidence of intracranial tumours in the Lothian region of Scotland, 1989-90. J Neurol Neurosurg Psychiatry. 1996;61:143–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Schouten LJ, Rutten J, Huveneers HA, Twijnstra A. Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma. Cancer. 2002;94:2698–705.

    Article  PubMed  Google Scholar 

  4. Barnholtz-Sloan JS, Sloan AE, Davis FG, Vigneau FD, Lai P, Sawaya RE. Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J Clin Oncol. 2004;22:2865–72.

    Article  PubMed  Google Scholar 

  5. Tabouret E, Chinot O, Metellus P, Tallet A, Viens P, Gonçalves A. Recent trends in epidemiology of brain metastases: an overview. Anticancer Res. 2012;32:4655–62.

    PubMed  Google Scholar 

  6. Percy AK. Neoplasms of the central nervous system: epidemiologic considerations. Neurology. 1970;20:398–9.

    CAS  PubMed  Google Scholar 

  7. Posner JB, Chernik NL. Intracranial metastases from systemic cancer. Adv Neurol. 1978;19:579–92.

    CAS  PubMed  Google Scholar 

  8. Nayak L, Lee EQ, Wen PY. Epidemiology of brain metastases. Curr Oncol Rep. 2012;14:48–54.

    Article  PubMed  Google Scholar 

  9. Berghoff AS, Schur S, Füreder LM, Gatterbauer B, Dieckmann K, Widhalm G, et al. Descriptive statistical analysis of a real life cohort of 2419 patients with brain metastases of solid cancers. ESMO Open. 2016;1:e000024.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Stark AM, Stöhring C, Hedderich J, Held-Feindt J, Mehdorn HM. Surgical treatment for brain metastases: prognostic factors and survival in 309 patients with regard to patient age. J Clin Neurosci. 2011;18:34–8.

    Article  CAS  PubMed  Google Scholar 

  11. Slimane K, Andre F, Delaloge S, Dunant A, Perez A, Grenier J, et al. Risk factors for brain relapse in patients with metastatic breast cancer. Ann Oncol. 2004;15:1640–4.

    Article  CAS  PubMed  Google Scholar 

  12. Kennecke H, Yerushalmi R, Woods R, Cheang MC, Voduc D, Speers CH, et al. Metastatic behavior of breast cancer subtypes. J Clin Oncol. 2010;28:3271–7.

    Article  PubMed  Google Scholar 

  13. Graesslin O, Abdulkarim BS, Coutant C, Huguet F, Gabos Z, Hsu L, et al. Nomogram to predict subsequent brain metastasis in patients with metastatic breast cancer. J Clin Oncol. 2010;28:2032–7.

    Article  PubMed  Google Scholar 

  14. Genre L, Roché H, Varela L, Kanoun D, Ouali M, Filleron T, et al. External validation of a published nomogram for prediction of brain metastasis in patients with extra-cerebral metastatic breast cancer and risk regression analysis. Eur J Cancer. 2017;72:200–9.

    Article  PubMed  Google Scholar 

  15. Won YW, Joo J, Yun T, Lee GK, Han JY, Kim HT, et al. A nomogram to predict brain metastasis as the first relapse in curatively resected non-small cell lung cancer patients. Lung Cancer. 2015;88:201–7.

    Article  PubMed  Google Scholar 

  16. Zhang F, Zheng W, Ying L, Wu J, Wu S, Ma S, et al. A nomogram to predict brain metastases of resected non-small cell lung cancer patients. Ann Surg Oncol. 2016;23:3033–9.

    Article  PubMed  Google Scholar 

  17. Nathoo N, Chahlavi A, Barnett GH, Toms SA. Pathobiology of brain metastases. J Clin Pathol. 2005;58:237–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Morita R, Fujimoto A, Hatta N, Takehara K, Takata M. Comparison of genetic profiles between primary melanomas and their metastases reveals genetic alterations and clonal evolution during progression. J Invest Dermatol. 1998;111:919–24.

    Article  CAS  PubMed  Google Scholar 

  19. Langley RR, Fidler IJ. The seed and soil hypothesis revisited--the role of tumor-stroma interactions in metastasis to different organs. Int J Cancer. 2011;128:2527–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Bos PD, Zhang XH, Nadal C, Shu W, Gomis RR, Nguyen DX, et al. Genes that mediate breast cancer metastasis to the brain. Nature. 2009;459:1005–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Lee JY, Park K, Lee E, Ahn T, Jung HH, Lim SH, et al. Gene expression profiling of breast cancer brain metastasis. Sci Rep. 2016;6:28623.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Gavrilovic IT, Posner JB. Brain metastases: epidemiology and pathophysiology. J Neuro-Oncol. 2005;75:5–14.

    Article  Google Scholar 

  23. Liotta LA, Kohn EC. Cancer’s deadly signature. Nat Genet. 2003;33:10–1.

    Article  CAS  PubMed  Google Scholar 

  24. Delattre JY, Krol G, Thaler HT, Posner JB. Distribution of brain metastases. Arch Neurol. 1998;45:741–4.

    Article  Google Scholar 

  25. Hwang TL, Close TP, Grego JM, Rannon WL, Gonzales F. Predilection of brain metastasis in gray and white matter junction and vascular border zones. Cancer. 1996;77:1551–5.

    Article  CAS  PubMed  Google Scholar 

  26. Cairncross JG, Kim JH, Posner JB. Radiation therapy for brain metastases. Ann Neurol. 1980;7:529–41.

    Article  CAS  PubMed  Google Scholar 

  27. Gállego Pérez-Larraya J, Hildebrand J. Brain metastases. Handb Clin Neurol. 2014;121:1143–57.

    Article  PubMed  Google Scholar 

  28. Forsyth PA, Posner JB. Headaches in patients with brain tumors: a study of 111 patients. Neurology. 1993;43:1678–83.

    Article  CAS  PubMed  Google Scholar 

  29. Argyriou AA, Chroni E, Polychronopoulos P, Argyriou K, Papapetropoulos S, Corcondilas M, et al. Headache characteristics and brain metastases prediction in cancer patients. Eur J Cancer Care. 2006;15:90–5.

    Article  CAS  Google Scholar 

  30. Lynam LM, Lyons MK, Drazkowski JF, Sirven JI, Noe KH, Zimmerman RS, et al. Frequency of seizures in patients with newly diagnosed brain tumors: a retrospective review. Clin Neurol Neurosurg. 2007;109:634–8.

    Article  PubMed  Google Scholar 

  31. Chang EL, Wefel JS, Maor MH, Hassenbusch SJ 3rd, Mahajan A, Lang FF, et al. A pilot study of neurocognitive function in patients with one to three new brain metastases initially treated with stereotactic radiosurgery alone. Neurosurgery. 2007;60:277–83.

    Article  PubMed  Google Scholar 

  32. Nutt SH, Patchell RA. Intracranial hemorrhage associated with primary and secondary tumors. Neurosurg Clin N Am. 1992;3:591–9.

    Article  CAS  PubMed  Google Scholar 

  33. Incorvaia L, Madonia G, Corsini LR, et al. Challenges and advances for the treatment of renal cancer patients with brain metastases: From immunological background to upcoming clinical evidence on immune-checkpoint inhibitors. Crit Rev Oncol Hematol. 2021;163:103390.

    Google Scholar 

  34. Fink KR, Fink JR. Imaging of brain metastases. Surg Neurol Int. 2013;4(Suppl 4):S209–19.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Lee EK, Lee EJ, Kim MS, Park HJ, Park NH, Park S 2nd, et al. Intracranial metastases: spectrum of MR imaging findings. Acta Radiol. 2012;53:1173–85.

    Article  PubMed  Google Scholar 

  36. Rohren EM, Provenzale JM, Barboriak DP, Coleman RE. Screening for cerebralmetastases with FDG PET in patients undergoing whole-body staging of non-central nervous system malignancy. Radiology. 2003;226:181–7.

    Article  PubMed  Google Scholar 

  37. Hustinx R, Pourdehnad M, Kaschten B, Alavi A. PET imaging for differentiating recurrent brain tumor from radiation necrosis. Radiol Clin N Am. 2005;43:35–47.

    Article  PubMed  Google Scholar 

  38. Unterrainer M, Galldiks N, Suchorska B, Kowalew LC, Wenter V, Schmid-Tannwald C, et al. (18)F-FET PET uptake characteristics in patients with newly diagnosed and untreated brain metastasis. J Nucl Med. 2017;58:584–9.

    Article  CAS  PubMed  Google Scholar 

  39. Becher MW, Abel TW, Thompson RC, Weaver KD, Davis LE. Immunohistochemical analysis of metastatic neoplasms of the central nervous system. J Neuropathol Exp Neurol. 2006;65:935–44.

    Article  CAS  PubMed  Google Scholar 

  40. Gaspar L, Scott C, Rotman M, Asbell S, Phillips T, Wasserman T, et al. Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys. 1997;37:745–51.

    Article  CAS  PubMed  Google Scholar 

  41. Sperduto PW, Berkey B, Gaspar LE, Mehta M, Curran W. 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. 2008;70:510–4.

    Article  PubMed  Google Scholar 

  42. Sperduto PW, Chao ST, Sneed PK, Luo X, Suh J, Roberge D, et al. 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. 2010;77:655–61.

    Article  PubMed  Google Scholar 

  43. Sperduto PW, Kased N, Roberge D, Xu Z, Shanley R, Luo X, et al. Summary report on the graded prognostic assessment: an accurate and facile diagnosis-specific tool to estimate survival for patients with brain metastases. J Clin Oncol. 2012a;30:419–25.

    Article  PubMed  Google Scholar 

  44. Sperduto PW, Kased N, Roberge D, Xu Z, Shanley R, Luo X, et al. 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. 2012b;82:2111–7.

    Article  PubMed  Google Scholar 

  45. Griguolo G, Jacot W, Kantelhardt E, Dieci MV, Bourgier C, Thomssen C, et al. External validation of modified breast graded prognostic assessment for breast cancer patients with brain metastases: a multicentric European experience. Breast. 2018;37:36–41.

    Article  PubMed  Google Scholar 

  46. Sperduto PW, Yang TJ, Beal K, Pan H, Brown PD, Bangdiwala A, et al. Estimating survival in patients with lung cancer and brain metastases: an update of the graded prognostic assessment for lung cancer using molecular markers (lung-molGPA). JAMA Oncol. 2017;3:827–31.

    Article  PubMed  Google Scholar 

  47. Soffietti R, Abacioglu U, Baumert B, Combs SE, Kinhult S, Kros JM, et al. Diagnosis and treatment of brain metastases from solid tumors: guidelines from the European Association of Neuro-Oncology (EANO). Neuro-Oncology. 2017;19:162–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Lin X, DeAngelis LM. Treatment of brain metastases. J Clin Oncol. 2015;33:3475–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Stummer W. Mechanisms of tumor-related brain edema. Neurosurg Focus. 2007;22:E8.

    Article  PubMed  Google Scholar 

  50. Ryken TC, McDermott M, Robinson PD, Ammirati M, Andrews DW, Asher AL, et al. The role of steroids in the management of brain metastases: a systematic review and evidence-based clinical practice guideline. J Neuro-Oncol. 2010;96:103–14.

    Article  CAS  Google Scholar 

  51. Vecht CJ, Hovestadt A, Verbiest HB, van Vliet JJ, van Putten WL, et al. Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain tumors: a randomized study of doses of 4, 8, and 16 mg per day. Neurology. 1994;44:675–80.

    Article  CAS  PubMed  Google Scholar 

  52. Sarin R, Murthy V. Medical decompressive therapy for primary and metastatic intracranial tumours. Lancet Neurol. 2003;2:357–65.

    Article  CAS  PubMed  Google Scholar 

  53. Frank J. Management of intracranial hypertension. Med Clin North Am. 1993;77:61–75.

    Article  CAS  PubMed  Google Scholar 

  54. Roberts PA, Pollay M, Engles C, Pendleton B, Reynolds E, Stevens FA. Effect on intracranial pressure of furosemide combined with varying doses and administration rates of mannitol. J Neurosurg. 1987;66:440–6.

    Article  CAS  PubMed  Google Scholar 

  55. Mikkelsen T, Paleologos NA, Robinson PD, Ammirati M, Andrews DW, Asher AL, et al. The role of prophylactic anticonvulsants in the management of brain metastases: a systematic review and evidence-based clinical practice guideline. J Neuro-Oncol. 2010;96:97–102.

    Article  Google Scholar 

  56. Forsyth PA, Weaver S, Fulton D, Brasher PM, Sutherland G, Stewart D, et al. Prophylactic anticonvulsants in patients with brain tumour. Can J Neurol Sci. 2003;30:106–12.

    Article  PubMed  Google Scholar 

  57. Perry J, Zinman L, Chambers A, Spithoff K, Lloyd N, Laperriere N. The use of prophylactic anticonvulsants in patients with brain tumours—a systematic review. Curr Oncol. 2006;13:222–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Glantz MJ, Cole BF, Forsyth PA, Recht LD, Wen PY, Chamberlain MC, et al. Practice parameter: anticonvulsant prophylaxis in patients with newly diagnosed brain tumors. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2000;54:1886–93.

    Article  CAS  PubMed  Google Scholar 

  59. Temkin NR. Prophylactic anticonvulsants after neurosurgery. Epilepsy Curr. 2002;2:105–7.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Patchell RA, Tibbs PA, Walsh JW, Dempsey RJ, Maruyama Y, Kryscio RJ, et al. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med. 1990;322:494–500.

    Article  CAS  PubMed  Google Scholar 

  61. Vecht CJ, Haaxma-Reiche H, Noordijk EM, Padberg GW, Voormolen JH, Hoekstra FH, et al. Treatment of single brain metastasis: radiotherapy alone or combined with neurosurgery? Ann Neurol. 1993;33:583–90.

    Article  CAS  PubMed  Google Scholar 

  62. Mintz AH, Kestle J, Rathbone MP, Gaspar L, Hugenholtz H, Fisher B, et al. A randomized trial to assess the efficacy of surgery in addition to radiotherapy in patients with a single cerebral metastasis. Cancer. 1996;78:1470–6.

    Article  CAS  PubMed  Google Scholar 

  63. Pollock BE, Brown PD, Foote RL, Stafford SL, Schomberg PJ, et al. Properly selected patients with multiple brain metastases may benefit from aggressive treatment of their intracranial disease. J Neuro-Oncol. 2003;61:73–80.

    Article  Google Scholar 

  64. Ferguson SD, Wagner KM, Prabhu SS, McAleer MF, McCutcheon IE, Sawaya R. Neurosurgical management of brain metastases. Clin Exp Metastasis. 2017;34:377–89.

    Article  CAS  PubMed  Google Scholar 

  65. Paek SH, Audu PB, Sperling MR, Cho J, Andrews DW. Reevaluation of surgery for the treatment of brain metastases: review of 208 patients with single or multiple brain metastases treated at one institution with modern neurosurgical techniques. Neurosurgery. 2005;56:1021–34.

    PubMed  Google Scholar 

  66. Vogelbaum MA, Suh JH. Resectable brain metastases. J Clin Oncol. 2006;24:1289–94.

    Article  PubMed  Google Scholar 

  67. Warnick RE, Darakchiev BJ, Breneman JC. Stereotactic radiosurgery for patients with solid brain metastases: current status. J Neuro-Oncol. 2004;69:125–37.

    Article  Google Scholar 

  68. Minniti G, D’Angelillo RM, Scaringi C, Trodella LE, Clarke E, Matteucci P, et al. Fractionated stereotactic radiosurgery for patients with brain metastases. J Neuro-Oncol. 2014;117:295–301.

    Article  CAS  Google Scholar 

  69. Auchter RM, Lamond JP, Alexander E, Buatti JM, Chappell R, Friedman WA, et al. A multiinstitutional outcome and prognostic factor analysis of radiosurgery for resectable single brain metastasis. Int J Radiat Oncol Biol Phys. 1996;35:27–35.

    Article  CAS  PubMed  Google Scholar 

  70. 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. 1999;91:35–43.

    Article  CAS  PubMed  Google Scholar 

  71. Muacevic A, Wowra B, Siefert A, Tonn JC, Steiger HJ, Kreth FW. 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 Neuro-Oncol. 2008;87:299–307.

    Article  Google Scholar 

  72. Lippitz B, Lindquist C, Paddick I, Peterson D, O'Neill K, Beaney R. Stereotactic radiosurgery in the treatment of brain metastases: the current evidence. Cancer Treat Rev. 2014;40:48–59.

    Article  PubMed  Google Scholar 

  73. Yamamoto M, Serizawa T, Shuto T, Akabane A, Higuchi Y, Kawagishi J, et al. Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study. Lancet Oncol. 2014;15:387–95.

    Article  PubMed  Google Scholar 

  74. 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. 2004;363:1665–72.

    Article  PubMed  Google Scholar 

  75. Manon R, O’Neill A, Knisely J, Werner-Wasik M, Lazarus HM, Wagner H, et al. Eastern Cooperative Oncology Group. 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. 2005;23:8870–6.

    Article  PubMed  Google Scholar 

  76. Sperduto PW, Shanley R, Luo X, Andrews D, Werner-Wasik M, Valicenti R, et al. Secondary analysis of RTOG 9508, a phase 3 randomized trial of whole-brain radiation therapy versus WBRT plus stereotactic radiosurgery in patients with 1-3 brain metastases; poststratified by the graded prognostic assessment (GPA). Int J Radiat Oncol Biol Phys. 2014;90:526–31.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Bhatnagar AK, Flickinger JC, Kondziolka D, Lunsford LD. Stereotactic radiosurgery for four or more intracranial metastases. Int J Radiat Oncol Biol Phys. 2006;64:898–903.

    Article  PubMed  Google Scholar 

  78. Gans JH, Raper DM, Shah AH, Bregy A, Heros D, Lally BE, et al. The role of radiosurgery to the tumor bed after resection of brain metastases. Neurosurgery. 2013;72:317–25.

    Article  PubMed  Google Scholar 

  79. Maldaun MV, Aguiar PH, Lang F, Suki D, Wildrick D, Sawaya R. Radiosurgery in the treatment of brain metastases: critical review regarding complications. Neurosurg Rev. 2008;31:1–8.

    Article  PubMed  Google Scholar 

  80. Tsao MN, Lloyd N, Wong RK, Chow E, Rakovitch E, Laperriere N, et al. Whole brain radiotherapy for the treatment of newly diagnosed multiple brain metastases. Cochrane Database Syst Rev. 2012a;4:349.55.

    Google Scholar 

  81. Langley RE, Stephens RJ, Nankivell M, Pugh C, Moore B, Navani N, et al. Interim data from the Medical Research Council QUARTZ trial: does whole brain radiotherapy affect the survival and quality of life of patients with brain metastases from non-small cell lung cancer? Clin Oncol (R Coll Radiol). 2013;25:23–30.

    Article  Google Scholar 

  82. Patchell RA, Tibbs PA, Regine WF, Dempsey RJ, Mohiuddin M, Kryscio RJ, et al. Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial. JAMA. 1998;280:1485–9.

    Article  CAS  PubMed  Google Scholar 

  83. 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. 2006;295:2483–91.

    Article  CAS  PubMed  Google Scholar 

  84. Kocher M, Soffietti R, Abacioglu U, Villà S, Fauchon F, Baumert BG, et al. Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952-26001 study. J Clin Oncol. 2011;29:134–41.

    Article  PubMed  Google Scholar 

  85. Tsao M, Xu W, Sahgal A. A meta-analysis evaluating stereotactic radiosurgery, whole-brain radiotherapy, or both for patients presenting with a limited number of brain metastases. Cancer. 2012b;118:2486–93.

    Article  PubMed  Google Scholar 

  86. Sahgal A, Aoyama H, Kocher M, Neupane B, Collette S, Tago M, et al. Phase 3 trials of stereotactic radiosurgery with or without whole-brain radiation therapy for 1 to 4 brain metastases: individual patient data meta-analysis. Int J Radiat Oncol Biol Phys. 2015;91:710–7.

    Article  PubMed  Google Scholar 

  87. 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. 2007;68:1388–95.

    Article  PubMed  Google Scholar 

  88. 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. 2009;10:1037–44.

    Article  PubMed  Google Scholar 

  89. Soffietti R, Kocher M, Abacioglu UM, Villa S, Fauchon F, Baumert BG, et al. A European Organisation for Research and Treatment of Cancer phase III trial of adjuvant wholebrain radiotherapy versus observation in patients with one to three brain metastases from solid tumors after surgical resection or radiosurgery: quality-of-life results. J Clin Oncol. 2013;31:65–72.

    Article  PubMed  Google Scholar 

  90. Churilla TM, Ballman KV, Brown PD, Twohy EL, Jaeckle K, Farace E, et al. Stereotactic radiosurgery with or without whole-brain radiation therapy for limited brain metastases: a secondary analysis of the North Central Cancer Treatment Group N0574 (Alliance) randomized controlled trial. Int J Radiat Oncol Biol Phys. 2017;99:1173–8.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Wong WW, Schild SE, Sawyer TE, Castel H, Laquerriere A, Freger P, et al. Analysis of outcome in patients reirradiated for brain metastases. Int J Radiat Oncol Biol Phys. 1996;34:585–90.

    Article  CAS  PubMed  Google Scholar 

  92. Sadikov E, Bezjak A, Yi QL, Wells W, Dawson L, Millar BA, et al. Value of whole brain re-irradiation for brain metastases--single centre experience. Clin Oncol (R Coll Radiol). 2007;19:532–8.

    Article  CAS  PubMed  Google Scholar 

  93. Brown PD, Pugh S, Laack NN, Wefel JS, Khuntia D, Meyers C, et al. Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double blind, placebo-controlled trial. Neuro-Oncology. 2013;15:1429–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Suh JH. Hippocampal-avoidance whole-brain radiation therapy: a new standard for patients with brain metastases? J Clin Oncol. 2014;32:3789–91.

    Article  PubMed  PubMed Central  Google Scholar 

  95. Walbert T, Gilbert MR. The role of chemotherapy in the treatment of patients with brain metastases from solid tumors. Int J Clin Oncol. 2009;14:299–306.

    Article  CAS  PubMed  Google Scholar 

  96. Dempke WC, Edvardsen K, Lu S, Reinmuth N, Reck M, Inoue A. Brain metastases in NSCLC - are TKIs changing the treatment strategy? Anticancer Res. 2015;35:5797–806.

    CAS  PubMed  Google Scholar 

  97. Magnuson WJ, Lester-Coll NH, Wu AJ, Yang TJ, Lockney NA, Gerber NK, et al. Management of brain metastases in tyrosine kinase inhibitor-Naïve epidermal growth factor receptor-mutant non-small-cell lung cancer: a retrospective multi-institutional analysis. J Clin Oncol. 2017;35:1070–7.

    Article  CAS  PubMed  Google Scholar 

  98. Metro G, Chiari R, Ricciuti B, Rebonato A, Lupattelli M, Gori S, et al. Pharmacotherapeutic options for treating brain metastases in non-small cell lung cancer. Expert Opin Pharmacother. 2016;16:2601–13.

    Article  Google Scholar 

  99. Jänne PA, Yang JC, Kim DW, Planchard D, Ohe Y, Ramalingam SS, et al. AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. N Engl J Med. 2015;372:1689–99.

    Article  PubMed  Google Scholar 

  100. Goss G, Tsai CM, Shepherd FA, Ahn MJ, Bazhenova L, Crinò L, et al. CNS response to osimertinib in patients with T790M-positive advanced NSCLC: pooled data from two Phase II trials. Ann Oncol. 2017; in press (epub ahead of print).

    Google Scholar 

  101. Mok TS, Wu Y-L, Ahn M-J, Garassino MC, Kim HR, Ramalingam SS, et al. Osimertinib or platinum-Pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med. 2017;376:629–40.

    Article  CAS  PubMed  Google Scholar 

  102. Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, et al. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018;378:113–25.

    Article  CAS  PubMed  Google Scholar 

  103. Reungwetwattana T, Nakagawa K, Cho BC, Cobo M, Cho EK, Bertolini A, et al. CNS response to Osimertinib versus standard epidermal growth factor receptor tyrosine kinase inhibitors in patients with untreated EGFR-mutated advanced non-small-cell lung cancer. J Clin Oncol 2018 in press.

    Google Scholar 

  104. Gainor JF, Ou SH, Logan J, Borges LF, Shaw AT. The central nervous system as a sanctuary site in ALK-positive non-small-cell lung cancer. J Thorac Oncol. 2013;8:1570–3.

    Article  CAS  PubMed  Google Scholar 

  105. Costa DB, Shaw AT, Ou SH, Solomon BJ, Riely GJ, Ahn MJ, et al. Clinical experience with Crizotinib in patients with advanced ALK-rearranged non-small-cell lung cancer and brain metastases. J Clin Oncol. 2015;33:1881–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Gadgeel SM, Shaw AT, Govindan R, Gandhi L, Socinski MA, Camidge DR, et al. Pooled analysis of CNS response to Alectinib in two studies of pretreated patients with ALK-positive non-small-cell lung cancer. J Clin Oncol. 2016;34:4079–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Peters S, Camidge DR, Shaw AT, Gadgeel S, Ahn JS, Kim DW, et al. Alectinib versus Crizotinib in untreated ALK-positive non-small-cell lung cancer. N Engl J Med. 2017;377:829–38.

    Article  CAS  PubMed  Google Scholar 

  108. Hida T, Nokihara H, Kondo M, Kim YH, Azuma K, Seto T, et al. Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial. Lancet. 2017;390:29–39.

    Article  CAS  PubMed  Google Scholar 

  109. Martínez P, Mak RH, Oxnard GR. Targeted therapy as an alternative to whole-brain radiotherapy in EGFR-mutant or ALK-positive non-small-cell lung cancer with brain metastases. JAMA Oncol. 2017;3:1274–5.

    Article  PubMed  Google Scholar 

  110. Johung KL, Yeh N, Desai NB, Williams TM, Lautenschlaeger T, Arvold ND, et al. Extended survival and prognostic factors for patients with ALK-rearranged non-small-cell lung cancer and brain metastasis. J Clin Oncol. 2016;34:123–9.

    Article  CAS  PubMed  Google Scholar 

  111. Zhuang H, Yuan Z, Wang J, Zhao L, Pang Q, Wang P. Phase II study of whole brain radiotherapy with or without erlotinib in patients with multiple brain metastases from lung adenocarcinoma. Drug Des Devel Ther. 2013;7:1179–86.

    Article  PubMed  PubMed Central  Google Scholar 

  112. Fan Y, Huang Z, Fang L, Miao L, Gong L, Yu H, et al. A phase II study of icotinib and whole-brain radiotherapy in Chinese patients with brain metastases from non-small cell lung cancer. Cancer Chemother Pharmacol. 2015;76:517–23.

    Article  CAS  PubMed  Google Scholar 

  113. Sperduto PW, Wang M, Robins HI, Schell MC, Werner-Wasik M, Komaki R, et al. A phase 3 trial of whole brain radiation therapy and stereotactic radiosurgery alone versus WBRT and SRS with temozolomide or erlotinib for non-small cell lung cancer and 1 to 3 brain metastases: Radiation Therapy Oncology Group 0320. Int J Radiat Oncol Biol Phys. 2013;85:1312–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Lee SM, Lewanski CR, Counsell N, Ottensmeier C, Bates A, Patel N, et al. Randomized trial of erlotinib plus whole-brain radiotherapy for NSCLC patients with multiple brain metastases. J Natl Cancer Inst. 2014;106:177–84.

    Article  Google Scholar 

  115. Landi L, Cappuzzo F. Achievements and future developments of ALK-TKIs in the management of CNS metastases from ALK-positive NSCLC. Transl Lung Cancer Res. 2016;5:579–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Goldberg SB, Gettinger SN, Mahajan A, Chiang AC, Herbst RS, Sznol M, et al. Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. Lancet Oncol. 2016;17:976–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Dudnik E, Yust-Katz S, Nechushtan H, Goldstein DA, Zer A, Flex D, et al. Intracranial response to nivolumab in NSCLC patients with untreated or progressing CNS metastases. Lung Cancer. 2016;98:114–7.

    Article  PubMed  Google Scholar 

  118. Inno A, Di Noia V, D'Argento E, Modena A, Gori S. State of the art of chemotherapy for the treatment of central nervous system metastases from non-small cell lung cancer. Transl Lung Cancer Res. 2016;5:599–609.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Galanti D, Inno A, La Vecchia M, et al. Current treatment options for HER2-positive breast cancer patients with brain metastases. Crit Rev Oncol Hematol. 2021;161:103329. https://doi.org/10.1016/j.critrevonc.2021.103329.

  120. Brufsky AM, Mayer M, Rugo HS, Kaufman PA, Tan-Chiu E, Tripathy D, et al. Central nervous system metastases in patients with HER2-positive metastatic breast cancer: incidence, treatment, and survival in patients from registHER. Clin Cancer Res. 2011;17:4834–43.

    Article  CAS  PubMed  Google Scholar 

  121. Park IH, Ro J, Lee KS, Nam BH, Nam BH, Kwon Y, Shin KH. Trastuzumab treatment beyond brain progression in HER2-positive metastatic breast cancer. Ann Oncol. 2009;20:56–62.

    Article  CAS  PubMed  Google Scholar 

  122. Swain SM, Kim SB, Cortés J, Ro J, Semiglazov V, Campone M, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2013;14:461–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Swain SM, Baselga J, Miles D, Im YH, Quah C, Lee LF, et al. Incidence of central nervous system metastases in patients with HER2-positive metastatic breast cancer treated with pertuzumab, trastuzumab, and docetaxel: results from the randomized phase III study CLEOPATRA. Ann Oncol. 2014;25:1116–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Lin NU, Carey LA, Liu MC, Younger J, Come SE, Ewend M, et al. Phase II trial of lapatinib for brain metastases in patients with human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2008;26:1993–9.

    Article  CAS  PubMed  Google Scholar 

  125. Lin NU, Eierman W, Greil R, Campone M, Kaufman B, Steplewski K, et al. Randomized phase II study of lapatinib plus capecitabine or lapatinib plus topotecan for patients with HER2-positive breast cancer brain metastases. J Neuro-Oncol. 2011;105:613–20.

    Article  CAS  Google Scholar 

  126. Bachelot T, Romieu G, Campone M, Diéras V, Cropet C, Dalenc F, et al. Lapatinib plus capecitabine in patients with previously untreated brain metastases from HER2-positive metastatic breast cancer (LANDSCAPE): a single-group phase 2 study. Lancet Oncol. 2013;14:64–71.

    Article  CAS  PubMed  Google Scholar 

  127. Bartsch R, Berghoff AS, Vogl U, Rudas M, Bergen E, Dubsky P, et al. Activity of T-DM1 in Her2-positive breast cancer brain metastases. Clin Exp Metastasis. 2015;32:729–37.

    Article  CAS  PubMed  Google Scholar 

  128. Krop IE, Lin NU, Blackwell K, Guardino E, Huober J, Lu M, et al. Trastuzumab emtansine (T-DM1) versus lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer and central nervous system metastases: a retrospective, exploratory analysis in EMILIA. Ann Oncol. 2015;26:113–9.

    Article  CAS  PubMed  Google Scholar 

  129. Trudeau ME, Crump M, Charpentier D, Yelle L, Bordeleau L, Matthews S, et al. Temozolomide in metastatic breast cancer (MBC): a phase II trial of the National Cancer Institute of Canada—Clinical Trials Group (NCIC-CTG). Ann Oncol. 2006;17:952–6.

    Article  CAS  PubMed  Google Scholar 

  130. Franciosi V, Cocconi G, Michiara M, Di Costanzo F, Fosser V, Tonato M, et al. Frontline chemotherapy with cisplatin and etoposide for patients with brain metastases from breast carcinoma, nonsmall cell lung carcinoma, or malignant melanoma: a prospective study. Cancer. 1999;85:1599–605.

    Article  CAS  PubMed  Google Scholar 

  131. Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer. 1981;47:207–14.

    Article  CAS  PubMed  Google Scholar 

  132. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst. 2000;92:20516.

    Article  Google Scholar 

  133. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.

    Article  CAS  PubMed  Google Scholar 

  134. Macdonald DR, Cascino TL, Schold SC Jr, Cairncross JG. Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol. 1990;8:1277–80.

    Article  CAS  PubMed  Google Scholar 

  135. Lin NU, Lee EQ, Aoyama H, Barani IJ, Barboriak DP, Baumert BG, et al. Response assessment criteria for brain metastases: proposal from the RANO group. Lancet Oncol. 2015;16:e270–8.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgical, Oncological and Oral Science, University of Palermo, Palermo, Italy

    Giuseppe Badalamenti

  2. Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy

    Lidia Rita Corsini

  3. Department of Surgical, Oncological, and Oral Sciences, University of Palermo, Palermo, Italy

    Massimiliano Cani

  4. Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, Palermo, Italy

    Lorena Incorvaia

  5. Department of Oncology, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar di Valpolicella, Verona, Italy

    Alessandro Inno & Stefania Gori

Authors
  1. Giuseppe Badalamenti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Massimiliano Cani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lidia Rita Corsini
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lorena Incorvaia
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alessandro Inno
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Stefania Gori
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alessandro Inno .

Editor information

Editors and Affiliations

  1. Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy

    Antonio Russo

  2. Oncology Department, University of Antwerp, Edegem, Belgium

    Marc Peeters

  3. Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, Palermo, Italy

    Lorena Incorvaia

  4. Center for Thoracic Oncology, Tisch Cancer Institute, Mount Sinai System & Icahn School of Medicine, Mount Sinai, NY, USA

    Christian Rolfo

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Badalamenti, G., Cani, M., Corsini, L.R., Incorvaia, L., Inno, A., Gori, S. (2021). Central Nervous System Malignancies. In: Russo, A., Peeters, M., Incorvaia, L., Rolfo, C. (eds) Practical Medical Oncology Textbook. UNIPA Springer Series. Springer, Cham. https://doi.org/10.1007/978-3-030-56051-5_44

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-56051-5_44

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-56050-8

  • Online ISBN: 978-3-030-56051-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation