Vol 70, No 3 (2020)
Review paper
Published online: 2020-06-16

open access

Page views 1276
Article views/downloads 830
Get Citation

Connect on Social Media

Connect on Social Media

An update on the epidemiology, imaging and therapy of brain metastases

Maciej Mielczarek1, Anna Kubica1, Mateusz Szylberg1, Karolina Zielińska1, Jakub Przybył1, Agata Sierzputowska2, Marek Harat1
Nowotwory. Journal of Oncology 2020;70(3):111-117.

Abstract

Introduction.The incidence of brain metastases (BM) is rapidly increasing, with most cases occurring in patients aged 50–80 years and in 10–40% of patients with systemic neoplastic disease. The Graded Prognostic Assessment (GPA) is the most impartial prognostic method, according to which the average survival rate of patients with brain metastases is only 7.18 months.

Purpose.To present a systematic review of the currently available evidence-based literature on the epidemiology, dia­gnosis, and treatment of BM.

Methods.The authors searched PubMed up to March 2020 using the phrases “brain metastases”, “brain metastasis surgery”, and “brain metastases treatment”, which returned 65 citations.

Conclusions.The choice of imaging and therapy for brain metastases remains a significant clinical problem. MRI, including T1, T1 + C, T2, FLAIR, and SWI sequences, is the most sensitive method for solitary BM detection, while other techniques such as spectroscopy, perfusion imaging, or fractional anisotropy contribute to diagnosis precision and neurological deficit avoidance in cases eligible for surgery. According to current treatment algorithms, three main methods are used to mana­ge BM: surgery, chemotherapy, and radiotherapy, depending on the expected effect and the patient’s clinical condition. Surgery is most often used, offering neurological deficit remission in 60 to 90% of patients. Most chemotherapeutics do not cross the blood-brain barrier, so immunotherapy with antibodies such as pembrolizumab and ipilimumab, as well as antineoplastic vaccines, are a promising therapeutic prospect.

Article available in PDF format

View PDF Download PDF file

References

  1. Cagney D, Martin A, Catalano P, et al. Incidence and prognosis of patients with brain metastases at diagnosis of systemic malignancy: a population-based study. Neuro-Oncology. 2017; 19(11): 1511–1521.
  2. Nayak L, Lee E, Wen P. Epidemiology of Brain Metastases. Curr Oncol Rep. 2011; 14(1): 48–54.
  3. Smedby KE, Brandt L, Bäcklund ML, et al. Brain metastases admissions in Sweden between 1987 and 2006. Br J Cancer Suppl. 2009; 101(11): 1919–1924.
  4. Giacomo ADi, Valente M, Cerase A, et al. Immunotherapy of brain metastases: breaking a “dogma”. J Exp Clin Cancer Res. 2019; 38(1).
  5. Muldoon L, Soussain C, Jahnke K, et al. Chemotherapy Delivery Issues in Central Nervous System Malignancy: A Reality Check. J Clin Oncol. 2007; 25(16): 2295–2305.
  6. Lim M, Puttick S, Houston Z, et al. Innovative Therapeutic Strategies for Effective Treatment of Brain Metastases. Int J Mol Sci. 2019; 20(6): 1280.
  7. Barnholtz-Sloan J, Sloan A, Davis F, et al. Incidence Proportions of Brain Metastases in Patients Diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J Clin Oncol. 2004; 22(14): 2865–2872.
  8. Walker AE, Robins M, Weinfeld FD. Epidemiology of brain tumors: The national survey of intracranial neoplasms. Neurology. 1985; 35(2): 219–219.
  9. Schouten L, Rutten J, Huveneers H, et al. Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma. Cancer. 2002; 94(10): 2698–2705.
  10. Barker F. Craniotomy for the resection of metastatic brain tumors in the U.S., 1988-2000. Cancer. 2004; 100(5): 999–1007.
  11. Aronson S, Garcia J, Aronson B. Metastatic neoplasms of the brain: Their frequency in relation to age. Cancer. 1964; 17(5): 558–563, doi: 10.1002/1097-0142(196405)17:5<558::aid-cncr2820170503>3.0.co;2-e.
  12. Posner J. Intracranial metastases from systemic cancer. Adv Neurol. 1978; 19: 579–592.
  13. Fox B, Cheung V, Patel A, et al. Epidemiology of Metastatic Brain Tumors. Neurosurgery Clinics. 2011; 22(1): 1–6.
  14. Siegel R, Miller K, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018; 68(1): 7–30.
  15. Wanleenuwat P, Iwanowski P. Metastases to the central nervous system: Molecular basis and clinical considerations. J Neurol Sci. 2020; 412: 116755.
  16. Suki D. The Epidemiology of Brain Metastasis. Intracranial Metastases. : 20–34.
  17. Porta R, Sanchez-Torres JM, Paz-Ares L, et al. Brain metastases from lung cancer responding to erlotinib: the importance of EGFR mutation. Eur Respir J. 2010; 37(3): 624–631.
  18. Cheng X, Hung MC. Breast cancer brain metastases. Cancer Metastasis Rev. 2007; 26(3-4): 635–643.
  19. Hicks D, Short S, Prescott N, et al. Breast Cancers With Brain Metastases are More Likely to be Estrogen Receptor Negative, Express the Basal Cytokeratin CK5/6, and Overexpress HER2 or EGFR. Am J Surg Pathol. 2006; 30(9): 1097–1104.
  20. Pestalozzi BC, Zahrieh D, Price KN, et al. Identifying breast cancer patients at risk for Central Nervous System (CNS) metastases in trials of the International Breast Cancer Study Group (IBCSG). Ann Oncol. 2006; 17(6): 935–944.
  21. Tham YL, Sexton K, Kramer R, et al. Primary breast cancer phenotypes associated with propensity for central nervous system metastases. Cancer. 2006; 107(4): 696–704.
  22. Graesslin O, Abdulkarim B, Coutant C, et al. Nomogram to Predict Subsequent Brain Metastasis in Patients With Metastatic Breast Cancer. J Clin Oncol. 2010; 28(12): 2032–2037.
  23. Network NCC. NCCN Clinical Practice Guidelines in Oncology—Melanoma Version 1. ; 2020: 2019.
  24. Togao O, Hiwatashi A, Yamashita K, et al. Additional MR contrast dosage for radiologists’ diagnostic performance in detecting brain metastases: a systematic observer study at 3 T. Jpn J Radiol. 2014; 32(9): 537–544.
  25. Krautmacher C, Willinek W, Tschampa H, et al. Brain Tumors: Full- and Half-Dose Contrast-enhanced MR Imaging at 3.0 T Compared with 1.5 T—Initial Experience. Radiology. 2005; 237(3): 1014–1019.
  26. Kushnirsky M, Nguyen V, Katz J, et al. Time-delayed contrast-enhanced MRI improves detection of brain metastases and apparent treatment volumes. J Neurosurg. 2016; 124(2): 489–495.
  27. Cohen-Inbar Or, Xu Z, Dodson B, et al. Time-delayed contrast-enhanced MRI improves detection of brain metastases: a prospective validation of diagnostic yield. J Neurooncol. 2016; 130(3): 485–494.
  28. Dolgushin M, Kornienko V, Pronin I. Brain Metastases: Advanced Neuroimaging. Springer International Publishing 2017.
  29. Valiente M, Obenauf A, Jin X, et al. Serpins Promote Cancer Cell Survival and Vascular Co-Option in Brain Metastasis. Cell. 2014; 156(5): 1002–1016.
  30. Fidler I. The role of the organ microenvironment in brain metastasis. Semin Cancer Biol. 2011; 21(2): 107–112.
  31. Lin Q, Balasubramanian K, Fan D, et al. Reactive Astrocytes Protect Melanoma Cells from Chemotherapy by Sequestering Intracellular Calcium through Gap Junction Communication Channels. Neoplasia. 2010; 12(9): 748–754.
  32. Berghoff A, Rajky O, Winkler F, et al. Invasion patterns in brain metastases of solid cancers. Neuro-Oncology. 2013; 15(12): 1664–1672.
  33. Siam L, Bleckmann A, Chaung HN, et al. The metastatic infiltration at the metastasis/brain parenchyma-interface is very heterogeneous and has a significant impact on survival in a prospective study. Oncotarget. 2015; 6(30): 29254–29267.
  34. Kamp MA, Grosser P, Felsberg J, et al. 5-aminolevulinic acid (5-ALA)-induced fluorescence in intracerebral metastases: a retrospective study. Acta Neurochir (Wien). 2012; 154(2): 223–228.
  35. Berghoff A, Ilhan-Mutlu A, Dinhof C, et al. Differential role of angiogenesis and tumour cell proliferation in brain metastases according to primary tumour type: analysis of 639 cases. Neuropathol Appl Neurobiol. 2015; 41(2): e41–e55.
  36. Sperduto P, Kased N, Roberge D, 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. 2012; 30(4): 419–425.
  37. Kim H, Lee K, Heo M, et al. The prognostic factors influencing overall survival in uterine cervical cancer with brain metastasis. Korean J Intern Med. 2019; 34(6): 1324–1332.
  38. Wang S, Hu C, Xie F, et al. Use of Programmed Death Receptor-1 and/or Programmed Death Ligand 1 Inhibitors for the Treatment of Brain Metastasis of Lung Cancer. Onco Targets Ther. 2020; 13: 667–683.
  39. Schouten L, Rutten J, Huveneers H, et al. Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma. Cancer. 2002; 94(10): 2698–2705.
  40. Sperduto P, Fang P, Li J, et al. Estimating survival in patients with gastrointestinal cancers and brain metastases: An update of the graded prognostic assessment for gastrointestinal cancers (GI-GPA). Clin Transl Radiat Oncol. 2019; 18: 39–45.
  41. Soffietti R, Chiavazza C, Rudà R. Imaging and clinical end points in brain metastases trials. CNS Oncology. 2017; 6(4): 243–246.
  42. Mintz A, Kestle J, Rathbone M, 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(7): 1470–1476, doi: 10.1002/(sici)1097-0142(19961001)78:7<1470::aid-cncr14>3.0.co;2-x.
  43. Patchell R, Tibbs P, Walsh J, et al. A Randomized Trial of Surgery in the Treatment of Single Metastases to the Brain. N Engl J Med. 1990; 322(8): 494–500.
  44. Pessina F, Navarria P, Cozzi L, et al. Role of Surgical Resection in Patients with Single Large Brain Metastases: Feasibility, Morbidity, and Local Control Evaluation. World Neurosurg. 2016; 94: 6–12.
  45. Kelly W, Shah N, Subramaniam D. Management of Brain Metastases in Epidermal Growth Factor Receptor Mutant Non-Small-Cell Lung Cancer. Front Oncol. 2018; 8.
  46. Kamp M, Rapp M, Slotty P, et al. Incidence of local in-brain progression after supramarginal resection of cerebral metastases. Acta Neurochir (Wien). 2015; 157(6): 905–911.
  47. Patel A, Suki D, Hatiboglu M, et al. Impact of surgical methodology on the complication rate and functional outcome of patients with a single brain metastasis. J Neurosurg. 2015; 122(5): 1132–1143.
  48. Nahed B, Alvarez-Breckenridge C, Brastianos P, et al. Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines on the Role of Surgery in the Management of Adults With Metastatic Brain Tumors. Neurosurgery. 2019; 84(3): E152–E155.
  49. Wang Y, Wang X, Guan Y, et al. Stereotactic radiosurgery combined with anlotinib for limited brain metastases with perilesional edema in non‐small cell lung cancer: Rvision‐001 study protocol. Thorac Cancer. 2020; 11(5): 1361–1364.
  50. Baumert B, Rutten I, Dehing-Oberije C, et al. A pathology-based substrate for target definition in radiosurgery of brain metastases. Int J Radiat Oncol Biol Phys. 2006; 66(1): 187–194.
  51. Lippitz B, Lindquist C, Paddick I, et al. Stereotactic radiosurgery in the treatment of brain metastases: The current evidence. Cancer Treat Rev. 2014; 40(1): 48–59.
  52. Karlsson B, Hanssens P, Wolff R, et al. Thirty years' experience with Gamma Knife surgery for metastases to the brain. J Neurosurg. 2009; 111(3): 449–457.
  53. Watanabe S, Yamamoto M, Sato Y, et al. Stereotactic radiosurgery for brain metastases: a case-matched study comparing treatment results for patients 80 years of age or older versus patients 65–79 years of age. J Neurosurg. 2014; 121(5): 1148–1157.
  54. Sperduto P, Shanley R, Luo X, 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(3): 526–531.
  55. Hervé F, Ghinea N, Scherrmann JM. CNS Delivery Via Adsorptive Transcytosis. The AAPS Journal. 2008; 10(3): 455–472.
  56. Moravan M, Fecci P, Anders C, et al. Current multidisciplinary management of brain metastases. Cancer. 2020; 126(7): 1390–1406.
  57. Network NCC. NCCN Clinical Practice Guidelines in Oncology- Non- Small Cell Lung Cancer Version 3. ; 2020.
  58. Jiang YZ, Jiménez J, Ou K, et al. Hemodynamic Disturbed Flow Induces Differential DNA Methylation of Endothelial Kruppel-Like Factor 4 Promoter In Vitro and In Vivo. Circ Res. 2014; 115(1): 32–43.
  59. Yu YJ, Zhang Y, Kenrick M, et al. Boosting Brain Uptake of a Therapeutic Antibody by Reducing Its Affinity for a Transcytosis Target. Sci Transl Med. 2011; 3(84): 84.
  60. Fallah J, Ahluwalia M. The role of immunotherapy in the management of patients with renal cell carcinoma and brain metastases. Ann Transl Med. 2019; 7(S8): S313–S313.
  61. Kamath S, Kumthekar P. Immune Checkpoint Inhibitors for the Treatment of Central Nervous System (CNS) Metastatic Disease. Front Oncol. 2018; 8.
  62. Tawbi H, Forsyth P, Algazi A, et al. Combined Nivolumab and Ipilimumab in Melanoma Metastatic to the Brain. N Engl J Med. 2018; 379(8): 722–730.
  63. Lehrer E, McGee H, Sheehan J, et al. Integration of immuno-oncology with stereotactic radiosurgery in the management of brain metastases. J Neurooncol. 2020.
  64. Du W, Seah I, Bougazzoul O, et al. Stem cell-released oncolytic herpes simplex virus has therapeutic efficacy in brain metastatic melanomas. Proceedings of the National Academy of Sciences. 2017; 114(30): E6157–E6165.