Осложнения стереотаксического радиохирургического лечения заболеваний головного мозга

Цель исследования – анализ осложнений стереотаксического радиохирургического лечения различных заболеваний головного мозга на аппарате Elekta Leksell Gamma Knife Perfexion.
Материалы и методы. Проведен ретроспективный анализ результатов радиохирургического лечения 3148 пациентов, из них пациенты с метастазами – 1621 (51,5 %), менингиомами – 732 (23,3 %), невриномами – 359 (11,4 %), артериовенозными мальформациями – 71 (2,3 %), каверномами – 118 (3,7 %), нейроэпителиальными опухолями – 114 (3,6 %), аденомами гипофиза – 46 (1,5 %), функциональными заболеваниями – 54 (1,7 %), с другими заболеваниями – 33 (1 %).
Для постановки диагнозов проводили неврологический осмотр, использовали данные магнитно-резонансной и компьютерной томографии, а также позитронно-эмиссионной томографии.
Тяжесть лучевых осложнений оценена по шкале Eastern Cooperative Oncology Group (ECOG).
Результаты. Из всех пациентов, которым было проведено стереотаксическое радиохирургическое лечение, у 96 пациентов было выявлено 97 различных осложнений. Среди неспецифических осложнений превалировали радионекроз (n = 43) и перифокальный отек (n = 38), реже встречались алопеция (n = 3) и учащение эпилептических приступов (n = 3). Специфических осложнений было меньше: неокклюзионная гидроцефалия развилась у 3 пациентов, поражение черепно-мозговых нервов – у 6 пациентов и эндокринные нарушения – у 1 пациента. Общий процент радиационно-индуцированных осложнений составил 3,08 %.
Заключение. На основе анализа данных, полученных в нашем центре, мы определили, что стереотаксическая радиохирургия является безопасным методом лечения различных заболеваний головного мозга с низким процентом развития послеоперационных осложнений. Частота развития осложнений не превысила процент осложнений по данным мировой и отечественной литературы.

1. Голанов А.В., Коновалов А.Н., Корниенко В.Н. и др. Первый опыт применения установки «Гамма-нож» для радиохирургического лечения интракраниальных объемных образований. Вопросы нейрохирургии им. Н.Н. Бурденко 2007;1:3–10. [Golanov A.V., Konovalov A.N., Kornienko V.N. et al. First experience of using Gamma Knife in radiosurgery for intracranial volumetric tumors. Voprosy neyrokhirurgii im. N.N. Burdenko = Burdenko's Journal of Neurosurgery 2007;1:3–10. (In Russ.)].

2. Barnett G.C., West C.M.L., Dunning A.M. et al. Normal tissue reactions to radiotherapy: towards tailoring treatment dose by genotype. Nat Rev Cancer 2009;9(2): 134–42. DOI: 10.1038/nrc2587.

3. De Sanctis P., Green S., Germano I. Communicating hydrocephalus after radiosurgery for vestibular schwannomas: does technique matter? A systematic review and meta-analysis. J Neurooncol 2019;145(2):365–73. DOI: 10.1007/s11060-019-03305-w.

4. Vellayappan B., Tan C.L., Yong C. et al. Diagnosis and management of radiation necrosis in patients with brain metastases. Front Oncol 2018;8:2–10. DOI: 10.3389/fonc.2018.00395.

5. Chin L.S., Ma L., DiBiase S. Radiation necrosis following gamma knife surgery: A case-controlled comparison of treatment parameters and long-term clinical follow up. J Neurosurg 2001;94(6):899–904. DOI: 10.3171/jns.2001.94.6.0899.

6. Minniti G., Clarke E., Lanzetta G. et al. Stereotactic radiosurgery for brain metastases: Analysis of outcome and risk of brain radionecrosis. Radiat Oncol 2011;6(1):1–9. DOI: 10.1186/1748-717X-6-48.

7. Sharma M., Jia X., Ahluwalia M. et al. First follow-up radiographic response is one of the predictors of local tumor progression and radiation necrosis after stereotactic radiosurgery for brain metastases. Cancer Med 2017;6(9):2076–86. DOI: 10.1002/cam4.1149.

8. De Azevedo Santos T.R., Tundisi C.F., Ramos H. et al. Local control after radiosurgery for brain metastases: predictive factors and implications for clinical decision. Radiat Oncol 2015;10:63. DOI: 10.1186/s13014-015-0367-y.

9. El Gantery M.M., Abd El Baky H.M., El Hossieny H.A. et al. Management of brain metastases with stereotactic radiosurgery alone versus whole brain irradiation alone versus both. Radiat Oncol 2014;9:116. DOI: 10.1186/1748-717X-9-116.

10. Miller J.A., Bennett E.E., Xiao R. et al. Association between radiation necrosis and tumor biology after stereotactic radiosurgery for brain metastasis. Int J Radiat Oncol Biol Phys 2016;96(5):1060–9. DOI: 10.1016/j.ijrobp.2016.08.039.

11. Lippitz B.E., Bartek J.J., Mathiesen T. et al. Ten-year follow-up after Gamma Knife radiosurgery of meningioma and review of the literature. Acta Neurochir (Wien) 2020;162(9):2183–96. DOI: 10.1007/s00701-020-04350-5.

12. O’Connor K.P., Algan O., Vesely S.K. et al. Factors associated with treatment failure and radiosurgery-related edema in WHO Grade 1 and 2 meningioma patients receiving Gamma Knife radiosurgery. World Neurosurg 2019;130:558–65. DOI: 10.1016/j.wneu.2019.06.152.

13. Gupta A., Xu Z., Cohen-Inbar O. et al. Treatment of asymptomatic meningioma with Gamma Knife radiosurgery: Longterm follow-up with volumetric assessment and clinical outcome. Neurosurgery 2019;85(5):889–99. DOI: 10.1093/neuros/nyz126.

14. Hasegawa H., Hanakita S., Shin M. et al. Single-fractionated stereotactic radiosurgery for intracranial meningioma in elderly patients: 25 year experience at a single institution. Oper Neurosurg (Hagerstown, Md) 2018;14(4):341–50. DOI: 10.1093/ons/opx109.

15. Sethi R.A., Rush S.C., Liu S. et al. DoseResponse relationships for meningioma radiosurgery. Am J Clin Oncol 2015;38(6):600–4. DOI: 10.1097/COC.0000000000000008.

16. Mahboubi H., Sahyouni R., Moshtaghi O. et al. CyberKnife for treatment of vestibular schwannoma: A metaanalysis. Otolaryngol Head Neck Surg 2017;157(1):7–15. DOI: 10.1177/0194599817695805.

17. Watanabe S., Yamamoto M., Kawabe T. et al. Stereotactic radiosurgery for vestibular schwannomas: average 10 year follow-up results focusing on long-term hearing preservation. J Neurosurg 2016;125(1):64–72. DOI: 10.3171/2016.7.GKS161494.

18. Johnson S., Kano H., Faramand A. et al. Long term results of primary radiosurgery for vestibular schwannomas. J Neurooncol 2019;145(2):247–55. DOI: 10.1007/s11060-019-03290-0.

19. Boari N., Bailo M., Gagliardi F. et al. Gamma Knife radiosurgery for vestibular schwannoma: clinical results at long-term follow-up in a series of 379 patients. J Neurosurg 2014;121:123–42. DOI: 10.3171/2014.8.GKS141506.

20. Daigle J.L., Hong J.H., Chiang C.S. et al. The role of tumor necrosis factor signaling pathways in the response of murine brain to irradiation. Cancer Res 2001;61(24):8859–65. PMID: 11751409.

21. Zhuang Н., Shi S., Yuan Z. et al. Bevacizumab treatment for radiation brain necrosis: mechanism, efficacy and issues. Mol Cancer 2019;18(1):21. DOI: 10.1186/s12943-019-0950-1.

22. Ali F.S., Arevalo O., Zorofchian S. et al. Cerebral radiation necrosis: incidence, pathogenesis, diagnostic challenges, and future opportunities. Curr Oncol Rep 2019;21(8):66. DOI: 10.1007/s11912-019-0818-y.

23. Lawrence Y.R., Li X.A., el Naga I. et al. Radiation dose-volume effects in brain. Int J Radiat Oncol Biol Phys 2010;76(3):20–7. DOI: 10.1016/j.ijrobp.2009.02.091.

24. Langleben D.D., Segall G.M. PET in differentiation of recurrent brain tumor from radiation injury. J Nucl Med 2000;41(11):1861–7. PMID: 11079496.

25. Brandsma D., Stalpers L., Taal W. et al. Clinical features, mechanisms, and management of pseudoprogression in malignant gliomas. Lancet Oncol 2008;9(5):453–61. DOI: 10.1016/S1470-2045(08)70125-6.

26. Verma N., Cowperthwaite M.C., Burnett M.G. et al. Differentiating tumor recurrence from treatment necrosis: A review of neuro-oncologic imaging strategies. Neuro Oncol 2013;15(5):515–34. DOI: 10.1093/neuonc/nos307.

27. Gardner W.J., Spitler D.K., Whitten C. Increased intracranial pressure caused by increased protein content in the cerebrospinal fluid. N Engl J Med 1954;250(22):932–6. URL: https://doi.org/10.1056/NEJM195406032502202.

28. Al Hinai Q., Zeitouni A., Sirhan D. et al. Communicating hydrocephalus and vestibular schwannomas: Etiology, treatment, and long-term follow-up. J Neurol Surg B Skull Base 2013;74(2):68–74. DOI: 10.1055/s0033-1333621.

29. Treglia G., Muoio B., Trevisi G. et al. Diagnostic performance and prognostic value of PET/CT with different tracers for brain tumors: A systematic review of published meta-analyses. Int J Mol Sci 2019;20(19). DOI: 10.3390/ijms20194669.

30. Griffeth L.K. Use of Pet/Ct scanning in cancer patients: Technical and practical considerations. Baylor Univ Med Cent Proc 2005;18(4):321–30. DOI: 10.1080/08998280.2005.11928089.

31. Ito K., Matsuda H., Kubota K. Imaging spectrum and pitfalls of 11C-methionine positron emission tomography in a series of patients with intracranial lesions. Korean J Radiol 2016;17(3):424–34. DOI: 10.3348/kjr.2016.17.3.424.

32. Yomo S., Oguchi K. Prospective study of 11C-methionine PET for distinguishing between recurrent brain metastases and radiation necrosis: Limitations of diagnostic accuracy and long-term results of salvage treatment. BMC Cancer 2017;17(1):1. DOI: 10.1186/s12885-017-3702-x.

33. Tan H., Chen L., Guan Y. et al. Comparison of MRI, 18F FDG, and 11Ccholine PET/CT for their potentials in differentiating brain tumor recurrence from brain tumor necrosis following radiotherapy Clin Nucl Med 2011;36(11):978–81. DOI: 10.1097/RLU.0b013e31822f68a6.

34. Öz G., Alger J.A., Barker P.B. et al. Clinical proton mr spectroscopy in central nervous system disorders. Radiology 2014;270(3):658–79. DOI: 10.1148/radiol.13130531.

35. Verma A., Kumar I., Verma N. et al. Magnetic resonance spectroscopy – Revisiting the biochemical and molecular milieu of brain tumors. BBA Clin 2016;5:170–8. DOI: 10.1016/j.bbacli.2016.04.002.

36. Sundgren P.C., Nagesh V., Elias A. et al. Metabolic alterations: a biomarker for radiation-induced normal brain injury – an MR spectroscopy study. J Magn Reson Imaging 2009;29(2):291–7. DOI: 10.1002/jmri.21657.

37. Lee M.C., Pirzkall A., McKnight T.R. et al. III-MRSI of radiation effects in normal-appearing white matter: dosedependence and impact on automated spectral classification. J Magn Reson Imaging 2004;19(4):379–88. DOI: 10.1002/jmri.20017.

38. Elias A.E., Carlos R.C., Smith E.A. et al. MR spectroscopy using normalized and non-normalized metabolite ratios for differentiating recurrent brain tumor from radiation injury. Acad Radiol 2011;18(9):1101–8. DOI: 10.1016/j.acra.2011.05.006.

39. Thompson E.M., Guillaume D.J., Dosa E. Perfusion MRI – technical aspect 2013;200(1):24–34. DOI: 10.2214/AJR.12.9543.

40. Cicone F., Minniti G., Romano A. et al. Accuracy of F-DOPA PET and perfusionMRI for differentiating radionecrotic from progressive brain metastases after radiosurgery. Eur J Nucl Med Mol Imaging 2015;42(1):103–11. DOI: 10.1007/s00259-014-2886-4.

41. Walker A.J., Ruzevick J., Malayeri A.A. et al. Postradiation imaging changes in the CNS: How can we differentiate between treatment effect and disease progression? Futur Oncol 2014;10(7):1277–97. DOI: 10.2217/fon.13.271.

42. Maier S.E., Sun Y., Mulkern R.V. Diffusion imaging of brain tumors. NMR Biomed 2010;23(7):849–64. DOI: 10.1002/nbm.1544.

43. William R., Wang P.I., Chenevert T.L. et al. Comparison of diffusion tensor imaging and magnetic resonance perfusion imaging in differentiating recurrent brain neoplasm from radiation necrosis. Acad Radiol 2016;23:569–76. DOI: 10.1016/j.acra.2015.11.015.

44. Маряшев С.А. Стереотаксическое облучение артериовенозных мальформаций головного мозга: автореферат дис. … доктора медицинских наук. М., 2016. 45 с. URL: https://search.rsl.ru/ru/record/01006658950. [Maryashev S.A. Stereotactic irradiation of arteriovenous malformations of the brain: summary of thesis ... of doctor of medical sciences. Moscow, 2016. 45 p. DOI: https://search.rsl.ru/ru/record/01006658950. (In Russ.)].

45. Kohutek Z.A., Yamada Y., Chan T.A. et al. Long-term risk of radionecrosis and imaging changes after stereotactic radiosurgery for brain metastases. J Neurooncol 2015;125(1):149–56. DOI: 10.1007/s11060-015-1881-3.

46. Cruz М.P. Edaravone (Radicava): A Novel neuroprotective agent for the treatment of amyotrophic lateral sclerosis. P&T 2018;43(1):25–8. PMID: 2929067.