Journal of Korean Neurosurgical Society

The Korean Neurosurgical Society (대한신경외과학회)
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Ki67 Index Is the Most Powerful Factor for Predicting the Recurrence in Atypical Meningioma : Retrospective Analysis of 99 Patients in Two Institutes

  • Lee, Sang Hyuk (Department of Neurosurgery, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine) ;
  • Lee, Eun Hee (Department of Pathology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine) ;
  • Sung, Kyoung Su (Department of Neurosurgery, Dong-A University Hospital, Dong-A University College of Medicine) ;
  • Kim, Dae Cheol (Department of Pathology, Dong-A University Hospital, Dong-A University College of Medicine) ;
  • Kim, Young Zoon (Department of Neurosurgery, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine) ;
  • Song, Young Jin (Department of Neurosurgery, Dong-A University Hospital, Dong-A University College of Medicine)
  • Received : 2021.07.29
  • Accepted : 2021.09.18
  • Published : 2022.07.01
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Abstract

Objective : The primary objective of this study was to identify predicting factors for local control (LC) of atypical meningioma, and we validated them with comparing the predicting factors for recurrence-free survival (RFS). We also examined the rate of LC after surgical resection with or without adjuvant treatment and RFS. Methods : Clinical and radiological records of patients with atypical meningiomas diagnosed at two institutes from January 2000 to December 2018 were reviewed retrospectively. Histopathological features were also reviewed using formalin-fixed paraffin embedded samples from pathological archives. Results : Of the 99 atypical meningiomas eligible for analysis, 36 (36.4%) recurred during the follow-up period (mean, 83.3 months; range, 12-232 months). The rate of 3-year LC and 5-year LC was 80.8% and 74.7%, respectively. The mean time-to-recurrence was 49.4 months (range, 12-150). The mean RFS was 149.3 months (95% confidence interval, 128.8-169.8 months) during the mean follow-up duration of 83.3 months (range, 12-232 months). Multivariate analysis using Cox proportional-hazard regression model showed that the extent of resection (hazard ratio [HR], 4.761; p=0.013), Ki67 index (HR, 8.541; p=0.004), mitotic index (HR, 3.275; p=0.044), and tumor size (HR, 3.228; p=0.041) were independently associated with LC. These factors were also statistically associated with RFS. In terms of radiotherapy after surgical resection, the recurrence was not prevented by immediate radiotherapy because of the strong effect of proliferative index on recurrence. Conclusion : The present study suggests that the extent of resection, proliferative index (according to Ki67 expression) and mitotic index, and tumor size are associated with recurrence of atypical meningiomas. However, our results should be further validated through prospective and randomized clinical trials to overcome the inborn bias of retrospective nature of the study design.

Keywords

Acknowledgement

This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean Government (The Ministry of Science and ICT) (Grant No. NRF 2019R 1F1A 1054681). This paper was also financially supported by Sungkyun Research Fund, Sungkyunkwan University (2016) and Samsung Changwon Hospital Research Fund (2020). The authors would like to thank Young Min Kim, M.D. and Mi-Ok Sunwoo, M.D. (Department of Radiology, Samsung Changwon Hospital), and Sun Sup Choi, M.D. (Department of Radiology, Dong-A University Medical Center) for reviewing neuroradiological images; Young Wook Kim, M.D. (Department of Biostatistics, Samsung Changwon Hospital) for assistance with statistical analysis, and Tae Gyu Kim, M.D. (Department of Radiation Oncology, Samsung Changwon Hospital), and Young Min Choi, M.D. (Department of Radiation Oncology, Dong-A University Medical Center) for applying the radiotherapy detailed in this work.

References

  1. Aghi MK, Carter BS, Cosgrove GR, Ojemann RG, Amin-Hanjani S, Martuza RL, et al. : Long-term recurrence rates of atypical meningiomas after gross total resection with or without postoperative adjuvant radiation. Neurosurgery 64 : 56-60, 2009 https://doi.org/10.1227/01.NEU.0000330399.55586.63
  2. Champeaux C, Dunn L : World health organization grade II meningioma: a 10-year retrospective study for recurrence and prognostic factor assessment. World Neurosurg 89 : 1801-186, 2016
  3. Champeaux C, Houston D, Dunn L : Atypical meningioma. a study on recurrence and disease-specific survival. Neurochirurgie 63 : 273-281, 2017 https://doi.org/10.1016/j.neuchi.2017.03.004
  4. Champeaux C, Wilson E, Shieff C, Khan AA, Thorne L : WHO grade II meningioma: a retrospective study for outcome and prognostic factor assessment. J Neurooncol 129 : 337-345, 2016 https://doi.org/10.1007/s11060-016-2181-2
  5. Choi Y, Lim DH, Yu JI, Jo K, Nam DH, Seol HJ, et al. : Prognostic value of KI-67 labeling index and postoperative radiotherapy in WHO grade II meningioma. Am J Clin Oncol 41 : 18-23, 2018 https://doi.org/10.1097/COC.0000000000000224
  6. Choy W, Kim W, Nagasawa D, Stramotas S, Yew A, Gopen Q, et al. : The molecular genetics and tumor pathogenesis of meningiomas and the future directions of meningioma treatments. Neurosurg Focus 30 : E6, 2011
  7. Clark VE, Erson-Omay EZ, Serin A, Yin J, Cotney J, Ozduman K, et al. : Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO. Science 339 : 1077-1080, 2013 https://doi.org/10.1126/science.1233009
  8. Detti B, Scoccianti S, Di Cataldo V, Monteleone E, Cipressi S, Bordi L, et al. : Atypical and malignant meningioma: outcome and prognostic factors in 68 irradiated patients. J Neurooncol 115 : 421-427, 2013 https://doi.org/10.1007/s11060-013-1239-7
  9. Eng J : Receiver operating characteristic analysis: a primer. Acad Radiol 12 : 909-916, 2005 https://doi.org/10.1016/j.acra.2005.04.005
  10. Gousias K, Schramm J, Simon M : The simpson grading revisited: aggressive surgery and its place in modern meningioma management. J Neurosurg 125 : 551-560, 2016 https://doi.org/10.3171/2015.9.jns15754
  11. Kane AJ, Sughrue ME, Rutkowski MJ, Shangari G, Fang S, McDermott MW, et al. : Anatomic location is a risk factor for atypical and malignant meningiomas. Cancer 117 : 1272-1278, 2011 https://doi.org/10.1002/cncr.25591
  12. Kaur G, Sayegh ET, Larson A, Bloch O, Madden M, Sun MZ, et al. : Adjuvant radiotherapy for atypical and malignant meningiomas: a systematic review. Neuro Oncol 16 : 628-636, 2014 https://doi.org/10.1093/neuonc/nou025
  13. Kim M, Cho YH, Kim JH, Kim CJ, Roh SW, Kwon DH : Role of gamma knife radiosurgery for recurrent or residual World Health Organization grade II and III intracranial meningiomas. Br J Neurosurg 34 : 239-245, 2020 https://doi.org/10.1080/02688697.2020.1726285
  14. Kim MS, Kim KH, Lee EH, Lee YM, Lee SH, Kim HD, et al. : Results of immunohistochemical staining for cell cycle regulators predict the recurrence of atypical meningiomas. J Neurosurg 121 : 1189-1200, 2014 https://doi.org/10.3171/2014.7.JNS132661
  15. Klinger DR, Flores BC, Lewis JJ, Hatanpaa K, Choe K, Mickey B, et al. : Atypical meningiomas: recurrence, reoperation, and radiotherapy. World Neurosurg 84 : 839-845, 2015 https://doi.org/10.1016/j.wneu.2015.04.033
  16. 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 131 : 803-820, 2016 https://doi.org/10.1007/s00401-016-1545-1
  17. Marcus HJ, Price SJ, Wilby M, Santarius T, Kirollos RW : Radiotherapy as an adjuvant in the management of intracranial meningiomas: are we practising evidence-based medicine? Br J Neurosurg 22 : 520-528, 2008 https://doi.org/10.1080/02688690802308687
  18. Marosi C, Hassler M, Roessler K, Reni M, Sant M, Mazza E, et al. : Meningioma. Crit Rev Oncol Hematol 67 : 153-157, 2008 https://doi.org/10.1016/j.critrevonc.2008.01.010
  19. Ostrom QT, Cioffi G, Gittleman H, Patil N, Waite K, Kruchko C, et al. : CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the united states in 2012-2016. Neuro Oncol 21(Suppl 5) : v1-v100, 2019 https://doi.org/10.1093/neuonc/noz150
  20. Park HJ, Kang HC, Kim IH, Park SH, Kim DG, Park CK, et al. : The role of adjuvant radiotherapy in atypical meningioma. J Neurooncol 115 : 241-247, 2013 https://doi.org/10.1007/s11060-013-1219-y
  21. Perry A : Unmasking the secrets of meningioma: a slow but rewarding journey. Surg Neurol 61 : 171-173, 2004 https://doi.org/10.1016/S0090-3019(03)00488-9
  22. Perry A, Giannini C, Raghavan R, Scheithauer BW, Banerjee R, Margraf L, et al. : Aggressive phenotypic and genotypic features in pediatric and NF2-associated meningiomas: a clinicopathologic study of 53 cases. J Neuropathol Exp Neurol 60 : 994-1003, 2001 https://doi.org/10.1093/jnen/60.10.994
  23. Proctor DT, Ramachandran S, Lama S, Sutherland GR : Towards molecular classification of meningioma: evolving treatment and diagnostic paradigms. World Neurosurg 119 : 366-373, 2018 https://doi.org/10.1016/j.wneu.2018.08.019
  24. Tanzler E, Morris CG, Kirwan JM, Amdur RJ, Mendenhall WM : Outcomes of WHO grade I meningiomas receiving definitive or postoperative radiotherapy. Int J Radiat Oncol Biol Phys 79 : 508-513, 2011 https://doi.org/10.1016/j.ijrobp.2009.11.032
  25. Vranic A, Popovic M, Cor A, Prestor B, Pizem J : Mitotic count, brain invasion, and location are independent predictors of recurrence-free survival in primary atypical and malignant meningiomas: a study of 86 patients. Neurosurgery 67 : 1124-1132, 2010 https://doi.org/10.1227/NEU.0b013e3181eb95b7
  26. Zaher A, Abdelbari Mattar M, Zayed DH, Ellatif RA, Ashamallah SA : Atypical meningioma: a study of prognostic factors. World Neurosurg 80 : 549-553, 2013 https://doi.org/10.1016/j.wneu.2013.07.001