title: Analysis of the results of recurrent intracranial meningiomas treated with re-radiosurgery.
abstract: OBJECTIVE
  Meningioma is the most common intracranial neoplasm, comprising approximately 30% of all primary intracranial tumors (Claus et al., 2005) [1]. Treatment options include observation, microsurgical resection, stereotactic radiosurgery (SRS), and whole brain radiation therapy (WBRT). Gamma knife radiosurgery (GKRS) is a very effective treatment for intracranial meningiomas; previous studies showed the tumor control rate at 5-10 years of follow-up as 84.3%-100% in all cases (Feigl et al., 2005; Linskey et al., 2005; Malik et al., 2005; Aichholzer et al., 2000; Hakim et al., 1998; Chang and Adler 1997; Lunsford, 1994; Ganz et al., 1993) [2-9]. Many studies have discussed issues like optimal dose, conformal configurations, and adverse effects to improve the treatment result with GKRS (Malik et al., 2005; Kenai et al., 2005; Rowe et al., 2004; Shrieve et al., 2004) [4,10-12]. There are some cases in which the radiosurgery result is unfavorable and perhaps further treatment is needed. In these cases, re-radiosurgery can be an option. However, there have not been comprehensive studies discussing the issues of re-radiosurgery. Therefore, we analyzed the result of re-radiosurgery for recurrent meningiomas and their impact on clinical outcomes.
  
  
  METHODS
  From 1995 to 2015, we retrospectively reviewed 1163 patients who underwent GKRS for intracranial meningioma at the Asan Medical Center. Patients with multiple meningiomas or a follow-up with a period of less than a year were excluded from this study. Finally, 865 patients were enrolled in this study. Clinical symptoms and brain magnetic resonance imaging (MRI) scans were assessed by neurosurgeons. When tumor size increased together with newly developed neurologic symptoms, further management, such as microsurgical resection or SRS, was considered. Histologic analysis of the resected tumors was performed by neuropathologists. Clinical data, including patient's sex, age, and tumor locations were recorded. Treatment data included tumor volume, tumor grade, radiation dose, and presence of edema. Final outcome data including follow-up period, time to progression, interval between first and second radiosurgery courses and interval between microsurgery and radiosurgery were obtained.
  
  
  RESULTS
  Among 865 patients, tumor recurrence was found in 63 patients (7.28%). Seven patients showed transient tumor growth after GKRS. These patients have been under close observation without any further treatments. Fifty-six patients (6.47%) showed permanent tumor growth on follow-up MRI. Thirty-three patients from this group underwent repeated radiosurgery owing to tumor growth, resulting in a re-irradiation rate of 3.82% at our radiosurgery center. The other 23 patients were treated using methods other than re-radiosurgery. Among the 33 patients, 25 underwent microsurgical resection prior to their initial course of GKRS, and the other 8 were treated with re-radiosurgery only. An analysis was performed to determine factors that may have a role in treatment results. Of the many variables, tumor grade (p=0.004, Fisher's exact test) was the only significant factor for progression-free survival (PFS). Thirteen patients with unbiopsied or benign meningioma showed stable tumor size, while there was tumor growth in 8 patients. Among high-grade meningioma patients, 3 and 9 showed stable disease and tumor growth, respectively. As a result of re-radiosurgery, 11 out of 17 patients showed tumor growth and needed further treatments; this involved a third GKRS for 4 patients, microsurgical resection for 6 patients, and cyber knife radiosurgery (CKRS) for 1 patient. Four patients from this group were also treated with WBRT.
  
  
  CONCLUSIONS
  We analyzed the results of re-radiosurgery for recurrent meningiomas and observed that World Health Organization (WHO) grade II and III was significantly associated with a lower PFS rate compared with low-grade meningiomas (p=0.004). Conversely, patients with benign meningioma or unbiopsied tumors had much better results. Hence, re-radiosurgery is recommended for patients with unknown or benign meningiomas if their first GKRS result is unsatisfactory. However, re-radiosurgery should be considered carefully for recurrent high-grade tumors. Owing to the small number of recurrent meningioma patients treated with re-radiosurgery, further studies are required to delineate the role of this treatment.
authors.affiliation: Graduate School of Medicine, University of Ulsan, Seoul 05505, Republic of Korea.
authors.forename: Moinay
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Neurological Surgery, Asan Medical Center, College of Medicine, University of Ulsan, Seoul 05505, Republic of Korea.
authors.forename: Do Hee
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Neurological Surgery, Asan Medical Center, College of Medicine, University of Ulsan, Seoul 05505, Republic of Korea.
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Kim Rn
authors.affiliation: Department of Neurological Surgery, Asan Medical Center, College of Medicine, University of Ulsan, Seoul 05505, Republic of Korea.
authors.forename: Young Hyun
authors.initials: YH
authors.lastname: Cho
authors.affiliation: Department of Neurological Surgery, Asan Medical Center, College of Medicine, University of Ulsan, Seoul 05505, Republic of Korea.
authors.forename: Jeong Hoon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Neurological Surgery, Asan Medical Center, College of Medicine, University of Ulsan, Seoul 05505, Republic of Korea. Electronic address: ykwon@amc.seoul.kr.
authors.forename: Do Hoon
authors.initials: DH
authors.lastname: Kwon
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008577:Meningeal Neoplasms / Q000453:epidemiology / Q000601:surgery*; D008579:Meningioma / Q000453:epidemiology / Q000601:surgery*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000601:surgery*; D017063:Outcome Assessment, Health Care; D016634:Radiosurgery / Q000379:methods / Q000592:standards* / Q000706:statistics & numerical data; D012086:Reoperation / Q000379:methods / Q000592:standards* / Q000706:statistics & numerical data; D012189:Retrospective Studies; D055815:Young Adult
keywords: Gamma knife; Histology; Meningioma; Microsurgery; Re-radiosurgery; Stereotactic radiosurgery