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复发性颅内脑膜瘤再行放射外科治疗的结果分析

Analysis of the results of recurrent intracranial meningiomas treated with re-radiosurgery.

作者信息

Kim Moinay, Lee Do Hee, Kim Rn Hyun Jung, Cho Young Hyun, Kim Jeong Hoon, Kwon Do Hoon

机构信息

Graduate School of Medicine, University of Ulsan, Seoul 05505, Republic of Korea.

Department of Neurological Surgery, Asan Medical Center, College of Medicine, University of Ulsan, Seoul 05505, Republic of Korea.

出版信息

Clin Neurol Neurosurg. 2017 Feb;153:93-101. doi: 10.1016/j.clineuro.2016.12.014. Epub 2016 Dec 29.

Abstract

OBJECTS

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.

CONCLUSION

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.

摘要

目的

脑膜瘤是最常见的颅内肿瘤,约占所有原发性颅内肿瘤的30%(克劳斯等人,2005年)[1]。治疗选择包括观察、显微手术切除、立体定向放射外科治疗(SRS)和全脑放射治疗(WBRT)。伽玛刀放射外科治疗(GKRS)是治疗颅内脑膜瘤的一种非常有效的方法;先前的研究表明,在所有病例中,5至10年随访期的肿瘤控制率为84.3% - 100%(费格尔等人,2005年;林斯基等人,2005年;马利克等人,2005年;艾希霍尔泽等人,2000年;哈基姆等人,1998年;张和阿德勒,1997年;伦斯福德,1994年;甘茨等人,1993年)[2 - 9]。许多研究讨论了诸如最佳剂量、适形配置和不良反应等问题,以改善GKRS的治疗效果(马利克等人,2005年;凯奈等人,2005年;罗等人,2004年;施里夫等人,2004年)[4,10 - 12]。在某些情况下,放射外科治疗结果不理想,可能需要进一步治疗。在这些情况下,再次放射外科治疗可以是一种选择。然而,尚未有全面的研究讨论再次放射外科治疗的问题。因此,我们分析了复发性脑膜瘤再次放射外科治疗的结果及其对临床结局的影响。

方法

从1995年到2015年,我们回顾性分析了在峨山医学中心接受GKRS治疗颅内脑膜瘤的1163例患者。患有多发性脑膜瘤或随访期少于一年的患者被排除在本研究之外。最终,865例患者纳入本研究。神经外科医生评估临床症状和脑部磁共振成像(MRI)扫描。当肿瘤大小增加并伴有新出现的神经症状时,考虑进一步治疗,如显微手术切除或SRS。神经病理学家对切除的肿瘤进行组织学分析。记录临床数据,包括患者的性别、年龄和肿瘤位置。治疗数据包括肿瘤体积、肿瘤分级、放射剂量和水肿情况。获得最终结局数据,包括随访期、进展时间、首次和第二次放射外科治疗疗程之间的间隔以及显微手术和放射外科治疗之间的间隔。

结果

在865例患者中,发现63例(7.28%)肿瘤复发。7例患者在GKRS后出现短暂肿瘤生长。这些患者一直在密切观察中,未进行任何进一步治疗。56例(6.47%)患者在随访MRI中显示肿瘤持续生长。该组中有33例患者因肿瘤生长接受了再次放射外科治疗,在我们的放射外科中心再次照射率为3.82%。其他23例患者采用了再次放射外科治疗以外的方法治疗。在33例患者中,25例在初次GKRS疗程之前接受了显微手术切除,另外8例仅接受了再次放射外科治疗。进行分析以确定可能对治疗结果有影响的因素。在众多变量中,肿瘤分级(p = 0.004,费舍尔精确检验)是无进展生存期(PFS)的唯一显著因素。13例未活检或为良性脑膜瘤的患者肿瘤大小稳定,而8例患者出现肿瘤生长。在高级别脑膜瘤患者中,分别有3例和9例病情稳定和肿瘤生长。再次放射外科治疗的结果是,17例患者中有11例出现肿瘤生长,需要进一步治疗;其中4例患者接受了第三次GKRS,6例患者接受了显微手术切除,1例患者接受了射波刀放射外科治疗(CKRS)。该组中有4例患者还接受了WBRT。

结论

我们分析了复发性脑膜瘤再次放射外科治疗的结果,观察到与低级别脑膜瘤相比,世界卫生组织(WHO)II级和III级脑膜瘤的PFS率显著较低(p = 0.004)。相反,患有良性脑膜瘤或未活检肿瘤的患者结果要好得多。因此,如果首次GKRS结果不理想,对于不明或良性脑膜瘤患者建议进行再次放射外科治疗。然而,对于复发性高级别肿瘤,应谨慎考虑再次放射外科治疗。由于接受再次放射外科治疗的复发性脑膜瘤患者数量较少,需要进一步研究来明确这种治疗的作用。

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