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立体定向放射外科加强治疗寡转移脑疾病的切除床:挑战辅助全脑放疗的传统

Stereotactic radiosurgery boost to the resection bed for oligometastatic brain disease: challenging the tradition of adjuvant whole-brain radiotherapy.

作者信息

Karlovits Brian J, Quigley Matthew R, Karlovits Stephen M, Miller Lindsay, Johnson Mark, Gayou Olivier, Fuhrer Russell

机构信息

Departments of Radiation Oncology, Allegheny General Hospital, Pittsburgh, Pennsylvania 15212, USA.

出版信息

Neurosurg Focus. 2009 Dec;27(6):E7. doi: 10.3171/2009.9.FOCUS09191.

Abstract

OBJECT

Whole-brain radiation therapy (WBRT) has been the traditional approach to minimize the risk of intracranial recurrence following resection of brain metastases, despite its potential for late neurotoxicity. In 2007, the authors demonstrated an equivalent local recurrence rate to WBRT by using stereotactic radiosurgery (SRS) to the operative bed, sparing 72% of their patients WBRT. They now update their initial experience with additional patients and more mature follow-up.

METHODS

The authors performed a retrospective review of all cases involving patients with limited intracranial metastatic disease (< or = 4 lesions) treated at their institution with SRS to the operative bed following resection. No patient had prior cranial radiation and WBRT was used only for salvage.

RESULTS

From November 2000 to June 2009, 52 patients with a median age of 61 years met inclusion criteria. A single metastasis was resected in each patient. Thirty-four of the patients each had 1 lesion, 13 had 2 lesions, 3 had 3 lesions, and 2 had 4 lesions. A median dose of 1500 cGy (range 800-1800 cGy) was delivered to the resection bed targeting a median volume of 3.85 cm(3) (range 0.08-22 cm(3)). With a median follow-up of 13 months, the median survival was 15.0 months. Four patients (7.7%) had a local recurrence within the surgical site. Twenty-three patients (44%) ultimately developed distant brain recurrences at a median of 16 months postresection, and 16 (30.7%) received salvage WBRT (8 for diffuse disease [> 3 lesions], 4 for local recurrence, and 4 for diffuse progression following salvage SRS). The median time to WBRT administration postresection was 8.7 months (range 2-43 months). On univariate analysis, patient factors of a solitary tumor (19.0 vs 12 months, p = 0.02), a recursive partitioning analysis (RPA) Class I (21 vs 13 months, p = 0.03), and no extracranial disease on presentation (22 vs 13 months, p = 0.01) were significantly associated with longer survival. Cox multivariate analysis showed a significant association with longer survival for the patient factors of no extracranial disease on presentation (p = 0.01) and solitary intracranial metastasis (p = 0.02). Among patients with no extracranial disease, a solitary intracranial metastasis conferred significant additional survival advantage (43 vs 10.5 months, p = 0.05, log-rank test). No factor (age, RPA class, tumor size or histological type, disease burden, extent of resection, or SRS dose or volume) was related to the need for salvage WBRT.

CONCLUSIONS

Adjuvant SRS to the metastatic intracranial operative bed results in a local recurrence rate equivalent to adjuvant WBRT. In combination with SRS for unresected lesions and routine imaging surveillance, this approach achieves robust overall survival (median 15 months) while sparing 70% of the patients WBRT and its potential acute and chronic toxicity.

摘要

目的

全脑放射治疗(WBRT)一直是脑转移瘤切除术后降低颅内复发风险的传统方法,尽管其存在迟发性神经毒性的可能性。2007年,作者通过对手术床进行立体定向放射外科治疗(SRS),证明了其局部复发率与WBRT相当,使72%的患者免于接受WBRT。他们现在报告纳入更多患者并进行更成熟随访后的初步经验。

方法

作者对在其机构接受手术切除后对手术床进行SRS治疗的所有颅内转移病灶局限(≤4个病灶)患者的病例进行了回顾性分析。所有患者均未接受过颅脑放疗,WBRT仅用于挽救治疗。

结果

2000年11月至2009年6月,52例中位年龄为61岁的患者符合纳入标准。每位患者均切除了单个转移瘤。其中34例患者有1个病灶,13例有2个病灶,3例有3个病灶,2例有4个病灶。手术床接受的中位剂量为1500 cGy(范围800 - 1800 cGy),中位靶体积为3.85 cm³(范围0.08 - 22 cm³)。中位随访13个月,中位生存期为15.0个月。4例患者(7.7%)手术部位出现局部复发。23例患者(44%)最终出现远处脑转移,中位时间为切除术后16个月,其中16例(30.7%)接受了挽救性WBRT(8例为弥漫性疾病[>3个病灶],4例为局部复发,4例为挽救性SRS后弥漫性进展)。切除术后接受WBRT的中位时间为8.7个月(范围2 - 43个月)。单因素分析显示,孤立肿瘤(19.0个月对12个月,p = 0.02)、递归分区分析(RPA)I级(21个月对13个月,p = 0.03)以及初诊时无颅外疾病(22个月对13个月,p = 0.01)等患者因素与较长生存期显著相关。Cox多因素分析显示,初诊时无颅外疾病(p = 0.01)和孤立性颅内转移(p = 0.02)这两个患者因素与较长生存期显著相关。在无颅外疾病的患者中,孤立性颅内转移具有显著的额外生存优势(43个月对10.5个月,p = 0.05,对数秩检验)。没有任何因素(年龄、RPA分级、肿瘤大小或组织学类型、疾病负担、切除范围或SRS剂量或体积)与挽救性WBRT的需求相关。

结论

对颅内转移瘤手术床进行辅助性SRS可使局部复发率与辅助性WBRT相当。结合未切除病灶的SRS和常规影像学监测,这种方法可实现较好的总生存期(中位15个月),同时使70%的患者免于接受WBRT及其潜在的急慢性毒性。

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