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复发性胶质母细胞瘤的放射外科治疗及影响治疗结果的预后因素

RADIOSURGICAL TREATMENT OF RECURRENT GLIOBLASTOMA AND PROGNOSTIC FACTORS AFFECTING TREATMENT OUTCOMES.

作者信息

Glavatskyi O Ya, Griazov A B, Chuvashova O Yu, Kruchok I V, Griazov A A, Khmelnytskyi H V, Shuba I M, Stuley V A, Zemskova O V

机构信息

State Institution "Academician Romodanov Institute of Neurosurgery, the National Academy of Medical Sciences of Ukraine", Kyiv 04050, Ukraine.

Institute for Applied Systems Analysis, National Technical University of Ukraine "Igor Sikorsky Kyiv Polytechnic Institute", Kyiv 03056, Ukraine.

出版信息

Exp Oncol. 2022 Dec;44(4):307-313. doi: 10.32471/exp-oncology.2312-8852.vol-44-no-4.18920.

Abstract

BACKGROUND

Glioblastoma (GBM) is the most prevalent malignant tumor of the brain in adults with the inherent aggressive behavior and high recurrence rate. The stereotactic radiosurgery (SRS) is currently considered as one of the effective modalities for GBM treatment allowing for the improvement of survival with the acceptable toxicity level.

AIM

To assess the effects of various factors on the survival of GBM patients following SRS.

PATIENTS AND METHODS

We retrospectively reviewed treatment outcomes of 68 patients who received SRS for recurrent GBM treatment in 2014-2020. SRS was delivered with Trilogy linear accelerator (6 MeV). The area of recurrent tumor/continued tumor growth was irradiated. For the treatment of the primary GBM, the adjuvant radiotherapy was provided at the standard fractionated regimen with the total boost dose of 60 Gy divided to 30 fractions (Stupp's protocol) in the setting of the concomitant chemotherapy with temozolomide. 36 patients then received temozolomide as the maintenance chemotherapy. SRS for the treatment of recurrent GBM was provided at a boost dose of 20.2 Gy on average being delivered into 1-5 fractions with average single dose of 12.4 Gy. The survival was analyzed by the Kaplan-Meier method with a log-rank test used for assessing the impact of the independent predictors on the survival risks.

RESULTS

The median overall survival (OS) was 21.7 months (95% confidence interval (CІ) 16.4-43.1), median survival after SRS was 9.3 months (95% CІ 5.6-22.7). The majority of patients (72%) were alive for at least 6 months following SRS and about half of patients (48%) survived for at least 24 months following the resection of the primary tumor. OS and survival after SRS depend significantly on the extent of the surgical resection of the primary tumor. The addition of temozolomide to radiotherapy prolongs survival in GBM patients. The relapse time affected significantly OS (p = 0.00008), but not survival after SRS. Neither OS, nor survival after SRS were affected significantly by such factors as the age of patients, the number of SRS fractions (one fraction vs several fractions), and target volume.

CONCLUSION

Radiosurgery improves the survival in patients with recurrent GBM. The extent of the surgical resection and adjuvant alkylating chemotherapy of the primary tumor, overall biologically effective dose and time between the primary diagnosis and SRS affect significantly the survival. The search for the more effective schedules for treating such patients requires further studies with more numerous cohorts of patients and extended follow-up.

摘要

背景

胶质母细胞瘤(GBM)是成人中最常见的脑恶性肿瘤,具有内在的侵袭性和高复发率。立体定向放射外科手术(SRS)目前被认为是GBM治疗的有效方式之一,可在可接受的毒性水平下提高生存率。

目的

评估各种因素对GBM患者SRS治疗后生存的影响。

患者与方法

我们回顾性分析了2014年至2020年期间接受SRS治疗复发性GBM的68例患者的治疗结果。使用Trilogy直线加速器(6 MeV)进行SRS治疗。对复发性肿瘤/持续肿瘤生长区域进行照射。对于原发性GBM的治疗,在同步使用替莫唑胺化疗的情况下,按照标准分割方案进行辅助放疗,总增敏剂量为60 Gy,分30次给予(Stupp方案)。36例患者随后接受替莫唑胺作为维持化疗。复发性GBM的SRS治疗平均增敏剂量为20.2 Gy,分1 - 5次给予,平均单次剂量为12.4 Gy。采用Kaplan-Meier法分析生存率,并使用对数秩检验评估独立预测因素对生存风险的影响。

结果

中位总生存期(OS)为21.7个月(95%置信区间(CI)16.4 - 43.1),SRS治疗后的中位生存期为9.3个月(95% CI 5.6 - 22.7)。大多数患者(72%)在SRS治疗后至少存活6个月,约一半患者(48%)在原发性肿瘤切除后至少存活24个月。OS和SRS治疗后的生存期显著取决于原发性肿瘤的手术切除范围。放疗联合替莫唑胺可延长GBM患者的生存期。复发时间对OS有显著影响(p = 0.00008),但对SRS治疗后的生存期无显著影响。患者年龄、SRS分次次数(单次与多次)和靶体积等因素对OS和SRS治疗后的生存期均无显著影响。

结论

放射外科手术可提高复发性GBM患者的生存率。原发性肿瘤的手术切除范围和辅助烷化剂化疗、总体生物有效剂量以及原发性诊断与SRS之间的时间显著影响生存期。寻找更有效的治疗此类患者的方案需要对更多患者队列进行进一步研究并延长随访时间。

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