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立体定向放射外科手术联合依匹单抗治疗黑色素瘤脑转移患者:临床结局和毒性。

Stereotactic radiosurgery and ipilimumab for patients with melanoma brain metastases: clinical outcomes and toxicity.

机构信息

Harvard Medical School, Boston, MA, USA.

Department of Radiation Oncology, Keck School of Medicine of USC, Los Angeles, CA, USA.

出版信息

J Neurooncol. 2018 Sep;139(2):421-429. doi: 10.1007/s11060-018-2880-y. Epub 2018 Apr 25.

Abstract

INTRODUCTION

There is evidence that the combination of ipilimumab and stereotactic radiosurgery (SRS) for brain metastases improves outcomes. We investigated clinical outcomes, radiation toxicity, and impact of ipilimumab timing in patients treated with SRS for melanoma brain metastases.

METHODS

We retrospectively identified 91 patients treated with SRS at our institution for melanoma brain metastases from 2006 to 2015. Concurrent ipilimumab administration was defined as within ± 4 weeks of SRS procedure. Acute and late toxicities were graded with CTCAE v4.03. Overall survival (OS), local failure, distant brain failure, and failure-free survival were analyzed with the Kaplan-Meier method. OS was analyzed with Cox regression.

RESULTS

Twenty-three patients received ipilimumab concurrent with SRS, 28 patients non-concurrently, and 40 patients did not receive ipilimumab. The median age was 62 years and 91% had KPS ≥ 80. The median follow-up time was 7.4 months. Patients who received ipilimumab had a median OS of 15.1 months compared to 7.8 months in patients who did not (p = 0.02). In multivariate analysis, ipilimumab (p = 0.02) and diagnosis-specific graded prognostic assessment (p = 0.02) were associated with OS. There were no differences in intracranial control by ipilimumab administration or timing. The incidence of radiation necrosis was 5%, with most events occurring in patients who received ipilimumab.

CONCLUSIONS

Patients who received ipilimumab had improved OS even after adjusting for prognostic factors. Ipilimumab did not appear to increase risk for acute toxicity. The majority of radiation necrosis events, however, occurred in patients who received ipilimumab. Our results support the continued use of SRS and ipilimumab as clinically appropriate.

摘要

简介

有证据表明,伊匹单抗联合立体定向放射外科(SRS)治疗脑转移可改善预后。我们研究了 SRS 治疗黑素瘤脑转移患者的临床结果、放射性毒性以及伊匹单抗治疗时机的影响。

方法

我们回顾性地确定了 2006 年至 2015 年在我们机构接受 SRS 治疗的 91 例黑素瘤脑转移患者。伊匹单抗联合 SRS 治疗定义为 SRS 治疗前后 4 周内。采用 CTCAE v4.03 分级评估急性和迟发性毒性。采用 Kaplan-Meier 方法分析总生存期(OS)、局部失败、远处脑失败和无失败生存率。采用 Cox 回归分析 OS。

结果

23 例患者在 SRS 治疗时接受伊匹单抗,28 例患者非同时接受伊匹单抗,40 例患者未接受伊匹单抗。中位年龄为 62 岁,91%的患者 KPS≥80。中位随访时间为 7.4 个月。接受伊匹单抗的患者中位 OS 为 15.1 个月,而未接受伊匹单抗的患者为 7.8 个月(p=0.02)。多因素分析显示,伊匹单抗(p=0.02)和诊断特异性分级预后评估(p=0.02)与 OS 相关。伊匹单抗的使用或时间对颅内控制无差异。放射性坏死的发生率为 5%,大多数事件发生在接受伊匹单抗的患者中。

结论

即使在调整了预后因素后,接受伊匹单抗治疗的患者的 OS 仍得到改善。伊匹单抗似乎没有增加急性毒性的风险。然而,大多数放射性坏死事件发生在接受伊匹单抗的患者中。我们的结果支持在临床适当的情况下继续使用 SRS 和伊匹单抗。

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