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接受免疫检查点阻断治疗的脑转移患者姑息性放疗的急性神经毒性

Acute neurologic toxicity of palliative radiotherapy for brain metastases in patients receiving immune checkpoint blockade.

作者信息

Arscott W Tristram, Zhu Simeng, Plastaras John P, Maity Amit, Alonso-Basanta Michelle, Jones Joshua

机构信息

Department of Radiation Oncology, Perelman Center for Advanced Medicine, University of Pennsylvania Philadelphia, PA.

College of Medicine, University of Florida, Gainesville, FL.

出版信息

Neurooncol Pract. 2019 Jul;6(4):297-304. doi: 10.1093/nop/npy042. Epub 2018 Oct 25.

Abstract

BACKGROUND

The interaction between immune checkpoint blockade (ICB) and radiation (RT) for brain metastases has not been well understood. Given that acute neurotoxicity from this combination is not well characterized, we reviewed patients receiving ICB and RT for brain metastases.

METHODS

Patients treated with ICB and cranial RT from 2010 through 2017 were reviewed. ICB and RT must have been administered within 30 days of each other. Treatment parameters, performance status, symptoms prior to treatment, and toxicity were extracted from the electronic medical record. Survival was calculated from the end of RT to last follow-up or death.

RESULTS

Seventy-eight patients were included. Median follow-up was 177 days (range, 12-1603). Median age was 64 years old (range, 29-98) and 47 (63%) were male. The main tumor types were melanoma (n = 47) and nonsmall-cell lung cancer (n = 19). Fifty-seven patients were treated with stereotactic radiosurgery (SRS) and 21 with whole-brain radiotherapy (WBRT). Most patients received single-agent ICB, though 4 patients received nivolumab and ipilimumab. Forty-one (53%) patients reported no neurologic toxicity. Grade 2 or greater neurologic toxicities were reported in 12 (21%) and 8 (38%) patients in the SRS and WBRT groups, respectively. WBRT was associated with a greater risk of any neurotoxicity, though there was no correlation between ICB agent and toxicity. Sequencing of ICB and RT (ie, <30 days vs <7) did not influence rates of toxicity.

CONCLUSIONS

ICB during SRS or WBRT does not appear to worsen acute neurotoxicity compared to historical controls of RT alone.

摘要

背景

免疫检查点阻断(ICB)与放疗(RT)联合用于脑转移瘤的相互作用尚未得到充分理解。鉴于这种联合治疗的急性神经毒性特征尚不明确,我们对接受ICB和RT治疗脑转移瘤的患者进行了回顾性研究。

方法

回顾了2010年至2017年期间接受ICB和颅脑RT治疗的患者。ICB和RT必须在彼此30天内给药。从电子病历中提取治疗参数、体能状态、治疗前症状和毒性。从RT结束到最后一次随访或死亡计算生存率。

结果

纳入78例患者。中位随访时间为177天(范围12 - 1603天)。中位年龄为64岁(范围29 - 98岁),47例(63%)为男性。主要肿瘤类型为黑色素瘤(n = 47)和非小细胞肺癌(n = 19)。57例患者接受了立体定向放射外科治疗(SRS),21例接受了全脑放疗(WBRT)。大多数患者接受单药ICB治疗,不过有4例患者接受了纳武单抗和伊匹单抗联合治疗。41例(53%)患者报告无神经毒性。SRS组和WBRT组分别有12例(21%)和8例(38%)患者报告了2级或更高级别的神经毒性。WBRT与任何神经毒性的风险更高相关,不过ICB药物与毒性之间无相关性。ICB和RT的给药顺序(即<30天与<7天)不影响毒性发生率。

结论

与单纯RT的历史对照相比,SRS或WBRT期间使用ICB似乎不会加重急性神经毒性。

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