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抗生素暴露与接受免疫检查点抑制剂治疗的广泛期小细胞肺癌患者生存的关系。

Association of antibiotic exposure with survival in patients with extensive-stage small cell lung cancer receiving immune checkpoint inhibitor therapy.

机构信息

Clinical Medical College, Southwest Medical University, Luzhou, China.

Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.

出版信息

Thorac Cancer. 2024 Jan;15(2):152-162. doi: 10.1111/1759-7714.15172. Epub 2023 Nov 27.

Abstract

BACKGROUND

Immune checkpoint inhibitors (ICIs) have dramatically shifted the therapeutic paradigm of extensive-stage small cell lung cancer (ES-SCLC). Antibiotic (ATB) exposure before or during ICI therapy can harm the integrity of the gut microbiome and lead to intestinal dysbiosis, which has a profoundly negative impact on the treatment response for various malignancies. Whether this is applicable to ES-SCLC remains unclear.

METHODS

We retrospectively reviewed the electronic medical records of all patients diagnosed with ES-SCLC who were treated with ICI-based immunotherapies from July 2019 to December 2020 at Shandong Cancer Hospital and Institute, China. Outcomes with the use of ATBs before or after the first infusion of ICI, including progression-free survival (PFS) and overall survival (OS), were investigated using the Kaplan-Meier method. Multivariate analyses were also conducted using a Cox proportional hazards model.

RESULTS

A total of 214 patients were included, among whom 41 (19.2%) received ATBs within 2 months before or after the first initiation of ICI therapy and were assigned to the ATB group. The ATB group showed a shorter median PFS (4.3 vs. 6.3 months; HR = 1.43, 95% CI: 0.97-2.11; p = 0.043) and a significantly shorter median OS (6.9 vs. 13 months; HR = 1.47, 95% CI: 0.98-2.20; p = 0.033) than the non-ATB group. In the multivariate analysis, ATB exposure was markedly associated with worse PFS (HR = 1.47, 95% CI: 1.03-2.09, p = 0.035) and OS (HR = 1.46, 95% CI: 1.01-2.11, p = 0.043).

CONCLUSIONS

Our results demonstrate that ATB exposure was significantly associated with worse survival in ES-SCLC patients who received ICI therapy.

摘要

背景

免疫检查点抑制剂 (ICI) 极大地改变了广泛期小细胞肺癌 (ES-SCLC) 的治疗模式。ICI 治疗前或治疗期间使用抗生素 (ATB) 会损害肠道微生物组的完整性并导致肠道菌群失调,这对各种恶性肿瘤的治疗反应有深远的负面影响。这是否适用于 ES-SCLC 尚不清楚。

方法

我们回顾性分析了 2019 年 7 月至 2020 年 12 月在中国山东肿瘤医院和研究所接受 ICI 为基础的免疫治疗的所有 ES-SCLC 患者的电子病历。使用 Kaplan-Meier 方法研究了 ICI 首次输注前后使用 ATB 的患者的无进展生存期 (PFS) 和总生存期 (OS)。还使用 Cox 比例风险模型进行了多变量分析。

结果

共纳入 214 例患者,其中 41 例 (19.2%) 在 ICI 治疗首次启动前或后 2 个月内接受 ATB,归入 ATB 组。与非 ATB 组相比,ATB 组的中位 PFS 更短 (4.3 与 6.3 个月;HR=1.43,95%CI:0.97-2.11;p=0.043),中位 OS 更短 (6.9 与 13 个月;HR=1.47,95%CI:0.98-2.20;p=0.033)。多变量分析显示,ATB 暴露与较差的 PFS (HR=1.47,95%CI:1.03-2.09,p=0.035) 和 OS (HR=1.46,95%CI:1.01-2.11,p=0.043)显著相关。

结论

我们的研究结果表明,在接受 ICI 治疗的 ES-SCLC 患者中,ATB 暴露与生存状况较差显著相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd4c/10788467/300f68e1d713/TCA-15-152-g003.jpg

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