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评估影响晚期非小细胞肺癌患者免疫检查点抑制剂联合放疗疗效的潜在因素:一项系统评价和荟萃分析

Assessing Potential Factors Influencing the Efficacy of Immune Checkpoint Inhibitors with Radiation in Advanced Non-Small-Cell Lung Cancer Patients: A Systematic Review and Meta-Analysis.

作者信息

Xu Huilin, Cao Dedong, Zhou Dingjie, He Anbing, Ge Wei, Xu Ximing

机构信息

Department of Oncology, The Fifth Hospital of Wuhan, Wuhan, Hubei 430000, China.

Department of Oncology, RenMin Hospital of Wuhan University, Wuhan, Hubei 430000, China.

出版信息

J Oncol. 2023 Jan 13;2023:4477263. doi: 10.1155/2023/4477263. eCollection 2023.


DOI:10.1155/2023/4477263
PMID:36688004
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9859691/
Abstract

OBJECTIVE: Recent evidence suggests that combining radiotherapy (RT) with immune checkpoint inhibitors (ICIs) may result in better outcomes. In this study, we assessed the efficacy and safety of ICI plus radiation versus ICI alone and explored potential factors affecting its efficacy in advanced non-small-cell lung cancer (NSCLC) patients. METHODS: The databases including PubMed and Embase were searched to retrieve eligible studies comparing the efficacy and safety outcomes in advanced NSCLC patients after ICIs ± RT treatments. We performed subgroup analyses to identify potential prognostic factors from radiation details and study types. The odds ratio (OR) of objective response rate (ORR) and disease control rate (DCR), hazard ratio (HR) of progression-free survival (PFS) and overall survival (OS), and risk ratio (RR) of adverse events were used to represent the outcome effects. RESULTS: 26 eligible studies with 14192 cases were included. The results showed that the ORR (OR = 0.63, 95% CI: 0.42, 0.93;  = 0.02) and DCR (OR = 0.55, 95% CI: 0.36, 0.82;  < 0.01) of RT + ICIs groups were significantly higher than those of the ICIs alone group. The median PFS and OS for ICIs versus RT + ICIs were 2.2 versus 4.4 months and 9.0 versus 13.4 months, respectively. Patients in the ICIs plus RT group had a significantly better PFS (HR = 0.72, 95% CI: 0.64, 0.81;  < 0.01) and OS (HR = 0.74, 95% CI: 0.65, 0.83;  < 0.01) when compared to those in the ICIs group. In terms of adverse events, the risk of pneumonia was not significantly increased in patients treated with both ICIs and RT when compared to ICIs group alone (risk ratio = 0.89; 95% CI: 0.55, 1.44;  = 0.63). The correlation analysis found that PFS was significantly correlated with OS (p = 0.02). The subgroup analysis results showed that significant improvements in OS were observed in non-palliative RT group (HR = 0.29, 95% CI: 0.13, 0.65;  < 0.01) and extracranial RT group (HR = 0.70, 95% CI: 0.59, 0.83;  < 0.01). RT type could also be a prognostic factor associated with the OS (for conventional RT: HR = 0.68 and  = 0.22; for stereotactic body radiation therapy: HR = 0.77 and  < 0.01). However, concerning RT timing, the results showed a similar trend in reducing mortality risk (for previous RT: HR = 0.64 and  = 0.21; for concurrent RT: HR = 0.35 and  = 0.16). CONCLUSION: RT plus ICIs is associated with improved survival for advanced NSCLC patients, especially for those with non-palliative RT. Further clinical trials are needed to validate its effect on survival outcomes.

摘要

目的:近期证据表明,放疗(RT)与免疫检查点抑制剂(ICI)联合使用可能会带来更好的治疗效果。在本研究中,我们评估了ICI联合放疗与单纯使用ICI的疗效和安全性,并探讨了影响晚期非小细胞肺癌(NSCLC)患者疗效的潜在因素。 方法:检索包括PubMed和Embase在内的数据库,以获取比较晚期NSCLC患者接受ICI±RT治疗后疗效和安全性结果的符合条件的研究。我们进行了亚组分析,以从放疗细节和研究类型中确定潜在的预后因素。客观缓解率(ORR)和疾病控制率(DCR)的比值比(OR)、无进展生存期(PFS)和总生存期(OS)的风险比(HR)以及不良事件的风险比(RR)用于表示结果效应。 结果:纳入了26项符合条件的研究,共14192例患者。结果显示,RT+ICI组的ORR(OR=0.63,95%CI:0.42,0.93;P=0.02)和DCR(OR=0.55,95%CI:0.36,0.82;P<0.01)显著高于单纯ICI组。ICI组与RT+ICI组的中位PFS分别为2.2个月和4.4个月,中位OS分别为9.0个月和13.4个月。与ICI组相比,ICI联合RT组患者的PFS(HR=0.72,95%CI:0.64,0.81;P<0.01)和OS(HR=0.74,95%CI:0.65,0.83;P<0.01)明显更好。在不良事件方面,与单纯ICI组相比,接受ICI和RT联合治疗的患者发生肺炎的风险没有显著增加(风险比=0.89;95%CI:0.55,1.44;P=0.63)。相关性分析发现,PFS与OS显著相关(P=0.02)。亚组分析结果显示,在非姑息性RT组(HR=0.29,95%CI:0.13,0.65;P<0.01)和颅外RT组(HR=0.70,95%CI:0.59,0.83;P<0.01)中,OS有显著改善。RT类型也可能是与OS相关的预后因素(传统RT:HR=0.68,P=0.22;立体定向体部放疗:HR=0.77,P<0.01)。然而,关于RT时机,结果显示在降低死亡风险方面有类似趋势(既往RT:HR=0.64,P=0.21;同步RT:HR=0.35,P=0.16)。 结论:RT联合ICI可改善晚期NSCLC患者的生存期,尤其是对于接受非姑息性RT的患者。需要进一步的临床试验来验证其对生存结局的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f25e/9859691/c095c374001d/JO2023-4477263.005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f25e/9859691/c2b3f963b923/JO2023-4477263.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f25e/9859691/770d4088b5e5/JO2023-4477263.003.jpg
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引用本文的文献

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本文引用的文献

[1]
Survival Is Worse in Patients Completing Immunotherapy Prior to SBRT/SRS Compared to Those Receiving It Concurrently or After.

Front Oncol. 2022-5-27

[2]
Durvalumab plus tremelimumab alone or in combination with low-dose or hypofractionated radiotherapy in metastatic non-small-cell lung cancer refractory to previous PD(L)-1 therapy: an open-label, multicentre, randomised, phase 2 trial.

Lancet Oncol. 2022-2

[3]
Efficacy and Safety of Stereotactic Radiosurgery for Brainstem Metastases: A Systematic Review and Meta-analysis.

JAMA Oncol. 2021-7-1

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Nat Med. 2021-2

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Diagnostics (Basel). 2020-12-16

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