Department of Medical Oncology, Guizhou Province People's Hospital, Guiyang, China.
Department of Nephrology, Guizhou Provincial People's Hospital, Guiyang, China.
Front Immunol. 2023 Mar 13;14:1065510. doi: 10.3389/fimmu.2023.1065510. eCollection 2023.
It is now widely accepted that radiotherapy (RT) can provoke a systemic immune response, which gives a strong rationale for the combination of RT and immune checkpoint inhibitors (ICIs). However, RT is a double-edged sword that not only enhances systemic antitumor immune response, but also promotes immunosuppression to some extent. Nevertheless, many aspects regarding the efficacy and safety of this combination therapy remain unknown. Therefore, a systematic review and meta-analysis was performed in order to assess the safety and efficacy of RT/chemoradiotherapy (CRT) and ICI combination therapy for non-small cell lung cancer (NSCLC) patients.
PubMed and several other databases were searched (according to specific criteria) to find relevant studies published prior to the 28 of February 2022.
3,652 articles were identified for screening and 25 trials containing 1,645 NSCLC patients were identified. For stage II-III NSCLC, the one- and two-year overall survival (OS) was 83.25% (95% confidence interval (CI): 79.42%-86.75%) and 66.16% (95% CI: 62.3%-69.92%), respectively. For stage IV NSCLC, the one- and two-year OS was 50% and 25%. In our study, the pooled rate of grade 3-5 adverse events (AEs) and grade 5 AEs was 30.18% (95% CI: 10.04%-50.33%, I: 96.7%) and 2.03% (95% CI: 0.03%-4.04%, I: 36.8%), respectively. Fatigue (50.97%), dyspnea (46.06%), dysphagia (10%-82.5%), leucopenia (47.6%), anaemia (5%-47.6%), cough (40.09%), esophagitis (38.51%), fever (32.5%-38.1%), neutropenia (12.5%-38.1%), alopecia (35%), nausea (30.51%) and pneumonitis (28.53%) were the most common adverse events for the combined treatment. The incidence of cardiotoxicity (0%-5.00%) was low, but it was associated with a high mortality rate (0%-2.56%). Furthermore, the incidence of pneumonitis was 28.53% (95% CI: 19.22%-38.88%, I: 92.00%), grade ≥ 3 pneumonitis was 5.82% (95% CI: 3.75%-8.32%, I: 57.90%) and grade 5 was 0%-4.76%.
This study suggests that the addition of ICIs to RT/CRT for NSCLC patients may be both safe and feasible. We also summarize details of different RT combinations with ICIs to treat NSCLC. These findings may help guide the design of future trials, the testing of concurrent or sequential combinations for ICIs and RT/CRT could be particularly useful to guide the treatment of NSCLC patients.
现在人们普遍认为放射治疗（RT）可以引发全身性免疫反应，这为 RT 与免疫检查点抑制剂（ICI）联合治疗提供了强有力的依据。然而，RT 是一把双刃剑，它不仅增强了全身抗肿瘤免疫反应，而且在某种程度上促进了免疫抑制。然而，这种联合治疗的疗效和安全性的许多方面仍然未知。因此，进行了一项系统评价和荟萃分析，以评估 RT/放化疗（CRT）和 ICI 联合治疗非小细胞肺癌（NSCLC）患者的安全性和疗效。
检索了 PubMed 和其他几个数据库（根据具体标准），以找到截至 2022 年 2 月 28 日之前发表的相关研究。
筛选出 3652 篇文章，确定了 25 项试验，共纳入 1645 例 NSCLC 患者。对于 II-III 期 NSCLC，1 年和 2 年总生存率（OS）分别为 83.25%（95%置信区间（CI）：79.42%-86.75%）和 66.16%（95% CI：62.3%-69.92%）。对于 IV 期 NSCLC，1 年和 2 年 OS 分别为 50%和 25%。在我们的研究中，3-5 级不良事件（AE）和 5 级 AE 的总发生率为 30.18%（95% CI：10.04%-50.33%，I：96.7%）和 2.03%（95% CI：0.03%-4.04%，I：36.8%）。疲劳（50.97%）、呼吸困难（46.06%）、吞咽困难（10%-82.5%）、白细胞减少（47.6%）、贫血（5%-47.6%）、咳嗽（40.09%）、食管炎（38.51%）、发热（32.5%-38.1%）、中性粒细胞减少（12.5%-38.1%）、脱发（35%）、恶心（30.51%）和肺炎（28.53%）是联合治疗最常见的不良反应。心脏毒性（0%-5.00%）的发生率较低，但死亡率（0%-2.56%）较高。此外，肺炎的发生率为 28.53%（95% CI：19.22%-38.88%，I：92.00%），≥3 级肺炎为 5.82%（95% CI：3.75%-8.32%，I：57.90%），5 级肺炎为 0%-4.76%。
本研究表明，ICI 联合 RT/CRT 治疗 NSCLC 患者可能既安全又可行。我们还总结了不同 RT 联合 ICI 治疗 NSCLC 的细节。这些发现可能有助于指导未来试验的设计，同时测试 ICI 和 RT/CRT 的同期或序贯联合治疗可能特别有助于指导 NSCLC 患者的治疗。
