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抗PD-1治疗所致肺炎的放射学特征的预后意义

Prognostic significance of the radiologic features of pneumonitis induced by anti-PD-1 therapy.

作者信息

Watanabe Satoshi, Ota Takeshi, Hayashi Masachika, Ishikawa Hiroyuki, Otsubo Aya, Shoji Satoshi, Nozaki Koichiro, Ichikawa Kosuke, Kondo Rie, Miyabayashi Takao, Miura Satoru, Tanaka Hiroshi, Abe Tetsuya, Okajima Masaaki, Terada Masaki, Ishida Takashi, Iwashima Akira, Sato Kazuhiro, Yoshizawa Hirohisa, Kikuchi Toshiaki

机构信息

Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

Niigata Prefectural Shibata Hospital, Niigata, Japan.

出版信息

Cancer Med. 2020 May;9(9):3070-3077. doi: 10.1002/cam4.2974. Epub 2020 Mar 9.

Abstract

BACKGROUND

Interstitial lung disease (ILD) induced by anti-programmed-cell death-1 (PD-1) and anti-PD-ligand 1 (PD-L1) is potentially life-threatening and is a common reason of the discontinuation of therapy. In contrast, an enhancement in antitumor effects was reported in patients who developed immune-related adverse events, including ILD. Although recent evidence suggests that radiologic patterns of ILD may reflect the severity of ILD and the antitumor immune responses to anti-PD-1/PD-L1 therapies, the association between radiologic features and clinical outcomes remains unclear.

METHODS

Patients with advanced non-small-cell lung cancer who were treated with 1st to 3rd line anti-PD-1 therapy from January 2016 through October 2017 were identified at multiple institutions belonging to the Niigata Lung Cancer Treatment Group. ILD was diagnosed by the treating physicians, and chest computed tomography scans were independently reviewed to assess the radiologic features of ILD.

RESULTS

A total of 231 patients who received anti-PD-1 therapy were enrolled. Thirty-one patients (14%) developed ILD. Sixteen patients were classified as having ground glass opacities (GGO), 16 were classified as having cryptogenic organizing pneumonia (COP), and one was classified as having pneumonitis not otherwise specified. Patients with GGO had significantly worse overall survival time compared to patients with COP (7.8 months (95% CI: 2.2-NE) versus not reached (95% CI: 13.2-NE); P = 0.0175). Multivariate analysis of all 231 patients also revealed that PS = 1 and ≥2 and GGO were significant predictors of a worse overall survival.

CONCLUSIONS

This study demonstrated that patients who developed GGO exhibited worse outcomes among non-small-cell lung cancer patients receiving anti-PD-1 therapies.

摘要

背景

抗程序性细胞死亡蛋白1(PD-1)和抗程序性死亡配体1(PD-L1)诱导的间质性肺疾病(ILD)可能危及生命,是治疗中断的常见原因。相比之下,有报道称发生包括ILD在内的免疫相关不良事件的患者抗肿瘤效果增强。尽管最近的证据表明ILD的放射学模式可能反映ILD的严重程度以及对抗PD-1/PD-L1治疗的抗肿瘤免疫反应,但放射学特征与临床结局之间的关联仍不清楚。

方法

在新潟肺癌治疗组所属的多个机构中,确定了2016年1月至2017年10月接受一线至三线抗PD-1治疗的晚期非小细胞肺癌患者。ILD由治疗医生诊断,并独立复查胸部计算机断层扫描以评估ILD的放射学特征。

结果

共有231例接受抗PD-1治疗的患者入组。31例患者(14%)发生ILD。16例患者被分类为磨玻璃影(GGO),16例被分类为隐源性机化性肺炎(COP),1例被分类为未另行特指的肺炎。与COP患者相比,GGO患者的总生存时间显著更差(7.8个月(95%CI:2.2-未达到)对未达到(95%CI:13.2-未达到);P=0.0175)。对所有231例患者的多因素分析还显示,PS=1及≥2和GGO是总生存较差的显著预测因素。

结论

本研究表明,在接受抗PD-1治疗的非小细胞肺癌患者中,发生GGO的患者预后较差。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7e7/7196069/93fd5a185133/CAM4-9-3070-g001.jpg

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