Distinct Clinicogenomic Features and Immunotherapy Associations in Pulmonary Sarcomatoid Carcinoma: A Multi-Center Retrospective Study.

IF 20.8 1区 医学 Q1 ONCOLOGY
Lingzhi Hong, Alessandro Di Federico, Bolun Liu, Alissa J Cooper, Joao V Alessi, Phoebe Clark, Waree Rinsurongkawong, Chingyi Young, Hui Li, Kang Qin, Muhammad Aminu, Yasir Elamin, Boris Sepesi, Jeff Lewis, Don L Gibbons, Ara A Vaporciyan, J Jack Lee, Xiuning Le, Jia Wu, Sinchita Roy-Chowdhuri, Mark J Routbort, P Andrew Futreal, John V Heymach, Mark M Awad, Adam J Schoenfeld, Jianjun Zhang, Biagio Ricciuti, Lei Deng, Natalie I Vokes
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引用次数: 0

Abstract

Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare non-small cell lung cancer (NSCLC) subtype with poor prognosis. Outcomes to immune checkpoint inhibitors (ICIs) and genomic features in PSC remain underexplored compared to other NSCLC subtypes.

Patients and methods: Patients from three institutions and the National Cancer Database (NCDB) with metastatic NSCLC treated with ICI alone or with chemotherapy were identified. Clinicogenomics and treatment outcomes were compared across PSC, lung adenocarcinoma (LUAD), and lung squamous cell carcinoma (LUSC).

Results: We analyzed 4,841 patients including 165 PSC cases treated with ICI-based therapy from three institutions, and 201 PSC from NCDB. In MDACC, 65 (4.3%) were PSC, 1,138 (75.1%) LUAD, and 312 (20.6%) LUSC. PSC patients were older and more likely to present with metastatic disease. In both the MDACC and NCDB cohorts, ICIs resulted in better outcomes for PSC patients compared with chemotherapy. In these patients, there was no difference in outcome between ICI-monotherapy and ICI-chemotherapy. Across the three institutional cohorts, 37%-43% of patients with PSC who received ICIs were responders, compared to 26%-29% in LUAD and 22%-46% in LUSC (P < 0.05). Improved ICI outcomes in PSC appeared driven by high PD-L1 (≥50% in 73%-77% cases). Among patients with high PD-L1, response rates were similar across histologic subtypes. Conversely, TMB was similar in PSC compared to LUAD/LUSC, and was not associated with ICI outcomes. Across cohorts, PSC tumors were enriched for TP53, NF1, NF2, and NRAS, with relative depletion of STK11 and KEAP1 compared to LUAD. Case observation showed relatively better outcomes to ICI than targeted therapies in PSC patients with MET exon 14 skipping or KRAS G12C.

Conclusion: PSC exhibits improved outcomes to ICI relative to other therapies, potentially driven by high PD-L1 expression. Genomic analysis highlights a distinct genomic landscape of PSC when compared with LUAD.

肺肉瘤样癌不同的临床基因组学特征和免疫治疗相关性:一项多中心回顾性研究。
背景:肺肉瘤样癌(PSC)是一种罕见的非小细胞肺癌(NSCLC)亚型,预后较差。与其他NSCLC亚型相比,免疫检查点抑制剂(ICIs)的结果和PSC的基因组特征仍未得到充分研究。患者和方法:来自三个机构和国家癌症数据库(NCDB)的转移性非小细胞肺癌患者被确定为单独使用ICI或化疗。比较PSC、肺腺癌(LUAD)和肺鳞状细胞癌(LUSC)的临床基因组学和治疗结果。结果:我们分析了4,841例患者,其中包括来自三家机构的165例PSC患者,以及来自NCDB的201例PSC患者。在MDACC中,PSC 65例(4.3%),LUAD 1138例(75.1%),LUSC 312例(20.6%)。PSC患者年龄较大,更有可能出现转移性疾病。在MDACC和NCDB队列中,与化疗相比,ICIs对PSC患者的预后更好。在这些患者中,ici单药治疗和ici化疗的结果没有差异。在三个机构队列中,接受ICIs的PSC患者中有37%-43%的患者有应答,而LUAD为26%-29%,LUSC为22%-46% (P < 0.05)。PSC患者ICI预后的改善似乎是由高PD-L1(73%-77%病例≥50%)驱动的。在高PD-L1患者中,不同组织学亚型的反应率相似。相反,与LUAD/LUSC相比,PSC中的TMB相似,并且与ICI结果无关。在所有队列中,PSC肿瘤中TP53、NF1、NF2和NRAS富集,与LUAD相比,STK11和KEAP1相对缺失。病例观察显示,在MET外显子14跳过或KRAS G12C的PSC患者中,ICI的治疗效果相对优于靶向治疗。结论:相对于其他疗法,PSC对ICI表现出改善的结果,可能是由高PD-L1表达驱动的。与LUAD相比,基因组分析突出了PSC的独特基因组景观。
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来源期刊
Journal of Thoracic Oncology
Journal of Thoracic Oncology 医学-呼吸系统
CiteScore
36.00
自引率
3.90%
发文量
1406
审稿时长
13 days
期刊介绍: Journal of Thoracic Oncology (JTO), the official journal of the International Association for the Study of Lung Cancer,is the primary educational and informational publication for topics relevant to the prevention, detection, diagnosis, and treatment of all thoracic malignancies.The readship includes epidemiologists, medical oncologists, radiation oncologists, thoracic surgeons, pulmonologists, radiologists, pathologists, nuclear medicine physicians, and research scientists with a special interest in thoracic oncology.
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