Associations of Clinical and Molecular Characteristics with the Response to Immune Checkpoint Blockade in Advanced Gastric Cancers

doi:10.1155/2022/2162229

	Associations of Clinical and Molecular Characteristics with the Response to Immune Checkpoint Blockade in Advanced Gastric Cancers
	Xu, Xiaoqing 1,2; Li, Jingjing 2; Gao, Yiding 3; Lv, Wangxia 4; Wei, Qing 2; Tang, Xiaowan 5; Hu, Jinlin 6; Yuan, Xing 7; Wu, Wei 6; Zhang, Lingnan 8
刊名	JOURNAL OF ONCOLOGY
	2022-03-04
卷号	2022
ISSN号	1687-8450
DOI	10.1155/2022/2162229
通讯作者	Zhu, Xiu(zhuxiu2005@163.com) ; Xu, Qi(hzxuqi@sina.cn)
英文摘要	Purpose. Immunotherapy provides a new treatment option for advanced gastric cancer (AGC). This study aims to explore the response markers of immunotherapy in AGCs. Methods. Next-generation sequencing was performed on 44 AGC patients who received immune checkpoint inhibitors and the associations between their outcomes after combination immunotherapy, and the clinicopathological/molecular characteristics were analyzed. Results. The current study cohort had a median progression-free survival (PFS) of 5.9 months, an overall survival (OS) of 12.1 months, and an objective response rate (ORR) of 36.4%. Through multivariable analysis of the clinical characteristics, primary tumor resection (HR = 2.66, 95% CI: 1.06-6.70, p=0.037) and increased proportion of lymphocytes after combination immunotherapy (HR = 0.40, 95% CI: 0.16-0.99, p=0.048) were revealed as independent predictors for patient outcomes. All the 18 patients who underwent genetic profiling were microsatellite-stable with a median TMB of four mutations per Mb. ATM alterations, PI3K pathway mutations, increased TMB, and positive PD-L1 expression were associated with the increased trend of PFS and ORR. According to the combination of baseline lymphocyte count, ATM mutation, TMB status, and PD-L1 expression, patients were stratified into higher- and lower-risk groups, with the lower-risk group showing improved PFS (HR = 4.7e-10, 95% CI: 0-inf, p=0.02) and ORR (75% vs. 0%, p=0.007). Conclusion. Several highly relevant potential biomarkers predictive of immunotherapy response in AGC patients have been identified in this research.
资助项目	Program of Zhejiang Provincial TCM Sci-tech Plan[2021ZZ005] ; Medical Health Plan of Zhejiang Province[2022KY666]
WOS关键词	GASTROESOPHAGEAL JUNCTION ; PHASE-III ; 1ST-LINE THERAPY ; DOUBLE-BLIND ; OPEN-LABEL ; NIVOLUMAB ; 5-FLUOROURACIL/CISPLATIN ; CAPECITABINE/CISPLATIN ; CHEMOTHERAPY ; MULTICENTER
WOS研究方向	Oncology
语种	英语
出版者	HINDAWI LTD
WOS记录号	WOS:000783427200002
资助机构	Program of Zhejiang Provincial TCM Sci-tech Plan ; Medical Health Plan of Zhejiang Province
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/128559]
专题	中国科学院合肥物质科学研究院
通讯作者	Zhu, Xiu; Xu, Qi
作者单位	1.Zhejiang Chinese Med Univ, Clin Med Coll 2, Dept Med Oncol, Hangzhou, Peoples R China 2.Chinese Acad Sci, Dept Hepatopancreatobiliary & Gastr Med Oncol, Inst Basic Med & Canc IBMC, Zhejiang Canc Hosp,Univ Chinese Acad Sci,Canc, Hangzhou, Zhejiang, Peoples R China 3.Jiaxing Univ, Affiliated Hosp 2, Dept Oncol, Jiaxing, Peoples R China 4.Chinese Acad Sci, Univ Chinese Acad Sci, Inst Basic Med & Canc IBMC, Zhejiang Canc Hosp,Dept Colorectal Med Oncol,Canc, Hangzhou, Zhejiang, Peoples R China 5.Taizhou First Peoples Hosp, Dept Hematol Oncol, Taizhou, Peoples R China 6.Chinese Acad Sci, Univ Chinese Acad Sci, Zhejiang Canc Hosp, Dept Pathol,Inst Basic Med & Canc IBMC,Canc Hosp, Hangzhou, Zhejiang, Peoples R China 7.Hangzhou Hosp, Zhejiang Med & Hlth Grp, Dept Med Oncol, Hangzhou, Peoples R China 8.Chinese Acad Sci, Univ Chinese Acad Sci, Zhejiang Canc Hosp, Radiol Dept,Inst Basic Med & Canc IBMC,Canc Hosp, Hangzhou, Zhejiang, Peoples R China
推荐引用方式 GB/T 7714	Xu, Xiaoqing,Li, Jingjing,Gao, Yiding,et al. Associations of Clinical and Molecular Characteristics with the Response to Immune Checkpoint Blockade in Advanced Gastric Cancers[J]. JOURNAL OF ONCOLOGY,2022,2022.
APA	Xu, Xiaoqing.,Li, Jingjing.,Gao, Yiding.,Lv, Wangxia.,Wei, Qing.,...&Xu, Qi.(2022).Associations of Clinical and Molecular Characteristics with the Response to Immune Checkpoint Blockade in Advanced Gastric Cancers.JOURNAL OF ONCOLOGY,2022.
MLA	Xu, Xiaoqing,et al."Associations of Clinical and Molecular Characteristics with the Response to Immune Checkpoint Blockade in Advanced Gastric Cancers".JOURNAL OF ONCOLOGY 2022(2022).