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bITH, a blood-based metric of intratumor heterogeneity, is associated with clinical response to immune checkpoint blockade in non-small cell lung cancer

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收录情况： ◇ SCIE

作者：
Fan Yun[1] ; Liu Yang[2] ; Wang Liuchun[3] ; Cai Yiran[4] ; Cao Wen[5] ; Sun Wenjie[4] ; Zou Xiao[4] ; Li Bing[4] ; Zhang Zhou[4] ; Cai Shangli[4] ; Chuai Shannon[4] ; Han Yusheng[4] ; Pan Xiaojie[6,*2] ; Huang Dingzhi[3,*1] ;
机构： [1]Department of Medical Thoracic Oncology, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, China. [2]Department of Pathology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, China. [3]National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Cancer Institute & Hospital, Tianjin Medical University, China. [4]Burning Rock Biotech, Guangzhou, China. [5]Department of Oncology and Hematology, The Second Hospital of Hunan University of Chinese Medicine, China. [6]Department of Thoracic Surgery, Fujian Provincial Hospital, China
出处：
DOI： 10.1016/j.ebiom.2023.104564
ISSN：

关键词： Intratumor heterogeneity Immunotherapy Immune checkpoint blockade Predictive biomarker Blood biopsy NSCLC

摘要：
Intratumor heterogeneity (ITH) has been associated with poor prognosis in advanced non-small cell cancer (NSCLC) patients receiving immune checkpoint blockade (ICB) therapies. However, there is currently no evidence supporting an ITH metric as a predictor of clinical benefit from ICB. The unique advantages of blood make it a promising material for ITH estimation and relevant applications. This study aims to develop and validate a blood-based ITH index for predicting ICB response.NSCLC patients from the OAK and POPLAR clinical trials were used as the training cohorts for algorithm development. Survival analyses with overall survival (OS) and progression-free survival (PFS) as endpoints were performed to assess clinical response. The predictive value of bITH was subsequently validated with an independent cohort of 42 NSCLC patients treated with PD-1 blockade.bITH was significantly associated with the differential OS and PFS elicited by atezolizumab vs. docetaxel in both univariable and multivariable analyses in the OAK patients, suggesting bITH as an independent predictor for response to ICB. Moreover, compared with blood tumor mutation burden (bTMB), bITH enabled greater OS segregation and comparable PFS segregation, and obtained a predictive role regardless of bTMB status. Moreover, the association between bITH and PFS was validated with an independent cohort.Patients with low blood-based ITH metric manifest significant OS and PFS benefit from immunotherapy versus chemotherapy. Future research is awaited to corroborate our findings and to enrich the clinical utility of ITH.This study was supported by the National Natural Science Foundation of China (Nos. 81972718 and 81572321), the Natural Scientific Foundation of Zhejiang Province, China (No. LY19H160007), the Science and Technology Program for Health and Medicine in Zhejiang Province, China (No. 2021KY541), the Scientific Research Project, Science and Technology Department of Sichuan Province (No. 21YYJC1616), the Scientific Research Project, Sichuan Medical Association (No. S20002), Wu Jieping Medical Foundation (No. 320.6750), and 2018 Entrepreneurial Leading Talent of Guangzhou Huangpu District and Guangzhou Development District (No. 2022-L023).Copyright © 2023. Published by Elsevier B.V.

基金：
National Natural Science Foundation of China (Nos. 81972718 and 81572321), the Natural Scientific Foundation of Zhejiang Province, China (No. LY19H160007), the Science and Technology Program for Health and Medicine in Zhejiang Province, China (No. 2021KY541), the Scientific Research Project, Science and Technology Department of Sichuan Province (No. 21YYJC1616), the Scientific Research Project, Sichuan Medical Association (No. S20002), Wu Jieping Medical Foundation (No. 320.6750), and 2018 Entrepreneurial Leading Talent of Guangzhou Huangpu District and Guangzhou Development District (No. 2022-L023).
语种：
外文
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WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2023]版：
大类 | 1 区 医学
小类 | 1 区 医学：研究与实验
最新[2023]版：
大类 | 1 区 医学
小类 | 1 区 医学：研究与实验
JCR分区：
出版当年[2023]版：
Q1 MEDICINE, RESEARCH & EXPERIMENTAL
最新[2023]版：
Q1 MEDICINE, RESEARCH & EXPERIMENTAL

影响因子： 最新[2023版] 最新五年平均 出版当年[2023版] 出版当年五年平均 出版前一年[2022版]

第一作者：
第一作者机构： [1]Department of Medical Thoracic Oncology, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, China.
共同第一作者：
通讯作者：
通讯机构： [3]National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Cancer Institute & Hospital, Tianjin Medical University, China. [6]Department of Thoracic Surgery, Fujian Provincial Hospital, China [*1]Department of Thoracic Oncology, Tianjin Cancer Institute & Hospital, Tianjin Medical University, Huanhuxi Road, Tianjin, 300060, China. [*2]Department of Chest Surgery, Fujian Provincial Hospital, Fuzhou, Fujian, 350001, China.
推荐引用方式(GB/T 7714)：
Fan Yun,Liu Yang,Wang Liuchun,et al.bITH, a blood-based metric of intratumor heterogeneity, is associated with clinical response to immune checkpoint blockade in non-small cell lung cancer[J].EBIOMEDICINE.2023,91:doi:10.1016/j.ebiom.2023.104564.
APA：
Fan Yun,Liu Yang,Wang Liuchun,Cai Yiran,Cao Wen...&Huang Dingzhi.(2023).bITH, a blood-based metric of intratumor heterogeneity, is associated with clinical response to immune checkpoint blockade in non-small cell lung cancer.EBIOMEDICINE,91,
MLA：
Fan Yun,et al."bITH, a blood-based metric of intratumor heterogeneity, is associated with clinical response to immune checkpoint blockade in non-small cell lung cancer".EBIOMEDICINE 91.(2023)

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