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Preclinical study and phase II trial of adapting low-dose radiotherapy to immunotherapy in small cell lung cancer

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收录情况： ◇ ESCI

作者：
Wang Hui[1] * ; Yao Zhuoran[1,2] * ; Kang Kai[1,2] * ; Zhou Lin[1,2] * ; Xiu Weigang[1] * ; Sun Jianguo[3] ; Xie Conghua[4] ; Yu Min[1] ; Li Yanying[1] ; Zhang Yan[1,5] ; Zheng Yue[1] ; Lin Guo[1] ; Pan Xiangyu[6] ; Wu Yijun[1,2] ; Luo Ren[1,2] ; Wang Laduona[1] ; Tang Min[1] ; Liao Shuangsi[1] ; Zhu Jiang[1] ; Zhou Xiaojuan[1,2] ; Zhang Xuanwei[1,2] ; Xu Yong[1,2] ; Liu Yongmei[1,2] ; Peng Feng[1] ; Wang Jin[1,2] ; Xiang Lisha[1] ; Yin Limei[1,7] ; Deng Lei[8] ; Huang Meijuan[1] ; Gong Youling[1,2] ; Zou Bingwen[1,2] ; Wang Hui[9] ; Wu Lin[10] ; Yuan Zhiyong[11] ; Bi Nan[12] ; Fan Min[13] ; Xu Yaping[14] ; Tong Ruizhan[1] ; Yi Linglu[1] ; Gan Lu[15] ; Xue Jianxin[1,2] ; Mo Xianming[16] ; Chen Chong[6] ; Na Feifei[1] ; Lu You[1,2] ;
机构： [1]Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China. [2]Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China. [3]Cancer Institute, Xinqiao Hospital, Army Medical University, Chongqing, China. [4]Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China. [5]Center of Lung Cancer, West China Hospital, Sichuan University, Chengdu, China. [6]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China. [7]Department of Health Management & Institute of Health Management, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China. [8]University of Washington School of Medicine/Fred Hutchinson Cancer Center, Seattle, WA, USA. [9]Department of Radiation Oncology, Hunan Cancer Hospital, Changsha, China. [10]Department of Thoracic Medicine, Hunan Cancer Hospital, Changsha, China [11]Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China. [12]Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. [13]Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China. [14]Department of Radiation Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. [15]Research Laboratory of Emergency Medicine, Department of Emergency Medicine, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China. [16]Laboratory of Stem Cell Biology, West China Hospital, Sichuan University, Chengdu, China.
出处：
DOI： 10.1016/j.medj.2024.06.002
ISSN：

摘要：
Immune checkpoint inhibitors (ICIs) provide modest but unsatisfactory benefits for extensive-stage small cell lung cancer (ES-SCLC). Developing strategies for treating ES-SCLC is critical.We preliminarily explored the outcomes of salvage low-dose radiotherapy (LDRT) plus ICI on refractory SCLC patients. Next, we evaluated the combinational efficacy in murine SCLC. The tumor immune microenvironment (TIME) was analyzed for mechanistic study. Subsequently, we conducted a multicenter, prospective phase II trial that administered concurrent thoracic LDRT plus chemoimmunotherapy to treatment-naive ES-SCLC patients (MATCH trial, NCT04622228). The primary endpoint was confirmed objective response rate (ORR), and the key secondary endpoints included progression-free survival (PFS) and safety.Fifteen refractory SCLC patients treated with LDRT plus ICI were retrospectively reviewed. The ORR was 73.3% (95% confidence interval [CI], 44.9-92.2). We identified a specific dose of LDRT (15 Gy/5 fractions) that exhibited growth retardation and improved survival in murine SCLC when combined with ICIs. This combination recruited a special T cell population, TCF1+ PD-1+ CD8+ stem-like T cells, from tumor-draining lymph nodes into the TIME. The MATCH trial showed a confirmed ORR of 87.5% (95% CI, 75.9-94.8). The median PFS was 6.9 months (95% CI, 5.4-9.3).These findings verified that LDRT plus chemoimmunotherapy was safe, feasible, and effective for ES-SCLC, warranting further investigation.This research was funded by West China Hospital (no. ZYJC21003), the National Natural Science Foundation of China (no. 82073336), and the MATCH trial was fully funded by Roche (China) Holding Ltd. (RCHL) and Shanghai Roche Pharmaceuticals Ltd. (SRPL).Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

基金：
This preliminary clinical work and experiment research were supported by 1$3$5 project for disciplines of excellence, West China Hospital, Sichuan University (no. ZYJC21003), the National Natural Science Foundation of China (no. 82073336), Wu Jieping Medical Foundation Project (no. 320.6750.2022-17-10), CAMS Innovation Fund forMedical Sciences (CIFMS) (no. 2022-I2M-C&T-B-101), and Sichuan Provincial Research Foundation (nos. 2022NSFSC0770 and 2023NSFSC0699), and the MATCH trial was fully funded by Roche (China) Holding Ltd. (RCHL), Shanghai Roche Pharmaceuticals Ltd. (SRPL).
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外文
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出版当年[2024]版：
无
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[2023版]

第一作者：
第一作者机构： [1]Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
共同第一作者：
通讯作者：
通讯机构： [1]Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China. [2]Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
推荐引用方式(GB/T 7714)：
Wang Hui,Yao Zhuoran,Kang Kai,et al.Preclinical study and phase II trial of adapting low-dose radiotherapy to immunotherapy in small cell lung cancer[J].Med (New York, N.Y.).2024,5(10):doi:10.1016/j.medj.2024.06.002.
APA：
Wang Hui,Yao Zhuoran,Kang Kai,Zhou Lin,Xiu Weigang...&Lu You.(2024).Preclinical study and phase II trial of adapting low-dose radiotherapy to immunotherapy in small cell lung cancer.Med (New York, N.Y.),5,(10)
MLA：
Wang Hui,et al."Preclinical study and phase II trial of adapting low-dose radiotherapy to immunotherapy in small cell lung cancer".Med (New York, N.Y.) 5..10(2024)

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