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Preclinical study and phase II trial of adapting low-dose radiotherapy to immunotherapy in small cell lung cancer.
Wang, Hui; Yao, Zhuoran; Kang, Kai; Zhou, Lin; Xiu, Weigang; Sun, Jianguo; Xie, Conghua; Yu, Min; Li, Yanying; Zhang, Yan; Zheng, Yue; Lin, Guo; Pan, Xiangyu; Wu, Yijun; Luo, Ren; Wang, Laduona; Tang, Min; Liao, Shuangsi; Zhu, Jiang; Zhou, Xiaojuan; Zhang, Xuanwei; Xu, Yong; Liu, Yongmei; Peng, Feng; Wang, Jin; Xiang, Lisha; Yin, Limei; Deng, Lei; Huang, Meijuan; Gong, Youling; Zou, Bingwen; Wang, Hui; Wu, Lin; Yuan, Zhiyong; Bi, Nan; Fan, Min; Xu, Yaping; Tong, Ruizhan; Yi, Linglu; Gan, Lu; Xue, Jianxin; Mo, Xianming; Chen, Chong; Na, Feifei; Lu, You.
Affiliation
  • Wang H; Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
  • Yao Z; Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China; Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
  • Kang K; Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China; Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
  • Zhou L; Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China; Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
  • Xiu W; Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
  • Sun J; Cancer Institute, Xinqiao Hospital, Army Medical University, Chongqing, China.
  • Xie C; Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China.
  • Yu M; Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
  • Li Y; Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
  • Zhang Y; Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China; Center of Lung Cancer, West China Hospital, Sichuan University, Chengdu, China.
  • Zheng Y; Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
  • Lin G; Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
  • Pan X; State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
  • Wu Y; Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China; Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
  • Luo R; Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China; Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
  • Wang L; Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
  • Tang M; Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
  • Liao S; Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
  • Zhu J; Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
  • Zhou X; Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China; Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
  • Zhang X; Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China; Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
  • Xu Y; Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China; Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
  • Liu Y; Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China; Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
  • Peng F; Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
  • Wang J; Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China; Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
  • Xiang L; Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
  • Yin L; Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China; Department of Health Management & Institute of Health Management, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, C
  • Deng L; University of Washington School of Medicine/Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Huang M; Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
  • Gong Y; Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China; Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
  • Zou B; Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China; Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
  • Wang H; Department of Radiation Oncology, Hunan Cancer Hospital, Changsha, China.
  • Wu L; Department of Thoracic Medicine, Hunan Cancer Hospital, Changsha, China.
  • Yuan Z; Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
  • Bi N; Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  • Fan M; Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
  • Xu Y; Department of Radiation Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
  • Tong R; Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
  • Yi L; Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
  • Gan L; Research Laboratory of Emergency Medicine, Department of Emergency Medicine, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
  • Xue J; Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China; Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
  • Mo X; Laboratory of Stem Cell Biology, West China Hospital, Sichuan University, Chengdu, China.
  • Chen C; State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
  • Na F; Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China. Electronic address: nafeifei@scu.edu.cn.
  • Lu Y; Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China; Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China. Electronic address: radyoulu@hotmail.com.
Med ; 2024 Jul 02.
Article in En | MEDLINE | ID: mdl-38964333
ABSTRACT

BACKGROUND:

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.

METHODS:

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.

FINDINGS:

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).

CONCLUSIONS:

These findings verified that LDRT plus chemoimmunotherapy was safe, feasible, and effective for ES-SCLC, warranting further investigation.

FUNDING:

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).
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Med / Med (New York. Online) Year: 2024 Type: Article Affiliation country: China
Fulltext
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PubMed Links
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Med / Med (New York. Online) Year: 2024 Type: Article Affiliation country: China