Circulating tumor DNA-based stratification strategy for chemotherapy plus PD-1 inhibitor in advanced non-small-cell lung cancer,Cancer Cell

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Circulating tumor DNA-based stratification strategy for chemotherapy plus PD-1 inhibitor in advanced non-small-cell lung cancer
Cancer Cell ( IF 48.8 ) Pub Date : 2024-09-09 , DOI: 10.1016/j.ccell.2024.08.013
Jiachen Xu ₁ , Rui Wan ₁ , Yiran Cai ₂ , Shangli Cai ₂ , Lin Wu ₃ , Baolan Li ₄ , Jianchun Duan ₁ , Ying Cheng ₅ , Xiaoling Li ₆ , Xicheng Wang ₇ , Liang Han ₈ , Xiaohong Wu ₉ , Yun Fan ₁₀ , Yan Yu ₁₁ , Dongqing Lv ₁₂ , Jianhua Shi ₁₃ , Jianjin Huang ₁₄ , Shaozhang Zhou ₁₅ , Baohui Han ₁₆ , Guogui Sun ₁₇ , Qisen Guo ₁₈ , Youxin Ji ₁₉ , Xiaoli Zhu ₂₀ , Sheng Hu ₂₁ , Wei Zhang ₂₂ , Qiming Wang ₂₃ , Yuming Jia ₂₄ , Ziping Wang ₂₅ , Yong Song ₂₆ , Jingxun Wu ₂₇ , Meiqi Shi ₂₈ , Xingya Li ₂₉ , Zhigang Han ₃₀ , Yunpeng Liu ₃₁ , Zhuang Yu ₃₂ , An-Wen Liu ₃₃ , Xiuwen Wang ₃₄ , Caicun Zhou ₃₅ , Diansheng Zhong ₃₆ , Liyun Miao ₃₇ , Zhihong Zhang ₃₈ , Hui Zhao ₃₉ , Jun Yang ₄₀ , Dong Wang ₄₁ , Yingyi Wang ₄₂ , Qiang Li ₄₃ , Xiaodong Zhang ₄₄ , Mei Ji ₄₅ , Zhenzhou Yang ₄₆ , Jiuwei Cui ₄₇ , Beili Gao ₄₈ , Buhai Wang ₄₉ , Hu Liu ₃₈ , Lei Nie ₅₀ , Mei He ₅₁ , Shi Jin ₅₂ , Wei Gu ₅₃ , Yongqian Shu ₅₄ , Tong Zhou ₅₅ , Jian Feng ₅₆ , Xinmei Yang ₅₇ , Cheng Huang ₅₈ , Bo Zhu ₅₉ , Yu Yao ₆₀ , Jianjun Yu ₆₁ , Sheng Yao ₆₁ , Runxi Shen ₆₂ , Zhijie Wang ₁ , Jie Wang ₁

Affiliation

State Key Laboratory of Molecular Oncology, CAMS Key Laboratory of Translational Research on Lung Cancer, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Burning Rock Biotech, Guangzhou, China.
Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
Beijing Chest Hospital, Capital Medical University, Beijing, China.
Jilin Cancer Hospital, Changchun, China.
Liaoning Cancer Hospital & Institute, Shenyang, China.
The First Affiliated Hospital, School of Clinical Medicine of Guangdong Pharmaceutical University, Guangzhou, China.
Xuzhou Central Hospital, Xuzhou, China.
Jiangnan University Affiliated Hospital, Wuxi, China.
Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, China.
Harbin Medical University Cancer Hospital, Harbin, China.
Taizhou Hospital of Zhejiang Province, Linhai, China.
Linyi Cancer Hospital, Linyi, China.
The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Guangxi Medical University Affiliated Tumor Hospital, Nanning, China.
Shanghai Chest Hospital, Shanghai, China.
Tangshan People's Hospital, Tangshan, China.
Shangdong Cancer Hospital, Jinan, China.
Qingdao Central Hospital, Qingdao, China.
Zhongda Hospital Southeast University, Nanjing, China.
Hubei Cancer Hospital, Wuhan, China.
The First Affiliated Hospital of Nanchang University, Nanchang, China.
Henan Cancer Hospital, Zhengzhou, China.
The Second People's Hospital of Yibin, Yibin, China.
Peking University Cancer Hospital, Beijing, China.
Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
The First Affiliated Hospital of Xiamen University, Xiamen, China.
Jiangsu Cancer Hospital, Nanjing, China.
The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, China.
The First Hospital of China Medical University, Shenyang, China.
The Affiliated Hospital of Qingdao University, Qingdao, China.
The Second Affiliated Hospital of Nanchang University, Nanchang, China.
Qilu Hospital of Shandong University, Jinan, China.
Shanghai Pulmonary Hospital, Shanghai, China.
Tianjin Medical University General Hospital, Tianjin, China.
Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.
Anhui Provincial Cancer Hospital, Hefei, China.
The Second Hospital of Anhui Medical University, Hefei, China.
The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Army Medical Center of PLA, Daping Hospital, Daping, China.
Peking Union Medical College Hospital, Beijing, China.
Shanghai East Hospital of Tongji University, Shanghai, China.
Nantong Tumor Hospital, Nantong, China.
The First People's Hospital of Changzhou, Changzhou, China.
The Second Affiliated Hospital of Chongqing University, Chongqing, China.
The First Hospital of Jilin University, Jilin, China.
Ruijin Hospital Shanghai Jiaotong University, School of Medicine, Shanghai, China.
Subei People's Hospital of Jiangsu Province, Yanghzou, China.
Shanxi Provincial Tumor Hospital, Xian, China.
Shanxi Provincial People's Hospital, Taiyuan, China.
Cancer Hospital of Chinese Academy of Medical Sciences, Shenzhen Center, Shenzhen, China.
Nanjing First Hospital, Nanjing, China.
The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
ChangZhou Cancer Hospital, Changzhou, China.
Affiliated Hospital of Nantong University, Nantong, China.
Jiaxing No. 1 Hospital, Jiaxing, China.
Fujian Cancer Hospital, Fuzhou, China.
Xinqiao Hospital of Army Medical University, Chongqing, China.
First Affiliated Hospital of Xi'an Jiaotong University, Xian, China.
Shanghai Junshi Biosciences, Shanghai, China.
BeiGene Co., Ltd, Beijing, China.

Stratification strategies for chemotherapy plus PD-1 inhibitors in advanced non-small-cell lung cancer (NSCLC) are critically demanded. We performed high-throughput panel-based deep next-generation sequencing and low-pass whole genome sequencing on prospectively collected circulating tumor DNA (ctDNA) specimens from 460 patients in the phase 3 CHOICE-01 study at different time points. We identified predictive markers for chemotherapy plus PD-1 inhibitor, including ctDNA status and genomic features such as blood-based tumor mutational burden, intratumor heterogeneity, and chromosomal instability. Furthermore, we established an integrated ctDNA-based stratification strategy, blood-based genomic immune subtypes (bGIS) scheme, to distinguish patients who benefit from the addition of PD-1 inhibitor to first-line chemotherapy. Moreover, we demonstrated potential applications for the dynamic monitoring of ctDNA. Overall, we proposed a potential therapeutic algorithm based on the ctDNA-based stratification strategy, shedding light on the individualized management of immune-chemotherapies for patients with advanced NSCLC.

中文翻译：

晚期非小细胞肺癌化疗加 PD-1 抑制剂的循环肿瘤 DNA 分层策略

迫切需要化疗加 PD-1 抑制剂治疗晚期非小细胞肺癌（NSCLC）的分层策略。我们对 3 期 CHOICE-01 研究中 460 例患者在不同时间点前瞻性收集的循环肿瘤 DNA （ctDNA）标本进行了高通量基于面板的深度下一代测序和低通全基因组测序。我们确定了化疗加 PD-1 抑制剂的预测标志物，包括 ctDNA 状态和基因组特征，例如基于血液的肿瘤突变负荷、肿瘤内异质性和染色体不稳定性。此外，我们建立了一种基于 ctDNA 的综合分层策略，即基于血液的基因组免疫亚型（bGIS）方案，以区分在一线化疗中加入 PD-1 抑制剂的患者。此外，我们展示了 ctDNA 动态监测的潜在应用。总体而言，我们提出了一种基于基于 ctDNA 的分层策略的潜在治疗算法，阐明了晚期 NSCLC 患者免疫化疗的个体化管理。

更新日期：2024-09-09

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