Fangfang Xie1, Yujun Zhang2, Xiaowei Mao3, Xiaoxuan Zheng4, Han Han-Zhang5, Junyi Ye6, Ruiying Zhao7, Xueyan Zhang8, Jiayuan Sun9. 1. Department of Endoscopy, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 West Huaihai Road, Shanghai 200030, PR China; Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 West Huaihai Road, Shanghai 200030, PR China. Electronic address: xiefang314@126.com. 2. Department of Endoscopy, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 West Huaihai Road, Shanghai 200030, PR China; Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 West Huaihai Road, Shanghai 200030, PR China. Electronic address: zhangyujun92@126.com. 3. Department of Endoscopy, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 West Huaihai Road, Shanghai 200030, PR China; Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 West Huaihai Road, Shanghai 200030, PR China. Electronic address: maoxwres@163.com. 4. Department of Endoscopy, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 West Huaihai Road, Shanghai 200030, PR China. Electronic address: milozheng59@163.com. 5. Burning Rock Biotech, Guangzhou 510000, PR China. Electronic address: han.han-zhang@brbiotech.com. 6. Burning Rock Biotech, Guangzhou 510000, PR China. Electronic address: junyi.ye@brbiotech.com. 7. Department of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 West Huaihai Road, Shanghai 200030, PR China. Electronic address: ruiyingzhao@foxmail.com. 8. Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 West Huaihai Road, Shanghai 200030, PR China. Electronic address: zhangxueyan570@163.com. 9. Department of Endoscopy, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 West Huaihai Road, Shanghai 200030, PR China; Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 West Huaihai Road, Shanghai 200030, PR China. Electronic address: xkyyjysun@163.com.
Abstract
OBJECTIVES: Genetic profiles of primary and metastatic lung tumor have been investigated by previous studies. However, whether they can be replaced by each other to guide treatment remains controversial. Moreover, it is unclear that whether genetic profiles of plasma can reflect genetic divergence between primary and metastatic lesions. MATERIALS AND METHODS: In this prospective study, we collected 35 pairs of matched primary tumor tissue, metastatic lymph nodes and plasma from treatment-naïve patients with advanced non-squamous non-small cell lung cancer (NSCLC) and applied to capture-based sequencing using a panel consisting 56 NSCLC-related genes to interrogate the heterogeneity and similarity among the 3 sites. RESULTS: We observed 62.0% (67/108) by-variant concordance rate among primary tumor, metastatic lymph nodes and plasma as well as 76.4% (81/106) by-variant concordance rate between primary tumor and metastatic lymph nodes. When the analysis restricted to driver genes, we achieved 60.9% (28/46) and 77.3% (34/44) concordance, respectively. Furthermore, there is no statistically significant difference in progression-free survival (PFS) of 17 patients who used matched targeted therapy between patients having 100% concordance rate between primary tumor and metastatic lymph nodes and patients having partially matched mutational profiles. CONCLUSION: Collectively, our study revealed a similar genetic profile shared between primary tumor and metastatic lymph nodes. The limited discordance observed can be partially reflected by plasma. Sequencing results obtained from either site can be utilized for providing treatment guidance.
OBJECTIVES: Genetic profiles of primary and metastatic lung tumor have been investigated by previous studies. However, whether they can be replaced by each other to guide treatment remains controversial. Moreover, it is unclear that whether genetic profiles of plasma can reflect genetic divergence between primary and metastatic lesions. MATERIALS AND METHODS: In this prospective study, we collected 35 pairs of matched primary tumor tissue, metastatic lymph nodes and plasma from treatment-naïve patients with advanced non-squamous non-small cell lung cancer (NSCLC) and applied to capture-based sequencing using a panel consisting 56 NSCLC-related genes to interrogate the heterogeneity and similarity among the 3 sites. RESULTS: We observed 62.0% (67/108) by-variant concordance rate among primary tumor, metastatic lymph nodes and plasma as well as 76.4% (81/106) by-variant concordance rate between primary tumor and metastatic lymph nodes. When the analysis restricted to driver genes, we achieved 60.9% (28/46) and 77.3% (34/44) concordance, respectively. Furthermore, there is no statistically significant difference in progression-free survival (PFS) of 17 patients who used matched targeted therapy between patients having 100% concordance rate between primary tumor and metastatic lymph nodes and patients having partially matched mutational profiles. CONCLUSION: Collectively, our study revealed a similar genetic profile shared between primary tumor and metastatic lymph nodes. The limited discordance observed can be partially reflected by plasma. Sequencing results obtained from either site can be utilized for providing treatment guidance.
Authors: Li-Hui Tseng; Federico De Marchi; Aparna Pallavajjalla; Erika Rodriguez; Rena Xian; Deborah Belchis; Christopher D Gocke; James R Eshleman; Peter Illei; Ming-Tseh Lin Journal: Am J Clin Pathol Date: 2019-10-07 Impact factor: 2.493
Authors: Won-Chul Lee; Alexandre Reuben; Xin Hu; Nicholas McGranahan; Runzhe Chen; Ali Jalali; Marcelo V Negrao; Shawna M Hubert; Chad Tang; Chia-Chin Wu; Anthony San Lucas; Whijae Roh; Kenichi Suda; Jihye Kim; Aik-Choon Tan; David H Peng; Wei Lu; Ximing Tang; Chi-Wan Chow; Junya Fujimoto; Carmen Behrens; Neda Kalhor; Kazutaka Fukumura; Marcus Coyle; Rebecca Thornton; Curtis Gumbs; Jun Li; Chang-Jiun Wu; Latasha Little; Emily Roarty; Xingzhi Song; J Jack Lee; Erik P Sulman; Ganesh Rao; Stephen Swisher; Lixia Diao; Jing Wang; John V Heymach; Jason T Huse; Paul Scheet; Ignacio I Wistuba; Don L Gibbons; P Andrew Futreal; Jianhua Zhang; Daniel Gomez; Jianjun Zhang Journal: Genome Biol Date: 2020-11-04 Impact factor: 13.583
Authors: Raghav Sundar; Drolaiz Hw Liu; Gordon Ga Hutchins; Hayley L Slaney; Arnaldo Ns Silva; Jan Oosting; Jeremy D Hayden; Lindsay C Hewitt; Cedric Cy Ng; Amrita Mangalvedhekar; Sarah B Ng; Iain Bh Tan; Patrick Tan; Heike I Grabsch Journal: Gut Date: 2020-11-23 Impact factor: 23.059
Authors: Moom R Roosan; Isa Mambetsariev; Rebecca Pharaon; Jeremy Fricke; Hatim Husain; Karen L Reckamp; Marianna Koczywas; Erminia Massarelli; Andrea H Bild; Ravi Salgia Journal: Chest Date: 2021-04-18 Impact factor: 9.410