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Wait-and-See Treatment Strategy and Genomic Alternations Associated with Progression in Lung Adenocarcinoma with Pleural Dissemination

28 Pages Posted: 9 May 2019

See all articles by Ying Chen

Ying Chen

Guangdong Academy of Medical Sciences - Guangdong Lung Cancer Institute

Wen-Fang Tang

Guangdong Academy of Medical Sciences - Guangdong Lung Cancer Institute; Shantou University - Medical College

Huan Lin

Guangzhou University of Chinese Medicine

Hua Bao

Geneseeq Technology Inc.

Wei Li

Guangdong Academy of Medical Sciences - Guangdong Lung Cancer Institute

Ao Wang

Geneseeq Technology Inc.

Xue Wu

Geneseeq Technology Inc.

Jian Su

Guangdong Academy of Medical Sciences - Guangdong Lung Cancer Institute

Yang Shao

Geneseeq Technology Inc. - Nanjing Geneseeq Technology Inc.; Nanjing Medical University - School of Public Health

Xue-Ning Yang

Guangdong Academy of Medical Sciences - Guangdong Lung Cancer Institute

Yi-Long Wu

Guangdong Academy of Medical Sciences, Guangdong General Hospital, Guangdong Lung Cancer Institute, Department of Pulmonary Oncology

Wen-Zhao Zhong

Guangdong Academy of Medical Sciences - Guangdong Lung Cancer Institute

More...

Abstract

Background: To evaluate the feasibility of postoperative wait-and-see strategy, as well as identify genomic alternations of progression for lung adenocarcinoma with pleural dissemination (pM1a).  

Methods: 131 patients diagnosed with malignant pleural dissemination either unexpectedly found during primary tumor resection or recurred post-surgery were retrospectively selected. We evaluated survival difference among three postoperative initial treatments: chemotherapy, targeted therapy and wait-and-see strategy. Whole-exome sequencing were performed on 26 patients with dramatic progression or gradual progression, aiming to identify markers associated with progression pattern.  

Findings: In the entire cohort, the wait-and-see group showed significantly longer progression-free survival (PFS) than chemotherapy group (P < 0.001) but similar PFS with targeted group (P = 0.984). This pattern persisted in EGFR-positive patients. However, in patients with EGFR-negative/ unknown, PFS was significantly extended in wait-and-see group compared to the other two strategies. Furthermore, better overall survival was seen in patients who received chemotherapy or targeted therapy after wait-and-see than those received initial chemotherapy or targeted therapy. Results from WES analysis demonstrated that high genomic instability index (GIS) and chromosome 18q loss were enriched in metastasis tumors, and high GIS was significantly associated with poor PFS (P = 0.029).  

Interpretation: These findings suggest wait-and-see is a feasible treatment strategy for pM1a patients. Dramatic and gradual progression may be attributed to high and low level of genomic instability, respectively.  

Funding Statement: This work was supported by Project of National Natural Science Foundation (grant numbers 81673031, 81872510 to WZ Zhong).  

Declaration of Interests: The authors have no conflict of interest to declare.

Ethics Approval Statement: This study was approved by the Ethics and Scientific Committees of Guangdong Provincial People’s Hospital (No. GDREC2016175H(R2)).

Keywords: Lung adenocarcinoma, pleural dissemination, wait-and-see, genome instability, progression

Suggested Citation

Chen, Ying and Tang, Wen-Fang and Lin, Huan and Bao, Hua and Li, Wei and Wang, Ao and Wu, Xue and Su, Jian and Shao, Yang and Yang, Xue-Ning and Wu, Yi-Long and Zhong, Wen-Zhao, Wait-and-See Treatment Strategy and Genomic Alternations Associated with Progression in Lung Adenocarcinoma with Pleural Dissemination (August 5, 2019). Available at SSRN: https://ssrn.com/abstract=3384881

Ying Chen

Guangdong Academy of Medical Sciences - Guangdong Lung Cancer Institute

China

Wen-Fang Tang

Guangdong Academy of Medical Sciences - Guangdong Lung Cancer Institute

China

Shantou University - Medical College

Shantou
China

Huan Lin

Guangzhou University of Chinese Medicine

Guangzhou
China

Hua Bao

Geneseeq Technology Inc.

Toronto, Ontario
Canada

Wei Li

Guangdong Academy of Medical Sciences - Guangdong Lung Cancer Institute

China

Ao Wang

Geneseeq Technology Inc.

Toronto, Ontario
Canada

Xue Wu

Geneseeq Technology Inc.

Toronto, Ontario
Canada

Jian Su

Guangdong Academy of Medical Sciences - Guangdong Lung Cancer Institute

China

Yang Shao

Geneseeq Technology Inc. - Nanjing Geneseeq Technology Inc.

Nanjing, Jiangsu
China

Nanjing Medical University - School of Public Health

Nanjing
China

Xue-Ning Yang

Guangdong Academy of Medical Sciences - Guangdong Lung Cancer Institute

China

Yi-Long Wu

Guangdong Academy of Medical Sciences, Guangdong General Hospital, Guangdong Lung Cancer Institute, Department of Pulmonary Oncology ( email )

China

Wen-Zhao Zhong (Contact Author)

Guangdong Academy of Medical Sciences - Guangdong Lung Cancer Institute ( email )

China

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