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Pulmonary venous circulating tumor cell dissemination before tumor resection and disease relapse

Item Type:Article
Title:Pulmonary venous circulating tumor cell dissemination before tumor resection and disease relapse
Creators Name:Chemi, F. and Rothwell, D.G. and McGranahan, N. and Gulati, S. and Abbosh, C. and Pearce, S.P. and Zhou, C. and Wilson, G.A. and Jamal-Hanjani, M. and Birkbak, N. and Pierce, J. and Kim, C.S. and Ferdous, S. and Burt, D.J. and Slane-Tan, D. and Gomes, F. and Moore, D. and Shah, R. and Al Bakir, M. and Hiley, C. and Veeriah, S. and Summers, Y. and Crosbie, P. and Ward, S. and Mesquita, B. and Dynowski, M. and Biswas, D. and Tugwood, J. and Blackhall, F. and Miller, C. and Hackshaw, A. and Brady, G. and Swanton, C. and Dive, C.
Abstract:Approximately 50% of patients with early-stage non-smallcell lung cancer (NSCLC) who undergo surgery with curative intent will relapse within 5 years. Detection of circulating tumor cells (CTCs) at the time of surgery may represent a tool to identify patients at higher risk of recurrence for whom more frequent monitoring is advised. Here we asked whether CellSearch-detected pulmonary venous CTCs (PV-CTCs) at surgical resection of early-stage NSCLC represent subclones responsible for subsequent disease relapse. PV-CTCs were detected in 48% of 100 patients enrolled into the TRACERx study, were associated with lung-cancer-specific relapse and remained an independent predictor of relapse in multivariate analysis adjusted for tumor stage. In a case study, genomic profiling of single PV-CTCs collected at surgery revealed higher mutation overlap with metastasis detected 10 months later (91%) than with the primary tumor (79%), suggesting that early-disseminating PV-CTCs were responsible for disease relapse. Together, PV-CTC enumeration and genomic profiling highlight the potential of PV-CTCs as early predictors of NSCLC recurrence after surgery. However, the limited sensitivity of PV-CTCs in predicting relapse suggests that further studies using a larger, independent cohort are warranted to confirm and better define the potential clinical utility of PV-CTCs in early-stage NSCLC.
Keywords:Circulating Neoplastic Cells, Gene Expression Regulation, Human Genome, Local Neoplasm Recurrence, Neoplasm Metastasis, Neoplasm Staging, Neoplastic Tumor Biomarkers, Non-Small-Cell Lung Carcinoma, Pulmonary Veins
Source:Nature Medicine
Publisher:Nature Publishing Group
Page Range:1534-1539
Date:October 2019
Additional Information:Erratum in Nat Med. 26, 1147(2020). Roland Schwarz is a member of the TRACERx Consortium.
Official Publication:https://doi.org/10.1038/s41591-019-0593-1
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

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