Pulmonary venous circulating tumor cell dissemination before tumor resection and disease relapseMore about Open Access at the Crick
Authors listFrancesca Chemi Dominic G Rothwell Nicholas McGranahan Sakshi Gulati Chris Abbosh Simon P Pearce Cong Zhou Gareth Wilson Mariam Jamal-Hanjani Nicolai Birkbak Jackie Pierce Chang Sik Kim Saba Ferdous Deborah J Burt Daniel Slane-Tan Fabio Gomes David Moore Rajesh Shah Maise Al Bakir Crispin Hiley Selvaraju Veeriah Yvonne Summers Philip Crosbie Sophia Ward Barbara Mesquita Marek Dynowski Dhruva Biswas Jonathan Tugwood Fiona Blackhall Crispin Miller Allan Hackshaw Ged Brady Charles Swanton Caroline Dive TRACERx Consortium
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Approximately 50% of patients with early-stage non-small-cell lung cancer (NSCLC) who undergo surgery with curative intent will relapse within 5 years1,2. 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 study3, 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.
Journal Nature Medicine
Issue number 10