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

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Item Type:	Article
Title:	Pulmonary venous circulating tumor cell dissemination before tumor resection and disease relapse
Creators Name:	Chemi, F., Rothwell, D.G., McGranahan, N., Gulati, S., Abbosh, C., Pearce, S.P., Zhou, C., Wilson, G.A., Jamal-Hanjani, M., Birkbak, N., Pierce, J., Kim, C.S., Ferdous, S., Burt, D.J., Slane-Tan, D., Gomes, F., Moore, D., Shah, R., Al Bakir, M., Hiley, C., Veeriah, S., Summers, Y., Crosbie, P., Ward, S., Mesquita, B., Dynowski, M., Biswas, D., Tugwood, J., Blackhall, F., Miller, C., Hackshaw, A., Brady, G., 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
ISSN:	1078-8956
Publisher:	Nature Publishing Group
Volume:	25
Number:	10
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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