Chemi, F;
Rothwell, DG;
McGranahan, N;
Gulati, S;
Abbosh, C;
Pearce, SP;
Zhou, C;
... TRACERx Consortium, .; + view all
(2019)
Pulmonary venous circulating tumor cell dissemination before tumor resection and disease relapse.
Nature Medicine
, 25
pp. 1534-1539.
10.1038/s41591-019-0593-1.
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Jamal-Hanjani_Pulmonary venous circulating tumor cell dissemination before tumor resection and disease relapse_AAM.pdf - Accepted Version Download (851kB) | Preview |
Abstract
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.
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