Pulmonary venous circulating tumor cell dissemination before tumor resection and disease relapse
Authors
- F. Chemi
- D.G. Rothwell
- N. McGranahan
- S. Gulati
- C. Abbosh
- S.P. Pearce
- C. Zhou
- G.A. Wilson
- M. Jamal-Hanjani
- N. Birkbak
- J. Pierce
- C.S. Kim
- S. Ferdous
- D.J. Burt
- D. Slane-Tan
- F. Gomes
- D. Moore
- R. Shah
- M. Al Bakir
- C. Hiley
- S. Veeriah
- Y. Summers
- P. Crosbie
- S. Ward
- B. Mesquita
- M. Dynowski
- D. Biswas
- J. Tugwood
- F. Blackhall
- C. Miller
- A. Hackshaw
- G. Brady
- C. Swanton
- C. Dive
Journal
- Nature Medicine
Citation
- Nat Med 25 (10): 1534-1539
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.