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

TRACERx Consortium

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1534-1539
Number of pages6
JournalNature Medicine
Volume25
Issue number10
DOIs
Publication statusPublished - 7 Oct 2019

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor/genetics
  • Carcinoma, Non-Small-Cell Lung/diagnosis
  • Female
  • Gene Expression Regulation, Neoplastic/genetics
  • Genome, Human/genetics
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local/diagnosis
  • Neoplasm Staging
  • Neoplastic Cells, Circulating/pathology
  • Pulmonary Veins/pathology

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