Tracking viable circulating tumor cells (CTCs) in the peripheral blood of non-small cell lung cancer (NSCLC) patients undergoing definitive radiation therapy: pilot study results

Cancer. 2015 Jan 1;121(1):139-49. doi: 10.1002/cncr.28975. Epub 2014 Sep 19.

Abstract

Background: Assays identifying circulating tumor cells (CTCs) allow noninvasive and sequential monitoring of the status of primary or metastatic tumors, potentially yielding clinically useful information. However, to the authors' knowledge, the effect of radiation therapy (RT) on CTCs in patients with non-small cell lung cancer (NSCLC) has not been previously explored.

Methods: This report describes results from a pilot study of 30 patients with NSCLC who received RT. Peripheral blood samples obtained from these patients were assayed for CTCs using an assay that identified live cells using an adenoviral probe that detected the elevated telomerase activity present in almost all cancer cells, but not in normal cells, and the validity of the assay was confirmed with secondary tumor-specific markers. Patients were assayed before initiation of RT (pre-RT), during the RT course, and/or after the completion of RT (post-RT).

Results: The assay successfully detected CTCs in the majority of patients, including 65% of patients before the start of RT, and in patients with both epidermal growth factor receptor wild-type and mutation-positive tumors. The median CTC counts in patients before RT was 9.1 CTCs per mL (range, undetectable to 571 CTCs per mL) and was significantly higher than the average post-RT count of 0.6 CTCs per mL (range, undetectable to 1.8 CTCs per mL; P<.001). Sequential CTC counts were available in a subset of patients and demonstrated decreases after RT, except for 1 patient who subsequently developed distant failure.

Conclusions: The current pilot data suggest that CTC counts appear to reflect response to RT in patients with localized NSCLC. On the basis of these promising results, the authors have launched a more comprehensive and detailed clinical trial.

Keywords: assay; biomarkers; circulating tumor cells; non-small cell lung cancer; telomerase.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Non-Small-Cell Lung / blood
  • Carcinoma, Non-Small-Cell Lung / diagnosis*
  • Carcinoma, Non-Small-Cell Lung / radiotherapy
  • Cell Line, Tumor
  • Female
  • Humans
  • Lung Neoplasms / blood
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / radiotherapy
  • Male
  • Middle Aged
  • Neoplastic Cells, Circulating / metabolism*
  • Pilot Projects
  • Telomerase / blood
  • Telomerase / metabolism*
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • Telomerase