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

Abstract

Background Assays identifying circulating tumor cells (CTC) allow noninvasive and sequential monitoring of the status of primary or metastatic tumors, potentially yielding clinically useful information. However, the effect of radiation therapy (RT) on CTC in patients with non-small cell lung cancer (NSCLC) to our knowledge has not been previously explored. Methods We describe here results of a pilot study of 30 NSCLC patients undergoing RT, from whom peripheral blood samples were assayed for CTC via an assay that identifies live cells, via an adenoviral probe that detects the elevated telomerase activity present in almost all cancer cells but not normal cells, and with validity of the assay confirmed with secondary tumor-specific markers. Patients were assayed prior to initiation of radiation (Pre-RT), during the RT treatment course, and/or after completion of radiation (Post-RT). Results The assay successfully detected CTC in the majority of patients, including 65% of patients prior to start of RT, and in patients with both EGFR wild type and mutation-positive tumors. Median counts in patients Pre-RT were 9.1 CTC/mL (range: undetectable - 571), significantly higher than the average Post-RT count of 0.6 CTC/mL (range: undetectable - 1.8) (p < 0.001). Sequential CTC counts were available in a subset of patients and demonstrated decreases after RT, except for a patient who subsequently developed distant failure. Conclusions These pilot data suggest that CTC counts appear to reflect response to RT for patients with localized NSCLC. Based on these promising results, we have launched a more comprehensive and detailed clinical trial.

A Pilot Study of Circulating Tumor Cells in Stage IV Non-Small Cell Lung Carcinoma

“…Using an adenoviral probe that detected the elevated telomerase activity present in almost all cancer cells but not in normal cells, the median number of CTCs was assayed in 30 patients with non-small cell lung carcinoma. 19 Median CTC counts declined from 9.1 CTCs/ml to 0.6 CTCs/ml post-radiation therapy. Even the type of surgery appears to have an impact on the number of CTCs.…”

Challenges and unanswered questions for the next decade of circulating tumour cell research in lung cancer

“…In contrast, an increase in CTC numbers is indicative of failure to respond to therapy. Changes in CTC numbers were also examined in patients with localised NSCLC undergoing radiation treatment the change in CTC numbers post treatment was evaluated as a surrogate for disease response (171). Additional studies have investigated subsets of CTCs linked to the therapy used.…”

Critical issues in the clinical application of liquid biopsy in non-small cell lung cancer

“…Several studies associate CTC number to OS and/or PFS of metastatic NSCLC patients (32,33,48,57), meanwhile others do not find these associations (70,71). Many small trials have also demonstrated the association between CTC count and therapy efficacy, comparing the count before and after therapy (38,(72)(73)(74), or during target therapy, in order to detect the onset of resistance mutations (50,54,62,66,75). Even though most data suggest the utility of CTCs as biomarkers for assessing prognosis and monitoring therapy response in NSCLC, these assays are still not used in routine clinical practice, mainly due to the lack of standardized procedures allowing reliable and reproducible results that could be compared among different cohorts of patients.…”