Findings from a prospective study done by a team of investigators from Spain demonstrated that circulating tumour cells (CTCs) could be detected in blood samples of some patients after they underwent radical resection for non-small-cell lung cancer (NSCLC). The team also found that the post-surgical presence of CTCs in the blood associated significantly with early disease recurrence.
These findings were presented by Prof. Clara Bayarri-Lara, Department of Thoracic Surgery, Hospital Universitario Virgen de las Nieves, Granada, Spain, during the Best Abstracts session at the European Lung Cancer Conference held 15-18 April 2015 in Geneva, Switzerland.
Detection of circulating tumour cells one month after surgery (CTC2 +) was significantly correlated with a shorter disease-free survival in patients undergoing radical resection for non-small-cell lung cancer.
© Clara Bayarri-Lara
Detection of CTCs in blood is becoming increasingly important in cancer biomarker research. The CTCs detection and enumeration can give early information on the risk of relapse and disease progression, which frequently occurs even with optimal surgical treatment for NSCLC, according to Prof. Bayarri-Lara.
This study enrolled 56 patients who had undergone radical surgery for previously untreated NSCLC. Blood samples taken before and one month after surgery from each patient were analysed for the presence of CTC’s, which were isolated using both an inmunomagnetic technique and by size. Patients having at least one CTC isolated per sample were identified as CTC positive. The CTCs were also analysed for epidermal growth factor receptor (EGFR) expression, which could identify cells that are susceptible to specific targeted therapies.
Analysis of the presurgical samples identified 29 (51.8%) patients as CTC-positive with a median 3 CTCs per sample. At one month following surgery, 18 (32.1%) patients were CTC-positive, and a median of 2 CTCs were isolated per sample (p = 0.035).
Fewer CTCs were isolated in blood samples of patients undergoing pneumonectomy compared to other types of surgery (p = 0.034).
Post-surgical CTC detection associates with early distant recurrence and shorter disease-free survival rates
The CTC count in post-surgical sample showed an association with the max SUV of PET scan (p = 0.046). Within a median follow-up of 16 months, 16 (28.6%) patients experienced early disease recurrence. Disease recurrence significantly associated with the detection of CTCs in post surgical blood samples of patients (p = 0.018).
Shorter disease free survival (DFS) was also observed in patients with a CTC-positive post-surgical sample. The one-year DFS rate was 51% in CTC-positive patients compared to 87.7% in patients having a CTC-negative post-surgical blood sample (log rank test p = 0.008).
The presence of CTCs following surgery and node status emerged as independent prognostic factors for DFS by multivariate analysis.
EGFR expression was decreased on CTCs following resection; EGFR was expressed on 89.7% and 38.9% of CTCs isolated from blood samples taken before and after surgery, respectively.
Dr Egbert Smit of the Netherlands Cancer Institute and Vrije Universiteit VU Medical Centre in Amsterdam, the Netherlands, who discussed the study results, said that biosources in the circulation are plasma (characterised by low DNA/mRNA yield, nuclease prone), CTCs (characterised by complex isolation, low CTC yield), platelets (characterised by easy isolation, high quality mRNA), and microvescicles (characterised by complex isolation, low mRNA yield). Their application in the clinic might be in diagnosis and prediction, follow-up after curative treatment, stratification for adjuvant therapy, and detection of resistance to systemic treatment. According to Dr Smit, CTCs await more robust isolation methods before this technology can be routinely applied.
Conclusion
The investigators concluded that CTCs can be detected in the blood of patients following surgery for NSCLC and results from this study suggest that CTC detection may contribute to risk stratification by identifying patients with increased risk of early recurrence. Prof. Bayarri-Lara announced that a larger study to further validate CTCs as a prognostic marker for elevated risk of disease recurrence is underway.
Reference
No conflict of interest to be disclosed.