The present study is the first to evaluate the relationship between CTCs and the pathological effects of induction chemoradiotherapy in NSCLC patients. CTC count was found to be significantly higher in pulmonary than in peripheral blood. In patients who underwent induction chemoradiotherapy, pvCTC count was negative in the case of CR, whereas it was positive in the other cases.
While patients who achieved pathological CR by induction chemoradiotherapy plus surgery achieved favorable prognosis , it is difficult to evaluate pathological CR following induction therapy. If it is possible to confirm CR patients before operation, patient selection based on surgical indications will be possible and may contribute to a prognostic improvement. Usage of pvCTCs has the potential to accurately reflect the pathological effects of induction therapy, and their measurement is useful in the prediction of pathological CR. This suggests that it would be possible to conduct a prospective study of patients achieving pathological CR by induction chemoradiotherapy. The question of whether pulmonary resection is necessary in patients achieving CR may then be easier to answer, because preoperative evaluation would be possible when a pulmonary vein catheter technique (e.g., pulmonary vein isolation) is used .
In the IT group, the number of patients with squamous cell carcinoma was greater than that of patients with adenocarcinoma. Three patients with squamous cell carcinoma were positive for pvCTCs and 3 were negative. Two and 1 patient with adenocarcinoma were positive and negative for pvCTCs, respectively. Okumura and colleagues reported that the incidence of positive periCTCs was significantly higher in squamous cell carcinoma than in adenocarcinoma, but no correlation was observed between pvCTC count and histological type . To investigate the correlation between pvCTC count and histological type, futher study is required. The cause for the difference in the number of pvCTCs and periCTCs remains unclear. As for the result, the role of destruction within the blood stream or seeding to tissue bed is considered as a hypothesis.
The major limitation of this study is that the study population was small, and greater patient numbers are desirable for further study. Further study using a large sample size is important for making definitive conclusions. Sawabata and colleagues reported that periCTCs were detected in NSCLC cases following surgical manipulation . That study also raised concerns over the use of pvCTCs. However, since periCTCs and pvCTCs (in cases showing CR) obtained intraoperatively were all negative, this concern may be ruled out.
In CTC detection, clustered cells were hardly extracted from the blood using the CellSearch™ system. EpCAM-based enrichment methods such as use of the CellSearch™ system have a limitation in that EpCAM can be downregulated during epithelial–mesenchymal transition . A recent study indicated that this process is attributable to metastasis . Various alternate methods are currently available [23–27], and it may be necessary to verify results using other methods.
The present study has established a new role for CTC analysis in the evaluation of induction chemoradiotherapy. While sampling of pulmonary venous blood is currently not easy, the development of a new, non-invasive procedure for sampling pulmonary venous blood would enable determination of pathological CR preoperatively. We may be able to verify the likely efficacy of surgery after induction chemoradiotherapy in the treatment of locally advanced NSCLC.